B Y t V khoa hc v o to

Hp cht hu c n chc v a chc

(Sch dng o to dc s i hc) M s: 20 Y13 Tp II

Nh xut bn Y hc H ni - 2006 1

Ch bin: PGS. TS. Trng Th K Tham gia bin son: ThS. Nguyn Anh Tun TS. Phm Khnh Phong Lan ThS. Th Thu PGS. TS. ng Vn Tnh ThS. Trng Ngc Tuyn

Tham gia t chc bn tho: TS. Nguyn Mnh Pha ThS. Ph Vn Thm

Bn quyn Thuc B Y t (V Khoa hc v o to)

Li gii thiu
Thc hin Ngh nh 43/2000/N-CP ngy 30/08/2000 ca Chnh ph quy nh chi tit v hng dn trin khai Lut Gio dc, B Gio dc v o to v B Y t ph duyt, ban hnh cc chng trnh khung cho o to Dc s i hc. B Y t t chc thm nh sch v ti liu dy hc cc mn hc c s v chuyn mn theo chng trnh mi nhm tng bc xy dng b sch chun trong cng tc o to Dc s i hc ngnh Y t. B sch Ho hu c c bin son theo chng trnh o to mn Ho hc hu c thuc chng trnh gio dc ca i hc Y Dc thnh ph H Ch Minh trn c s chng trnh khung c B Gio dc & o to, B Y t ph duyt. Ni dung b sch ch cp nhng kin thc l thuyt v ho hu c, gm 40 chng v chia lm 2 tp trnh by nhng kin thc c bn v danh php, cu trc, c ch phn ng, tnh cht l hc v tnh cht ho hc ca cc hp cht hydrocarbon, cc hp cht n chc, cc hp cht a chc, hp cht tp chc, hp cht thin nhin v hp cht cao phn t. i tng s dng b sch ny l cc sinh vin ang theo hc ti Trng i hc Dc, khoa Dc thuc cc trng i hc ngnh Y t. ng thi cng l ti liu tham kho tt cho nhng hc vin sau i hc. Sch Ho hu c c cc ging vin giu kinh nghim ca Khoa Dc - i hc Y Dc Thnh ph H Ch Minh bin son. Sch c Hi ng chuyn mn thm nh sch gio khoa v ti liu dy hc chuyn ngnh Dc ca B Y t thm nh v c B Y t ban hnh lm ti liu dy hc chnh thc dng o to dc s i hc ca Ngnh Y t trong giai on hin nay. Trong thi gian t 3 n 5 nm, sch cn c chnh l, b sung v cp nht. V Khoa hc v o to, B Y t xin chn thnh cm n Khoa Dc - i hc Y Dc Thnh ph H Ch Minh cng cc tc gi b nhiu cng sc bin son cun sch ny. V l ln u xut bn nn chc chn cn nhiu thiu st, chng ti mong nhn c kin ng gp ca ng nghip v bn c cun sch ngy cng hon thin.

V khoa hc v o to B Y t

MC LC
M u 9 11 13 13 14 16 18 18 18 19 21 21 24 28 28 30 33 33 51 56 62 62 73 75 79 79 79 5

HP CHT TP CHC
Chng 25: Halogenoacid (ThS. Th Thy) 1. Phng php iu ch 2. Cc phn ng ha hc ca halogenoacid 3. Mt s halogenoacid c nhiu ng dng Chng 26: Hydroxyacid (ThS. Th Thy) 1. Danh php 2. ng phn 3. iu ch 4. Tnh cht l hc 5. Tnh cht ha hc 6. ng dng Chng 27: Hp cht hai chc c nhm carbonyl (ThS. Th Thy) 1. Hydroxy - aldehyd v hydroxy - ceton 2. Ceto-aldehyd, ceto-acid, ceto-ester Chng 28: Carbohydrat (ThS. Th Thy) 1. Monosaccharid 2. Oligosaccharid 3. Polysaccharid Chng 29: Acid amin, peptid v protid (TS. Phm Khnh Phong Lan) 1. Acid amin 2. Peptid 3. Protid

HP CHT D VNG
Chng 30: Hp cht d vng (TS. Phm Khnh Phong Lan) 1. nh ngha

2. Phn loi hp cht d vng 3. Danh php hp cht d vng 4. Cu to cc d vng thm 5. Tnh cht ha hc ca d vng c tnh thm 1. Nhm furan 2. Nhm pyrrol 3. Nhm thiophen Chng 32: Hp cht d vng 6 cnh 1 d t - D t l nit hoc oxy (TS. Phm Khnh Phong Lan) 1. Pyridin 2. Pyran 1. Nhm oxazol 2. Nhm thiazol 3. Nhm imidazol 4. Nhm pyrazol Chng 34: Hp cht d vng 6 cnh 2 d t (TS. Phm Khnh Phong Lan) 1. Hp cht d vng 2 d t l nit 2. Hp cht d vng 2 d t l nit v lu hunh 3. Hp cht d vng 2 d t l nit v oxy 4. Hp cht d vng 2 d t l oxy Chng 35: Hp cht d vng 7 cnh (TS. Phm Khnh Phong Lan) 1. Azepin 2. Oxepin v thiepin 3. Diazepin v benzodiazepin Chng 36: Hp cht d vng ngng t (TS. Phm Khnh Phong Lan) 1. Dng h bin ca vng lactam 2. Tnh cht ca purin 3. Mt s alcaloid c khung purin

79 81 88 91 94 97 101 105 105 117 120 122 124 126 128 129 134 136 136 137 138 139 140 142 142 143 143 145 145 145 146

Chng 31: Hp cht d vng 5 cnh 1 d t (TS. Phm Khnh Phong Lan) 93

Chng 33: Hp cht d vng 5 cnh nhiu d t (TS. Phm Khnh Phong Lan) 120

HP CHT THIN NHIN

Chng 37: Acid nucleic (TS. Phm Khnh Phong Lan) 1. nh ngha 2. Phn ng ca acid nucleic

3. Phn base ca acid nucleic 4. Cu to ca cc nucleosid 5. Cu to ca nucleotid 6. Cu to ca acid nucleic Chng 38: Terpen (TS. Phm Khnh Phong Lan) 1. nh ngha v phn loi 2. Monoterpen 3. Sesquiterpen 4. Diterpen 5. Triterpen 6. Tetraterpen 7. Polyterpen Chng 39: Steroid (TS. Phm Khnh Phong Lan) 1. nh s trn khung steroid 2. Cu hnh v danh php ca khung steroid 3. Cu hnh v danh php cc nhm th trn khung steroid 4. Cu dng ca steroid 5. Sterol 6. Cc acid mt 7. Cc hormon Ti liu tham kho

146 147 148 148 150 150 151 161 165 166 167 170 173 174 174 175 175 176 179 181 183

M U
i tng ca ha hc hu c: Ha hc hu c l mn khoa hc nghin cu thnh phn v tnh cht cc hp cht ca carbon. Trong thnh phn hp cht hu c, ngoi carbon cn c nhiu nguyn t khc nh H, O, N, S, P, halogen... nhng carbon c xem l nguyn t c bn cu to nn hp cht hu c. S lc lch s pht trin ca Ha hc hu c T xa xa ngi ta bit iu ch v s dng mt s cht hu c trong i sng nh gim (acid acetic long), ru (ethanol), mt s cht mu hu c. Thi k gi kim thut cc nh ha hc iu ch c mt s cht hu c nh ur, ether etylic... Cui th k 18 u th k 19, cc nh ha hc chit tch t ng, thc vt nhiu acid hu c nh acid oxalic, acid citric, acid lactic ... v mt s base hu c (alcaloid). Nm 1806 ln u tin nh ha hc ngi Thy in Berzelius dng danh t Ha hc hu c ch ngnh ha hc nghin cu cc hp cht c ngun gc ng vt v thc vt. Thi im ny c th xem nh ct mc nh du s ra i ca mn ha hc hu c. Nm 1815 Berzelius a ra thuyt Lc sng cho rng cc hp cht hu c ch c th c to ra trong c th ng vt v thc vt nh mt lc sng ch con ngi khng th iu ch c. Thuyt duy tm ny tn ti trong nhiu nm nhng dn dn b nh bi cc cng trnh tng hp cc cht hu c t cc cht v c. Nm 1824, nh ha hc ngi c Wohler tng hp c acid oxalic bng cch thy phn dixian l mt cht v c. Nm 1828 cng chnh ng, t cht v c amoni cyanat tng hp c ur. Tip theo Bertholet (Php) tng hp c cht bo nm 1854 v Bulerov (Nga) tng hp ng glucose t formalin nm 1861. Cho n nay hng triu cht hu c c tng hp trong phng th nghim v trn quy m cng nghip. Con ngi khng ch bt chc tng hp cc cht ging thin nhin m cn sng to ra nhiu cht hu c, nhiu vt liu hu c cc k quan trng v qu gi m t nhin khng c. Tuy nhin tn gi hp cht hu c vn c duy tr, nhng khng phi ch vi ngha l cc cht c ngun gc ng vt v thc vt m mang ni dung mi: l cc hp cht ca carbon.

c im ca cc hp cht hu c v phn ng hu c Mc d ra i mun hn ha hc v c nhng cc hp cht hu c rt phong ph v s lng, chng loi. S lng cht hu c cho n nay nhiu gp vi chc ln cc cht v c bit. Nguyn nhn c bn l do carbon c kh nng to thnh mch di v tn theo nhiu kiu khc nhau. Ni cch khc hin tng ng phn (tc l cc cht c cng thnh phn phn t nhng khc nhau v cu to) l cc k ph bin v c trng trong ha hc hu c. Cu trc phn t ca hp cht hu c c th n gin nhng cng c th rt phc tp, vic xc nh cu trc ca chng nhiu khi rt kh khn, phi s dng nhiu phng php ha hc v vt l hc hin i. Nu nh lin kt ion kh ph bin trong hp cht v c th lin kt ch yu gia cc nguyn t trong phn t hu c li l lin kt cng ha tr. c im ny nh hng nhiu n tnh cht l ha v c bit l kh nng phn ng ca chng. Cc phn ng hu c thng xy ra vi tc chm, khng hon ton v thng theo nhiu hng khc nhau, v vy vai tr ca nhit ng hc, ng hc v xc tc trong ha hu c rt quan trng. Vai tr ca ha hc hu c Cc cht hu c c vai tr rt quan trng trong i sng ca con ngi. Khng nhng hu ht thc phm chng ta n (glucid, protid, lipid), vt dng hng ngy (cellulose, si tng hp, cao su, cht do...) l cc cht hu c m nhiu cht hu c cn l c s ca s sng (protid, acid nucleic..). Nhin liu cho ng c t trong, cho nh my nh xng, du l hn hp hydrocarbon mch di ngn khc nhau. Cc vt liu hu c nh, khng han g, tin s dng, nhiu mu sc a dng ang ngy mt thay th cho cc kim loi, hp kim trong nhiu lnh vc, k c nhng lnh vc tng nh khng th thay th c nh bn dn, siu dn... Do tt c nhng c im trn, ha hc hu c c tch ra nh mt ngnh khoa hc ring i hi nhng phng php nghin cu v thit b ngy cng hin i hn, i hi n lc khng ngng ca cc nh ha hc khng nhng bt chc thin nhin tng hp nn cc cht phc tp phc v cho nhiu lnh vc ca cuc sng m cn vt xa hn c thin nhin. T c s ha hc hu c, c rt nhiu ngnh nghin cu ng dng ra i: ha cng nghip, ha du, cng nghip dt, ha thc phm, dc phm v ha m phm.

HP CHT TP CHC
nh ngha Hp cht tp chc l hp cht hu c, trong phn t c t nht hai nhm chc khc nhau. Cng c th xem hp cht tp chc l dn xut ca hydrocarbon m t nht c hai hydro c thay th bi cc nhm chc hon ton khc nhau.
CH3 - CHOH - CH = O CH3 - CH(NH2) - COOH CH2Cl - CHCl - CH2OH HOC6H4COOH H2NC6H4COOH HOC6H4CHO

phn t c chc alcol v chc aldehyd phn t c chc amin v chc acid phn t c Cl v chc alcol phn t c chc phenol v chc acid phn t c chc amin v chc acid phn t c chc phenol v chc aldehyd

Phn bit Hp cht a chc: nhiu nhm chc cng mt loi. Hp cht tp chc: nhiu chc khc nhau (xut hin tnh cht mi). Trong cc hp cht tp chc cc nhm chc nh hng ln nhau lm tng hoc gim kh nng phn ng ca nhm chc c bn hoc to ra nhng tnh cht phn ng c th ca hp cht tp chc. V d: Phenol c tnh acid yu hn acid carbonic. Phenol khng tc dng vi Na2CO3 nhng clorophenol li tc dng vi Na2CO3

OH Cl + Na2CO3

ONa + NaHCO3 Cl

iu chng t rng nguyn t clor nh hng n tnh acid ca chc phenol. Hp cht tp chc c nhiu nhm chc khc nhau rt ph bin trong i sng hng ngy. Cc dc phm thng c nhiu nhm chc khc nhau trong phn t. Danh php Cc hp cht tp chc c loi gi theo danh php thng thng nh cc acid amin, nhng gi tn theo danh php quc t l chun mc bit r cu trc 11

ca mt hp cht tp chc phc tp. C nhng quy c khi gi tn theo danh php h thng: a- Chn mch di nht cha nhm chc c u tin cao nht. b- Cc nhm chc cn li c gi tn theo tip u ng. c- nh s trn mch chnh t nhm chc. Gi tn hp cht c mch chnh tng ng vi nhm chc u tin c tip v ng ca nhm chc v v tr, tip u ng ca cc nhm chc khc theo th t u tin. Bng lit k sau trnh by th t u tin ca cc nhm chc:
Tn gi tip v ng, tip u ng v th t u tin ca cc nhm chc
Nhm chc Cation Anion -COOH -SO3H -COX -CONH2 -CONHCO-CN -CHO C=O S=O -OH -SH -NH2 =NH oni at, id, ur oic, carboxylic sulfonic oylhalogenid, carbonylhalogenid amid, carboxamid imid, dicarboximid. nitril, carbonitril. al, carbaldehyd. on thion ol thiol amin imin Tip v ng Tip u ng onio ato, ido carboxy sulfo haloformyl carbamoyl iminodicarbonyl cyano oxo, formyl oxo thioxo hydroxyl, hydroxy mercapto amino imino

V d V:
H2N CH2 CH CH2 CH COOH CH3 CH C O

NH2 OH 4-Hydroxy-2,5-diaminopentanoic

C N Cl 2-Cyanopropanoyl clorid

12

Chng 25

HALOGENOACID

Mc tiu 1. c c tn cc halogenoacid. 2. Nu c ha tnh ca halogenoacid v ng dng ca mt s cht in hnh. Halogenoacid l nhng hp cht c to thnh do s thay th mt hay nhiu nguyn t hydro trn gc hydrocarbon ca acid carboxylic bng cc nguyn t halogen. Cc halogenoacid ca acid monocarboxylic no c nhiu ng dng, c bit l cc -halogenoacid.
R CH X -Halogenomonocarboxylic 2-Halogenocarboxylic COOH R CH X -Halogenomonocarboxylic 3-Halogenocarboxylic CH2 COOH R CH X -Halogenomonocarboxylic 4-Halogenocarboxylic CH2 CH2 COOH

1. Phng php iu ch 1.1. Halogen ha acid carboxylic Acid -monocarboxylic no c th c iu ch bng cch halogen ha trc tip bng fluor (F2), clor (Cl2), brom (Br2) khi c mt ca acid cha proton, acid Lewis. Nu c xc tc nh sng (h), phn ng th xy ra theo c ch th gc v khng th vo v tr .
+ Cl2 (H+) CH3 CH2 COOH + Cl2 (h) CH3 CH Cl CH2 CH2 Cl COOH + HCl COOH + HCl

Trong phn ng halogen ha acid, thu c sn phm th vo v tr thng s dng thm phosphor (P) vi vai tr to acylhalogenid v s halogen ha vo acylhalogenid xy ra nhanh hn vo acid carboxylic. 2P + X2 2PX3

13

R R

CH2 C CH2 C

O OH O X

PX3

CH2 C O OH

O X

R + X2 R

CH C - HX CH C X

OH X O X

+R

CH C X

+ RCH2COOH

Nhm COX c hiu ng - I mnh cho nn hydro ca C _H v tr c tnh acid hn so vi cc hydro khc trong phn t acid RCH2CH2COOH. Halogen ha acid benzoic bng halogen c xc tc Lewis to acid meta halogenobenzoic.
COOH + X2 AlCl3 X COOH + HX

Acid carboxylic - RCOOH hoc CH2(COOH)2 b halogen ha d dng khi tng tc vi thionylclorid (SOCl2). 1.2. Cng hp HX vo acid cha no Cng hp HX vo acid ,-cha no thu c -halogenoacid. Phn ng tri quy tc Markonikov. CH2=CH-COOH + HX X - CH2-CH2-COOH

2. Cc phn ng ha hc ca halogenoacid 2.1. Phn ng th i nhn - Phn ng thy phn Halogenoacid l acid mnh hn acid carboxylic. Nguyn t halogen ca halogenoacid thuc dy aliphatic tham gia phn ng th i nhn. Halogenoacid rt d thy phn.

R-CHX-COOH + OH -

R-CHOH-COOH

Nhm carboxyl nh hng n s phn cc ca lin kt C -X. Phn ng th xy ra theo c ch SN2 v khng thay i cu hnh. Gii thch nh sau:
HO .. H R

..
C C S

O .. -H+ Br

..

.. -: O
H

.. C
C R

O .. - Br Br

..

:O H

..

C C

O ..

..

R -Lacton

14

:O H R

..

C C

O .. -: OH

..

:O ..

- ..

C C

O ..

..
+ H+ H COOH C

.. ..

H R

OH

OH R S Acid -hydroxycarboxylic

Cc gem -dihalogen acid thy phn bng H2O to thnh oxo acid:
CHCl2 COOH
Acid dicloroacetic

H2O

CH O COOH

2HCl

Acid glyoxalic

Cc hp cht , v -halogenoacid c kh nng to cc vng lacton tng ng:

H2O , CHCl3 -BrC CH3 O O

CH3

CH Br

CH2

COOH

utyrolacton ,Butanolid

O C O Br (CH2)5 C O OH H2O , Ag2O Caprolacton , (1,6-hexanolid) HO (CH2)5 C O

OH Acid 6-hydroxycaproic; 6-Hydroxyhexanoic

2.2. Phn ng tch loi to acid cha no Trong mi trng kim c - alcol, c phn ng loi HX.
2NaOH CH3 CH CH2 COOH Cl Acid -clorobutyric 2NaOH CH 3 CHOH CH 2 COONa + NaCl + H 2O -hydroxybutyrat natri CH 3 CH = CH COONa Nnatric crotonat + NaCl + 2H 2O

Phn ng ph xy ra khi tch loi c th l s decarboxyl ha v to hydrocarbon cha no. Phn ng ph ny thng xy ra i vi hp cht -halogenoacid. .. O X CH CH2 C R CH CH2 + CO2 + X : O: .. R
Halogenocarboxylat

15

3. Mt s halogenoacid c nhiu ng dng 3.1. Monocloroacetic ClCH2COOH Monocloroacetic c iu ch bng cch clor ha acid acetic trong hn hp anhydrid acetic v acid sulfuric m c hoc thy phn tricloroetylen bng acid sulfuric 75% 140C.
Cl H C C Cl Cl 2 H2O , H2SO4 Cl-CH2-COOH + 2HCl

Monocloroacetic l tinh th, tnc = 63C, d tan trong nc v etanol, c s dng tng hp acid malonic, ester malonat v cc cht mu. 3.2. Dicloroacetic - Cl2CHCOOH iu ch dicloroacetic bng cch un cloralhydrat vi calci carbonat c xc tc l natri cyanid NaCN.
Cl3-CH(OH) 2 2CaCO3 , NaCN -2CO 2 , -CaCl 2 , -2H 2O (Cl 2 CH-COO ) 2Ca + 2 H+ -Ca 2+ 2Cl2 CH-COOH

Hoc thy phn tetracloroetylen bng hi nc:

Cl Cl C C Cl Cl 2H2O Cl2 CH-COOH + 2HCl

iu ch dicloroacetylclorid: Oxy ha tricloroetylen bng khng kh 70100C. Cht trung gian l tricloroxiran khng bn b chuyn v.
Cl Cl C C H Cl O2 , Cl Cl O C C H Cl Cl2CH C O Cl

Gc dicloroacetyl c trong thnh phn ca chloramphenicol. 3.3. Tricloroacetic - Cl3C-COOH Oxy ha cloralhydrat bng acid nitric HNO3 m c thu c tricloroacetic.
Cl3-CH(OH) 2 [O] ,HNO 3 Cl3 C-COOH + H 2O

Oxy ha tetracloroetylen bng oxy khng kh thu c tricloroacetylclorid Cl3C-COCl. Tricloroacetic l mt acid mnh. Khi un nng tricloroacetic vi dung dch kim long hoc hi nc s thu c cloroform.

Cl3 C-COOH

[H2O ]

Cl3 CH + CO2

16

C ch:
Cl O Cl C : C .. : Cl O Cl Cl C : Cl H+ Cl3C _ H + C O O

Bi tp 1. Vit cng thc cu to ca cc cht sau: a- Acid -bromopropionic. b- Acid -cloro--metylbutyric c- Acid o-clorobenzoic. d- ,-Dibromopropionat kali. e- 2,3-Dicloropropionylclorur. g- Acid p-bromophenylacetic. 2- Vit phn ng ca acid -bromobutyric trong cc iu kin sau: a- Thy phn trong mi trng base. b- Thu phn khi c Ag2O. c- Tch loi trong mi trng alcol /KOH.

17

Chng 26

HYDROXYACID

Mc tiu 1. c c danh php cc hydroxyacid theo IUPAC v thng thng. 2. Trnh by c ha tnh ca hydroxyacid v tnh cht tng h gia hai nhm chc. Hydroxyacid cn c gi l hp cht oxyacid. C hai loi hp cht hydroxyacid quan trong:

Acid carboxylic cha chc alcol: HO -R-COOH (Alcol-acid) Acid carboxylic cha chc phenol: HO -Ar-COOH ( Phenol-acid)
1. Danh php
Tn v v tr nhm OH + Tn acid tng ng

nh s hoc dng ch ci , , ,.. ortho, meta, para ch v tr ca nhm OH.

CH3-CH2-CH2-CHOH-CH2-COOH Acid Hydroxycaproic

COOH

COOH

OH Acid 3-Hydroxybenzoic Acid m-Hydroxybenzoic

OH Acid 4-Hydroxybenzoic Acid p-Hydroxybenzoic

2. ng phn

S ng phn ph thuc v tr nhm OH. Thng c ng phn quang hc.

18

Cng thc HO-CH2-COOH

Danh php Acid glycolic -

ng phn quang hc

R- Lactic CH2-CHOH-COOH Acid lactic S-Lactic R,S-Lactic R-Malic HOOC-CHOH-CH2-COOH Acid malic S-Malic R,S-Malic 2R,3R-Tartaric HOOC-CHOH-CHOH-COOH Acid tartaric 2S,3S-Tartaric. 2R,3S-Mesotartaric
CH2 COOH

HO C COOH CH2 COOH C6H5 CH COOH CH2OH

Acid citric

Acid tropic

R(+)-Tropic S(-)-Tropic R,S-Tropic

C6H5-CHOH-COOH

Acid mandelic

R(-)-Mandelic

3. iu ch 3.1. Thy phn halogenoacid R CHCl- COOH + H2O R -CHOH- COOH + HCl 3.2. Kh ha ester ca oxoacid (aldehyd-ceton acid) Kh ha bng hydro mi sinh (hn hng natri) hay H2 / Ni
H / Ni CH 3 CHOH CH 2CO2Et CH 3 CO CH 2CO2Et 2 o Aceto acetat ethyl 120 C ,100 atm -Hydroxy butyrat ethyl H2O -EtOH CH 3 CHOH CH 2COOH Aacid -hydroxy butyric

R C (CH2) n COOR O

2 H (Ni) R CH (CH ) n COOR 2 to OH

H2O -ROH

R CH (CH2) n COOH OH

19

3.3. T aldehyd -ceton Cng hp HCN vo aldehyd - ceton, thy phn tip theo thu c -hydroxyacid.
R CH2 CH = O H CN R CH2 CHOH CN H3O+ R CH2 CHOH COOH

3.4. T cc hp cht etylen oxyd Etylen oxyd tc dng vi HCN v thy phn tip theo thu c - hydroxyacid.
CH2 O CH2 HCN HO CH2 CH2 CN H3O + HO CH2 CH2 CO2H

3.5. Phn ng Reformatski (1889) Ester ca acid -halogencarboxylic tc dng vi aldehyd hoc ceton c Zn lm cht trung gian s to thnh acid -oxycarboxylic. Phn ng xy ra nh sau:
R' R C=O Br CH2 CO2Et Zn R' R C O Zn Br CH2CO2Et H2O R' R C OH CH2CO2Et

3.6. T acid amin Acid amin tc dng vi HNO2

CH 3 CH (NH 2) CO 2H + HO N = O

- Aalanin
3.7. iu ch cc phenolacid Phng php Kolbe -Schmitt

CH 3 CH OH CO 2H + H2O + N2 Aacid lactic

Phenolat kh tc dng vi CO2 c nhit v p sut. ng dng sn xut acid salicylic trong cng nghip.
OH CO 2 200oC COONa p - Oxybenzoat natri ONa CO 2 125oC , 7 atm Natri salisilat OH COONa

Cc phenol khc c phn ng tng t:

O Na CO 2 130oC , 5 atm -Naphtolat natri
2- Hydroxy-naphtalen-1-carboxylat natri

COO Na OH

CO 2 250oC , 5 atm

OH COO Na
3-Hydroxy-naphtalen-2-carboxylat natri

20

4. Tnh cht l hc Hydroxyacid thng l cht kt tinh, c lin kt hydro tan tt trong nc, d phn hy khi c nhit . 5. Tnh cht ha hc Cc hydroxyacid th hin tnh cht c trng ca chc acid COOH, chc OH ca alcol hay chc OH ca phenol. 5.1. Cc phn ng ca alcolacid (HO -R-COOH)

Phn ng ca chc -COOH (tnh acid, to ester...) Phn ng ca chc -OH (to ester vi dn xut acid, phn ng SN...)
5.2. Phn ng tch nc Ty thuc v tr nhm OH, khi c nhit , phn ng tch nc ca hydroxyacid xy ra trong cc trng hp sau y: 5.2.1. Vi -hydroxy acid

2 phn t -hydroxy acid tch 2H2O to vng lactid (diester vng).

O C C OH + R OH HO C O - Hydroxy acid HO C R O O C O CH R

R HC C O

+ 2 H2O

Lactid

Cc lactid khng bn d b thy phn. Khi chng ct, cc lactid d b decarbonyl ha (gii phng CO) v to thnh aldehyd.
5.2.2. Vi - hydroxy acid.

-Hydroxacid khi tch H2O ni phn t to acid cha no ,-etylenic

R _ CH OH _ CH 2_ CO 2H -Hydroxy acid

R _ CH = CH _ CO 2H+ H 2O Aacid - ethylenic

5.2.3. Vi , -hydroxy acid Khi c nhit hoc xc tc acid, cc phn t hoc -hydroxy acid tch H2O to vng v -lacton. Nhm OH alcol v nhm OH ca acid b loi nc to ester ni phn t (vng lacton).

21

CH2 CH2 H2C C O

Hoc H+

H2C H2C

H2C + 2 H 2O

OH HO Acid -hydroxybutyric
CH2 H2C OH HO CH2 CH2 C O

C O O -Butyrolacton
CH2 H2C CH2 CH2 C O

Hoac H+

+ H2O

Acid -Hydroxyvaleric

Valerolacton

Khng th iu ch vng -lacton trc tip t -hydroxyacid. C th iu ch vng -lacton bng cch cho hp cht ceten tc dng vi aldehyd formic:
H2C C O + H2C O CH2 CH2 C O O

Propiolacton

Cc hydroxy acid c nhm OH cc v tr v xa hn na thng khng to vng lacton. Trong nhng iu kin nh trn cc acid ny thng to thnh cc polyester. Bng cc phng php ha hc c bit, c th tng hp cc lacton c vng ln:
CH2 CH2 (CH2 )6 O (CH2 )6 CH2 CH2 (CH2 )8 O (CH2 )5

OH C

C O

C O

Eczaltolid

Ambrettolid

Mevalolacton

Vng lacton nh l mt ester ni phn t, do nhng hp cht c vng lacton rt d b thy phn. Mt s phn ng c trng ca vng lacton:
NaOH , 2H [Na/Hg] 4H[LiAlH4] CH2 CH2 O CH2 C O HX KCN NH3 -H2O CH3NH2 -H2O HO (CH2)2COOH CH3(CH2)2COOH HO(CH2)4OH X(CH2)3COOH NC(CH2)3COOK CH2 CH2 CH2 CH2 N H CH2 C O CH2 C O N CH3

Butyrolacton

Pyrrolidon

N-Metylpyrrolidon

22

Cc vng lacton c vai tr quan trng trong mt s dc phm: Artemisinin l mt cht hu c chit c t cy Thanh hao hoa vng (Chenpodium ambrosioides) c cha vng lacton. Artemisinin v cc dn xut ca n c tc dng cha bnh st rt.
O CH3 O H O C O Artemisinin H H CH3 O CH3 O H O CH OH H H CH3 O O CH3 O H O H H CH CH3 O C CH2CH2COONa O Natri artesunat

Hydroartemisinin

5.3. Cc phn ng ca phenolacid (HO -Ar-COOH) 5.3.1. Tc dng vi FeCl3 Acid salicylic cho mu tm. Acid p-hydroxybenzoic cho mu . Acid m-hydroxybenzoic khng cho mu 5.3.2. Phn ng vi Na2CO3 v NaOH Ch c chc acid mi tc dng vi Na2CO3
OH COO H + Na 2CO3 Acid salicylic OH COO Na + NaHCO 3

Vi NaOH c 2 chc cng phn ng.

OH COO H + 2NaOH Acid salicylic O Na COO Na + 2H 2O

5.3.3. Phn ng acetyl ho vo chc phenol to ester

OH COO H + (CH CO) O 3 2 O - COCH 3 COO H + Pyridin.CH 3COOH Aspirin

Pyridin

Acid salicylic

23

5.3.4. Kh ha acid salicylic to acid pimelic

COOH OH 4 [H] Na / C 5H11 OH Acid salicylic COOH OH H bin H COOH O H 2O COO H CH 2COOH Acid pimelic

Acid pimelic hay heptandioic hay 1,5-pentandicarboxylic Acid salicylic c tnh acid mnh hn acid benzoic v cc ng phn meta v para. Acid salicylic c lin kt hydro ni phn t to iu kin thun li cho s phn ly proton.

OH C O
6. ng dng

O . .

O C O

O. .

+ H+ pKa =2,79

6.1. Mt s alcol acid ph bin

Acid glycolic: HOCH2-COOH (Acid hydroxyacetic, hydroxyetanoic).

iu ch acid glycolic bng phng php in phn acid oxalic hoc tng hp t formaldehyd v oxyd carbon:
HCHO + CO + H2O H+ , HO-CH2-COOH + H2O

Acid lactic: CH3CHOH-COOH (Acid -hydroxypropionic, 2-oxypropanoic).

Phn t c 1 carbon khng i xng. Nm 1780 Scheeler pht hin acid R,Slactic c trong sa chua khi ln men sa. Acid S (+)-lactic c trong cc c bp ca ngi v ng vt, l sn phm trung gian ca qu trnh glycolyse. Acid R(-)-lactic thu c t dung dch acid R,S-lactic. Acid L(+) lactic, acid R(-)-lactic u th rn. Acid R,S-lactic dng lng. iu ch acid lactic bng phng php ln men lactose, maltose hoc glucose.
C12H22O11 + H2 O Men Bacillus acidi lacti 4 CH3-CHOH-COOH (raxemic)

Oxy ha acid lactic bng thuc th H2O2/Fe2+ to ra acid pyruvic (2-oxopropanoic)

CH3 CH COOH OH H2O2, Fe 2+ CH3 C COOH +2 H2O O Acid pyruvic

Cc lactat c nhiu ng dng trong dc phm, thc phm v cng nghip. 24

 Acid malic: HOOC-CHOH-CH2-COOH (Acid hydroxysuccinic; 2-hydroxybutandioic).

Dng racemic to thnh do phn ng tng hp t acid R,S-bromomalic v AgOH hoc phn ng hp nc ca acid maleic.
HOOC CH2 CH COOH Br Acid R,S-Bromomalic + AgOH -AgBr HOOC CH2 CH COOH OH Acid R,S-Malic + H2O (H+) H C C H COOH

HOOC

Acid R,S-Maleic

Dng R (+)v Sv (-)-malic u dng tinh th.

Acid tartaric: HOOC-CHOH -CHOH-COOH (Acid ,,-dihydroxysuccinic; 2,3dihydroxybutandioic)

Acid 2R,3R-(+)-tartaric tn ti dng t do hoc dng mui tartarat kali c trong dch qu nho. Acid 2S,3S-(-)-tartaric khng c trong thin nhin. Khi un nng vi s c mt ca KHSO4, acid tartaric b loi nc, loi carbon dioxyd v to thnh acid pyruvic. Phn ng nh sau:
HO COOH C HO CH COOH KHSO4 C HO CH COOH -H2O H COOH Acid tartaric Acid oxymaleic O C COOH CH2 COOH - CO2 O C COOH CH3 Acid pyruvic

Mui kali, natri tartarat (mui Seignette) c s dng pha thuc th Fehling.

Acid citric: HOOC-CH2 -C(OH)(COOH)-CH2 COOH (Acid 2-hydroxypropan1,2,3-tricarboxylic, acid -hydroxytricarballylic).

Acid citric c trong nhiu hoa qu, trong sa v trong mu. Trong dch nc chanh c t 6 - 10% acid citric. Acid citric c vai tr quan trng trong cc chu trnh chuyn ha. Sn xut acid citric trn quy m cng nghip bng phng php ln men cc mono hoc disaccharid. un nng 175C acid citric b loi 1 phn t nc to acid cha no aconitic. Acid citric tc dng vi acid sulfuric m c hoc oleum to thnh acid acetondicarboxylic.

