Giao trnh Tong hp Hoa Hu c 121

Chng 5 : BAO VE NHOM CHC

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'
3
SiX + R O SiR'
3


RCH O R'OH + RCH(OR')
2
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 :

O O
H
+
+


O
+
ROH +
O RO
+
H
O RO
H
+
+


Tach nhom bao ve :


ROH
O RO
+
H
O RO
+
H
+ H
2
O
O HO


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.


CH
2
C
CH
3
OCH
3
ROH
H
2
O
ROC(CH
3
)
2
OCH
3
+


Ethyl vinyl ether cung rat hu dung e bao ve nhom hydroxyl di dang 1-
ethoxyethyl 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.


RO
-
M
+
CH
3
OCH
2
Cl
CH
3
OCH
2
CH
2
OCH
2
Cl
CH
3
OCH
2
OR
CH
3
OCH
2
CH
2
OCH
2
OR

Giao trnh Tong hp Hoa Hu c 123

Nhom bao ve MEM c tach ra de dang bi cac acid Lewis, nh ZnBr
2
,
MgBr
2
, TiCl
4
, (CH
3
)
2
BBr, (CH
3
)
3
SiI 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.


CH
THPO
OMEM
CH
2
CH
3
COOH , H
2
O
30 C , 40h
o
CH
HO
OMEM
CH
2


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
+
CH
3
SCH
2
Cl
Cl
-
CH
3
SCH
2
OR MCl + +


+ ROH CH
3
SOCH
3
CH
3
COOH
(CH
3
CO)
2
O
CH
3
SCH
2
OR


+ + ROH CH
3
SCH
2
OR (CH
3
)
2
S (PhCO
2
)
2


Nhom MTM c tach ra mot cach chon loc trong dung dch nc muoi
Ag
+
hoac Hg
2+
. 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 BBr
3
. Nhom t-butyl thng c a vao do phan ng cua
alcohol vi isobutylene co xuc tac acid.


ROH CH
2
C(CH
3
)
2
H
+
ROC(CH
3
)
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 S
N
1. 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
NH
4
OH. 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.


CH
2
OH
Cl
3
CCN +
CH
2
O C
NH
CCl
3



CH
2
O C
NH
CCl
3
+ ROH
CH
2
OR
Cl
3
C C
O
NH
2
+


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 :

CH CH R
OH OH
R'
CH
3
COCH
3
H
+
+
O O
H
3
C
R
R
CH
3

Giao trnh Tong hp Hoa Hu c 125

Nhom isopropylene cung co the gan vao do phan ng xuc tac acid vi 2,2-
dimethoxypropane.


CH CH
2
OH R
OH
H
+
+ O O
H
3
C
R
CH
3
OCH
3
C CH
3
CH
3
OCH
3
CH
3
OH + 2


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.


O
O
O
Ph
HO
OH
OCH
3
N
N
O Ph
+
CHCl
3

O
O
O
Ph
HO
O
OCH
3
Ph
O
(78%)


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
O
OCH
2
CCl
3
Zn
ROH CH
2
CCl
2
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.


CH
2
OCNR
2
O
H
2
/ Pd
[HOCNR
2
]
O
CO
2 R
2
NH +


Nhom Cbz cung co the c tach ra do s phoi hp cua mot Lewis acid nh
BF
3
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 t-
butoxypyrocarbonate hay hon hp carbonate ester.


(CH
3
)
3
COCOCOC(CH
3
)
3
O O
t-But oxypyrocarbonat e
(CH
3
)
3
COCON
O
CPh
CN
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.


NR
O
O
NH
2
NH
2
+
NH
NH
O
O
RNH
2
+


Phan ng kh vi NaBH
4
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 127

NR
O
O
RNH
2
+
BH
4
-
NR
O
H
OH
CHO
NHR
O
BH
4
-
CH
2
OH
NHR
O
O
O


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 CH
2
CH
NHCCF
3
O
COOCH
2
CH
3
Ba(OH)
2 Ar CH
2
CH
NH
2
COOH


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.


R
2
NCPh
O
R
2
AlH
R
2
NCPh
H
OAlR
2
H
+
H
2
O
RNH
2
PhCHO +


Trichloroacetamide co the tach ra do NaBH
4
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 128

ArNH
2
(CH
3
)
2
SiCH
2
CH
2
Si(CH
3
)
2
H H
CsF , HMPA
Si
N
Si
H
3
C CH
3
H
3
H
3
C
Ar
+
100 C
o



ArNH
2
Si
N
Si
H
3
C CH
3
H
3
H
3
C
Ar
+
(CH
3
)
2
SiH
(CH
3
)
2
SiH
(PPh
3
)
3
RhCl


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-.


