Tổng hợp một số hợp chất hữu cơ có hoạt tính sinh học

DAI HOC QUOC
GIA
HA
NOI
TRlrtTNG
DAI HOC KHOA HOC
TITNHIEN
• • •
•
Ten de tai
" TONG
HOP MOT SO HOP
CHnt HUU
CO
ft
CO
HOflT TINH SINH
HOC
MA
SO: QT-05- 19
OAl
HOC QUOC GIA HA
MOl
Oi
I
5fib
CHU
TRI
D£
TAI:
Th.S THAN THI

THANH
VAN
CAN BO THAM GIA: Cac sinh vien
phong
THHC
HA NOI- 2006
l.BAOCAOTOMTAT:
a. Ten de
tai:
"Tong
hop mot so hop chat
huru
ca c6 boat
tinh
sinh hoc"
Ma so:
QT-05-19
b.
Cbu
tri
de tai: Th.S Trdn Thi Thanh Van
c.
Can bo tham gia: Cac sinh vien phong THHC 2
d. Muc tieu va
no!
dung nghien
cufu:
- Muc tieu:
Tie'n
hanh t6ng hop, nghien

cuu ca'u
tao va thu hoat
tinh
sinh hoc
ctia m6t
so
dan xu^t
ciia axit arylacrylic. Trong do quan tarn han ca la t6ng hgp
m6t
s6' hidrazit cua
axit arylacrylic va
chuy^n
hoa thanh hidrazon
chiia nhan
5-nitrofuranyl
c6 hoat
tinh
sinh
hoc cao.
- Not dung: Tien hanh phan
vtng
t6ng hgp cac
ch^t
huu ca, xac dinh
c^u
tao san pham nha
cac
phuong
phap ph6
IR,

UV-VIS,
MS,
'H-NMR,
thu hoat
tinh
khang
khu&,khang na'm
cua
mOt
s6' chat
tdng
hgp dugc.
e. Ket qua
dat
dugc:
• Da tong hgp
m6t
s6
metyl
va
etyl
este cua axit arylacrylic,
tir
do t6ng hgp cac hidrazit
va
ih
cac hidrazit tong hgp cac hidrazon
ciia
axit arylacrylic.
•

C^u
true
cua cac hgp
cha't
mod
nh^n
dugc da dugc xac
nh^n nhcy
cac phuong phap
phd
h6ng ngoai, ph6
c6ng hucmg ttf
hat
nhan
va ph6
kh6'i
lugng.
• Hoat
tinh
sinh hoc cua mot so san
phSm
dugc
thir
tren
mOt s6
chung
n&i
va vi
khu^n.
•

V6i
ke't qua do da va se cong bo cac c6ng
trinh
sau day:
Tong hap, xac dinh
cdu
tao va thi hoat tinh sinh hoc cua mot so dan xud't cua axit
arylacrylic,
bai
giri
tap chi Hoa hoc va
umg
dung, se dang trong nam 2006
• Dua tren de tai nay da gop
phin
dao tao dugc:
-\-
Da gop phin h6 trg 01 hoc vien cao hoc bao ve thanh c6ng
luan
van cao hoc:
f.
Tinh
binh sii dung kinb phi:
Tong kinh
phi
dugc
ca'p
cho
viec
thuc hien

d6
tai la 10 trieu d6ng chu yeu dugc
dung de mua hoa chat nghiem. Mot
phSn
chu yeu khac dugc
diing
d^
thue
mucm
chuyen
mon va
lao
dong.
KHOA HOA HOC
Hd
not,
ngayi^
thdng
^
nam 2006
CHU
NHllM Dfi
TAI
"u-
PGS TS. Tran Thi
Nhu
Mai , . ThS. Tran
Thj
Thanh Van
S.

j:>t4ln
i^y!n/u'
2.
SUMMARY:
a. Reaserching Project: "Synthesis of some organic compounds have biological
activity"
Code: QT.
05-19
b.
Director: Tran Thi Thanh Van, M.S.
c.
Members: Some students in Organic Synthesis Group
U.
d. Researching Attitudes and Contents:
- Researching Attitudes: synthesis of, study on structure and test biological activity of
some derivatives of arylacrylic acid.
- Researching Contents: Perfoming synthetic reactions of the organic compounds,
determining the constitutions of the products by spectroscopies as
IR,
UV-VIS, MS,
'H-NMR, test of some biological activity of some compounds.
e. Results:
• Several of methyl, ethyl este hidrazides and hidrazones of
arylacryhc
acid have been
synthesized.
• The constitutions of the products have been determined by using IR-, UV-VIS, MS-
and 'H-NMR- spectroscopies.
• The bioactivity of some compounds have been tested.
• One reaserching paper has been published and submitted.

