B GIO DC V O TO

K THI CHN HC SINH VO CC I TUYN QUC GIA D THI OLYMPIC QUC T NM 2008

HNG DN CHM MN HA HC Ngy thi th hai: 30/3/2008 Cu I (2,5 im) 1. Styryllacton c phn lp t thc vt c cng thc (hnh bn). Vit cng thc cu dng cc cp ng phn i quang v gi tn styryllacton theo danh php R IUPAC. 2. Dng mi tn cong ch r c ch chuyn 7ehirocholesterol (I) thnh vitamin D3 (II) v cho bit cu dng bn ca n.
R: -CH(CH3)-(CH2)3-CH(CH3)2
HO
(I)
6 7

O
8

5 9 1

4 3 2

HO

O
R

(II)

HO

Hng dn6O 5 :4 chm 1. 3-on

7 8 9 1

HO

O
2

Tn: 8-hiroxi-7-phenyl-2,6-ioxabixiclo[3.3.1]nonan-

Cng thc cu dng:

4

H 5C 6

O
8 1

O O
3

O O
2

5 1

O
8

O C6 H 5 OH
7

O
5 5 1

O
7

H 5C 6

O
8 1

O
8

HO
2.

HO

C6H5 OH

R H H2C R

as
HO HO

to
R

HO

HO

Cu dng b S-trans n:

Cu II (4,5 im) 1. Hp cht A (C10H18O) c phn lp t mt loi tinh du Vit Nam. A khng lm mt mu nc brom v dung dch thuc tm long, cng khng tc dng vi hiro c xc tc niken, nhng li tc dng vi axit clohiric m c sinh ra 1-clo4-(1-clo-1-metyletyl)-1-metylxiclohexan. Hy xut cu trc ca A. 2. Hp cht B (C10H20O2 ) c trong mt loi tinh du Nam M. T B c th tng hp c A bng cch un nng vi axit. a. Vit cng thc cu to v gi tn B. b. Dng cng thc cu trc, vit phng trnh phn ng v trnh by c ch y ca phn ng tng hp A.

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3. Hp cht B thng c iu ch t C (2,6,6-trimetylbixiclo[3.1.1] hept-2-en) c trong du thng. Dng cng thc cu to, vit phng trnh phn ng v ch r cc lin kt ca C b t ra. 4. Trong cy long no c hp cht D tn l 1,7,7-trimetylbixiclo[2.2.1]heptan-2-on (hay l campho). Vit s cc phn ng tng hp D t C v cho bit c ch ca giai on u. 5. V cu to ha hc, cc hp cht A, B, C v D trn c c im g chung nht? minh ha vn tt c im trn cc cng thc cu to ca chng. Hng dn chm : 1. Xc nh cng tc cu trc ca A(C10H18O) A c cha bo ho l 2; A khng lm mt mu dung dch nc brom v dung dch thuc tm long chng t trong A khng c ni i hay ni ba; A khng tc dng vi hiro trn cht xc tc niken chng t trong A khng c nhm chc cacbonyl; A tc dng vi axit clohiric m c sinh ra 1-clo-4-(1-clo-1-metyletyl)-1metylxiclohexan, trong A c vng no v c lin kt ete. Suy ra cng thc cu trc ca A
CH3
O O

CH3 O

H3C

CH3 O CH3

CH3

2. a.

B (C10H20O2)

- H2O

A (C10H18O)

Suy ra B l mt iol c b khung cacbon nh A

OH
H H2O
+

OH B

Gi tn B: 1-hiroxi-4-(-1-hiroxi-1-metyletyl)-1-metylxiclohexan b. Dng cng thc cu trc, vit phng trnh phn ng v trnh by c ch y ca phn ng. C 2 dng trans v cis ca B u cu dng gh bn vng, tuy vy cu dng gh khng th tham gia ng vng m phi i qua dng thuyn km bn. Dng thuyn s tham gia phn ng SN1 ni phn t.
(+)

OH

OH

OH

OH OH
H
+

O OH
(+)

Cis-B

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(+)

OH OH OH Trans-B OH OH
H
+

O OH
(+)

3. Lin kt ca C b t cc ng chm chm:

OH +
2 H2O H
+

OH

4.
HCl

Cl
H2O

HO
O

C
H+ Cl-

(+)

chuy v n

(+)

