Nghiên cứu tổng hợp, cấu trúc và hoạt tính sinh học của các hợp chất tương tự Flavon, có chứa nhân dị vòng

DAI HOC ou6c
(;f
A
HA
NAI
BAO CAO
KfiT
QUA THUC
HI$N
Dfi
TAI
DAc
BlfiT
CA'P
DHQG:
2001
- 200.1
T«n
dt
Ml
•
"NGHIEN CtJtJ
T6NG
HOP,
CAU
TRUC VA HOAT
TfNH
SINH
HOC
COA
CAC

HOP
CHAT TlTONG
TV
FLA
VON,
C6 CHtTA
NHAN
DI
VONG"
M&s6
:
QG.01-02
Chu
i.hi«m
d^
m:
GS.
TSKH.
Nguyin
Minh Thdo
Hh
n6l- 2003
PHAN MO DAU
MUC LUC
Trang
PHAN
Md
DAU
'
Danh sdch

nhChig ngUiVi
tham gia
dC
tai
3
Danh muc cac bang s6
li6u ^
Danh
miic
c^c
hinh ^
TOM TAT NHUNG KET QUA CHINH
^
L
Ke't
qua
v6
mat khoa hoc 4
2.
K6t
qua phuc vu thuc
te 5
3.
K6x
qua dao tao 5
4.
K6'l
qua niing cao
tiOm
luc khoa hoc 6

5.
Tmh
hinh
su dung kinh
phi
6
ABSTRACT 7
PHAN
NOI
DUNG CHINH
8
I.
DillvAiid^
8
II.
Tdng quan cac
vA'n de nghien
cuu 9
2.1
Ve pli.ln
inij.'
(.huven
vj I
rii*s 9
2.2 Ve cac xeton a.
(3-khong
no 10
2.3
Vrti net v6 riavon
va flavonoit

11
IIL Phuang phap nghien cuu va
Ihuc
nghiem 12
3.1
Pliuotig
phap xac djnh cau tao do tinh
khiet yh
hoat tfnh sinh hgc
ciia
12
cac hgp
cliiit
tdng hop dugc
3.2 Tdng hgp cac este
ciia
phenol va thuc hien phan ung
chuyen
vi Fries 12
cua chiing
'5-3 HiU(/ng
phap chung tdng hgp cac xeton
a,
\\-
khAng no: 14
3.4
Pliuang
phap chung tdng hgp cac hgp chat tuong tu flavon 19
.^.5 Hurtrng
phap chung (dng hgp cac

pira/olin
thua nhan di vong: 21
24
4.1 Axetyl hoa
c^c
phenol
vh chuyen
vj
Fries
cua chiing 24
4.2 Tdng hgp cdc
xclon
a.
\\- khOng
no
25
4.3 Tdng hgp cac hgp
chAt tuctng tir
flavon co dura nhAn di vong 25
4.4 Tdng hgp cdc hgp
chflft kieu
pira/olin
chi'fa nhrui <li
vong 26
4.5 Tinh toan hoa lugng tir 26
4.6
Thdm
do hoat tfnh sinh hoc 26
V. Ke't luan 30
VI.

Kie'n nghj 30
TAI
LifiU
THAM KHAO 31
IHCNG
NGUOI
THAM
(ilA
DE TAI
1.
Nguyen Minh Thao - GS. TSKH - Truong Dai hoc Khoa hoc Tu nhicn- DHQG HN.
2.
Pham
Van
Phong - ThS. - Trucmg Dai hgc Khoa hgc Tu nhien- DHQG HN.
3.
M6t
s6' hgc vien cao hgc va sinh vien.
DANH MUC CAC BANC; SO
LI$U
Bang
I:
Cac san phiim phan
ihig
chuyen vi
Irics
Bang 2: Cdc xeton a.
p-
khAng no day agienol va iso(rgicnol
(E,.;)

Bang 3: Cac xeton a.
P-
khong no di
tir
resoxinol
(K,
s
va
DKr
m)
Bang 4: Cac xeton a.
P-
khong no di
ti^
hidroquinon (H,.?)
Bang 5: Cac xeton a,
P-
khdng-no
di
ti^
7- hidroxi- 8- axelylquinolin (Q,
4)
Bang
6:
Cac xeton a,
p-kh6ng
no di lii axit
dehidroaxctic (DHAin)
Bang 7: Cdc xeton a,
P-

khdng no di
tir
7- hidroxi- 4- metylcumarin
(C|.g)
Bang 8: Cdc hgp
ch^t
tucmg tu flavon di
tir
agienol va
iso(tgicnol
{FEU.)
Bang 9: Cdc hgp chat tuong tu flavon di tu resoxinol
(F,i,.s
va
F„K6 >)
Bang
10:
Cdc hop chat tuong lu flavon di lu
hidrcxjuinon
(F,,,
0
Bang
11:
Cac hgp chat luang tu
llavon
di lu
hidroxiquinolin (F,^,^)
Bang
12:
Cac

luirp chAI
tucmg tu flavon di Iff axit
dcliidroaxclic
(F„HA
112)
Bang
13:
Cac
pira/t)lin
chua
lutj)
phdn
(tgicnol
v;i
isoofgicnol (IVi (d
Bang 14: Cdc
pirazolin
chira hgp phAn resoxinol
(P,(,
^
va
F*,,^^,
.,):
Bang 15: Cdc pira/olin chua hgp phdn
hidrocpiinon
(P,,,
0
Bang
16:
C{ic piia/olin cliu;i

hgp phdn axil
deiiidroaxclic
(PDHA,
,,)
Bang 17: Cac
pinizolin clura
vong
tiuinolin (P^i i)
Bang
18:
Cac pirazolin chua hgp phan cumarin
(Pf,.,)
Haiij^
10;
Kli;i
iiAiij;
kh;uig
khuan
\
a
1.
liOnji
nam
cim
c:\c
xclon
(X,
p-
khAng no day
hidroquinon va resoxinol

Bang 20: Kha nang khang khuan va cho'ng nam cua cac
xeton
a.
P-
khong no day cumarin
Bang 21: Kha
nang
khdng
khuAii vu
chong
nam
cua cac
[)ira/olin
day
cuiiiarin
DANH MUC CAC HINH
Hinh
1: Phd cong huang
ti^
proton cua san phiim chuyen vi Fries 8- axetyl- 7- hidroxi- 4-
inetylcumarin.
Ffinh 2: Phd khoi lugng cua san pham
chuyen
vj Fries 8- axetyl- 7- hidroxi- 4-
metylcumarin.
Ffinh 3: Phd
cOng
huong tu prolon
cija
xeton a,