• The reaserching project has contributed to the graduations of one master.
PHAN
NOI
DUNG
CHINH
MUC LUC
Trang
A.
Ldl Md
DAU 4
B.
NOI
DUNG
CHINH 5
1.
Tdng
hgp cac metyl va etyl este ciia axit arylacrylic 5
2.
T6ng
hgp cac hidrazit cua axit arylacrylic 5
3.
T6ng hgp cac hidrazon cua axit arylacrylic 8
4.
Thir
hoat
tinh
sinh hoc cua mot
s6'
cha't
tdng hgp dugc

10
5 Thuc nghiem
11
6 Ket
luan
12
C. TAI LIEU THAM
KHAO
12
A.
L61
MO
DAU
Nham
gop
phSn tim
ra nhung chat c6 hoat
tinh
sinh hoc cao phuc vu cho muc
dfch
tim
ra
nhung loai thu6'c
m6i ch6'ng
lai
nhung can benh the ki, chung toi da thuc hien de
tai "tdng hgp
m6t
so hgp
ch^t hOu

ca c6 hoat
tinh
sinh hoc"
vcd
mong muon gop mot
phin
nho cho muc
dich
tren. Trong
d6
tai chung t6i quan
tam
han ca den viec tdng hgp mot
s6
dan xuit
cia axit arylacrylic nhu cac este, hidrazit, hidrazon
chiia nhan
5-nitro furanyl da
dugc bie't la c6 hoat
tinh
sinh hoc cao.
Cac
cha't
tdng hgp dugc da dugc xac dinh
ca'u
tao bang cac phuong phap vat
ly
hien
dai va m5t
s6'

ch^t
da dugc thu hoat
tinh
sinh hoc tren mot
s6'
chung vi khuan va na'm.
B.
PHAN
NOI
DUNG
CHINH
1.
Tdng hgp cac metyl va etyl este cua axit arylacrylic.
Metyl va etyl este cua axit arylacrylic dugc tdng hgp
true
tiep
tir
phan
ung
cua cac
ancol
va axit arylacrylic trong su c6 mat cua
H2SO4
lam xuc tac. De tang hieu suat phan
ung
chung t6i da dung du ancol va dun nong nhe h6n hgp phan
vtng.
Cac
meiyi
va etyl este

thu dugc
a
dang tinh
th^
hay dang long a dieu kien
thucmg,
c6 diem nong chay hoac diem
spi
xac
dinh.^
Ca^u true
cua san
phim
dugc xac dinh bang cac phuang phap phd hong ngoai,
tu ngoai, phd
cdng huong
tu nhan proton va phd kh6'i lugng.
Sa dd phan
utig:
R-CH=CH-COOH
+
R'-OH
^ "
R-CH=CH-COOR'
+ H2O
R:
C^H^-,
P-CH3O-C6H4-,
m-N02-C6H4-,
m-Cl-C6H4-

R
'.
C2H5-,
CH3-
Bdng 1: Ket qua
tdng
hop va xac dinh cdu tao cac este cua axit arylacrylic.
TT
1
2
3
4
5
6
R
C6H3-
P-CH3O-
CfiH4-
m-NOj-
CfiH4-
m-Cl-QH4-
2-C4H4O-
NO2-
C4H,0-
R'
-QH3
-CH3
-CH3
-CH3
-CH3

-QH3
*
nc
cnai)
(271)
93-94
125-126
53-54
(146-147)
91-92
Hieu
suat
79,4
74,6
74,1
81,9
72,6
63,8
Phd hong ngoai
(cm"^
Vc=o
1711
1711
1708
1732
1717
1706
Vc=C
1638
1639

1638
1715
1641
1640
^c-o-c
1313
1270
1206
1173
1323
1295
1318
1258
1017
1211
1282
1213
VN02
1524
1355
1512
1349
Vri
793
677
Pho
tu
ngoai
(A,^3„
nm)

277,5
216,5
260,3
203,0
272,4
220,8
303,0
Tren phd
hdng
ngoai cua cac metyl va etyl este
ciia
axit arylacrylic cho tha'y
cue
dai ha'p thu cua nhom -OH axit c6 chan rong
(tir
2313-2512 cm') da
m^t
han, thay vao do
la
sir
xua't hien cac
cue
dai hap thu ciia lien ke't
C-O-C
este
a
khoang 1200-1300 cm"' (xem
hinh 1 va 2).
2.
Tdng hgp cac hidrazit cua axit arylacrylic.

Cac hidrazit dugc tdng hgp
true
tie'p
tiJ
phan
ung
cua cac etyl va metyl este cua axit
acrylic vdi hidrazin hidrat trong dung m6i etanol hoac metanol. Cac phan ung thuc hien
tuang
dO'i
de nhung
then
gian phan
utig
thuang keo dai (khoang
12
gid). Cac san pham thu
dugc
a
dang long hoac tinh the c6 nhiet
d6
s6i hoac nhiet do nong chay xac dinh. Ca'u
triic
ciia cac san
ph^m
dugc xac dinh bang phuang phap phd
hdng
ngoai, tu ngoai va phd cong
huong
tijf

hat nhan proton. Ke't qua tdng hgp cac hidrazit dugc cho
a
bang 2.
San
ph^m
hidrazit tao thanh c6 phd
hdng
ngoai khac vdi cac este ban dau. Tren phd
hdng
ngoai xua't hien cac
cue
dai ha'p thu cua lien ket NH
a
vung
tir
3230-3416 cm"',
cue
dai
h^p
thu cua lien ket C=0
a
1664-1716 cm', nhung cac
cue
dai hap thu thuang tu,
khOng
sac net do c6 hien tugng tao lien ke't hidro giua nhom C=0 cacbonyl va
NH2.
Bang
2:
Ket qua tong hap vd xac dinh cdu tao

cac
hidrazit R-CH=CH-C0-NH-NH2
TT
1
2
3
4
5
R
QH5-
P-CH3O-
C6H4-
m-N02-
CftH4-
m-Ci-C5H4-
NO2-
C4H,0-
*•
nc
24-25
85-86
103-
105
23-24
120-
121
Hieu
suat
55,5
58,5

