51

OLYMPIC HA HC QUC T 1996:

i khi ho hc lp th ca cc hp cht hu c c th c xc nh bng
cch kho st tnh cht ha hc c trng ca chng. Cu to ca mt trong cc ng
phn ca axit 5-norbonen-2,3-dicacboxylic, hp cht X (k hiu ~ ch khng nu r
ha hc lp th) c hnh thnh nh cc th nghim sau:
COOH
COOH
X
Khi un nng X nng chy v tch nc to ra hp cht mi Y. Hp cht Y
tan chm trong lng d dung dch nc ca NaOH to X1, cng mt sn phm
nh X to thnh trong lng d dung dch nc ca NaOH. Dung dch thu c ca
X1 trong NaOH c tc dng vi iot, to thnh cc hp cht c cha iot. Axit ha
dung dch to mt hn hp hai cht ng phn trit quang (tiu trin hay raxemic) A
v B theo t l 3:1. Chun 0,3913g hp cht A vi NaOH 0,1000M c mt
phenolphtalein cn dng 12,70mL baz. Cn cng mt th tch NaOH 0,1000M
NaOH chun 0,3913g hp cht B. Khi un nng, hp cht A chuyn chm
thnh hp cht mi C khng cha iot v c th phn ng vi nc. Trong cng iu
kin, hp cht B khng xy ra chuyn ha ny nhng khi un nng vi axit clohydric
th chuyn chm thnh A.
Phi vit v cn bng mi phng trnh phn ng. Khng cn vit c ch
phn ng.
1) nh du (*) cc nguyn t cacbon phi i xng (asymmetric) trong axit 5norbonen-2,3-dicacboxylic.
2) Vit cng thc ha hc lp th ca tng ng phn lp th c th c ca hp
cht X v cu to ca sn phm tch nc nu c xy ra.
3) Vit cc phng trnh phn ng ca mt ng phn lp th bt k ca X v
hp cht tng ng Y vi lng d dung dch NaOH trong nc.
4) Tnh khi lng mol phn t ca cht A. Vit cc phng trnh phn ng t
X1 n A.
5) Vit phng trnh phn ng to thnh C t A v phn ng ca C vi nc.
6) Vit cng thc ha hc lp th ca hp cht X tho mn tt c cc d kin
cho.
7) Vit cc phng trnh phn ng dn t B n A.
8) A v B c phi l cc ng phn khng i quang (diastereoisomers)?

BI GII:
1) Cc trung tm bt i ca X:
*
*

COOH

COOH
*
2) Cng thc cu to ca cc ng phn lp th ca X c ghi bn tri, ct
bn phi l cu to ca sn phm tch nc tng ng (nu sn phm khng
tn ti c du gch ngang).

52

COOH

OC

COOH

OC

O
C

COOH

O
COOH

C
O

COOH

COOH

COOH
COOH

3) Phn ng ca mt ng phn lp th ca X vi NaOH:

COONa

COOH

+ 2NaOH

2H2O

COONa

COOH

Phn ng ca mt ng phn lp th ca Y vi NaOH:

O
C

COONa
O

+ H2O

+ 2NaOH
COONa

C
O

4) MA = 0,3913/(12,7.0,100/1000) = 308 (g/mol-1)

Cc phn ng t X n A:
I

COONa
COONa

5) Chuyn ha A thnh C:

I2
-NaI

HCl
COONa -NaCl
O

CO

C
O

CO

53

COOH
O

CO

CO

HI

CO

Phn ng ca C vi nc:

O
O

CO

2H2O

OH

CO

OH

COOH
COOH

6) Cu to ca X:

COOH
COOH

7) Chuyn ha B thnh A:
I

+H2O

-H2O
COOH

CO
O

COOH

OH

COOH

8) Khng, A v B khng phi l cc ng phn khng i quang.

OLYMPIC HA HC QUC T 1997:
Hp cht X l mt ng ba (tri saccarit) c ch yu trong cc thc n lm
t ht bng. Hp cht X khng phn ng vi dung dch Benedict cng nh khng i
quang. S thu phn xc tc axit to ra ba ng D hexoz khc nhau A, B v C.
Tt c cc hp cht A v B cng nh hp cht I (xem di y) u cho cng mt
osazon khi phn ng vi lng d phenylhydrazin trong mi trng axit. Hp cht C
phn ng vi axit nitric to thnh mt hp cht D khng c tnh quang hot (khng
trit quang). thit lp quan h gia cu hnh gia D glyxerandehit v C, cht
ng andehit 4 cacbon (andotetroz) trung gian khi b oxy ha bi axit nitric khng
to thnh c mt hp cht meso. Khi A c x l bi axit nitric to thnh axit
aldaric c tnh quang hot. C A v B u phn ng vi 5 mol HIO4; A to thnh 5
mol axit metanoic (axit fomic) v 1 mol metanal (fomandehit), trong khi B to
thnh 4 mol axit metanoic, 1 mol metanal v 1 mol CO2. C A v B c lin quan vi 1
andotetroz, andotetroz ny l mt ng phn khng i quang (diastereoisomer)

CO

54
ca cht m C c tng quan. S metyl ha ca X ri thy phn k tip to thnh
2,3,4-tri-O-metyl-D-hexoz (E) (chuyn ha t A); 1,3,4,6-tetra-O-metyl-D-hexoz
(F) (chuyn ha t B) v 2,3,4,6-tetra-O-metyl-D-hexoz (G) (chuyn ha t C).
1) Xc nh cng thc chiu Fischer ca A, B, C v D.
2) V y cng thc chiu Haworth tng ng ch r kch thc vng v
ha hc lp th tuyt i ca E, F v G.
3) Vit cng thc chiu Haworth ca X.
O
C

O
C
H

HO

HO

H
OH
H

OH

OH

CH2OH

D-glyxerandehit

CH2OH

BI GII:
Hp cht X l mt tri-saccarit, khng phn ng vi dung dch thuc th
Benedict, khng quang hot. iu ny cho thy X l mt ng khng kh v v vy
ch c cc lin kt axetal v xetal tn ti tt c cc cacbon anome. Trong ba
monosaccarit th A v B cho cng mt osazon nh vy c ha hc lp th nh nhau
ti C-3; C-4 v C-5 (v C-6). A v B cng khc vi hp cht I (l D-mannoz) tuy
cho cng mt osazon v nh vy mt trong s phi l C-2 epime ca D-mannoz
(l D-glucoz) v cht kia phi l ng xeton tng ng C-2 (nh D-fructoz)
(Suy lun ny c kim nhn sau ny bng cc phn ng ct mch oxy ha). Hp
cht C, sau phn ng vi axit nitric to mt axit dicacboxylic khng quang hot l axit
andaric D. Axit andaric nh vy c th c hai dng: l AA1 (D) v AA2
Andotetroz to thnh trc C (cng nh trc D) khng cho mt hp cht
meso sau phn ng vi axit nitric v nh vy buc phi l D-threoz:

55
COOH

CHO
H

OH

OH

meso
H

CHO
H

OH
COOH

CH2OH

OH

COOH

CHO

CH2OH

D-glyxerandehit

OH

HO

HO

OH

OH

doi xung
guong

COOH

CH2OH

D-threoza

Nh vy axit andaric D to thnh t C nu trn l AA1 v nh vy C phi l

D-galactoz. Hp cht A phn ng vi 5 mol axit HIO4 to ra 5 mol axit metanoic
(axit fomic) v mt mol metanal (fomandehit) cho php ngh A l mt andohexoz
trong khi B phn ng vi 5 mol HIO4 to c 3 mol axit metanoic, 1 mol metanal
v 1 mol CO2 gip d on n l mt xetohexoz.
Cc hp cht A v B c lin h vi mt tetroz khng ging nh C (lin quan
vi D erithreoz). Tetroz lin quan n A v B v th phi c cu to sau y v A
l D glucoz cn B l D fructoz.
CHO
H

CHO
H

OH

OH
CH2OH

OH

HO

CHO

CH2OH

HO

HO

H
H

OH

OH

HO

OH

OH

CH2OH

A
(D-glucoza)

CH2OH

B
(D-fructoza)

Metyl ha X ri thu phn k tip to thnh E, F v G di y:

OH

OH
CH2OH

C
(D-galactoza)

56
CHO
CH2OH
H

OCH3

H3CO

OCH3

OH

OH

H
H

OCH3

OCH3
H

OCH3

CH2OH

E chuyn ha t A
CH2OH
O
CH2OCH3
HO

H
H

OH

OCH3

OH

CH2OCH3

H
H

OH

OCH3

CH2OH

F chuyn ha t B
CHO
CH2OCH3
H

OCH3
O

H
H3CO

H3CO

H
OCH3

OCH3
H

OH

OH
H

OCH3

CH2OCH3

G chuyn ha t C
Trong s metyl ha, ch cc nhm hydroxyl khng tham gia vo s hnh thnh
axetal/xetal (hoc ni phn t hoc lin phn t) mi b ete ha. T d kin metyl
ha, ch E c hai nhm hydroxyli t do c th lin kt vi cc cacbohydrat khc. Nh
vy A phi l cacbohydrat trung tm.
Cc kt qa ny ch ra rng trt t ca cc monosaccarit trong X l C-A-B
(hay B-A-C)
Nu: A5 biu th dng furanoz (vng 5 cnh) ca cacohydrat A.
A6 biu th dng pyranoz (vng 6 cnh) ca cacbohydrat A.