P-
khong no CL
Hinh
4: Phd kho'i lugng cua xeton a,
P-
khong no
Cl.
Hinh
5: Phd cong huong
tir
proton cua hgp chat loai pirazolin
P^.
ffinh 6: Phd khA'i lugng cua hgp chat loai pirazolin
IVi-
AT
NHUNG
KEI
QUA CHINH
D6
tai: "Nghien ciiru tdng hgp,
caiu true
va
lioiit
tinh sinh hoc
ciia
cac
ligp chai
tuong lu
Flavon, co
chiira nlian

cij
von^"
Chinh thirc dugc phe duyet la de tai dac
biet
cap Dai hgc Qudc gia Ha ngi vao Ihdng 05 nam
2001.
vdi thdi han 24 thdng (ke tu ngay kf) va ldng kinh
phi
60 trieu dAng. Den nay, de lai
da
dugc
lumn lhanh
va
dai dugi ci\c kei ipid
chinh nhu sau:
1.
Ke't qua ve
mat
khoa hoc:
Da nghien
cihi
phan ung
chuyen
vi Fries cdc
aryl axetat
di tu ddn xuat cua quinolin,
Ogicnol vii
isoogicnol,
cdc
dihidroxibcn/cn,

cdc hidroxi
ciia
cumarin va quinolon- 2. San
phdm cua phan
ihig
nay la cdc chdt ddu cho cac chuyen hod licp theo.
Da thuc hien phan
ung
ngung tu giua cac san pham
chuyen
vi Fries
a
tren
v6i
cac
indol - 3 - andehit
hodc v6i
cdc
andehit
day Furan lrong dieu
kiCn ciia
phan
ihig
Claisen-
Smith
d^
nhan dugc cac day xeton
rx,
p - khAng no luong ung co chira cdc nhan di vong
(khoang 50 hgp chat mdi).

Ti^
cdc hgp
chai
xclon
(/.,
\\
- khAng no nhan dugc d Iren da cho phan ung cAng hop
vong oxi hod boi
lim
huynh de lao thanh khoang 40 hgp
chai
mdi tuong lu Flavon nhung
chua nhan di vong hoac cho ngung lu ddng vong vdi
phenylhydrazin
de lao thanh khoang 50
hop chai
niiVi ciia
vdng pira/olin.
Cau
true
cua cac
iigp
chdl mdi nhan
dxsac
da dugc xac nhan nhd cac phuong phap phd
hdng ngoai, tir ngoai. phd cAng
hmmg
lir hat nhdn va phd khdi lugng.
Da van dung cdc
plurctng

phdp ti'nh Hod lugng lir ti'nh gan dung dc xdc djnh mat dd
dien tfch
Iren
cac vi
Iri
lrong phan tir. xac dinh do dai va nang lugng
lien
ke't trong phan tir.
Tren CO sd do da xdc dinh cau
h'mh
uu tien
ciia
phAn
tif,
ddng thdi gdp phdn lam sang ro
them ve chieu hudng va co che phan
i'mg.
Da tham dd hoat tfnh smh
IIDL
ciia
mgl
.so
Ja\
chat tdng hgp dugc va xdc djnh dugc
khoang 30 hgp chat cd hoat tinh khang khuan
vii
chdng nam d muc do khac nhau. trong dd
cd mot sd chat rat dang
chii
y va cdn dugc nghien

cirii
sau hon.
Vdi ke'l qua
do
da cAng bd cdc cong trinh sau
dav:
1.
Nguyen Minh
Thao,
Nguyen
Oinh
Dong,
^Tdng
hap
vd
chuyen hod mat
sd
xeton
a,
P-
kliong no co
chim
vong indol vd
quinolin \
Tap chi Hod hoc.
T.3^).
so
2, Tr.
f^O
(2001)

2.
Nguyen Minh Ihao,
Fhani
Van Phong,
'Tong
hap vd chuyen hod cdc hap chdt tuang tu khan con cd
chda
vong
indndTi.
T6t^
hap vd chuyen hod cdc hap chat xeton
a,
p-
khdny,
no
tif
cdc
3-fom\lin£n
w
J^
tuai
agienol \
Tuyen
tap cdc cong trinh Hoi nghi khoa hoc Idn thu hai
Tntang
Dai
htx KJtau
hpc Tu nhien
• DHQGHN, Hd Noi - 2000. Nhd .\udt bdn
"DHQCHN",

Hd Noi -
2(MJI.
tr I3H
•
14J
J.
Nguyen
Minh
Ihao.
liiin
V::;i
(hien,
Pham
Van Phong,
veton
ce,
fi- khong no tii ddn xudt cua isoagienol vd cdc
indol -3- andehit
\
Tuyen tap cdc cdng trinh klioa hpc ki niem 45 ndm ngdy thdnh lap Khoa Hod hpc
(1956 -
lOQIh
Nhd
xudt
hdn "DHQGHN" - Hd Noi -
2001,
tr.
52-55.
4. Nguyen Minh Thao, Pham Vdn Phong.
'Xdc dinh cdu hinh cua agienyl axetat vd sdn phdm chuyen vi Fries cua nd bdng phuang

phdp tinh Hod luang
tu\
Tap
chi
Hod hpc, T.40,
so
J, tr. 9 (2002)
5. Nguyen Minh Thao, Pham
Vdn
Phong,
*Xdc
dinh cdu hinh cua xeton a,
/?-
khdng no (td o
-axetylagienol
vd
3-fomylindol)
vd mot
vdi sdn phdm chuyin hod cua nd hdng phuang phdp tinh todn Hod luang
td\
Tap
chi
Hod hpc, T.40,
so
2, tr.
I-10
(2002)
6. Nguyen Minh
I
hao, Nguyen Van

Ndm,
l*ham
Van Phong,
*Tdng
hap vd chuyen hod mat sd xeton a, fi- khdng no
ta
axit
dehidroaxetic
vd cdc
furfural\
Tap
chi
Hod hoc, T.40,
so
3,
tr.43
(2002)
7. Nguyen Minh Thai), Pham
Vs^n
Phong,
Biii
Manh Tung, Phi Thi Minh Hai,
'Tong hap vd chuyen hod mot sd xeton a, fi khdng no di
tut
ddn xudt cua Hidroquinon vd
cdc indol-
3-
andehit
\
Tap chi Hod hoc,

T.41.
so
I.
tr.
6/
(200.^
H.
Nguyen Minh Thao, Pham Van Phong,
'The
quantum calculating application in Fries rearrangement of resorcinol diacetate
\
Bdo cdo lai Hdi nghi Khoa hoc Chdu A lan
tht'r 10
hop tai
lid
noi vdo ngdy
21-
24 thdng
10
ndm 2003.
9.
Nguyen Minh Thao, Pham Van Phong, Nguyen Xuan Tu,
\Synthesis
and transformation of some
ac,
fi unsaturated ketones from coumarine
derivatives and
indole-
3- aldehydes
\

Bdo cdo tai Hoi nghi Klioa hoc Au- A Idn
thif
VIII hop tai Hd noi vdo ngdy
21-
24 thdng
10
ndm 2003.
2.
Ket qua phuc vu thuc tc:
Viec tham dd va xac dinh dugc mot loat hgp chat c6 kha nang khang
khu an
va chdng
nahi
da
la
su dinh hudng ung dung thuc le. Hien nay mot vai hgp chat dang
chii
y dang dugc
tie'n hanh thir hoat
tinh
chdng ung thu va cd the ca chdng HIV. Ne'u cd ket qua tdt
thi
dd se
la cu ddng gdp tdt cho phuc vu thuc tc.
Ngoai ra. ke't qua dao tao ve mat nao do cung cd the coi nhu la kel qua phuc vu thuc
te.
3.
Ket qua dao tao:
Dua tren de tai nav da dao
t;io