71,4
50,0
62,1
Pho hong ngoai
(cm')
Vc=0
1714
1716
1644
1692
1705
Vc=C
1636
1639
1664
1640
1642
Vc-N
1279
1202
1174
1207
1211
1175
1284
1242
VNOI
1532
1344
1511

1315
Vci
786
Phottf
ngoai
(X^,„
nm)
275,4
216,4
309,8
210,8
260,8
206,4
269.2
214,0
1#
Hinh 1:
Pho
hong ngoai cua este metyl
m-cloxinamat
Tren phd
c5ng
huong
tir
hat nhan proton, ngoai cac
tin
hieu cua cac proton trong
nhan thom
thi
tin hieu cua proton trong nhom

-CH=CH-
cung xua't hien rat ro net va dac
biet la cac pic c6
cucmg
do ye'u 6 do chuyen dich hoa hoc 8,0 va 2,lppm dac
trung
cho
proton cua nhom
-NH-NH-
(xem bang 5).
Dai
hoc
Ouoc gia
turyi acrylalTTiRfyr
-^-r-r
n H-r.,.,.
Hinh 2: Pho hong ngoai cua metyl
3-furyl
acrylat.
96
94
92
90
m
B6
64
82
80
78
76

74
72
70
68
66
64
62
60
58
56
!
ill
'ij
^
I
! ^
!
S ! i
'!' i
l!
;l
Hinh 3:
Phd
cong hong ngoai cua
2-(5-nitrofuryl-2)
acryloyl hidrazit
1
3.
Tong hgp cac hidrazon cua axit arylacrylic.
Thuc hien phan

iJng
ngung tu cac hidrazit
vcd
furan-2 andehit the thu dugc cac
hidrazon khac nhau. Tren phd hong ngoai cua hidrazon
khOng
tha'y xua't hien dao dong
hoa tri
ciia
lien ke't N-H cua nhom
NH2
trong khoang 3416-3230
cm'
ma thay vao do la
lien ke't C-H cua vong furan
6
khoang 3199-3016
cm'
va C-O-C a
1348-1184
cm' va dac
biet
d viing
1684-1600
cm"'
xua't hien them nhieu dinh dan xen nhau, dieu do cho tha'y
lien ke't C=N da dugc
hinh
thanh (xem bang 3).
Bang 3: Ket qua tong hgp

vd
xac dinh cdu tao cac hidrazon.
Ar-CH=CH-C-NH-N=CH-^
J^—X
O'
TT
1
2
3
4
5
Ar
QH,-
QH,-
P-CH30-QH4-
m-NOj-QH^-
P-CI-C6H4
X
H
NO2-
H
NO2-
H
-yO
'•
nc
224-
225
198-
200

228-
230
232-
234
228-
230
Hieu
suat
67,2
65,0
64,0
65,5
64,0
Phd
hong ngoai (cm'^)
Vc=0
1648
1678
1642
1684
1675
Vc=c
1623
1623
1603
—
1644
Vc=N
1662
1678

1642
1639
1675
"^c-o-c
1345
1207
1316
1294
1348
1258
1295
1096
1254
1087
Pho
ttr ngoai
(>^„,
nm)
326.6
277,0
221,8
376,6
281,0
214,8
324,0
228,0
204,0
380,8
323,4
316,8

260,4
Phd kh6'i lugng cua cac hidrazon cho cac ion phan tu dung
vcd
du kien. Lien ket
0=C-NH-
ciia cac hidrazon kh6ng ben, de bi cat dut va nhung hidrazon
chiia
Cio trong
nguyen
tir
c6 xua't hien ion dong vi (xem so do phan manh).
CI
^O^CH=
o
II
CH-C-NH-N=CH
M""
319/321
'I
W
O'
NO-
NH-N=CH
m/e 139
O
o
NO2
C1-^Q^CH=CH-C-
m/e
165/167

H-i*^=CH-^
/^N02
m/e 125
^
<Q^CHECH
m/e 103
So d6 phan manh ciia 5-nitro
fufuryUden
p-clo
xinamoyl hidrazon
gij
^^ TFiuJunO7
0S4;
42
85
80
75
70
65
60
55
50
45
40
35-
30 -
25
20
15
10-1

•
i;
1">,N
c.^
^
Hinh 4.
Phd
hong ngoai cua 5-nitro
furiliden-m-nitro
xinamoyl hidrazon
Bang 4.
Phdkhdi luang
cua mot
so
chat tdng hgp
duac
CTPT
C9H9O5N
C.SHHOJNJ
C,4H,o04N3Cl
C,4Hn04N3
Khoi
luong
PT
211
270
319/321
285
m/e
(1%)

211(35); 166(67), 137(100), 109(35),
92(30),
81(28), 63(70)
204(5),
161(100), 133(45), 118(15),
107(30), 94(25), 77(30), 67(40)
319/321(50), 304(23), 273(35), 257(5),
165/167(60), 139(100), 125/127(65),
103(70), 77(30)
285(15), 239(5), 131(100), 103(45),
77(30)
Bang 5:
Phd
cong huong
tit
hat nhan proton cua mot
so
chat tdng hgp duac.
Chat
02N-<^
3^CH=CH-COOC2H5
O2N
4
3
//
w
o
2
'
II