CH COOH COOH CH2 COOH Acid acotinic C

-H2O

CH2 COOH HO COOH CH2 COOH Acid citric C

Oleum

CH2 COOH O CH2 COOH Acid acetondicarboxylic (3-oxopetandioc) C

-HCOOH

25

6.2. Mt s phenol acid Cc ester ca phenolacid c nhiu ng dng:

Acid o-hydroxybenzoic
Acid o-hydroxybenzoic hay acid salicylic c dng iu ch metylsalicylat c tc dng gim au, c dng lm hng liu trong mt s dc phm v iu ch aspirin (acid acetyl salicylic), phenylsalicylat (salol) c tc dng khng nm.
OH OH OCOCH3

COOCH3

COOC6H 5

COOH

Metylsalicylat

Phenylsalicylat (Salol)

Acid acetylsalicylic (Aspirin)

Acid p-hydroxybenzoic
Acid p-hydroxybenzoic c s dng iu ch cc ester nh metyl -phydroxybenzoat (Nipagin), isopropyl-p-hydroxybenzoat (Nipazol) dng lm cht chng oxy ha trong dc phm v thc phm.
COOH + ROH OH H2SO4 COOR + H2O OH

to

R = -CH3 Nipagin R= -C3H7(n) Nipazol

Acid o-hydroxy cinnamic

Acid o-hydroxycinnamic cn gi l acid o -coumaric tn ti 2 dng ng phn hnh hc cis v trans. Loi nc t acid coumaric to thnh coumarin.
H C O CH C _ O H2O OH H C H C COOH C

CH COOH

Coumarin

Aacid o-coumaric (dng cis)

H OH Acid o-coumaric (dng trans)

Coumarin c th c tng hp t aldehyd salicylic (phng php Perkin), coumarin c dng trong k ngh hng liu, dc phm.
CH = O + OH
+

... ... H
CH2CO CH3CO O_

K2CO3 CH3COO H

CH

. O. H

..

CH

C....O .. . . OH

_ H2O

O O Coumarin

26

 Acid Galic: Acid 3,4,5-trihydroxybenzoic

COOH

HO

OH

OH

Trong thin nhin acid galic ch tn ti di dng ester. Tannin l ngun nguyn liu chnh iu ch acid galic. Acid galic d b decarboxyl ha di tc dng ca nhit.
COOH

to
HO OH OH HO OH

+ CO2 OH

Acid tc dng vi alcol n -propylic to ester n -propylgalat ng dng lm cht bo qun trong thc phm v dc phm.
COOH H2SO4 COOC3H7(n) + H2O HO OH OH Ester n-propylgalat

HO

OH

OH + n-C3H7OH

to

Acid galic rt d b oxy ha. Vi dung dch FeCl3, acid galic cho mu xanh en. Bi tp 1. Vit cng thc cu to v gi tn theo danh php quc t ca cc acid sau: a- Acid lactic b- Acid malic c- Acid tartaric d- Acid mandelic e- Acid citric 2. Hy vit phn ng cc qu trnh tng hp cc acid sau: a- Acid glycolic t acid acetic b- Acid lactic t acetylen c- Acid mandelic t toluen 3. Hy lp s tng hp cc acid sau y theo phn ng Reformatski: a- Acid n-valeric b- Acid ,-dimetylvaleric t ester malonic 4. Khi un nng 10-hydroxydecanoic to thnh hp cht c phn t lng ln (1000-9000). Vit phn ng. 27

Chng 27

HP CHT HAI CHC C NHM CARBONYL

Mc tiu 1. c c tn cc hp cht c hai nhm chc carbonyl 2. Trnh by c ha tnh ca cc hp cht trn 1. Hydroxy aldehyd v hydroxy - ceton 1.1. iu ch

-Hydroxy-ceton c iu ch bng cch kh ha ester bng natri kim loi trong dung mi tr v ha hc.
O NaO ONa H2O 2CH3CH2CH 2COC 2H5+ 4Na CH CH CH C= CH 2CH2CH 3 - 2C 2H5ONa 3 2 2 O OH CH 3CH2CH2C_CHCH 2CH2CH3

Sn phm -hydroxyceton c lin kt -CO-CHOH- l acyloin, v vy phn ng trn gi l phn ng ngng t acyloin. C ch phn ng tng t vi phn ng pinacolin v cng ging phn ng ngng t Claisen. 1.2. Cc phn ng ha hc 1.2.1. Loi nc Trong mi trng acid hoc base, cc -hydroxy-aldehyd hoc -hydroxyceton u c kh nng b loi nc v to aldehyd hoc ceton cha no. Trong mi trng acid:
OH C CH O C O C

H+

+ H2O

C ch:
OH C CH O C

OH C C

OH C

H+

+ OH2 C C

OH C

- H2O

+ C

OH C

+ OH C C C C C

O C + H+

28

Trong mi trng base:

C ch C:

OH C CH

O C

HO-

OH C CH

O C

+ H2O

OH C CH

O C

+ HO

- H2O

OH C C

OC

O C

+ HO

1.2.2. Phn ng oxy ha

-Hydroxy-ceton b oxy ha bi acid periodic HIO4, mch carbon b ct t to acid v aldehyd.

O CH3 C OH CH CH3 + HIO4 O CH3 C OH + O CH3 C H + HIO3

1.2.3 Phn ng to bn acetal v bn cetal vng

HOCH2CH2CH2CHO

H O OH

Ban acetal vong

HOCH2CH2CH2CH2CCH3

O O

CH3 OH

Ban cetal vong

Cc bn acetal vng l nhng cht trung gian tng hp nhiu hp cht hu c.

NaBH 4 H2NOH
1- CH3MgBr 2-

HOCH 2CH2CH2CH2CH2OH HOCH 2CH2CH2CH2CH=NOH OH HOCH 2CH2CH2CH2CHCH 3

Aldoxim

H O OH

H3O+

CH3COCl O

H OCOCH3

Ester

H2Cr2O7

Lacton
29

2. Ceto-aldehyd, ceto-acid, ceto-ester 2.1. Cng thc cu to

R C (CH2)n CHO R C (CH2)n COOH R1 C O Ceto-ester (CH2)n COOR2

O Ceto-aldehyd

O Ceto-aldehyd

2.2. Phng php tng hp 2.2.1. Oxy ha trc tip cc ceton n gin bng selen dioxyd (SeO2)
C6H5 C CH3 O H2O C6H5 C CHO + SeO2 oc O 70% Dioxan , 50

2.2.2. ng dng phn ng ngng t Claisen

Ceton ngng t vi ester thu c -diceton v -ceto-aldehyd:

CH3 C CH3 O
O + HCOOC2H5 NaOC2H5 C2H5OH H3O+

CH3 C OC2H5 O

Base Ether

H3O+

CH3 C CH2 C CH3 O O 85%

O

CHOH

CHO 75%

Hai phn t ester ngng t vi nhau:

Phn ng xy ra trong mi trng base v to thnh ceto -ester.
2 CH3 C OC2H5 O NaOC2H5 H3O+ CH3 C CH2COOC2H5 O

2.3. Tnh cht 2.3.1. Cn bng ceton -enol Nguyn t hydro ca nhm methylen gia 2 nhm carbonyl thng rt linh ng, s chuyn v ca nguyn t hydro ny to nn s cn bng ceton -enol.

30

H O CH3 C CH2 Ceton Dung dch nc Dung dch hexan 84% 8% O C CH3 CH3 O C O C CH Enol 16% 92% CH3

S cn bng ny thng xy ra trong cc hp cht c nhm carbonyl. 2.3.2.Tnh acid ca hp cht c 2 nhm carbonyl Hydro trong nhm methylen ca ceto-aldehyd, ceto-acid, ceto-ester c tnh acid. Di tc dng ca base, carbanion c to ra. Carbanion ny bn vng do s khng nh v ca in tch m.
O C CH2 O C - H+ O C CH O OC CH O C O C CH

-O
C

acid ca mt s hp cht c 2 nhm carbonyl c trnh by di y:

O O O O O O O O Hp cht: NCCH 2COCH 3 CH 3CCH 2CCH 3 CH 3CCH 2COCH 3 CH 3CCHCCH 3 NCCH 2CN CH 3OCCH 2COCH 3 CH3 11 11 13 pKa: 11 9 9

2.3.3. Cc phn ng ha hc a. Hp cht -diceton tham gia chuyn v benzylic. Trong mi trng base mnh, -diceton b chuyn v v to -hydroxyacid.
O C6H5 C O C C6H5 KOH H2O , C2H5OH H3O+ OH O C6H5 C C6H5 C OH 95%

Benzil

Acid benzylic O- O HO C R O C C OC R R O- O C R O C C R + H2O

C ch:
O R C O C R + - OH + OH

-O

O- O C R C R

+ H2O

OH C R

R + - OH

31

Nu hp cht -diceton vng, sau khi chuyn v kiu benzylic s thu c sn phm c vng b hn.
O NaOH O H2O 250oC H3O+ OH 80% COOH

b. Phn ng decarboxyl. Khi c tc dng ca nhit, hp cht -ceto-acid d b decarboxyl ha v to ceton.

O CH3CH2CH2CCHCOOH C2H5 O 50oC H2O, 2gi CH3CH2CH2CCH 2CH2CH3 + CO 2

c. Cc ceto-ester c kh nng ngng t ni phn t v to hp cht vng.

O C NaOH EtOH H3O+ O O 90%

COOEt

32

Chng 28

CARBOHYDRAT

Mc tiu 1. Nm c cch phn loi cht ng, cu to, danh php ca chng. 2. Nu c ha tnh ca glucose. 3. Gii thch c tnh kh ca cht ng. Carbohydrat l hp cht thin nhin c thnh phn chnh l C, H v O. C th xem carbohydrat nh l hp cht m nguyn t carbon b hydrat ha. Cn(H2O)n Phn loi: Tu theo cu trc, tnh cht l hc v ha hc, c 3 loi carbohydrat:

Monosaccharid Oligosaccharid Polysaccharid

1. Monosaccharid Monosaccharid cn gi l ng n, v chng l thnh phn n gin nht ca carbohydrat v khng b thy phn. Monosaccharid c xem nh l sn phm oxy ha khng hon ton ca cc polyalcol c chc aldehyd hoc ceton. Cc monosaccharid c s carbon bng s oxy trong cng thc phn t. 1.1. Danh php Cc carbohydrat u c tip v ng l ose

Monosaccharid c chc aldehyd gi l aldose Monosaccharid c chc ceton gi l cetose

1.1.1. Tn gi monosaccharid ph thuc s oxy, chc aldehyd hoc ceton. Biose, triose, tetrose, pentose, hexose l tn gi chung cc monosaccharid c 2,3,4,5,6 nguyn t oxy (cng l s nguyn t carbon).

33

Tn gi chung cc monosaccharid c chc aldehyd v ceton:

S C v s O 2 3 4 5 6 Cng thc C2H4O2 C3H6O3 C4H8 O4 C5H10O5 C6H12O6 Aldose Aldo-diose Aldo-triose Aldo-tetrose Aldo-pentose Aldo-hexose Cetose Ceto-diose Ceto-triose Ceto-tetrose Ceto-pentose Ceto-hexose

1.1.2. Monosaccharid c tn ring cho mi cht ty thuc vo v tr cc nhm OH. V d: Glucose, Fructose, Mannose, Galactose, Ribose, Arabinose... 1.1.3. Tn gi monosaccharid ty thuc vo ng phn quang hc

Danh php D v L
Monosaccharid dng mch thng c nhm OH nguyn t carbon khng i xng xa nht so vi nhm carbonyl c cu hnh ging D -Aldehyd glyceric hoc ging L -Aldehyd glyceric th monosaccharid thuc dy D hoc dy L.
CHO H C OH CHO HO C H

CH2OH D- Aldehyd glyceric (R-Aldehyd glyceric)

CH2OH L- Aldehyd glyceric (S-Aldehyd glyceric)

Cc ng phn dy D ca monosaccharid:
CHO D- Aldehyd glyceric H C OH CH2OH CHO HO C H H C OH CH2OH D- Threose (Thr)

CHO C OH H H C OH CH2OH D-Erythrose (Ery)

34

CHO H H H C C C OH OH OH HO H H

CHO C C C H OH OH H HO H

CHO C C C OH H OH HO HO H

CHO C C C H H OH

CH2OH

CH2OH

CH2OH

CH2OH

D-Ribose (Rib)

D-Arabinose (Ara)

D-Xylose (Xyl)

D-Lixose (Lix)

CHO H H H H C C C C OH HO OH OH OH H H H

CHO C C C C H OH OH H H H OH HO

CHO C C C C OH H OH OH HO HO H H

CHO C C C C H H OH H H H

CHO C C C C OH OH H OH HO H HO H

CHO C C C C H H OH H HO H OH HO

CHO C C C C OH H H OH HO HO HO H

CHO C C C C H H H OH

OH HO

CH2OH

CH 2OH

CH2OH

CH2OH

CH 2OH

CH 2OH

CH2OH

CH2OH

D-Allose (All)

D-Altrose D-Glucose D-Mannose (Alt) (Glu) (Man)

D-Gulose (Gul)

D-Idose D-Galactose (Ido) (Gal)

D-Talose (Tal)

1.1.4. Monosaccharid cu to vng c tn gi theo vng Cc monosaccharid c cc vng tng t vng pyran v vng furan.
O

Furan
O

pyran

Cho nn cc monosaccharid dng vng c tn gi pyranose v furanose. V d: Glucopyranose (vng 6 cnh) Fructopyranose (vng 6 cnh) Mannopyranose (vng 6 cnh) Galactopyranose (vng 6 cnh)
1 CHO H HO HO C C OH H H H HO HO H C C C C C CH2 OH 1 OH OH H H

Glucofuranose (vng 5 cnh) Fructofuranose (vng 5 cnh) Mannofuranose(vng 5 cnh) Galatofuranose (vng 5 cnh)

C H H 5C O H CH2 OH

CH2 OH OH 5 O H H 1 OH 1H H OH H OH

CH2 OH OH 5 O OH H OH 1 H 1 H H H OH

D-Galactose

-D-Galactopyranose

-D-Galactopyranose

-D-Galactopyranose

35

 Danh php Cahn -Ingol-Prelog (danh php R,S).

D(+)-Glucose v L (-)-Glucose c gi theo danh php R, S nh sau:
1CHO 2
1CHO 2

H C OH HO 3 C H H 4C H
5

H C OH HO C H H 4C
HO
5C 3

OH

OH H

C OH

6 CH2OH

6 CH2OH

D (+)Glucose (2R,3S,4R,5R)-Pentahydroxy-2,3,4,5.6-hexana

L (-)-Glucose

(2R,3S,4R,5S)-Pentahydroxy-2,3,4,5.6-hexana

t s dng danh php R, S gi tn monosaccharid. Ch : Mt s monosaccharid b loi nguyn t oxy (deoxy) th gi tn chnh monosaccharid v thm tip u ng deoxy.
1CHO 2 1CHO 2

H C OH HO 3 C H H C H
5 4

H C H HO C H H C H
5 4 3

H 1C OH H C H HO C H H C H
5 4 3 2

OH

OH

C OH

C OH

OH

6 CH2OH

6 CH2OH

CH2 OH OH 5 O H H OH H 1 H OH H H

OH CH OH 2 H HO H

H H

O H OH

D (+)Glucose

2-Deoxy-D Glucose

6 CH2OH

2-Deoxy-D- Glucopyranose

1.2. Cu to 1.2.1. Cu to mch thng ca monosaccharid Cng thc phn t C6H12O6 c cc cng thc cu to nh sau:
OH 5 1 O 4 3 2 HOCH2 CH CH C CH C H OH OH H OH OH OH HOCH2 CH CH CH CH C 2 1 OH OH
6 5 4 3

O H

OH HOCH 2
6

CH CH C C CH2OH OH OH H O

3 2

Glucose

Mannose

Fructose

1.2.2. Cu to mch vng ca monosaccharid Monosaccharid tn ti dng vng 6 cnh, 5 cnh. Trong vng c nguyn t oxy.

36

 Cng thc chiu Fischer:

H H HO H H C OH 2 C OH C
3 1

C 4 OH 5 C 6 CH2OH

HO C H 2 H C OH HO C H
3

CH2OH
O HO C
2 3

HO C H

H C4 OH 5 H C CH2OH
6

H C4 OH H C5
6 CH2OH

-D-Glucopyranose I
6

-D-Glucopyranose -D-Fructofuranose II III

Cng thc chiu Haworth: Vng phng

5

CH2OH H OH

O H
H
1

CH2OH H OH

H H
5

O H

H H OH H -D-Glucopyranose -D-Mannopyranose -D-Fructopyranose

OH

OH

OH

OH 1 OH

H H

O CH OH 2
OH 2 OH H

CH2OH O
5

OH OH 2 CH2OH
1

OH OH

H OH

H -D-Fructofuranose

Cng thc vng ca monosaccharid l dng bn acetal hoc bn cetal vng. Bn acetal vng c to thnh do s tng tc gia chc alcol ti carbon s 5 v chc aldehyd hoc ceton.

Cng thc cu dng (Reeves):

Glucose c cng thc cu dng gh bn vng
H HO HO H H HO CH 2OH O H OH
1

D-Glucopyranose

Cc cu dng lp th ca vng pyranose: c 8 cu dng khc nhau

O
C1
O
B1 1B

O
1C
O

O
B2
O O
B3 3B

O
2B

Theo Reeves cu dng C1 l bn nht v c nhiu OH c lin kt e (equaterial). Cc monosaccharid vng 6 cnh thng c cu dng gh.

37

Vng 6 cnh (pyranose) ca monosaccharid tn ti 2 cu dng gh C1 v 1C nh sau:

4 5 3 2
1

O
4

5 O 3 2

Dang C1

Dang 1C

Mi monosaccharid vng 6 cnh u c kh nng tn ti theo 2 loi cu dng trn. V d: -D-glucopyranose c th c 2 cu dng nh sau:
H HO HO H H HO CH2OH O H OH
1

CH2OH H
H

H
1

H OH H

OH O OH

OH

Dang C1 D-Glucopyranose

Dang 1C D-Glucopyranose

Dng C1, -D-glucopyranose cc nhm OH v CH2OH c v tr equatorial (e) (tr nhm OH carbon s 1 c v tr axial a). Dng 1C, -D-glucopyranose cc nhm OH v CH2OH c v tr axial (a) tr nhm OH carbon s 1 c v tr equatorial e. Dng C1 -D-glucopyranose bn hn v cc nhm OH v CH2OH c nng lng thp hn dng 1C -D-glucopyranose. Ch : Trong cc monosaccharid dng vng, glucose c cc nhm OH v CH2OH lun v tr equatorial (tr nhm OH v tri s 1). Cc monosaccharid khc th cc nhm c v tr ty thuc vo cc cht c th.
6 HOCH2 O 5 HO 4 OH H HO H 3 2 1 H OH H H -D-Mannopyranose OH 6 HOCH2 O 5 4 H H HO 3 H H 2 1 HO OH H -D-Galactopyranose

1.3. ng phn ca monosaccharid Cc monosaccharid cng cng thc phn t c cc loi ng phn sau:

38

1.3.1. ng phn chc Glucose v fructose l nhng ng phn chc vi nhau. 1.3.2. ng phn do v tr ca cc nhm OH alcol Cc aldohexose c cc ng phn dy D mch thng do v tr nhm-OH
CHO H C H H H C OH OH HO H H H CHO C C H OH HO H H CHO H C C OH H HO HO H H CHO C C H OH H H HO H CHO C C OH OH HO H HO H CHO C C H OH CHO H C HO HO H C OH H HO HO HO H CHO C C H H

C OH C OH CH2 OH

C OH C OH CH2 OH

C OH C OH CH2 OH

C OH C OH CH2 OH

C H C OH CH2 OH

C H C OH CH2 OH

C H C OH CH2 OH

C H C OH CH2 OH

D-Allose I (All)

D-Altrose II (Alt)

D-Glucose III (-Glc)

D-Mannose IV (Man)

D-Gulose V (Gul)

D-Idose VI (Ido)

D-Galactose VII (Gal)

D-Talose VIII (Tal)

1.3.3. ng phn quang hc Monosaccharid c nguyn t carbon khng i xng nn c ng phn quang hc. S ng phn quang hc ty thuc vo s carbon khng i xng v cu to phn t. Cc aldohexose dng thng c 16 ng phn quang hc. Cetohexose c 8 ng phn quang hc. Monosaccharid dng mch vng c s carbon khng i xng nhiu hn dng thng tng ng nn s ng phn quang hc dng vng tng ln. ng phn quang hc quyt nh kh nng tc dng sinh hc ca monosaccharid. 1.3.4. ng phn epimer Cc monosaccharid cng cng thc phn t c cu hnh ca cng mt carbon bt i xng (k t chc aldehyd) hon ton khc nhau th gi l ng phn epimer. Glucose, mannose, fructose l cc ng phn epimer vi nhau. V d: 4 cp ng phn ca aldohexose dy D l 4 cp epimer. Tng t c 4 cp ca dy L hoc cp ng phn epimer D (+)-erythro v D (+)-threo.
CHO H C2 OH HO C H H C H OH C OH CH2OH D-Glucose 1 1CHO HO C2 H HO C H H C H OH C OH CH2OH D-Mannose HO H 1CH OH 2 2C O C H OH Gio ng nhau C OH CH2OH D- Fructose H C

Kha c nhau

39

1.3.5. ng phn anomer Trong cng thc chiu mch thng Fischer ca phn t D -glucose, nguyn t carbon s 1 thuc chc aldehyd l carbon i xng. Khi D -glucose dng vng, carbon s 1 mang chc OH v tr thnh carbon khng i xng. Nguyn t carbon s 1 gi l carbon anomer. Nhm OH ti carbon anomer c to thnh do tng tc gia nhm OH alcol ti carbon s 5 v chc aldehyd (ging phn ng to bn acetal gia aldehyd v alcol). Nhm OH ny gi l nhm OH bn acetal c tnh cht khc vi nhng chc alcol khc. Trong cng thc chiu vng (Fischer) nhm OH bn acetal bn phi vng (cng pha vi vng) gi l -D-glucose (cng thc I), nhm OH bn tri vng (khc pha vi vng) gi l -D-glucose (cng thc II). -D-glucose v -D-glucose l 2 ng phn anomer vi nhau.
H C OH HO 3 C H H C H
5 6 4 1CHO 2

H C OH 2 H C OH HO C H
6 3

1 HO C H 2 3

H C OH

OH

C OH CH2OH

H C 4 OH 5 H C CH2OH

HO C H

H C4 OH 5 H C CH2OH
6

D-Glucose

-D-Glucopyranose I

-D-Glucopyranose II

Biu din cc ng phn anomer theo cng thc chiu Haworth:

Nhm OH bn acetal v pha di vng l ng phn -D-glucose. Nhm OH bn acetal pha trn vng l ng phn -D-glucose.
Cch biu din cc nhm OH t cng thc chiu Fischer sang cng thc chiu Haworth:

Trn cng thc chiu Fischer nhm OH bn acetal bn phi so vi mch thng ng ca carbon. Trn cng thc chiu Haworth nhm OH bn acetal pha di ca vng. Nhm OH bn acetal bn tri so vi mch thng ng ca carbon th trn cng thc chiu Haworth pha trn ca vng.
5

CH2OH

H OH

O H
H OH
1

CH2OH H OH

O OH
H OH
1

OH H

OH

-D-Glucopyranose

OH H

-D-Glucopyranose

Trn cng thc -D-glucopyranose 2 nhm OH ti carbon 1 v 2 c v tr cis v trn cng thc -D-glucopyranose 2 nhm OH ti carbon 1 v 2 c v tr trans.

40

Cc ng phn anomer c th chuyn ha ln cho nhau. Trong dung dch glucose, khi cc ng phn v c thit lp s cn bng th c hn hp gm 36% ng phn v 64% ng phn . Biu din cc ng phn anomer ca monosaccharid theo cng thc cu dng:
H HO HO H H HO CH2OH O H H
1

HO HO H

H HO

CH2OH O H
1

OH

OH

D-Glucopyranose

D-Glucopyranose

ng phn c nhm OH bn acetal v tr axial (a). ng phn c nhm OH bn acetal v tr equatorial (e).

Hin tng bi quay (Mutarotation).

Tinh th -D-(+)-glucose c nhit nng chy 146C. Khi ha tan vo nc c dung dch c quay cc +112. Mt thi gian sau quay cc gim dn v t n gi tr khng i +52,7. Mt khc tinh th -D(+)-glucose kt tinh nhit 98C c nhit nng chy 150C, khi ha tan vo nc c dung dch c quay cc +19 v dn dn tng ln n gi tr khng i + 52,7.

Gii thch hin tng bi quay:

H HO HO H CH2 OH H HO H H O H OH CH2 OH H H HO H

+ H+

HO HO

+ OH
H OH

M vong

H CH OH 2 H H HO H

HO HO

OH

H C
OH

D-Glucopyranose
H HO HO H H HO CH2 OH O H H CH2 OH H H HO H H HO HO O H+ OH H CH OH 2 HO HO H H HO H

Quay
OH

OH

-H+

OH

ong vong

C H

D-Glucopyranose

S thay i gc quay cc t n gi tr cn bng ca mi loi ng phn ny gi l s bi quay (mutarotation). Tt c cc monosaccharid u c hin tng bi quay (tr mt vi cetose). Hin tng bi quay l nguyn nhn to ra cc ng phn anomer (s anomer ha) trong cc monosaccharid. 41

H C OH H C OH H
5 4C 3

1 CHO 2

H C H HO C H H C
5 4 3

1CHO 2

HO 1C H H C H HO 3 C H H 4C
2

CH2OH O H H H

OH H

OH

OH

CH2OH

D-Ribose (Rib)

CH2OH

2-Deoxy- D-Ribose

H OH CH2OH 2-Deoxy-D-ribofuranose

1.4. Tnh cht l hc ca monosaccharid Monosaccarid dng rn, kt tinh c, khi chng ct b phn hy, khng mu, d tan trong nc, rt kh tan trong ether hay cloroform, trung tnh, c v ngt khc nhau, c tnh quang hot []D. C hin tng bi quay v c cn bng ng 1.5. Tnh cht ha hc ca monosaccharid 1.5.1. Phn ng oxy ha Ging nh cc hp cht -hydroxycarbonyl (-oxycarbonyl), monosaccharid rt d b oxy ha v to cc acid tng ng bi cc tc nhn oxy ha nh thuc th Fehling Cu (OH)2, thuc th Tollens Ag (NH3)2NO3.
COO
H HO HO H CH2 OH H H
-

H C OH
O

HO C H
OH

HO

+ 2 Cu(OH)2
H

H C H

OH

C OH CH2 OH

+ Cu2O

+ 2H2O

Mau o gach
COOH

H HO HO

CH2 OH H H H

H C OH
O OH

HO C H

+ 2Ag+ + H2O

H C H

OH

HO

C OH CH2 OH

+ 2Ag

D-Glucose

Acid Gluconic

Cc phn ng ny dng nh lng hm lng ng trong nc tiu v mu. Cc monosaccharid b oxy ha bi thuc th Fehling v Tollens gi l ng kh Fructose khng b oxy ha bi cc thuc th trn. Mt s cht oxy ha khc c th oxy ha chc alcol bc 1 v to thnh diacid.

42

H CH2OH O HO H H HO H HO H

COOH H C OH OH HO C H

COOH OH CH2OH O H H H HO H HO H H C OH OH HO C H

+ 3[O]

H C H

- H 2O

OH C OH COOH

+ 3[O] HO C H - H 2O
H C OH COOH

D-Glucose

Acid Saccharic

D-Glactose

Acid Galactosaccharic Acid Galactaric

Acid periodic tc dng vi monosaccharid, mch carbon b ct t v to dialdehyd.

H
1 2

C OH O + HIO 4

H C OH
2

HO C H H C OH H C 5 H C
6 4 3

CHO O + HCOOH + HIO 3 CHO C CH2OH

OH

CH2OH

D-Glucose
H HO H OH

Cat mach carbon

H
H O O CH 3

H O

CHO
H
O O CH 3

C
O

H C H O CH3 O C H H C H CHO

+ HIO4

- HIO3

C
H

Metyl -D-2-Deoxyribopyranosid
1.5.2. Phn ng kh

Kh ha nhm carbonyl ca monosaccharid bng hn hng natri trong H2SO4 long, natrihydrid bo (NaBH4) hoc bng H2 c xc tc th to thnh cc polyalcol no. Polyalcol to thnh c tn gi nh monosaccharid tng ng nhng thay tip v ng ose bng it hoc itol.
CHO H C OH OH H CH2OH H C OH CH2OH H C OH

H HO HO

CH2OH O H H H OH

HO C H
H C H OH C OH CH2OH

H2-Ni

HO C H
H C H OH C OH CH2OH

[H]

HO C H
H C H OH C OH CHO

D-Glucose

D-Sorbit , D-Glucitol

L-Glucose

43

CHO HO C HO C H H C C H H OH OH

CH2OH

NaBH 4

HO C HO C H H C C

H H OH OH

CH2OH

NaBH 4

HO H H

C O C H C C OH OH

CH2OH

CH2OH

CH2OH

D - Mannose
CH = O
NaBH4

D - Mannit , Mannitol
CH2OH OH OH CH2OH D-manitol CH2OH C O OH OH CH2OH D-fructose

D - Fructose
CH2OH OH NaBH4 OH OH CH2OH D-sorbitol CH = O OH HO OH OH CH2OH D-glucose

HO HO

OH OH CH2OH D-manose

HO HO

NaBH4

HO

NaBH4

HO

1.5.3. Phn ng epimer ha Trong mi trng kim long hoc pyridin, mi monosaccharid nh Dglucose, D-Mannose, D-Fructose b epimer ha v to thnh hn hp 3 epimer. S epimer ha xy ra nh sau:

Trong mi trng kim long

CH O H H H C OH CH O

HO C
C

H
OH

C OH CH 2 OH

CHOH C OH HO C H

HO H H

C H

HO C
C

H
OH

D-Glucose

H C OH H C OH CH2OH
CH2 OH C O

C OH CH 2 OH

D- Mannose

HO C
H H C

H
OH

Gio ng nhau D-Fructose

C OH CH 2 OH

S epimer ha cng c kh nng xy ra trong iu kin khi monosaccharid tip xc vi dung dch brom, pyridin v tip theo l qu trnh kh ha. 44

CHO
H H H C OH

COOH
H C OH Br2+H2O HO C
H C H

COOH
HO C H Pyridin HO C
H H C

O C
HO C H -H2O HO C
H C C OH CH 2 OH H HO

CHO
C H C

HO C
C

H
OH

H
OH

H
OH

O+Na(Hg), CO

HO C
H H

H
OH

C OH CH2 OH

C OH CH2 OH

C OH CH2 OH

C OH CH2 OH

D-Glucose

Hn h p epimer acid gluconic

Gluconolacton

D- Mannose

Ch : Trong mi trng kim c mch carbon b ct t v to thnh cc cht c mch carbon ngn hn. V d D -Fructose trong mi trng kim c to thnh hn hp gm 1,3-dioxyceton, glycerin, aldehyd glycolic v aldehyd formic. 1.5.4. Phn ng loi nc - dehydrat ha Khi un vi acid, cc pentose b loi 3 phn t H2O to furfural.
C5H10O5 Pentose un no ng Acid CHO O Furfurol , Furfural + 3 H2 O

Phn ng Selivanop Di tc dng ca HCl, cc pentose, hexose to ra furfural v chuyn ha nhanh thnh hydroxymethylfurfural, n ngng t tip vi resorcinol to phm vt mu anh o (phn ng ny dng phn bit aldose v cetose).
CH2OH C O H C OH HO C H H C OH CH2OH HO CH2OH OH

CH2OH

D-fructose

D-fructofuranose

-3H2O Nhanh
CH2OH 4-Hydroxymethylenfurfural O CH=O

HCl

Resorcinol OH

OH

ngng tu

Sa n pha m co ma u o anh a o

H HO HO H H

CH2OH H OH H

O OH

CHO H C OH HO C H H C OH H C OH CH2OH

HCl Cham

-3 H2O

-D-glucose

D-glucose

1.5.5. Phn ng to osazon 45

Monosaccharid tc dng vi 3 mol phenylhydrazin to phn t osazon.

CHO H C OH H C N NH C6H5 HO C H H C H OH C OH CH2OH CH N NH C6H5
H

HO C H
H C H OH C OH CH2OH

+ 3C6H5-NH-NH2 - C6H5-NH2; -2 H2O; -NH3

CH2OH H
H

HO HO

OH

D-Glucose

D-Glucozazon

CH N NH C6H5 N NH C6H5

Cc ng phn epimer u cho cng mt loi osazon. Osazon l cht kt tinh c hnh th xc nh, c th dng nhn bit cc monose Cc ng phn epimer ca aldose v cetose c cu hnh *C3,*C4,*C5 ging nhau, chng c cng 1 osazon v khi to osazon khng cn carbon bt i xng ti C2. V d: D-glucose, D-mannose v D-fructose c chung mt osazon. Theo Fischer, osazon bn l do to "phc cng cua". Bng ph hng ngoi (IR), cho thy phn t osazon bn v tn ti h lin hp v c lin kt hydro ni phn t (C - O... H - N).
Theo Fischer : Theo IR :

N CH

N C

H N N H

.N H . . . . . . .N. . . CH ..N C
N...

CH2OH

. .H O. (HOCH)2 CH2OH
C

Osazon cu a D-glucose

1.5.6. Phn ng to acetal vng v cetal vng Monosaccharid c 2 nhm OH cnh nhau v tr cis ngng t vi ceton to cetal
CH3 cis OHCH2OH O H H H HO
H OH HO

CH3 + 2 H3C C O CH3

C O

O CH2OH O H H H CH3 CH3 O O H + 2H 2O

cis

46

1.5.7. Phn ng to glycosid Alcol hoc phenol tc dng vi nhm OH bn acetal ca monosaccharid to thnh hp cht alkyl (hoc aryl) glycosid.
H CH OH 2 O HO H H H HO + ROH OH HO H -glucose H CH OH 2 O HO H H HO OH H H -glucose H HO HO CH2OH O H H + H2 O Lie n ke t glycosid

HCl kho

OH H O R Alkyl -glucosid H CH OH Lie n ke t glycosid 2 O HO H O R H HO + H 2O OH H H Alkyl -glucosid

OH + ROH HCl kho

Glycosid to thnh t glucose th gi l glucosid; t mannose th gi l mannosid; t galactose gi l galactosid; t fructose gi l fructosid.
H CH OH 2 O HO H H HO H OH H OHCH OH 2 O H H OCH3 H HO OH H H Methyl -galactosid H CH OH 2 O HO OH OCH3 H HO H H H Methyl -Mannosid

O CH3

Methyl -glucosid

Cc glycosid bn vng trong mi trng kim nhng rt d phn ly thnh monosaccharid v alcol trong mi trng acid v di tc dng ca enzym.
H HO HO CH2OH O H H H OH H H CH OH 2 O HO H H HO H OH H -glucose

O R

+ H2 O

Acid hoc men

OH

+ ROH

Alkyl -glucosid

Cc enzym c tc dng thy phn rt chn lc. V d: Enzym maltase ch thy phn -glycosid. Enzym tc dng nh ha ch tc dng vi -glycosid. Lin kt glycosid cn c to thnh gia cc phn t monosaccharid vi nhau cho ra oligosaccharid (di, tri, tetraose) v polysaccharid. Cc glycosid khng c hin tng bi quay (Mutarotation) v khng tc dng vi thuc th Fehling v thuc th Tollens.

