Giao trnh Tong hp Hoa Hu c Chng 5 : BAO VE NHOM CHC

121

Ngay nay trong tong hp hu c moi day chuyen phan ng cho ra san pham thng bao gom khoang 15-20 cong oan hoac hn the na. Trong qua trnh thc hien phan ng co the co trng hp mot tac chat mi a vao e thc hien mot cong oan nao o lai tac dung khong mong muon vi mot nhom chc khac san co trong phan t lam bien oi cau truc cua chat nen. Nh the can thiet phai bao ve nhng nhom chc nao co kha nang b tac chat mi a vao tac dung va sau o, khi phan ng ket thuc, nhom bao ve c tach ra e tai sinh lai nhom chc ban au. V du alcohol thng c bao ve di dang mot silyl ether t cap va aldehyde di dang mot acetal.
R OH + R'3SiX R O SiR'3

RCH O

2 R'OH

RCH(OR')2

Gan nhom bao ve vao mot nhom chc va sau o tach nhom bao ve ra lam tang them cong oan cua day chuyen lam giam hieu suat phan ng chung tuy nhien cac phan ng nay co hieu suat rat cao. e chon nhom bao ve can phai xet ba van e : - Tnh chat cua nhom chc can phai bao ve. - Cac ieu kien phan ng e nhom bao ve c ben. - Cac ieu kien can thiet e tach nhom bao ve. I. BAO VE NHOM HYDROXYL : Nhom hydroxyl c bao ve bang cach chuyen thanh dan xuat khong con cha H cua OH e khi a tac chat Grignard hay hp chat c nguyen to vao moi trng phan ng, H nay khong phan huy anion do cac tac chat tren sinh ra. Phng phap thong thng dung e bao ve OH la chuyen OH thanh alkyl hoac silyl ether. Viec chon nhom ether thch hp tuy thuoc vao kha nang tach nhom bao ve. Mot phng phap quan trong e bao ve OH la cho OH tac dung vi dihydropyran tao thanh tetrahydropyranyl ether (THP) vi xuc tac acid va sau o

Giao trnh Tong hp Hoa Hu c

122

thuy giai ether trong moi trng acid yeu e tai sinh lai OH. Nhieu chat xuc tac khac cung c s dung nh p-toluensulfonic acid hoac dan xuat pyridinium. Gan nhom bao ve :
H O
+ +

ROH

+ O
+

+ RO
+

RO

Tach nhom bao ve :

H RO O
+

H2O RO
+

ROH

+ HO O

Nhom THP giong nh cac cetal va acetal khac, bao ve c nhom OH oi vi cac tac nhan than hach, cac hp chat c nguyen to, cac tac chat kh hydride, cac phan ng oxy hoa va cac phan ng trong moi trng kiem. Khi thay 2-propenyl ether cho dihydropyran, phan ng thuy phan tach nhom bao ve xay ra trong ieu kien em du hn.
CH3 ROH + CH2 C OCH3 H2O

ROC(CH3)2OCH3

Ethyl vinyl ether cung rat hu dung e bao ve nhom hydroxyl di dang 1ethoxyethyl ether (EE). Nhom methoxymethyl (MOM) va -methoxyethoxymethyl (MEM) c s dung rong rai e bao ve nhom alcohol va phenol di dang formaldehyde acetal. Cac nhom nay c a vao do tac dung cua muoi kiem cua alcohol vi methoxymethyl chloride va -methoxyethoxymethy chloride.
CH3OCH2Cl
+

CH3OCH2OR

RO M

CH3OCH2CH2OCH2Cl

CH3OCH2CH2OCH2OR

Giao trnh Tong hp Hoa Hu c

123

Nhom bao ve MEM c tach ra de dang bi cac acid Lewis, nh ZnBr2, MgBr2, TiCl4, (CH3)2BBr, (CH3)3SiI eu co the s dung c. Trai lai, MEM ben hon THP trong phan ng thuy phan acid. Nh the MEM va THP c s dung bo sung cho nhau e bao ve cac nhom OH, khi cac nhom nay oi hoi ieu kien khac nhau e kh nhom bao ve.
CH2 CH CH3COOH , H2O OMEM THPO 30o C , 40h HO OMEM CH2 CH

