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HP CHT CARBONYL
- Hp cht cha nhm C=O Dn xut acid carboxylic - Bao gm:
4,4-Dimethylpentanal
5-Hexenal 2-Phenylpropanedial
Cyclopentanecarbaldehyde
2-Naphthalenecarbaldehyde
4
SH
2 3
cis-2-mercaptocyclohexanecarbaldehyde
HO O 4-Acetylbenzenecarboxylic acid
Br
Trans-4-bromo-2-oxo-3-butenal
DANH PHP
Nhm Tip v ng Nhm th V d
COOH
O COOH H
oxooxohydroxy aminomercapto
NH2
Butanoic acid
3-Oxopropanoic acid
O COOH
3-Oxobutanoic acid
COOH
HO
4-Hydroxybutanoic acid
COOH
3-Aminobutanoic acid
HO
SH
2-Mercaptoethanol
9
V d
O O H HO CHO
3-Oxobutanal
(R)-2,3-Dihydroxypropanal
OH O
OH
(R)-6-Hydroxy-2-heptanone
H2N CHO
4-Aminobutanal
10
CU TRC
Carbon lai ha sp2 Gc lin kt khong 120
11
TNH CHT VT L
Aldehyde v ketone l nhng phn t phn cc do lin kt C=O c moment lng cc: Acetone: Propene: = 2.7 D (t= 56.5 C) = 0.4 D (t= -47.4 C)
Isopropanol: = 1.7 D (t= 82.3 C) Aldehyde v ketone tan tt trong nc do to c lin kt hydro vi cc phn t nc::
12
TNH CHT VT L
Tn Cu trc KLPT (g/mol)
Nhit si (oC)
CH 3CH 2OCH2CH 3
74 72 72 72 74 74
34 36 76 80 117 141
13
CH3CH2CH2CH2CH3
CH3CH2CH2CHO CH3CH2COCH3
CH3CH2CH2CH2OH
CH3CH2CH2COOH
HA TNH
Phn ng ca aldehyde v ketone c chia thnh 2 loi chnh: Phn ng nhm C=O Phn ng v tr C-
Cc phn ng chnh xy ra nhm C=O bao gm: Phn ng vi acid Phn ng cng vi cht thn hch Phn ng oxy ha
14
PHN NG VI ACID
Oxy ca nhm carbonyl c tnh base yu. C acid Brnsted v acid Lewis u c th lin kt vi cp in t t do trn O ca nhm carbonyl.
Ion oxonium
15
PHN NG VI ACID
Ion oxonium bn vng nh hiu ng cng hng. Kt qu ca s cng hng lm cho ion oxonium mang c im ca mt -hydroxy carbocation:
-hydroxy carbocation
-alkoxy carbocation
16
-alkoxy carbocation
-hydroxy carbocation
17
19
20
Go = RT ln K
21
22
Nhm th rt in t gip phn ng cng vo nhm carbonyl thun li hn (K ln). Nhm th y in t lm gim khuynh hng cng ca nhm carbonyl (K nh). Carbonyl lin hp: gim khuynh hng cng ca nhm carbonyl (K nh). Nhm th kch thc ln lm gim kh nng cng ca nhm carbonyl (K nh).
23
PHN NG CNG
Cng vi nc xc tc acid: ging alkene
24
PHN NG CNG
Cng vi nc, xc tc base: Phn ng tri qua 2 bc: Cng ca nhm OH- vo carbon ca nhm carbonyl. Proton ha O ca nhm carbonyl.
25
NaOH
C ch:
PHN NG CNG
3. Cng vi alcol: To hemiacetal v acetal
Xc tc bi acid hoc base Ch xc tc bi acid
27
PHN NG CNG
3. Cng vi alcol: C ch ca qu trnh to sn phm acetal:
28
gii bo v
(C ch qu trnh gii bo v?)
Acetal bn i vi tc nhn Base, Oxy ha, Cht thn hch (Grignards, alkyllithium, hydride), nhng khng bn trong mi trng acid. 29
O +
H+
Br O O
Mg
H+
HO OH
Deprotection:
32
33
PHN NG CNG
4. Cng vi amine
Aldehyde v ketone phn ng vi amine bc 1 to imine, cn gi l Schiff base:
Cng vi amine bc 1
35
PHN NG CNG
4. Cng vi amine: Aldehyde v ketone phn ng
vi amine bc 2 to enamine:
Cht trung gian phn ng cng l mt carbinolamine. Enamine ch c to ra nu hp cht carbonyl c H-.