duac:
Ig)
Ngoai ra
ci>n
I hgc
vien
cao hgc khac da hoan
th^h
chuong trinh hgc tap nhimg chua bao ve
luAn
van.
- Da hudng ddn 08 sinh vien bao
ve
thanh cAng khoa luan
lAt
nghiep: Trdn Van
Chie'n. Nguyen Manh Cudng, Nguyen Van
Nam.
Bui Manh Tung, Hoang
Hie
Thdng.
Duong Thi Hd.
Rii
Thi Minh Hai. Le Thanh Nghi.
- Da hudng
d^
mdt sd sinh vien lam nghien cuu khoa hgc lhu dugc ket qua tdt, Irong
66 cd sinh vien Nguyen XuAn
Tir
dat ket qua rat tot, dat giai

nhi
NCKH
ciia
sinh vien
Trudng DHKHTN va giai khuye'n khfch nghien
cmi
Khoa hgc Sinh vien cdp Dai hgc Qudc
gia Ha ndi nam
2003.
4.
Ket qua ndng cao tiem
lire
khoa hoc:
Tren CO sd
Ihuc
hien de tai. da dao lao mol
<6
thac si va cu
nlmn.
trong dd co
nhi^u
ngudi trd thanh can bA cd nang luc. MAl sd sinh vicn sau khi bao vc khoa
iuAn
tot
nghiCp
da
dugc de nghj
chuy^i
tie'p cao hoc nhu Phf Thi Minh Hai.
Ilianh viCn

de lai
Fliam
V.ln
Phong
sau khi bao
ve
xua't siic luan vdn thac sT cung
dii heu
chuan de dugc xet chuye'n tie'p nghien
cun
sinh.
Ve mat
thi6^t
bi, nhd viec thuc hien de tai vdi ngudn kinh phi dugc cdp ciing da tang
cudng mdt sd dung cu cdn thiet cho qua
trinh
thf nghiem nhu
lii
dd, bep dien, cac dung cu
ihuy
linh
di^c
biei.
va dac
biei
cd ngudn kinh phf dd mua cdc loai hod chdt dac biet phuc vu
qud trinh nghien
ci'm.
5.
Tmh

hinh
stir dung
kinh
phi:
Tdng kinh
phi
dugc cdp cho 2 nam
Ihirc liiCn
dc tai la 60 trieu ddng
(niAi
nam 30 trieu
ddng).
Kinh
phi
chu ye'u dugc diing dc mua hod chat va dung cu thf nghiem . Mot phdn chu
yeu khac
disac
dung de thue mudn chuyen mdn va lao dong. De'n nay da quyet loan dugc
khoang 52
IriCii.
Cdn hu khoang S Iricu sc dugc
qiiycl (odii
ngay sau khi
nghiem
thu
de
lai.
Hd noi. ngdy
i^'thdng
tenant

2003
XAC NHAN CUA
TRUONC;
OAI HOC
TUNHIEN.
DHQC.HN
OHO
MIEL
TRJONO
^^'
'
(
IIUNIIlftMDft IAI
.'C'^ffhi Jfrj/fU
GS.
TSKH.
Nguyin Minh
Tndo
XAC NHAN CUA DAI HOC OUOC GIA HA NOI
e and biological activity of the analogs
offlavone
compounds containing heterocyclic
nucleus'*
ABSTRACT
The Fries rearrangement reactions of aryl acetates from
derivatives
of
quinoline.
eugcnole,
isoeugenole,

dihydroxybcnzenes,
hydroxyquinoloncs, hydroxycoumarincs have been
studied. These products have been used as starting
reagents
for conscqucnl
lransii>rmalit)ns.
Tlicn,
the
Fries
rearrangement
producls have
been condensed
in the conditions of Claisen-
Schmidt reaction with indole- 3- andehydes or furfuraldehydes to give a,
P-
unsaturated
ketones
containing
heterocyclic
nucleus ( about .50
new
compounds).
The a, p- unsaturated ketones were
cyclo-aditionaly
transformed by Sulfur as an oxidizing
reagent,
forming about 40 new
flavone
analogs containing heterocyclic nucleus. The a.
P-

unsaturated ketones also easily reacted with phenylhydrazine to form about 50 new
derivatives of pirazoline ring.
The constitutions of the producls have been determined by using IR-,
UV-,
MS- and
'H-
NMR- spectroscopies, and the their antibiotic abilities have
also
been tested. Some of them
have shown good results and wc have been proposed to
enlarge
the research in order to
dclerminc and developc the resulls.
Besides synthetic
reactions.
Chemical
Softwares,
such as
HypcrCiicm
7.0. have also been
used lo
help
determining charge
density,
binding
length,
and binding energy of
molecularly
optimal confonnations and studying mechanisms of
the

reactions.
The
anli-bacleria
and
anli-ycarst
abilities of
Ihc
(X,
\\~
unsaturated
ketones
and pyrazolines
were tested.
Tlicse
synthetic products
have showed the
biological
activities
m
different
levels.
Some considerable ones need more
deeply
studying.
>an
phim thu dugc bang cdc phuong phap pho hien dai :
hdng ngoai, tir ngoai, cong hudng tir proton va khdi lugng cung nhu sir dung cac phuong
phap
tinh
hoa lugng tir gdn dung de xdc dinh

mdi d<}
dicn tfch, dA dai va nang luong lien
k^t.
cQng nhu cdc cdu
hinh
ben
ciia
phan tir. Tir dd cd
the
gdp phdn lam sang ro them chieu
hudng va co
ch^
phan ung.
-
Ti^n
hanh tham dd hoat tfnh khang
khudn,
chdng ndm va
xay
duu^
Inrdc
ddu mdi
quan he giGa cdu tnic phdn tir vdi hoat
linh
sinh hgc
ciia
hgp chat ldng
hgj)
dugc.
De thuc hien

66
tai. chiing ldi da sir dung cac phuong phdp thuc nghiem lien lien
trong tdng hgp huu co, cac phuang phap phd hien dai va phuong phdp
tinh
gan dting cua hoa
lugng tir de xem xet cdu tnic phan tir va phucrng phap tham dd hoat Ifnh sinh hgc theo lieu
chu^
trong dugc dien Viet nam.
n.
TONG QUAN CAC VAN
D£
N(;HIEN
CUU:
2.1.
Ve phdn
Umg
chuyen vi
Fries:^^-'^'
^'
'
Phan ling chuyen vj Fries la qud trinh chuyen \'i ngi phdn tir
ciia
cac phenyl este nhd
su
xiic
lac
ciia
axil Lewis
(AlCl^,
ZnCl2,

BF^ ).
Phan ung xay ra vd ban chat gidng vdi su
the'electrophin
(Sg).
Thf du:
OCOR OH OH
AK.h
COR
Co
che'chung ciia
phan ung dugc
trinh
bay Irong so dd sau:
'OAlt'h
»
KC
-c>
-
COR
oil
O^
R
/?-axy^>hL'nr)l
Al(t,
li
(I
a.\ylplfc;ni)l
Thong
thirdng.
ti lc cstc:

AlCi,
khim
la 1:1
fmol).
Tuy nhien neu trong phdn tir este
chua cdc nhdm cd kha nang tao phuc vdi nhdm clorua
thi
cdn dimg ti le nhom clorua khan
cao hon.
2,
dieu
kien
cd dung mdi vkhi este d Ihe
ran
va cd nhiet
dd ndng chay cao) hodc khong cdn dung mdi.
Ca»;
dung moi thdng dung !a
liilrobenzen,
caebon
disunfua hodc
diclocian
Iiong dd
liiii'ihcn/m (d mi liie
fi*ni'
a vt no \ir:i
hoa tan
nliAm
clorua khan,
viTa

hoa tan este.
2.2.
Vi
cdc xeton
a;
fi khdng no:
2.2.1.
Cdu
fuocac xolon
a,
\\-
khong no:
Cdc xeton a,
p-
khAng no
Id
cdc hgp chdl
hihi at
ma trong phan lir
ciia
chiing cd chira
nhdm vinyl xeton
(-CH=CH-CO-).
Chi'nh vl vdy ma cdc xeton a,
P-
khdng no cd kha ndng
tham gia
nhi^u
phan
ling

dd lao thanh cdc hgp chdt
hiru
co khdc nhau.
Plid
hdng ngoai cua xeton a,
p-
khAng no thudng xudt hien cdc pic ddc
liimg
cho dao
dOng
hda trj cua nhdm C=0
lien
hgp trong klioang 1630-
1690cm'.
ciia ndi ddi lien hop
ciing vdi cac ndi ddi cua vdng thom lrong khoang 1550-
16I5rw"'
va pic dac tnmg cho dao
ddng
bi^n
dang khdng phang
ciia
nhdm trans- vinyl d 960-
990c7« ' ''*'
Hid
lir ngoai
ciia
cdc xclon <x,
\\-
khdng no Ihuirng cd 3- 4

cue
dai ha'p lhu ndm d viing
tir
300«w
trd len vdi he sd tdt phdn tir khoang
lO'^
dac Irung cho budc chuyen electron
n->7r*.
240-
290nm
vdi he sd
Idt
phdn fir khoang
10^
dac
Irung
cho su chuyen budc
chuydn
electron
n->n*
va 200-
2?iOnm
dac
Inmg
cho su
chuyen
budc
chuyen electron
K—>7i*
cua

nlian
benzen''*''.
Ngoai ra cdn cd cdc
cue
dai vdi
^,„;„
nhd hon dac trung cho nhan thom, di vdng
2.2.2. Cdc phuong phap tdng hgp xeton a,
P-
khdng no:
Cac xeton a.
P-
khdng no cd
ihd
dugc ldng hgp bang
nhidu
phuong phdp khac nhau.
chdng han
lx\ng
phan
ihig ngimg
tu
ciia ankyltriphenyl
photphoclorua vdi andehit
piruvic'''.
bang su quang ddng phdn hda 4-
(benzanamino)-
3-
melyl-
5-

sliryloxazol'"',
bdng su phan
huy cdc
p-
aminoxeton''^-'"
'",
bdng
each
loai phan tir nudc
ciia
diaxetoancol''^'
va dac biet
bang phan ung ngung tu
Claisen-
Schmidt"^':
*^0-<N O OH O
^+'1^-'^
H"(HO")
M
I -
H7O II
AAC-CH3
+
R~CHO
5
U-Ar-C-CH2
CF*-R ^ • Ar-C-CH=:CH-R
I II
lluin
ung cd

ihc
dugc
f.huc
hiCn
vdi
xiic
tac axil hoac
h•<^z^1,
nhung thudng
xiic
tac
bazo cho ket qua lot hon. Co the ndi
ddy
ia
phumig
phdp phd bien nhat dd tdng hgp cac
xeton a,
P-
khdng no.
2.2.3.
Tmh chat
ciia
cac
xeton
a, fi- khdng no:
Cac
xelon
a.
p-
khdng no cd the Iham

;^ia
ra<;
pluin
\sv\)j.
a
i\-)i
doi
;ieng biet (cAng
bn>m
hay oxi hod bdi
KMnO,) hojc
phdn
(m,u tivit
nhdm CO
iihi du
lao ra 2,4-
10
di ca he xelon
a,
p- khAng no lien hgp de lao thanh cac
dJn
xuit cua vong pirazolin hoac
isoxazolin
Thfdu"^':
o
KCftll.,
C
CM
CM—t\.ii,ir
r,,HsNiiNn>M(

ni.o
R'\UCu
N
I
2.3.
Vdi net ve flavon
vd
flavonoit:
Flavonoit ndi rieng va flavonoit ndi chung la mgl
nlidrn
hop chdl rat rdng Idn va
phong
phii
lrong nhien thuc
vdi.
Chiing cd the d dang tu do hodc dang glycozil.
Chung cd Ihe dugc tdng hgp bang
nhidu phuofng
phap khac nhau.
(Jhiing
han:
Tdng hgp theo Koslaneski- Robinson"
*':
COCH
Oil
{Co\hCOhO/i'tM,0
Q
CO( II
o(
r)(

f.Ms
M.O
Cf^lh
Tif
o-
axelylphenol
va cdc
csli
COCMj
Cf.tlsCfX'l
»>
Pirklin
I4|.
((KM
KOII
OH
- " \/ OC(X
ftlls
Tit o-
axelylphenol
va andehit
Ihom"'*
'"^
o
COCHj
KOII
60%
+
CftHsCIIO
»-

Pirtdin
C
M((
(K)ll
MjSO^
(r Cf,Us
OM
C>llsOM
M.
O^
"CftH5
(NaHCO^.
20**C)
O
(C,.H5)3C*CI04
(CMiCO),0
^o-
-c:,,H5
Cdc Idc gia
[15]
da long
luyi")
dugc day flavon khi khudy trdn hdn hgp ddng phdn tir
gam
ciia
o- axelylphenol vdi benzandehil trong dung dich NaOH
0,1N
d nhiet
dc> 37"C
sudt

48-
216
gid\di hieu
sudi
cao.
U VA
THUCNGHlfeM:
3.L
Phuang phdp xdc dinh cdu tao dp tinh khiet vd hoat tinh sinh hpc cua cdc hap
chdi tong hap duac:
- Sdc kl lop mdng dugc thuc hien tren ban mdng trdng silicagel. He dung mdi etyl
axetat: clorofom
=1:4.
Hien
hinh
bang hoi idt hoac
d\ia\
dnh sdng tir ngoai.
- Phd hdng ngoai
dvxoc
ghi dudi dang cp vien vdi KBr
tren
may
PI-
IK 1801
Shimadzu
tai vien Khoa hgc
Hinh
su- Bg cong an, Trung ldm Hod
inAi

trudng va phat tricn bdn vung,
may Nicolet 760 E. S. P. Trung tdm Hod dau, mdy Nicolet Avatar 360 Sl -
IR
eP
ciia
phdng
thi
nghiem
VH-I
Trudng Dai hgc Khoa hgc tu nhien- Dai hgc Qudc gia Ha ndi.
- Phd tu ngoai ciia cac hgp chdt dugc ghi Iren may Spectrophotometer UV- 2001 trong
dung mdi etanol tai Phdng may- Bg mon Hod Vo co- Khoa Hod hgc- Trudng Dai hgc Khoa
ligc
lu nhien- Dai hgc QuAc gia Ha noi .
- Phd cAng hudng tir proton cua cac hgp chdt dugc ghi Iren may BRUKER
AVANCE
500
MHz trong dung mAi DMSO-
d^,
vdi chdt ndi chuan IMS tai phdng Hod cdu
true
Trung tarn
Khoa hgc Tu nhien va CAng nghe Qudc gia.
- Phd khdi lugng
ciia
cdc
h(;p
chdt
dmc
ghi