47

1.5.8. Phn ng to ether Glucosid tc dng vi dimethylsulfat hoc methyliodid trong mi trng kim to thnh methyl tetra o -methyl glucosid. V d: Khi cho Methyl -D-glucosid tc dng vi methyliodid hoc dimethylsulfat v NaOH to hp cht c chc ether l methyl -2,3,4,6-tetra-Omethyl-D- glucosid.
H HO HO H CH2OH H HO H Methyl - D-glucosid H O OCH3 + 4 (CH 3O) 2SO 2NaOH , - 4 CH 3OSO 3H H CH OCH 2 3 O CH3O H H CH3O CH3O H H

OCH3

Methyl -2,3,4,6-tetra-o-methyl D-glucosid

Hp cht methyl -2,3,4,6-tetra-O-methyl-D-glucosid tc dng vi H2O trong mi trng acid th ch c lin kt osid O-CH3 ti nguyn t carbon s 1 b thy phn. Cc nhm O -CH3 khc hon ton khng b thy phn (v chng l lin kt ether).
H CH2OCH 3 O CH3O H H CH3O CH3O H H CH2OCH 3 OCH3 + H 2O , H + - CH 3OH CH3O CH3O H CH3O H H O OH H

H Methyl -2,3,4,6-tetra-o-methyl D-glucosid

-2,3,4,6-tetra-o-methyl D-glucose

CHO
H CH3O C OCH3 C H

HO H CH3O

C H C OCH3 C H O

H C OCH3 H C OH CH2OCH3

H C OCH3 H C CH2OCH3

2,3,4,6-Tetra-O-methyl-D-Glucose

2,3,4,6-Tetra-O-methyl- -D-Glucopyranose

1.5.9. Phn ng to ester Aldohexose b acetyl ha (to ester) bi anhydrid acetic to hp cht acetylpyranose. V d: -D-Glucose tc dng vi anhydrid acetic to hp cht -D pentaacetylglucose. 48

H CH OH 2 HO HO H H

H CH2OAc O OH
1

+5 (Ac) 2O - 5CH 3COOH

AcO AcO

O OAc

HO H -D-glucose

1 AcO H H - D-Pentaacetylglucose

Khi cho -D-pentaacetylglucose tc dng HBr trong mi trng acid acetic th ch c chc ester ti carbon s 1 tham gia phn ng.
H AcO AcO H CH2OAc H AcO H O OAc
1

H + HBr - CH 3COOH AcO AcO

CH2OAc H H AcO H

O H
1

Br

1,2,3,4,6-Penta-acetyl- -D-Glucopyranose

1-Brom-2,3,4,6-tetra-acetyl- - D-Glucopyranose

Phn ng gia 1-brom-2,3,4,6-tetraacetyl--D-glucose vi phenolat hoc alcolat v sau phn ng vi alcol methylic trong amoniac (thc hin phn ng trao i ester) s thu c phenyl --D-glucosid hoc alkyl --D-glucosid.
H AcO AcO H CH2OAc H AcO H O H AcO H ROAcO -Br H CH2OAc H AcO H O OR
1

H + 4CH3OH (NH3) - 4CH3COOCH3 HO HO

CH2OH H H HO H

O OR
1

Br

1-Brom-2,3,4,6-tetra-acetyl- D-Glucopyranose

Phan ng trao o i ester

Alkyl-- D-Glucopyranosid

Trong thin nhin thng gp mt s glucosid nh sau:

H HO HO H CH2OH H HO H H O O
1

CH2OH H H HO H

CHO

HO HO

O O
1

CH=CH CH2OH

CH3O

CH3O

Vanilin- - D-Glucopyranosid
CH2OH HO HO O O HO
1

Coniferin-- D-Glucopyranosid

CH2

HO HO

C6H5 O C H CN

Amygdalin

HO

49

1.5.10. Phn ng to phc mu xanh vi Cu (OH)2 Cc 3,4-diol ca 2 monosaccharid c th quay ngc nhau to phc ng
4

HO HO

CH2OH H

O
1

OH

Cu (OH)2

OH H1

OH O

H O
4

H O

Cu

O H

H O

CH2OH H

O OH
1

OH

OH

HOH2C

H phc ong

1.5.11. Phn ng tng mch carbon Khi cho cc aldose tc dng vi HCN, thy phn, to lacton v sau kh ha th mch carbon ca aldose c tng ln. V d: T aldopentose s to thnh aldohexose.
CN H C OH
HO C H

COOH H C OH

C O H C OH

CHO H C OH O Na (Hg) CO2

HO H C H C OH

CHO
HO C H H C OH H C OH

HO C H + H 2O HO C H H C OH H+ H C OH - H 2O H C OH H C OH H C OH H C

H C OH

+ HCN

CH2OH

CH2OH

CH2OH

CH2OH

Aldopentose

CH2OH

CN HO C H
HO

COOH HO C H
HO H C H C OH

+ H 2O H C OH H+
H C OH

C H

C O HO C H
HO C H C OH

CHO HO C H O Na (Hg) HO C H CO2

H C OH H C OH

H C OH

- H 2O

CH2OH Cyanhydrin

CH2OH Acid Gluconic

H C

Gluconolacton

CH2OH

CH2OH Aldohexose

1.5.12. Phn ng gim mch carbon C th gim mch carbon ca aldose theo cc bc sau:

Oxy ha aldose bng dung dch brom. Chuyn ha thnh mui calci. Oxy ha mui calci bng H2O2 vi s c mt ca mui st Fe3+, aldose to thnh c s carbon gim mt nguyn t.

50

CHO H C OH
HO H C H C OH Br2 + H 2O

COOH H C OH
HO H C H C OH

Ca COO- 2 H C OH + CaCO 3
HO H C H C OH

CHO + H 2O2
HO H C H

H C OH

H C OH

H C OH

Fe 3+

H C OH

C OH + CO 3

2-

CH2OH Aldohexose

CH2OH Acid Gluconic

CH2OH Calci gluconat

CH2OH Aldopentose

Cc phn ng to glycosid, to ether, ester, tng, gim mch carbon l nhng phn ng quan trng xc nh cu to cu monosaccharid. 1.5.13. Phn ng ln men Ln men l qu trnh sinh ha rt phc tp xy ra do enzym tc dng ln c cht, ngoi sn phm chnh cn c sn phm ph:
Le n men R u Le n men Lactic 2 C2H5OH + 2 CO2

D-glucose

C6H12O6

2CH3CHOHCO 2H OH Le n men Citric HOOCCH2CCH2COOH + H2O COOH Le n men Butyric CH3CH2CH2CO2H+ 2 CO2 + 2 H2 Le n men CH3COCH 3 + C4H9OH + C2H5OH + 3 CO2 + H 2 Aceton-Butylic

2. Oligosaccharid Oligosaccharid l nhng hp cht c to thnh do cc monosaccharid kt hp vi nhau bng lin kt glycosid. Oligosaccharid (oligo: mt vi) b thy phn cho mt vi monosaccharid. Trong t nhin c: maltose, cellobiose, saccharose (ng ma), lactose (ng sa), melibiose, gentiobiose, manniotriose, raffinose, gentianose. n gin v quan trng nht l cc disaccharid. 2.1. Disaccharid Disaccharid c cng thc phn t: C12H22O11. Thy phn disaccharid to ra 2 phn t monosaccharid.
C12H22O11 + H2O C6H12O6 + C6H12O6

C th chia disaccharid thnh 2 loi: ng kh v ng khng kh. 51

2.1.1. Disaccharid c tnh kh: Maltose, cellobiose, lactose ng kh l ng cn nhm OH bn acetal c th chuyn v dng aldehyd.

(+) Maltose hay [4-O-(-D-glucopyranosyl)]-D-Glucopyranose.

Thy phn maltose to ra 2 phn t -glucose. Biu din cng thc cu to ca maltose di dng cng thc chiu Fischer, cng thc chiu Haworth, cng thc cu dng nh sau:
H HO HO
4

CH2OH H H
2

OH H O D- Glucopyranose

H 1 H
4

CH2OH H H H
2

HO

D- Glucopyranose H
1

LK glycosid

OH

OH

HO ba n acetal

Co ng th c ca u da ng cu a (+) Maltose

Maltose do 2 phn t -D-glucose to thnh. Lin kt glycosid trong phn t maltose do nhm OH bn acetal ca phn t -glucose th nht tc dng vi nhm OH alcol v tr s 4 ca phn t -D- glucose th 2. Trong phn t (+)maltose cn c nhm OH bn acetal. Nhm OH bn acetal ny c th chuyn v chc aldehyd. Vy (+)maltose tc dng vi thuc th Fehling v thuc th Tollens. (+)Maltose l mt ng kh. Maltose tc dng vi phenylhydrazin to osazon C12H20O9 (=N-NH-C6H5).
H HO HO
4

CH2OH H H H
2

O OH

H 1 H O
4

Osazon cua (+) maltose CH2OH H C

2

OH CH N NH C6H5 N NH C6H5
1

HO H

Maltose tc dng vi dung dch nc brom to acid maltobionic (C11H21O10)COOH

H HO HO H
4

CH2OH H H
2

O OH

H 1 H
O
4

CH2OH H H
2

Acid maltobionic

HO

H C

OH COOH
1

OH

(+)-Maltose cng tn ti anomer v . Di tc dng ca enzym maltase hoc thy phn acid, maltose chuyn ha hon ton thnh 2 phn t -(+)-D- glucose. Phn ng chng minh (+)matose l [4-O-(-D-glucopyranosyl)-D-glucopyranose: 52

H HO HO H

CH2OH H H

OH

H H O H

CH2OH H H

O H OH OH

Oxy ho a

HO (+) Maltose , Anomer + Br 2 , H 2O H HO HO H CH2OH H H O

Acid D-maltobionic

H H CH2OH OH OH H O H C HO H

COOH OH

Methyl hoa

H CH3O CH3O

CH2OCH3 H H

(CH 3)2SO 4 , NaOH

O

H H CH2OCH3 OCH 3 OCH3 H H O H C CH3O COOH OCH3 Acid octa-O-methyl-D-maltobionic H

Thu y pha n
H CH3O CH3O CH2OCH3 O H H H OCH3 H OH

H2O , H +

COOH

H C OCH3 CH3O C H
H C OH

( Anomer ) 2,3,4,6-Tetra-O-methyl-D-glucopyranose

H C OCH3 CH2OCH3 Acid-2,3,5,6-Tetra-O-methyl-D-gluconic

Enzym maltase l enzym chn lc c trng ch thy phn vi lin kt -glycosid.

Cellobiose hay [4-O-(-D-glucopyranosyl)]-D-glucopyranose.

Cellobiose l sn phm phn hy ca cellulose. Cellobiose thuc loi ng kh. Hai phn t -D-glucose lin kt vi nhau ti v tr 1 v to phn t cellobiose c lin kt 1,4--glycosid.
H HO 4 HO
6 CH OH 2 5 3

LK glycosid O
1

H
3 4

HO O H

OH H
1

H H D- Glucopyranose

OH

5 6 CH

OH

2OH

D- Glucopyranose

Co ng th c ca u da ng cu a (+) Cellobiose ( anomer)

53

Lactose hay [4-(-D-galactopyranosido)-D-glucopyranose: ng sa.

Thy phn lactose to ra phn t -D-galactose v D -glucose. Lactose cng ging phn t maltose c 2 dng ng phn v .
OH 6 CH OH 2 H HO
4 5

LK glycosid O HO O
4

H
3

H 3 H 1 2 OH H H D- Galactopyranose

H
5

OH H
1

OH

H D- Glucopyranose

6 CH2OH

Cong thc cau dang cua Lactose ( anomer)

Tnh cht: Cc loi ng kh u tham gia cc phn ng nh cc aldose:

H OH H CH 2 OH H H H O OH OH H HO H H C=N NHC6 H 5 C=N NHC6 H 5 C H C OH C OH CH 2 OH OH H CH 2 OH H H H O OH OH H COOOH H HO H C OH C H C OH C OH CH 2 OH

HO

HO

D (+)-Galactose

D -Glucosazon

D (+)-Galactose

D -(-) - Acid gluconic

OH H HO

CH 2 OH H H

Thuy phan
O O OH H H HO

NNHC6 H5 Thuy phan OH CH 2 OH C=NNHC6 H5 O H C H H H O H OH HO CH 2 OH OH H H

H HO H H H

OH

COOH

CH 2 OH

OH

Lactosazon

Acid Lactobionic

+ C6 H5NHNH2 OH H HO H CH2 OH H H H O O OH H H HO H H OH O H

+ Br2 ,H2 O

OH

CH2 OH

Lactose ( -Anomer )

Lactose c ng phn v l do s chuyn quay. S chuyn quay ca lactose c th minh ha nh sau:

54

OH

CH2OH

O O OH

OH HO

ban acetal OH
OH

CH2OH

O O OH

OH HO CH2OH

chuyen quay
+ OH2

HO

O CH2OH (dang) OH OH

H + HO
OH H HO

OH

OH

CH2OH

O O OH

HO CH2OH O (dang )

CH2OH

O O OH

OH HO CH2OH

+ OH2 H

HO

OH

2.2. Disaccharid khng kh. ng khng kh ng khng kh l ng khng cn nhm OH bn acetal chuyn thnh aldehyd. Do ng khng kh khng tc dng vi thuc th Fehling v thuc th Tollens. 2.2.1. Saccharose hay -Glucopyranosido--D-fructofuranosid: ng ma. Saccharose c gc quay cc (+),c trong ng ma, ng c ci. Saccharose c cng thc phn t C12H22O11. Khc vi cc disaccharid khc, saccharose khng tc dng vi cc thuc th Tollens v Fehling cho nn saccharose l ng khng kh. (+)-Saccharose khng to osazon, khng c ng phn anomer v cng khng c hin tng bi quay trong dung dch. Nhng tnh cht trn chng t (+)-saccharose khng c chc aldehyd trong phn t. Saccharose b thy phn to thnh D -(+)-glucose v D -(-)-fructose. (+)-Saccharose c cng thc cu to nh sau:
HO HO
4

CH2OH
5

H
3

H
2

D-Glucopyranse

H CH2OH H O OH OH O H CH2OH HO H

D-Fructofuranose

Thy phn saccharose bng dung dch acid long hay enzym invertase s to thnh hn hp D -(+)-glucose v D -(-)-fructose c khi lng nh nhau. S thy phn ny dn n s thay i gc quay cc ban u ca saccharose. Gc quay cc t (+)chuyn thnh (-). Hin tng gi l s nghch quay (o quay) ca (+)saccharose. Hn hp thy phn trn gi l "ng nghch quay". Mt ong l ng nghch quay. S nghch quay l do s b tr gc quay cc ca D -(+)-glucose v D -(-)fructose. Gc quay cc ca (+) saccharose +66,5, ca D -(+)-glucose +52,7 v ca 55

D -(-)-fructose 92,4. Kt qu l dung dch saccharose sau khi thy phn c gc quay cc (-). V vy D -(+)-glucose cn gi l Dextrose v D -(-)-fructose gi l Levulose. 3. Polysaccharid Polysaccharid l nhng hp cht bao gm hng trm n hng nghn gc monosaccharid kt hp vi nhau bng lin kt glycosid. Cc polysaccharid quan trng hay gp l tinh bt v cellulose. Chng u c cng thc phn t l (C6H10O5) n. Cc polysaccharid l nhng thnh phn quan trng trong th gii ng vt v thc vt. Polysaccharid c hnh thnh do qu trnh quang hp trong t nhin. Di tc dng ca nh sng, CO2 v H2O to thnh monosaccharid. Cc monosaccharid mt nc to thnh polysaccharid.
6CO2 + 6 H 2O
nC6H12O6

C6H12O6

+ 6O 2

(C 6H10O5)n + n H 2O

Tinh bt v cellulose l nhng cht quan trng i vi con ngi. Thc phm chng ta dng hng ngy, o ta mc, vt dng ta dng trong gia nh u c ngun gc t tinh bt v cellulose. 3.1. Tinh bt Tinh bt c cu to dng ht v kch thc khc nhau. Tinh bt c 20% amylose v 80% amylopectin. Amylose c cu trc mch thng v tan c trong nc. Amylopectin c cu trc phn nhnh v khng tan trong nc. Di tc dng ca acid hoc enzym, tinh bt b thy phn dn thnh cc phn t c phn t lng nh hn l dextrin, maltose v glucose. 3.1.1. Cu trc ca amylose Amylose c cu trc mch thng do cc phn t -glucose lin kt vi nhau bng lin kt -[1,4]-glucosid.
CH2OH OH H OH H O H OH H OH CH2OH OH H OH H O H OH CH2OH OH H OH H O CH2OH OH H OH H O H OH

H O

D-Glucose

(+)Maltose

D-Glucose

Amylose da ng co ng th c Haworth

56

H CH 2OH O 4 HO H H

1 H OH H H O 4 D-Glucose HO

D-Glucose
CH2OH H H H O 1 H H OH O 4 HO

D-Glucose
CH2OH H H H O

n
CH2OH H H H

(+) Maltose

1 H H OH O 4 HO

O 1 H OH O

Amylose da ng co ng th c ca u da ng

D-Glucose

Cc phn ng chng minh cu to amylose: Methyl ha amylose bng dimethylsulfat v NaOH. Sn phm methyl ha em thy phn to thnh 2,3,4,6-tetra-O-methyl -D-glucose v 2,3,6-tri-O-metyl-D-glucose. iu chng t trong amylose c lin kt [1-4]-glucosid.
H CH OCH 2 3 CH3 O CH3 O H H H O H H O CH3 O CH2 OCH3 O H H H OCH3

OCH3

H H O CH3 O

CH2 OCH3 O H H H OCH3 O

n
H H CH3 O CH2 OCH3 O H H H OCH3

H OCH3

HCl

H CH OCH 2 3 CH3 O CH3 O H H H

O H OH

OCH3

va

HO CH3 O

CH2 OCH3 O H H H OCH3 O

2,3,4,6-Tetra-O-metyl- -D-gluccose hieu suat 0,5%

2,3,6-Tri-O-metyl- -D-gluccose ( n+1) phan t

3.1.2. Cu trc ca amylopectin Amylopectin cng gm cc phn t -D-glucose to thnh bng lin kt glucosid v tr [1-4] v [1-6].

57

H O HO

CH 2OH H H H

D-Glucose
CH 2OH H H H O

1 H H OH O 4 HO

Lie n ke t glucosid 1,4

D-Glucose

Lie n ke t glucosid 1,6

1 H OH O 6 H CH2 HO H H

O OH

D-Glucose
1 H H O 4 HO H

D-Glucose
CH 2OH H H O H OH O

Lie n ke t glucosid 1,4

Co ng th c ca u da ng cu a amylopectin

Cc phn ng chng minh cng thc cu to ca amylopectin: Methyl ha amylopectin sau em thy phn trong mi trng acid th thu c 2,3,6-tri-O-methyl--D-glucose (chim 90%), 2,3,4,6-tetra-O-methyl--Dglucose (chim khong 5%) v 2,3-di-O-methyl--D-glucose (chim khong 5%).
6 H CH OCH 2 3 4 O HO H H CH3O 2 3 OCH 3 H 6 CH 2OCH 3 O CH3O H H H CH 3O 2 3 1 OCH 3 OH H H 4 H 6CH OH 2 4 O HO H H H CH3O 2 3 1 OCH 3 OH H

H 1 1 OH

2,3,6-Tri-O-methyl- D-Glucose (90%)

2,3,4,6-Tetra-O-methyl- D-Glucose 2,3,-Di-O-methyl- D-Glucose ( Khoa ng 5%) ( Khoa ng 5% )

3.1.3. Glycogen L hp cht c cu to gn ging vi amylopectin nhng phn t glycogen c mch phn nhnh nhiu hn v c s n v glucose (12-18 n v glucose) t hn amylopectin. Glycogen l hydrat carbon d tr ca c th. 3.2. Cellulose 3.2.1. Cu to Cellulose l thnh phn ch yu ca g v si thc vt. Bng c xem l cellulose nguyn cht. Cellulose khng tan trong nc. Cellulose khng c tnh kh. Phn t lng ca cellulose rt ln (250.000 - 1.000.000) bao gm trn 1500 n v glucose. Cellulose c cng thc phn t (C6H10O5)n. Thy phn hon ton cellulose bng acid ch thu c -D-(+)-glucose. Trong phn t cellulose, cc phn t -D-(+)-glucose lin kt vi nhau bng lin kt -[1-4]-D-glucosid.

58

D-Glucose

CH2 OH O H O H OH H H O H OH

D-Glucose
H OH H O OH H H H O CH2 OH

CH2 OH O H H OH H H

D-Glucose
H O H OH OH H H O CH2 OH

H OH

D-Glucose

Cong thc cau tao cua cellulose dang Haworth

Lien ket 4- -Glucosid
H O 4 HO CH2 OH H H H 2 H O O OH 1 H 4 H HO H 2 H

Lien ket 4- -Glucosid Lien ket 4- -Glucosid

OH O H 1 O H CH2 OH H H H 2 H 4 HO O O OH 1 H HO 4 H H 2 H OH O

H 1 O

CH2 OH

CH2 OH

Cellobiose

Cong thc cau dang cua cellulose

Cellobiose

Cellulose c cu trc mch thng, do cellulose d ko thnh si. 3.2.2. Cc phn ng ca cellulose Trn mi mt xch D -glucose c 3 nhm OH t do. Chnh cc nhm OH ny tham gia cc phn ng ester ha v phn ng to ether... a. Nitrat cellulose Cellulose tc dng vi hn hp acid nitric v acid sulfuric to nitrat cellulose. Nitrat cellulose nh l mt ester. Tnh cht v lnh vc s dng ca nitrat cellulose ty thuc vo mc nitrat ha. Nitrat cellulose c ng dng lm cc mng phim, lm cht do, cht keo dn, thuc sng khng khi... b. Acetat cellulose Cellulose tc dng vi hn hp anhydrid acetic v acid acetic c mt t acid sulfuric to ra hn hp triacetat cellulose. Acetat cellulose km bn hn nitrat cellulose. Acetat cellulose c s dng lm phim nh. Ho tan acetat cellulose trong aceton sau c th ko thnh si gi l t acetat. c. Ether cellulose Alkyl ha cellulose bng alkyl halogenid trong mi trng kim to ra ether cellulose. Cc ether methyl, benzyl ca cellulose c s dng trong cng nghip dt, to mng mng, to nguyn liu cht do. Carboxy Methyl Cellulose (CMC) cng thuc loi ether ca cellulose.
H CH 2OH O O H OH H H O H OCH 2COOH

Carboxy Methyl Cellulose (CMC)

59

d. T visco v Cellophan Cellulose tc dng vi carbor disulfid CS2 v NaOH to dung dch Xanthogenat cellulose c nht rt cao gi l visco. Ko visco qua khe nh v qua b ng acid thu c si cellulose gi l t visco. Mng mng visco c cht do ho l glycerin gi l cellophan. Cellophan thng c gi l giy bng knh, dng gi hng ha. C th hnh dung cu to ca cc loi polysaccharid nh hnh v di y:
Polysaccharid ma ch tha ng

Polysaccharid ma ch nha nh

Polysaccharid ma ch vo ng

3.3. Pectin Pectin c ngun gc t thc vt, c to thnh t acid -D-galacturonic v mt s methylester. Acid -D-galacturonic lin kt vi nhau to acid pectic. Acid pectic l khung c bn ca pectin.
Acid D - galacturonic
O COOH O OH OH OH O O COOH OH O COOH O OH OH OH O O COOH OH O COOH O OH OH O

Acid pectic

3.4. Acid alginic Acid alginic c trong mt s loi rong bin. Tn ti dng t do hoc dng mui calci. Thy phn acid alginic thu c acid D -mannuronic. 3.5. Chitin Chitin l mt loi polysaccharid c trong v tm, cua.... Thy phn chitin thu c acid acetic v D -glucosamin (chitosamin, 2-aminoglucose). Thy phn chitin bng enzym s thu c N -acetylglucosamin. 60

Cu to ca chitin cng ging cu to ca cellulose. N -methyl-L-glucosamin l thnh phn ca streptomycin.

CHO H CH 3 O H O H OH H H NH C NH NH

N-Methyl-L-glucosamin
H OH H

HO

H O

O CH 2OH H CH 3NH OH H

NH C NH2

H OH

NH OH

Streptomycin

Bi tp Monosaccharid 123Phn t (-)-fructose c bao nhiu nguyn t carbon khng i xng? Phn t 2-cetohexose c bao nhiu cp i quang? V cng thc chiu Fischer v cng thc Haworth i vi mt cp i quang ca D -(-)-Fructose. Vit phn ng to osazon ca cc cht sau, cc osazon c cu hnh th no? a ) D-glucose; b) D-Mannose; c ) D-Fructose. 45C bao nhiu aldotetrose thu c khi xut pht t D -(+)-aldehyd glyceric. Vit cc phng trnh phn ng theo s sau:
D-(+)-Glucose A B Na ( Hg) Na ( Hg) HNO 3 C ( Acid gluconic ) C ( Acid gluconic ) Acid(+)-Saccharic - H 2O - H 2O - H 2O A va B (e u la Lacton) Na ( Hg) Na ( Hg) D-(+)-Glucose (+)-Gulose

( Lacton ) E ( Lacton )

Vit cng thc cu to ca cc cht A E. (+)Gulose thuc loi cu hnh no, D hay L ? Disaccharid 6Vit phng trnh phn ng oxy ha, methyl ha v thy phn ca cc cht: (+)- Lactose, (+)-Maltose, (+)-Saccharose. 7Vit cng thc cu hnh ca: (+)- Lactose, (+)-Maltose,(+)- Saccharose v (+)- Cellobiose. 8Gii thch s nghch quay ca (+)-saccharose. 61

Chng 29

ACID AMIN, PEPTID V PROTID

Mc tiu 1. Gi c tn v xc nh c cu hnh ca acid amin. 2. Trnh by c ha tnh ca acid amin. 3. Nm c cc kiu cu to ca protid. 1. Acid amin 1.1.nh ngha Acid amin l nhng hp cht tp chc, c hai nhm nh chc khc nhau l: chc amin (NH2) v chc acid (COOH). C 2 loi acid amin:

H2N-R-COOH: R l gc hydrocarbon no, cha no, vng khng thm, d vng

H2N-Ar-COOH: Ar l gc hydrocarbon thm

1.2. Cu to 1.2.1. Cc acid amin thin nhin: l nhng -aminoacid Cng thc chung:
H2N CH R

COOH

Trong gc R

Alkyl (mch h hay nhnh) Cycloalkyl, Ar -, gc d vng Cha hoc khng cha mt s nhm chc ( -SH, -OH)
(Nhng nhm chc ny thng u mch ca gc R) S nhm chc ca mi loi c th mt hoc hai nhm:

Acid monoamino monocarboxylic Acid monoamino dicarboxylic Acid diamino monocarboxylic Acid diamino dicarboxylic

(1 nhm NH2 v 1 nhm COOH) (1 nhm NH2 v 2 nhm COOH) (2 nhm NH2 v 1 nhm COOH) (2 nhm NH2 v 2 nhm COOH)

Nhng acid amin c s chc acid nhiu hn chc amin th gi l acid amino acid v ngc li th gi l acid amino base. 62

1.2.2. Cu hnh ca acid amin Tr glycin, cc acid amin u c t nht mt nguyn t carbon khng i xng. Cc acid amin thu c t protid bng phng php thy phn acid hoc base u c tnh quang hot. Cc acid amin thin nhin l nhng -aminoacid v c cu hnh ging nhau thuc dy L so vi (-)-L- aldehyd glyceric v C* c cu hnh (S).
COOH H H2N R L -Aminoacid HO CHO H CH2OH

L -Aldehyd glyceric

1.3. Danh php 1.3.1. c tn v v tr nhm amino v tn acid tng ng Tn v v tr nhm amino + Tn acid tng ng 1.3.2. Tn ring v dng cc ch ci u k hiu tn acid V d: H2N-CH2-COOH Aminoetanoic Acid aminoacetic Glycin, Glycocol, Gly H2N-CH2-CH2-COOH 3-Aminopropanoic Acid -Aminopropionic 2-H2N-C6H4-COOH 2-Aminobenzoic. Acid o-aminobenzoic Acid Anthranilic

-Alanin, Ala

Bng 29.1: 20 acid amin ph bin

Cng thc cu to
NH2 H _ CH COOH
NH2 CH3 _ CH COOH

Danh php Glycin L (+)-Alanin

L (+)-Valin L (-)-Leucin L (+)-Isoleucin L (-)-Methionin L (-)-Prolin

K hiu Gly Ala

Val Leu Ile Met Pro

pK1 2.35 2.35

2.29 2.33 2.32 2.17 1.95

pK2 9.78 9.87

9.72 9.74 9.76 9.72 10.6

Pk3 -

CH 3 NH2 CH 3CH _ CH COOH

CH3 NH2 CH3CHCH2 _ CH COOH

CH3 NH2 CH3CH2 CH _ CH COOH NH2 CH3 SCH2 CH2 _ CH COOH

NH

_ COOH

63

_ CH

NH2 _ CH COOH
NH2 _ CH COOH

L(-)-Phenylalanin

Phe

2.58

9.24

_ CH
N H

L(- )-Tryptophan

Try

2.43

9.44

NH2 HO _ CH2 _ CH COOH

L (- )-Serin L (+ )-Threonin L (- )-Cystein L (- )-Tyrosin

Ser Thr Cys Tyr

2.19 2.09 1.86 2.20

9.44 9.10 8.35 9.11

10.34 10.0

OH NH2 CH 3 CH _ CH COOH NH2 HS_ CH2 _ CH COOH

HO NH 2 CH 2 _ CH COOH

NH2 O H2N_C CH2 _ CH COOH O NH2 H2 N_C CH2 CH2 _ CH COOH

NH 2 O HO _C CH 2 _ CH COOH

Asparagin Glutamin
AcidL(-)- Aspartic AcidL(+)- Glutamic
L (+)-Lysin

Asn Gln
Asp Glu
Lys

2.02 2.17
1.99 2.13
2.16

8.80 9.13
3.90 4.32
9.20

10.00 9.95
10.80

O NH2 HO_C CH2 CH2 _ CH COOH

NH 2 H 2 N CH 2 CH 2 CH 2 CH 2 _ CH COOH

O NH2 H2N C (CH2)3 CH COOH

N N H NH2 CH2 _ CH COOH

Arginin

Arg

1.82

8.99

13.20

L (-)-Histidin

His

1.81

6.05

9.15

1.4. Tnh cht l hc ca acid amin Acid amin l cc cht hu c kt tinh khng mu, nhiu cht c v ngt. 1.4.1. Phn t acid amin l ion lng cc (mui ni phn t)

C nhit nng chy cao v b phn hy. Acid amin d tan trong nc, khng bay hi, kh tan trong dung mi hu c. Hng s acid v base ca nhm acid -COOH v base -NH2 rt nh.

64

V d: i vi glycin c Ka= 1,6.10-10 v Kb = 2,5.10-12. Phn ln acid carboxylic c Ka 10-5 v cc amin khng vng c Kb 10-4.