36
C ch phn ng:
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Phn ng kh Wolff-Kishner
To Hydrazone
Kh Wolff-Kishner
A diazaallylic anion
Trong thc t, qu trnh c thc hin khng cn c lp cht trung gian hydrazone.
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Phn ng kh Wolff-Kishner l mt phng php kh oxy ca nhm carbonyl ca aldehyde v ketone bn cnh phng php kh Clemmensen (acid mnh, m c) v desulfur ha thioacetal (c th kh c cc nhm d kh bi H2).
Br
Br
5. Phn ng Wittig
c khm ph trong qu trnh nghin cu phn ng th SN2 ca cc phosphine vi haloalkane.
Georg Wittig (18971987) NP 1979
in tch trn P lm tng tnh acid ca C-H: Deproton ha to ra cht trung gian ylide
Nucleophilic
So snh:
PHN NG CNG
6. Cng vi hp cht c kim
C th xem nh
C ch:
44
PHN NG CNG
6. Cng vi hp cht c kim
C ch:
V d
46
47
7. CNG VI HYDRIDE
LiAlH4 v NaBH4 cng vo nhm C=O tng t hp cht Grignard. Hydride ng vai tr l tc nhn thn hch.
48
7. PHN NG TI V TR C-
H v tr C- c tnh acid yu, pKa ~ 15-20 (ging alcol)
H-
49
7. PHN NG TI V TR C-
Deproton ha H v tr C- to ion enolate.
Tnh acid yu
50
TNH ACID TI V TR C-
TNH ACID TI V TR C-
O c m in ln hn C lm cho ion enolate bn vng hn. Lin kt C=O phn cc cng gip bn vng ha ion enolate
52
S TO THNH ENOL
Qu trnh chuyn i mt hp cht carbonyl thnh dng enol tng ng c gi l qu trnh enol ha (enolization).
i vi cc aldehyde v ketone n gin: dng ketone bn hn dng enol. Phn ng c xc tc bi acid hoc base.
54
BN CA ENOL
Hp cht -dicarbonyl to dng enol kh bn vng nh vo hiu ng cng hng lin hp v kh nng to lin kt hydro. Phenol l mt trng hp c bit: Tnh thm lm cho dng enol bn vng hn dng ketone.
55
Xc tc bi acid:
56
+ Cl2 Xc tc base:
O
HCl
Cl
+ HCl
Phn ng ngng ti y
+ Cl2
NaOH
Cl Cl
Cl Cl
+NaCl
Sn phm polychloro ha
Trong mi trng base hoc acid, phn ng tip din bng s loi i mt phn t nc to hp cht carbonyl bt bo ha: Phn ng ngng t aldol.
60
Deproton ha to enol
Trong mi trng acid, sn phm cng aldol khng bn, b mt mt phn t nc to sn phm ngng t aldol.
63
Qu trnh tch nc kh khn hn do ion OH- l mt nhm xut yu. Cn s dng base nng cao. Cc alcol thng thng khng cho phn ng tch nc trong mi trng base. Ti sao ch xy ra i vi -hydroxy aldehyde hoc ketone? 64
65
Phn ng Alkyl ha
Enamine trung ha in v lin kt C=C c mt in t ln. V tr C- c tnh thn hch nh hiu ng cng hng.
Ethenamine
V d:
Lu : Trnh c phn ng Aldol ha gia ion enolate to thnh t aldehyde vi chnh nhng phn t aldehyde cha b deproton ha.
Sn phm ngng Khng th to ion enolate t cho (chnh) Ion enolate to thnh s phn ng vi aldehyde nhanh hn vi ketone
72
73
74
Aldehyde hoc ketone lin hp c th cho phn ng cng vi cht thn hch vo lin kt C=C (khng xy ra i vi alkene thng thng). Phn ng din ra c do to ra cht trung gian bn vng l ion enolate. 75
Hai yu t quy nh: Yu t ng hc (Kinetics): Phn ng no nhanh hn? Yu t nhit ng hc (Thermodynamics): Phn ng no to sn phm bn hn?
