PHNG PHP TO LIN

KT CACBON-CACBON
QUA CC PHN NG
NGNG T

NHM 7

2.4.1phn ng ngng t gia hp cht

cacbonyl vi cacbanion c n nh bi hai
nhm ht electron bn cnh
Mt cch tng qut, phn ng ngng t ca cacbanion c th
c gii thiu bng s sau y:
XCH2Y

BH(hay BH )

BH(Hay BH )

XCHY

B (Hay B)

RCOR'

R
C
R'

OH

R
C
R'

B (hay B)

H2 O

CHXY

CHXY
R
C
R'

n gin hn c th vit nh sau:

XCH2Y

RCOR'

RR'C

CXY

H 2O

CXY

Nh vy bazo y khng cn phi rt mnh v cng

khng cn i hi t l ng lng 1:1 nh trong phn
ng ankyl ha v axyl ha. Cng cn ch rng ton b
qu trnh l thun nghch, do cn c bin php loi
nc to ra trong phn ng. Mc khc nu trong h phn
ng c nhiu ngun cacbanion v nhiu nhm cacbonyl
khc nhau th s ngng t xy ra ch yu cacbanion n
nh nht vi cacbon ca nhm cacbonyl no c
electrophin ln nht.
Vi nhn xt trn th xc tc cho phn ng ngng t gia
andehit hay xeton vi cacbanion n nh nhtbi hai nhm
ht electron X v Y) ch cn cc bazo tng i yu nh
piperidin chng hn. Trong trng hp ny phn ng c
mang tn ngng t knoevenagel. Th d

PhCHO

CH2(COOC2H5)2
CH2(CN)2

Piperidin
0OC

PhCH

C(COOC2H5)2

PhCH2NH2

97%

CHO

CH

CH3
CH3

CH2

CH

C(CN)2

CH3
CHO

CH3COCH2COOC2H5

Piperidin CH

CH2

CH

COCH3
CH

0 C

75%

85%

y xc tc l bazo yu nn ngay c andehit c nh

RCH2CHO cng khng b t ngng t.

COOC2H5

Trong phn ng ngng t Knoevenagel, nu b sung them mt

cht axit hu c hoc thay amin t do bng mui amoni
(thng l axetat) th c th nng cao c hiu sut sn
phm. Hn na n cn lm tang tc andedrat ha giai
on cui cng ca qu trnh ngng t
Th d:
CH3(CH2)2CHO + CH2(COOC2H5)

Piperidini axetat CH (CH ) CH=C(COOC H )

3
2 2
2 5 2
benzen si
(59%)

(CH3)2CH
CH3COCH(CH3)2 + NCCH2COOC2H5

CH3COONH4
benzen si

CN
(64%)

C
CH3

COOC2H5

Mt chiu hng quan trng ca ngng t Knoevenagel l

khi mt hoc c hai nhm ht electron lm n nh
cacbanion (X v Y) l cacboxyl (-COOH). Khi phn ng
mang tn s ngng t Doebner,trong thng km theo
c qu trnh ecacboxyl ha v to ra ch yu ng phn E
(hay trans). Th d:
Ph
PhCHO + CH3CH(COOH)2

Piridin
Piperidin

CH3
C =C

(96%)
COOH

i khi s ngng t Knoevenagel gia mt andehit vi mt

ngun cacbanion khng dn ti sn phm bnh thng m
li to ra sn phm phn ng ca mt phn t andehit vi
hai phn t cacbanion:

ng dng ca phn ng ngng t Knoevenagel:

Tng hp ethoxuximid (thuc ng kinh)
- tng hp ethoxuximid ngi ta thc hin phn ng ngng
t Knoevenagel gia etyl ,metyl xetonvowis etylxiano axetat
c hp cht khng no, sau cho hp cht ny cng hp
vi ion xianua i ti dn xut initrin este. Thy phn
initrin trong dd axit v c long nng c dn xut axit
succinimit, gi thit l qua phn ng decacboxyl ha hp cht
tricacbonxylic. Cui cng l ng vng vi aminiac c
ethoxuximid

Quy trnh tng hp ethosuximid

H 3C

CN
C

O + H 2C

C2H5
C2H5
C

H 3C

CH

COOC2H5

CN

H2O/H+

COOC2H5

CH3
C2H5
H3C

CN

H3C

COOH

C2H5
H3C

C=C
COOC2H5

CH
COOH
O

NH3 nng

CN

COOH

COOH

CH2COOH
C2H5

C2H5

BAZO (AMIN)

NH
O

dun nng
-CO2

CN-

2.4.2 Phn ng ngng t gia

hp cht cacbonyl

vi cacbanion c n nh bi mt nhm ht
electron bn cnh
Phn ng ngng t ca cc anehit v xeton
Phn ng andol v ngng t crotonic ngha l s tng tc ca
hai phn t mt anehit hoc xeton trong mi tng bazo (axit)
to thnh hp cht -khng no.
OH H
2 RCH2COR'

Bazo

RCH2C C COR'
R' R

B
H 2O

RCH2C
R'

C COR'

Trong cc iu kin nht nh c th tch c

sn phm trung gian ca qu trnh ( hp cht
anol).
NaOH
2CH3(CH2)2CHO

(H2O)

CH3(CH2)2CH

CHO

86%

CH2CH3
O
O

C2H5ONa

48%

=> Cho hiu sut thp v sn phm to thnh c

th tham gia qu trnh ph.