Nhom methylthiomethyl (MTM) cung c s dung e bao ve alcohol. Co nhieu cach gan nhom MTM. Alkyl hoa alcoholate do methythiomethyl chloride vi xuc tac ion chloride la phng phap thng hay s dung. Alcohol cung c chuyen thanh MTM ether do tac dung cua DMSO vi s hien dien cua acetic acid hoac vi benzoyl peroxide va dimethyl sulfide. Trong hai phng phap sau co sinh ra ion methylthiomethylium do s ion hoa cua acyloxysulfonium.
RO M
+

CH3SCH2Cl

Cl

CH3SCH2OR

MCl

ROH

CH3SOCH3

CH3COOH (CH3CO)2O

CH3SCH2OR

ROH

(CH3)2S

(PhCO 2)2

CH3SCH2OR

Nhom MTM c tach ra mot cach chon loc trong dung dch nc muoi Ag hoac Hg2+. Trong ieu kien nay THP va MOM kha ben. MTM cung c tach ra do phan ng vi methyl iodide va sau o thuy giai muoi sulfonium vi acetone loang.
+

Nhom alkyl n gian t c dung e bao ve alcohol mace dau nhom nay c a vao kha de dang e bao ve nhng e tach no ra can phai co cac tac chat than ien t manh nh BBr3. Nhom t-butyl thng c a vao do phan ng cua alcohol vi isobutylene co xuc tac acid.
ROH + CH2 C(CH3)2 H
+

ROC(CH3)3

Giao trnh Tong hp Hoa Hu c

124

Nhom triphenylmethyl (Trityl, Tr) c tach ra di ieu kien nhe nhang hn nhom t-butyl nen c s dung rong rai, nhat la dung e bao ve OH cua carbohydrate. Nhom nay c a vao do phan ng cua alcohol vi triphenylmethyl chloride theo c che SN1. Dung dch acetic acid nong cung u e tach nhom trityl. Nhom benzyl cung c s dung e bao ve OH v e cat t C-O ether e tach nhom bao ve ch can hydrogen giai xuc tac hoac kh vi Na trong dung dch NH4OH. Nhom benzyl c gan vao alcohol do phan ng cua benzyl alcohol vi trichloroacetonitril cho ra trichloroacetinate e hp chat nay tac dung vi alcohol.
CH2OH + Cl3CCN CH2O C CCl3 NH

CH2O

C CCl3 NH + ROH

CH2OR +

Cl3C

C NH2 O

Silyl ether ong vai tro rat quan trong e bao ve nhom hydroxyl. Alcohol c chuyen thanh trimethylsilyl (TMS) ether do tac dung cua trimethylsilyl chloride vi s hien dien cua mot amine. t-Butyldimethylsilyl (TBDMS) ether vi cau truc kenh cang tng oi ben vi cac phan ng kh hydride va oxy hoa nen cung c s dung e bao ve OH. Nhom TBDMS c a vao do tac dung cua alcohol vi t-butyldimethylsilyl chloride hoac triflat vi chat xuc tac amine tam, sau o ch can thuy giai e tach TBDMS. Nhng nhom kenh cang hn va ben hn TBDMS cung c s dung nh nhom triisopropylsilyl (TIPS), triphenylsilyl (TPS) va t-butyldiphenylsilyl (TBDPS). e bao ve cac diol nh 1,2 va 1,3-diol, phan ng vi aldehyde hoac ketone tao ra acetal vong thng c ap dung. Th du :
R R CH CH R' OH OH + CH3COCH3 H
+

R O CH3

O H3C

Giao trnh Tong hp Hoa Hu c

125

Nhom isopropylene cung co the gan vao do phan ng xuc tac acid vi 2,2dimethoxypropane.
R R CH CH2OH OH OCH3 + CH3 C CH3 OCH3 H
+

O H3C

O CH3

2 CH3OH

Nhom ketal co the khang lai cac tac nhan than hach va tac nhan kiem nhng de b tach ra do dung dch acid. Bao ve alcohol do nhom ester oi khi thuan li hn acetal hoac ether, ac biet oi vi cac phan ng oxy hoa. Acetate va benzoate thong thng c s dung va a vao alcohol do phan ng cua alcohol vi acetic anhydride va benzoyl chloride co s hien dien cua pyridine hoac mot amine tam cap lam xuc tac. Dung N-acylimidazolide co the acyl hoa OH trc tiep khong can xuc tac va do co tnh chon loc cao nen c dung cho nhng hp chat co cha nhieu OH.
Ph Ph O HO OH OCH3 N O O + N O CHCl3 Ph O HO O O Ph (78%) OCH3 O O