5. c im chung nht v cu to ho hc: mi phn t gm 2 n v isopren (hoc isopentan) ni vi nhau. Cu III (4 dim) Sildenafil (mt loi thuc tng lc) c tng hp theo s :
O O O C
SOCl2, DMF, toluen, 55 C, 6 h dd NH3, 20 C, 2 h
o o

OEt

NH2NH2

1. Me2SO4, dd NaOH 2. NaOH, H2O

HNO3, H2SO4 50 C, 2 h
o

H2 (50 psi), 5% Pd/C EtOAc, 50 C, 4 h

0

OEt

O OH
ClSO3H, SOCl2 to phng, 18 h

CH3-N

NH , H2O
o

(N

N)2CO NH

10 C, 2 h

hi l u, 2 h,- N

O OEt HN
N NH

CH3 N N Pr

E, EtOAc
to phng, 70 h

L O2 S N

Sildenafil

N CH3

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1. Hy hon chnh dy phn ng trn, bit rng: * Qu trnh chuyn sang G c to thnh axit sunfonic trung gian sau mi chuyn thnh sunfonyl clorua. * N,N -cacbonyliimiazol (CDI) l mt loi tc nhn dng hot ho axit cacboxylic cho phn ng th nucleophin ca nhm cacbonyl. 2. Vit c ch phn ng chuyn [I] thnh K. Hng dn chm :
O
O O O OEt
NH2NH2

EtO

H N

O
1. Me2SO4, dd NaOH

N 2. NaOH, H2O A Pr H2N O2N D Pr

HO

CH3 N HNO3, H2SO4 N 50oC, 2 h Pr H2N H2N E

O HO O2N

CH3 N N C Pr

B CH3 N N

SOCl2, DMF, toluen, 55 C, 6 h dd NH3, 20 C, 2 h

o

H2 (50 psi), 5% Pd/C EtOAc, 50 C, 4 h

0

CH3 N N Pr

OEt

O OH ClSO3H, SOCl2
to phng, 18 h

OEt

O OH CH3-N NH , H2O
10 C, 2 h
o

OEt

O OH

G SO2Cl OEt
(N N)2CO

H O2 S N O OEt N N
N NH

N CH3 O N N

O O

hi l u, 2 h ,

-N

NH

Me

O2 S N

N CH3

K O2 S N

N CH3

O OEt K E, EtOAc
to phng, 70 h

H2N

O N H

CH3 N N Pr

L O2 S

N CH3

2. C ch t [I] sang K
OEt O C O N O N N
- H+

OEt

(- )

O N N N
+ H+

C N
O2 S

OEt

O N N
+ CO2 + HN

HN
O2 S

N CH3

N CH3

O2 S N

N CH3

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Cu IV (4 im) 1. Sau khi x l hn hp li ng hoc v tru c cha pentozan (C 5H8O4)n vi dung dch axit clohiric 12% ri tin hnh chng ct, nhn c cht lng A (C5H4O2) mu vng c mi thm. Cho A phn ng vi KOH ri axit ha th nhn c B (C5H4O3) v C a.(C5H6O2). Vit phng trnh phn ng thu phn pentozan to thnh A v cng thc ca A, B, C. b. Vit phng trnh phn ng ca B tc dng vi C khi c xc tc axit. O O NH H2N-N c. Hy trnh by iu kin nitro ho A nhn c D NH S (C5H3NO4). S d. Vit phng trnh phn ng ca D tc dng vi: (I) ; (II). (II) (I) O . 2. Geniposit (hnh bn) l mt hp cht c tch ra t qu dnh COOCH3 dnh. Thu phn geniposit sinh ra hai sn phm l genipin v D-glucoz. Genipin tham gia phn ng to mu vi gelatin (y l O HOH2C c s pht hin du vn tay trong k thut hnh s). O HO Hy vit s phn ng to genipin v phn ng ca genipin vi O mt aminoaxit gii thch hin tng trn HO CH OH
OH
2

Hng dn chm : 1. Trong li ng v v tru c cha pentozan,khi un nng vi dung dch HCl 12% chuyn thnh pentoz ri tch nc cho fufurol
(C5H8O4)n HCl 12% CHO - 3H2O (CHOH)3 CH2OH 2 O A CHO
KOH