tren
may 5989 BMS tai phdng hoa cdu tnic
Trung tam Khoa hgc Tu nhien va Cong nghe Qudc gia.
~ niir lu)al Ifnh
khang khuan
\l\
chdng
nam diroc Ihuc hicn
lhc(^
phuiyng
phdp ghi trong
dugc die'n Viet nam
(Idp kluiiig
sinh
dC))
tai Phdng
ihi nghiem
Hoa sinh
XMzuh
\
ien 19-8 B(>
cdng an va lai Medilalec Co. Ltd (38 Chau Long- Ha ngi).
3.2.
Tdng hap cdc este cda phenol vd thuc
hien
phdn
iaig
chuyen vi Fries cua chiing:
3.2.J.
Tdng

h(/p
cac aryl axetat
WsXa
cda cac phenol):
Dun
si\\
hdn hgp
phciu>I
\d\
juhldiil
;i\clit.
(ti
Ic mol
1:1
\ai monophcnol
vd
1:2
vdi
dihidroxiaren) vdi
sued
mat
ciia Iml
a\il
photpiioric
dac ldm
xiic
tac lrong sudt 3- 5 gid.
Cai
loai axil axetic tao ra lrong phan ung va anhidrit
a:<ctic

du. Tach lay
Idp
huu ca, rira bang
dung dich NaOH
loiing
rdi nra lai nhieu Idn bdng nuoc. lam khd rdi cat lay cstc d dp sudt
thdp (trong trudng hgp cd dung mdi de chicl
thi
trudc khi cat Idy este phai cdt loai dung
nidi
trudc).
Vdi cac dihidroxibcn/cn
thuinig chi
diing
axil
sunfuric
dixc
h\m
xiic lacva
chi cdn
khuay trdn hon hgp
plu'ui
iuv^^
d
nhiel
dd phdng
sO
(hu dugc cstc thudng d trang thai
rdn.
Dudi day la cdc este khdi ddu tdng hgp: duac:

- Qgienyl axetat:
t",
163-
l67"C/23minHgi"'.
Hieu
suat 53%.
-
MYM/gicnyl
axelal:
I',„
78- 8(r'C. Hieu
sudi
Ky/v.
- Resoxinyl diaxelal;
i'\
278"C
(Theo lai lieu
'"'.
I';
278"C).
Hieu sudt 70%.
-
Hidr(K|uinyl
diaxelal:
t"„.
I22'C (Theo
lai
lieu '"'.
t',„
I22'C).

Hieu sudt 84%.
12
Icumarin:
C,.,
150-
15r'(:
niico
lai
lieu ""'.
t",,
L50-
I51"C).
Hieu sudt
90%.
•
8-
Quinolinyl
axetat:
C,,
56- 57'C
(TIKM.
lai
lieu ''"'.
i".,.
56-
57C).
Hien sudt 60%.
3-2.2.
Thuc hien phan
utig

chuyen vj Frits este cua cac phenol:
Dun ndng hdn hop este
ciia phenol
vdi
AICL
khan Ihco li
le mol
I: 2 hay I: 3 luy theo
este hodc
diesie
(cd Ihe' khong dung dung
moi
hoac dimg dung mAi
iiitiol)en/eu)
d 170-
180"C
sudt 3 gid. Sau dd phan huy hdn hgp bang nudc da va axil clohidric dac. San
ph^m
d
dang ke't tinh dugc lgc
hiit.
rira vu lam khd ngoai khAng khf
(in)ng
trudng hgp dimg
nitrobenzen lam dung mdi
thi
phai cdl loai nitrobenzen bdng chung cdt Idi cudn hoi nudc).
Cac san
ph£m
phan ung chuyen vi Fries duac ghi trong bang

I.
Bdng
I:
Cdc sdn phdm phdn ifng chuyen vi
Fries
^
Phenol khdi
dSu
San pham
chuydn vi
urc)
Hieu
suat
(%)
Phd
hong ngoai
(cm ^)
'on
agienol
oil
II^CO^
J^
^((K
II,
100-102 50
CIU
H-Clh
3442 1603
Isoogienol
on

H3CO.
J\
/COCMj
179-180
( II
CIKII
Resoxinol
1^6-
UJ
COCH^
Resoxinol
Hidroquinon
CH.CO
OM 84-85
110 /r ^\ COill
202-
203 74
31
60
64
3366 1615
3200
3200
3248
1620
1630
1640
13
7
methylcumarin

8-
hidroxiquinolin
COC
.<^^^^^^
(
111
^o-^o
^H^^^^COCU,
OH
162-163
'82-83
73
75
3370 1632
*: Hid 'IK
NMU,d/vw/:
'.53
{(\\d\
(^.?^(>i\\
<'
):
<>^^
(I I (\):
7,72
(IL
i\,)
*=*=:
I^d
'H-
NMR.

bppm:
2,53
va 2.73
(2CTL);
6.48
(ll-C\);
8,(K)
(H-
C,)
***:
Phd
'H-
NMR,
hppnr.
2,6()(CH,);
6,80
(H-C.);
7,00
(H-C,);
7,20
(H-
C);
9,20 (HO-
CV 11.30
(HO-C,).
MS:
I52(M*);
137 (KK)';;-)
(M'-
CH,);

109
(M'
(II.CO).
****:
Phd 'H- NMR,
bppm:
2,40(CH,);
2,60(CH,C());
6,20
(H-C,):
6,90
(H-C,);
7.70 (H-
C,);
11.30
(HO-CJ.
MS:
218(M*);
203(UX)%)
(M'
- CH,);
190
(M*
- CO).
3.3.
Fhuang
phdp chung tdng hap cdc xeton
a,
/A
khdng no:

a. Trong su lam lanh ben ngoai bang
nuc'jfc
dd, khuay trdn hdn hgp ddng tl le
mol ciia
cdc hop chdt kieu o-
hidroxiaxclophciioii (c;ic
s;in
phiim
chuyen
vi
Fries-
Bang I) vdi cdc
andehit day indol hoac furan lrong etanol vd cd mat
xiic
tac la dung dich NaOH 30- 60%.
Sau dd de
yen
hdn hgp phan ung d nhict do phdng
120
gid. Tie'p theo pha loang hdn hgp
phan ling bang
nU('/c
dd de'n gdp doi
the
tfch ban dau rdi trung hoa bdng lugng axit axetic
dugc
linh
sdn den phan ung trung tfnh. Lgc hut ket
tiia
tdch ra, dc khd ngoai khong khf va

cd
the
ket tinh lai
tijrdung
dich etanol- nudc.
h.
D6i vdi cac hgp chat la axil
dehidio axclic
hay axctylcumarin
thi
thuc hien phan
i'rng bdng
each
dun ndng hdn
h(;p
ddng li lc mol
ciia
hai chdt phan ung lrong clorofom vdi
vai gigt piperidin lam
xiic
lac lrong sudt
3-
5 gid. San phdm o dang
ket tiia
dugc tach ra
bang lgc
hiit
va do khd ngoai khdng kin'.
Ke't qua dugc gidi thieu d cac hang 2. 3. 4, 5. 6. vd 7.
14

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CD
CO
CD

cn
to
CO

CJ
to
,._
CO
CD
CD
r
CM
t)'>
to
<M
1
U)
•u
CI
TO
to
"0
TJ
«>
E
CM
>M
tz
(D
CD
IZ
d
TO
E

