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 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

O1

234

5 6 7

8 OHC6H5

1

234

567

8HOH5C6 O

O

O

O

O

1

23

4

567

8 9HOH5C6 O O

O

O

1

234

5 6 7

89 OHC6H5

R

HO

H

CH2

HO

R

R

HO

as

to

HO

R Cu dng bn: S-trans

2.

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-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 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.

1/7 trang

O

OO

HO 1 2

3456

78

9

O

OO

HO 1 2

3456

78

9Vit cng thc cu dng cc cp ng phn i quang v gi tn styryllacton theo danh php IUPAC.2. Dng mi tn cong ch r c ch chuyn 7-ehirocholesterol (I) thnh vitamin D3 (II) v cho bit cu dng bn ca n.

HO

R

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

R

(I)

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)-1-

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

OCH3CH3

CH3

CH3H3C

CH3O

OO

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

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

H+ H2O

A

OH

OH

B

Gi tn B: 1-hiroxi-4-(-1-hiroxi-1-metyletyl)-1-metylxiclohexanb. 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.

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Cis-BA

OHOH HOOH

HO

H+ O

H+

H+

(+)OH

(+)

(+)

Trans-BA

OHOH OH

OH

(+)OH

H+O

H+

OH

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

H+ 2 H2O

OH

OH

+

HCl

DH+

(+)

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, H2SO450oC, 2 h

A B C

SOCl2, DMF, toluen, 55oC, 6 h

dd NH3, 20oC, 2 h

C

OEtO

O

O

H hi l u, 2 h,- NHN

ClSO3H, SOCl2to phng, 18 h G 10oC, 2 h

NH , H2ONCH3-N)2CO(N

EtOAc, 500C, 4 hH2 (50 psi), 5% Pd/C E D

OH

OOEt

O

O

NN CH3S

HN

NPr

NN

Et

O2

CH3

KINHN

E, EtOAc to phng, 70 h L

3/7 trang

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 :

NH2NH2 HNO3, H2SO450oC, 2 h

C

OEtO

O

O

EtOAc, 500C, 4 hSOCl2, DMF, toluen, 55

oC, 6 h dd NH3, 20

oC, 2 h

H2 (50 psi), 5% Pd/C

E

C

D

H2N

O

NN

PrH2N

CH3CH3

H

A

1. Me2SO4, dd NaOH 2. NaOH, H2O

H2N

O

NN

PrO2N

EtO

O

NN

Pr B

CH3HO

O

NN

Pr

HO

O

NN

PrO2N

CH3

ClSO3H, SOCl2to phng, 18 h

H

Me hi lu, 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

OOEt

S

O

O2 N CH3N

NHN

NN NHN NN

K E, EtOAc to phng, 70 h

L

OEt

SO2 N CH3N

H

O

O

N

H2NN

NCH3

Pr

2. C ch t [I] sang K

- H+

OEt

S

OC

O

O2N CH3N

NN

O

NHN

OEt

S

OC

O2N CH3N

NN

O

NN

O

+ H+

+ CO2 +

OEt

S

O

O2 N CH3N

NN

NHN

(- )

4/7 trang

Cu IV (4 im)1. Sau khi x l hn hp li ng hoc v tru c cha pentozan (C5H8O4)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 (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 C2

O

CHO

(C5H8O4)n HCl 12%CHO

(CHOH)3CH2OH

- 3H2O

A(C5H4O2)O

CHO

KOH

O

CH2OH

O

COOK

B

H3O+

O

COOK

O

COOH

H+b.

OCOOH +

OCH2OH

OCOOCH2

O

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

(CH3CO)2O

OCH(OCOCH3)2

OCHO

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

H3O+

OCH(OCOCH3)2 CHO

OO2NO

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 A v 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).

.

OO

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

D I

CHOO

O2NN

ONH

OH2N

CHO

O2N N N

ONH

O

II S

NH

S

O

CHOO

O2N CHOO2N

S

NH

S

O

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

OHOH2C O

COOCH3

OHOH2C O

COOCH3

O

CH2OHOH

HO

HO

H

HO

HO

O+

OH

OH

OH

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

+O

HOH2C O

COOCH3

H

H2N-CH2-COOH N-CH2-COOH

HOH2C O

COOCH3

Hsn 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 Leu-Glu-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

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 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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2,5

1,7

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.

XCO2

CH2 CH COOHNH2

CH2HOOC

HOOC CH2 CHCHNH2COOH

COOHX :Vy

Gi tn: Axit 3-aminopropan-1,1,3-tricacboxylic2. Cc sn phm oxi ho D-glucoz v cc lacton ca n

CHO

HOOH

CH2OH

Br2 H2O

CH2OH

CH2OH

OH

OH

OHOH

OHHOHO

COOH

COOH

COOH

HNO3

OHOH

OH

OH

HOOH

O

C

O

O

OH

CH2OH

OH

OO

axit gluconic D- -gluconolacton

1,4-lacton ca axit glucaric

OO

OH

OH

COOHOH

OO

OH

OH

3,6-lacton ca axit glucaric1,4:3,6-dilacton ca axit glucaric

COOHOH

OOHOOH

O

7/7 trang

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