57
B5 biu th dng furanoz (vng 5 cnh) ca cacbohydrat B.v.v
th saccarit X c th c biu th l C6 A6 B5
Mt trong 4 cu to khc nhau c th c ca X c cho di y:
B

CH2OH
O

OH

H
H

OH

CH2

C
H

OH

H
H

OH

Tri-saccarit X

CH2OH

OH
H

OH

OH

CH2OH

OH

Ghi ch: Bn cht ca cc lin kt anome l khng thit yu trong bi. S

sp xp cc lin kt ca A vi B v C cng c th c o li (lin kt 1,1 gia C v
A v lin kt 1,6 gia A v B.
OLYMPIC HA HC QUC T 1997:
Cc nh ha hc ca cng ty Merck Frosst Cnda Montral pht trin mt
dc phm rt c trin vng v hu hiu tr bnh suyn. Cu to ca MK-0476 nh
sau.
COOH
CH3
H3C
S

Cl

MK-0476

Trong qa trnh kim tra, h pht minh mt qa trnh tng hp n gin v

hiu qa, m t di y cho s thiol ha mt phn ca MK 0476 bt u t este
dietyl A

OH

58
1) Hy cho bit cu to ca cc sn phm trung gian B F trong qa trnh tng
hp ny.
COOC2H5

1) LiAlH4
2) H3O+

C6H5COCl
Pyridin

1) CH3-SO2Cl/(C2H5)3N

C (C12H14O3)

2) NaCN

D(C12H13O2N

COOC2H5

1) KOH(aq)
2) CH2N2
COOH 1) NaOH(aq)

2) H3O+

F(C9H14O3S)

1) CH3-SO2Cl/(C2H5)3N
E
2) CH3COS-Cs+

SH

Mt trong nhng giai on cui ca qa trnh tng hp MK 0476, mui diliti

ca thiol axit (G) trn c ghp vi mch ca phn t nu di y:
H3C

CH3

S
O

Cl

H3C

OH

H
1)
- +

CO2-Li+

S Li

2) H+
COOH
CH3
H3C
S

Cl

MK-0476
2) Cn c trn ha hc lp th quan st c ca phn ng trn, gi tn c ch
ca qa trnh ghp ny?

OH

59
3) Nu qa trnh phn ng xy ra theo c ch c ngh nh trn th tc
ton phn (chung) s thay i nh th no nu nng ca c mui thiolat v
cht nn u cng lc tng gp ba?
4) Cc nghin cu mu c tin hnh vi vic s dng brom etan nh l mt
cht nn ti u ha qa trnh ghp ni trn. V cu to sn phm chnh ca
phn ng gia mt mol ng lng brom etan vi:
a) G thm hai mol ng lng baz.
b) G thm mt mol ng lng baz.
5) Qa trnh ghp c th tr nn phc tp do s nh hp oxi ha (dime ha oxy
ha ca G)
Vit cng thc cu to Lewis, ch r tt c cc electron khng lin kt ca sn
phm nh hp - oxy ha trn.
BI GII:
1) Cng thc cu to ca cc cht:
O

O
CH2O

CH2O

CH2OH

H2C

CH2OH

CH2OH

D
CH2S

CH2OH

C
O

CH2CO2CH3

CH2CO2CH3

2) SN2: th nucleophin lng phn t.

3) v = k[tc nhn][tc cht nucleophin]
Tc chung ty thuc vo nng ca c tc nhn ln tc cht nucleophin.
Nh vy, gp ba nng ca cc cht tham gia phn ng s dn n tc chung ca
phn ng tng gp 9 ln.
4) Vi hai ng lng baz:
CH2SCH2CH3

CH2CO2H

Vi mt ng lng baz:
CH2SH

CH2CO2CH2CH3

5) Cng thc Lewis ca sn phm dime:

CH3

60

CH2S

SCH2

H2C

CH2

HO

OH

OLYMPIC HA HC QUC T 1998:

Nm Aspergillus nidulans to ra hai lacton (este vng) thm A v B
(C10H10O4) mi ng phn tan trong dung dch NaOH lnh trong nc nhng khng
tan trong dung dch NaHCO3 trong nc. C A v B u cho mu tm vi dung dch
FeCl3 trong nc. Phn ng ca A vi CH3I c mt K2CO3 to thnh C (C11H12O4)
m ph 1H NMR ca n thy c cha ba nhm metyl khng ging nhau, mt nhm
lin kt trc tip vi vng thm. S tch loi nhm metyl c chn lc ca C vi BCl3
ri x l kt\ tip trong nc to ra D l mt ng phn mi ca A. Ph 1H NMR ca
hp cht D cho thy r s hin din ca mt nhm hydroxyl c to lin kt hydro ni
phn t ti = 11,8pm
OH
H3C

H3C

CO2CH3

O
HO

I
E
Hp cht D c tng hp nh sau: Phenol E c metyl ha (MeI/K2CO3)
to F(C9H12O2) sau F c kh bng liti kim loi trong amoniac lng v 2
metylpropan 2 ol cho mt dien i xng v khng lin hp G. C th chuyn
dien ny thnh lin hp bng phn ng vi KNH2 trong amoniac lng ri x l k tip
trong nc, qa trnh ny ch to mt sn phm H. S ozon phn H ri x l khng
kh l tip to ra nhiu sn phm, trong c xetoeste I. Thc hin phn ng Diels
Alder hp cht H vi dimetyl but 2 indioat J to thnh K (C15H20O6) m khi un
nng s loi eten to ra mt este thm L. Thy phn L trong mi trng baz ri
axit ha dung dch to thnh M(C11H12O6) m khi un nng trong chn khng to ra
N (C11H10O5). Kh N bng NaBH4 trong dimetylfomamit to thnh C v mt lacton O
ng phn, O cng c th thu c nh metyl ha B.
1) Vit cng thc cu trc ca tt c cc hp cht t A n O.
2) Hy trnh by mt cu trc khc ca B.
BI GII:
1) Cng thc cu to ca cc cht:

61
OCH3

OCH3

OCH3

H3C

H3C

H3C

HO

H3CO

B
O

OH

OH

O
HO

C
OCH3

OCH

H3C

H3C

H3C

H3C

HO

H3CO

H3CO

O
H3CO

OCH3

G
OCH3

CO2CH3
H3C

H3C

CO2CH3

H3C

O
H3CO

H3CO

CO2CH3

OCH3

OCH3
H3C

CO2CH3

H3C

H3CO

CO2CH3

H3CO

L
OCH3
H3C
O
H3CO

O
O

2) Cng thc khc ca B:

OCH3
CO2H

H3C

CO2H

H3CO

N
O

62
OH
H3C
O
H3CO
O

OLYMPIC HA HC QUC T 1999:

Glycozit A (C20H27NO11) c trong ht Rosaceae khng phn ng vi dung
dch Benedict cng nh nc Fehling. S thu phn bng enzym ca A cho (-)B
(C8H7NO) v C ( C12H22O11) nhng s thu phn hon ton bng axit to thnh cc
sn phm hu c (+) D (C6H12O6) v (-) E (C8H8O3).
C c mt lin kt - glycozit v cho phn ng vi dung dch Benedict cng
nh nc Fehling. Metyl ha C vi MeI/Ag2O to thnh C20H38O11 m khi thu phn
trong mi trng axit cho 2,3,4-tri-O-metyl-D-glucopyranoz.
() B c th c iu ch t benzandehit v NaHSO3, tip theo vi NaCN.
Thu phn () B trong mi trng axit cho () E (C8H8O3).
1) Vit cc cu to ca A D vi ha hc lp th ph hp theo cng thc chiu
Haworth tr cht B.
Glycozit A c c tnh v c cho l do hp cht F rt c, c gii phng
trong iu kin thy phn. S kh c ca hp cht F trong cy ci c th km theo
cc phn ng (khng trnh by ha hc lp th).
O

F + H2N

CH

O
OH

enzym

H (C4H6N2O2)

enzym

H2N

CH

CH2

CH2

SH

L - cystein

NH2

L - asparagin

Mt lng nh hp cht F trong c th ngi c gii c bng mt phn

ng trc tip vi cystin cho L cystein v hp cht I (C4H6N2O2S) c bi tit theo
nc tiu (khng trnh by ha hc lp th).
NH2
S

H2
C

H2
C

F +

NH2
C
H
H
C

COOH
COOH

enzym

HS

H2
C

C
H

COOH

L - c y s te in

NH2

c y stin

Hp cht I cho thy khng b hp th ti 2150 2250cm-1 trong ph IR ca n

nhng quan st thy mt di ti 1640cm-1 v cc di ng vi nhm cacboxyl.