ZJ
CD
OJ
r-
0
06
to
0
CO
CD
CO
to
CM

10
r—
CO
CO
-^1
o>
•o
CD
to
•rf
i
•t—
"
ai
•0
tz

to
CO
0
c
tz
at
JZ
Ck.
CM
->%
N
d
CD
m
tz
"d
(O
E
u
CJ
OJ
X
CJ)
r-
X
0
•o
Icz
CO
0

VO
.—<
'~
VO
VO_
>
vo
>)
n
U
MD
-X
»/~<
«r".
—i
"~
OG
00
>•
VO
00
• 1
•—>
X
u
II
'-O
(i
s
1

:c
'•0
Of
vc
—
VO
>
r
'
11
:^
X
0
N
u
X
'O
ci:
S
y,
1
X
a-
X
00
3,4.
Phuang
phdp chung long hap
cdc
hap chdt tuang

tu
flavon:
Dun
sAi hdn hgp theo
ll le
mol
i:
I
cua
xclon (x,
|1-
khAng
no
vdi
luu
huynh trong
xilen
sudt
6-
8
gid. San phim tach
ra d
dang linh Ihe dugc Igc
hiit
va
de khA ngoai khdng
kill.
(
O
diO''

kci linh
lui
lir
dtiiif;
ilii
h
rlaiiol:
tiuac
K6i
qua dugc gidi thieu trong cac bang 8, 9, 10, 11,
12.
/?a/ig
8:
Cdc hap chdt tuang
tu flavon
di tit
agienol
vd isoagienol
(Fp,^)
TT.
FEI
Fs2
Fn
F^
Fes
F^
xeton
a,
p-
khongno

l£1
E2
E3
E4
E5
F6
1
U'^)
200-202
198-200
224-226
194-196
73-75
189-191
Rf
0.60
0,35
0.54
0.55
0.36
0.54
,
1
Hi6u
suat
(%)
IX)
85
80
60

48
40
%N
Tinh
4.23
4.06
3,44
3.33
-
-
Tim
4.38
4.34
3.72
3.57
-
'
Phd
h(V)g
ngoai
(cm')
Vc^
1632
1629
1624
1658
1645
1615
vcoc
1130;

1240
1245
1174.1247
1175.1260
1043; 1265
1037;
1267
Phd
tGrngoa
KJnm)(}QE)
241(4.19); 257(4.10); -;
294(4,42)
243(4.45); 264(4.51);
-;
301(4,54)
-;
255(4.71);-; 312(4.41)
244(4.40);-;-; 298(4.43)
-
-
n
F„,
FR,
FR,
FR,
FR,
'Dttti
•"DRZ
'DWJ
|Fn«,

xclon
Rl
R2
R3
R4
R5
l)1W
DR7
DR8
DR9
Bdng ^>
wrc)
193-194
203-204
255-256
150-151
105-106
20!>
?0(J
21S-216
161-162
242-243
';
Cdc
hap
elicit
tuang
tu
R,
1.54

0.70
0.45
0.63
0.48
O.Mi
0.73
0,52
0.50
Hi6u
sunt
(%)
64
75
50
65
52
wi
78
69
67
%N
Tinh
5.05
4.81
3.97
4.81
3.81
r» u)
5,93
5.93

-
Tim
5.25
4.78
3.83
4.95
3.54
Ei.)2
6.12
6,10
-
flavon
di tit resoxinol
(FRJ.S
vd
Fpufi.
9)
Phd
hong ngoai
(cm')
v«i
3169
3165
3137
3245
3136
-
-
-
-

^'c-fl
1637
1633
1629
1643
1623
m.\r
1615
1693
1628
Vcor
1128:1214
1084; 1263
1085; 1244
1170;
1257
1084; 1243
\\yf.
VM
1161;
1243
1125;
1210
1175;
1245
Phd
tiJr
ngoai
X^(nm)
(tge)

210(3.71); 250(3.46); -; 407(3.60)
-;
256(3.90); 364(3.68)
204(3.94); 245(3.71); 266(3.59);
302(3.55)
2(Xi(3.64);
-,
258(3,37);
362(3.62)
?2:'H3.75).
253(3.39). 412(3.58)
210(3.83); 240(3,75); 263(3,56);
314(3.65)
209(3,65); 245(3.31); 300(3,34)
TT
F,„
F„2
F.n
F,M
F,.s
xeton
HI
H2
H3
H4
H5
bane
W:
L
UfC)

178-179
19&-199
230-231
152-153
192-193
R.
0.52
0.53
0.56
0.61
0.63
ac
hap
Hieu
suai
(%)
65
75
71
64
70
Chdt
tuang
tu
flavon
di tit hidroquinon
(F^.^)
%N
Tfoh
5.05

4.81
3,97
4.81
3.81
Tim
5.21
4.91
3.75
4.88
3.60
Phd
h6ng
ngoai
(on')
Va.
3167
3245
3200
3259
3248
Vco
1644
1634
1618
1635
1642
Vcoc
1132;
1217
1162;

1218
1176;
1241
1137;
1211
1135;
1216
Phd
tungoai
X^(wn)(tgf:)
222(4.38);
257(4;25);
287(4.18);
412(4.41)
210(4.75);
2*^5(4.36);
266(4.15);
303(4.28)
-
208(4.76);
259(4.54); 303(4.16);
364(4,12)
-
Bdnn
11:
Cdc hap chat luang tu flavon di tir hidroxiquinolin
(FQI,^)
TT
Fo,
Fo,

Fo,
xeton
Ql
Q2
Q3
04
wrc)
191-192
180-181
251 252
102-103
R.
0,49
0.43
0.42
0.46
Hieu
su^
{%)
7a,
80
69
72
%N
hnt)
8.9
8.6
7.2
6.9
Tim

9.1
8.2
/.o
7.1
Phd hdng ngoai
(cm^)
V.i,
1634
1635
1621
1661
Vux;
1124;1242
1160.124?
1U5.
1245
1174;1244
VMI
3167
3266
3128
-
Ptid turngoai
X^(nm)(l9E)
241(4.58); 256(4.48); 294(3.94)
241(4.46); 263(4.31); 300(4.45)
-;
256(4.62); 312(4.35)
242(4.48);-; 298(4,40)
Bdng

12:
Cdc hap chdt
titang tu
flavon di tir axit dehidroaxetic
(Ff),f^
,.12)
TT.
*lH4t
^BHA2
^0HA3
FoHA4
FBHAS
FBHAS
1 ^BNA7
'^OHAM
FBHAS
'DHA1$
'BHAIt
*BHAt2
_
1
Xeton
DHAl
DHA2
DHA3
\)\\M
DHA5
DHA6
DHA7
0HA8

DHA9
DHA10
DHA11
DHA12
1
urc)
258-260
208-210
212-m
2/4-2/5
207-209
215-216
247-248
259-260
185-186
173-174
119-120
158-159
1
^
0,40
0.47
0,56
0.4/
0.54
0.42
0.5C
0.57
0,59
0.44

0.35
0.65
HI6u
(%)
73
75
55
83
92
71
P^
C3
78
69
GO
47
%N
rmh
4.81
nm
5.03
4.M
j 4.31
3.81
4.59
3.67
-
3.a3
-
•