76
Cng lin hp
Cng vo carbonyl
Sn phm bn hn
Lin kt C=O mnh hn lin kt C=C Sn phm cng lin hp: cn lin kt C=O, mt lin kt C=C.
77
Trong mt phn ng thun nghch: sn phm to thnh do yu t ng hc quy nh (nhanh hn) cui cng s chuyn thnh sn phm to thnh do yu t nhit ng hc (sn phm bn hn). Nhit cao: u tin cng lin hp
79
Cng lin hp s u tin khi cc cht thn hch c tnh base yu nh CN-, amine, ion enolate (to thnh t cc -dicarbonyl). Cng trc tip vo nhm carbonyl s u tin khi cc cht thn hch mch nh dung dch OH- nng cao. 80
OH Ion cyanide, CN OR (H-CN pKa = 9.4) Enolate t ester Amines: R3N Enolate t aldehyde, ketone (R3N-H+ pKa = 9-11) PhLi Thiolate (t thiol) Grignard C2H5S-H (pKa = 10.5) Enolate (t -dicarbonyl) diethyl malonate (pKa =12.9) ethyl acetoacetate (pKa = 10.7 (CH3)2CuLi 81
82
N
Pyridine
Allylic H is reactive
4. Hydrat ha alkyne
Cng nc vo alkyne to enol km bn, h tng ha to thnh hp cht carbonyl.
Markovnikov: S dng Hg2+, H2O, H+:
5. Acyl ha Friedel-Crafts
(Phn ng th thn in t vo nhn benzene
ACID CARBOXLIC
Nhm carboxy Carboxylic acid hin din ph bin trong t nhin. Gi vai tr quan trng trong tng hp hu c.
Tnh base Lewis (mnh hn) Tnh base Lewis (yu hn) Tnh acid Bronsted Tnh acid Lewis
88
Phn ng ca H-
4-Methylhexanoic acid
OH
Cyclohexanecarboxylic acid
1-Naphthalenecarboxylic acid
91
CU TRC
So snh di lin kt v gc lin kt C=O v C-O
Carboxylic acid c nhit si cao do to c lin kt hydro mnh. Carboxylic acid c th to dimer trong dung dch
92
TNH ACID
Carboxylic acid c tnh acid mnh hn alcohol rt nhiu do hiu ng cng hng v hiu ng cm gip bn vng ho ion carboxylate.
93
TNH BASE
Ging aldehyde v ketone, oxy ca nhm carbonyl ca carboxylic acid phn ng vi acid (Brnsted hoc Lewis) to dng acid lin hp bn vng nh hiu ng cng hng.
S proton ho khng xy ra oxy ca nhm OH do dng acid lin hp to thnh khng bn vng.
94
PHN NG ESTER HA
Ester l dn xut ca carboxylic acid trong nhm OH c thay th bi nhm OR. Carboxylic acid phn ng vi lng d alcol to thnh ester. Phn ng cn s dng xc tc acid. Phn ng thuc loi th thn hch vo nhm carbonyl. Phn ng kh thc hin i vi alcol bc 3.
(lng d)
95
C CH PHN NG ESTER HA
PHN NG ESTER HA
Mt phng php khc ester ha carboxylic acid: alkyl ha ti v tr O ca carboxylate s dng diazomethane (CH2N2), mt cht kh c, d n v c tnh gy d ng.
C ch:
97
O R H
Al
C O Li
:H
P + Br2
PBr3
ng dng quan trng: Tng hp -amino acid. C ch: Ging phn ng -halogen ha aldehyde v ketone s dng xc tc acid.
C ch phn ng:
Trong phn ng halogen ha C- ca aldehyde v ketone, tc nhn phn ng l enol c to thnh trong mi trng acid. Tuy nhin, trong trng hp acid carboxylic, s to thnh enol rt kh do nhm COOH rt bn vng. Chnh v vy nhm COOH cn c hot ha thnh RCH2C(O)Br.
Bc 1. To thnh acid bromide
Bc 2. Enol ha
pKa ~ 16!