Phn ng ngng t hn hp
Thc hin ngng t hai anehit hay xeton
khc nhau nhng c kh nng to ra
cacbanion d dng nh nhau v c cha
nhm cacbonyl vi kh nng phn ng nh
nhau, th c th nhn c hn hp 4 sn
R
R'
phm.
bazo
RCH CHO
R'CH CHO
RCH CH C CHO
R'CH CH C CHO
VD:
(I)
( II )
2

(sp ngung tu)

RCH2CH C CHO

R'CH2CH

R'
( III )

C CHO
R

( IV )
(sp ngung tu hon hop)


to ra sn phm duy nht (hn hp c
sn phm chnh) th mt trong hai cht
phn ng c cha hiro c axit cao
cha
to ra mt
sn cacbonyl vi
nht, cht kia
nhm
phm duy nht th
eletrophin cao nht.
mt trong hai cht
+ eletrophin
ca
nhm
P
phi
nh cacbonyl:
th no?
Anehit > xeton
> este v Ankyl-CO >
Aryl-CO
+ axit gim theo dy
Anehit _ xeton _ este

Phn

ng ngng t Claisen-Smith
Mt trong cc cht phn ng khng
cha hiro axit nh cc andehit thm
v d vng thm khng cha
c thc hin vi xc tc kim hoc
axit.
NaOH
PhCHO
CH
COC(CH
)
3 3
85%
VD: 3
PhCH CH COC(CH3)3
(C H OH, H O)
2 5

C6H5CHO

CH3COC6H5

NaOH

C6H5COCH

CHC6H5
OH

ng dng: tng hp Chalcon(

O
)

Phn

ng Perkin
Phn ng gia anehit thm khng c
vi anhidrit axit trong mi trng kim
nh.
K2CO3
H2O
C
H
C
H
CHO
(CH
CO)
O
VD:
6 5 CH
CH CO O COCH3
6 5
3
2
( H O)
2

C6H5 CH

CH COOH

CH3COOH

ng
dng: tng hp axit khng no nh:
C 6H 5

CH

CH

:axit -phenyl acrylic trong

COOH

tinh du qu.
Cumarin trong cy u Tonka, cy ci
O
O
hng, c ngt v cam tho, qu du ty.
CHO
(CH3CO)2O

CH3COONa
t0

OH

COOC2H5

CHO
CH2
OH

C
O

OC2H5

CH3COOH
O

O
piperidinaxetat
C2H5OH, t0c

Phn
ng ngng t Claisen (ankyl ha cacbanion
bng este):
L s tng tc gia hai phn t este ( c H) vi nhau. P
xy ra trong mi trng kim dn ti sn phm dng
-xetoeste hoc 1,3-ixeto.
VD:
CH3COOC2H5

CH3COOC2H5

C2H5ONa

C6H5COCH2COCH3

(-C2H5OH)

Phn t este ng vai tr hp cht cacbonyl cn phn t

este kia ng vai tr to ra cacbanion khi c tc dng ca
bazo.

2.4.3 Cc phn ng ngng t khc

Phn ng ngng t thc hin trong mi trng axit, khi
phn ng ng khng th i qua nucleophin l cacbanion. V
vy, phn ng ngng t vi xc tc axit th enol ng vai tr
nuleophin v phn t cacbonyl c proton ha ng vai tr
electrophin.
OH
RCH2COR'

OH

H
RCH2C

R'

RCH2C
R CH

H
RCH
H2O
H

RCH2C
R'

C
R

OH2

R'

COR'

R'
COR'

RCH2C
R CH

R'
COR'

VD:

O
O

H2SO4
83%

Ngng t hn hp trong mi trng axit:

PhCHO

CH3COCH2CH3

HCl
( H2O)

PhCH

CH CO CH3

85%

Phn ng Mannich:
CH3
L phn ng ca hp cht cacbonyl c th enol ha trong
mi trng axit vi andehit (thng dng fomandehit) v
amin bc hai cho sn phm l dialkylaminoalkylxeton
thng gi l baz Mannich.

 y, nhm cacbonyl khng b proton ha hoc ion metylen

imini ng vai tro tc nhn electrophin.
Khc vi phn ng ngng t c xc tc bi axit, P
Mannich l s cng hp n gin khng c s tch loi cui
cng ( N HR2 b tch loi km hn nhm OH2 )
CH2O

CH2OH

R2NH

H2 N
H

CH2OH

R2 N
H

CH2

OH

H2O

R2 N

CH2

Vd:
CH3COCH3

(C2H5)2NH

HCHO

C2H5

HCl

CH3COCH2CH2N
C2H5

C2H5
OH

C2H5

C2H5

H3C

CH3
O

C2H5

OH

NH

C2H5

HCl

H3C

CH2
O

C2H5

C2H5
OH2

NH

C2H5

H2C

NEt2

H3C

CH2
O

CH2

H
N

NEt2

Phn
t nucleophin trong phn ng
Mannich c th l enol, hidrocacbon thm
c hot ha hoc d vng thm d
electron .
VD:
OH
PhCOCH3

PhC

CH2

CH2

N(CH3)2Cl

PhCO(CH2)2N(CH3)2

60%

CH2N
OH

OH
HCHO

82%
N

ng dng: iu ch dc phm chng st rt thuc

OH
dn xut AmidoquinOH(
) v Amopyroqui (
CH
)
CH
NH

(C2H5)2N
N

NH

ngi ta s dng phn ng Mannich chuyn

p-axetamidophenol thnh cc dn xut aminometyl
tng ng, sau cho cc hp cht ny tc dng
vi
4,7-dicloquinolin c cc hp cht trn.