Acid amin c dng ion lng cc (mui ni phn t) c cng thc cu to

+ H3N CH COO

R Acid amin da ng ion l ng c c

Trong cng thc trn ion amoni NH3+ c tnh acid v ion -COO- c tnh base. Hng s Ka ca glycin chnh l lc acid ca ion NH3+ v hng s Kb ca glycin chnh l lc base ca ion -COO-. Gi tr Ka v Kb c tnh theo phng trnh phn ly ca ion lng cc trong dung dch nc.
+ H3N CH R Acid + H3N CH R Base COO + H2O Base COO + H2O Acid

H3O+ + H2N CH COO Ka = R Acid Base

+ HO - + H3N CH COOH Kb = R Base Acid

[H3O+][H2N-CHR-COO -] + [ H3N-CHR-COO -] + [HO -][H2N-CHR-COOH ] + [ H3N-CHR-COO -]

Trong dung dch nc, lc acid v base ca base lin hp (v d CH3COOH v CH3COO- hoc CH3NH3 v CH3 NH2) c mi lin h Ka.Kb= 10-14 Xut pht t gi tr Ka ca glycin 1,6. 10-10, tnh c g tr Kb ca chc amin t do NH2. Cng tng t t gi tr Kb ca glycin, tnh c gi tr Ka ca acid t do -COOH. Khi kim ha dung dch acid amin (ion lng cc), ion I s chuyn thnh ion II. Mt base mnh (HO-) ly proton khi ion amoni v chuyn thnh mt base yu l amin NH2.
+ H3N CH COO R I Acid rt mnh + HO Base rt mnh H2N CH COO R II Base rt yu

+ H 2O Acid rt yu

Khi acid ha dung dch acid amin, ion I chuyn thnh ion III; acid mnh H3O nhng proton cho ion carboxylat v hnh thnh acid carboxylic rt yu.
+

+ H3N CH COO R

+ H3O

+ H3N CH COOH R

+ H2O

Base rt mnh Acid rt mnh

Acid rt mnh

Base rt yu B

65

Nh vy trong nhng acid amin n gin:

COOH khng phi l chc acid m l nhm NH3

NH2 khng phi l mt base m l -COO-

Ion II v III c chc -NH2 v -COOH t do tn ti trng thi cn bng vi ion I, phn ng ca acid amin l phn ng ca chc amin -NH2 v chc acid COOH. Acid amin c tnh cht lng tnh. Tnh lng tnh ca acid amin c biu din bng ng cong chun . Th d: Trng hp glycin
13 12 11 10 98765+ 4 - H N CH CO H 3 2 2 32pK1 = 2,35 1-

H2N CH2CO2

.
pK2 = 9,78

pH

H3+N CH2 COO c:

pH = 6,07 + H3N CH2CO2

PI = 2,35 + 9,78 = 6,05

2 (pK2 = pKb ; pK = pKa) 1

0,5

1,0

1,5

2,0

Lng NaOH, mol

ng cong chun NH3CH2COOH

1.4.2. im ng in ca acid amin Khi t dung dch acid amin vo trong mt in trng, c cc trng hp sau:
Anod (c c dng)

H3N CH COO
R II Base lie n h p

H+ HO -

+ H3N CH COO R I Dung dch acid amin

H+ HO -

Catod (c c a m) + H2N CH COOH R III Acid lie n h p

Nu dung dch l kim mnh th nng ion II ln hn ion III, acid amin chuyn dch v pha anod (cc dng ca in trng). Nu dung dch l acid mnh th nng ca ion III ln hn ion II, acid amin chuyn dch v pha catod (cc m ca in trng). Nu nng ca ion II v III bng nhau th khng c s chuyn dch no v hai cc ca in trng.
Gi tr pH (nng ion H+) khng lm chuyn dch acid amin v cc in cc gi l im ng in ca acid amin. Ti gi tr ny nng ca ion m II bng nng ca ion dng III v ha tan vo nc ca acid amin l nh nht. 66

V d: Acid monoaminocarboxylic -OOC-CHR-NH3 c lc acid ln hn mt t so vi lc base (glycin c Ka=1,6.10-10 v Kb = 2,5.10-12). Nu ha tan acid vo nc th nng ion II (H2N-CHR-COO-) ln hn ion III (HOOC-CHR-NH3+). C th hn ch s ion ha ca ion amoni -NH3+ thnh -NH2 bng cch thm vo mt t acid (H+) t n ng in. Ngha l cho nng ca II v III bng nhau th gi tr im ng in lch v pha acid. im ng in ca glycin c pH = 6,1. im ng in c k hiu l PI. Cng thc tnh gi tr PI khi bit pKa = -log Ka v pKb = - logKb.
PI =

pKa +pKb
2

im ng in l tnh c trng cho mi acid amin. Bng 29-2 trnh by im ng in v chiu quay ca mt s acid amin.
Bng 29.2: Gi tr im ng in ca mt s acid amin
Acid Glycin L(+)-Alanin L(+)-Valin L(-)Leucin L(+)-iso-Leucin L(-)-Phenylalanin L(-)-Tyrosin L(-)-Serin L(-)-Cystein L(-)-Cystin L(-)-Threonin t C 292 297 315 337 280 278 343 228 260 257 PI 6,10 6,00 5,96 6,02 5,98 5,48 5.66 5,68 5,05 4,80 Acid L(-)-Methionin L(-)-Tryptophan L(-)-Prolin L(-)-Hydroxyprolin L(-)-Acid Aspartic L(-)-Asparagin L(+)-Acid Glutamic L(+)-Glutamin L(+)-Arginin L(+)-Lysin L(-)-Histidin t C 280 289 215 270 251 227 248 227 224 277 PI 5,74 5,89 6,30 5,83 2,77 3,22 10,76 9,74 7,59

1.5. Tng hp cc acid amin 1.5.1. T -halogenoacid Perkin-Duppa (1858) tng hp glycin:
CH2 COONa + 2 NH3 X - NH4 X CH2 COONa NH2 CH2 COOH NH2

67

1.5.2. Tng hp Strecker (1850)

Tng hp ()-Alanin
CH3 CHO + NH3 , HCN CH3 CH C N NH2 CH3 CH COOH NH2

Tng hp ()-Methionin
CH 2 = CH _CHO CH 3SH + HCN CH 3S_CH2CH2CHO Aldehyd -thiomethyl propionic

CH3SCH2CH2 CH C N OH

1 2

) NH3

) 2 H2O

CH3SCH2CH2 CH COOH NH2 D, L -methionin

Tng hp acid ()-glutamic: Kt hp vi tng hp oxo

CH 2 = CH _CN NH 2 CN CO2 ,H 2 (t o,p) O=CH _CH2CH2_CN Co(CO) 8 Aldehyd cyanopropionic

NC CHCH2 CH2 C N NH2

H 3O

HOOC CHCH2 CH2 COOH NH2 Acid D, L -glutamic

1.5.3. T ester malonat

Tng hp ester malonat

CH 2 (COOEt) 2 NaOEt EtOH iso C4H9 leucin
-

i - C 4H9_Br iso - C H CH (COOEt) HCl a c 4 9 2 115oC (80- 90%) iso-butylmalonat diethyl CH COOH NH2

iso-C 4H9 CH2 COOH Br2

i - C 4H9 CH Br COOH

Kt hp vi kali phtalimid (tng hp Gabriel)

COOEt CH2 COOEt COOEt CHBr COOEt + H3O to + O O O

CCl4

Br2

N K+
O O Ar N C ( COOEt )2

N CH ( COOEt )2

Ar CHCOOH NH2

Ar- X

EtO -

68

 Kt hp vi HNO2
COOEt CH2 COOEt HNO 2 COOEt O N CH COOEt
NaOEt CH2=O O CH3 C NHCH(COOEt)2 NaOEt

COOEt HO N CH COOEt
HNCOCH3 HOCH2CH(COOEt)2 N N H CH2Cl

H 2 ,Pt Ac 2O
H2O to

O CH3 C NHCH(COOEt)2 Ester acetamidomalonat ethyl

+ NH3

HOCH2CHCOO Serin + NH3 N CH2 CH COO

N H Histidin + NH3

to H2O to

NaOEt

i-C4H9Br

C4H9 CH COO Leucin

1.6. Tnh cht ha hc ca acid amin Cc acid amin th hin tnh cht ha hc c trng ca mi chc. 1.6.1. Tnh acid base ca acid amin Tt c cc acid amin trong dung dch u phn ly v to nn cn bng sau:
O _CH_C R O_ H NH 2 .. Acid amin R_CH_COO NH 3 + ion l ng c c

Trong dung dch H2O c cn bng: Dung dch acid amin trong mi trng acid th acid lin hp chim u th. Dung dch acid amin trong mi trng base th base lin hp chim u th. 1.6.2. Phn ng loi nc ca acid amin Acid amin d tch H2O t NH2 v COOH to ra amid. Sn phm to thnh ph thuc vo v tr ca NH2 so vi COOH. Ngc li cc amid cng d thy phn cho acid amin.

Phn ng loi nc -aminoacid - amino acid (c bit ester ca n) d tch H2O (tch ROH) to amid vng dicetopiperazin.
H O C C R N H H H O O H H N C C O R H

- 2H2O, to
+ 2H2O, xt

O C R C

N N H

C C

Dicetopiperazin

69

 Phn ng loi nc -aminoacid - amino acid d tch NH3 to acid -etylenic

H R CH CH COOH NH2 - NH 3 - H 2O R_CH = CH _COOH CH2 C O R CH N H -lactam Acid -ethylenic

Vi cht ht nc cc mnh c th to vng -lacton (trong penicillin).

Phn ng loi nc cc ,,-acid amin.

Cc ,,-acid amin d tch H2O t NH2 v COOH trong cng 1 phn t to ,, hay -lactam (amid ni phn t)
O CH2 H2C CH2 CH2 C OH H N H CH2 - H2O H2C CH2 CH2 C N H O

-aminoacid

-lactam (valerolactam)

Phn ng loi nc gia cc acid amin l c s to lin kt amid trong cc polyamid hoc lin kt peptid trong polypeptid v protein.
Lien ket amid n H2 N CH COOH R H2N CH COHN CH COOH n R R + (n-1) H2O

1.6.3. Phn ng to mu ca acid amin Cc acid amin c kh nng to mu vi mt s hp cht nht nh. Dng phn ng ny nh tnh cc acid amin:

Vi ninhydrin:
un nng acid amin vi dung dch ninhydrin trong alcol to mu xanh tm.
O OH OH O + R CH COOH NH2 N O HO Co mau xanh O + RCHO + 3H2O + CO2

O Ninhydrin

Phn ng vi mt s ion kim loi v cc cht hu c v v c khc: + Vi Pb2+ / HO cho mu en khi acid amin cha lu hunh. + Vi Hg (NO3)2 + Hg(NO2)2, cc acid amin c nhn phenol cho mu hng.
70

+ Vi HNO3, cc acid amin cha nhn benzen to mu vng. + Vi HOOC - CHO, cc acid amin cha nhn indol cho mu xanh tm. + Vi acid diazobenzensulfonic, cc acid amin c nhn imidazol s to hp cht azo c mu anh o.
1.6.4. Tnh cht ca chc COOH

Vi base to mui
Acid amin tc dng vi base to mui carboxylat. Ngoi ra n cn c th to mui ni phc vi cation kim loi nng:
O C 2 H CH COOH + NH2 Glycin Cu2+ O NH2 .. O CH2 + C O

CH2 NH2

..

Cu

2 H+

Muo i no i ph c (ma u xanh tha m)

To ester
Acid amin tc dng vi ROH (c hi HCl) s to ester ca acid amin (thng dng mui clorhydrat).
H2N_CH2_COOH + C2H5OH + H Cl - H2O + Cl- [ H3N_CH2_COOC2H5 ]

Mun thu c ester t do, cho sn phm clorhydrat phn ng vi Ag2O hoc N (C2H5)3 :
+ Cl- [ H3N_CH2_COOC2H5 ] + Ag2O H2N_CH2_COOC2H5 + AgCl + H2O

Cc ester ca acid amin l nhng cht lng, d ct p sut thp. Fischer dng phn ng ny tch cc acid amin.

To clorid acid
H2N_CH2_COOH + P Cl5 - P OCl3 + Cl-[ H3N_CH2_COCl]

Phn ng decarboxyl (tch CO2):

CH3 CH NH2 Alanin Ethylamin COOH Men carboxylase CH3 CH NH2 + CO2

1.6.5. Tnh cht NH2

To mui vi cc acid
Acid amin tc dng vi acid v c, to mui 71

H2N CH COOH CH3

+ HCl

+ Cl- H3N CH COOH CH3

Tc dng vi HNO2
To acid -hydroxycarboxylic, gii phng N2 v H2O.
H2N CH COOH + HNO2 R HO CH COOH R + N2 + H2O

Van Slyke dng phn ng ny nh lng NH2 trong acid amin bng cch o kh N2 gii phng ra (qua nit k).

To dn xut N -acyl
Cc acid amin phn ng vi tc nhn acyl ha nh RCOCl, (RCO)2O, carbobenzyloxyclorid (benzylcloroformiat) C6H5CH2OCOCl to dn xut N -acyl.
H2N CH COONa R + CH3COCl CH3COHN CH COOH R + NaCl

Tc dng vi aldehyd
mi trng kim, acid amin ngng t vi aldehyd to base Schiff (lin kt imin).
CH2 O + H2N CH COOH R HO
-

CH2

N CH COOH R

Aldehyd

Lin kt imin

Sorensen dng phn ng ny nh lng nhm -COOH t do ca acid amin

Mt s phn ng vi enzym
Khi oxy ha, acid amin b loi nhm NH2, to ceto acid:
R_CH_COOH NH2 +

[O ]

R _ CO _ COOH cetoacid

N H3

hoc c th do enzym oxydase:

R_CH_COOH NH2 men R_CH_COOH NH H2O R _ CO _ COOH cetoacid + N H3

Acid ny b loi CO2 to aldehyd:

CH3_CO_COOH CH3CHO + CO2

72

Nh cc enzym c hiu, c th xy ra phn ng trao i gc R ca cc acid amin

R CH COOH NH2

R' C COOH O

R' CH COOH + R C COOH NH2 O

2. Peptid 2.1. nh ngha Peptid l amid c hnh thnh do cc chc acid v chc amin ca acid amin tng tc vi nhau. Chc amid -NHCO- c gi l lin kt peptid. Ty thuc s gc acid amin c trong phn t ngi ta phn chia cc loi peptid: dipeptid, tripeptid...., polypeptid. Cc peptid c phn t lng n 10.000 l polypeptid. Peptid c phn t lng ln hn l nhng protid.
+ H3NCH 2CONHCH2COO Dipeptid GlycinGlycin (Gly-Gly) + + , H3NCH2CONHCHCONHCHCOO , H3NCHCO (NHCHCO)nNHCHCOO CH3 CH2C6H5 Tripeptid GlycinAlaninPhenylalanin (Gly-Ala-Ph) R R Polypeptid R

2.2. Cu to polypeptid 2.2.1. Cu to Cc phng php vt l xc nh chc amid (lin kt peptid) c cu to phng v v c cu hnh trans.
H N R
O C

R N
H

O C R

Trans

O Trans

C nhiu trng hp acid amin c 2 nhm acid hoc cc nhm chc khc (OH, SH...). Cc nhm chc ny c trong gc R l c s lm cho cu trc ca protid c cc hnh dng khc nhau. V d: Phn t tripeptid glutathion, nonapeptid ocytocin minh ha iu :
+ H3NCHCH2CH2CONHCHCONHCH2COOH COOCH2SH Glutathion (GlutamylCysteinGlycin)

Glu-Cys-Gly

73

CH3 CH2 CH3CH

OH CH2

NH2 CHNHCOCHNHCOCH Hoac

CH2 O C S S NH CH2 CHNHCOCHCONHCHCO N CH2 CH2 CH2 CONH2 CONH2 Ocytocin

lle Tyr Cys S Glu Asp Cys S Pro Leu Gly(NH2) NH2 NH2

CONHCHCONHCH2CONH2 CH3 CH2 CH CH3

2.2.2. Xc nh cu trc ca peptid

C nhng acid amin no trong phn t. C bao nhiu phn t acid amin trong phn t. Trt t lin kt ca cc acid amin trong phn t.
a. p dng phng php xc nh cc gc cui mch peptid:
N-goc cuoi mach C-goc cuoi mach

n H2 N CH COOH R

H2N

CH COHN CH COOH n R R

+ (n-1) H2O

Nhm N-gc cui mch cha chc amin t do c xc nh vi thuc th 2,4-dinitrofluorobenzen (NO2)2C6H3F hoc vi hp cht phenylisothiocyanat C6H5NCS. Nhm C -gc cui mch cha chc acid t do c xc nh nh enzym carboxypeptidase c trong rut.
b. p dng phng php thy phn tng phn. xc nh s lng v trt t sp xp cc acid amin trong phn t. 2.3. Tng hp peptid Phng php trng ngng acid amin ch p dng iu ch cc peptid n gin. Phng php c hiu qu l phng php ghp ln lt cc acid amin li vi nhau. C cc giai on thc hin mt qu trnh tng hp peptid nh sau:

74

2.3.1. Bo v nhm chc amin Thc hin phn ng acyl ha bng carbobenzyloxyclorid (benzylcloroformiat) C2H5CH2OCOCl v chuyn nhm acid thnh clorid acid.
+ H3N CH COO R
+ C6H5CH2OCOCl - HCl

Q = C6H5CH2OCO Q HN CH COOH R

+ HCl

Q HN CH COCl R

2.3.2. To lin kt peptid

+ Q HN CH COCl + H3N CH COO R R Q HN CH CONH CH COOH R R

2.3.3. Gii phng chc amin

Q HN CH CONH CH COOH R R + H3N CH CONH CH COO R R

Nh ha hc Du Vigneaud v cng s (1963) tng hp ton phn phn t Insulin c 51 acid amin theo th t xc nh. 3. Protid 3.1. nh ngha Protid l nhng polypeptid c phn t lng ln (>10.000). 3.2. Phn loi: C nhiu cch phn loi protid

Protid c 2 loi, loi protid dng si (khng tan trong nc) v protid dng hnh cu (tan c trong nc, tan trong dung dch acid, base hoc dung dch mui). Cch phn loi ph bin: Protid n gin (protein) v protid phc tp (proteid). Protid n gin cn gi l protein, khi thy phn ch thu c cc acid amin.
Protein n gin tan c trong nc (hoc acid v kim), b ng vn khi c tc dng ca nhit th v b kt ta khi bo ha bng dung dch nhm sulfat. Thuc loi ny c: albumin, globulin, prolamin, glutelin, cc cht ging albumin (albuminoid, scleroprotein) nh keratin, collagen... Protid phc tp (conjugated protein) l nhng protein cha cc nhm khng phi protein nh: Acid nucleic, chromoprotein, glycoprotein, phosphoprotein, lipoprotein v protein cha kim loi nng.

75

3.3. Cu to ca protid: C 3 kiu cu to: 3.3.1. Cu trc bc mt Ch s lng, thnh phn v th t ni tip ca cc acid amin thnh mch polypeptid. Cc acid amin lin kt vi nhau thnh mt mch n. V d: NH2-A-CO-NH-B-COOH. hay HOOC-A-NH-CO-B-NH2 3.3.2. Cu trc bc hai Mch polypeptid c dng xon c hay gp khc do lin kt hydro gia cc nhm chc C =O, NH2, NH3+, COOH v COO - ca hai lin kt amid khc nhau.
H C N C O H C H N N C O n ng O C khng gian CH CH2 CH NC 2 O C O NC CH2 ....H C O C

R N R CH CH C O N

C O

Mnh ct 1 vng xon c

R Ba c xoa n o c 0,54 nm go m 3,6 -Aminoacid H N R C O = 1,05nm H N CH C O CH

3-6 - Aminoacid

Hai xon c song song

6 ,7A o

R R R R R

R R R R R R
10 A o

H N

O R H CH N

O C

Lin kt hydrogen

CH N C CH R H O R

Mch peptid

R O H CH C N
C O

CH

N CH C N H R O H

Lin kt ni phn t

76

3.3.3. Cu trc bc ba L hnh dng ring bit tht trong khng gian 3 chiu cho ton b i phn t protein v kch thc c th xc nh chnh xc. Khi cun li vi nhau hoc un khc c peptid dng xon th cc gc acid amin trong chui peptid u hng ra ngoi v cc chc ha hc c trong cc gc ny c th tng tc vi nhau. Kt qu l trn phn t protid c cc v tr li lm. Chnh cu hnh khng gian cp III c cc ch li lm mang theo cc nhm chc bn ngoi l nguyn nhn lm phn t protid c hot tnh sinh hc c th. V d: -SH (sulfurhydryl) vi SH to lin kt disulfur (-S-S-), n l lin kt c bn duy tr cu trc cp III. Hoc OH vi COOH to ester (-O-CO-). Nhm COOH vi NH2 to mui amoni (-COONH4). 3.3.4. Cu trc bc bn Ging cu trc bc ba nhng cc lc ht tc dng gia cc phn t l khc nhau. 3.4.Tnh cht ca protid Protid l nhng cht keo, khng c nhit nng chy c trng. Protid c tnh quang hot v quay tri. Cc enzym v mt s hormon nh insulin l nhng protein. Protein c th b ng kt khi c tc dng ca nhit, acid v base mnh (s kt ta khng hon nguyn). Protein b kt ta khng hon nguyn gi l protein bin tnh (denatured). S bin tnh lm thay i ho tan, tc dng sinh hc,... ca protid. Cc sn phm thy phn do acid, base hoc cc enzym ln lt qua cc giai on:

77

Protid

Protid bin tnh (protein khng tan do tc dng ca nhit) Khng tan trong nc hoc dung dch mui nhng tan trong dung dch acid hoc base. Loi ny kt ta vi amoni sulfat

Protein bc mt (metaprotein)

Protein bc hai

Tan trong nc, di tc dng ca nhit khng b ng li. Kt ta khi bo ha bng dung dch amoni sulfat

Pepton Tan trong nc, di tc dng ca nhit khng b ng li nhng khng b kt ta khi bo ha bng dung dch amoni sulfat

Polypeptid

Peptid n gin

Acid amin

Bi tp 1. Vit cng thc cu to ca cc acid amin c tn gi sau: Glycin, (+)-Alanin, (+)-Valin, (-)-Leucin, Isoleucin, (+)-Lysin, Acid (+)-glutamic, (+)-Glutamin, (-)-Methionin, (-)-Phenyalanin, (-)-Tryptophan, (-)-Histidin. 2. Bng phng php no c th tng tc phn ng ester ha v phn ng acyl ha ca acid amin? 3. Trong dung dch kim mnh, acid amin cha 2 nhm chc NH2 v -COO. Nhm chc no c tnh base mnh hn? Khi thm acid vo th nhm no b proton ha trc tin v hp cht no c to thnh? 4. Trong dung dch acid mnh, acid amin cha 2 nhm chc NH3+ v -COOH. Nhm chc no c tnh acid mnh hn? Nhm no d nhng proton hn khi thm kim vo v hp cht no c to thnh? 5. Hy chn cht u tng hp cc acid amin theo cc phng php cho: a. Amin ha trc tip iu ch: glycin, alanin, valin, leucin, acid asparagic. b. Tng hp cc cht Glycin, Leucin theo phng php Gabriel. c. Tng hp cc cht Valin, Isoleucin theo phng php malonat. 6. Nhng cht no c to thnh khi cho glycin tc dng vi cc cht sau: Dung dch NaOH; dung dch HCl; benzoylclorid + dung dch NaOH anhydrid acetic; NaNO2 + HCl; C2H5OH + H2SO4; Carbobenzyloxyclorid C6H5CH2OCOCl. 78

Chng 30

HP CHT D VNG

Mc tiu hc tp 1. Gii thch c tnh thm ca cc loi hp cht d vng. 2. Nu c danh php v c c tn theo thng thng cc hp cht d vng. 3. Trnh by c cng thc cng hng d vng 5 v 6 cnh. 1. nh ngha D vng l nhng hp cht vng. Vng c to thnh khng nhng do cc nguyn t carbon m cn c cc nguyn t khc nh oxy O, nit N, lu hunh S. Cc nguyn t ny gi l d t. 2. Phn loi hp cht d vng Ty theo cu to, c th chia hp cht d vng thnh 2 loi chnh: D vng thm v d vng khng thm. D vng thm l nhng d vng c cu trc in t ca vng ph hp vi cng thc Huckel (4n+2) e V d:
. . . . . . Pyridin
N

. . . .. . Furan
O

D vng khng thm l d vng no hoc cha no: V d:

N H

N H

N H

Trong cc hp cht d vng th d vng thm l quan trng. Phn loi d vng thm nh sau:

79

2.1. D vng 5 cnh, 6 cnh, 7 cnh c 1 d t 2.1.1. D vng 5 cnh, 6 cnh c 1 d t

Furan

S Thiophen

NH Pyrrol

N Pyridin

2.1.2. D vng 5 cnh, 6 cnh ngng t vi vng benzen

O Benzofuran

S Benzothiophen

N H Benzopyrrol

N Benzopyridin (Quinolin)

2.2. D vng 5 cnh, 6 cnh c nhiu d t 2.2.1. Hai d t ging nhau

N N H N N H N N N N N N

Pyrazol

Imidazol

Pyridazin

Pyrimidin

Pyrazin

2.2.2. Hai d t khc nhau

N O S N

Oxazol

Thiazol

2.2.3. D vng 5 cnh, 6 cnh c 2 d t ngng t vi vng benzen

N N N S N O N N N N N N N

Benzoimidazol Benzothiazol

Benzoxazol Benzopyridazin Benzopyrimidin Benzopyrazin

2.3. Cc d vng ngng t vi nhau

N N N N N N N N N

Purin

Pteridin

80

3. Danh php hp cht d vng 3.1. Danh php thng thng Danh php thng thng xut pht t ngun gc hoc tnh cht ca mt hp cht c trong thin nhin.

CH3

Gi l Picolin v cht ny ly t nha than (coaltar). Theo ting Latinh Picatus c ngha l ging nha hc n (tarry).

CH2OH

y l mt alcol trch ly t cm (bran) gi l "furfurol" c ngha l du cm.

N H

Gi l "Pyrrol". Pyrrol theo ting Hy Lp c ngha l chy , v mu g thng c tm acid d bc chy vi picolin.

Tn thng thng khng phn nh cu trc phn t. Danh php thng thng ca hn 60 hp cht d vng tr thnh ph bin nh l mt quy c ca h thng danh php IUPAC. Sau y l danh php thng thng ca cc cht c quy c nh l danh php quc t:
Bng 30.1: Cc hp cht c tn thng thng quy c.
N N H Pyrrol O Furan S Thiophen N N H Pyrazol N H Imidazol N O N

Furazan

N Pyridin

N N Pyridazin

N N Pyrimidin

N N Pyrazin O a-Pyran
1N 2 6 5

N H Indol

NH
1

Isoindol

N N H Indazol
N N
5

1 8

N 4 N9 3 H Purin
4

Indolizin
1

N N
4

Quinolin

Isoquinolin

N2

Quinazolin

Pteridin

Quinolizin

81

N 10 1 N
5

2 9

S5 N 10 1 H
2 1

N5

N H

2 1

Carbazol

Phenazin
H N

Phenothiazin
H N

Phenanthridin

N H

N H

N H O O

Pyrolidin

Piperidin

Piperazin

Morpholin

Chroman

nh s cc d vng theo quy c:

Xut pht t d t v theo chiu ca d vng. i vi hp cht a vng th nh s bt u t nguyn t cnh vng kt hp.
3.2. Danh php h thng i vi hp cht n vng Danh php Hantzsh -Widman Hantzsh-Widman ngh h thng danh php i vi hp cht n vng c ng dng rng ri nh sau: Tn gi ca d vng gm 2 phn.

Phn tip u ng (Preffixes ): Ch tn cc d t. Phn thn (stems): Ch khung vng, ln ca vng no hoc cha no c s ni i ln nht.
Bng 30.2: Tip u ng ch tn cc d t.
D t Oxy Lu hunh Selen Telur Nit Phosphor Arsen Silic Germani Bo O S Se Te N P As Si Ge B Ha tr II II II II III III III IV IV III Tip u ng Oxa Thia Selena Telura Aza Phospha Arsa Sila Germa Bora

82

Bng 30.3: Tn gi phn thn cc vng n

ln ca vng Vng khng c N Vng cha no 3 4 5 6 7 8 9 10 iren et ol in epin ocin onin ecin Vng no iran etan olan inan epan ocan onan ecan Vng c N Vng cha no irin et ol in epin ocin onin ecin Vng no V iridin etidin olidin perhydro perhydro perhydro perhydro perhydro

Nguyn tc nh s: + Nu d vng c nhiu d t th nh s theo chiu u tin theo th t cc d t sp xp trong bng 30.2: O > S > N > P + Nu d vng c nhiu d t cng loi th bt u t d t cao nht v dng cc ch di, tri, tetra... ch s lng d t cng loi.
V d:
S Thieren O
1

N3 N 1,3-Diazet

N H
2

Oxiran

1,2-Oxazetidin

O O 1,3-Dioxolan

N N N 1,2,4-Triazin S Thiepan N Azocin

Khi h thng vng c s ni i cc i c no ha dn, cch gi tn nh sau: V tr ca nguyn t bo ha c nh s km theo tip u ng (preffixe) H v gi tn ca d vng cha no (vi s ni i cc i) tng ng. V d:
H N1 1H-Azirin N
2

N O 2H-1,3-Oxazin
2 6

N O1 6H-1,3-Oxazin

2H-Azirin

N 3H-Azepin

83

Cch gi tn nh th ny khng p dng vi cch gi tn theo danh php thng thng. V d: Khng gi l 1H- Pyrol.
N H

* Ch gi l 1H-azol

3.3. Danh php ca h thng vng ngng t Phn ln cc hp cht d vng u cha hai hay nhiu vng ngng t vi nhau. Mt s hp cht loi vng ngng t c tn thng thng quy c. Nhng phn ln hp cht loi ny phi c danh php h thng d dng khi gi tn chng. Tn gi cc d vng ngng t phi xut pht t nguyn t chung thuc c h thng vng. Tn gi d vng ngng t c gi bng cch kt hp tn gi ca cc d vng ring bit. V d:
N O Benzoxazol + Benzen N O Oxazol
5 4 3 2

N N Pyrrolo[1,5a]pyrimidin

Nb

a N

N
1

Pyrimidin

Pyrol

Nguyn t Nit chung cho c 2 vng

3.3.1. Nguyn tc gi tn Phi bit cch chn v gi tn cc thnh phn ngng t vi nhau.

Tn gi cc thnh phn ngng t phi l tn thng thng c quy c.

Nu hp cht n vng cha c tn thng thng quy c th d vng gi tn theo h thng Hantzsch -Widman. Vng ln c tn gi thng thng quy c s c chn u tin. V d nu trong h thng a vng c cha vng indol v pyrrol th vng indol s c chn hn l vng pyrrol.

Tn gi ca d vng ngng t c hai thnh phn: Thnh phn c s v thnh phn th hai. V d: Trong cng thc Pyrrolo [1,5-a] pyrimidin th pyrimidin l thnh phn c s. Pyrrol l thnh phn th hai.
3.3.2. Cch chn thnh phn c s theo quy tc sau

Nu d vng ch c mt thnh phn nit N: chn thnh phn c s cha nit.

84

V d:
N O N

Thnh phn c s l pyrrol

Nu d vng khng c nit: chn thnh phn c s l vng c d t cao hn.

V d:
O Thnh phn c s l Furan S O

Nu vng ngng t c s vng ln hn hai vng: chn thnh phn c s cha s vng ln nht.
V d:
N Thnh phn c s l quinolin N N N

Nu hai vng c ln khc nhau: chn vng ln nht l thnh phn c s.

V d:
O N Thnh phn c s l vng 7 cnh azepin

Cc vng cha s d t khc nhau: chn vng c s d t nhiu nht.

V d:
N H N O Thnh phn c s l vng isoxazol N

C s khc nhau v s loi d t trn 2 vng: Chn vng c nguyn t vi v tr ln nht (sp xp theo th t ln gim dn trong bng 30.2).
N O S N Thnh phn c s l vng oxazol O

V vng oxazol cha oxy c th t u tin hn lu hunh trong vng thiazol.

85

 Thnh phn c s l vng c d t c nh s nh hn.

V d:
N N
3 1

N1 N2

N Thnh phn c s l vng pyrazol

3.3.3. Cu to tip u ng Tn ca thnh phn th hai nh l tip u ng ca thnh phn c s. Cu to tip u ng bng cch thm ch " O" sau tn gi ca d vng th hai. V d: Tn d vng l pyrazin th cu to thnh tip u ng l pyrazino Tn d vng l pyrol c cu to thnh tip u ng l Pyrolo
Bng 30.4: Mt s ngoi l v tip u ng
Tn d vng Furan Imidazol Isoquinolin Pyridin Quinolin Thiophen Tn tip u ng Furo Imidazo Isoquino Pyrido Quino Thieno

3.3.4. K hiu v gi tn Cc cnh ca vng trong thnh phn c s c k hiu bng cc ch ci a,b,c,d,e...theo chiu nh s. Cc nguyn t to vng ca thnh phn th hai c nh s bng cc ch s 1,2,3.. (nh nh s d vng). Cnh chung ca c 2 vng c gi theo ch s ca thnh phn th 2 v ch ci ca thnh phn c s (tt c t trong du mc vung). V d 1:
D vng ngng t Dvog ngng tu n Thnhh pha th th hai Tha phn n hai n
3

Thnhh pha c s c Tha phn n s n

N N

N1 Imidazo Imidazo

a O b N Oxazol
Oxazol

Imidazo[2,1-b]oxazol Imidazo [2,1-b] oxazol

Chn oxazol l thnh phn c s v oxazol c oxy O u tin hn nit N trong vng imidazol.

86

V d 2:
D vng ngng tu Dvog ngng t n Thnh phn th hai Thah pha th n n hai
4 5 3

Thnh phn c s Thah pha c s n n c d

+

d e

N
2

b N a N f

e Pyridazin Pyridazin

N1

b N f Na

Imidazo[1,5-b]pyridazin Imidazo[1,5-b] pyridazin

Imidazo Imidazo

Chn pyridazin l thnh phn c s v pyridazin l vng ln hn vng imidazol. 3.3.5. Cch nh s trn d vng ngng t Cch nh s trn d vng ngng t khng ph thuc vo cch nh s trn cc thnh phn c s v thnh phn th hai. nh s trn d vng ngng t xut pht t nguyn t cnh nguyn t u cu (nguyn t chung cho 2 vng) i theo chiu sao cho cc d t c s nh nht. Nu khng tha mn iu kin ny th d t c u tin nh s b nht. "Ch s hydro" H c ch ra trn h vng n (nu c). V d:
D vo ng ngng tu
4 O 4a 3 6 e N2 7 7a O1 5

Tha nh pha n th hai O

1 2 3

Tha nh pha n c s d4 c + e
5 6

4H-Furo[2,3-e]-1,2-Oxazin a nh so va te n go i d vo ng ngng tu

Furan

4H-1,2-Oxazin a nh so va te n go i d vo ng

b N2 f Oa 1

3.4. Danh php th C th xem hp cht d vng l hp cht vng hydrocarbon m mt hay nhiu nguyn t carbon c thay th bi cc d t. V vy gi tn nh sau:

Tn d t nh l tip u ng v tn hydrocarbon vng tng ng.

N N N P Si H N

Azabenzen

1,3-Diazabenzen

Silabenzen

1-Aza-4-phosphabenzen

Cc tip u ng ghi trong bng 2 c s dng trong danh php th. Danh php th t thng dng vi hp cht d vng. Danh php th thng c s dng vi hp cht d vng cha cc d t t ph bin v hay p dng danh php th gi tn cc hp cht vng spiro, hp cht vng c cu (a vng ngng t). 87

7O 3 2 6 5 1 4 3 2

S1

Oxacyclopetan

1,4-Dithiacyclohexa-2,5-dien 7-Oxabicyclo[2,2,1]hepta-2,5-dien

4. Cu to cc d vng thm Vng c to thnh do s xen ph ca nguyn t carbon trng thi lai ha sp2 v cc orbital ca cc d t. H thng in t ca d vng thm l h lin hp v s in t trong vng ph hp vi cng thc Huckel (4n+2) in t .
sp2 . . . sp2 . . . sp2 N sp2 sp2

N N N N

Cau tao cua pyridin

sp2 . . sp2 .. . sp2 N. sp2

H

H N

N H

..

N H

Cau tao cua pyrol

Mt in t.
Mt in t trn cc nguyn t c khc nhau ty theo v tr ca chng trong d vng.
0,967 1,004 0,968 1,004 1,090 1,087 1,090 1,067 1,078 1,067 1,078

1,048

0,968

N H

1,087 1,647

1,710

di lin kt
1,394 1,395 1,340 1,394 1,395 1,382 1,370 1,417 1,382 1,361 1,362 1,431 1,361 1,370 1,714 1,423 1,370 1,362

1,340

N H

1,370

1,714

Cn c vo di lin kt c th xc nh d vng thm hoc khng thm. Cc s liu v di lin kt ca d vng thm v khng thm trong bng 30.5.