CH=CH-C-NH-NH2
5 (ppm)
6,66(d,
J=16Hz,
IH,
H'); 7,33(d, J=3,5Hz,
IH,
H');
6,75(d,
J=4Hz,
IH,
H^);
7,4(d,
J=16Hz,
IH,
H');
l,34(t,3H,
-CH3);
4,28(q,
2H,
-CH2)
6,8(d,
J=15,5Hz,
IH,
H');
7,81(d,
J=4Hz,
IH,
H');
7,5(d,

J=2Hz,
IH,
tf); 7,55(d,
J=15,5Hz,
IH,
H');
8,0(q,J-l,0Hz,
IH,
H');
6,0(d,
J=:2,0Hz,
2H,
H')
4.
Thiif
boat
tinh
sinh hoc cua mot
so
chat tdng hgp dugc.
Tien
hanh
thir
hoat tinh khang
khudn,
khang
n^m
cua
m5t
s6' este, hidrazit va

hidrazon. Ke't qua cho tha'y miu T2, T4, T7, T8 c6 tac dung doi vci chung S.A, S.B, P.A.
Cac mau
Tl
den T5 deu c6 tac dung vci na'm men. Dac biet miu T4 c6 tac dung vci ca 4
chung tren. Ke't qua thu hoat tinh sinh hoc
th^
hien a bang 6.
Chung S.A: Staphylococus Aureus (Tu
cSu
vang
thu6c
c^u
khuan gam
(+))
Chung P.A: Pseudomonas Aeraginosa
(Mii
xanh
thuCc true khudn
gam (-))
Chung B.A: Bacillus Subtilis
(ThuOc
gam (+))
Na'm men: Candida albicans
10
Bang 6: Ket qua thu hoat tinh sinh hoc cua mot
so
dan xudt cua axit arylacrylic.
Mhx
(50^1)
Tl

T2
T3
T4
T5
T6
Cong
thijfc
<0>-CH=CH-C0-NHNH2
a-{^;^CH=CH-C0-NHNH2
<0)-CH=CH-CO-NHNH2
O2N
<^;^CH=CH-CO-NH-N=CH-^
^^NO:
(QyCH=CH-CO-NH-N=CH<^
\
^^ 0
02N-'<!
>-CH=:CH-COOC2H5
0
Duong
kinh
vong v6 khuan (mm)
S.A
0
14
20
20
0
23
P.A

0
0
0
12
0
16
B.A
0
10
0
20
0
30
Nam
men
Co tac
dune
Co tac
dune
Co tac
dung
Co tac
dung
Co tac
dung
Khong
tac dung
5.
Thuc nghiem
Diem chay cua cac san

phSm
duoc do bang phuang phap mao quan.
Phd hdng ngoai dugc do tren may AVATAR 760-FnR cua hang NICOLET.
Phd tu ngoai do tren may UVCP39 hang SHIMAZU.
Phd kh6'i lugng dugc do tren may HP.4989B.
Phd
c6ng
huong
tir
hat nhan dugc do tren may
500MHz.
Hoat tinh sinh hoc dugc thu tai Khoa Hoa Sinh Vien
19-8 B6
Cong an.
• Cac metyl va etyl este cua axit arylacrylic dugc tdng hgp
true
tiep tir axit
tuang
utig
va metanol, etanol. Dun hoi
luu each
thuy
hdn hiap
axit arylacryhc,
rugu va axit sunfuric trong 5 gia. Thay sinh han de ca't loai
bdt
rugu du,
d^
nguOi
roi chiet

la'y
lap
dlu,
trung hoa
Icfp
d^u
bang
Na2C03,
lam
lanh
bang da
mu<5i.
Thu san pham va ket tinh lai trong
etanohnudc.
• Cac hidrazit cua axit arylacrylic dugc tdng hgp
true
tie'p tu cac este va
hidrazinhidrat.
ViTa khua^y
va dun
each
thuy
hCn
hgp phan tog trong 12
gicf.
ca't loai
bcft
etanol sau do dd
true
tiep

hdn
hop vao
cdc nude
da, lam lanh ve
0-5*'C.
Ket tinh lai trong etanol.
• Cac hidrazon dugc tdng hgp bang
each
dun h6i luu
each
thuy trong khoang 6
giof hdn
hgp hidrazit va fufurol trong dung moi etanol. Ca't loai het etanol sau
do lam lanh
hdn
hgp den
0-5^C.
Ket tinh lai san
ph&n
trong etanol.
11
6. Ket luan
1.
Da tdng hgp dugc 6 este, 5 hidrazit va 5 hidrazon ciia axit acrylic the. San pham
dugc
kidm
tra do tinh khie't bang sac
ki
ban mong, tach tinh khiet bang
sdc ki

cot
tren he dung moi thich hgp.
2.
Xac dinh
c^u
tao ciia cac san pham ran bang phuang phap phd hong ngoai,
tir
ngoai,
phd cong huong
tir
hat nhan proton va phd khoi lugng.
3.
Mot
s6 cha't
duoc thu hoat tinh sinh hoc tren mot so chung vi
khu^n
va na'm.
C.TAI
LIEU THAM
KHAO
1.
American Medical Association (1994),
'Drug Eva/uarian
"chapter 73.
2.
Dimmock J.R., Taylor
U.G
(1984),
''Synthesis
and physical propeties of

substituted
4-dimethylaminomethyl-l-phenyl-l-nonen-3-
ones possecing
antitumor
propeties'\
J. Pharm.Sci, Vol 63,
N°l.
3.
Stephen Gillespie (2004),
''Medical
Microbiology
illustrated",
Butterworth
Heinemnn.
4.
Kirrk Othmer (1994),
"Encyclopedia
of Chemical
technology",
John. Wiley
and sons, NewYork, Vol.13,
3^^
ed.
12
TOM
TAT
CAC CONG TRINH NCKH CUA CA NHAN
Nganh: Hoa hoc Chuyen nganh: Hoa Huu ca
1.
Nguyen