Nhom ester co the tach ra de dang do phan ng thuy giai kiem. Nhng neu phan ng thuy giai kiem khong thch hp, mot so acyl ac biet khac can c a vao e sau o tach ra ma khong qua phan ng thuy giai kiem. Th du trichloroethyl carbonate ester c a vao va sau o tach ra do phan ng kh vi Zn.
RO C OCH2CCl3 O Zn ROH + CH2 CCl2 + CO 2

II. BAO VE NHOM AMINO :

Giao trnh Tong hp Hoa Hu c

126

Nhom amino nhat va nh co tnh than hach va b oxy hoa de dang. Neu cac tnh chat nay cua nhom amino lam can tr phan nao qua trnh tong hp, th no can phai c bao ve. Phng phap thong thng la dung phan ng acyl hoa, tac chat carbobenzyloxy (Cbz) c s dung rat rong rai v noi C-O cua benzyloxy rat de b cat t trong qua trnh hydrogen hoa.
CH2OCNR2 O H2 / Pd [HOCNR2] O CO2 + R2NH

Nhom Cbz cung co the c tach ra do s phoi hp cua mot Lewis acid nh BF3 va chat than hach nh dimethyl sulfide hoac ethyl sulfide. Nhom t-butoxycarbonyl (t-Boc) cung la nhom bao ve amine hu hieu. Nhom bao ve c tach ra vi trifluoroacetic acid hoac p-toluensulfonic acid. Nhom t-butoxycarbonyl c a vao do phan ng cua amine vi tbutoxypyrocarbonate hay hon hp carbonate ester.
CN (CH3)3COCOCOC(CH3)3 O O t-Butoxypyrocarbonat e (CH3)3COCON CPh O 2-(t-But oxycarbonyloxyimino)-2-phenylacet onit ril

Phthalimide c s dung e bao ve amine nhat v nhom nay co the tach ra de dang vi hydrazine.
O NR O + NH2NH2 O O NH NH + RNH2

Phan ng kh vi NaBH4 trong ethanol loang cung tach c phthalimide. Phan ng bao gom s tao thanh mot o-hydroxymethylbenzamide trong giai oan kh.

Giao trnh Tong hp Hoa Hu c

O NR O BH4
-

127
H OH NR O O BH4
-

CHO NHR

CH2OH O O + RNH2 O NHR

Do kha nang hut ien t manh cua nhom trifluoromethyl, trifluoroacetamide c thuy giai di ieu kien nhe nhang. ieu nay giup cho nhom trifluoroacetyl c s dung e bao ve amine trong mot vai trng hp.
Ar CH2 CH COOCH2CH3 NHCCF3 O Ba(OH)2 Ar CH2 CH COOH NH2

Amide cung co the tach ra do phan ng kh tng phan. Neu phan ng kh dng lai giai oan carbinolamine, phan ng thuy phan ke tiep co the tach nhom bao ve e giai phong amine.
H R2NCPh O R2AlH R2NCPh OAlR2

RNH2

PhCHO

H2O

Trichloroacetamide co the tach ra do NaBH4 trong alcohol theo c che tren. Benzamide va cac amide n gian co the tach ra do phan ng kh tng phan cua diisobutyl nhom hydride. Cac dan xuat bis-silyl ang c s dung rong rai e bao ve amine nhat. Th du aniline c chuyen thanh disilylazolidine.

Giao trnh Tong hp Hoa Hu c

H3C ArNH2 + (CH3)2SiCH2CH2Si(CH3)2 H H CsF , HMPA 100 oC Si Ar N Si H3C H3 CH3

128

(CH3)2SiH ArNH2 + (CH3)2SiH

H3C (PPh3)3RhCl Si Ar N Si H3C

CH3

H3

Th du : Bao ve amine trong day tong hp peptide. Polypeptide c tao thanh do nhieu aminoacid giong nhau hoac khac nhau qua phan ng tao noi peptide NH-CO-.
H2N CH C NH CH C NH CH C R1 O R2 O R3 O NH CH COOH Rn

Theo phng phap mi tong hp polypeptide, nguyen lieu au la acid chloride cua moat aminoacid hoac moat nhom chc khac co kha nang acyl hoa cao ma au amino a c bao ve. Nhom amino cua acid chloride can phai c bao ve e tranh cho nhom acid chloride acyl hoa vao chnh uoi amino cua no ma phai acyl hoa phan t aminoacid mi c a vao. Trong trng hp nay, ngi ta khong the s dung nhom acyl e bao ve amine, v sau o khi kh nhom bao ve acyl bang phan ng thuy phan th cac noi peptide cua polypeptide cung b t. Ngi ta thng dung cac nhom bao ve nh CF3CO- do nhom nay de b kh vi acid yeu, hoac nhom C6H5CH2OCO- v nhom nay de b kh do phan ng hydrogen hoa xuc tac, hoac dan xuat nhom phthalyl C6H4(CO)2N- v nhom nay de b kh bi hydrazine. Sau nay la mot so th du cua s bao ve nhom chc amine trong qua trnh tong hp peptide va sau o kh nhom bao ve.

