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B GIO DC V O TO K THI CHN HC SINH VO CC I TUYNQUC GIA D THI OLYMPIC QUC T NM 2008

HNG DN CHMMNHA HCNgy thi th hai: 30/3/2008

Cu I (2,5 im)1. Styryllacton c phn lp t thc vt c cng thc (hnh bn).

Hng dn chm :

1. Tn: 8-hiroxi-7-phenyl-2,6-ioxabixiclo[3.3.1]nonan-3-on

Cng thc cu dng:

9 9

O

O

O

1

234

5 67

8OH

C6H51

23 4

567

8HO

H5C6 O

O

O

O

O

1

23

4

567

8 9HO

H5C6 O O

O

O

1

23

4

5 67

89OH

C6H5

R

HO

H

CH2

HO

R

R

HO

as

to

HO

RCu dng bn: S-trans

2.

Cu II (4,5 im)1. Hp cht A (C10H18O) c phn lpt mt loi tinh du Vit Nam. A khnglm mt mu nc brom v dung dch thuc tm long, cng khng tc dng vihiro c xc tc niken, nhng li tc dng vi axit clohiric m c sinh ra 1-clo-4-(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 tnghp 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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O

OO

HO1 2

3

456

7

89

O

OO

HO1 2

3

456

7

89Vit cng thc cu dng cc cp ng phn i

quang v gi tn styryllacton theo danh phpIUPAC.2. Dng mi tn cong ch r c ch chuyn 7-ehirocholesterol (I) thnh vitamin D3 (II) vcho bit cu dng bn ca n.

HO

R

(II)R: -CH(CH3)-(CH2)3-CH(CH3)2HO

R

(I)

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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 rcc 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)-1-metylxiclohexan, trong A c vng no v c lin kt ete.Suy ra cng thc cu trc ca A

O

CH3CH3

CH3

CH3

H3CCH3

O

OO

B (C10H20O2) A (C10H18O)- H2O2. a.

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

H+

H2OA

OH

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. Dngthuyn s tham gia phn ng SN1 ni phn t.

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Cis-BA

OHOH HOOH

HO

H+ O

H+

H+

(+)OH

(+)

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(+)

Trans-BA

OH

OH OH

OH

(+)OH

H+ O

H+

OH

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

H+

2 H2O

OH

OH

+

HCl

D

H+

(+)

chuyn v

H2O O

OHOCl

(+)

Cl-

4.

C

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 :

I

Sildenafil

NH2NH2 1. Me2SO4, dd NaOH

2. NaOH, H2O

HNO3, H2SO4

50oC, 2 h

A B C

SOCl2, DMF, toluen, 55

o

C, 6 hdd NH3, 20

oC, 2 h

C

OEtO

O

O

Hhi l- u, 2 h,- NHN

ClSO3H, SOCl2

tophng, 18 hG

10oC, 2 h

NH , H2ONCH3-N)2CO(N

EtOAc, 500C, 4 h

H2 (50 psi), 5% Pd/C ED

OH

OOEt

O

O

NN CH3S

HN

N

Pr

N

NEt

O2

CH3

KI

NHNE, EtOAc

tophng, 70 hL

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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 axitcacboxylic cho phn ng th nucleophin ca nhm cacbonyl.

2. Vit c ch phn ng chuyn[I] thnh K.

Hng dn chm :

NH2NH2 HNO3, H2SO4

50oC, 2 h

C

OEtO

O

O

EtOAc, 500C, 4 h

SOCl2, DMF, toluen, 55o

C, 6 h

dd NH3, 20oC, 2 h

H2 (50 psi), 5% Pd/C

E

C

D

H2N

O

N

N

Pr

H2N

CH3CH3

H

A

1. Me2SO4, dd NaOH

2. NaOH, H2O

H2N

O

N

N

Pr

O2N

EtO

O

N

N

Pr B

CH3

HO

O

N

N

Pr

HO

O

N

N

Pr

O2N

CH3

ClSO3H, SOCl2

tophng, 18 h

H

Me

hi l-u, 2 h , -

N)2CO(N

K

10oC, 2 h

H

I

OEt

OH

O

NH , H2ONCH3-

OEt

SO2Cl

OH

O

G

OEt

S

OH

O

O2 N CH3N

OEt

S

O

O

O2 N CH3N

O

OEt

S

O

O2 N CH3N

NHN

NN NHNNN

K

E, EtOActophng, 70 h

L

OEt

SO2 N CH3N

H

O

O

N

H2N

NNCH3

Pr

2. C ch t [I] sang K

- H+

OEt

S

OC

O

O2 N CH3N

NN

O

NHN

OEt

S

OC

O2 N CH3N

NN

O

N

N

O

+ H+

+ CO2 +

OEt

S

O

O2 N CH3N

NN

NHN

(-)