H
2
N CH
R
1
C
O
NH CH
R
2
C
O
NH CH
R
3
C
O
NH CH
R
COOH
n


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 CF
3
CO- do nhom nay de b
kh vi acid yeu, hoac nhom C
6
H
5
CH
2
OCO- v nhom nay de b kh do phan ng
hydrogen hoa xuc tac, hoac dan xuat nhom phthalyl C
6
H
4
(CO)
2
N- 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 129
Th du 1 :
a) Bao ve nhom amino bang benzyloxycarbonyl :


CH
2
OH ClCOC
2
H
5
O
CH
2
O C
O
OC
2
H
5
HCl + +
Benzyl alcohol
Benzylethylcarbonat


CH
2
O C
O
OC
2
H
5
+ H
2
N CH
R
C
O
OH
+ CH
2
O C
O
NH CH
R
C
O
OH C
2
H
5
OH
Aminoacid


b) Chuyen nhom carboxyl thanh nhom chc co hoat tnh cao hn (chuyen thanh
acid chloride) :

CH
2
O C
O
NH CH
R
C
O
OH
PCl
5
CH
2
O C
O
NH CH
R
C
O
Cl


c) Ghep cap thanh dipeptide :

+ H
2
N CH
R'
C
O
OH CH
2
O C
O
NH CH
R
C
O
Cl CH
2
O C
O
NH CH
R
C
O
NH CH
R'
C
O
OH


d) Kh nhom bao ve :

+
CH
2
O C
O
NH CH
R
C
O
NH CH
R'
C
O
OH
H
2
/ Pd
CH
3
CO
2
CH
R
C
O
NH CH
R'
C
O
OH H
2
N
Dipeptide


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 130

Aminoacid
+
H
2
N CH
R
C
O
OH C
O
NH CH
R
C
O
OH CF
3
(CF
3
CO)
2
O


b) Chuyen nhom carboxyl thanh nhom chc co hoat tnh cao hn (moat anhydride
cong kenh) :


C
O
NH CH
R
C
O
OH CF
3
(CH
3
)
3
N
C
O
NH CH
R
C
O
O
-

+
NH(CH
3
)
3
CF
3


+ C
O
NH CH
R
C
O
O
-

+
NH(CH
3
)
3
CF
3 Cl C
O
OCH
2
CH(CH
3
)
2
C
O
NH CH
R
C
O
O CF
3
C
O
OCH
2
CH(CH
3
)
2



c) Ghep thanh mot dipeptide :


H
2
N CH
R'
C
O
OH
+ C
O
NH CH
R
C
O
O CF
3
C
O
OCH
2
CH(CH
3
)
2
C
O
NH CH
R
C
O
NH CF
3
CH
R'
C
O
OH
(CH
3
)
2
CHCH
2
OH CO
2
+ +


d) Kh nhom bao ve :

C
O
NH CH
R
C
O
NH CF
3
CH
R'
C
O
OH
H
3
O
+
+ CH
R
C
O
NH CH
R'
C
O
OH H
2
N
CF
3
COOH
Dipeptide


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 131

O
O
O
H
2
N CH
R
C
O
OH
+ N
O
O
CH
R
C
O
OH
H
2
O +


b) Chuyen nhom chc carboxyl thanh dan xuat acyl cua dicyclohexylisourea hoat
ong :

+ N
O
O
CH
R
C
O
OH C
6
H
11
N C NC
6
H
11
Dicylcohexylcarbodiimid
N
O
O
CH
R
C
O
O C
NC
6
H
11
NHC
6
H
11


c) Ghep thanh mot dipeptide :


H
2
N CH
R'
C
O
OH +
N
O
O
CH
R
C
O
O C
NC
6
H
11
NHC
6
H
11
+ N
O
O
CH
R
C
O
NH CH
R'
C
O
OH C
6
H
11
NH C
O
NHC
6
H
11
Dicyclohexylurea


d) Kh nhom bao ve :

N
O
O
CH
R
C
O
NH CH
R'
C
O
OH
NH
2
NH
2
+ H
2
N CH
R
C
O
NH CH
R'
C
O
OH
Dipeptide
NH
NH
O
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 :

CH
2
O C
O
Cl H
2
N CH
R
C
O
OH +
CH
2
O C
O
NH CH
R
C
O
OH
PCl
3
CH
2
O C
O
NH CH
R
C
O
Cl

CH
2
Cl
N
O
O
O
R
H
+


Anhydrid vong khi un nong c m vong phong thch CO
2
va a phan
hoa.