Giao trnh Tong hp Hoa Hu c Th du 1 : a) Bao ve nhom amino bang benzyloxycarbonyl :

129

CH2OH Benzyl alcohol

ClCOC2H5 O

CH2O C OC2H5 O Benzylethylcarbonat

HCl

CH2O

C OC2H5 O

H2N CH C OH R O Aminoacid

CH2O

C NH CH C OH O R O

C2H5OH

b) Chuyen nhom carboxyl thanh nhom chc co hoat tnh cao hn (chuyen thanh acid chloride) :
CH2O C NH CH C OH O R O PCl5 CH2O C NH CH C Cl O R O

c) Ghep cap thanh dipeptide :

CH2O C NH CH C Cl O R O + H2N CH C OH R' O CH2O C NH CH C NH CH C OH O R O R' O

d) Kh nhom bao ve :
H2N CH C NH CH C OH H2 / Pd CH2O C NH CH C NH CH C OH O R O R' O CH3 + CO2 R O R' Dipeptide O

Tiep tuc giong nh tren e cho ra tripeptide va polypeptide. Th du 2 : a) Bao ve nhom amino bang trifluoroacetyl :

Giao trnh Tong hp Hoa Hu c

(CF3CO)2O + H2N CH C OH CF3 C NH CH C OH O R O

130

R O Aminoacid

b) Chuyen nhom carboxyl thanh nhom chc co hoat tnh cao hn (moat anhydride cong kenh) :
(CH3)3N CF3 C NH CH C OH O R O
-+

CF3

C NH CH C O NH(CH3)3 O R O

CF3

C NH CH C O NH(CH3)3 O R O

-+

Cl

C OCH2CH(CH3)2 O

CF3

C NH CH C O O R O

C OCH2CH(CH3)2 O

c) Ghep thanh mot dipeptide :

CF3 C NH CH C O O R O C OCH2CH(CH3)2 O + H2N CH C OH R' O

CF3

C NH CH C NH CH C OH O R O R' O

(CH3)2CHCH2OH

CO 2

d) Kh nhom bao ve :
H3O
+

CF3

C NH CH C NH CH C OH O R O R' O

H2N CH C NH CH C OH R O Dipeptide R' O

CF3COOH

Tiep tuc giong nh tren e cho tripeptide, tetrapeptide va polypeptide. Th du 3 : a) Bao ve nhom amino di dang phthaloyl :

Giao trnh Tong hp Hoa Hu c

O O O + H2N CH C OH R O O O N CH C OH R O + H2O

131

b) Chuyen nhom chc carboxyl thanh dan xuat acyl cua dicyclohexylisourea hoat ong :
O N CH C OH R O O + C6H11N C NC6H11 Dicylcohexylcarbodiimid O NHC6H11 N CH C O R O O C NC6H11

c) Ghep thanh mot dipeptide :

O NHC6H11 N CH C O R O O C NC6H11 + H2N CH C OH R' O

O N CH C NH CH C OH R O O R' O + C6H11NH C NHC6H11 O Dicyclohexylurea

d) Kh nhom bao ve :
O N CH C NH CH C OH R O O R' O O NH2NH2 O NH NH + H2N CH C NH CH C OH R O R' Dipeptide O

Tiep tuc giong nh tren e cho ra tripeptide, tetrapeptide va polypeptide.

Giao trnh Tong hp Hoa Hu c

132

Trong trng hp day polypeptide ch do moat aminoacid tao thanh, phng phap sau nay c ap dung :

CH2O

C Cl O

H2N CH C OH R O

CH2O

C NH CH C OH O R PCl3 O

O R CH2Cl + HN O O CH2O C NH CH C Cl O R O

hoa.