Dinh
Trieu, Phan
Dinh
Long,
Trfo
Thi Thanh Van, Doan Manh Chat, Tran
Thi Phuong Thao
Tdng hgp, xac dinh ca'u tao va thir hoat tinh sinh hoc cua mot so dan xua't 5-aryl-2-
mecapto-1,3,4-oxadiazol.
Bao cao
6
Hoi nghi khoa hoc
Trucmg
Dai hoc Khoa hoc Tu
nhien,
tr. 129-133
2.
Nguyen
Dinh
Trieu, Doan buy Tien,
Trkn
Thi Thanh Van
Phd hdng ngoai
ciia
mot so fomazan
chu:a
di vong quinolin
Bao cao
6
Hoi nghi khoa hoc Truong Dai hoc Khoa hoc Tu nhien, tr.

134-137
3.
Trdn Thi Thanh Van, Vu Van Ha, Nguyen
Dinh
Trieu
Tdng hgp, nghien curu ca'u tao va su tao
phiic
cua mot so dan xuat fomazan c6 kha
nang tan trong nu6c
Bao cao
6 H6i
nghi Hoa hoc toan quo'c nam
2003.
4.
Trfo
Thi Thanh Van, Dang Ba Dung, Dang
Tni
Tuyet Anh, Nguyen
Dinh
Trieu
Nghien curu tdng hgp
m6t
so fomazan
chtia
di vong
pirol,
tdng hop phuc
ciia
fomazan
chiia

di vong pirol va
4,5-dimetylthiazolyl
fomazan vdi mot so ion kim loai
chuyen
tie'p.
5.
Nguyen
Dinh
Trieu,
TrSn
Thi Thanh Van
^
Tinh
hang s6
b6n ciia phiic
fomazan
chura
di vong vdi
m6t
so ion kim loai chuyen
tiep
Tap
chi
Phan
tich
Ly Hoa Sinh, so 2, tap 10, tr. 31-36, 2005
6. Trdn Thi Thanh Van, Nguyen
Dinh
Trieu
Tdng hgp va nghien cuu ca'u tao mot so hgp cha't fomazan

chiia
di vong furan,
thiophen va pirol
Tap chi Hoa hoc, so 3, tap 43, tr. 302-306, 2005
7.
Nguyen
Dinh
Trieu,
Trdn
Thi Thanh Van, Dang Ba Dung, Dang
Thi
Tuyet Anh
Nghien
ciJu
tdng hgp mot so difomazan chua di vong
Tuyen tap cac cong
trinh
hoi nghi khoa hoc va cong nghe hoa huu
co,
tr. 177-180,
2005
8.
Trdn
Thi Thanh Van, Nguyen Hai Doan, Nguyen
Dinh
Tneu
Tdng hgp, xac dinh ca'u tao va thir hoat tinh sinh hoc cua mot so dan
xu£t ciia
axit
arylacrylic,

Bai giri tap
chi
Hoa hoc va
ling
dung, se dang trong nam 2006
13
SCIENTIFIC PROJECT
BRANCH: Chemistry
PROJECT CATEGORY:
Fundemental
Project of Hanoi University of Science.
1.
Title
"Synthesis of some organic compounds have biological
activity''
2.
Code QT-05-19
3.
Managing Institution: Hanoi University of Science
4.
Implementing Institution: Faculty of Chemistry
5. Key implementors: - Tran Thi Thanh Van, M.A - Director
6. Duration: 12 months since
January,
2005.
1.
Budget: 10 millions VND
8. Main results:
- Results in science and technology
- Results in practical

apphcation
- Results in training
- Publications
Result in science and practical application:
Several of methyl, ethyl este hidrazides and hidrazones of arylacrylic acid have
been synthesized.
The constitutions of the products have been determined by using 1R-, UV-VIS,
MS-
and
^H-NMR-
spectroscopies.
The bioactivity of some compounds have been tested.
Result in training: The reaserching project has contributed to the graduations of a
master.
Publication: One reaserching paper have been reported.
Tran Thi Thanh Van, Nguyen Hai Doan, Nguyen Dinh Trieu, . Synthesise, establish
structure and bioactivity of some derivatives of arylaerylie
acid,
Journal of Chemistry
and using (submitted)
9. Evaluation grade
14
PHIEU
DANG KY
KET QUA NGHIEN
ClJtJ
KH-CN
Ten de tai (hoac du
an):
"Tdng hgp mot

so phufc
hgp chat huru ca c6 hoat tinh sinh
hoc"
Ma so: QT-
05-19
Co quan chu
tri
de tai (hoac du
an):
Khoa Hda-Trudng DHKHTN
Dja
chi:
19 Le Thanh Tong Ha noi
Tel:
04 8 533 503
Co quan quan ly de tai (hoac du
an):
Trudng
Dai hoc Khoa hoc Tu nhien
Dia chi: 334 Nguyen
Trai-
Thanh Xuan-Ha noi
Tel:
Tdng kinh
phi
thuc chi: 10 000 000 dong (Mudi trieu dong)
Trong do: -
Tuf
ngan sach Nha
nude:

0
- Kinh phi cua
trudng:
10 000 000 dong
- Vay
tin
dung: 0
- Von
tuco:
0
- Thu hoi: 0
Thoi
gian nghien cufu: 12 thang
Thdi
gian bat dau:
1/2005
Then gian
ket thuc: 12/2005
Ten cac can bo phdi hgp nghien cum:
Cac sinh vien phong THHC 2
So dang ky de
tai:
QT.
05.19
Ngay:
So
chihig
nhan dang ky
ket qua nghien
cihi:

Bao mat:
a. Phd bien rong rai:
0
b.
Phd bien han che:
D
c. Bao mat:
D
Tom tat ket qua nghien curu:
• Da nghien cuu phan
vcng
tdng hgp mot so metyl, etyl este, hidrazit, hidrazon
ciia
axit arylacrylic.
• ca'u true cua cac hgp chat mdi nhan dugc da dugc xac nhan nhd cac phuong phap
phd hong ngoai, phd cong huong tu hat nhan va phd khoi lugng.
• Mot so cha't tdng hgp dugc da dugc thir hoat
ti'nh
khang khuan, khang nam.
Kien nghi
v^qliT^^i^T^
ddi tugng ap dung nghien cuu;
Chu
nhieni
de tai
Thu truong
caquan
chu tn de tai
Chu
Ijch

Hoi dong
danh gia
chi'nh
thuc
Thu truong
caquan
quan
ly
de tai
15
;
niiN'^-RO'-^
Ho ten
Hoc ham
hoc vi
Trdn
Thi Thanh
van
Thac
sT
Kiten
Dong
dfifu
fKjiU^> llbiMB
(fS-moi.
f
Vt(^'^
16
TAP CHI
H(DA

HOC VA
ONIG
DUNG
So:
03 - 2006/GCN
CONG HOA
XA
HOI
CHU
NGHiA
VIET NAM
Doclap-Tudo-Hanhphuc
Hi) Noi.
ngay
07
thdng
03
lulm 200()
GIAY
CHONG
NHAN
Tap
chi
Hoa hoc va
U"ng
dung
chilng
nhan
bai
bao:

"TONC
HOP, XAC DINH CAU TAO VA
THL HOAT
TINH SINH HOC CUA MOT
SO DAN XUAT CUA AXIT
ARYLACRYUIC"
ciia
tac
gia
Trdn Thi
Thanh Van, Nguyin Hai Doan va Nguyin Dinh Trieu. Toa
soan da nhan bai bao ngay 07 thang 03 nam 2006 do PGS.TS
Nguy§n
Dang Quang - Dai hoc Bach khoa Ha
Noi
phan
bion.
Bai se
diidc
dang vao so 04 nam 2006.
soan
^^ILan \jdnn
TONG HOP XAC
DJNH CAU
TAO VA
THl^
HOAT TINH SINH HOC CUA
MOT SO
DAN
XUAT CUA AXIT

ARYLACRYLIC ' "^
SYNTHESISE, ESTABLISH STRUCTURE AND BIOACTIVITY OF
SOMF
DERIVATIVES OF ARYLACRYLIC ACID
^^^^ ^i
Thanh Van,
Nsuven
H^i
n^^
XT
^ ,
. . SUMMARY
syntheztT
00^0^
^T^^':^^^^:Z ^H
^r^^'^^"
^^ —^ of
spectroscopy.
The
bioactivity
of sorecomTnlrh I ^^"' ^^•' ^^ ^"'^ ^MR
been shown good inhibition
aiLsTsti,
'A'
" ''''"^- '^^'
°^
"^^''^ ^ave
Bacillus Subtms and Cand^^aalSs at
stgi""
"

^^^"^°—
^erag^nosa,
M6
DAU
khang vi khuan.
Nhan thrvrd/X It tfi'.'";•''tf '•'
'°.'^
''"'^ '^'^"^ "^-'
tao va thir hoat
tmh
sinh hoc
cL mot
.A'
H
- ^ " '''"^ '°"S ^^'
"g^'^"
^"^
c^"
K£T
QUA
VATHAO
LUAN
Tdng hop cac metyl este va etyl este cua axit arylacrylic.
Jw do
phan
utig:
R-CH=CH-COOH
-
R-OH
^^=^

R-CH=CH-COOR'
.
H^G
R:
QH5-,
P-CH3O-C6H4-,
m-N02-QH4-,
m-Cl-QH4-
R
-^QHs-,
CH3-
Hnn ^^*^^" "^f ^^^^
^°^
^^
P''^"
"^S ^'"^ ^^^'" ^^
^^"^f^
^^?"
tirong
doi
dl
dang
Chune
toi
dung du ancol de tang hieu
sua't
phan ung este hoa. Ket qua tdng hap cac este duac cho
6
Tong hop cac hidrazit cua axit arylacrylic.
Cac hidrazit