I (C 4 H 6 N 2 O

63
2) Hy vit cng thc phn t ca cc hp cht F v G v cc cng thc cu to
ca cc hp cht H v I. Ch r ha hc lp th ca H.
(-) 1 Phenyletan 1 d C6H5CHDCH3 c th c iu ch dng quang
hot v kh nng trin quang kh mnh []D = -0,6.
CH3

C8H10O
(-)N

C6H5SO2Cl
Pyridin

1) LiAlD4/ete
2) H3O+

H
C6H5

(-) - 1 - phenyletan -1 -d
Cu hnh tuyt i ca (-) 1 phenyletan 1 d lin h vi (-) E theo cc
phn ng sau:
Ag2O
1) LiAlH4/ete
C8H8O3
C10H14O2
C12H16O3
C
H
I
2) H3O+
2 5
(-) E
(-) J
(-) K

1) LiAlH4/ete C H CHCH (OC H )

C6H5SO2Cl
6 5
3
2 5
L
2) H3O+
Pyridin
(-) M
Hp cht (-) M cng c th thu c t hp cht M nh sau:
1)K
C6H5CHCH3(OC2H5)
C8H10O
(-) M
(-) N 2) C2H5I

3) Suy ra cu hnh tuyt i ca (-) E v cu to vi cu hnh ca mi cht trung

gian ( J O) trong qa trnh.
4) Cho bit c ch c lin quan trong s chuyn hp cht O thnh 1 phenyletan
1 d.
BI GII:
1) Cng thc cu to ca cc cht:
CH2OH
O

CH2

H
OH

H
O

H H

OH

H
H

OH

OH

H
H

OH
H

OH

H
C

CN

64

HO

H
C

CH2OH

CN

CH2

H
H

OH

H H

OH

OH

H
H

OH

OH

OH
H

CH2OH

OH

C
O

OH

H
H

OH

OH
H

OH

2) Cng thc phn t F: HCN

Cng thc phn t G: H2S
HOOC

COOH
H2N

H
N

HOOC

hay

NH

NH2

CH2CN

H
3) Cng thc cu to ca cc cht t E n O:
COOC2H5

COOH

OH

OC2H5

C6H5

C6H5

(-) E

(-) J

CH2OSO2C6H5

CH2OH
H

OC2H5
C6H5

(-) K

OC2H5
C6H5

65
CH3

CH3

CH3

CH3

R
H

OC2H5 H

OH

C6H5

C6H5

(-) M

(-) N

OSO2C6H5 D
C6H5

H
C6H5

(-)1 - phenyletan - 1 -d

4) C ch ph hp: SN2.
OLYMPIC HA HC QUC T 1999:
Peptit A c khi lng phn t 1007. Thu phn hon ton bng axit cho cc
aminoaxit sau vi s mol bng nhau: Asp, Cystin, Glu, Gly, Ile, Leu, Pro v Tyr. Oxy
ha A vi HCO2OH ch cho B cha hai gc axit cysteic (k hiu l Cya), l mt dn
xut ca cystein vi nhm thiol b oxy ha thnh axit sunfonic.
1) C bao nhiu nhm cha axit sunfonic c to thnh t s oxy ha mt lin
kt disunfua?
Thu phn khng hon ton B cho mt s di v tri-peptit (B1 B6). Trt t
ca mi sn phm thu phn c xc nh trong nhng cch sau.
Aminoaxit c N cui c xc nh bng cch x l peptit vi 2,4
dinitroflobenzen (DNFB) cho DNP peptit. Sau khi thu phn hon ton DNP
peptit bng axit, thu c mt DNP aminoaxit, cht ny c th c xc nh d
dng bng cch so snh vi cc DNP aminoaxit chun.
2) Khi x l B1 vi DNFB ri thu phn k tip bng axit to thnh mt sn
phm l DNP Asp. iu ny cho thy B1 c axit aspartic ti N cui. Hy
vit cu to y ca DNP Asp ti im ng in ca n (khng cn ha
hc lp th).
K , aminoaxit c C cui c xc nh bng cch un nng peptit ti
100oC vi hydrazin, cht ny b gy tt c cc lin kt peptit v chuyn tt c tr
aminoaxit C cui thnh hydrazit ca aminoaxit, cn nhm cacboxyl C cui cn
nguyn vn.
Theo cch ny, cc aminoaxit N- v C- cui c xc nh th t ton b ca
B1 B6 nh sau:
B1: Asp Cya
B4: Ile Glu
B2: Cya Tyr
B5: Cya Pro Leu
B3: Leu Gly
B6: Tyr Ile - Glu.
Thu phn B vi mt enzym t Bacillus subtilis cho B7 - B9 vi thnh phn
nh sau:
B7: Gly NH2 (glyxinnamit)
B8: Cya, Glu, Ile, Tyr
B9: Asp, Cya, Leu, Pro
3) Vit trnh t ca B8 nu thu c DNP Cya khi x l B8 vi DNFB ri thu
phn hon ton sau bng axit.
4) Nu cc aminoaxit N- v C- cui ca B9 c xc nh theo th t l Asp v
Leu, vit trnh t ca B9.
5) Vit cu to y ca A v ch r v tr ca lin kt disunfua.
Tuy nhin khi lng phn t ca A tnh c th ln hn ga tr thc nghim
hai n v. Quan st k lng hn hp thu c t s thy phn hon ton bng axit
ca A ngoi cc aminoaxit tm c lc u cn c 3 ng lng mol amoniac cng
c to thnh.

66
6) ngh cu to iu chnh ca A v khoanh trn (mt hay nhiu v tr) trn
cu to ny cho thy tt c cc ngun to amoniac c th c.
BI GII:
1) 2
2) Cng thc cu to:
O
O2N
OH
OH
N
H
NO2

3) Trnh t ca B8 l: Cya Tyr Ile Glu.

4) Trnh t ca B9 l: Asp Cya Pro Leu.
5) Cu to y ca A l: Cys Tyr Ile Glu Asp Cys Pro Leu Gly
NH2
6) Cu to iu chnh ca A:
Cys Tyr Ile Gln Asn Cys Pro Leu Gly NH2
Cc v tr gch chn l cc v tr to amoniac.
OLYMPIC HA HC QUC T 2000:

Shikonin l hp cht c mu c tm thy r ca cy

Lithospermum erythorizon mc Chu . Mt on r c s dng trong
nhiu th k lm bi thuc dn gian v ngy nay c s dng lm thuc
m cha cc vt bng. Shikonin c cng thc cu to nh sau:
OH

OH

OH

1. Shikonin c bao nhiu ng phn lp th?

2. C phi cc ng phn lp th ca Shikonin c cng nhit nng chy
khng?
y l mt phn trong qa trnh tng hp Shikonin:

67
O

OCH3

OH

OH

+A
B (xt)

OCH3

OH
+C

OH

OH

OH

3. Vit cng thc cu to A.

4. Gi tn A.
5. Vit cng thc cu to C
Lng ln nhng hp cht tng t Shikonin c tng hp nhn
c cc cht c hiu lc hn. Mt chui phn ng c dn ra di y
Shikonin