Anhydrid vong khi un nong c m vong phong thch CO2 va a phan

O R n HN O O H2O H2N CH C R O ( NH CH C R O )n- OH 1 + n CO 2

Ghi chu : 1. Giong nh cac aminoacid, polypeptide co tnh lng tnh va moi polypeptide co iem ang ien rieng. 2. Mot so polypeptide co tac dung sinh ly quan trong en c the song. Th du : Glutathion ong vai tro quan trong trong s oxy hoa - kh trong c the la moat tripeptide co cha ba aminoacid la glycine, glutamic acid va cystein.
HO C CH CH2CH2 C NH CH C NH CH2 C OH O NH2 O CH2 O SH Glutathion O

Giao trnh Tong hp Hoa Hu c

133

Trong hoa hoc protein va polypeptide, cong thc phan t c viet bang ten viet tat cua cac aminoacid lien ket vi nhau. Th du : Glutathion c viet la : Glu Cys Gly. Gramicidine la moat chat khang sinh c ghi la :
Val Pro Orn Phe Leu Leu Phe Orn Pro Val

Trong o Val ch valine, Orn ch ornitine, Leu ch leucine, Phe ch phenylalanine va Pro ch praline. III. BAO VE NHOM CARBONYL Phng phap tong quat bao ve aldehyde va ketone oi vi phan ng cong than hach va phan ng kh la chuyen cac nhom carbonyl nay thanh acetal va ketal vi ethylene glycol.
R C O R' + HOCH2CH2OH
+

R O C R' O Dioxolane

H2O

Scandium triflate (trifluoromethylsulfonate) la chat xuc tac hu hieu e ieu che dioxolane. Dimethyl hoac diethyl acetal va ketal co the ieu che mot cach thuan li do phan ng trao oi xuc tac acid vi mot ester hoac motketal nh 2,2dimethoxypropane.
OCH3 R C R' + HCOOCH3 OCH3

C O

R'

CH(OCH3)3 Orthoester

Giao trnh Tong hp Hoa Hu c

OCH3 R C R' + (CH3)2C O OCH3

134

C O

R'

(CH3O)2C(CH3)2

Acetal va ketal c ieu che mot cach rat em du do tac dung cua hp chat carbonyl vi alkoxytrimethylsilane, s dung trimethylsilyl triflate lam xuc tac.
+ 2 R'OSi(CH3)3 (CH3)3SiO 2SCF3

R2C O

R2C(OR')2

(CH3)3SiOSi(CH3)3

Dioxolane va cac ketal acetal khac thng rat ben oi vi cac tac nhan than hach manh bao gom cac tac nhan c kim va cac phan ng chuyen nhng hydride. Nhom bao ve carbonyl c kh de dang do phan ng thuy phan acid giong nh phan ng thuy phan acetal. Neu nhom bao ve carbonyl can c tach ra ma khong phai qua phan ng thuy phan acid, ngi ta thng s dung mot -haloalcohol nh 3-bromo-1,2dihydroxypropane hoac 2,2,2-trichloroethanol e tao ra acetal. Cac nhom bao ve nay co the tach ra do phan ng kh vi Zn theo c che kh .
R O BrCH2 O R Zn R2C O + HOCH2CH CH2

OCH2CCl3 R C R' OCH2CCl3

Zn THF

C O

R'

CH2

CCl2

Nhom bao ve carbonyl khac la dan xuat 1,3-oxathiolane c ieu che do tac dung cua carbonyl vi mercaptoethanol, xuc tac acid hoac BF3. Nhom bao ve c tach ra do tac dung cua Ni Raney trong alcohol hoac do tac nhan halogen hoa nhe nh chloramines T. Tac nhan nay oxy hoa S thanh muoi chlorosulfonium nham e hoat hoa vong cho phan ng thuy phan m vong ket tiep.

Giao trnh Tong hp Hoa Hu c

R C R S Chloramine T O + H3C R
+

135

Cl Na

O C S
+

SO 2N

H2O

R2C O

X X : Cl hoac NSO2Ar
-

Dithioketal, ac biet dithiolane va dithiane vong, cung rat hu hieu e bao ve carbonyl. Cac hp chat nay c ieu che do tac dung cua dithiol tng ng vi xuc tac Lewis acid nh BF3 hoac (CF3SO3)2Mg hay (CF3SO3)2Zn. Bistrimethylsilyl sulfate vi s hien dien cua SiO2 cung c s dung e ieu che dithiolane. Cac nhom bao ve dithioacetal hoac ketal co the tach ra do cac tac chat oxy hoa X e hoat hoa cho phan ng thuy phan.
+
+ +

R2C(SR')2

R2C
+

SR'

R2C

S R'

H2O

R2C OH

SR'

R2C O

SR'