Bc 3. Bromo ha
Bc 4. Chuyn i
C ch chi tit ca bc 2 v 3:
iu ch acid carboxylic
1. Oxi ha alcohol bc 1 v aldehyde
Tc nhn oxy ha: KMnO4; hoc CrO3, H2SO4; hoc HNO3; Nhc li: Oxy ha bi tc nhn Cr(VI):
V d:
C ch:
Tautomerization
C N
1.NaOH, H2O 2. H+, H2O 90%
COOH
Cl
Cl
DN XUT CA ACID CARBOXYLIC Dn xut ca acid carboxylic c cng thc tng qut:
-OH c thay th bi L
Ester, L= OR
107
Anhydride, L= OCOR
DN XUT CA ACID CARBOXYLIC Cc dn xut acid carboxylic u th hin ha tnh c trng: phn ng th vi cht thn hch. Phn ng gm hai bc: cng tch:
Qu trnh th c quy nh bi hai yu t quan trng: bn ca dn xut acid carboxylic. Bn cht ca nhm xut L:
108
Cc dn xut acid carboxylic u bn vng nh hiu ng cng hng. Cc lin kt C-O v C-N trong ester v amide ngn hn so vi trong ether v amine do mang c tnh ca lin kt 109 i.
Acyl chloride km bn vng (nh cng hng) nht. Cc dn xut halide c nhm xut tt nht.
110
Hot tnh tng bn (do cng hng) gim Kh nng xut tng
111
Tnh Differences base: Kh reflected nng proton in pK ha a values cc dn xut acid carboxylic: Tng dn t L = X < O < N
Cng thc cng hng ny quyt nh bn ca tiu phn to thnh sau qu trnh proton ha.
Phn ng cng
Trong c hai trng hp: ban u u c s to ra cht trung gian t din. Phn ng din ra theo c ch th hay cng ty thuc vo kh nng xut ca nhm xut.
113
:Nu
Nhm xut
Tch
C ch phn ng th xc tc bi base
Bc 1: Deproton ha cht thn hch
Bc 2: Cng Tch
Bc 3: Ti to cht xc tc
C ch phn ng th xc tc bi acid
Bc 1. Proton ha
Bc 2. Cng Tch
Bc 3. Deproton ha
IU CH ACID CHLORIDE T CARBOXYLIC ACID Acid chloride c tng hp t carboxylic acid s dng thionyl chloride (SOCl2) hoc phosphorus pentachloride (PCl5). Phn ng thuc loi phn ng th vo nhm carbonyl.
118
C ch:
Tm thn in t rt mnh
119
IU CH ACID ANHYDRIDE T ACID CARBOXYLIC Acid anhydride c th c xem nh sn phm ngng t ca 2 phn t acid carboxylic. Anhydride c to thnh khi cho acid carboxylic phn ng vi tc nhn kh nc mnh.
Anhydride cng c to thnh khi cho acid carboxylic phn ng vi acid chloride.
120
H ~ 0, S ~ 0, G ~ 0
Phn ng thy phn ester: dng lng d H2O. Hoc s dng dung dch NaOH.
C ch: Acid v c nh H2SO4, HCl xc tc phn ng theo c ch tng t phn ng to thnh acetal t aldehyde v ketone.
Bc 1. Proton ha O ca nhm carbonyl
Lu : Oxy ca nhm carbonyl c tnh base mnh hn nhm O ca nhm hydroxy do sn phm to thnh bn vng nh s cng hng.
Bc 2. Tc kch ca methanol
Lactone
C ch phn ng
S to thnh amide s d dng hn nu hot ha nhm carboxyl bng cch chuyn acid carboxylic thnh acid chloride, anhydride hoc thm ch l ester.
S to thnh Lactam:
Penicillin l mt lactam:
RHN H H N OH
O R'
COOH
Cyclohexanecarbonyl fluoride
HOT TNH CA ACID CHLORIDE - Acid chloride l dn xut c hot tnh mnh nht i vi cht thn hch.
Phn ng vi nc to acid carboxylic (phn ng thy phn) Phn ng vi alcol to ester
H2O
130
HOT TNH CA ACID CHLORIDE - C ch phn ng to amide: amine ng vai tr l cht thn hch thay th Cl ng thi ng vai tr l base deproton ha ion ammonium: cn 2 mole amine.
- Trong trng hp amine t tin, c th s dng mt amine bc 3 (nh pyridine, triethylamine,m nhn vai tr base. Ti sao phi l amine bc 3?
HOT TNH CA ACID CHLORIDE - Ester c to thnh t phn ng th thn hch ca acid chloride vi alcol. Phn ng to ra sn phm ph l HCl, v vy, mt amine bc 3 cng thng c thm vo trung ha HCl.