4.19
4.32
4.01
-
Pttd
tiong rejoai
(cm')
Vco
1695;
162a
1695;
1528
1716;
1647
1714.1041
1713;
irvt?
1722.1060
1718.
1540
3,97
-
4.81
1
4.65
•1-
1720:1660
1685;
1666
1728;

1640
1718;
1641
1719-154((
Vcoc
1244
1244
1224
1180
1242
1263
1249
1253
1233
1245
1252
1253
Phd
II;
ngoai
>_(«m)(tg,:)
221(4.?^).
263(4.64);
284(3.76); 432(4,33)
210(4.56);
244(4^:5);
302(4.21).
452{?,53)
-; 239(4.33):
30:

(4.19);
446(4,40)
22/(<.12):
28'l{:i.r)9),
;-;i6(3.62);
431(4.46)
22/(4.27).
235(3.73):
32a(3.G9);
432(4.42)
209:241;-;
383
209;
255; -;
381
209;251;35G;;«'.9
210;
23a.
317;-
201;
248;-; 393
201.225:308:364
201;
231;-;
356
20
J.J.
rnuangpnap
chung tdng
hgp

cac pirazolin chua nhdn di
vdng:
Dun sAi
h6i
luu hAn hgp theo
ti
le mol I: 1 ctia xclon
r/,
p-
khong no
v(5ri
phenylhidrazin trong etanol
vi
su c6 mat vai gigt axil axetic liim
xiic
tac
suAt
3- 5
gi5.
San
pliiim tach ra
(V
dang ke't tua dugc Igc hut va de khA
ngo^i
khAng
khi.
K^t
qua dugc
gidri
thieu 6 cdc bang 13,

14,
15,
16,
17 va
18.
Bdnz
13:
Cdc
pirazolin chita
hgp
phdn agienol vd isoagienol
(PEL
6)
TT.
PE.
PD
PE3
Pw
P
PE«
Xeton
El
E2
E3
E4
E5
E6
ticTC)
158-160
166-168

138-140
114-116
177-179
107-109
R,
0.71
0.65
0.83
0,77
0.56
0,53
Ht^suat
(%)
74
61
55
75
78
72
%N
Tnh
9.93
9.61
8,42
8.22
-
-
Tim
9,64
9,33

8.25
8.50
^
-
Phd hdng
ngoai
Vc^cm')
3358
3378
3395
3296
3385
3285
Phd
tur
ngoai:
A^(nrn)
(Ige)
225(4.45); 305(4.41); 341(4.55)
224(4.19); 266(4.10); 300(4,07)
-;
254(4.36):
306(4.09)
-;
302(4.32); 341(4.52)
205(4.17); 225(4.28);
250.280.
305(vai); 340(4.77)
202;
225(4,64); 235; 283;

305(vai); 340(394)
Ddng
14:
Cdc
pirazolin chda hgp phdn resoxinol
(Pjf,,^
vd
PoRf,.9)
TT.
PRI
P.«
Pm
Pw
PRS
PD«
•
t«7
Pt«l
PDTS
xeton
Rl
R2
R3
R4
R5
DR6
DR7
DR8
DR9
W(°C)

173-174
144-145
237-238
170-171
139-140
165-166
199-200
277-278
171-172
Rf
0,56
0.67
0.74
0.71
0.78
0.57
0.62
0.66
0,75
Hi6usuat
(%)
74
72
51
46
60
65
73
40
1

''
1
%N
TWi
11.38
10.97
9.44
10.97
9,15
13.38
12.80
-
12,80
Tim
11.10
10.85
9,30
11,17
9.33
13.12
12.50
-
1^50
Phd hdng
ngoai
V^Jon')
3432.
3381
3118,3380
3150.3138

3311
4448.3312
3400.3388
3417.
3379
3448
3448
Phd ttf
ngoai:
^™.('wn)Ogi:)
220(3,85);-;
338(3.56)
225(3,55);
-; 344(3.67)
-
-
250(4.05);-;
340(4.21)
230(3.69);
291P.36);
337(3,52)
230(3,66);
266(3.24); 346(3.33)
-
223(3,48);
291(3,11); 365(3.15)
21
J.J.
rnuungpnap
cnung

long
nap cac pirazolin chua nhdn di
vong:
Dun sAi h6i luu hAn hgp theo
(i le
mol 1: 1
ciia
xeton a,
^~
khong no
voi
phenylhidrazin trong etanol
\h.
su co mat vai gigt axil axetic
lim xiic
lac suol 3- 5
gicr.
San
pliiim tdch ra
(V
dang ke't tua dugc Igc
hiit
va de khA
ngoii
khAng
khi.
K^t
qua dugc
gidri
thieu

6
cac bang 13, 14,
15,
16,
17 va 18.
Bdne
13:
Cdc
pirazolin chiia
hgp
phdn agienol vd isoagienol
(PEI.6)
TT.
PE.
PK
PB
PB4
P.^
PE«
Xeton
El
E2
E3
E4
E5
E6
wrc)
158-160
166-168
138-140

114-116
177-179
107-109
R,
0.71
0.65
0.83
0.77
0.56
0.53
Hteusu^
(%)
74
61
55
75
78
72
%N
Tffih
9.93
9.61
8,42
8,22
-
-
Tim
9.64
9.33
8.25

8,50
-
Phd hdng
ngoai
Vc^cm')
3358
3378
3395
3296
3385
3285
Phd lu
ngoai:
Kmknm)
(Ige)
225(4,45); 305(4.41); 341(4.55)
224(4.19);
266(4.10);
300(4,07)
-; 254(4,36): 306(4.09)
-;
302(4.32); 341(4.52)
205(4,17); 225(4,28);
250.280,
305(vai);
340(4,77)
202;
225(4.64); 235; 283;
305(vai); 340(394)
Bdng

14:
Cdc pirazolin chda
hgp
phdn
resoxinol
(Pf^,,^
vd
PDR^-V)
TT.
PR.
P.U
PR3
PR*
P«.
Ptw
"vm
PpB.
1 Pora
xelon
Rl
R2
R3
R4
R5
DR6
DR7
DR8
[)R9
tncTC)
173-174

144-145
237-238
170-171
139-140
165-166
199-200
277-278
171-172
R,
0.56
0.67
0.74
0.71
0.78
0.57
0.62
0.66
0,75
Hi6usuat
(*)
74
72
51
46
60
65
73
40
''
1

%N
Vnt\
11.38
10.97
9,44
10.97
9.15
13.38
12.80
-
Tim
11.10
10.85
9.30
11.17
9.33
13.12
1Z50
-
12,80
12.50
Phd hdng
ngoai
V.„{rm')
3432.
3381
3418,3380
3150,3138
3311
4448.3312

3400.3388
3417.
3379
3448
3448
1
Phd
hjr
ngoai:
A„Jnm)(Igc)
220(3.85);-;
338(3.56)
225(3.55); -; 344(3.67)
-
-
250(4.05);-: 340(4.21)
230(3.69).
291P.36);
337P.52)
230(3.66); 266(3.24);
346(3.33)
-
223(3.48);
291(3,11); 365(3.15)
2J
n.
PH,
P«
PH,
P«