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Cu IV (4 im)1. Sau khi x l hn hp li ng hoc v tru c cha pentozan (C5H8O4)n vi dung dchaxit clohiric 12% ri tin hnh chng ct, nhn c cht lng A (C5H4O2) mu vng cmi thm. Cho A phn ng vi KOH ri axit ha th nhn c B (C5H4O3) v C(C5H6O2).

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

A C

2

OCHO

(C5H8O4)n HCl 12%CHO

(CHOH)3

CH2OH

- 3H2O

A(C5H4O2)

OCHO

KOH

OCH2OH

OCOOK

B

H3O+

OCOOK

OCOOH

H+b.

O

COOH +

O

CH2OH

O

COOCH2O

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

(CH3CO)2O

O

CH(OCOCH3)2

OCHO

Thc hin phn ng nitro ho, sau thu phn phc hi nhm -CHO

H3O+

O

CH(OCOCH3)2 CHO

O

O2NO

CH(OCOCH3)2O2NHNO3

Dd. Phn ng ca D vi I v II

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a. Vit phng trnh phn ng thu phn pentozan to thnh Av cng thc ca A, B, C.

b. Vit phng trnh phn ng ca B tc dng vi C khi cxc tc axit.c. Hy trnh by iu kin nitro ho A nhn c D(C5H3NO4).d. Vit phng trnh phn ng ca D tc dng vi: (I) ; (II).

.

O

O

O

OH

HO

HO

HOH2C

COOCH3

CH2OH

(II)

NH-N

O

OH2N

(I)

S

NH

S

O

2. Geniposit (hnh bn) l mt hp cht c tch ra t qu dnhdnh. Thu phn geniposit sinh ra hai sn phm l genipin vD-glucoz. Genipin tham gia phn ng to mu vi gelatin (y l

c s pht hin du vn tay trong k thut hnh s).Hy vit s phn ng to genipin v phn ng ca genipin vimt aminoaxit gii thch hin tng trn

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D I

CHOO

O2NN

ONH

OH2N

CHO

O2N N N

ONH

O

II S

NH

S

O

CHOOO2NCH

O

O2NS

NH

S

O

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

O

HOH2C O

COOCH3

O

HOH2C O

COOCH3

O

CH2OH

OH

HO

HO

H

HO

HO

O+

OH

OH

OH

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

+O

HOH2C O

COOCH3

H

H2N-CH2-COOH N-CH2-COOH

HOH2C O

COOCH3

H

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 toca peptit A c tin hnh xc nh nh sau:a. Bng phng php Edman th nhn c trnh t aminoaxit ca peptit A l Leu-Glu-Glu-Val.

b. tip tc xc nh cu to, ngi ta tin hnh in di trn giy pH 6,5 peptitA 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

0 1 2 3 n v dic. Khi thu phn hai peptit A v B bng HCl 6N 110oC, th c A v B u cho Leu(1),Glu(2), Val(1); nhng khi thu phn bng kim th peptit B choLeu(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 cclacton y.

Hng dn chm :6/7 trang

2,5

1,7

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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 qutrnh ny thc hin mi trng axit mnh,pH thp. pH thp phn t X becacboxyl 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 trngkim 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 Glutc l khi loi 1 nhm COO th X chuyn thnh Glu.

XCO2

CH2 CH COOH

NH2

CH2HOOC

HOOC CH2 CHCH

NH2COOH

COOHX :Vy

Gi tn: Axit 3-aminopropan-1,1,3-tricacboxylic

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

CHO

HO

OH

CH2OH

Br2 H2O

CH2OH

CH2OH

OH

OH

OH

OH

OH

HOHO

COOH

COOH

COOH

HNO3

OH

OH

OH

OH

HO

OH

O

C

O

O

OH

CH2OH

OH

OO

axit gluconic D- -gluconolacton

1,4-lacton caaxit glucaric

OO

OH

OH

COOHOH

OO

OH

OH

3,6-lactoncaaxit glucaric1,4:3,6-dilactoncaaxit glucaric

COOHOH

OOHOOH

O

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