SOCl2

C6H15ClO4

KOH/EtOH
70oC

C16H14O4

6. Vit cng thc cu to ca E.

7. E c th c bao nhiu ng phn lp th.
Mt cch khc iu ch nhng dn xut c ch ca Shikonin l:
OCH3

OCH3

HBr

F
C21H29BrO5

OCH3

OCH3

OCH3

1) Mg/(C2H5O)2
2) CO2
3) HCl(dd)
G
C22H30O7

8. Vit cng thc cu to F.

9. Vit cng thc cu to G.
BI GII:

1. C 2 ng phn.
2. Tt c cc ng phn lp th ca Shikonin u c cng nhit nng chy.
3. A c cng thc cu to nh sau:

68

Cl

4. Tn IUPAC ca A: 4-Metyl-3-pentanoylclorua.
5. Cng thc ca C: NaBH4 (LiAlH4 cng c th c chp nhn).
6. Cng thc cu to ca E:
OH
O

OH
O
7. E c th c 2 ng phn lp th .
8. Cng thc cu to ca F :
OCH3 OCH3
OCH3

Br
OCH3 OCH3
9. Cng thc cu to ca G:
OCH3 OCH3
OCH3

COOH
OCH3

OCH3

OLYMPIC HA HC QUC T 2000:

Hp cht thin nhin A cha C, H, O c % mi nguyn t theo khi

lng nh sau: C: 63,2%; H: 5,3%; O: 31,5%.
Ph khi ca A:

69

1. Xc nh cng thc nguyn ca A.

2. Vit cng thc phn t cht A.

Dung dch cht A trong ete c lc vi dung dch NaOH trong ete. Sau
phn ng thy A khng cn trong ete. Li lc k dung dch A trong ete vi
dung dch NaHCO3 ri yn thy A vn cn trong ete.
3. A c th c nhng nhm chc no?
A phn ng c vi thuc th Tollens.
4.4. A c nhm chc no?

Ph HNMR ca A ghi tn s 300MHz cho hnh sau (dung mi

CDCl3). Cho vch 7,27ppm v 3 vch n 3,9; 6,3 v 9,8ppm.
Hnh sau l s c th ha hnh ph trong khu vc t 6,9 n 7,6ppm:

70

Tn hiu 6,3ppm mt i khi nh D2O vo:

5. Thng tin no sau y ng:
+ Trao i lin kt gia C v H.
+ Trao i lin kt gia O v H.
+ Hiu ng pha long.
+ S thy phn.
Khi them CDCl3 th vch ny xut hin tn hiu thp hn.
6. Thng tin no sau y ng:
+ Tng mc lin kt hydro.
+ Gim mc lin kt hydro.
+ C lin kt hydro lin phn t.
+ C lin kt hydro ni phn t.
+ Khng c lin kt hydro.
7. Vit 4 cng thc cu to c th c ca A.
8. Mnh no bin mt ti pic c khi lng 137 v 123.
9. Hai trong s 4 ng phn vit c pKa thp hn hai ng phn cn li.
Xc nh chng.
BI GII:

1.
2.
3.
4.
5.
6.

C8H8O3.
C8H8O3.
Nhm phenol.
Nhm andehit.
Trao i lin kt O-H.
Gim mc lin kt hydro v c s to thnh lin kt hydro lin phn
t

7.
CHO

CHO
OCH3
HO

OCH3
CHO
CHO

OH

OH
OH

8. CH3 v HC=O
9

OCH3

OCH3

71

CHO
OCH3

CHO

OH

OH

OCH3

OLYMPIC HA HC QUC T 2001:

R gng (Zingiber officinale) c bit nhiu v mt dc tnh v nhng tnh
cht ca hng liu. Ti Ayurveda (Ni c truyn thng v thuc n ), rt nhiu
ng thuc c s dng gng nh l mt v thuc tr cc bnh lin quan n rut, cm
lnh thng thng v mt s bnh khc. Mt vi hp cht c coi nh l nguyn
nhn gy ra v cay ca gng. Rt nhiu trong s l nhng dn xut th n gin
ca vng thm vi di mch c khc nhau. Ba trong s l Zingeron; (+)[6]
Gingerol v Shogaol l quan trng nht.
Cng thc phn t ca cc cht ny l:
+ Zingeron: C11H14O3.
+ Gingerol: C17H26O4.
+ Shogaol: C17H24O3.
1) Zingeron cho phn ng dng tnh vi FeCl3 v 2,4 DNP (2,4
dinitrophenylhydrazin). N khng cho phn ng vi thuc t Tollens. Vy c
th kt lun n c nhng nhm chc no?
Brom ha Zingeron bng dung dch nc brom ch thu c duy nht mt sn
phm monobrom. Ph IR ca zingeron cho bit c s xut hin ca lin kt hydro lin
phn t (yu). iu tng t cng xut hin khi kt thc phn ng kh ha Zingeron
theo Clemensen.
2) T cc thng tin trn cho bit:
(i)
Mch chnh ca Zingeron
(ii)
Cc nhm th vo vng thm.
(iii) V tr ca tt c cc nhm th.
3) Vit cng thc cu to ca Zingeron.
4) Hon thnh quy trnh tng hp sau:
+ H2/to
dd NaOH
Zingerol
A +
B
C
xt
(C
11H14O3)
(C3H6O)

Bit A c CTCT:

72
CHO

HO
OCH3

5) Zingeron c th d dng chuyn ha thnh Gingerol bng cc phn ng sau:

Zingeron 1) Me3SiCl/(Me3Si)2NH D 1) hexanal
Gingerol
(C11H14O3) 2) LDA; -78oC
(C17H26O4)
2) H3O+
Ch :
(1) Me3SiCl/(Me3Si)2NH c s dng chuyn nhm OH thnh nhm
SiMe3; nhm
-SiMe3 d b thu phn trong mi trng axit cho tr li nhm OH ban u.
(2) LDA: liti diisopropylamit l mt baz mnh nhng rt cng knh (v mt
cu to).
(ii)
Vit CTCT D.
(iii) Vit CTCT ca Gingerol.
(iv)
Vit cng thc chiu Fischer ng phn (R) ca Gingerol.
(v)
Ngoi Gingerol ta cn c th nhn c sn phm E ( 2 3%) l
ng phn ca Gingerol. Vit CTCT E
(vi)
Thng tin no sau y ng v s hnh thnh E?
a) Sn phm ca phn ng iu ch Gingerol l mt cp ng
phn i quang.
b) Thu c hn hp cc ng phn quang hc khng i
quang.
c) Thu c hn hp ca cp ng phn i quang v ng
phn meso.
(vii) Loi nc ca Gingerol bng cch un n vi KHSO4 thu c
Shogaol. Vit CTCT ca Shogaol.
7) C ngh (Curcuma Longa) l mt loi gia v trong thc phm ca ngi n.
N cng c s dng nhiu trong cc n thuc vng Ayurvedic.
Curcumin (C21H20O6) l thnh phn chnh ca c ngh c cu trc tng t
nh Gingerol. N c cn bng xeto enol. Curcumin lin quan n mu vng
ca c ngh v cng gp phn to ra v cay.
Ph 1H NMR ca hnh dng xeto trong Curcumin cho tn hiu vng thm
tng t Gingerol. N cng cho mt vch n chuyn dch = 3,5 (2H) v hai
vch i (mi 2H l mt vch vng =6-7 vi J = 16Hz. N c th c tng hp
bng cch ngng t hai mol A (cu 4) vi 1 mol pentan2,4-dion.
(i)
Vit CTCT ca Curcumin.
(ii)
Vit CTCT dng enol ca Curcumin.
(iii) Curcumin c mu do:
a) C vng thm.
b) C nhm cacbonyl.
c) C h lin hp.
d) C nhm hydroxyl.
BI GII:
1) Cc nhm chc c th c: xeton, hydroxiphenolic
2) Ta c:

73
Cu to mch chnh ca Zingeron: CH2CH2COCH3.
(i)
(ii)
Nhm th vo vng thm: OH, CH3.
(iii) Cc v tr c nhm th: 1, 2, 4.
3) Cu to ca Zingeron:
CH2CH2COCH3

HO
OCH3

4) Cc phn ng:
H
C

CHO

dd NaOH
H3C

CHC
O

CH3

HO

HO
O
OCH3

OCH3

H2; to/xt

CH2CH2COCH

HO
OCH3

zingeron

5) Ta c:
(i)

Cng thc cu to D:
O
H3CO

CH2CH2C

(H3C)3SiO

(ii)

Cng thc cu to ca Gingerol:

CH2-Li+

74
O
H3CO

CH2CH2C

H2
C

H
C

(CH2)4CH3

OH
(H3C)3SiO

(iii)

Cng thc chiu Fischer ng phn R ca Gingerol:

CH2COR
HO

(CH2)4CH3
H

(iv)

Cng thc cu to ca E:
O
H2
C

H3CO

(H3C)3SiO

H
C

CH3

HC

(CH2)4CH3

OH

(v)
Cu b ng.
6) (i) Cng thc cu to ca Curcumin:
O

O
H2
C

H3CO

OCH3
H

HO

OH

(ii) Cng thc cu to dng enol ca curcumin:

OH
H3CO

H
C

C
H

O
C
H

C
H

H
C

HO

(iii) Cu c ng
OLYMPIC HA HC QUC T 2001:
1. Dng gp np ca protein:
Protein (polipeptit) c nhiu loi khung c cu dng khc nhau. mt cu
dng khung trng thi b ko cng hu nh hon ton ( dng song song hay dng
i song trong dng gp np ) v mt cu dng khc xy ra s xon hon ton ( cu
trc xon ).