P«
xeton
HI
H2
H3
H4
H5
Bane
UfC)
154-155
162-163
140-141
187-188
124-125
15:
Cdc pirazolin chiia hgp phdn hidroquinon
(Pfn-s)
Rr
0.61
0,66
0.46
0,53
0.44
HiOusuJt
(%)
66
47
42
72
64

%N
linti
11.38
10.97
9.44
10.97
9.15
Inn
11.50
11.20
9.29
10,78
9.00
Phd hdng
ngoai
Vo„(an')
3425.
3383
3414.3372
3283
3314
3288.3230
Phd hJT
ngoai:
A,«("m)(k|c)
225(3.93): 310(3.85); 340(3.95)
227(3.48); 316(3.45); 344(3,55)
-
222(3.90); 294(3.37);
368(3.40)

-
Bang
16:
Cdc pirazolin chua hgp phdn axit dehidroaxetic
(PouAi-n)
TT.
PewM
PfHU
PoHU
' MM
Pavw
Pom;
PuM
POM
' DWMO
PflHAn
Pn«B
Pomu
xeton
DHAl
DHA2
0HA3
DHA4
DHA5
DHA6
DHA7
DHA8
DHA9
DHA10
DHA11

0HA12
DHA13
W^)
221-223
205-207
283-284
224-225
115-117
80-81
127-128
170-171
65-66
ISO-181
240-241
179-180
220-221
R,
0,60
0,70
0,63
0.66
0.75
0,69
0.47
0.66
0.38
0.40
0,52
0.50
0.49

Hi&usuat
(%)
75
96
93
82
87
91
87
82
86
89
72
70
73
%N
Tinh
7,27
7.01
6,07
7,01
5.89
-
-
12,80
-
-
11,09
-
-

lim
7.32
6,70
5,68
7.31
6.07
-
-
12.50
-
-
10.72
-
-
Phd hdng
ngoai
(cm')
Vc,,
3400
3381
3450
3450
3420
3433
3429
:M65
3452
3427
3450
3348

3443
Vcoc
1240
1244
1246
1245
1255
1253
1241
1265
1257
1213
1275
1253
1212
Phd tu ngoai:
^(nm)
(lgc)
218(4.48); -; 283(4,20); 424(4.17)
225(4.41): -; 344(4,36); 434(2,45)
-:
295(4.17)-;
392(3,85)
220(4.53); 285(4.13);
-;
392(3,99)
-; -; 287(4.02); 354(3,69)
-:
235:
-;

394
202.234;
296; 359
203;
-;
284;
383
203;
-:
284;
381
207;
-;
293.
308
203;
252;
-;
-
202;
248;
-;
350
201; 251:-;
350
1
22
uuriK
M.
/_.

\.u%.
yuu4,olin
chita vdng quinolin
(PQI^)
TT.
Pu.
Paz
Po,
Po*
xeton
Ql
02
03
04
U^)
210-211
200-201
111-112
i7&-ieo
Rr
0,58
0.64
0.76
0.61
Hieu
suat
(%)
*
58
64

70
%N
rrtfi
i:t.9
13.4
11.7
11.3
Tim
13,6
13.2
11.4
11.2
Phd
hong
ngoai
(cm')
Va,
3422
3416
3387
3450
VNH
3277
3281
3057
-
Pho tu ngoai
X_(nm)(lgr)
221(4.21)
-; 340(4.32)

238(4.81): 303(3,92);
341(3,82)
236(4,43); 297(3.92); -
-: -:
341(4.45)
Bang
18:
Cdc pirazolin chUa hgp phdn cumarin
(Pci.9)
TT.
P*c.
Pc
Pa
PM
P«
Pes
Pa
Pes
P«
xeton
01
C2
C3
C4
05
06
07
08
09
U(^)

258-259
292-293
328-329
235-236
241-242
277-278
188-189
281-282
200-201
R,
0,66
0.68
0.83
0.78
0.73
0.82
0.79
0.71
0,66
Hr^sual
(%)
88
57
67
75
70
50
53
90
69

Phd
hdng
ngoai
(cm')
Vc.
3303
3277
3211
3411
3118
3510
3482
3273
3472
Vc01ac»on
1710
1710
1700
1721
1747
1726
1726
1722
1726
*: PhA
lil-NMK.
cS/7>//;:
2.4()(CI1,);
.>,7()
va 4.

U)
(CII.);
5.SO
(IIC);
i
1,10
(HO);
12,10 (HN): 6,20
-
7,70 (cac H nhiin
therm).
MS:
435
(M'')
23
IV.
I
HAU LUAN
KEI
QUA:
4.1.
Axetyl hod cdc phenol vd chuyen vi Fries cua chung:
•J*
Ddi
vdri
cac monophcnol day benzen va quinolm chiing
lAi
thuc hien phan
ling
axetyl

ho^
nhom hidroxi bing anhidrit axetic trong su co mat cua mgl ft axil axit pholphoric
l^m
xiic
uic. DA'i
vdi c«ic
phenol dihidric
(hidrotiuinon
\a
rcs(>:\inol)
hoac hidroxicumarin cluing
t6i thuc hien phan
ling
tuong
lu nhinig thuiifng
dung axit
sunluric
lam
xiic
tac.
(Zac
este
nh$n
dugc co nhiet dA nong chay phu hgp voi du kicn trong tai lieu tham
khao.
tren phd hong ngoai cua chiing deu khong con pic dac trung cho dao dAng hoa tri cua
nh6m OH phenol, trong khi do xua't hien pic dac trung cho dao dAng hoa tri
cOa
nhom
cacbonyl este

0
khoang 1650-
1720c/?/'.
•
Cac
ddn
xuat axetyl cua phenol dugc chiing
lAi
dua vao phan
ling
chuyen vj Fries
nhim
tao ra cac
chft't
d^u
ihuAc
loai 1-
axetyl
2-
hidroxiaron.
Phan ung dugc thuc hien
vdi
lugng
AICI3
khan lam
xiic
tac theo ti le mol vdi este 2: I hay 3: 1 tuy theo monoeste hay dieste
a
nhiet dA
160-

180"C
trong dung mAi nitrobenzen hoac khAng co dung mAi.
San
ph^
ciia phan
iimg chuyen
vi Fries deu
la chat rdn
va co
di^m
chay ro rang, cung
nhu c6 gia tri
R,
tren
s;1c
ki
ban mong khac vcri
csle
ban ddu. Tren pho hong ngoai ciia
chiing deu
xua't
hien tra lai pic dac trung cho dao dong hoa tri cua nhom hidroxi phenol
trong khoang 3200-
3400c7/7''
va pic dac lrung cho nhom CO axetyl, thudng vdi sd sdng
nho hon cua nhdm CO este. PhA cong hudng
tir
proton cua cac san pham
chuyin
vj Fries

deu xuat
ihen
cac
tin liicu
cua
uhdiu
ClirCO,
cua hidro trong nhdm OH va cac tut hieu
khac phu hgp vdi
cau
triic pham
tir (hinh
1). Pho khAi
lucmg
cua chiing deu cho pic ion
phan lir
phii
hgp vdi phan
lu
khA'i (hinh 2) va cho su phan manh
phii
hgp vdi ca'u tao phan
lir.
IIH^
du:
DAi
vdi sin phfim
chuytin
vj
h'ries

la
H-
axetyl-
7- hidroxicumarin cd su phan
manh nhu sau:
CM.
O^
"^Ctb
190
24