88

Bng 30.5: di lin kt trong cc d vng

C-C C-N C-O C-S N-N 1,48 1,45 1,36 1,75 1,41 C=C C=N C=O C=S N=N 1,34 1,27 1,22 1,64 1,23

Nng lng cng hng v nng lng thm ha.

Theo phng php tnh gn ng Huckel, gi tr nng lng cng hng c c trng vi gi tr . l gi tr ca tch phn cng hng. Gi tr nng lng thm ha c n v l kj.mol -1. Gi tr nng lng cng hng (REPE) v nng lng thm ha ca mt s d vng trnh by trong bng 30-6 v 30-7 (gi tr l thuyt).
Bng 30.6: Gi tr nng lng cng hng v nng lng thm ha (theo l thuyt)
D vng Pyridin Pyrimidin Pyrazin Quinolin Isoquinolin Pyrol Pyrazol Imidazol Thiophen Furan Indol Benzofuran Benzo[b]thiophen Isoindol Isobenzofuran Benzo[c]thiophen Nng lng cng hng () 0.058 0,049 0,049 0,052 0,051 0,039 0,055 0,042 0,032 0,007 0,047 0036 0,044 0,029 0,002 0,025 Nng lng thm ha (kj.mol-1) 107 104 103 94 69 51 -

89

Bng 30.7: Nng lng cng hng thc nghim mt s d vng

Hp cht Benzen Pyridin Quinolin Pyrol Indol Thiophen Furan Kcal.mol-1 35,9 27,9 48,4 21,6 46,8 29,1 16,2 Kj.mol-1 150 117 200 90 196 122 68

Qua cc gi tr trn chng ta thy rng: Benzen c tnh thm mnh hn pyridin v cc d vng 5 cnh mt d t. Benzen c tnh thm yu hn quinolin v indol. C th so snh tnh thm: Benzen > Thiophen > Pyridin > Pyrol > Furan Cc c trng v cu to cn th hin qua cc gi tr v ph t ngoi UV, ph hng ngai IR, ph cng hng t ht nhn NMR.
Bng 30.8: Ph t ngoi ca mt s hp cht d vng
Hp cht Benzen Pyridin Pyridazin Pyrimidin Pyrazin 1,2,4,5-tetrazin Naphtalen Quinolin Isoquinolin Quinazolin 1,5-Naphtyridin Indol

m ( *)
256 251 246 243 260 252 218 ; 275 ; 311 225 ; 270 ; 311 217 ; 266 ; 317 220 ; 267 ; 311 206 ; 257 ; 308 215 ; 226 ; 279

log 2,40 3,30 3,11 3,31 3,75 3,33 5,10; 3,75; 2,39 4,48; 3,59; 3,37 4,57; 3,61; 3,49 4,61; 3,45; 3,32 4,73; 3,69; 3,84 4,38; 3,70; 3,62

m ( *)

log

270 340 298 328 542 330 330

2,65 2,50 2,51 3,02 2,92 2,30 2,70

90

5. Tnh cht ha hc ca d vng c tnh thm 5.1. Tnh thm ca d vng Cc d vng thm c h thng lin hp cho nn cc d vng c s phn b mt in t trn cc nguyn t. C th minh ha cc cng thc gii hn (cng thc trung gian) ca mt s d vng nh sau:

D vng thm 5 cnh:

X

..

X l S, N H, O Nhn xt: Ti cc v tr c in tch (-)d xy ra phn ng th i in t v tr 2 v 3. Vng thm 5 cnh c h thng dien lin hp nn th hin tnh cht ca hydrocarbon cha no. C cc phn ng cng hp, phn ng cng Diels - Alder, phn ng oxy ha.

D vng thm 6 cnh:

Cc cng thc cu to v cng thc gii hn c th c ca d vng pyridin:
+ N N N N N N

- +

Nhn xt: in tch m tp trung trn d t. Pyridin c tnh base. in tch dng xut hin carbon 2,4, 6. Phn ng th i nhn xy ra cc v tr ny. d vng thm 6 cnh, phn ng th i in t xy ra kh khn ti v tr 3, 5. D vng thm 6 cnh c cu trc nh benzen cho nn nhn d vng kh b oxy ha. Cng nh cc ng ng ca benzen, d vng ch b oxy ha mch nhnh. 5.2.Tnh cht ca d t D t c in tch m hoc c cp in t khng lin kt nn d vng c tnh base. Cp in t ca d t trn d vng thm 5 cnh tham gia to h thng thm (h thng lc t) cho nn tnh base ca d vng thm 5 cnh yu hn tnh base ca d vng thm 6 cnh. Tnh base ca pyridin mnh hn pyrrol l do cp in t t do trn nit khng tham gia h thng thm. Pyridin th hin tnh base nh mt amin bc ba.
. . . .. . . . . . . . N ..
2,3.10-9

Kb

N H 2,5.10-14

91

Tnh base ca d vng khng ph thuc vo s lng d t c trong vng.Yu t phn b mt in t v yu t lp th nh hng mnh n tnh base.
N N pKa =5,2 N pKa =1,3 N H N N N pKa =2,3

N N pKa =2,3

N N pKa =1,3

N N pKa =0,7 N pKa =4,7 N pKa =5,4

Bi tp 1- Gi tn cc cht sau:
N N N H N N O N O N

a- Theo danh php thng thng. b- Theo danh php Hantzsch -Widman. c- Theo danh php th. 2- V cng thc cu to cc cht c tn gi sau: a- 1,8-Diazanaphthalen; c- Selenacyclopentan; e- 2H-1,2-benzoxazin; h- Furo[3,2-d]pyrimidin ; b- 1-Oxa-2-azacyclobut-2-en; d- 1-Thia-3-azacycloheptatrien; g- Thieno [3,4-b]furan; i- 4H-[1,3]thiazino[3,4-a]azepin.

3- Gi tn cc cht sau y theo danh php Hantzsch -Widman.

1

N N

O4
N O

N5

92

Chng 31

HP CHT D VNG 5 CNH 1 D T

Mc tiu 1. Gii thch c cu to ca furan, pyrrol v thiophen. 2. Trnh by c tnh cht ha hc ca chng. Furan, pyrol, thiophen l nhng d vng n gin nht ca hp cht d vng 5 cnh mt d t.

O Furan

..

N H Pyrrol

..

S Thiophen

Cc d vng 5 cnh 1 d t nh l cc dien lin hp. Furan nh l mt ether vng, pyrrol nh l mt amin vng v thiophen nh l mt sulfid vng. Nhng nhng hp cht ny khng th hin y tnh cht ca mt ether, amin, sulfur. V d: iu kin thng thiophen khng b oxy ha (phn ng c trng ca sulfur), pyrrol khng c tnh base nh mt amin. Cp in t t do trn d t cng vi cc in t p ca nhng nguyn t carbon xen ph vi nhau to h thng lin hp c tnh thm nn lm mt i tnh cht c bn ca ether, amin v sulfid. Cc d vng thm 5 cnh mt d t th hin nhng tnh cht ca hydrocarbon thm nh phn ng th i in t: phn ng nitro ha, phn ng sulfon ha, phn ng halogen ha, phn ng acyl ha theo Friedel -Crafts v cng c th tham gia phn ng Reimer -Tieman, phn ng ngng t vi mui diazoni. Phn ng th i in t hp cht d vng thm 5 cnh mt d t c th xy ra theo s nh hng nh sau:
3

+ E+

- H+

hoac

+ E+

- H+

Nu tc nhn th i in t E+ tng tc vo v tr 3 s to thnh 2 carbocation c th c l I v II. Nu tc nhn E+ tng tc vo v tr 2 th to thnh 3 carbocation c th c l III, IV v V.

93

E
3

E + X II + H

X
1

+ E+

X I

+ +

E H

E X IV H

X III

+ X V

E H

Co nang lng thap hn

Thc t khi tc nhn i in t tng tc vo v tr 2 th carbocation bn vng hn (v c 3 trng thi carbocation). Vy s th i in t vo d vng thm 5 cnh u tin xy ra v tr 2 (v tr ). Mi d vng thm 5 cnh c nhng iu kin khc nhau v phn ng th i in t. Kh nng phn ng th i in t c th sp xp theo th t: Pyrrol > Furan > Thiophen > Benzen 1. Nhm Furan nh s: S 1 ti d t oxy. V tr 2 gi l , v tr 3 l .

, 4 3 , 5 . . 2 O . .1
1.1. Tng hp nhn furan 1.1.1. Dehydrat ha hp cht 1,4-dicarbonyl
R C O C R' O

C HO

C R'

HO

R' + 2 H2O

1.1.2. Ngng t -halogenoceton vi ester ca -ceton acid

R C O + Cl O C COOC2H5 R R COOC2H5 O R + H2O + HCl

1.2. Tnh cht ha hc Furan c tnh thm yu, th hin tnh cht ca dien -1,3, c khuynh hng tham gia phn ng cng hp. Trong mi trng H2SO4 c furan b polymer ha. Trong mi trng acid long vng furan b ph v thnh hp cht dicarbonyl. 94

H2O (H+)

C O

C R' O

.. O ..

Furan b hydro ha c xc tc to tetrahydrofuran

.. O .. Furan + 2H 2

xu c ta c
.. O .. Tetrahydrofuran

Furan tham gia cng hp dien (Phn ng Diels -Alder)

C O O O C O C O O C O

Furan ch tham gia phn ng th i in t trong iu kin rt nh nhng.

Furan c th b halogen ha to 2-clorofuran hoc 2,5-diclorofuran; nitro ha hay sulfon ha.
.. O .. + Cl 2 to= -40 oC .. Cl O .. 2-Clorofuran + HCl

.. O ..

+ CH3COONO2

.. NO2 O .. 2-Nitrofuran

+ CH3COOH

.. O ..

+ Pyridin . SO3

+ Pyridin .. SO3H O .. Acid 2-furansulfonic

(C 2H5)2 O : BF3 0oC O 2-Acetylfuran + CH 3COOH

+ O

( CH 3CO) 2O

COCH3

Furan d dng to hp cht c thy ngn theo phn ng sau:

.. O ..
+ HgCl2 CH3COONa O HgCl + HCl

95

1.3. Cc dn xut quan trng ca furan 1.3.1. Furfural: Furan-2-aldehyd

.. O . .1

CHO

Furfural

iu ch:

Furfural c th c trch ly t li ng hoc tru bng phng php ct li cun hi nc. Trong ng, tru, cm c pentozan.
H O , H+ (C5H8O4) n 2 Pentozan CHO (CHOH)3 CH2OH Pentose - 3H2O O Furfural CHO

Ha tnh: Furfural c tnh cht ging nh furan.

C th nitro ho furfural bng hn hp acid HNO3 v H2SO4 m c khi c anhydrid acetic lm dung mi v nhit thp (-20C). Phn ng th v tr 5.
2

CHO

HNO 3

H2SO 4 -20 oC

Anhydrid acetic

O2N

CHO O 5-Nitrofurfural

+ H 2O

Furfural c tnh cht ca mt aldehyd thm, tham gia phn ng Cannizaro to acid v alcol.
2 O KOH () O

CHO

CH2OH

COOH

Furfural tc dng vi anilin khi c mt ca acid HCl, vng furan b ph v v to hp cht c mu (phn ng Dieckmann 1905) ng vi cng thc cu to sau:
.. C6H5NH2 + + C6H5NH2 .. :O .. CHO

.. O

CHO

-H2O C6H5NH

C6H5NH2.HCl + HNC6H5 Cl

OH

96

 Hp cht 5-nitrofurfural ngng t vi cc cht semicarbazid, thiosemicarbazid to thnh cc cht semicarbazon v thiosemicarbazon ca 2-nitrofurfural c tc dng khng nm.
O2N .. O .. CHO + H2N HN C NH2 O (S) O2N .. O .. CH N HN C NH2+ H2O O (S)

1.3.2. Benzofuran - Coumaron

4
5

6 7

.. .O.1

Coumaron c tng hp bng cch cho phenolat tc dng vi -halogenoceton v loi nc tip theo.
O + ONa Cl C R - NaCl O O C R - H2O O R

1.3.3. Mt s dc cht c nhn furan Nitrofuran:

O O2N O CH N N N R O O2N O CH N R

Khng khun ng tiu tin

Khng khun ng rut

Acid ascorbic (Vitamin C):

OH HOCH2 CH HO O O OH

2. Nhm pyrrol
, , . .
N H

S phn b mt in t lm cho vng pyrrol tr nn bn vng. Cp in t t do ca nit tham gia to h thng thm nn nit mt kh nng tng tc vi proton H + ca acid nn tnh base ca pyrrol gim.

97

Pyrrol c cc cng thc gii hn:

H N H

+ N H N H

..

+ - N H

+ N H

- H

2.1. Tng hp vng pyrrol 2.1.1. Phng php Knorr 1885 Cho amoniac, amin bc 1 hoc hydrazin tc dng vi hp cht 1,4-dicarbonyl
R C O C R' O R C HO H C R' R R' + 2 H2O

+
N R

HO H

N R

2.1.2. i t acetylen v aldehyd formic sau tc dng vi amoniac

HC CH + 2HCHO Cu2C 2 HOCH2 C C CH2OH 1,4-Butyndiol NH3
a p sua t

N H

2.2. Tnh cht ha hc 2.2.1. Tnh acid -base

Pyrrol l mt base rt yu (Kb= 10-14). Pyrrol li l mt acid yu (pKa 15).

Trong trng hp v tr 1 c mt nguyn t H, pyrrol to mui kali v magnesi theo cc phn ng sau:
+ KOH .. .N . + H 2O

.. N H + RMgBr

.. N MgBr

RH

Pyrrolat kali tc dng vi CO2 to mui kali pyrrol -2-carboxylat (ging phn ng Kolbe -Shmidt)
.. N K + C O2 .. N H C OOK

98

 Pyrolat tc dng vi acylclorid hoc vi anhydrid acid to thnh 1-acylpyrrol.

.. N K + RCOCl .. N R-C=O

nhiet o

.. N H

C R O

1-Acylpyrol nhit cao chuyn v thnh -acylpyrol. Pyrolat kali tc dng vi diclorocarben (t cloroform v etylatnatri) t thnh 3-cloropyridin. 2.2.2. Phn ng th i in t

Clor ho pyrol bng SO2Cl2 20C s to thnh 2-cloropyrol hoc 2,5dicloropyrol. Brom ha pyrol bng N -bromosuccinimid thu c 2bromofpyrol. Nitro ho pyrol bng hn hp HNO3v anhydrid acetic thu c 2-nitropyrol. Sulfon ha pyrol bng SO3 trong pyridin thu c acid pyrol -2-sulfonic. Pyrol tc dng vi N,N-dimetylformamid v POCl3 thu c pyrol -2-aldehyd
.. N H CH3 + H C N CH3 O POCl3 .. N H CHO + H N CH3 CH3

Pyrol-2-aldehyd cng c th thu c bng phn ng Reimer -Tieman:

.. N H
+ CHCl3 + 3KOH

.. N H

CHO + 3 KCl + 2H2O

Ging anilin, pyrol ngng t vi mui diazoni to hp cht azo.

+ [C6H5N N]+Cl + HCl N N C6H5

N H

..

..

H 2-phenylazopyrol

2.2.3. Phn ng cng hp: Pyrol d tham gia phn ng cng hp

.. N H Pyrol + 2[H] .. N H 3-pyrolin + 2[H] .. N H pyrolidin

Pyrolin v pyrolidin c tnh base mnh hn pyrol. Chng c xem nh mt amin bc hai. 99

2.3. ng dng Pyrol l thnh phn chnh to thnh khung clorophyl v Pheophorbid.
CH2 CH3 CH3 H CH CH3 C2H5 CH2 CH3 CH3 H CH3 CH CH3 C2H5

Mg
N N

H H

CH3

CH2 CH2

H H COOCH3

COOC20H29

CH2 CH2

H H COOCH3

COOC20H29

Clorophyl a

Pheophorbid a

Cc alcaloid thuc nhm pyrolidin: Hygrin, Cuscohygrin, Stachydrin, Gramin.

N CH3

CH2 CO CH3

(+) Hygrin -

N CH3

CH2 CO CH2 Cuscohygrin

N CH3

+ COO N (CH3)2 Stachydrin

N H Gramin

CH2 N(CH3)2

2.4. Benzopyrol (Indol)

4
5

6 7

..

N1 H

Vng Indol c th c tng hp bng cch un nng phenylhydrazon vi ZnCl2, H2SO4 hoc acid polyphosphoric.
R R N R R N R R R

R R N H

N H

N H

HN N H

HN NH2 - NH3

S th i in t xy ra v tr 3. Nu khi v tr 3 th th s th xy ra vo v tr 2.

100

CHO

N H N H N H

Indol-3-aldehyd

CH2N(CH3)2

3-(Dimethylaminomethyl)indol

Cc hp cht c cha khung Indol Acid indol-3-acetic c tc dng kch thch s pht trin ca thc vt.
CH2COOH N H Acid -3-Indol acetic

Mt s acid amin c cha khung Indol:

CH2CHCOOH
3

CH2CH2NH2 HO

CH2CH2N(CH3)2 HO

NH2
2 1

N H

N H Serotonin

N H Bufotonin

Tryptophan

3. Nhm thiophen
, 4 3 , 5 . . 2 S1

3.1. Tng hp nhn thiophen Nhn thiophen c tng hp bng cch cho phosphor pentasulfid tc dng vi hp cht 1,4-dicarbonyl hoc cho hp cht -clovinylcarbonyl hay hp cht 1,3dicarbonyl ngng t vi cc dn xut ca acid thioglycolic.

101

C O

C R' O

C HO

C R' HO

P2S5

R'

+ P2O5

H O COOC2H5

R S + H2O + HCl COOC2H5

Cl HS

3.2. Tnh cht ha hc 3.2.1. Phn ng th i in t Ging nh furan, thiophen c h thng lin hp. Thiophen c tnh thm mnh hn furan v pyrol. Thiophen tham gia phn ng th i in t. Brom ha thiophen bng N -bromosuccinimid thu c 2-bromothiophen. Nitro ha thiophen thu c 2-nitrothiophen. Sulfon ha thiophen bng H2SO4 c thu c acid thiophen -2-sulfonic. Thiophen cng c th b formyl v acyl ha.
N-Bromosuccinimid S 2-Bromothiophen HNO 3 Anhydrid acetic SO 3.Pyridin S RCOCl AlCl 3 COR S 2-Acylthiophen CHO S Thiophen-2-aldehyd + HCl + Pyridin SO3H S Acid-2-thiophensulfonic NO2 S 2-Nitrothiophen Br
O

H N O

C C

CH2 CH2

+ H 2O

CO+HCl AlCl 3

3.2.2. Phn ng cng Vi Hydro c xc tc

H2 Ni + S 2-Thiolen S 3-Thiolen H2 S Thiolan

S Thiophen

102

Oxy ha tetrahydrothiophen (thiolan) to ra tetramethylensulfon (sulfolan) c s dng lm dung mi.

2 [O] S Thiolan S O O Tetramethylensulfon (sulfolan)

3.3. Benzo[b]thiophen - Thianaphthen - Thionaphthen

4
5

6 7

Benzo[b] thiophen c tnh cht ging naphthalen. C mi. Nhit nng chy 32C, si 221C. 3-Hydroxythianaphthen thng c gi l Thioindoxyl. Thioindoxyl c ng phn h bin.
4
5

C
1

O S

OH

6 7

Thioindoxyl

Thioindoxyl ngng t vi aldehyd hoc ceton to hp cht c mu.

4
5

C
1

O + OHC-R S

O + H2O

6 7

C CH R

Thioindoxyl

Thiophen, Furan v Pyrrol c th chuyn ha ln nhau qua cc phn ng sau:

b a, H2S+
b a, ,
4 5 3

,
4 5 3

b a + H2 O H2S + b a, ,
4 5 3

.. S1

+ NH3
b

..2 a N1 H

b a

+ H2O + NH3

.. O . .1

103

Bi tp 1- Vit cng thc cu to v gi tn cc sn phm to thnh ca cc phn ng sau: a- Thiophen + H2SO4 b- Thiophen + Anhydrid acetic, ZnCl2 c- Thiophen + Acetylclorid, TiCl4 d- Thiophen + Acid nitric trong acid acetic A. e- A + Sn+ HCl g- Thiophen + Br2 B. h- B + Mg (ether) Sn phm + CO2 v tip theo tc dng vi H +. i- Pyrrol + SO3 / Pyridin k- Pyrrol + HO3S-C6H4N2+ C. l- C + SnCl2 / HCl m- Pyrrol + H2 ( Ni) C4H9N. n- Furfural + Aceton (base) 2- Furan v cc dn xut ca n d dng tc dng vi H +. Vit cng thc cu to cc sn phm to thnh: 2,5-Dimetylfuran + H2SO4 long A (C6H10O2). A + Na2O Acid succinic. 3- Hy vit phng trnh phn ng iu ch: a - Acid furylacrylic t furfural. b- 1,2,5-Tricloropentan t furfural.

104

Chng 32

HP CHT D VNG 6 CNH 1 D T D T L NIT HOC OXY

Mc tiu 1. Nu c cu to v tnh cht thm ca d vng 6 cnh. 2. Nu c cc ha tnh ca pyridin. 1. Pyridin 1.1. Cu to ca pyridin Pyridin tng t vi benzen. Nhm CH ca benzen c thay th bng nguyn t nit. Cp in t khng lin kt ca N chim mt orbital sp2 v thng gc vi h thng in t ca vng. H thng in t ca vng c to thnh do 5 in t p ca 5 nguyn t carbon v 1 in t p ca nit. C th minh ha cng thc ca pyridin theo cc cng thc sau: Cu trc orbital ca pyridin
H H

. . .

. H . . . N .
H

54 3 61 2

Cau truc orbitalcua pyridin

. . . . . N ..

0,822 o,947 o,947

sp2 sp2

sp2 N ..

sp2 sp2

N ..

0,849

N ..

0,849

Khc vi benzen mt in t trn cc nguyn t carbon ca pyridin khc nhau. Nguyn t N c m in ln hn nn phn t pyridin c s phn cc. Momen lng cc ca pyridin l 2,5 D.Pyridin c cc cng thc gii hn sau:
0,822 0,947 0,849 0,947

+
0,849

N ..

N ..

N ..

.. N + ..

.. N ..

.. N ..

Mt in t cc v tr 2, 4 v 6 nh hn so vi cc v tr 3 v 5. 105

nh s v k hiu cc nguyn t trn vng pyridin:

4 5 6 3

N
1

1.2. Tng hp vng Pyridin Pyridin c trong nha than (khong 0,1%). Khi chng ct nha than c th thu c hn hp gm pyridin, metylpyridin (picolin), dimetylpyridin (lutidin) v trimetylpyridin (colidin). Vng pyridin c th c tng hp theo cc phng php: 1.2.1. Ngng t hp cht ,-aldehyd cha no vi amoniac
2 CH2=CH-CHO + NH3 CH3 - 2H2O N

1.2.2. Ngng t -cetoester vi aldehyd v amoniac - Tng hp Hantzsch

R C2H5OOC C R O CHO + C O NH 3 R HOOC - 2CO 2 R N R R N R R COOC2H5 C2H5OOC R N H R - 3H 2O H R COOC2H5 R C2H5OOC R N COOC2H5 R

- 2[ H ]

+ H 2O - 2C H OH 2 5 H+ R COOH

Vi phng php ny c th tng hp c cc alkylpyridin. 1.3. Tnh cht ha hc ca pyridin Pyridin c h thng lin hp ging benzen nn th hin tnh cht hydrocarbon thm. Pyridin c tnh base. Pyridin l cht lng khng mu, rt bn, si 115 - 116OC, c mi hi c trng. 1.3.1. Phn ng th i in t Pyridin tc dng yu vi cc tc nhn i in t so vi benzen. ng dng bn ca ion carbonium trung gian gii thch s nh hng ca tc nhn th i in t vo nhn pyridin: 106

Nu tc nhn i in t tn cng vo v tr 4 hoc v tr 2 th ion carbonium l s t hp ca 3 cng thc I, II, III. Nu tc nhn i in t tn cng vo v tr 3 th ion carbonium l s t hp ca cc cng thc IV, V, VI.
H N .. I H + N .. IV E +
4 3

H +

H N .. II

H + N ..

+ E+

III E

N
1

E H H + N .. V

E H N .. VI

+ H H

Tt c trng thi trn u km bn so vi cc trng thi ca benzen, v nguyn t nit N ht in t v pha mnh. Trong cc trng thi trn th trng thi III km bn nht v nguyn t nit N ch c 6 in t. Phn ng th i in t xy ra ti cc v tr 3 v 5 (v tr ) l ch yu v phn ng xy ra chm hn phn ng ca benzen.

Phn ng nitro ha trc tip bng HNO3 v H2SO4 hoc KNO3 300C thu c 3-nitropyridin vi hiu sut thp (vi phn trm). Phn ng sulfon ha pyridin xy ra vi hn hp H2SO4 + SO3 (oleum 20%) nhit 230C trong 24 gi thu c acid pyridin - 3-sulfonic vi hiu sut kh cao. Halogen ha trc tip pyridin bng clo, brom hoc iod, 300C thu c hn hp 3-halogenopyridin v 3,5-dihalogenopyridin. Pyridin khng xy ra phn ng alkyl ha, acyl ha theo Friedel -Craft.
H2SO 4 + KNO 3 300oC H2SO 4 + SO 3 230oC Br2 N 300oC (CH 3COO) 2Hg N +RX hoac RCOX , AlCl 3 N HgOCOCH3 + CH 3COOH N Br + HBr N SO3H + H 2O NO2 + H 2O

Khng xy ra phn ng

107

1.3.2. Phn ng th i nhn Cc tc nhn i nhn tng tc vi pyridin ti cc v tr 2, 6 v 4 (v tr v ). un nng natri amidid vi pyridin trong dung mi toluen thu c 2aminopyridin hoc 2,6-diaminopyridin. Nu v tr 2, 6 c nhm th th phn ng th i nhn xy ra v tr 4. n-Butyllithium hoc phenyllithium l nhng tc nhn i nhn mnh tc dng vi pyridin thu c 2-n-butylpyridin hoc 2-phenylpyridin.
NaNH2 NH2 - NaH + NaH N NH2 2-aminopyridin C4H9 N 2-butylpyridin N + H2 NHNa

N - H Na+ N C4H9Li N Li+

C4H9 - LiH H

Cc dn xut ca pyridin cng d b thay th bi cc tc nhn i nhn.

+ NH 3 N Br 2-Bromopyridin 180-200oC N NH2 + HBr

Cl N 4-Cloropyridin + CH3ONa

OCH3 + N 4-metoxypyridin NaCl

Phn ng th i in t v th i nhn vo pyridin rt ging phn ng th ca nitrobenzen. Tnh cht ca pyridin gn ging tnh cht ca nitrobenzen. V tr 3 ca nitrobenzen c tnh i in t, v tr 2 v 4 c tnh i nhn tng t vi pyridin.
4 4 3 1 2 3 4 3 1N+ 2

N
1

1.3.3. Phn ng oxy ho Vng pyridin khng b oxy ho bi dung dch brom v dung dch KMnO4 long. Gc hydrocarbon gn trn khung pyridin d b oxy ha to acid.

108

3[ O ] N CH3 N COOH

+ H2O

-Picolin 2-Methylpyridin
CH 3 3[ O ] N -Picolin 3-Methylpyridin

Acid Picolic Pyridin-2-Carboxylic

COOH + H 2O

N Acid Nicotinic Pyridin-3-Carboxylic

CH3 3[ O ] N -Picolin 4-Methylpyridin

COOH + H 2O N Acid Izonicotinic Pyridin-4-Carboxylic

1.3.4. Phn ng kh Phn ng hydro ha c xc tc

+ 3H2 N Kb = 2,3 . 10
-9

Pt

.. piperidin N H -3 Kb = 2 . 10

C th kh ho pyridin bng hn hp alcol v natri

C2H5OH + Na N pyridin

N H 1,4-Dihydropyridin

..

C2H5OH + Na

N H 1,2,3,4-Tetrahydropyridin

..

C2H5OH + Na

N H piperidin

..

Pyridin b kh bi lithium nhm hydrid LiAlH4 to 1,2-dihydropyridin

+ LiAlH4 N

..

1,2-dihydropyridin

1.3.5. Tnh base ca pyridin Pyridin l mt base yu ( Kb= 2,3.10-9). Pyridin cng nh cc alkylpyridin to mui vi cc acid mnh. Tnh base ca mt s dn xut ca pyridin c trnh by trong bng sau:

109

Nhm th pKa

H 5,23

2-NH2 6,86

3-NH2 5,98

4-NH2 9,17

2-OCH3 3,28

4-OCH3 6,62

4-NO2 1,61

2-CN -0,26

4-CN 1,90

Nhm th v tr 4 lm tng tnh base trn nit N ca pyridin. 4-Dimethylaminopyridin b proton ha vo nguyn t N ca pyridin v cation c n nh hn.
CH3 N N 4- Dimethylaminopyridin CH3 H+ CH3 N CH3 CH3 + N CH3

+ N H 4- Dimethylaminopyridin b proton ha

N H Trng thi n nh

4-Dimetylaminopyridin l mt base c s dng nh l mt xc tc trong cc phn ng c cu trc lp th. Pyridin to mui tan trong nc vi cc acid mnh.
+ HCl

Cl + N H Clohydratpyridin

2 N

+ H2SO4

SO 2 + 2 4 N H Sulfat pyridin

Pyridin nh l mt amin bc ba c kh nng to mui alkylhalogenid bc 4.

+ CH 3I + N I CH3 - N-methylpyridini iodid - Methylatpyridin iodid

Cc mui alkyl halogenid ca pyridin trong dung dch base c cn bng to sn phm d b oxy ha bi kaliferocyanid K3Fe(CN)6 to 1-alkyl-2-pyridon.
HO
+ -

K3Fe(CN)6 N R H OH N C O

N XR

R 1-alkyl-2-pyridon

Nguyn t N trong pyridin c kh nng to lin kt oxyd N O

+ RCOOOH N + RCOOH

N O

110

N-oxyd pyridin l cht trung gian tng hp cc ha chc khc gn trn vng pyridin. Cc dn xut thu c c tnh cht tng t cc dn xut ca benzen.
NH2 8[ H ] ( Ni ) - 3H2O NO2 HNO3 - H2O PCl3 N O HCl - HNO2 N O - POCl3 N Cl + 2[ H ] ( Fe , H ) - 3H2O N Cl N NO2

N O

Chc amin ca aminopyridin c kh nng b diazo ha.

NaNO 2 + HCl NH 2 0 _ 5oC

+ N N Cl -

Chc phenol c hin tng h bin.

OH

N H

1.4. Mt s hp cht cha d vng pyridin 1.4.1. Picolin Nhm CH3 gn trc tip vi vng pyridin gi l picolin. Lin kt C -H ca nhm CH3 tr nn linh ng v c nh hng siu lin hp v s ht in t ca nguyn t N. Cc picolin c tnh acid mnh hn toluen v tc dng vi cc hp cht c chc aldehyd theo kiu phn ng ngng t aldol.
H N C H H

nh hng siu lin hp

CH3 + O = CH-C6H5

(CH3COO)2O -2CH3COOH ,-H2O

CH = CH C6H5

111

CH3

+ C4H9Li

CH2Li

+ C4H10

Nhm CH3 rt d b oxy ha to acid pyridin carboxylic. Cc amid v hydrazid ca acid picolin carboxylic c nhiu ng dng trong dc phm nh Vitamin PP, Rimifon.
O C N (CH3 )2 N Vitamin PP Dimetylnicotinamid
N Izoniazid , Rimifon , Tubazid Izonicotinhydrazid O C NH NH2

1.4.2. Quinolin: Benzo[b]pyridin Quinolin C9H7N cha nhn benzen v nhn pyridin c cng thc nh sau:
5 6 7 8 4 5 3 1 2 6 7 8 4 3

b a N

N
1

Quinolin c trong nha than . Tnh cht ca quinolin cng gn vi tnh cht ca naphthalen v pyridin. a. Tng hp quinolin

Tng hp Skraup (1880):

Amin thm bc mt tc dng vi glycerin, acid sulfuric m c, nitrobenzen v sulfat st (II).
CH2OH H2SO4 , FeSO4 CHOH + C6H5NO2 CH2OH

+ NH2

+ C6H5NH2 + H2O

C ch: Di tc dng ca H2SO4 v nhit , glycerin b loi nc to aldehyd acrylic

CH2OH CHOH CH2OH H2SO4 , CH2 CH CHO + 2 H2O

Aldehyd acrylic

112

 Cng hp i nhn ca anilin vo aldehyd acrylic:

O C O H C

+ NH2

CH CH2

CH2

CH2 N H Aldehyd -phenylaminopropionic

Tng tc i in t ca nhm carbonyl proton ha vo nhn benzen (qu trnh ng vng).

O H C N H
+ OH

CH2 CH2

+ H+

H C N H

H CH2 CH2 - H+

OH - H2O

N H

N H 1,2-Dihydroquinolin

Oxy ha bng nitrobenzen:

3 + C6H5NO2 H+ 3 N Quinolin + C6H5NH2 + 2H2O

N H 1,2-Dihydroquinolin

Sulfat st (II) c tc dng tng tc phn ng. Nu thay i bn cht cc cht phn ng th c th thu c cc dn xut ca quinolin. V d:

Nu cho anilin tc dng vi aldehyd crotonic th thu c 2metylquinolin. Nu cho 3-nitro-4-aminoanisol tc dng vi glycerin to thnh 6-metoxy8-nitroquinolin. Tng hp Friedlander (1882):
CHO CH3 CHO CHO -H O NH2 2
CHO CH3 N CH

+
NH2

- H2O

b. Tnh cht ca quinolin. Quinolin l cht lng (ts = 238C). Tnh cht ha hc ca quinolin ging pyridin. Quinolin l mt base yu hn pyridin. Quinolin to mui kh tan vi mt s acid mnh nh acid dicromic H2Cr2O7 hoc vi acid H2PtCl6 to mui (C9H7N7) H2CrO7 v mui (C9H7N7). H2PtCl6.2H2O. Quinolin to mui picrat vi acid picric. 113

Phn ng th i in t xy ra trn vng benzen c s nh hng nh vng naphthalen. Nitro ha bng hn hp HNO3 v H2SO4 0C thu c hn hp 5 v 8-nitroquinolin. Sulfon ha 200C thu c acid quinolin -8-sulfonic. Phn ng th i nhn ch yu xy ra trn vng pyridin. Cc tc nhn i nhn nh NaNH2, RMgX hoc KOH ( 250C) u th vo v tr 2 ca pyridin.
5 4

+ HNO3 H2SO4
5 4

NO2

N
1 4

+ H2O

N
1

+ SO3 H2SO4

SO3H + NaNH2
8

N1
4

+ H2O

N
1

+ NaH NH2

Quinolin tc dng vi cc alkylhalogenid RX, cc acylhalogenid RCOX hoc dialkylsulfat (RO)2SO2 u to mui bc 4 tng ng.
+ RX
X

N
R

Hp cht 8-hydroxyquinolin l hp cht hu c quan trng c dng trong phn tch hu c cng nh c dng tch cc ion kim loi nh Al3+, Mg2+, Zn2+. Cc ion kim loi to phc khng tan vi 8-hydroxyquinolin. 8-Hydroxyquinolin to lin kt hydro ni phn t:
5 4 3 8

N
8

O 8 M N
1

6 7

N1 H

: .