OCH3

OH

75
1) Khong cch gia hai ui mch trong mt hexapeptit trong cu dng xon
hon ton l:
a) 10
b) 15
c) 20
d) 25
2) Gi s rng hexapeptit cho c cu trc xon , v mt mi lin kt ni gia
nguyn t oxy v hydro ca nhm NH nu c lin kt hydro tn ti gia hai
nguyn t .
O
+

R2

H3N

R4

N
O

R6

N
R1

R3

N
O

R5

3) Hai hexapeptit (A v B) biu din hai cu dng tng phn trong nc ti

pH = 7,0, c bit l nhm hydro serin c photphoryl ha. A c s
xon va phi v s xon tr nn mnh hn khi serin c photphoryl ha.
B c s xon rt yu v hon ton tr nn ri lon khi serin c photphoryl
ha. V cc mi tn ch s nh hng gia cc phn cn li ph hp vi s
khc nhau nu.
Ser
Leu
Phe
Glu
Arg
COOCH3
CH3CONH Lys
Ser
Leu
Phe
Arg
Glu
COOCH3
CH3CONH Lys
2. - lactamaza v tnh khng thuc.
Penixilin l mt dc phm c hu lc chng li s nhim khun. Tuy
nhin thnh trjang vi khun khng thuc tr nn ng bo ng. Xut hin s
khng penixilin trong vi khun c quy kt cho mt enzym cha bit gi l lactamaza (hay cn gi l penixilinaza), n lm gim hot tnh ca vng penixilin
bng cch m vng - lactam. C ch ca phn ng m vng - lactam lin quan
n s tn cng nucleophin bng nhm OH ca serin hng tn cng ca enzym.
C ch qa trnh ny c trnh by nh sau:

76
R

N
COO

E nz - Ser - O H

COO

E n z -S e r-O H

N
O

HO

COO

OH

E nz - Ser

HO

HN
O

+ E nz - Ser - O H

+ H 2O

COO

+
O

HN
O

COO

E nz - S er

Cc nh khoa hc c gng xc nh c enzym - lactamaza t

Staphylococcus aureus. Khi enzym tinh khit c nh du bng ng v 32P th ta
ch nh du mt mnh Serin. Trong phn tch th serin ch chim 0,35% v khi
lng ca enzym - lactamaza. Bit MSerin = 105 Da (n v khi lng nguyn t).
4) c lng Menzym.
5) S lng aminoaxit cn li hin din trong protein ca mch ny s l:
a) 100
b) 150
c) 275
d) 375
6) nh du u hot ng, - lactamaza c phn ct bi tripsin.
Hexapeptit ban u (P1) cha cc aminoaxit sau: Glu, Lys, Met, Phe v Ser
S dng phng php Edman ta bit c aminoaxit u N l Phe
v dy peptit P2.
S dng BrCN ct mch P1 thu c dipeptit P4 v tetrapepetit P3
S dng 1 flo 2,4 dinitrobenzen sau thu phn hon ton ta
thu c N2,4dinitrophenylGlu .
Bit P1; P2; P3 u cha Ser. Hy xc nh v tr cc aminoaxit trong P1; P2; P3;
P4.
7) Tnh M(P3) bit MPhe = 165Da; MGlu = 147Da; MHms = 119Da (Hms:
Homoserin); Mnc = 18Da.
8) Ch vi mt lng nh enzym - lactamaza th phn ng s xy ra nhanh hn
so vi serin t do. Khi s dng enzym - lactamaza lm xc tc th hng s
tc phn ng k1 = 350s-1 cn nu khng s dng enzym th k1 = 0,5s-1.

H 2O

77
T nhng thng tin cho trn, tnh nng hiu lc ca tc nhn
nucleophin lin kt vi trung tm hot ng ca enzym. Cho bit trong trng hp
khng s dng enzym th nng Ser OH t do trong dung dch l 1M.
9) Khi cho cht c ch lin kt vi trung tm hot ng ca - lactamaza th c
th c ch c enzym. Hng s phn ly ca phc cht c ch - lactamaza i
vi ba cht c ch khc nhau c cho nh sau:
Cht c ch
Hng s phn ly (KD)
A
2,0.10-3
B
1,0.10-6
C
5,0.10-9
Trong ba cht A, B, C cht no c hiu qa bo v penixilin khi enzym lactamaza
Cng thc cu to ca cht c ch:
Br

H2C
N
O

COO-

c th lin kt vi trung tm hot ng ca enzym th nhm OH ca

Serinsex tn cng nucleophin v kt qa dn n s m vng v tch Br- ra khi cht
c ch. Tc nhn electrophin mnh s c sinh ra v s tn cng vo trung tm hot
ha ca enzym lm mt hot tnh ca enzym.
10) Vit s cc phn ng xy ra.
BI GII:
1) Cu d ng.
2) Ta c:
O
+

R2

H3N

R4

N
N

R6

N
R1

R3

3) Ta c:
CH3CONH

Lys

Ser

Leu

Phe

Glu

Arg

COOCH3

CH3CONH

Lys

Ser

Leu

Phe

Arg

Glu

COOCH3

R5

78
4) 30000Da.
5) Cu c ng
6) P1: Phe Glu Ser Met Leu Lys.
P2: Glu Ser Met Leu Lys.
P3: Phe Glu Ser Hms/Met.
P4: Leu Lys.
7) 482Da
8) 700M
9) Cu c ng
10) S phn ng:
Br

H2C

Enz - Ser - OH

+
O

COO-

CH2
N

hay
O

O
COO-

Enz - Ser

Enz - Ser

H2C

HN
O
O

Enz - Ser
COO-

OLYMPIC HA HC QUC T 2004:

COO-

79
Phn ng Diels Alder l phn ng ng vng [4 + 2] gia mt olefin v mt
dien to thnh xiclohexen c khm ph bi gio s Otto Diels v ng s
Kurt Alder khi h trn benzoquinon vi lng d xiclopentadien v nhn c kt
qa sau:
O

A
(C11H10O2)

1) Vit CTCT A (khng cn ch n mt lp th)

Phn ng Diels Alder l ng b, mt giai on v c tnh c th lp th
cao. V d: ch mt ng phn C c to thnh t phn ng sau:
H
CN

CN

+
CN
CN

CN

m khng to thnh:
CN
H

H
CN

Nu s dng (E) 1,2 dixianmetylen th thu c hai ng phn lp th D1

v D2
2) Vit CTCT D1; D2.
phn ng ban u (to ra B t xiclopentadien v benzoquinon). Diels v
Alder thu c mt trong 6 ng phn lp th ca B.

CN
H

80
O

3) Hy cho bit l ng phn no?

Sau khi un nng lu (15h, 120oC) th t B (tonc = 157oC), Diels v Alder thu
c hai ng phn lp th mi l E(tonc = 153oC) v F (tonc = 163oC). Di tc dng
ca xc tc 25oC ta thu c ng phn lp th G (tonc = 184oC).
B E + F
10%
20% 70%
B G
60%
40%
Khng cn thit phi bit E, F, G l cht no trong s 6 ng phn lp th trn
4) Cc cu khng nh sau l ng hay sai hoc khng d kin chng
minh:
Phn ng Diels Alder l thun nghch.
B bn nhit ng hn E.
E km bn nhit ng hn F.
G l ng phn quang hc khng i quang ca B.
G bn nhit ng hn F.
5) Cho s phn ng:

81
OMe
O

CO2Me

bazo manh

+
MeO

CO2Me

bazo manh
I
K
(C12H16O5)
(C11H12O4)

Xc nh I, K, L. Bit K ch c mt nhm metyl v L l sn phm cng Diels

Alder ca K v anken cho trc.
BI GII:
1) Cng thc cu to ca A:
O

2) Cng thc cu to ca D1 v D2:

H

H
CN

D1 :

CN

D2 :
CN
H

CN
H

D1 v D2 l hai ng phn i quang.