dirge tdng
hap
true
tiep tir phan
ling
cua cac etyl va metyl este cua axit
acrylic vdi hidrazin hidrat trong dung moi etanol hoac metanol. Cac phan ung thuc
hien
tucjng doi de
nhung
thcd
gian phan ung thudng keo
dai
(khoang 12 gia). Cac san pham thu
dirge
or dang long hoac tinh the cd nhiet do soi hoac nhiet do ndng chay xac dinh Ca'u
triic
cua cac san
ph&i
dugc xac dinh bang phuang phap phd hdng ngoai,
tir
ngoai va phd
cdng hirdng tiir
hat nhan proton. Ket qua tdng hgp cac hidrazit dugc cho d bang 2
Tren phd cong hudng tir hat nhan proton, ngoai cac
tin
hieu cua cac proton
trone
nhan thom thi
tin

hieu cua proton trong nhom
-CH=CH-
cung xua't hien ra't ro net va
d'
biet la
cac pic cd cudng do yeu d do chuyen dich hda hoc 8,0 va 2
I ppm
dac
fnm
i!*^
proton cua nhom -NH-NH- (xem bang 4). '
^^"^
•
'
™^
^^°
Bang 1: Ket qud
tSng
hap
vd
xac dinh cdu tao cdc este
cda
axit
arylacryll
TT R
C^<
R'
-QH
(T»,)
P-CH3O-QH4-

m-NOj-C^Ii,-
•CH
(271)
Hieu
suat
93-94
m-a-CJL-
2-C4H4O-
•CH.
-CH
125-126
79,4
J^|i2JI2ni_Qgoal
(cm"')
Vf^.
c=o
74,6
1711
1711
'c=c
1638
X-O-C
1313
1270
^102
1639
53-54
NO2-C4H3O-
-CH
•QH,

74,1
81,9
1708
1638
1206
1173
1732 1715
(146-147)
91-92
72,6
63,8
1717
1706
1323
1295
'CI
Pho
tu
ngoai
(^iiia>.
nm)
1641
1640
1318
1258^
1017
1211
1524
1355
277,5

216,5
793
677
260,3
203,0
1282
1213
1512
1349
272,4
220.8
303,0
Bang
2: Kit qud
tSng hop yd
xdc dinh cdu tao cdc hidrazit.
R-CH=CH-C0-NT1-
NH;
TT
1
2
3
w
\l
R
C5H5-
P-CH3O-QH4-
m-NO^-CJI^-
m-a-QH-
NO2-QH3O-

'
nc
24-25
85-86
103-105
23-24
120-121
Hieu
suat
55,5
58,5
71,4
50,0
62,1
Pho
hong ngoai (cm'i
Vc=o
1714
1716
1644
1692
1705
Vc=r
1636
1639
1664
1640
1642
VCN
1279

1202
1174
1207
1211
1175
1284
1242
'
INO/.
1532
1344
1511
1315
V^.
*^CI
786
Pho
tur
ngoai
(^-maxi
nm)
275,4
309,8
227,6
210
8
260,8
206 4
269,2
214 0

Tong hgp cac hidrazon cua axit arylacrylic,
Thirc
hien phan
ling ngimg
tu cac hidrazit vdi furan-2 andehit the thu
dirac
cac
nidrazon
khac nhau. Tren ph6 hdng ngoai cua hidrazon khong tha'y xua't hien dao dong
,
["
'"^''^" ^^^ ^"" '"^ "''""^ ^2
trong khoang 3416-3230 cm' ma thay vao do
ll
lien
ket C-H cua vong furan d khoang 3199-3016 cm' va C-O-C d
1348-1184
cm' va dac
biet
a
viing
1684-1600 cm' xua't hien them nhieu
dinh
dan xen nhau,
didu
do cho tha'v
lien
ket
C=N
da dugc hinh thanh (xem bang 3).

^
Phd khdi lugng cua cac hidrazon cho cac
ion
phan tu
diing
vai du kien Lien ke't
U-C-NH-
cua cac hidrazon khong ben, da bi cat dut va nhirng
hidrazon
chira
CIo
trong
nguySn tiir
cd xua't hien ion ddng vi (xem sa dd phan manh).
Bdng 3: Ket qud
tSng
hap vd xdc dinh can tao cdc hidrazon
O
IT
Ar
QH,-
QH
•e^s-
P-CH3O-QH
m-NO QH,-
P-a-QH4
H
NO,
H
NO,

H
Ar-CH=CH-C-NH-N=CH-/~\-
-yO
224-
225
Hieu
suat
198-
200
67,2
Vc=0
Ph6ji6ngngoai(cm')
1648
228-
230
65,0
CHC___VC=N
1623
1662
1678
232-
/J4
64.0
65.5
1623
1678
1642
228-
230
64,0

1684
1603
1642
1675
1644
1639
1675
O
!-<P>-CH=CH-C-NH-N=CH-^
)>—
lU+^iomi
O
NO-
IC-O-c
1345
1207
Pho tu ngoai
(^„.,,
nm)
1316
1294
1348
1258
1295
1096
1254
1087
M"*"
319/321
326,6

277,0
221,8
376,6
281,0
214,8
324.0
228,0
204,0
380,8
323,4
316,8
260,4
te-N=CH-
'' ^
O
m/e 139
O
NO2
C1^^^CH=CH-C-
o
NO
m/e 165/167
<^CHECH
m/e 125
^
m/e 103
So dd phan manh cua 5-nitro fufuryliden p-clo xinamoyl hidrazon
^ang
4: Pho cong huong tic hat nhdn proton cua mot
so

chat tong hop duoc.
Chat
0,N
n
CH=CH-COOC.H
O
2J^5
5 (ppm)
OoN
n
2 ' ^
•CH=CH-C-NH-NH-
O
6,66(d, J=16Hz,
IH,
H');
7,33(d, J=3,5Hz,
IH,
H*);
6,75(d,
J=4HZ,
IH,
H^);
7,4(d,
J=I6Hz,
IH,
H^);
l,34(t,3H,
-CH,);
4,28(q,