Lin kt phi tr

Lie n ke t hydro trong pha n t 8-Hydroquinolin

1.4.3. Isoquinolin: Benzo[c]pyridin Isoquinolin c vng benzen v d vng pyridin ngng t vi nhau v c cng thc:
5 6 4 3
7 6 5 4 8 1

c
7 8

N2
3

4 3

6 7 8 1

b
1

N2

N2

114

Tng hp vng isoquinolin: S ng vng ca mt base Schiff trong mi trng acid v sau kh ha.
+ RCHO NH2 - H2O HC R N HCl

N H R

( Pd ) - 4H R

Cng c th to vng isoquinolin bng phn ng ng vng dn xut acyl ha ca -phenylethylamin khi c mt ca acid (thng s dng P2O5).
P 2O5 toC Pd N + H2

N-(2-phenylethyl) acetamid

O C CH3

NH

N CH3

1-Methyl-3,4-dihydroisoquinolin

CH3 1-Methylisoquinolin

1.4.4. Cc hp cht alcaloid cha khung pyridin

Nhm pyridin: Cc alcaloid cha vng pyridin b hydro ha.

Thuc nhm ny c cc alcaloid nh: Trigonellin c trong ht c ph; Ricinin c trong du thu du; Guvacin, guvacolin, Arecadin, Arecolin l nhng alcaloid chit xut t cc b phn ca cy cau ; Coniin c trong cy c cn (hemlock); Piperin c trong ht tiu en.
COO N CH3 Trigonellin
+ -

OCH3 CN N O CH3 Ricinin

COOH N H Guvacin

COOCH3 N H Guvacolin

COOCH3 N CH3 Arecolin

COOH N CH3 Arecadin

N H (+) Coniin -

CH2 CH2 CH3

H2C

O O

CH CH CH CH CO N Piperin

Nhm Pyrolidin -Pyridin: Nicotin

C trong thuc l. Trong thin nhin tn ti dng (-)nicotin c nhit nng chy 247C v []D = -169. Nicotin b mt nhm metyl gi l nor -nicotin.
N CH3 Nicotin N H nor -Nicotin

115

 Atropin
Atropin l ester ca acid tropic vi tropin (alcol). Atropin c trong c c dc (Atropa belladonna). Atropin c cng thc cu to:
CH2 CH2 CH2 CH2 C6H5 NCH3 CH O C CH CH2OH O CH CH2 Atropin

Thy phn Atropin thu c acid tropic v tropin (alcol)

CH COOH CH2OH Acid tropic CH2 + CH2 CH2 CH2 NCH3 CHOH CH CH2 Tropin

C17H23O3N + H2O Atropin

1.4.5. Cc hp cht alcaloid cha khung quinolin: Quinin, Chloroquin, Plasmoquin l nhng thuc iu tr bnh st rt.
CH3 CH CH2 CH2 CH2 N(C2H5)2 NH CH3O N Plasmoquin NH CH CH2 CH2 CH2 N(C2H5)2

Chloroquin
Cl N HO H C 5 H 4
6 7 8 3

CH3
CH2 CH2

CH CH2

CH3O

N
2

N
1

Quinin

1.4.6. Cc hp cht alcaloid cha khung isoquinolin Nhiu loi alcaloid c tch t cy thuc phin. Nhm isoquinolin c papaverin, laudanosin, narcotin...

116

CH3O N CH2 OCH3 CH3O N CH3 OCH3 CH2 OCH3

H2C

O O N CH3 CH O OCH3 CO OCH3 OCH3 Narcotin

OCH3

Papaverin

OCH3 Laudanosin

1.4.7. Acridin-Dibenzo[b,e]pyridin Acridin c cu trc phng ging anthracen.

8 7 6 5 c b a 10 9 d e 1 2 3 4

C th tng hp nhn acridin theo phng php sau:

R COOH R - 2H2O ZnCl2 N

+
N H

Mt s aminoacridin nh 9-aminoacridin, 3,6-diaminoacridin c tc dng khng khun. Mt s aminoacridin dng lm thuc nhum nh 3,6dimetylaminoacridin. Cation ca n c h lin hp ko di gi l acridin vng L.

(CH3)2N

+ N H

N(CH3)2

..

(CH3)2N

Acridin vang L

N H

+ N(CH3)2

2. Pyran Pyran tn ti 2 dng cu to: -Pyran v -Pyran

O
1 2 4 R R 2
+

-Pyran (2H-Pyran)

-Pyran (4H-Pyran)

Mui Pyrilium

117

2.1. - Pyran: 2H-pyran ; 1,2-oxin

-Pyran c h thng lin hp. Pyran khng tn ti dng t do. Khung -pyran ch c trong hp cht di dng mui pyrilium. Thng gp hp cht ca -pyran di dng -pyron v -cromon.

-Pyron (2H-pyranon-2)

-Cromon( 2H-Cromon)

O O Coumarin (2H-Benzopyranon-2)

Mui pyrilium thng gp dng benzopyrilium. Benzopyrilium c trong thnh phn cu to ca cht mu thc vt cyanin. Cyanin tn ti cc dng cng thc khc nhau c gi tr pH thay i.
O Glucose O + O ClCyanin OH OH O O HO O O O C C C OH O

HO

Can bang acid-base cua cyanin

C C C

OH O

- Pyron:
-Pyron c trong khung coumarin. Coumarin c th c tng hp bng cch cho aldehyd salicylic tc dng vi anhydrid acetic c xc tc l natri acetat.
CHO OH + (CH3CO)2O CH3COONa O C + CH3COOH O

Khung coumarin c trong cng thc cu to ca hp cht varfarin c tc dng chng ng mu.
OH C C6H5 CH CH2 COCH3 O

Varfarin

2.2. - Pyran hay 4H-Pyran; 1,4-oxin Thng gp dng -Pyron v - Cromon. 118

Trong cc hp cht flavonoid c cha khung -Cromon

O C O - Pyron O C O - Cromon

O C O Flavon

O C

OH

O Flavonol

Cc cht mu thc vt thng cha khung flavon. Mt s cht hu c cha khung -cromon dng trong dc phm nh nedocromilnatri.
OH O C O R OH O C NaOOC N Et O C O CH(CH3)2 COONa

HO

OH (R = H , OH hoac O-goc n g )

Cac flavon mau vang

Nedocromilnatri

Bi tp 1- Vit cng thc cu to v gi tn sn phm to thnh ca cc phn ng sau (nu xy ra): a- Pyridin + Br2 300oC. i- Pyridin + NaOH long. k- Pyridin + Anhydrid acetic. b- Pyridin + H2SO4, 350oC. l- Pyridin + Benzensulfoclorid. c- Pyridin + Acetyl clorid, AlCl3. m- Pyridin + Etylbromid. d- Pyridin + KNO3, H2SO4, 300oC. n- Pyridin + Benzylclorid. e- Pyridin + NaNH2, un nng. o- Pyridin + Acid peracetic. g- Pyridin + C6H5Li. p- Pyridin + H2, Pt. h- Pyridin + HCl long. 2- Cng nh amin bc ba, pyridin tc dng vi acid peracetic to thnh hp cht N -oxyd pyridin. Khc vi pyridin, N-oxyd pyridin nitro ha xy ra d dng v tr 4. Hy gii thch kh nng phn ng v s nh hng. 3. N-oxyd pyridin khng nhng c kh nng th i in t m cn c kh nng c phn ng th i nhn vo v tr 2 v 4. V d: N-oxyd-4-nitro pyridin tc dng vi HBr to thnh 4-bromo-N-oxyd pyridin. Gii thch kh nng phn ng . 4- Nhng sn phm no c to thnh khi thc hin phn ng tng hp Skraup vi cc cht sau: a- o-Nitroanilin. b- o-Aminophenol. c- o-Phenylendiamin. 119 d- m-Phenylendiamin. e- p-Toluidin.

Chng 33

HP CHT D VNG 5 CNH NHIU D T

Mc tiu 1. Nu c cch phn loi v c c tn d vng 5 cnh nhiu d t. 2. Nu c mt s ng dng ca d vng 5 cnh nhiu d t trong ngnh Dc. Phn loi. Cc d vng 5 cnh nhiu d t thng gp

D vng thm 2 d t khc nhau v ging nhau:

N3
1

N2

N3 S
1

N3 N2 N1 H 1,2-Diazol N1 H 1,3-Diazol

O
1

N2

S
1

1,2-oxazol

1,3-oxazol

1,2-Thiazol

1,3-Thiazol

D vng 3 v 4 d t khc nhau v ging nhau:

N N2 N3 N2
4N 5N

O
1

O
1

S
1

N2

1,2,5-Oxadiazol 1,2,3-Oxadiazol 1,2,5-Thiadiazol

N2 N1 H 1,2,3-Triazol

5N

N N1 2 H 1,2,4-Triazol

N H Tetrazol

N N

1. Nhm oxazol 1.1. Tng hp nhn oxazol C nhiu phng php tng hp nhn oxazol 1.1.1. Ngng t -bromoceton vi amid
C6H5 C O CH2 Br Bromoacetophenon C6H5 C OH CH Br + HN CH HO Formamid C6H5 O 4-Phenyl-1,3-oxazol N

120

1.1.2. Ngng t hp cht nitrilmandelic vi aldehyd thm

C H5C6 CH N N + O CH C6H5 H5C6 O C6H5

OH Nitrilmandelic

Aldehyd benzoic

2,5-Diphenyl-1,3-oxazol

Tnh thm ca oxazol thp hn thiazol. Oxazol th hin tnh cht ca mt dien lin hp c phn ng cng Diels -Alder.
CN N O + CH2 CH CN Et3N , 180 oC O N CN N

ng dng phn ng ny tng hp cc dn cht ca pyridin. V du: Vitamin B6 c cha d vng pyridin c tng hp nh sau:
Me EtO O N EtOOC H COOEt H 110oC EtOOC COOEt OEt O Me N + H+ HOCH2 CH2OH OH N Me + LiAlH 4 EtOOC COOEt OH N Me EtOOC COOEt OEt N
+ O H

Pyridoxol (Vitamin B6)

Me

Mt vi hp cht cha vng oxazol nh 2,5-diaryloxazol c tnh hunh quang c s dng nh mt tc nhn pht quang. 5 (4H)-oxazolon cn gi l azalacton nh l mt anhydrid ca N-acylaminoacid.
N O 2,5-Diaryl-1,3-oxazol Ar' Ar R N

R' O C O Azalacton

1.2. Benzoxazol Benzoxazol c iu ch bng cch un o-aminophenol vi acid carboxylic hoc anhydrid acid 160C.
NH2 OH + HCOOH - H2O NH CHO OH N O

- H2O , + -H

121

2. Nhm thiazol 2.1. Tng hp nhn thiazol 2.1.1. Cho cloracetaldehyd tc dng vi thioformamid
HC O CH2 Cl

+
S

H2N CH

N3 - H2O , - HCl S
1

1,3-Thiazol

2.1.2. Cho cloracetaldehyd tc dng vi thioure to 2-amino-1,3-thiazol

HC O

+
S

H2N NH2 Thioure C - H 2O ,- HCl S1

N3 NH2

CH2 Cl Cloacetaldehyd

2-Amino -1,3-Thiazol

Thiazol l cht lng khng mu c ts = 117C. 2-Aminothiazol l tinh th khng mu c t nc = 90C. Sulfathiazol l mt loi sulfamid c vng thiazol.
N S NH SO2 NH2

Nhn thiazol c trong hp cht t nhin nh penicillin, vitamin B1 (thiamin), khng sinh bleomycin l phc hp c cu trc aminoglycosid cha vng thiazol. Mt s hp cht tng hp vng -lactam, vng 2-aminothiazol c tc dng tr liu nh cefotaxim.
Me HOCH2CH2 S
+

NH2 N N H
+

2 ClMe H2N

N S

NOMe H N C O Cefotaxim N

S CH2OA COOH

Vitamin B1 ( thiamin)

2.2. Penicillin

Trong phn t cc penicillin thng c vng thiazol ngng t vi vng lactam. Ph thuc vo gc R ta c cc penicillin khc nhau.

122

Vo ng Thiazol H3C H3C HOOC S N Penicillin C=O Vo ng Lactam NHCOR

R C6H5CH2C6H5-O-CH2C6H5-CH=CH-CH2CH3CH2-CH2-CH2-CH2-

Tn Penicillin G Penicillin V Penicillin F Penicillin K

2.3. Benzothiazol
NH2 SH + O HO C H N S

Benzothiazol c tnh base yu. Tc dng vi alkylhalogenid to mui amoni bc 4

N + CH 3I S + N CH3 I+ CH 3I CH3 S 2-Methylbenzothiazol N + N CH3 IS CH3

S Benzothiazol

Trong mi trng kim mui b mt mt phn t HI v chuyn v theo phn ng:

CH3 N+ I NaOH toc H - HI S C s chuyn v nhm methyl
CH3 N+ I CH3 S

N S CH3

NaOH - HI

tc

CH3 N S C CH2

Mui 3-alkyl-2-methylbenzothiazol d tham gia phn ng kiu aldol ha. 2-Mercaptobenzothiazol uc s dng lm cht tng nhanh qu trnh lu ha trong cng nghip ch bin cao su.
NH2 SH 2-Aminothiophenol N + CS2 - H2O C SH S 2-Mercaptobenzothiazol

123

3. Nhm Imidazol: 1,3-Diazol Imidazol l mt d vng phng c nng lng cng hng cao hn mt t so vi pyrrol.

N1 H

..

N3
2

N3 N1 H
2

Vng imidazol c vai tr quan trng v n c trong thnh phn ca acid amin cn thit l histidin. Sn phm decarboxyl ha histidin l histamin.
HOOC H2N C H N H N H H2N C H N H Histamin N

Histidin

Thnh phn histidin l trung tm hot ng ca ribonuclease v ca mt s enzym (men). Chc nng ca imidazol trong cc enzym ng vai tr xc tc trao i proton. H thng imidazol c tc dng nh mt base hoc mt acid. Imidazol t do l mt base "cng" (pKa = 7.0) v n cng tc dng nh mt acid "mm" (pKa= 14,5). Cation v anion ca n l nhng cu trc i xng khng n nh. C th minh ha cc cu trc nh sau:
NN N N + H+ - H+ pKa = 14,5 N H N + H+ - H+ pKa = 7,0 N H H N+ N N+ H H

Dung dch sinh l c pH khong 7, 4 nng ca cc n v imidazol t do cng nh imidazol proton ha c gi tr gn nhau, do trung tm ny ca enzym tc dng nh mt base th trung tm kia tc dng nh mt acid. 3.1. Tng hp nhn imidazol 3.1.1. un nng glyoxal vi amoniac v aldehyd
H C O H C O + NH3 NH3 + O = CH2 - 3H2O N H N

3.1.2. C th thay th glyoxal bng hp cht dicarbonyl khc

C6H5 C O C6H5 C O Benzil NH 3 NH 3 - 3H 2O H5C6 H5C6 N

O = CH-C 6H5 Benzaldehyd

N H5C6 H 2,4,5-Triphenylimidazol

124

3.1.3. Cho -aminonitril tc dng vi aldehyd thm

C H5C6 CH N H + O CH C6H5 H5C6 N N H5C6 + H 2O H 2,5-Diphenylimidazol

N H Aminonitril

Benzaldehyd

3.2. Tnh cht

Bng 33.1: Nhit nng chy v nhit si ca mt vi hp cht azol
Pyrol t s tnc 130 Cht lng Imidazol 256 90 1,3,4-Triazol 260 121 Tetrazol Thng hoa 156

Imidazol c nhit si cao l do gia cc phn t imidazol c lin kt hydro:

H N: N : . . .H N : N: . . . H N: 2,0 A N:

Mt s dc phm c vng imidazol nh 2-nitroimidazol (azomycin), metronidazol, bifonazol, clotrimazol.

N N N H NO2 O2N N CH3 N CH2CH2OH Ph Bifonazol N Ph N N Ph Ph Cl Clotrimazol

2-Nitroimidazol

Metronidazol

3.3. Benzimidazol
N N H

Tng hp nhn benzimidazol:

Ngng t o -phenylendiamin vi formaldehyd

NH2 NH2 + O C H HO N H N

125

 Ngng t o-phenylendiamin vi ester phenylcyanat

NH2 NH2 N + C6H5O C N N H NH2 + C6H5OH

4. Pyrazol: 1,2-Diazol
N2

N1 H

4.1. Tng hp nhn pyrazol

Ngng t hydrazin, alkyl hoc arylhydrazin vi hp cht 1,3-dicarbonyl

R C O C O + R NH2 H N R

R R N R N
+ 2H2O

Cng hp diazoalkan hoc diazoceton vi alkyn

R R CH N N : C C R R R H N R N R R N H R N

..

R CH N N : .. +

..

4.2. Tnh cht Pyrazol to lin kt hydro gia 2 phn t vi nhau. Pyrazol to mui vi kim loi. Pyrazol l mt base yu v c kh nng to ta picrat. Pyrazol c kh nng phn ng km hn pyrrol. Kh b kh v oxy ho. Metylpyrazol b oxy ha to acid pyrazolcarboxylic. Pyrazol tham gia phn ng halogen ho, nitro ha v sulfon ha. S th i in t xy ra v tr 4. 4-Aminopyrazol c th diazo ha. Vng pyrazol c hin tng h bin. V d: 3-metylpyrazol v 5-metylpyrazol l 2 ng phn h bin.

126

V vy t 3-metylpyrazol c th metyl ha v thu c hn hp gm 1, 3 v 1,5-dimetylpyrazol.

4 5 3

CH3

4 5

CH3

N1

N2

4 3

CH3

4 3

CH3

N1

N2

CH3 1,3-Dimethylpyrazol

H 3- Methylpyrazol

H 5- Methylpyrazol

N
2

N1

N
2

N1 CH3

1,5-Di methylpyrazol

Khung pyrazol c chc ceton v tr 5 gi l 5-pyrazolon. 5-Pyrazolon l khung c bn ca cc thuc h nhit nh antipyrin v pyramidon.
4 3 4 3 1 N N 2 C6H5

CH3 CH3

(CH3)2N

4 5

CH3

O C
5

N1 H

N2

O C

O C

N CH3 N1 2 C6H5

5-Pyrazolon

Antipyrin

Pyramidon 1-Phenyl-2,3-dimethyl-4-dimethylamino-5-Pyrazolon

1-Phenyl-2,3-dimethyl-5-Pyrazolon

Khung pyrazolon c dng h bin.

H1 H O C CH3 N N C6H5 O C CH3 N H1 N C6H5 HO C
1

CH3 N N C6H5

Da ng Metylenic

Dng Imin

Dng Phenolic

127

Chng 34

HP CHT D VNG 6 CNH 2 D T

Mc tiu 1. Bit cch phn loi v gi c tn d vng 6 cnh c 2 d t. 2. Nu c mt s ng dng ca chng trong ngnh Dc. Hp cht d vng thm 6 cnh cha 2, 3, 4 nguyn t nit N c gi theo danh php h thng l diazin, triazin, tetrazin. Hp cht d vng thm 6 cnh 2 d t N quan trng c 3 cht theo danh php thng thng c qui c l pyridazin (1,2-diazin), pyrimidin (1,3-diazin), pyrazin (1,4-diazin). Cc benzodiazin theo danh php thng thng quy c c cc cht ph bin nh cinnolin, quinazolin, quinoxalin.
N N Cinnolin N N Quinazolin N N Quinoxalin

D vng 2 d t khc nhau cha oxy, nit v lu hunh, nit. H thng d vng loi ny thng khng th hin tnh thm v tnh cht ca chng biu hin nh l cc hp cht khng vng cha cc chc tng ng. Phn loi

D t l 2 nguyn t N
N3 N
1

N2

N
1

N2

N3 N
1

N4 N

N4 N

1,2- Diazin Pyridazin

1,3- Diazin Pyrimidin

1,4- Diazin Pyrazin

D t l N v S
4 5 6 3

NH S
2 1

H N4

9 3 2 8 7 6

10N

1 2 3 4

2,3-Dihydro- 1,3- Thiazin

S1 1,4- Thiazin

Phenothiazin

128

D t l N v O
4 5
6

5 6

H N4 O1

9 3 2 8 7 6

10N

1 2 3 4

NH O1
2

O
5

2,3-Dihydro-1,3-oxazin

1,4-Oxazin

Phenoxazin

D t l 2 nguyn t O
O1 O4 1,4-Dioxan O1 O4 1,4-Dioxin

1. Hp cht d vng 2 d t l Nit (2N) 1.1. Pyridazin 1,2 -Diazin

4 5 6 3 5 6 4 3

N2

N1

N2

1,2-Diazin , Pyridazin

Cc v tr 3, 5 v 4, 6 nh v tr orto v para so vi nguyn t nit N trong vng. 1.1.1. Tng hp Ngng t hydrazin vi hp cht 1,4-dicarbonyl no hoc cha no.
R + H2N-NH2 C O - H2O R O R C R N N + Br2 - HBr R N N R C H2N-NH2+ C O - H2O R O R

Pyridazin l cht lng si 207C. L mt base yu (pKa = 2,24), to mui vi HCl v to picrat khi tc dng vi acid picric. Phn ng th i in t v phn ng th i nhn xy ra yu. Vng pyridazin b ph v khi tc dng vi cht oxy ha mnh. 1.1.2. Phtalazin: Benzo[d]pyridazin
8 7 6 5 4 1

N2 N3

129

1.2. Pyrimidin. 1,3-Diazin

4 5 6 4

N3

N3 2

6 2 N N1 1 1,3-Diazin , Pyrimidin

V tr 5 nh l v tr meta. V tr 2,4, 6 nh l v tr orto, para so vi mi nguyn t nit N 1.2.1. Tng hp nhn pyrimidin

Ngng t ur hoc thiour vi hp cht 1,3-dicarbonyl

R C R C O R O NH2 H2N C S - H2O R N NH C S R N R N SH

T acid barbituric.
O C O C N H C HO C HO C N N C OH POCl3 Cl C Cl C N N C Cl

6 H (Zn) - 3HCl N

O N H Acid barbituric

2,4,6-Trihydroxypyrimidin

2,4,6-Tricloropyrimidin

Pyrimidin

1.2.2. Tnh cht Pyrimidin nng chy 22,5C, si 124C. Pyrimidin l mt base yu hn so vi pyridazin v pyridin (pKa = 1,23). Cc phn ng th i in t xy ra kh khn v tr 5. V tr 5 nh l v tr meta gim kh nng hot ha do nguyn t nit ca vng. Nu trn vng pyrimidin c cc nhm th y electron th phn ng th i in t xy ra v tr 5 d dng hn. V d: Nitro ha hoc nitroso ha 4,6-diaminopyrimidin
O2N NH2
5

NH2
5

N N NH2

4,6-Diamino-5-nitropyrimidin

Nitro hoa

H2N

N N Nitroso hoa O = N H2N N N

H2N

4,6-Diaminopyrimidin

4,6-Diamino-5-nitrosopyrimidin

130

Phn ng th i nhn xy ra d hn v tr 2 v 4. V d: Sn phm th v tr 4 l ch yu.

NH2 + NaNH2 N N 4-Aminopyrimidin

N N

Cc nguyn t halogen, nhm metylsulfonyl gn vo cc v tr 2 v 4 d dng c thay th bi cc tc nhn i nhn.

Cl N N Cl NaOCH 3 ,CH 3OH 20oC N OCH3 N Cl

N N

KCN ,(CH 3)2NCHO SO2CH3 100oC N

N CN

Hydro ca nhm metyl c trn vng pyrimidin cc v tr 2, 4 c tnh acid v d ngng t vi cc cht c nhm carbonyl. Pyrimidin tc dng vi HgCl2 to phc kh tan. Cc dn xut th ca pyrimidin tch c t cc sn phm thy phn acid nucleic.
OH N N Uracil OH H3C N Thymin OH N OH N Cytosin NH2 N OH

Cc hp cht trn c cc dng h bin. Cc hydroxypyrimidin tn ti dng h bin ch yu dng vng lacton. Cc aminopyrimidin tn ti dng h bin enamin. Cc aminopyrimidin to c mui diazoni. Nhiu dng thuc l dn xut ca hydroxy -, amino- v mercaptopyrimidin. Cng thc cu to ca vitamin B1 (Thiamin) cha khung pyrimidin v khung thiazol.

131

Me HOCH2CH2 S

NH2 N N H
+

2 ClMe

Me HOCH2CH2 S

Cl+ N

NH2 N N Me

Vitamin B1 ( thiamin) dang clohydrat

Vitamin B1 ( thiamin)

Acid barbituric l 2,4,6-trihydroxypyrimidin (I), dng h bin 2,4,6tricetohexahydropyrimidin (II) c th xem nh l ureid vng ca acid malonic (III) (malonylur).
OH N HO N I OH O C O C H HO C O C N H

C O N H II

C O N H III

Khung acid barbituric l dn xut ca mt s dc phm: Veronal v Luminal l cc thuc gy ng cha khung acid barbituric
H

N 1

O C
6 5

C2H5 C C2H5 O

C2 3 4 N H

C2 H5 C N1 6 5 C6 H5 C2 3 4 C O O N H H

Veronal 5,5-Diethylbarbituric

Luminal 5-Etyl-5-Phenylbarbituric

Trong nhiu hp cht quinazolin, quinazolon cha d vng pyrimidin.

O C

N N Quinazolin

NH

N Quinazolon-4

Mt s cht hu c thuc dy quinazolon -4 c tc dng gy ng nh metaqualon

4

O C
1

CH3 N
3 2

CH3 N Metaqualon 2-Metyl-3-(o-Tolyl)-quinazolon-4

132

Trong phn t metaqualon, nhm CH3 v tr s 2 c hiu ng siu lin hp nn cc nguyn t hydro linh ng. Do c th ngng t metaqualon vi cc hp cht c nhm carbonyl to thnh cc hp cht mi c tnh cht thay i.
O
4C

CH3 N
3

+ RCHO CH3 - H 2O

O C N

CH3 N CH=CH R

2-Methyl-3-(o-Tolyl)-quinazolon-4

1.3. Pyrazin
N N N N

1.3.1. Tng hp nhn pyrazin

T ngng t ca phn t -aminoceton v oxy ha tip theo

R C O + H2N R - H2O R N N R [O] - H2O R N N R

C NH2 + O

Phn ng ngng t gia hp cht 1,2-diamino vi hp cht 1,2-dicarbonyl

NH2 + NH2 + O O C R R - H2O N N R R [O] - H2O N N R R

1.3.2. Tnh cht ca pyrazin Pyrazin l mt base yu hn pyridin v pyrimidin (pKa = 0,51). Khi tc dng vi alkylhalogenid th ch to mt mui amoni bc 4 trn mt nguyn t nit. Khi tc dng vi peracid, pyrazin b oxy ha to mono v di N-oxyd. Phn ng th i in t xy ra rt chm. Phn ng th i nhn xy ra nhanh hn. Pyrazin d cng hp vi hydro to piperazin. Piperazin l thuc tr giun.
H N N Pyrazin 6 [H] N N H Piperazin

133

Piperazin c tnh base nh mt base bc 2, c kh nng to mui vi acid hu c V d: Piperazin tc dng vi acid citric to mui citrat piperazin. 2. Hp cht d vng 2 d t l Nit v lu hunh Dn cht quan trng ca p-thiazin l phenothiazin hay dibenzo-p-thiazin
H N S
9 8 7 6 10

H N S
5

1 2 3 4

p-Thiazin

Phenothiazin

2.1. Tng hp nhn phenothiazin

H N AlCl3 hay I2 S H N + H2S S

2.2. Tnh cht Phenothiazin l tinh th khng mu n vng nht, tnc = 180C Tnh base khng ng k Nguyn t H linh ng: to cc dn cht alkyl ha hay aryl ha
H N S Na N NaNH2 S RX

R N + NaX S

134

C th to mui vi halogen:
H N S

Br2

N + HBr + S

Br

2.3. ng dng Phenothiazin l khung ca mt lot phm nhum, trong c xanh methylen.
N (CH3)2N + S N(CH3)2

Br

Xanh methylen

Dy hp cht phenothiazin c nhn amino -alkyl ha v tr 10 v nhm th v tr 2 thng c tc dng gim p trn h thn kinh trung ng, c dng lm: thuc an thn, khng histamin, chng nn.
R 10 N S X

Hot cht Promethazin H

Hot tnh Khng His H1

CH3 CH2 CH N(CH3)2

Chlorpromazin Alimemazin Fenoverin

H, Cl CN, CF3.... H

CH2 CH2 CH2 N(CH3)2

O O C CH2 N N CH2 O

An thn An thn Lit c

Diethazin

CH2 CH2 N(C 2H5)2

Tr Parkinson

135

3. Hp cht d vng 2 d t l Nit v oxy Dn cht quan trng l phenoxazin Tng hp nhn phenoxazin:
OH 2 NH2 H N + H2O O + NH3

o-aminophenol

ng dng:
H2N COOH O HO N O N O COOH

Xanthommatin: cht mu trong nm, a y v bm bm.

R O NH N O CH3 CH3 O R NH NH2 O O R = Thr D Val Pro MeVal Sa

Actinomycin tm c nhiu chng Streptomyces: Tc nhn ngng bo trong tr liu ung th (DNA Intercalant) 4. Hp cht d vng 2 d t l oxy
O O
1,4-dioxan

C tnh cht nh mt ether vng, dng lm dung mi trong tng hp hu c.

O O
1,4-dioxin: cht c ha hc

136

Chng 35

HP CHT D VNG 7 CNH

Mc tiu 1. Nu c cu to v cch gi tn d vng 7 cnh. 2. K c tn cc d vng 7 cnh quan trng v ng dng ca chng. Hp cht d vng 7 cnh c d t l Nit, Oxy hoc Lu hunh (N, O, S) c tn gi tng ng l azepin, oxepin v thiepin.

N H 1H-azepin

O Oxepin

S Thiepin

Thiepin ch tn ti dng hp cht c nhm th ln. Bng cc phng php tng hp thu c 1H-azepin v oxepin. 1H-azepin v oxepin khng ng phng, th nhng h thng in t ca nhng phn t ny li khng nh x. Khc vi pyrrol, nguyn t hydro gn trn nguyn t nit c hin tng h bin. V vy azepin c 2 ng phn 1H-azepin v 3H-azepin. iu lin quan n s khc nhau v s in t trong vng pyrol v vng azepin.
3

N H 1H-azepin

N 3H-azepin

Nu 1H-azepin l ng phng th h thng in t vng phi c 8 in t . Theo tnh ton cu trc phng ny c nng lng cng hng vi gi tr m so vi h thng khng vng, do azepin c tnh thm. Oxepin c cn bng gia cng thc I v II.
R O I R II

137

Nh vy, oxepin t n nh l hn hp khng tch c ca benzenoxyd. Cc aren oxyd nh l cht trung gian khi oxy ha hydrocarbon thm bng cc enzym. S cn bng oxepin v aren oxyd l iu l th trong nghin cu cc hp cht hu c. Cc nghin cu trong lnh vc hp cht d vng 7 cnh tm c nhiu hp cht c hot tnh sinh hc nh benzodiazepin, dibenzazepin, clordiazepoxid v diazepam.
N N H 1,4-Benzodiazepin N H Dibenzazepin
Ph Cl N
+

Ph Cl

N NHMe H Clorodiazepoxid

N O Me Diazepam

1. Azepin 1H-azepin khng c nhm th trn nit (N) rt khng bn v lp tc chuyn thnh ng phn h bin bn vng 3H-azepin. Hp cht azepin th ti nguyn t nit N c tng hp t aziridin. Aziridin thu c t phn ng cng hp iodoisocyanat I -N=C=O vi 1,4-cyclohexadien. Tip theo alkyl ha, brom ho v loi HBr th thu c azepin th.
Br INCO 1-Alkyl ho a 2-Brom ho a N H Aziridin N R N R Br

1,4-Cyclohexadien

Khng ging vi oxepin, 1H-azepin c khuynh hng ng phn ha thnh cu trc bicyclo. Bicyclo ny b proton ha v chuyn thnh dn xut ca benzen.
H+ N R N R NHR

Tnh cht polyen lin hp ca azepin th hin phn ng cng hp Diels -Alder. Ethyl-1-azepincarboxylat cng hp vi ester diethyl azodicarboxylat. Phn ng cng hp xy ra v tr C2 v C5.
5 3

N COOEt

COOEt N N COOEt Diethyl azodicarboxylat

COOEt N N COOEt
2

Ethyl-1-azepincarboxylat

COOEt

138

Khi chiu nh sng vo azepin th c s ng vng bicyclo.

5 3

h N COOEt

N 2 COOEt Ethyl-1-azepincarboxylat

3H-Azepin c iu ch t phenyl azid v amin bc nht hoc bc hai khi c chiu sng. Di tc dng ca nh sng phenyl azid chuyn thnh phenyl nitren. Cht trung gian c to thnh l ketenimin. Cht ny xy ra phn ng cng hp i nhn vi amin v to thnh 3H-azepin.
Ph-N3 Phenyl azid h

Ph-N:
Phenyl nitren

+ R2NH N Ketenimin N

NR2 2-Dialkylamino-3H-azepin

2. Oxepin v thiepin Oxepin c th c iu ch bng phn ng cng hp brom vi 1,4cyclohexadien v sau tch loi HBr.
1-Co ng Br2 2-Epoxi ho a 1,4-Cyclohexadien Br Br ( CH 3ONa) - 2HBr O O Benzen oxyd O Oxepin

S cn bng benzen oxyd v oxepin ph thuc vo v tr v bn cht nhm th c trn vng oxepin. Cc nhm th ht in t v tr 2 lm cho vng oxepin bn, cn v tr 3 th thun li cho benzen oxyd. S n nh ca cc cng thc cng hng (cng thc gii hn) c th gii thch cho s cn bng trn. V d: 2-Acetyloxepin c s lin hp ni phn t vi vng oxy. 2-Acetylbenzenoxyd khng c s lin hp vi vng oxy v nhm acetyl.