IV. BAO VE NHOM ACID Neu ch co OH cua COOH can c bao ve th co the s dung phan ng ester hoa, e sau o thuy phan trong moi trng kiem e tai sinh lai acid. Neu can phai tranh cac ieu kien cua phan ng thuy phan trong moi trng kiem, co the s dung t-butyl ester, v ester nay thuy phan de dang trong moi trng acid, hoac 2,2,2-trichloroethyl ester, v ester nay b phan tch do tac dung kh cua Zn. Mot so ester khac co the b kh do TBAF khan. e bao ve phan carbonyl cua COOH, ngi ta co the chuyen nhom chc nay thanh dan xuat oxazoline, thong thng nhat la dan xuat 4,4-dimethyl c ieu che do tac dung cua acid vi 2-amino-2-methylpropanol hoac 2,2dimethylaziridine.

Giao trnh Tong hp Hoa Hu c

CH3 N RCOOH + HOCH2C(CH3)2 NH2 2-Amino-2-methylpropanol R C CH3 O 1-Oxazoline

136

H3C H3C RCOOH + HN 2,2-Dimethylaziridine CH3 R C N O

CH3 H
+

CH3 O R C N CH3

Cac dan xuat d hoan nay bao ve acid oi vi tac chat Grignard va cac tac chat cung cap hydride. Acid co the tai sinh do phan ng thuy phan acid hoac chuyen thanh ester do phan ng xuc tac acid vi mot alcohol thch hp. Carboxilic acid cung co the c bao ve di dang mot orthoester. Cac orthoester dan xuat t alcohol n gian de dang b thuy phan va orthoester thong dung nhat e bao ve acid la 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane. Cac orthoester nh hoan nay co the c ieu che do phan ng trao oi vi mot so orthoester khac, hoac do phan ng vi iminoether, hay do phan ng chuyen v cua ester dan xuat t 3-hydroxymethyl-3-methyloxetane.
(HOCH2)3CCH3 O O O CH3 RCHCH2 O O BF3

RC(OCH3)3 RCOR' NH

(HOCH2)3CCH3 R

CH3

Cac phng phap bao ve va kh nhom bao ve cua acid khong thuan li bang cua alcohol va aldehyde. Nh the, neu can phai bao ve acid, ngi ta thng chuyen acid nay thanh aldehyde hoac keton hay alcohol, va sau khi phan ng ket thuc th tien hanh oxy hoa e tai sinh acid tr lai.

Giao trnh Tong hp Hoa Hu c

137

BAI TAP Bai 1 : Hay chon phng phap tot nhat e bao ve nhom OH cua cac chat trong cac chuyen hoa sau :
a)
b)

HOCH2C(CH3)2CH2Br
HOCH2C CH

HOCH2C(CH3)2CH2D
HOCH2C CCH3

c)

H2C

CHC(CH3)2OH

BrCH2CH2C(CH3)2OH

Bai 2 : T 1,3-propandithiol, formaldehyde, cac tac chat hu c can thiet, cung vi n-BuLi lam xuc tac base, hay tong hp cac chat sau : a) (CH3)2CHCH2CHO b) PhCH2CHO c) Cyclopentylcarbaldehyde d) Diethyl ketone e) Ethyl isopropyl ketone f) Acetophenon Bai 3 : Hay tong hp PhCH2CHOHCH2CH2COCH3 t PhCH2CHO va BrCH2CH2COCH3. Bai 4 : Hay xac nh cau truc cua cac chat t A en E trong chuoi cac phan ng sau :
BrCH2COOEt + (CH3)2CHCH2CHO Zn A CrO3 / Py B HOCH2CH2OH C LiAlH4 H3O
+

Bai 5 : Hay tong hp cyclohexancarbaldehyde t cac hp chat mach thang. Bai 6 : Hay tien hanh monobrom hoa va mononitro hoa aniline. Bai 7 : Mot sinh vien tien hanh tong hp o-methoxybenzyl alcohol t o-cresol theo chuoi phan ng sau :

Giao trnh Tong hp Hoa Hu c

CH3 OH Na2Cr2O 7 H2SO4 COOH OH CH2N 2 d ether 1. LiAlH4 / ether 2. H+ COOCH3 OCH3

138

CH2OH OCH3

nhng lai khong at c hieu qua. Ban hay neu iem sai trong chuoi tong hp tren. Bai 8 : Hay tien hanh chuyen hoa sau :
COOH CH2CH2NH2

HO OH

OH

HO OH

OH