3) Cu trc 2 (chnh) v cu trc 1 (ph). Theo bi th cu trc tho mn s l
2
Phn ng Diels Alder cho sn phm c ha hc lp th endo. Vn ny
c cp n cu 2, cu trc C. Nh ch ra cu trc C th cu dng endo
c c trng bi 2 nguyn t H v nhm CH2 ca h hai vng cng pha so vi
mt phng vng. Ch c cu trc 1 v 2 trong s 6 cu trc cho l c ha lp th
endo, endo. Tt c cc cu trc khc u c t nht mt nhm th theo hng exo.
Trong cu trc 1, 3 vng to ra phn t c hnh dng ch U b nh hng khng gian
nhiu hn so vi cu trc 2 c dng phn t hnh zig zag.
4) Cu ng: 1, 4.
Cu sai: 2, 3.
Cha d kin: 5
5) Cu trc ca I, K, L:

OMe

-M

82

CO2Me

OLYMPIC HA HC QUC T 2004:

Quy tc Cahn Ingold Prelog (CIP) c s dng xc nh ha lp th
ca phn t.
1) Da vo quy tc CIP hy xc nh hn cp ca cc nhm th sau:
a) -SCH3 v P(CH3)2
b) CCl3 v CH2Br.
c) Gia
O

CH3

Pseudoephedrin (1) l cht hay gp trong cc loi thuc thng thng chng
cm lnh. N c cng thc cu to:
OH
CH3

NHCH3

1
2) nh du * vo cc trung tm lp th v cho bit n l R hay S.
3) V cng thc Newman hay cng thc phi cnh ca (1) v v cng thc chiu
Fischer ca 1.
un nng 1 vi KMnO4 trong iu kin nh nhng thu c Methcanthinon 2
OH
CH3

CO2Me

CO2Me

CO2Me

MnO4-/H+

NHCH3

4) Vit cng thc cu to 2 (c xt lp th) v cn bng phng trnh phn ng

xy ra. Ch r s thay i s oxy ha ca tt c cc nguyn t c s thay i
s oxy ha.
un nng 2 vi LiAlH4 thu c 3. Cht ny ch khc 1 tonc.
5) a) Vit cng thc lp th ca 3
b) Pht biu no sau y ng?

83
1 v 3 l cc ng phn lp th.
1 v 3 l cp i quang.
1 v 3 l hai ng phn lp th khng i quang.
1 v 3 l hai ng phn cu dng.
c) Vit cng thc ca trng thi chuyn tip trong phn ng 2 3
BI GII:
1) Nhm c hn cp cao hn s l: -SCH3; -CCl3 v
O

CH3

2) Ta c:
OH

*
S

CH3

NHCH3

3) Cng thc chiu Newman hay cng thc phi cnh ca 1:

CH3

CH3
HO

H3CHN

H3CHN

hay
HO

Ph

Ph

Cng thc chiu Fischer ca 1:

Ph
H

CH3
OH

NHCH3

hay
H3CHN

H
CH3

HO

H
Ph

4) Phng trnh phn ng:

O

OH
+0

5 Ph

CH3

NHMe

+2

+ 2 MnO4
+7

6H

CH3

Ph
NHMe

+2

+ 2 Mn2+ +

84
5) a) Cng thc cu to ca 3 ( xc nh lp th):
OH
CH3

NHCH3

b) Cu ng: 1, 3
Cu sai: 2, 4
b) Cu trc ca cc sn phm trung gian:
CH3

CH3

H3C
H

Li+

Li

1) H+

H3CHN

2) H2O
HO

Ph

Ph
H
-

OLYMPIC HA HC QUC T 2005:

Phn ng ngng t gia axit cacboxylic v amin sinh ra amit. V d: ngng t
axit fomic vi dimetylamin sinh ra N,N-dimetylfomamit, n c cc cu trc cng
hng sau:
O

O
C
H

N
CH3

1.

CH3

CH3
H

N
CH3

Xp cc cht N,N-dimetylfomamit (A). N-metylaxetamit (B) v propanamit (C)

theo th t tng dn nhit si.
2. Nhm cacbonyl thng c nhn din bng di hp th mnh trong ph hng
ngoi (IR). V tr vn hp th ph thuc vo bn lin kt C = O. i vi amit
th bn ca lin kt C = O c th c xc nh da vo hnh v trn. V d:
nhm C = O ca xiclohexanon cho vn hp th 1715cm-1. so snh vi
xiclohexanon th cc gi tr no sau y l ph hp vi nhm C = O ca
propanamit?
a) 1660cm-1 do di lin kt ngn ca nhm cacbonyl.
b) 1660cm-1 do di lin kt di ca nhm cacbonyl.
c) 1740cm-1 do di lin kt ngn ca nhm cacbonyl.
d) 1740cm-1 do di lin kt di ca nhm cacbonyl.

85
3.
4.

Glyxin (H2N CH2 COOH) l - aminoaxit. Ba phn t glyxin c th to ra

tripeptit Gly Gly Gly thng qua phn ng ngng t to thnh amit v km
theo s tch loi hai phn t nc. Hy vit cng thc cu to ca tripeptit.
Khi - aminoaxit cha nhoam th thu lc ny s xut hin hin tng ng
phn quang hc. V d: L alanin v D alanin l hai enantiome. Nh vy i
vi 3 peptit glyxin, L alanin v D alanin ta c th thu c bao nhiu
tripeptit?
O

H2N

H2N

H2N
OH
H

OH

OH
H

H3C

CH3

Glyxin (Gly)
L - Alanin (L - Ala)
D - Alanin (D - Ala)
5. Tng cng c bao nhiu ng phn quang hc t cc tripeptit trn?
Hin nay, polyacrylamide gel with electrophoresis (PAGE) c s dng
rng ri trong vic phn tch protein v axit nucleic. Tuy nhin mt trong s nhng
ng dng ca keo polyamit l phn lp cc hp cht phenol bng sc k bn mng.
Cc phenol c cha cc nhm th khc nhau th c tnh axit khc nhau. Tnh axit khc
nhau th lin kt vi keo PAGE cng mnh.
6. Sp xp cc cht sau: phenol (D), 4 metylphenol (E) v 4nitrophenol (F) theo
th t gim dn kh nng lin kt vi PAGE.
Kh nng hp th mt cht trong ph t ngoi - kh kin (UV Vis) ph
thuc vo s lin kt i lin hp trong phn t . Mt hp cht c t 5 ni i lin
hp tr ln th c xu hng hp th nh sng trong vng kh kin nn kt qa l
chng c mu. V d phenolphtalein l mt cht ch th axit baz thng dng. Trong
dung dch c tnh axit v trung tnh n khng c mu cn trong dung dch baz n c
mu tm (pH: 8,3 10,0)
HO

OH

H2SO4 dac; 180oC, 5h

G +2

OH
H+

O
OH

phenolphtalein

7.
8

Vit cng thc cu to ca H.

Phenolphtalein c th c iu ch bng cch cho cht G phn ng vi hai mol
phenol. G phi l cht no trong s cc cht di y phn ng t hiu sut
cao nht.

86
O

(a)

(b)

(c)

OH

H
O

O
O

(d)

(e)

BI GII:
1. Th t sp xp cc cht theo nhit si: C > B > A.
Gii thch: T cu trc cng hng ca amit cho thy n c mt phn in tch
m trn nguyn t oxy v mt phn in tch dng trn nguyn t nit. Amin
bc 1 v bc 2 c lin kt hydro mnh hn amin bc 3 (Propanamit: 79oC; Nmetylaxetamit: 28oC v N,N-dimetylfomamit: -61oC).
2. Cu b
3.
H

hay

N
H

N
H

OH
O

Gly - Gly - Gly

O

H3N

N
N

H
O
4.
27
5 Trong s th 26 tripeptit c ng phn quang hc
Aminoaxit khng c tnh quang hot: H2N GGG OH
Aminoaxit c tnh quang hot: H2NGGLAOH; H2NGGDAOH
6 Kh nng lin kt vi PAGE gim dn theo th t F > D > E.
7.