N
O
O
O
R
H
+
H
2
O
n H
2
N CH
R
C
O
( NH CH
R
C
O
) OH
n-
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
O
CH
NH
2
CH
2
CH
2
C
O
NH CH
CH
2
C
O
NH CH
2
C
O
OH
SH
Glutathion


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 Orn Leu Phe Pro
Val Orn Leu Phe Pro


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
R
O HOCH
2
CH
2
OH
H
2
O +
O
O
C
R
R'
H
+
+
Dioxolane


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 2,2-
dimethoxypropane.


R C
O
R' CH(OCH
3
)
3
+
H
+
R C
OCH
3
OCH
3
R' HCOOCH
3
+
Orthoester


Giao trnh Tong hp Hoa Hu c 134

R C
O
R' +
H
+
R C
OCH
3
OCH
3
R' + (CH
3
O)
2
C(CH
3
)
2
(CH
3
)
2
C O


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.


R
2
C O R'OSi(CH
3
)
3
+ 2
(CH
3
)
3
SiO
2
SCF
3
R
2
C(OR')
2
(CH
3
)
3
SiOSi(CH
3
)
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-1,2-
dihydroxypropane 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 .


BrCH
2
O
O
R
R
Zn
R
2
C O HOCH
2
CH CH
2
+



+ R C
OCH
2
CCl
3
OCH
2
CCl
3
R'
Zn
R C
O
R'
THF
CH
2
CCl
2


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 BF
3
. 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 135

R
C
R
S
O
H
3
C SO
2
N
Cl
Na
+
-
+
R
C
R
S
O
X
+
H
2
O
R
2
C O
Chloramine T
X : Cl
-
hoa c
-
NSO
2
Ar


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 BF
3
hoac (CF
3
SO
3
)
2
Mg hay (CF
3
SO
3
)
2
Zn. Bis-
trimethylsilyl sulfate vi s hien dien cua SiO
2
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.

R
2
C(SR')
2
X
+
R
2
C
+
SR'
SR'
X
+ R
2
C S
+
R'
H
2
O
R
2
C
OH
SR' R
2
C O


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 2,2-
dimethylaziridine.

Giao trnh Tong hp Hoa Hu c 136

RCOOH HOCH
2
C(CH
3
)
2
NH
2
+
O
C
N
R
CH
3
CH
3
2-Amino-2-methylpropanol
1-Oxazoline



RCOOH +
N
C
O
R
CH
3
CH
3
N
H
3
C CH
3
H
N
H
3
C CH
3
C
O
R
H
+
2,2-Dimethylaziridine


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.


RC(OCH
3
)
3
RCOR'
NH
RCHCH
2
O
CH
3
O
BF
3
(HOCH
2
)
3
CCH
3
(HOCH
2
)
3
CCH
3
CH
3
R
O
O
O


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 :
HOCH
2
C(CH
3
)
2
CH
2
Br HOCH
2
C(CH
3
)
2
CH
2
D
a)

HOCH
2
C CH HOCH
2
C CCH
3
b)

H
2
C CHC(CH
3
)
2
OH BrCH
2
CH
2
C(CH
3
)
2
OH
c)


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) (CH
3
)
2
CHCH
2
CHO
b) PhCH
2
CHO
c) Cyclopentylcarbaldehyde
d) Diethyl ketone
e) Ethyl isopropyl ketone
f) Acetophenon

Bai 3 : Hay tong hp PhCH
2
CHOHCH
2
CH
2
COCH
3
t PhCH
2
CHO va
BrCH
2
CH
2
COCH
3
.

Bai 4 : Hay xac nh cau truc cua cac chat t A en E trong chuoi cac phan ng
sau :
BrCH
2
COOEt (CH
3
)
2
CHCH
2
CHO
Zn
CrO
3
/ Py
HOCH
2
CH
2
OH
LiAlH
4
H
3
O
+
A
B
C
D
E
+


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 138

CH
3
OH
H
2
SO
4
Na
2
Cr
2
O
7
COOH
OH
CH
2
N
2
ether
d
COOCH
3
OCH
3
LiAlH
4
/ ether 1.
H
+
2.
CH
2
OH
OCH
3

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
OH
OH
HO
CH
2
CH
2
NH
2
OH
OH
HO