O O O C + C CH3 CH3 S lie n h p cu a 2-acetyloxepin

Kho ng co s lie n h p cu a 2-acetybenzenoxyd

O C CH3

S lin hp ca 3-acetyloxepin khng tri rng ra, nhng 3-acetylbenzenoxyd c h thng lin hp vi nhm acetyl, v vy s tn ti ca 3-acetylbenzenoxyd c nhiu kh nng hn 2-acetylbenzenoxyd. 139

O
3

CH3

OCH3

;
O

O CH3 + O

OCH3

O +

S lie n h p cu a 3-acetyloxepin

Co s lie n h p cu a 3-acetybenzenoxyd

Oxepin cng hp vi anhydrid maleic, chng t oxepin c h thng lin hp.

O H + O R O R H C C C C O O O O O C C O

Anhydrid maleic

Thiepin n gin khng bn khi c nhit , nguyn t lu hunh b y ra khi vng v ng phn ha thnh benzensulfid. Cc thiepin vi nhm th c cn tr khng gian ln th cc thiepin ny c th phn ring c. V d: 2,7-di-tertbutylthiepin rt bn, v cc nhm th ln ngn cn s to thnh ng phn benzen sulfid.

S Thiepin

S Benzen sulfid

Me3C

CMe2

2,7-Di-tert-butylthiepin

3. Diazepin v benzodiazepin C 3 loi diazepin mt vng:

N N N N H 1,2-Diazepin N H 1,3-Diazepin N H 1,4-Diazepin

Hp cht 1H-1,2-diazepin c nghin cu nhiu. 1,2-Diazepin c 4 ng phn.

4 3 1 N N H 1H-1,2-Diazepin 5

3H-1,2-Diazepin

4H-1,2-Diazepin

5H-1,2-Diazepin

Hp cht 1H-1,2-diazepin c nhm th ti N -1 c tng hp bng phng php chiu nh sng ln hp cht pyridin imid v polyolefin thch hp. 140

Di tc dng ca nhit 150OC, 1H-1,2-diazepin ti to ra pyridini N -imid. Trong mi trng base c phn ng m vng 1H-1,2-diazepin.
h N N COOE t h N N

Pyridini N-imid

N o - NCOOEt > 150 C

C2H5O CN

COOEt

NH COOEt

Pha n ng cu a etyl-1,2-diazepin-1-carbocylat

3H-1,2-Diazepin c tng hp bng phn ng ng vng hp cht diazo cha no.

R2 R1 H N2 R3 R1 N
1

R2

R2 R3
[ 1,5] H

R3 N
1

S tao thanh 3H-1,2-diazepin

5H-1,2-Diazepin c khuynh hng tn ti ng phn bicyclo, v dng bicyclo l azin c s lin hp hn hp cht azo.
R R N N N N

i vi hp cht benzodiazepin th dn xut ca h thng 1,4-diazepin l quan trng v c rt nhiu cht thuc loi ny l thuc cha bnh. Tng hp loi hp cht ny u xut pht t cc dn xut th 1, 2 ca benzen. S tng hp clonazepam nh sau:
O C O C Ar Ar NH3 O2N N N C O H Clonazepam

O2N

Ar

O2N BrCH2COBr

NH2

NHCOCH2Br

(Ar = 2 Cl-C6H4- )

141

Chng 36

HP CHT D VNG NGNG T

Mc tiu 1. Gi c tn cc hp cht d vng ngng t theo quc t v thng thng. 2. Nu c ng dng ca chng v alcaloid. Purin: Imidazo[4,5-d]pyrimidin
6 1N 2 5 4

N7 N9 H
8

1N 2

5 d

N7 N 9b H
a 8

N
3

4c

Purin l khung d vng ngng t c bn ca nhiu hp cht thin nhin c trong ng vt v thc vt nh acid uric, xanthin, hypoxanthin v adenin.
1N 6

OH
5

OH N7
8

OH N N
6

NH2 N N
6

N HO N H Xanthin N

HO 2 N 4 N 9 3 H

OH

Acid Uric 2,6,8-Trihydroxypurin

N H Hypoxanthin 6-Hydroxypurin

N H Adenin 6-Aminopurin

2,6-Dihydroxypurin

1. Dng h bin ca vng lactam

OH N HO N N H N OH Acid Uric H O O N N H N H N H O

OH N HO N N H N H N O Xanthin C

O C N H N H N C

142

C th alkyl ha purin v to lin kt N -oxyd. Kh nng v v tr ca phn ng tu thuc vo v tr ca cc nhm th c trn khung purin. Metyl ha purin bng dimetyl sulfat trong mi trng nc xy ra v tr 9, nhng metyl ha adenin th xy ra v tr N -9, N-3 hoc N -1.
6 1N 2 5 4 6

N7 N9 H
8

(CH3)2SO4

1N 2

5 4

N7 N9 CH3
8

NH2 N
6

NH2 N (CH 3)2SO 4 N

6

NH2 N

N H Adenin

N CH3 9-N-methyladenin

NHCH3 N N H

N H 3-N-methyladenin 1-N-methyladenin

+ N CH3

+ N

2. Tnh cht ca purin Phn ng th i in t c th xy ra v tr 8 nhng vi hiu sut rt thp. Phn ng th i nhn xy ra cc v tr 2,6, 8. Kh nng phn ng cc v tr c khc nhau. V tr 8 > 6 > 2 V d:
Cl N Cl 2 N
6

NH2 N
6

NH 3- MeOH

N Cl 2 N N H 2-Cloradenin

N H 2,6-Diclopurin

Cl N Cl
2

Cl N 8 ddich NaOH Cl N
2

Cl N CH3

N H C8 O N CH3

3. Mt s alcaloid c khung purin

O C O C N3 N CH3 Cafein O C6
5 4 N3

HN O C

N CH3
7

CH3 N
1

N 7 CH3

N3 N CH3 Theobromin

CH3 N C O 2
1

N7 N9 H
8

3,7-Dimetylxanthin

1,3,7-Trimetylxanthin

CH3 Theophyllin 1,3-Dimetylxanthin

143

HN

O C N H

NH2 C N 3 Guanin

N7

HN

S C

NH2 C N

N7
3

N H Thioguanin

Adenin c trong thnh phn ca acid nucleic. Acid desoxyribonucleic (ADN) c 4 d vng base l thymin, cytosin, adenin v guanin. Cc base ny kt hp vi tng n v desoxyribose.
NH O Base N N O P O O OH O Base H N H ... O CH3 N O N goc n g

... H
b

N goc n g

P O

O OH

...H O
N N N

N H.

N N goc n g H

.. N N ...O H
c

goc n g

a-Hai n v cau truc bac nhat cua ADN b -Adenin-thymin c -Guanin - cytosin

144

Hp cht thin nhin

Chng 37

ACID NUCLEIC

Mc tiu 1. Nu c cc cu to ca acid nucleic. 1. nh ngha Trong cc t bo cha nucleoprotein. Nucleoprotein l mt protid phc tp. Thy phn nucleoprotein thu c protein v acid nucleic. Acid nucleic chnh l phn khng protein trong protid phc tp. Acid nucleic l mt polyester ca acid phosphoric vi ng pentose (D-(-)ribose v 2-desoxy-D-(-)-ribose) v cc base hu c (purin, pyrimidin). Thnh phn nguyn t ca acid nucleic gm C, H, O, N v P. Acid nucleic l nhng cht rn, khng mu. Khi thy phn acid nucleic trong cc iu kin khc nhau th to thnh cc phn on nh sau:
Dung dch NH3 115oC hoac Ba(OH) 2 . Nucleotid

Acid nucleic

Enzim ( nuclease ) . MgO trong dung dch , nhie t .

Dung dch NH3 175oC

Nucleosid + H 3PO4 Acid vo c . ng + Purin + Pyrimidin .

Nu mch polyamid l khung c bn ca protid th mch polyester l khung phn t ca acid nucleic. C th m t mt mt xch ca acid nucleic nh sau:
Nucleosid Base ng O O P O O Mt mt xch ca acid nucleic Nucleotid O Base ng O P O O

145

Trong mt xch trn:

T hp lin kt gia ng ribose v cc base purin hoc pyrimidin gi l nucleosid. T hp lin kt gia nucleosid vi acid phosphoric gi l nucleotid.
2. Phn ng trong acid nucleic C hai loi ng thu c khi thy phn acid nucleic l D (-)-ribose v 2desoxy-D-(-)-ribose. Chng l nhng pentose.
1 CHO

H 2 OH H 3 OH H OH CH2OH
D (-) -Ribose

HOH2C H H
3

OH
2

H 1 H

OH OH D (-) -Ribofuranose

1 CHO H 2 H H 3 OH H OH CH2OH

HOH2C H H OH
3

H
2

H 1 H

OH

2 -Deoxy-D (-) -Ribose

2 -Deoxy-D (-) -Ribofuranose

Ngi ta phn loi acid nucleic cn c trn s c mt cc loi ng ny. Acid nucleic c phn ng l Ribose (pentose) th acid nucleic c gi l Acid RiboNucleic (ARN) hay cn gi l pentonucleic acid. Acid nucleic cha desoxyribose (desoxypentose) th acid nucleic c gi l Acid Desoxyribo Nucleic (ADN). Ribonucleoprotein l thnh phn ch yu ca nguyn sinh cht (cytoplasma). Trong nhn t bo c desoxyribonucleoprotein. C cc k hiu s.ARN, t.ARN , r.ARN v m.ARN.

s-ARN k hiu cc ARN c chc nng chuyn ti acid amin (t.ARN ). r-ARN l k hiu ARN c trong ribosom. Ribosom c trong t bo l ribonucleoprotein gm 40-50% ARN v 50-60% protein. mARN l k hiu ca ARN c to thnh t ADN trong qu trnh sinh tng hp protein (mARN l ARN truyn cc thng tin, m = messenger).
3. Phn base ca acid nucleic 3.1. Cc base purin C 2 base purin c phn lp t acid nucleic l Adenin v Guanin.
NH2 6 5 N 4 3 NH2 6 5 N 4 3 H N N NH2 N N H N N CH3NH N N H N N

1N 2

N N H

1N 2

CH3

Adenin

1-Methyladenin

6-Methyaminopyrin

146

O H N 1 2 H2N N

H N N

O H N H2N N N N H H N CH3NH

H N N

O H N (CH3)2N N

H N N

O CH3 N H2N N

H N N

Guanin

2-Methylaminoguanin 2-dimethylaminoguanin 1-methylguanin

Chng thng di dng 1-methyladenin, 6-methylaminopurin, 2-methylaminoguanin hoc 2-dimethylaminoguanin. Cc base ny c trong thnh phn ca ribosom. 3.2. Cc base pyrimidin C 5 base pyrimidin tch c t acid nucleic l Uracil, Thymin, Cytosin, 5-Methylcytosin v 5-Hydroxymethylcytosin.
O H N 1 6 O 5 4 H N O N H CH3 O NH2 N N H O N N H NH2 CH3 O NH2 N N H CH2OH

O 2 N3 H

Uracil

Thymin

Cytosin

5-Methylcytosin 5-Hydroxymethylcytosin

Nucleosid: L t hp gia ng ribose hoc desoxyribose vi cc base (pyrimidin v purin). Nucleosid l nhng glycosid. Cc loi nucleosid:

Adenosin (Ribose + Adenin), Cytidin (Ribose + Cytosin), Thymidin (Desoxyribose + Thymin).

Guanosin (Ribose + Guanin) Uridin (Ribose + Uracil)

Nucleotid: L t hp gia nucleosid vi acid phosphoric. Nucleotid l nucleosid phosphat. Cc loi nucleotid: Adenylic, Guanylic, Cytidilic v Uridilic 4. Cu to ca cc nucleosid Lin kt gia ng ribose v base pyrimidin c to thnh ti v tr C1 ca ribose v nguyn t Nit N3 (v tr 3) ca pyrimidin (uracil, thymin, cytosin...).
O H N O N3 CH3 O NH2 N N3

HOH2C H H
3

OH

H 1 H

HOH2C H H

H 1 H

OH

Thymidin ( Deoxyribose + Thymin )

OH OH Cytidin ( Ribose + Cytosin )

147

Lin kt gia ng ribose v cc base purin (Adenin, Guanin) c to thnh ti v tr C1 ca ribose v nguyn t N9 ca purin.
NH2 N O N N9 H N H2N N N N 9

HOH2C H H

O H H
1

HOH2C H H

O H

OH OH Adenosin ( Ribose + Adenin )

OH

OH

Guanosin ( Ribose + Guanin )

5. Cu to ca nucleotid Nucleotid l nucleosid phosphat. Lin kt ester c to thnh do nhm OH ti C3 ca ng ribose vi acid phosphoric.
NH2 N O N N H N H2N N N N

HOH2C H H
3

O H H

HOH2C H H
3

O H H

O OH O P OH OH
Adenylic ( Adenosin + Acid phosphoric )

O OH O P OH OH
Guanylic ( Guanin + Acid phosphoric)

6. Cu to ca acid nucleic Acid nucleic c cu trc polymer gm 2 mch cu trc bc mt xon c vi nhau nh lin kt hydro gia cc base vi nhau. Mi mch cu trc bc mt bao gm cc mt xch nucleotid. Nucleosid t mch ny to lin kt hydro vi nucleosid ca mch kia c m t qua tng cp Adenin - Thymin (A=T), GuaninCytosin (GC).

148

O Base O O OH
5

N N

HN

H N

O H N O N

CH3

ng

P O

ng O Base
1 2 N N

Ca p Adenin-Thymin
H N N H N H N H H N O N

Mo t n v Nucleotid

ng

O OH

ng

Hai n v nucleotid trong ca u tru c ba c mo t

Ca p Guanin-Cytosin

Th t trao i hnh thnh lin kt hydro gia cc cp nucleosid vi nhau lm bin i cc chc nng ca acid nucleic. Acid nucleic ng vai tr quan trng trong sinh tng hp protein v tnh cht di truyn.

149

Chng 38

TERPEN

Mc tiu 1. Nu c cch phn loi v gi c tn cc terpen v dn cht ca chng. 2. Nu c tnh cht ha hc v ng dng ca chng trong cc loi tinh du gp trong thin nhin. 1. nh ngha v phn loi Terpen l nhng hydrocarbon cha no c cng thc chung (C5H8)n, c to thnh bng cc n v isopren lin kt vi nhau dng mch h hay mch vng, theo nguyn tc cng hp ''u - ui''.
nC5H8
nCH 2 C CH CH 3
Isopren + au

(C5H8)n
( CH 2 C CH CH 3 CH 2 ) n

CH 2

Monoterpen

au

uoi

uoi

Isopren

Monoterpen

Monoterpen vo ng

Sesquiterpen

Triterpen 5 vo ng

Gi tr n c dng phn loi terpen: n=1 n=2 n=3 n=4 Hemiterpen C5H8 ; Monoterpen (C5H8)2 Sesquiterpen (C5H8)3 Diterpen (C5H8)4 n=6 n=8 Triterpen (C5H8)6 Tetraterpen (C5H8)8 trong c Carotenoid

n = n Polyterpen (C5H8)n cao su

150

Terpen tn ti trong thin nhin ph bin trong tinh du thc vt (thu c bng cch ct ko theo hi nc hay chit bng dung mi hu c cc b phn thc vt). Trong tinh du, ngoi terpen cn c cc dn xut oxy ca chng, thng l alcol, aldehyd, ceton, acid. Tt c c gi chung l terpenoid Cc terpenoid c dng cu to khng vng hoc cu to vng, n vng hay a vng. 2. Monoterpen C10H16 C 3 loi monoterpen:

Monoterpen khng vng (c 3 lin kt i) Monoterpen 1 vng (c 2 lin kt i) Monoterpen 2 vng (c 1 lin kt i)
2.1. Monoterpen khng vng

Myrcen.
3 4 5 6 7

Myrcen c trong tinh du cy Myrcia acris

2 1 8

Myrcen l mt hydrocarbon terpenic khng vng c 3 lin kt i. Myrcen l cht lng c ts = 166-168C. Hydro ha c xc tc thu c decan C10H22 Myrcen c 2 lin kt i lin hp nn c phn ng Diels -Alder vi anhydrid maleic. Ozon ha myrcen to thnh aceton, formaldehyd v cetodialdehyd C5H6O3.
O O3 O C Aceton Myrcen + CHO CHO Cetodialdehyd + 2HCHO Aldehyd formic

7-Metyl-3-metylenoctadien-1,6

Myrcen Myrcen

Ocimen
5 4 6

Ocimen c trong tinh du l hng qu (Ocimum basilicum).

7 8

Ocimen l cht lng, ts = 81C / 30mmHg.

Cng nh myrcen, ocimen c 3 lin kt i, b hydro ha c xc tc to decan, tc dng c vi anhydrid maleic (phn 1 ng Diels -Ander). 2,6-Dimetyloctatrien-1,5,7 Oxy ha ocimen to thnh formaldehyd, aldehyd pyruvic, Ocimen Ocimen acid acetic v acid malonic.

3 2

151

CHO O3 O C CH3 Aldehyd pyruvic Ocimen CH3COOH + HOOC-CH2-COOH Acid malonic CHO + 2HCHO + C O

2.1.1. Cc dn xut ca monoterpen khng vng

Cc alcol ca monoterpen khng vng.

1 3 2 6 7 8 4 5 7 8 8 6

3 4 2 5 7 6

CH2 OH

3 4 5

OH
2 1 4 5

2 6

CH2 OH
1

CH2 OH
1 8

trans
Geraniol

cis
Nerol

Linalol 3,7-Dimethyl-1,6-octadienol-3

Citronellol (Rodinol) 3,7-Dimethyl-6-octenol-1

3,7-Dimethyl-2,6-octadienol-1

Geraniol v Nerol l cc ng phn cis v trans vi nhau.

3 4 2 5 7 6 8 5 7 6 1

CH2OH

3 4 1 2 4

3 2 5 7 6 8

CH2OH

3 4 5 7 1 6 2

CH2OH
8

CH2OH
8

H3C

CH3

trans Geraniol

H3C

cis Nerol

CH3

H2C

CH3 trans Geraniol

H2C

cis Nerol

CH3

Dng isopropyliden 3,7-Dimethyl-2,6-octadienol-1

Dng isopropenyl 3,7-Dimethyl-2,7-octadienol-1

Geraniol, Nerol, Linalol, Citronellol l thnh phn ch yu trong mt s tinh du lm hng liu: hoa hng, cam, chanh, s, geranium...

152

 Cc aldehyd ca monoterpen khng vng.

CHO CHO H3C CH3 H3C CHO

H3C

CH3

CH3

Geranial, Citral a

Neral, Citral b

Citronellal

Citral, citronellal c nhiu trong tinh du s, tinh du bch n. Tng hp Citral b Trong cng nghip, citral b c iu ch t aceton v acetylen.
C2H5OOC O CH3 C C2H2 HC C OH + 2 H C NaNH2 H3C CH3 CH3 H2C CH H3C OH H2O , HO - C2H5OH , -CO2 CH3 O +ClCH2COOC2H5 CH3 COOC2H5 CH3 COOC2H5 CH3 CH3 + H2O - C2H5OH - H2O CH3 CHO CH3 BrCH2 OH + PBr3 CH3 CH3 C2H5OOC C CH3 - HBr O CH3 CH3 O

- H2O

CH3

2.1.2. Tnh cht ca cc monoterpenoid khng vng

S ng vng xy ra theo hng to khung p -mentan.

CHO CH3 CH3 CH3

OH CH3

+ CH3

OH CH2

Citral b , Neral

Dehydropulegol CH3 H+ OH CH3 CH3 + H2O H+

Dehydroisopulegol CH3 OH

CH3

CH2OH CH3 CH3

OH CH3 CH3 cis-Terpin

Nerol

-Terpineol

153

 S ng vng xy ra theo hng to vng ionon

Tng hp -ionon v -ionon Ionon c trong thin nhin, l thnh phn quan trng trong nhiu hng liu v c trong thnh phn cu to ca caroten v vitamin A. Citral ngng t vi aceton c xc tc base hoc acid th to thnh ionon. Ty thuc vo tc nhn ng vng c th to -ionon hoc -ionon. Xc tc l acid phosphoric th -ionon c to thnh ch yu; xc tc l acid sulfuric th -ionon l ch yu. Phn ng to ionon qua nhiu giai on:
CHO + (CH3)2 CO - H2O CH3 CH3 CH3 C O H+ CH3 CH3 H + CH3 CH3 C O CH3 CH3
+

CH3 C O

CH3

ong vong

CH3 H - H + - H+ CH3 + H -Ionon CH3 CH3 C O

Cac giai oan tong hp Ionon citral va aceton

CH3

CH3 H CH3 -Ionon

CH3 C O

CH3

2.2. Monoterpen 1 vng 2.2.1. Limonen v ng phn Cc hp cht thuc loi monoterpen 1 vng c khung p-cymen hoc khung p-mentan

Khung p-mentan l hexahydro-p-cymen

CH3
6 5 1 2 4 3 6 5 10 CH
3

7 CH 1 4 8

7 2 3 6 5 4 1 2 3

CH3

CH3

p-Cymen 1-Methyl-4-isopropylbenzen

8 10 CH3 9 9 p-Mentan Khung p-Mentan 1-Methyl-4-isopropylcyclohexan

Tt c cc monoterpen 1 vng c cng thc C10H16 mang khung mentadien

1 7 2 6 5 4 10 8 9 10 8 1 7 2 3 4 9 1 3 5 1 2 4 4 8 1 2 6 5 1 1 7 2 3

Limonen

-Terpinen

-Terpinen

-Terpinen

Terpinolen

-Phelandren -Phelandren

154

 Danh php:
nh s ch v tr lin kt i. V tr carbon th nht v v tr carbon th hai t trong ngoc, c khi lin kt i c k hiu bng ch . Limonen 1,8-Mentadien 1,3-Mentadien 1(7),3-Mentadien 1,4-Mentadien 1,4(8)-Mentadien 1,5-Mentadien 1(7),2-Mentadien

1,8-Mentadien 1,3-Mentadien 1(7),3 -Mentadien 1,4-Mentadien 1,4(8)-Mentadien 1,5-Mentadien 1(7),2 -Mentadien

-Terpinen -Terpinen -Terpinen

Terpinolen

-Phelandren -Phelandren Tng hp limonen

Penten + Penten

Isopren

Limonen

Limonen - Dipenten

Limonen c nhit si 175-176C. Limonen c tnh quang hot. (+)Limonen c trong tinh du cam, chanh, (-)Limonen c trong tinh bc h, chanh, ()Limonen c trong tinh du thng. nhit 250C limonen b racemic ha. Phn t limonen cn gi l dipenten v c th xem limonen nh 2 phn t penten ng vng vi nhau. 2.2.2. Tnh cht chung ca monoterpen 1 vng

Phn ng cng hp.

Cng hp vi HX ( X = Cl, Br ,HO- )
Cl + 2 HCl Cl Limonen 1,8-Dicloro-p-mentan

155

Cng hp vi halogen:
Br + 2 Br2 Br

Br Limonen CH2Br 1,2,8,9-Tetrabromo-p-mentan

Phn ng oxy ho:

Clorophyl O O Ascaridol 150oc

+ O2

-Terpinen

2,3-Epoxy-cineol-1,4

2.2.3. Cc dn xut ca monoterpen 1 vng (Terpenoid 1 vng) a. Alcol vng no

1 2 3 2

OH

OH

OH

4 8

OH

Menthol 3-Hydroxy-p-mentan

Carvomenthol 2-Hydroxy-p-mentan

cis-Terpin-1,8 1,8-Dihydroxy-p-mentan

Menthol.
1 2 3

OH

Menthol l thnh phn ch yu trong tinh du bc h (Mentha piperita ). Menthol c tnh quang hot. Trong thin nhin ch tn ti dng (-) menthol. Menthol dng kt tinh nng chy 34C. Nhm OH ca menthol c th b ester ha to ester v oxy ha to menthon (p-mentanon-3). Menthol c nhiu ng dng trong dc phm, thc phm. Menthol c chit xut t tinh du bc h hoc tng hp ha hc.

Menthol 3-Hydroxy-p-mentan

Tng hp menthol
Kh ha thymol (t phn ng ca alcol iso -propylic vi m -cresol c xc tc acid)
CH3 + (CH3)2CHOH H2SO4 OH m-Cresol CH3 OH CH3 + 3 H2 Xuc tac CH3 OH CH3 Menthol CH3

CH3

Thymol

156

 ng phn ca menthol
Menthol c 3 carbon khng i xng s tn ti 8 ng phn quang hc, 4 bin th racemic. Nu hnh dung mt phng vng cyclohexan l ng thng m nm ngang, 8 i quang c th trnh by nh sau:
1

CH3 C H

OH
3

H C
4

C H

CH3 C H

CH(CH3)2

CH3 C

H
3

CH3 C H

OH
3

C H

CH(CH3)2 C H

CH(CH3)2

Menthol

H OH iso-Menthol

CH(CH3)2 OH neo-Menthol

neoiso-Menthol

Mi cng thc u c i quang (i gng). Nu ly nhm isopropyl lm chun: Menthol: Nhm CH (CH3)2 c v tr trans vi c 2 nhm CH3 v OH. neo-Menthol: Nhm CH (CH3)2 c v tr trans vi nhm CH3 v cis vi nhm OH iso-Menthol: Nhm CH (CH3)2 c v tr cis vi nhm CH3 v trans vi nhm OH. neoiso-Menthol: Nhm CH (CH3)2 c v tr cis vi vi c 2 nhm CH3 v OH. C th minh ha cc ng phn trn theo cu dng gh ca vng cyclohexan:
CH3 CH(CH3)2 OH Menthol (e,e,e) CH3 CH(CH3)2 OH neo-Menthol (e,a,e) CH3 CH(CH3)2 OH CH3 iso-Menthol (e,e,a) CH(CH3)2 OH neoiso-Menthol (e,a,a)

Phn ng ester ha vo menthol ph thuc vo cu hnh ca nhm OH. Tc xy ra nh sau: Menthol > iso-Menthol > neoiso-Menthol > neo-Menthol. iu chng t nhm OH cu hnh equatorial d xy ra phn ng ester ha. Oxy ha menthol v neo-menthol to thnh menthon (ng phn trans). Oxy ha iso-menthol v neoiso-menthol to thnh iso-menthon (ng phn cis).
e CH3 e O trans Menthon CH(CH3)2 CH3 CH3 a cis O CH3 1so-Menthon e CH(CH3)2

O CH3

157

 cis-Terpin
OH

OH
cis-Terpin-1,8 1,8-Dihydroxy-p-mentan

Terpin dng kt tinh khng mu, khng mi. Hai nhm OH ca 1,8-dihydro-p-mentan v tr cis gi l cis-terpin-1, 8. Terpin c ngm mt phn t nc gi l terpin hydrat, c t nc = 115-117C c quy nh l loi dc dng. Terpin d dng mt mt phn t nc to -terpineol hoc cineol (eucalyptol), ngoi ra cn to -terpineol v limonen. Terpin c tng hp t -pinen hoc t 1,8-dicloro-p-mentan. Terpin c dng lm thuc ho nh tc dng long m, st trng h hp.

Cineol -1,8 (Eucalyptol).

CH3 O CH3 CH3

Cineol c th c 2 loi, cineol -1, 4 v cineol-1,8. Cineol-1, 8 l thnh phn ch yu ca tinh du Eucalyptus (tinh du trm, bch n). Loi nc t terpin -1, 8 cng thu c cineol-1,8. C th xem cineol l mt ether ni phn t c cu trc loi bicyclo c carbon chung v mt nguyn t carbon trn mt mch cu c thay th bng nguyn t oxy. Cineol c tc dng st trng ng h hp.
CH3 - H 2O CH3 O CH3 Cineol-1,8

Cineol-1,8

CH3

OH

CH3

CH3 O CH3

CH3

OH CH3

cis-Terpin-1,8

p-Mentandiol-1,8

1,8-epoxy-p-mentan 1,3,3-trimetyl-2-oxabicyclo[2.2.1]octan

Ascaridol
CH3 O O CH3 CH3

Ascaridol c cng thc phn t C10H16O2. Nu cineol l oxyd th ascaridol l peroxyd. Ascaridol c trong tinh du giun. Ascaridol c to thnh khi chiu nh sng vo terpinen c xc tc clorophyl. Phn ng theo c ch gc t do. Kh ha ascaridol c xc tc to thnh terpin -1,4. Ascaridol c s dng lm thuc ty giun.

Ascaridol

1,4-Epidioxy-2-p-menten

158

b. Alcol c 1 lin kt i. L nhng monoterpenoid 1 vng khng no.

OH OH
-Terpineol -Terpineol -Terpineol

OH

OH OH Piperitol

OH Terpineol-1 Terpineol-4

Terpineol c iu ch t terpin.
OH H3PO4 OH cis-Terpin OH -Terpineol + H2O

2.3. Monoterpen 2 vng (bicyclo) Cng thc cu to c bn ca cc monoterpen 2 vng c cc loi sau:

Caran

Thuyan

Pinan

Camphan

Iso-Camphan

Fenchan

Iso-Bornilan

Chia monoterpen 2 vng thnh 3 loi ph thuc v ln ca vng th hai. Loi 1: Vng 6 cnh ngng t vi vng 3 cnh c caran v thuyan. Loi 2: Vng 6 cnh ngng t vi vng 4 cnh c pinan. Loi 3: Vng 6 cnh ngng t vi vng 5 cnh c camphan, iso-camphan, fenchan, isobornilan. C th gi tn theo danh php IUPAC ca cc cht trn nh sau: Caran Thuyan Pinan Camphan (Bornan) isocamphan Fenchan isobornilan 3,7,7-trimethyl bicyclo[4.1.0]heptan 1-isopropyl-4-methylbicyclo[3.1.0]heptan 2,6,6-trimethylbicyclo[3.1.1]heptan 1,7,7-trimethylbicyclo[2.2.1]heptan 2,3,3-trimethylbicyclo[2.2.1]heptan 1,3,3-trimethylbicyclo[2.2.1]heptan 2,7,7-trimethylbicyclo[2.2.1]heptan

Trong cc loi hp cht ny th nhm hp cht thuc dy pinan v camphan c nhiu ng dng v l thuyt cng nh thc t. 159

2.3.1. Nhm pinan Pinan khng tn ti dng t do trong thin nhin. Hp cht cha no c mt ni i ca pinan l pinen. Pinen c nhiu ng dng.

Pinen
Pinen c 2 loi: -Pinen (2,6,6-trimethylbicyclo[3.1.1]hepten-3(3)).

-Pinen (6,6-dimethylbicyclo[3.1.1]hepten-2(10)).
10 2 1 7 5 6 3 4 1 7 6 4 5 7 5 2 3 1 8 2 6 9 4 2 3 8 9 6 5 1 7 4 10 3

-pinen

-pinen

Pinen l thnh phn ch yu ca tinh du thng. -pinen chim 65-90%, -pinen chim 5-20%. iu ch: nha thng + Na carbonat em ct ko theo hi nc thu c tinh du thng. Ct phn on tinh du thng thu c -pinen v -pinen. Tnh cht ca pinen:

Phn ng cng hp:

Br + Br2
-Pinen

Br

2.3-Dibromopinan

OH +2 H2O , H+ C qu trnh chuyn v Wagner -Pinen OH cis-Terpin-1,8

Phn ng oxy ha.

OH OH KMnO4
-Pinen

CH3 CO COOH NaOBr Acid Pinonic

COOH COOH Acid Pinic

COOH

[O] Pinenglycol

COOH Br2 , CrO3 Acid cis-Norpinic

160

 Oxy ha -pinen:
CH2 KMnO4
-Pinen

COOH OH - HCOO Acid Norpinic

Norpinon

2.3.2. Nhm Camphan. Dn xut quan trng ca camphan (bornan) l Camphor v Borneol.

Camphor 1,7,7-trimethylbicyclo[2.2.1]heptanon-2
10 6 5

1 9

CH3
7 4 8

C2
3

O
5

CH3
6 4

CH3
1 3

CH3
2

C O

Camphor Dang phang

Camphor Dang lap the

Tnh cht ca camphor. Camphor l cht rn nng chy 179C, c tnh quang hot. Camphor c 2 nguyn t carbon bt i xng (1 v 4), nhng ch c mt cp i quang v mt racemic. (+)Camphor v (-)Camphor c trong tinh du long no Cinnamomum camphora, thu c bng cch ct ko theo hi nc. ()Camphor thu c bng phng php tng hp t Camphor -pinen. Camphor to oxim. Chng ct camphor c mt ca ZnCl2 hoc P2O5 s to thnh p-cymen. T camphor c th to thnh borneol.
H3C CH3 O C (+) Camphor H3C H HO (+) Borneol CH3 CH3 HO H3C CH3 H (-) iso-Borneol CH3 CH3 CH3 OH H (+) iso-Borneol (-) Borneol CH3 CH3 CH3 CH3 C O

(-) Camphor CH3 CH3 CH3 H

CH3

OH

161

 Borneol
Borneol l alcol no ca bornan (camphan). Cu trc lp th ca borneol v isoborneol: Borneol c cu hnh endo. Nhm gem-dimetyl pha trn mt phng vng cyclohexan. Nhm OH nm pha di mt phng . iso-Borneol c cu hnh exo. Nhm gem-dimethyl v nhm OH u pha trn mt phng ca vng cyclohexan.