87

HO

8 Cht e
OLYMPIC HA HC QUC T 2005:
Cc cacbohydrat thin nhin u c to thnh t phn ng quang hp trong
thc vt. Tuy nhin mt s cacbohydrat khng gp trong thin nhin c th c tng
hp nhn to trong phng th nghim. Sau y s trnh by s iu ch L riboz
(hp cht I):

88
B
CO2Me

O
HO

100oC

ong han kin

CO2Me

OsO4

HO

CO2Me
CO2Me
Me2C(OMe)2
H+, CH3COCH3

CO2Me

O
enzym pig liver

D (spc)

CO2Me

CO2H

CO2Me

F
+

O3; MeOH

CO2Me

O
O

MeO2C

CO2H

O
O

O
E (spp)

CO2Me

MCPBA
CO2Me
O
O

CH2OH

HO

O
H3O+

1) MeOH/H+

CO2Me

2) LiAlH4
sau do H2O

OH

OH
I

1. Hp cht A c cng thc phn t C10H10O5. Vit cng thc cu to A.

2. Trong cc mnh lin quan n vic chuyn ho t A thnh C sau y th mnh
no ng, mnh no sai?
a) OsO4 l tc nhn oxy ha trong phn ng chuyn A thnh B.
b) MeOH l sn phm ph trong phn ng chuyn ha B thnh C.
c) Proton ng vai tr xc tc trong phn ng chuyn ha B thnh C.
d) C c th c to thnh vi hiu sut thp khi khng c Me2C(OMe)2.

89
Enzym pig liver esteraza c th thy phn este thnh axit cacboxylic. Thu
phn C bng enzym pig liver esteraza sinh ra hn hp D v E trong E l sn phm
chnh. Gc quay cc ca hn hp l: []D20 = -37,1o cn ca E tinh khit l []D20 = 49,0o.
3. Tnh t l D/E (theo s mol) trong hn hp phn ng.
4 Phn ng ca F vi axit m clopebenzoic (MCPBA) sinh ra t sn phm G. Ch
ra rng cc mnh sau y l ng hay sai:
a) Bn cht ca phn ng l s oxy ha F.
b) Nguyn t oxy thm vo c ngun gc t MCPBA.
c) T l ca hai hp cht C1 (R) v C1 (S) trc v sau phn ng khng thay
i.
Cng thc phn t ca H l C9H16O5. Cc ga tr ph NMR ca H cho di
y: 1HNMR (CDCl3) 1,24 (s, 3H); 3,24 (m, 1H); 3,35 (s, 3H); 3,58 (m, 2H); 4,33
(m, 1H); 4,50 (d, J = 6Hz, 1H); 4,89 (s, 1H).
a) Vit cng thc cu to ca H.
b) Xc nh cu hnh tuyt i ca C1; C2; C3: C4 ca hp cht I.
c) Trong cng thc chiu Fischer ca I (L riboz) th cc ch ci P, Q, R, S, T
v U i din cho nhng nhm chc no?
CHO
P

U
CH2OH

Disaccarit l hp cht c to thnh t hai n v monosaccarit bi lin kt

glycozit. Polisaccarit cha t 10 n vi ngn n v monosaccarit. V d v
disaccarit cho di y:
H OH
H

HO
H

H
H
OH

OH

H OH
O
H

lien ket glycozit

O
OH

H
H
OH

OH
H

d) C bao nhiu ng phn dia to thnh t pentasaccarit J nu n c

to thnh t 5 n v D glucoz:

90

H OH
H
H

O
O

H
H

OH

OH

BI GII:
1.
O
CO2Me

CO2Me

2. Tt c u ng
3. 12,1 : 87,9 hay 12,2 : 87,8
4. a, b ng; cu c sai
5.
MeO

CH2OH

6. C1, 2, 4: S
7.

C3: R
CHO

HO

HO

HO

H
CH2OH

8. 2
OLYMPIC HA HC QUC T 2005:
Ete crown c th to c lin kt vi cc ion kim loi kim. V d cc hng
s lin kt ca hai azacrown (ete vng cha nit) vi Na+, K+, Cs+ c cho bng
di:

91
Hng s lin kt (lg10K)
Ion km loi
Bn knh (pm)
Hp cht A
Hp cht B
+
Na
98
2,49
3,57
K+
133
1,83
5,00
+
Cs
165
1,37
3,39
Antraxen cho s pht quang mnh vi bc sng pht x trung tm l 325nm.
Kt hp vi s lin kt chn lc ca cc azacrown i vi ion kim loi kim v s
pht quang mnh ca antraxen, mt ion kim loi pht quang chn lc E c pht
trin.
O
O

H2C

CH2

A
B
1. Cho bit cc cht C v D trong qa trnh tng hp sau:
H

1) NaBH4
2) PCl5/benzen

HO

pyridin
O
O

O
N

- +

SO2Cl

1)
OH

2) t - BuO K
HO(CH2)2NH(CH2)2OH

CH2

92
so snh, th dn xut th antraxen ca F v G cng c tng hp. Cc
hp cht E, F, G u khng c tnh pht quang cc iu kin trung tnh do hiu ng
chn s di chuyn ca electron (photoinduced electron transfer PET) do cp electron
khng phn chia ca nguyn t nit nm pha hot ng ca antraxen:
O

OH

OH
N
N

2.

H2C

H2C

Khi thm dung dch HCl hp cht no s pht quang?

a) Khng c.
b) E v F.
c) Ch G
d) Tt c.
3. Khi thm mt lng tng ng kali axetat vo dung dch long ca E, F v G
trong metanol th hp cht no s pht quang mnh nht?
a) E
b) F
c) G
4.
Khi thm mt lng tng ng axetat kim loi vo dung dch long ca F
th axetat kim loi no s pht quang mnh nht?
a) CH3COONa
b) CH3COOK
c) CH3COOCs
d) Khng c.
Trong qa trnh chiu x vi tia cc tm trans stinben chuyn ho thnh mt
cht trung gian H, H chu s vng ho quang ho sinh ra dihydrophenantren I. Oxy
ho tip I cho ta phenantren.

93

hv
nhiet

hv
nhiet

oxy hoa

3.5. Vit cng thc cu to H

3.6. Ho lp th ca hai nguyn t H trong hp cht I l g (cis hay trans)?
Dn xut ca Dihydroazulen J c tnh cht quang ho hc rt th v. Khi chiu
x th th cht J khng mu s chuyn v thnh vinylheptafulven K. un nng K th ta
li thu c J:
CN

CN

CH3

CN

CH3

CN

hv

10

nhiet

6
9
8

J
7. Hp cht no hp th nh sng bc sng di hn?
a) J
b) K
8. Hp cht K c th phn ng vi mt lng tng ng CF3CO2H to thnh
h thm bn vng. Nguyn t no cacbon no ca K d b proton ha nht?
a) C 2
b) C 3
c) C 4

94
d) C 5
BI GII:
1.
N
H

Cl
H2C

O
O

2. d
3. e
4. a
5. Cng thc cu to ca H:

6. trans
7. K
8. C3
I.
BI TP CHUN B CHO OLYMPIC HA HC QUC T:
OLYMPIC HA HC QUC T 1998:
Cht ong cha Q cha 65,2% cacbon v 6,75% hydro v khng c nguyn
t no thm na tr oxy. Q c bit c tnh cht axit v chun 43,7mg cht ny
cn 23,7mL dung dch nc ca natri hydroxit 0,0100M t n im tng
ng. Khi lng phn t ca Q nh hn 200.
a) Cng thc phn t ca Q l g v nhng nhm chc no gy nn tnh axit ca hp
cht?
Q phn ng vi hydro c mt bt mn platin to thnh hp cht mi A. Kh A
vi natri bohydrua trong etanol cho cht B. Hp cht B d dng loi nc khi un
nng vi axit sunfuric to anken C. Ph NMR 13C ca C cho thy s c mt ca
mt nhm metyl gn vo lin kt i.
b) Nhng nhm chc no ph hp vi nhng phn ng trn?
Phn ng ozon phn cht C ri oxy ha k tip ch cho hai phn l axit etanoic
v mt axit dicacboxylic mch thng D. S phn chia tng t ca Q to thnh axit
oxalic (axit etandioic) v cht E c cha mt nhm chc axit cacboxylic.
c) Suy ra cu to ca D v E, t hy xc nh cng thc cu to c th c ca Q.
BI GII:
Cng thc thc nghim: C10H16O3 (M = 184,13). Do MQ xp x 200 nn cng
thc phn t ca Q trng vi cng thc thc nghim (C10H16O3).
Q c tnh axit nn c th cha mt nhm CO2H (do ch c 3 nguyn t oxy
trong phn t). Vy Q l axit n chc, phn ng vi NaOH theo t l mol 1:1
R CO2H + NaOH = R CO2-Na+ + H2O
43,7mg 43,7.10-3g Q phn ng vi 23,7mL dung dch NaOH 0,0100M