2H,
-CH,)
6,8(d,
J=15,5Hz,
IH,
H'); 7,81(d, J=4Hz
IH,
H^);
7,5(d,
J=2Hz,
IH,
H^);
7,55(d,
J=15,5Hz,
IH,
H^);
8,0(q,J-l,0Hz,
IH,
H^)-
6£(dJ=2,0Hz,2H,
H')
3
Thu hoat
tinh
sinh hoc cua mot so chat tong hgp dugc.
Tien
hanh
thur
hoat
tinh

khang khua'n, khang na'm cua mot so este hidrazit
va
hidrazon. Ket qua cho
th^y
miu T2, T4, T7, T8 cd tac dung
ddi
vai chung
S
A
SB
P
A
Cac mau Tl
de'n
T5
d^u
cd tac dung
v6i nam
men. Dac
biel mfiu
T4 cd
t^c
dm.^
r
A
Chung tren. Ke't qua
thit
hoat
tinh
sinh hoc thi hien d bdng 5

" ' ^ ^° ^^^ '^'^"g ^oi
ca 4
S P A ••
^*"P^/°'^°'^"^
.A"'-^"^
(Tu
c^u
vang thugc
cSu khu&
gam
(+))
Chung RA: Pseudomonas Aeraginosa (Mu xanh thuoc
true
khua'n gam
(
Chung B.A: Bacillus Subtilis (Thuoc gam (+))
' ' '^'"'"^ Sam
(-))
Nam
men: Candida albicans
Bdng
5:
Ket qud thi hoat
Unh
sinh hoc cua mot so ddn xudt cua axit arylacryhc.
Miu
(50(il)
Tl
T2
13

T4
T5
T6
FHirc
NGH]
Cong thirc
<Q)-CH-CH-CO-NHNH2
CI^QKCH=CH-CO-NHNH2
O)-CH::CH-C0-NHNH2
O2N
<^CH=CH-CO-NH-N=CH-{
J^-NOj
<0)-CH=CH-CO-NH-N=CH-<'
\
^— 0
^0
£M
Duong
kinh von? vo khnap
(mm)
S.A
0
14
20
20
0
23
P.A
0
1

0
0
12
0
16
B.A
0
10
0
20
0
30
Nam
mpn
Cd tac
1 duno
1
^\'"f^
Co tac
1
dun?
Co lac
dung
Co tac
dung
Co lac
dung
Khong
tac dung
J

Didm
chay cua cac san
phfoi dugc
do
b^ng
phuang phap mao quan.
Ph6 hong ngoai dugc do tren may AVATAR 760-FnR cua hang NICOLET.
Phd tu ngoai do tren may UVCP39 hang SHIMAZU.
Phd khoi lugng dugc do tren may HP.4989B.
Phd cong hucmg tur hat nhan dugc do tren may
SOOiMHz.
Hoat tmh sinh hoc dugc thu tai Khoa Hoa Sinh Vien
19-8
Bo Cong an.
• Cac metyl va etyl este cua axit arylacryhc dugc tong hgp
true
tiep tu axit
tuofng
ling va metanol, etanol. Dun hoi luu
each thiiy
h6n hgp axit arylacryhc,
rugu va axit sunfuric trong 5 gia. Thay sinh han de cat loai bat rugu du, de
ngugi roi chiet
l^'y
lop dau, trung hoa lap
d^u
b^ng
Na2C03.
lam
lanh bang

da
muoi. Thu san
ph^'m
va ket tinh lai trong
etanol:nudc.
» Cac hidrazit cua axit arylacrylic dugc tong hgp
true
tiep tu cac este va
hidrazinhidrat.
Vijra khu^'y
va dun
each
thuy
h6n
hgp phan ung trong
12
gia.
Cat
loai bdt
etanol sau do dd
true
tiep h6n hgp vao coc
nude
da, lam lanh
v6
0-5"C.
Ket tinh lai trong etanol.
• Cac hidrazon duac tdng hgp
b^ng
each

dun hoi luu
each
thuy trong khoang 6
gia hdn
hgp hidrazit va fufurol trong dung moi etanol. Cat loai het etanol sau
do
lam
lanh hdn
hop
dtn
0-5°C.
Ket tinh lai san
ph^m
trong etanol.
TAI LifiU
THAM KHAO
1.
American Medical Association (1994),
"DrugEvaluation"ch^piev
73.
2.
Dimmock
J.R,,
Taylor U.G (1984), "Synthesis and physical propeties of
substituted
4-dimethylaminomethyl-l-phenyl-l-nonen'3'
ones possecing
antitumorpropeties'\
J. Pharm.Sci, Vol
63,

N^l.
3.
Stephen Gillespie (2004),
"Medical
Microbiology
illustrated",
Butterworth
Heinemnn.
4.
Kirrk Othmer (1994), "Encyclopedia of Chemical
technology',
John. Wiley and
sons,
NewYork, Vol.13,
3'^
ed.