CHO A(C5H4O2) O COOK

O C COOK
H3O+

CH2OH

O b. O

COOH B
H+

COOH +

CH2OH

COOCH2

c. nitro ho A cn phi bo v nhm anehit bng (CH3CO)2O

(CH3CO)2O

CHO

O
HNO3

CH(OCOCH3)2

Thc hin phn ng nitro ho, sau thu phn phc hi nhm -CHO
O CH(OCOCH3)2 O2N O CH(OCOCH3)2
H3O+

O2N

CHO D

d. Phn ng ca D vi I v II

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O2 N D

CHO

H2 N N I O O

O NH

O2N

CH O

N N O NH S

O NH

NH S O2N O CH

O2N

CHO II S
COOCH3

2. Phn ng thu phn geniposit thu c genipin v D-glucoz

COOCH3 O HOH2C HO HO OH O O CH2OH HOH2C O OH
+

OH HO HO O OH OH

Gelatin (c trong da) cu to t cc polipeptit, ly i din l mt aminoaxit nh glyxin, ta c phng trnh:

COOCH3 O HOH2C OH
+

COOCH3 H2N-CH2-COOH HOH2C N-CH2-COOH OH

sn phm c mu pht hin du vn tay trong k thut hnh s. Cu V (5 im) 1. Ngi ta phn lp c mt tetrapeptit (peptit A) t prothrombin ngi. Cu to ca peptit A c tin hnh xc nh nh sau: a. Bng phng php Edman th nhn c trnh t aminoaxit ca peptit A l LeuGlu-Glu-Val. b. tip tc xc nh cu to, ngi ta tin hnh in di trn giy pH 6,5 peptit A v mt peptit tng hp B (cng c trnh t aminoaxit l Leu-Glu-Glu-Val) th li nhn c qung ng di chuyn khng ging nhau, c th nh hnh di y: Peptit A Peptit B
1 ,7 2 ,5

2
o

n v di

c. Khi thu phn hai peptit A v B bng HCl 6N 110 C, th c A v B u cho Leu(1), Glu(2), Val(1); nhng khi thu phn bng kim th peptit B cho Leu(1), Glu(2), Val(1) cn peptit A cho Leu(1), X(2), Val(1). Hy gii thch cc kt qu thc nghim xc nh cu to ca X v gi tn X theo danh php IUPAC. 2. Vit s phn ng oxi ha D-glucoz to thnh axit anonic v axit anaric, cng thc Haworth cc mono v i -lacton ca chng v gi tn cc lacton y. Hng dn chm :
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1.Xc nh cu trc ca X - Phng php Edman thc hin pH thp,bit c trnh t l Leu-Glu-Glu-Val. - in di pH 6,5 cho thy peptit A dch chuyn nhanh hn v pha cc dng(+), chng t A c in tch m ln hn B,tnh axit ca A ln hn B. - Khi thu phn trong mi trng HCl 6N 110oC th c A v B u thu c Leu(1), Glu(2) v Val(1). Kt hp vi phng php Edman trn cho thy cc qu trnh ny thc hin mi trng axit mnh,pH thp. pH thp phn t X b ecacboxyl ho,loi CO2 mt i 1 nhm COOH. - Khi thu phn bng kim peptit A to ra Leu(1),X(2) v Val(1),trong mi trng kim khng c qu trnh decacboxyl ho nn nhn c X(2). - Kt hp cc kt qu trh nghim cho thy X c thm 1 nhm COOH so vi Glu tc l khi loi 1 nhm COO th X chuyn thnh Glu.
X Vy X :
CO2

HOOC CH2 CH2 CH COOH NH2 HOOC CH CH2 CH COOH NH2 COOH

Gi tn:

Axit 3-aminopropan-1,1,3-tricacboxylic
O

2. Cc sn phm oxi ho D-glucoz v cc lacton ca n

CHO OH HO OH OH CH2OH
HNO3 Br2

COOH OH HO OH CH2OH axit gluconic COOH OH O

OH OH H2O

C OH HO O OH CH2OH D- -gluconolacton OH COOH O

OH HO

CH2OH OH O
OH OH

COOH OH HO OH OH COOH

OH O O O

O O

OH 1,4-lacton ca axit glucaric 1,4:3,6-dilactonca axit glucaric 3,6-lacton ca axit glucaric

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