95
Vy nNaOH = 23,7.10-3.0,0100 (mol)
Nu 43,7.10-3g Q phn ng vi 23,7.10-3.0,0100mol NaOH th 43,7.103
.(103/23,7.0,01)g Q phn ng vi 1 mol NaOH, ngha l 184,3g Q phn ng vi 1
mol NaOH. iu ny chng t rng 1 mol Q phn ng vi 1 mol NaOH v nh th
cho php ta kt lun Q l axit n chc dng R CO2H.
K tip ta cn xc nh nguyn t oxy cn li trong C10H16O3. (hay C9H15O
CO2H)
C th l:
ete:
R O R.
ru: R O H.
xeton: R CO R.
andehit: R CHO.
S lin kt i trong Q = 3. R rng cha xc nh c hai trong s ba lin
kt i nhng xc nh c 1 (ca nhm CO2H).
Mt khc, theo cc th nghim:
+
/
2 / Pt
4 / EtOH
Q H
A NaBH

B H
C + H 2O
C l mt anken nn B l ru v B loi nc cho ra anken C khi un nng vi
+
H
Ngoi ra, C cn c mt nhm metyl gn vo ni i cho nn ta d on:
H3C

H
C

H2
C

H3C

OH

Nu iu ny ng th A phi l mt xeton
H3C

H2
C

NaBH4

H3C

H
C

H2
C

H3C

OH

Cn bit rng nhm andehit v xeton b kh bng NaBH4 cho ru bc 1 v

ru bc hai.
Nu A cha nhm xeton v nhm chc axit cacboxylic th A c cng thc cu
to:
H3C

H2
C

(CH2)7 CO2H

v gii thch c 2 trong s cc lin kt i tng ng. Mt trong nhm

chc axit v mt trong nhm xeton.
C ngha l trong Q cn mt lin kt i na v do Q phn ng cng vi
hydro nn c im cu to cn li phi l mt lin kt i. Vn l v tr ca lin
kt i trong Q.
H3C

H2
C

(CH2)7 CO2H

H3C

H
C

H2
C

(CH2)7 CO2H

CH3CH=CH(CH
O

OH

B
A
v gi thit c xc nhn do C b ph v bi ozon v mt cht oxy ha to thnh axit
axetic v mt axit dicacboxylic mch khng nhnh.

96
H3C

CH3CH=CH(CH2)6CO2H

C(CH2)6CO2H

OH

OH

iu ny cho php khng nh C duy nht v t khng nh A

Q ny chc chn ch n gin l mt phn t c cha nhm chc xeton (tng
t A) v axit cacboxylic (tng t A) v mt lin kt i.
Nhng Q khi ozon phn v oxy ha to thnh HOOC COOH cng vi E.
Khng quan tm n E v mt mnh nh ch c th xut pht t phn t c
dng tng qut:
R

R - CH=CH - CO2H

OH

OH

OH

Nh vy xc nh c Q duy nht l:
H3C

(CH2)5C
H

C
H

CO2H

Vn cui cng cn li l s ng phn ha cis trans ca lin kt i:

H3C

H3C

C
O

O
(H2C)5

(H2C)5

CO2H

CO2H

trans
cis
Vn ny khng th kt lun c vi cc gi thit cho.
OLYMPIC HA HC QUC T 1998:
Axit crisophanic c trong sc t antraquinon thin nhin c lp c t r cy
i hong vi cu to di y. Mt phng php tng hp phn t ny do Khoa
Nghin Cu Ha Hc thuc i Hc Quc Gia Australia ngh:
OH

OH

CH3
O

axit crisophanic
a) 3-metylanisol (3-metyl-metoxybenzen) c kh bng kim loi liti trong hn hp
amoniac ha lng khan nc, tetrahydrofuran v t-butanol to B (C8H12O). X
l B vi kali amidua trong amoniac lng khan nc ri x l tip trong dung dch
nc dn n s ng phn ha B thnh C. Hy vit ba cng thc cu to c th
c ca C.

97
b) Ph NMR 1H ca C cho thy c hai proton ca lin kt i khng k cn nhau.
Ngoi ra, cn cho bit c hai nhm metylen cnh nhau, mt trong hai nhm ny
k cn mt proton ca lin kt i. Hy vit cc cng thc cu to ca C tho mn
iu kin trn.
c) Phn ng ca C vi 5-hydroxi-naphtalen-1,4-dion to sn phm ghp Diels
Alder D(C18H18O4). Ph NMR 1H ca D cho thy mt cng hng 10,5 thng
nht vi mt proton v l ch nh ca mt nhm hydroxyl lin kt ni phn t.
Hy ngh ba cng thc cu to c th c ca hp cht D.
d) Enol ha D bng cch x l vi kali cacbonat trong metanol nng ri oxy ha k
tip vi kali nitrosodisunfonat (mui Fremy) to mt sn phm kiu quinon mu
vng E (C18H16O4). Ph NMR 13C ca E cha tng cng 9 cng hng c th quy
cho nhng cacbon bc 4. Nhit phn E ti 180oC trong 15 pht li phng thch
eten bng phn ng ngc Diels Alder ng thi to thnh F (C16H12O4). Ph
NMR 1H ca F cho thy ba vch n, mi vch tng ng vi mt proton (vch
thp nht ti 11,00) v hai vch n 3 proton, mt vch ti 4,01 v mt vch ti
2,25ppm. Cn c trn cc chng c ny, ngh cc cng thc cu to c th c
ca cc hp cht E v F.
e) Khi cho F tc dng vi bo triclorua trong diclometan ti 10oC ri x l tip thu
c mt cht rn mu cam, khi ph cho m/e = 245. Tr s ny ging nh axit
crisophanic thin nhin. Vit ton b cng thc cu to ca qa trnh tng hp
axit crisophanic.
BI GII:
Ton b qa trnh tng hp axit crisophanic ca cu hi din ra nh sau:

98
OCH 3

OCH 3

OCH 3

OH

CH 3

OH

OH

OH

OH

OH

OCH 3

OCH 3

CH 3

CH 3
O

OH

OH

OCH 3

OH

OCH 3

CH 3
OH

OH
O

OCH 3

OH
O

axit crisophanic

Hp cht B l sn phm kh Birch d kin

C l mt ng phn lin hp (tip cch) ca B, c th c bt c cu to no:
C1; C2; C3.

99
CH3

OCH3

OCH3

CH3

CH3

CH3

C1
C2
C3
Trong nhng cu to ny, ch c hai cu to C1 v C2 tho cc s liu NMR.
Nh vy loi C3.
Bt k ba sn phm Diels Alder no xut pht t C1 n C3 cng chp nhn
c cho li gii ca phn th ba do chng u cha nhm hydroxyl c lin
kt hydro ni phn t. Tuy nhin phi ngh cn thn xc nh li gii ng.
thi im ny, cha th xc nh C1 hay C2 l cu to ng ca C. Tuy
nhin phn cui c th thy r li gii xut pht t D1 hoc D11, sn phm cng
vng ca C1 l khng th chp nhn c do khng b kh metyl vi BCl3. -10oC
y l tc nhn chn lc ct nhm ete peri vi mt nhm cacbonyl; v mt ny th
BCl3 chn lc hn BBr3
OH

OH

CH3

OH

OCH3
O

D1

CH3

D11

Tuy nhin ngay c y c th c mt kt qa khc nhng khng phi cht c

th to axit crisophanic. Ha hc vng ca s cng vng nu trn thc t c th c
c, nhng phn ng cng Diels-Alder c th tip din to mt ng phn khc
nu di y. ng phn ny khng dn n axit crisophanic v do cu to ny c
cho trong cu hi nn c th d dng on c li gii. Cng cn thit thy rng
xt v mt tng hp cht th y cng khng thc s l cch khng c sai lm v
khng th dng nh l mt chng c cho cu to ca axit crisophanic. Vi chi tit y,
c th tr li cu hi d vi ha hc vng ca s cng vng C2 v 5hidroxinaphtalen-1,4-dion.
OH

OH

OH

CH3

CH3

OH