OH

OH

exo
Dang phang Dang lap the

endo

OH

Acid camphorsulfonic
C th sulfon ha camphor to thnh acid. S sulfon ha xy ra v tr 10 hoc v tr 8.
CH3 CH3 CH2SO3H C O CH3 CH2SO3H CH3 C O

Acid 10- Camphorsulfonic

Acid 8- Camphorsulfonic

Tng hp Camphor t -pinen

Tng hp camphor c cc giai on: t -pinen qua cc giai on to bornylclorid, to camphen, to iso-bornylacetat, to iso-borneol v cui cng l camphor.
Cl HCl - 15o -Pinen CH2 - Cl+ +

+ Cl-

Cl Bornylclorur - HCl

Chuyen v Wagner CH2

HCOOH

Camphen

OOCH OH {O} + NaOH - H2O - HCOONa bornylformiat Borneol

O Camphor

C th tng hp camphor t -pinen qua giai on to camphen. Oxy ha pinen bng titan oxyd to thnh camphen. T camphen tng hp camphor. 162

3. Sesquiterpen (C5H8)3 Sesquiterpen c 3 n v isopren. 3.1. Phn loi Sesquiterpen khng vng c 4 lin kt i. Sesquiterpen 1 vng c 3 lin kt i. Sesquiterpen 2 vng (bicyclo) c 2 lin kt i. Sesquiterpen 3 vng (tricyclo) c 1 lin kt i. 3.2. Cc hp cht sesquiterpen 3.2.1. Sesquiterpen khng vng Farnesen C15H24: tn ti 2 dng ng phn v .
7 8 9 6 10 1 11 12 2 5 4 3 8 9 10 11 7 6 1 2 12 3 5 4

-Farnesen
11 12 10 9 7 6 5 4 3 2 11 1 12

-Farnesen
9 10 8 7 6 5 4 3 2 1

Cc dn xut c oxy ca farnesen l Nerolidol, Farnesol, acid Farnesenic.

OH

HOCH2

HOOC

Nerolidol

Farnesol

Acid farnesenic

.3.2.2. Sesquiterpen 1 vng C cc khung c bn Bisabolan, Eleman, Humulan, Germacran.

Bisabolan

Eleman

Humulan

Germacran

163

Cc sesquiterpen c khung bisabolan l bisabolen (C15H24), Zingiberen (C15H24), Bisabolen c 3 ng phn do khc nhau v v tr ca lin kt i.

-Bisabolen

-Bisabolen

-Bisabolen

Zingiberen

3.2.3. Sesquiterpen 2 vng: Bicyclosesquiterpen. Sesquiterpen 2 vng c cc cht nh Cadinen, Selinen, Azulen Cadinen Hai cng thc ng phn c th c:

-Cadinen

-Cadinen

Selinen C 2 ng phn.

-Selinen

-Selinen

Cc dn xut cha oxy ca salinen l Eudesmol v Santonin.

O OH -Eudesmol OH -Eudesmol OH

-Eudesmol

O Santonin

Guaiazulen Phn ln cc tinh du u cha cc hp cht c mu xanh hoc tm. Cc cht mu c khung azulen v sesquiterpen l guaiazulen. Dn xut cha oxy ca guaiazulen l guaiol.

OH Azulen Guaiazulen Guaiol

164

4. Diterpen (C5H8)4 Diterpen c cng thc phn t (C5H8) 4 gm 4 n v isopren. C 2 loi diterpen: Diterpen khng vng v diterpen vng 4.1. Diterpen khng vng Phytol Phytol l dn xut cha oxy ca diterpen khng vng c cng thc phn t C20H40O, l cht lng, nhit si 145C/ 0,03mmHg. Phytol c 1 lin kt i v mt chc alcol bc nht. Thy phn chlorophyl thu c Phytol. Phytol l mt phn cu trc ca vitamin E v vitamin K. Cng thc cu to ca Phytol nh sau:
CH2OH
1

16

11

Phytol (2E)-(7R,11R)-3,7,11,15-Tetramethyl-2-hexadecen-1-ol

Phytol c 2 nguyn t carbon khng i xng (7 v 11) v mt ni i carbon 2 v 3. Phytol thin nhin c gc quay cc bn phi (+)v c cu hnh D c 2 nguyn t carbon khng i xng (Weedon, 1959), nhng theo Djerassi, 1959 th ch C7 mi c cu hnh D. Trong cng thc cu to ca vitamin K1 v nhm vitamin E c gc phytyl.
O CH3 go i Phytyl

CH3 CH3 CH3 CH2 CH C (CH2)3 CH (CH2)3 CH (CH2)3 CH(CH3)2 Vitamin K 1 (2-methyl-3-phytyl-1,4-naftoquinon)

Dy vitamin E thuc nhm tocopherol gm 2 thnh phn cu to l croman v gc phytyl hydro ha.
HO CH3 CH3 O (CH2)3 CH3 goi Phytyl a hydro hoa CH3 CH3 CH (CH2)3 CH (CH2)3 CH(CH3)2

CH3

(+ ) -Tocopherol ( thuoc nhom vitamin E ) -

4.2. Diterpen vng Diterpen 3 vng u c khung carbon 1-methyl-7-isopropylphenanthren hydro ha.

165

CH3
2 3 1

11

10

CH3 CH CH3 Khung carbon cua tricycloditerpen

5 6

4 12

14 8 7

13

Cc diterpen vng loi ny gm c: acid abietic, acid sapietic, acid neo-abietic, acid palustric, acid pimaric, acid iso-pimaric. Chng u l nhng hp cht c 2 ni i c v tr khc nhau. Chc acid ti nguyn t carbon s 1 ca vng. Acid abietic l dn xut cha oxy tiu biu ca diterpen 3 vng (tricycloditerpen). Acid abietic c trong thnh phn ca collophan ph thi khi chng ct nha thng. Acid abietic l cht rn nng chy 170-174C.
CH3
1 2 A 3 4

COOH
10 11 12 B 13 CH3 5 9 14

CH3

COOH

CH3

COOH

C
6

8 7

Acid Abietic

CH CH3

CH3

CH3

CH

CH3 CH3

CH3

CH3 CH3

Acid Sapietic

Acid neo-Abietic

CH3

COOH

CH3

COOH

CH3

COOH

CH3

CH3 CH CH3

CH3

CH CH2 CH3

CH3

CH3 CH CH2

Acid Palustric

Acid Pimaric

Acid iso-Pimaric

5. Triterpen (C5H8)6 Triterpen c cng thc phn t (C5H8)6. Cht tiu biu thuc triterpen l squalen. Squalen c cu trc khng vng, c 6 lin kt i. C 4 n v isopren, trong c 2 n v isopren kt hp vi nhau theo "ui" v "ui". Cng thc cu to nh sau:

166

6 22 23 24 18 19 15 14 10 9 8 7 1

5 4 2 3

Squalen
18 15 14 10 9 8 7 6 5 4 3 2 1

24 23

22 19

Squalen c trong mt s tinh du thc vt v du liu. 6. Tetraterpen (C5H8)8 Tetraterpen c cng thc phn t (C5H8)8 gm 8 n v isopren. Tetraterpen c dng vng v dng khng vng. Carotenoid thuc loi tetraterpen. 6.1. Carotenoid Nhng hp cht thuc dy caroten gi l carotenoid c cng thc cu to nh sau:
H R H CH3 H H H CH3 H
uoi uoi

H CH3 H

H CH3 H

2 n v isopren trung tam

Khung carbon ca carotenoid c cu trc polyisopren. V cu to cc carotenoid, phn trung tm l mch di carbon lin hp gm 4 n v isopren m tm l im kt hp "ui" v "ui " vi nhau ca 2 n v isopren. 2 u mch trung tm l 2 gc R. Cu to ca gc R c th c hai u l mch h, c hai u mch vng hoc gc ny l mch h th gc kia l mch vng. Carotenoid l cc cht mu thc vt hoc ng vt c mu vng hoc vng cam caroten v lutein kt hp vi chlorophyl. Khi kt hp vi chlorophyl, carotenoid c tc dng nh l mt cht nhy cm quang ha. Trong cc loi nm khng cha chlorophyl th mu ca nm l mu ca cc carotenoid. Carotenoid tan c trong du, m v vy cc lipid v cc lipoid u c mu vng nht. Carotenoid kt hp vi acid sulfuric m c v vi dung dch SbCl3 trong cloroform to mu xanh m (Phn ng Carr -Price). ng dng phn ng Carr Price nh lng carotenoid. Mt s carotenoid l hydrocarbon nh caroten, mt s khc l dn xut cha oxy ca caroten nh xanthophyl, acid carotenoid , ester ca xanthophyl.

167

6.1.1. Caroten Caroten c cng thc phn t C40H56. C cc ng phn , ,, v caroten. Caroten chit c t c c rt, v vy hp cht ny u tin c tn gi l carotin sau ny i thnh caroten. Caroten chit t c rt c 15% ng phn , 85% ng phn v khong 0 - 1% ng phn -caroten.

-Caroten -Caroten c nhit nng chy 184-185C, cha 11 lin kt i v cha 2 vng -ionon trong phn t. Khng quang hot.
Khung -ionon CH3 H H H H H CH3 H H H H H CH3 H H H CH3 H Khung -ionon

Caroten

C th vit di dng:

Caroten

Khi tip xc ngoi khng kh -caroten b oxy ha v chuyn thnh mu tm, mu c trng ca vng -ionon.
H H CH3 O Phan t -ionon

-Caroten -Caroten l ng phn ca -caroten, nng chy 187-187,5C. -Caroten d chuyn thnh -caroten. Trong phn t -caroten c vng ionon v vng -ionon. -Caroten c mt carbon khng i xng nn -caroten quang hot v quay phi.
Khung -ionon CH3 H H H H H

CH3 H H H

H CH3 H

H CH3 H Khung -ionon

Caroten Caroten

168

 - Caroten
Nhit nng chy 176,5C, khng quang hot. C 12 lin kt i. Trong phn t c mt vng -ionon. C th xem phn t -caroten gm mt na phn t -caroten v mt na phn t licopen kt hp li vi nhau.
Khung -ionon CH3 H H H H H CH3 H H H H H CH3 H H H CH3 H

Caroten

Mot na phan t Licopen

Caroten

6.1.2. Licopen Cng thc phn t C40H56, c 13 lin kt i trong phn t. Licopen l mu ca c chua. Phn t khng quang hot v khng c vng ionon.
H H CH3 H H H CH3 H H H Licopen H H CH3 H H H CH3 H

Licopen

6.1.3. Vitamin A Cng thc phn t C20H30O. Cc vitamin A c ngun gc t -caroten, nh l mt na phn t -caroten v cha nhm chc alcol. Vitamin A1 v A 2 khc nhau mt lin kt i trong vng.
H H CH3 H H H CH3 H CH2OH H H CH3 H H H CH3 H CH2OH

Vitamin A 1

Vitamin A 2

Vitamin A cn gi l Retinol v n c th thu c khi kh ha Retinal.

169

Cc caroten cn gi l tin sinh t A. C th minh ha s chuyn ha Licopen c trong c chua thnh vitamin theo s :

Licopen

Caroten

Caroten

Caroten

CH2OH Vitamin A 1

7. Polyterpen 7.1. Cao su thin nhin Cao su thuc loi polyterpen c cng thc phn t (C5H8)n. Cao su thin nhin c trch ly t m cao su. Trong m cao su c hydrocarbon (90-95%), protein, ng, acid bo v nha. Thm acid acetic hoc acid formic vo m cao su th cao su ng vn li v tch ra khi dung dch. p, ng khun v sy kh bng khng kh hoc hun khi thu c cao su th. Cao su t nhin l polyisopren c cu hnh cis. Cao su thin nhin mm, dnh kt v d ha nha khi c nhit . Tnh n hi v tnh do ca cao su thin nhin thp. Cao su thin nhin phn ln ha tan c trong dung mi hu c nh benzen, eter, eter du ha. Phn khng tan l cc protein khng tinh khit. Cao su khng tan trong aceton, methanol. C mt s nha nh nha kt (guttapercha) c thnh phn ging cao su thin nhin nhng c cu hnh trans.
CH2 CH3 C C CH2 CH2 H CH3 C C CH2 H CH2 CH3 H C C CH2 H Cao su thien nhien (dang cis )

CH3 CH2

CH2 CH2 H CH3

CH3

CH2 CH2

CH2 H

Nha ket ( gutta-percha) (dang trans )

170

Tin hnh lu ha cao su th tnh cht l ha ca cao su thay i ph hp vi yu cu s dng. un cao su vi mt lng nh lu hunh th cao su b lu ha. Cao su lu ha c n hi tt hn cao su thin nhin. Cao su lu ha khng ha tan trong dung mi hu c. S lu ha c tc dng ni mng cc mch cao su li vi nhau. S lu ha c th tng nhanh hn v thc hin nhit bnh thng bng cch s dng thm cc cht xc tin s lu ha cha lu hunh v nit nh diphenylguanidin, tetramethylthiuramsulphid, Km dimetyldithiocarbamat v mercaptobenzothiazol.
HN C NHC6H5 NHC6H5 Diphenylguanidin S S S S (CH3)2N C S S C N(CH3)2 (CH3)2N C S Zn S C N(CH3)2 SH S Tetramethylthiuramdisulphid Ke m dimethyldithiocarbamat Mercaptobenzothiazol N

7.2. Cao su tng hp Nhiu cng trnh nghin cu tng hp cao su thin nhin nhng kh thc hin cu hnh cis. Nhiu loi cao su tng hp c sn xut v ng dng rng ri.

Cao su Buna
Polymer ha butadien c natri thu c cao su Buna. Thc hin phn ng ng trng hp gia butadien v vinylcyanur thu c cao su Buna N. Cao su Buna S l sn phm ng trng hp gia butadien v styren.

Cao su Butyl
ng trng hp isobutylen vi mt lng nh isopren thu c polyisobutylen gi l cao su Butyl.

Neopren
Khi qua dung dch ng (I) clorid trong amoni clorid, acetylen b dimer ha thnh vinylacetylen. Vinylacetylen cng hp vi HCl thu c cloropren (2clobutadien-1,3). Trng hp cloropren thu c cht cao phn t gi l neopren. 7.3. Cao su silicon Cao su silicon c thnh phn cu to:
Si(CH3)2 O Si(CH3)2 O Si(CH3)2 O

iu ch cao su silicon bng cch tc dng cc sn phm thy phn ca dimethyldiclorosilan (CH3)2SiCl2 vi cc cht c kh nng li ha v tng trng lng phn t. Cao su silicon c tnh cch in cao, khng b thay i khi tip xc vi nh sng, khng tc dng vi acid v kim.

171

Bi tp 1- Cht A c tn gi theo danh php IUPAC l 1-methyl-4-isopropylcyclohexadien-1, 5. nh du ch r cht A thuc loi terpen no: a/ Monoterpen khng vng. b/ Monoterpen 2 vng. c/ Diterpen. d/ Sesquiterpen. e/ Monoterpen 1 vng 2- Vit cng thc cu to cc hp cht sau y v c tn chng theo danh php IUPAC a- Citral a (geranial) b- Citral b (Neral) c- Citronellal d- Geraniol e- Nerol f- Terpin g- Cineol h- Camphor.

3- T citral a hy vit cc phn ng iu ch -ionon v -ionon. Gii thch c ch ca phn ng. 4- Trnh by cc dng ng phn quang hc ca menthol. 5- nh du ch r tn gi ng ca cht c cng thc c cu to sau
b- pinen a- pinen

c-1,7,7-trimethylbicyclo[3.1.1]hepten-3 d-2,7,7-trimethylbicyclo[3.1.1]hepten-3 e-2,6,6-trimethylbicyclo[3.1.1]hepten-2 g-1,7,7-trimethylbicyclo[3.1.1]hepten-2 f-1,7,7-trimethylbicyclo[3.1.1]hepten-3

6- Cc cng thc c k hiu a,b,c,d,e,f, g di y:

Cng thc no l camphan? Cng thc no l pinan?

Gn thm mt nhm OH vo cng thc no trn th thu c borneol?

172

Chng 39

STEROID
Mc tiu 1. Nm c cu to ca steroid, th vo 5 v 5. 2. Bit cch phn loi cc steroid. Steroid l mt nhm hp cht c cu trc tng t nhau c trong thc vt v ng vt. Steroid bao gm cc loi hp cht nh sterol, vitamin D, acid mt, cc hormon sinh dc, cc hormon tuyn thng thn, cc hydrocarbon gy ung th v mt s sapogenin. Steroid l nhng hp cht c khung carbon: cyclopentanoperhydrophenanthren (I).
R
11 2 3 1 4 5 10 9 6 12 13 14 8 7 17 16 15 4 5 6 7 8 9 10 8 9 3 2

3' 2' 1'

5 4

CH3
2

3'

2' 1'

1 10

Theo Diels (1927), nu dehydro ha cc steroid c xc tc Selen (Se) 360C th to thnh mt hydrocarbon thm l 3'-metyl-1,2-cyclopentenophenanthren gi l hydrocarbon Diels (III). V vy cn c th xem cc steroid nh l cc hp cht c ngun gc ca hydrocarbon Diels. l nguyn tc Diels trong cc phng php phn loi v nh ngha steroid. Cc loi steroid khc nhau do c cc nhm th khc nhau hoc v tr cc lin kt i khc nhau trn khung steroid. Ty thuc cc nhm th c trn khung 1,2-cyclopentanoperhydrophenanthren m c cc khung steroid no nh:

Khung carbon cua steroid I

1,2-Cyclopentenophenantren II

Hydrocarbon Diels III

Steran (Gonan)

Estran

Androstan

Pregnan

Cholan

Cholestan

173

1. nh s trn khung steroid Khc vi cch nh s trn vng phenanthren, nh s trn khung steroid c quy nh thng nht nh trn cng thc I. Nu trn khung steroid c cc mch carbon th nh s ln lt tip theo cc nguyn t carbon trn mch carbon theo quy nh.
21 18 CH 20
3 12 17

22 24

23 25

26 27

19 CH
2 3 1 4 5 10

11

13 14

3 9 6

16 15

8 7

anh so tren khung Cholestan

2. Cu hnh v danh php ca khung steroid Khung steroid c 6 nguyn t carbon bt i xng (5, 8, 9, 10, 13 v 14) do c 26= 64 ng phn quang hc. Khung steroid c cc vng 6 cnh A, B, C v vng 5 cnh D. Vng B v C lun c v tr trans vi nhau. Cc vng A /B, C/D c th cis hoc trans vi nhau. Cc khung steroid no c ngun gc thin nhin chia lm 2 dy:
CH3 CH3
10 5

R
17

H
CH3
10 5

CH3 H
9 8 13 14

R
17

H
9 8

13

14

Cholestan A/B trans B/C trans C/D trans Dy 5 hoc dy normal

Coprostan A/B cis B/C trans C/D trans Dy 5 hoc dy allo

Dy Cholestan:

vng A / B v tr trans. vng A /B v tr cis.

Dy Coprostan:

Trong c 2 dy cc vng B /C v C /D u c v tr trans vi nhau. Cc nhm methyl v tr 10 v 13 lun lun trn mt phng ca vng v biu din bng ng lin nt (hoc ng m nt). Trong dy cholestan nguyn t H hydro ti carbon C5 pha di mt phng, biu din bng ng ri nt. Cu hnh carbon ny gi l cu hnh 5. Nhm methyl v tr 10, nguyn t H hydro v tr 5 c cu hnh trans. Trong dy coprostan, nguyn t hydro H v tr C5 c v tr cis ( trn mt phng vng) so vi nhm metyl CH3 C10, c biu din bng ng lin nt (m nt) v c cu hnh 5.
174

 Cc nguyn t hydro trn C8 v C9 lun c v tr trans vi nhau. Nguyn t hydro C14 v nhm metyl CH3 v tr 13 lun c v tr trans. Mch nhnh R gn vo C17 trn mt phng, cng v tr cis vi 2 nhm CH3 v tr 10 v 13.
Nhng steroid l dn xut ca cholestan c tn gi hp cht normal (dy normal). Nhng steroid l dn xut ca coprostan c tn gi hp cht allo (dy allo) 3. Cu hnh v danh php cc nhm th trn khung steroid

Nhm OH alcol v tr C3. V d: phn t Cholestanol v Cholesterol.

Nhm OH trn mt phng vng, c v tr cis so vi nhm metyl CH3 v tr 10 thuc cu hnh . Nhm OH pha di mt phng vng thuc cu hnh hay epi. Cc sterol thin nhin u c nhm OH vi cu hnh , chng thuc dy .

Tip u ng lun ch v tr ca nhm th trn mt phng vng. Tip u ng epi ch ng phn epimer do nghch o cu hnh ti carbon C3.
Cc hp cht steroid thin nhin c cu hnh ti bt k trung tm bt i trn khung steroid khc vi cu hnh ca C5 (c s o ngc cu hnh) th gi l hp cht iso
CH3 CH3 H
9 8

CH3 CH3 H
9 8 13 14 17

3 HO

10 5

3 HO

10 H

14

H 3 Cholestanol 4. Cu dng ca steroid

3 Cholestanol

Cc vng cyclohexan trong khung steroid u c cu dng "gh ". Cholestan v coprostan c cu dng nh sau:
CH3
11 9 H 12 8 13

CH3
15

1 4

10 5

17 16

B
H

14

10 5

CH3 B

11 9

H 12 8

13

CH3
15

R D
17 16

3 a II

6 H 7

H
2

6 H 7

14

a
3

Cholestan A/B trans

III

Coprostan A/B cis

Trong cu dng cholestan, nhm CH3 C10 v H C5 ; H C8 v H C9 ; nhm CH3 C13 v H C14 u c hng axial (a). 175

Trong cu dng ca coprostan nhm CH3 C10 c hng axial (a) v v H C5 c hng equatorial (e); H C8 v H C9 ; nhm CH3 C13 v H C14 u c hng axial (a). Cc hng cu dng c nh hng n kh nng phn ng:

Nhm th v hydro c hng equatorial bn hn hng axial. Trong dung dch kim alcol bc hai dng vng c hng equatorial chim nhiu hn trong hn hp cn bng. Tng t, khi kh ha ceton a vng bng Na /C2H5OH th ng phn cu dng equatorial ca alcol c to thnh nhiu hn. S cn bng ca cc sterol trong dung dch natri etylat 180C nh sau:
Cholestanol {3 (e)} (5 -Cholestanol-3 -ol) Coprostanol {3 (a)} (5 -Cholestanol-3 -ol) 10% 90% 90% 10% Epi Cholestanol {3 (a)} (5 -Cholestanol-3 -ol) Epi Coprostanol {3 (e)} (5 -Cholestanol-3 -ol)

Nhm -OH alcol v nhm -COOH c hng equatorial (e) b ester ha nhanh hn hng axial (a). Tng t khi thy phn cc ester, nhm acyloxy c hng equatorial xy ra nhanh hn hng axial. Cc alcol bc hai c hng axial (a) d b oxy ha hn hng equatorial.
5. Sterol (Sterin) Sterol c trong m v du thc vt, l nhng cht kt tinh. Trong phn t cha chc alcol. Sterol tn ti dng t do hoc dng ester vi cc acid bo cao. Cholesterol, cholestanol, coprostanol (coprosterol) l nhng sterol ng vt (zoosterol). Ergosterol , stigmasterol l nhng sterol thc vt (phytosterol). C nhng sterol tch c t nm, mc gi l cc sterol vi sinh vt. 5.1. Cholesterol
CH3 CH3
10

H
9 8

13 14

17

Cholesterol c cng thc phn t C27H46O, l tinh th, nhit nng chy 149C, quang hot []D= - 39. Cholesterol c trong mt, trong du gan c, trong no b, trong ct sng. Lanolin, cht bo trch ly t g l hn hp ester cholesteryl palmetat, stearat v oleat. Trong phn t c mt lin kt i C5=C6 .

H
6

HO

Cholesterol

176

Cc phn ng mu c trng ca cholesterol:

Dung dch cholesterol trong cloroform vi acid sulfuric to mu (phn ng Salkowski) . Dung dch cholesterol trong cloroform tc dng vi hn hp acid sulfuric m c v anhydrid acetic cho mu xanh l cy (phn ng Liebermann Burchard).
Cholesterol c phn ng ca nhm OH alcol:
Cholesterol H2- Pt Co ng hydro Cholestanol CrO 3 Oxy ho a Cholestanon Zn-Hg ,HCl Kh ho a Cholestan

Cholesterol gi vai tr quan trng trong s hnh thnh cu trc t bo v cc kch thch t (hormon). V khng tan trong nc, cholesterol ni kt vi lipoprotein LDL (low-density lipoprotein) v HDL (high-density lipoprotein) lu hnh trong mu. LDL c nhim v chuyn cholesterol ti cc t bo, HDL chuyn cholesterol v gan bi tit. Vy khi lng LDL nhiu hn HDL th t l cholesterol trong mu s tng ln gy cc triu chng bnh tim mch nguy him . 5.2. Ergosterol
22

CH3 CH3
5

23

Cng thc phn t C28H44O, nhit nng chy 163C, quang hot, []D= -130. C 3 lin kt i ti C5=C6 ; C7=C8 v C22=C23. Ergosterol to ester vi acid. Kh ha ergosterol to ergostanol C28H44O. Oxy ha ergostanyl acetat, lin kt ti C22=C23 b ct t v to thnh acid 3-hydroxynorallocholic. Nhm OH alcol ca ergosterol c th b oxy ha to thnh ceton. Ergosterol l tin vitamin D.

8 7

HO

Ergosterol

5.3. Vitamin D Di tc dng ca nh sng, ergosterol hp th tia t ngoi to thnh hp cht c tc dng chng bnh ci xng. Hp cht ny gi l Calciferol (theo Medical Research Council 1931) hay vitamin D1 (theo Windaus 1931). Nhng em kt tinh phn on thu c hai cht c phn t lng ging nhau l Calciferol v Lumisterol. Calciferol tinh khit ny gi l vitamin D2 (Windaus 1932) hoc ergoscalciferol (theo Chemical Society 1951). S to thnh cc vitamin D t ergosterol theo s phn ng sau: (K hiu mch nhnh v tr 17 ca ergosterol bng gc R).

177

CH3 CH3
5 6

R OH

CH3

R H

CH3

8 7

h
5

HO

Ergosterol

H H pre-ergocalciferol

OH Tachysterol h

CH3

R
CH3

H CH2 HO

CH3

HO Ergocalciferol (calciferol , Vitamin D 2 )

Lumisterol

Cc vitamin D3 l 5,6-cis-cholecalciferol, Vitamin D4 l 22,23-dehydro-5,6cis-ergoscalciferol. Mt s vitamin khc thuc nhm ny l cc vitamin D5, D6, D7.
22 22 23

CH3 CH2
8 5

CH3 CH2
8 5 7

23

HO

HO

Vitamin D3

Vitamin D4

Cc vitamin D c chc nng chuyn ha calci v phosphor trong c th . 5.4. Stigmasterol

22

CH3 CH3
8 5 7

23

24

28

29

26 25 27

Cng thc phn t C29H48O. Nhit nng chy 170C, quang hot v []D= - 40. Stigmasterol c trong du u nnh v tn ti di dng acetat.

HO

Stigmasterol c 2 lin kt i v tr C5=C6 v C22=C23. Brom ha stigmasterol to sn phm Stigmasqsterol cng hp c 4 nguyn t brom. Cc sterol thin nhin v c th c hnh thnh bng qu trnh sinh tng
6

hp. 6. Cc acid mt Acid mt c trong ti mt. Acid mt thng di dng amid ca acid cholic, acid allocholic vi glycin ( H2N-CH2-COOH ) hoc vi taurin (H2N-CH2CH2-SO3H ). 178

Cc amid gi l glycocholic (glycin + acid cholic) v taurocholic (taurin + acid cholic). Acid mt di dng mui kim c chc nng nh ha cht bo thm c vo rut. Acid mt c xem l dn xut hydroxy ca acid cholanic v acid allocholanic. Loi nc acid mt v hydro ha s to thnh acid cholanic v acid allocholanic. C khong 20 acid mt t nhin v mt s acid mt tng hp. V tr ca nhm OH thng gn vo cc nguyn t carbon 3, 6, 7, 11, 12 v 23. Trong cc acid mt t do nhm OH c cu hnh . Nu th cc nhm OH vo acid cholanic thu c nhng acid mt: Tn acid mt t C V tr nhm OH []oD
21 18 CH 20
3 12 17

22

23

Acid Cholic Acid Deoxycholic Acid Lithocholic

195 172 186 197

3, 7, 12 3, 12 3 3 , 7 3 , 6

+37 +53 +32 +11 +8

COOH

19 CH
2 3 1 4 5 10

11 3 9 6

13 14

16 15

8 7

Acid Chenodeoxycholic 140 Acid Hyodeoxycholic

H Acid Cholanic

Cu to ca acid cholic, acid cholanic v acid allocholanic nh sau:

OH
CH3 21 22
3

CH3

COOH
19 CH
11 3 9 6 2 3 1 4 5 10

18 CH 20
12 13 14 8 7 17 16 15

23

COOH
CH3

CH3

COOH

HO

H Acid Cholic

H OH

H Acid Cholanic

H Acid allo Cholanic

Acid cholanic c cu hnh 5. Acid allocholic c cu hnh 5. Acid cholic c 3 nhm OH v tr 3, 7 v 12 ca acid cholanic. T cholesterol c th to thnh acid allocholanic (acid-5-cholanic) v acid cholanic (acid 5-cholanic) qua cc phn ng:
CH3 CH3
10 9 8 13 14 17

CH3 CH3 CH3

CH3

H2-Pt HO

CrO 3 O H Cholestanon
CH3

HO

Cholesterol
CH3

Cholestanol

COOH

Zn-Hg , HCl

CH3

CrO 3

CH3

H Cholestan

Acid allo Cholanic (acid 5 -Cholanic)

179

CH3 CH3
10 9 13 17

CH3 CH3 CH3

CH3

8
7

14

HO

Oxy ho a Oppenauer O

H2-Pt

HO

Cholesterol

Cholet-4-en-3-on

Coprostanol

CH3

CH3 CH3

CrO 3 2-) Zn-Hg , HCl

1-)

COOH

CH3

H Coprostan
O COOH

Cc acid mt c nhm OH v tr s 3 vi cu hnh 3 gi l acid lithocholic.

Acid Cholanic (acid 5 -Cholanic)

HO

HO

HO

Acid lithocholic

5-isoandrostenon

epicoprostanol

7. Cc hormon Hormon l nhng cht do cc tuyn ni tit sinh ra, c tc dng gy nn cc phn ng sinh l khc nhau. Phn loi cc hormon da vo tnh cht sinh l. C hn 80 hormon khc nhau, hn mt na s thuc loi steroid. Ba khung steroid c bn cu thnh hormon:
21 18 19 18 19 18 20

Khung Estran

Khung Androstan

Khung Pregnan

Estrogen

Androgen

Progestagen Mineralocorticoid Glucocorticoid

7.1. Cc hormon sinh dc Cc hormon thuc loi steroid c trong cc tuyn sinh dc nam v n. Cc hormon sinh dc iu khin qu trnh giao hp v c chc nng phn bit gii tnh nam v n

180

C 3 loi hormon sinh dc: Androgen (hormon nam), Estrogen (hormon n), Gestogen (the corpus luteum hormones)..

Androgen
C khung c bn Androstan. Androsteron c cng thc phn t C19H30O2, c mt nhm OH alcol v mt chc ceton. Tu thuc v tr ca cc nhm chc m c nhiu loi androsteron khc nhau:
O O O OH

H HO H HO H HO O

Androsteron

5-iso-aldrosteron

Dehydro epi androsteron

Testosteron

(17-hydroxyandrosten-4-on-3)

Estrogen
Vi khung estran, trong phn t ca nhm estrogen c mt vng benzen, chc OH alcol, chc ceton v ch c mt nhm metyl CH3. Thuc nhm estrogen c cc cht sau:
O OH OH HO H H OH

HO Estron

HO Estriol

HO -Estradiol (Estradiol-17 )

HO -Estradiol (Estradiol-17 )

(3-Oxyestratrien-1,3,5(10)-on-17)

Mt s hp cht c tc dng ging cc hormon estrogen nhng khng c khung steroid nh Stilbestrol (4,4'-dihydroxydietylstilben) c tng hp (Dodds1939).
C2H5 HO C C OH C2H5 trans- Stilbestrol

Gestogen (Progestagen)
Khung c bn l Pregnan. Thuc nhm gestogen c Progesteron (C21H30O2), Pregnandiol (C21H36O2).

181

CH3 C O

CH3 CHOH

HO

Progesteron (Pregnen-4-dion-3,20)

Pregnandiol (5 -Pregnan-3 :20 -diol)

7.2. Cc hormon tuyn thng thn tuyn thng thn c 2 vng, mt vng tit ra adrenalin v mt vng tit ra cc hormon steroid. Cc hormon ny gi l hormon v thng thn. Hormon v thng thn Corticosteroid c 21 nguyn t carbon sp xp theo khung Pregnan. Ty theo bn cht ca X m ta c Mineralocorticoid (X = H) hay Glucocorticoid (X = OH)
21

OH O

HO
11

17

X = H : Mineralocorticoid X = OH : Glucocorticoid

Cc mineralocorticoid c tc dng tng thi K +, H+, ti hp thu Na + v gi nc. i din cho nhm ny l Aldosteron (t nhin) v cc thuc tng hp.
OH CHO HO O

Aldosteron Cc glucocorticoid tc ng trn s chuyn ha glucid, protid, lipid. T cc glucocorticoid t nhin (cortisone, cortisol, corticosteron..), c nhng n lc tm ra nhng glucocorticoid tng hp nhm tng tc dng khng vim, chng thi ghp v gim cc tc dng ph (dexamethason, betamethason, prednisolon, triamcinolon...)
OH O HO O OH O OH HO OH O OH

O Corticosteron (11,21-dihydroxyprogesteron)

O Cortison

O Cortisol (Hydrocortison)

182

Ti liu tham kho

1. E.Angeletcu - Nhng vn l thuyt ca Ho hu c - Rumani Bucarest, 1969. 2. Clayden, Greeves, Warren, Wothers - Organic chemistry - Oxford, 2001 3. I.L.Finar - Organic chemistry, 1969 4. Boyd Harrisson - Organic chemystry, 1999 5. Jerry March - Advanced organic chemistry - Wiley, 1992 6. C.D. Neninetscu - Ho hc hu c - Nga - Matxcva, 1963 7. Trn Quc Sn - C s l thuyt Ho hu c - Nh xut bn Gio dc, 1974 8. Phan Tng Sn, Trn Quc Sn, ng Nh Ti, C s Ho hc hu c - H Ni, 1976 - 1978. 9. Streitwieser, Heathcock - Introduction la chimie organique, 1995 10. L Vn Thi - Ho hc lp th hu c - B Vn ho Gio dc v Thanh nin, 1974 11. http:// www.uis.edu - University off lllnois 12. http:// www.ouc.bc.ca/chem

183