B. Dn xut Anhydride
Danh php: Thm anhydride vo tn ca acid
Phn ng:
= Nhm xut
C ch phn ng:
V d:
C. Dn xut Ester
Danh php: Alkyl alkanoate
Mch vng: Lactone
Methyl acetate
O O
1,1-Dimethylethyl butanoate
Phn ng ca Ester
1. Vi nc: phn ng thy phn to acid carboxylic Phn ng thy phn ester trong mi trng base c gi l phn ng x phng ha. C ch phn ng:
V d:
V d:
4. Vi tc nhn Grignard: Ester chuyn thnh alcol Cn s dng 2 ng lng tc nhn Grignard
C ch phn ng:
5. Vi cc tc nhn hydride: Ester b kh thnh alcol hoc aldehyde Tc nhn LiAlH4 kh ester to alcol:
C ch phn ng:
O C R
DIBAL(H) or
H C R
H2O
OAl OCH3
LiAlH4
H2O
OCH3 LiAlH4
RCH2OH
H C R
OH OCH3
-CH3OH
O C R H
Hemiacetal
O R H
Aldol-like
O O
O
CH3I
O O
HO
R O O
O OH O
-
O
CH3OH
D. Dn xut amide
Lin kt amide gip kt ni cc phn t protein. - Danh php: Thay ic hoc oic trong acid carboxylic bi -amide - Nhm th trn N c k hiu N hoc N,N - Cycloalkane amide: Cycloalkanecarboxamide - Amide mch vng: Lactam
Amide bc 1 Amide bc 2
Formamide
N-Methylacetamide
Amide bc 3
4-Bromo-N-ethyl-N-methylpentanamide
Phn ng ca amide
O C R OH
H+ or HO-, H2O
O C R NH2
LiAlH4 DIBAL(H)
O C R H
H H C R NH2
Mi trng acid:
Mi trng base:
PHN NG THY PHN AMIDE Amide b thy phn chm hn ester v phn ng thng cn phi gia nhit.
C ch phn ng:
3. Kh amide to aldehyde
C ch: Phn ng xy ra do tc kch ca hydride to trung gian hemiaminal sau thy phn.
Amide Enolate
Tnh acid ging cc hp cht carbonyl khc Tnh acid ging acid carboxylic
Gi tr pKa ln hn do amide carbonyl bn vng hn nh hiu ng cng hng v N c m in nh hn O. Cho php alkyl ha ti N hoc C (nu N c che):
O R NH CH3
1. LDA 2. CH3I
O R N CH3
1.NaNH2 2. Br
O R N CH3
CH3
CH3
V d:
C ch phn ng:
Bc 1. To thnh amidate
Bc 2. Halogen ha
Bc 3. To thnh N-haloamidate
Bc 5: Chuyn v
E. Alkanenitrile: RCN
Danh php: Alkanoic acid alkanenitrile Nhm th CN c gi l cyano Cyanocycloalkane c gi l cycloalkanecarbonitrile.
Cu trc
C v N trng thi lai ha sp ging C trong alkyne:
PHN NG CA NITRILE
Nitrile l loi hp cht c trng thi oxy ha tng t acid carboxylic v cc dn xut ca acid carboxylic Nitrile b thy phn tng t nh trng hp cc dn xut ca acid carboxylic. Phn ng din ra trong c mi trng acid v base nhng vi tc chm hn so vi ester v amide.
PHN NG CA NITRILE Nitrile phn ng vi cht thn hch ging hp cht carbonyl. Cht trung gian l anion imine c carbon trng thi lai ha sp2.
O Nu
+ C
sp3
R R Carbonyl compound
+
R R
C Nu
Product S n phm
C Nitrile
Nu R
N C Nu
sp2
Product S n phm
PHN NG CA NITRILE
- Phn ng thy phn trong mi trng base
+ OH N
OH R C N H2O R
OH C N H R
O C N H H
C Nitrile O
Amide
OH
+ NH3
Amide H
Carboxylic acid
- Phn ng kh bi LiAlH4
R C Nitrile N N H R C H
RCH2NH2 Amine 1 O R C H
Anion imine
Aldehyde
Amide H
Amine 1
Aldehyde
Carboxylic acid