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 o u 6 c (;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 T 6 N G HOP, CAU TRUC VA HOAT TfNH
SINH HOC COA CAC HOP CHAT TlTONG TV FLA VON,
C6 CHtTA NHAN DI VONG"

M&s6

:

Chu i.hi«m d^ m:

QG.01-02
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

4

Ke't qua v6 mat khoa hoc

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 N O I 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
cac hgp cliiit tdng hop dugc

12

3.2

Tdng hgp cac este ciia phenol va thuc hien phan ung chuyen vi Fries
cua chiing

12

'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

.^.5

Hurtrng phap chung (dng hgp cac pira/olin thua nhan di vong:

flavon

19
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

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- 4inetylcumarin.
Ffinh 2: Phd khoi lugng cua san pham chuyen vj Fries 8- axetyl- 7- hidroxi- 4metylcumarin.
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-


A T 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 ClaisenSmith 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.
1.

Vdi ke'l qua do da cAng bd cdc cong trinh sau dav:
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
agienol \

w J^

tuai

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 ( h i e n , 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
derivatives and indole- 3- aldehydes \

coumarine

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 t h ^ 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

( IIUNIIlftMDft IAI

TUNHIEN. DHQC.HN
OHO MIEL T R J O N O

.'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
compounds

containing

heterocyclic

offlavone

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 ClaisenSchmidt 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. Punsaturated 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 'HNMR- 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
c h u ^ 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
COR

AK.h

COR
Co che'chung ciia phan ung dugc trinh bay Irong so dd sau:
'OAlt'h

» KC -c>

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 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-O
OH
O
^+'1^-'^
H"(HO")
M
I
- H7O
II
AAC-CH3 + R~CHO
5
U - A r - C - C H 2 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
10

iihi du lao ra 2,4-

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 C M — t \ . i i , i r

r,,HsNiiNn>M( n i . 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

CO( II

{Co\hCOhO/i'tM,0

Q

Oil

Tif o- axelylphenol va cdc csli

COCMj
Cf.tlsCfX'l
»>
-Pirklin
"

OH

M.O

o ( r)( f.Ms

I4|.

((KM

KOII
Pirtdin

\ /

Cf^lh

C M(( (K)ll
MjSO^

(r

OC(X ftlls

Cf,Us

Tit o- axelylphenol va andehit Ihom"'* "' ^

o
COCHj
+ CftHsCIIO
OM

KOII 60%
»C>llsOM

O^

M.

"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: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",, L50I51"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 170180"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
agienol

San pham chuydn vi

urc)

Hieu suat
(%)

oil
II^CO^ J^ ^((K II,

100-102

50

3442

1603

179-180

31

3366

1615

1^6- UJ

60

3200

1620

84-85

64

3200

1630

202- 203

74

3248

1640

Phd hong ngoai (cm ^)
'on

C I U H-Clh

Isoogienol

on
H3CO.

J \

/COCMj

( II CIKII

Resoxinol
COCH^

Resoxinol

CH.CO

110

/r ^\

OM

COill

Hidroquinon

13


162-163

111

73

methylcumarin

^o-^o
COC
7

8hidroxiquinolin

'82-83

.<^^^^^^

75

3370

1632

(
^H^^^^COCU,
OH

*:

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 (HC,); 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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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.

U'^)

xeton a , p-

Hi6u

Rf

Phd tGrngoa
KJnm)(}QE)

suat

khongno

Phd h(V)g ngoai (cm')

%N

(%)

Tinh

Tim

Vc^

vcoc

FEI

l£1

200-202

0.60

IX)

4.23

4.38

1632

1130; 1240

241(4.19); 257(4.10); -; 294(4,42)

Fs2

E2

198-200

0,35

85

4.06

4.34

1629

1245

243(4.45); 264(4.51); -; 301(4,54)

Fn

E3

224-226

0.54

80

3,44

3.72

1624

1174.1247

-; 255(4.71);-; 312(4.41)

F^

E4

194-196

0.55

60

3.33

3.57

1658

1175.1260

244(4.40);-;-; 298(4.43)

Fes

E5

73-75

0.36

48

-

-

1645

1043; 1265

-

F^

F6

189-191

0.54

40

-

1615

1037; 1267

-

1

'

, 1

Bdng ^>'; Cdc hap elicit tuang tu flavon

n

xclon

wrc)

R,

Hi6u
sunt

(%)

%N

di tit resoxinol

(FRJ.S vd Fpufi. 9)

Phd hong ngoai (cm')

Phd tiJr ngoai
X^(nm) (tge)

Tinh

Tim

v«i

^'c-fl

Vcor

Rl

193-194

1.54

64

5.05

5.25

3169

1637

1128:1214

210(3.71); 250(3.46); -; 407(3.60)

FR,

R2

203-204

0.70

75

4.81

4.78

3165

1633

1084; 1263

-; 256(3.90); 364(3.68)

FR,

R3

255-256

0.45

50

3.97

3.83

3137

1629

1085; 1244

204(3.94); 245(3.71); 266(3.59);

F„,

302(3.55)
FR,

R4

150-151

0.63

65

4.81

4.95

3245

1643

1170; 1257

FR,

R5

105-106

0.48

52

3.81

3.54

3136

1623

1084; 1243

l)1W

20!> ?0(J

O.Mi

wi

r»..u)

Ei.)2

-

m.\r

\\yf. VM

?2:'H3.75). 253(3.39). 412(3.58)

DR7

21S-216

0.73

78

5,93

6.12

-

1615

1161; 1243

210(3.83); 240(3,75); 263(3,56);

'Dttti

•"DRZ

2(Xi(3.64); -, 258(3,37); 362(3.62)

314(3.65)
'DWJ

|Fn«,

DR8

161-162

0,52

69

5.93

6,10

-

1693

1125; 1210

DR9

242-243

0.50

67

-

-

-

1628

1175; 1245

209(3,65); 245(3.31); 300(3,34)

bane W: Lac hap Chdt
TT

xeton

UfC)

178-179

65

0.52

(F^.^)
Phd tungoai

Phd h6ng ngoai (on')

Tfoh

Tim

Va.

5.05

5.21

3167

(%)

HI

di tit hidroquinon

X^(wn)(tgf:)

suai

F,„

tu flavon

%N

Hieu

R.

tuang

Vco

1644

Vcoc

222(4.38); 257(4;25); 287(4.18);

1132; 1217

412(4.41)

F„2

H2

19&-199

75

0.53

4.91

4.81

1634

3245

210(4.75); 2*^5(4.36); 266(4.15);

1162; 1218

303(4.28)

F.n

H3

230-231

0.56

71

3,97

3.75

3200

1618

1176; 1241

-

F,M

H4

152-153

0.61

64

4.81

4.88

3259

1635

1137; 1211

208(4.76); 259(4.54); 303(4.16);
364(4,12)

F,.s

H5

192-193

70

0.63

1642

3248

3.60

3.81

-

1135; 1216

Bdnn 11: Cdc hap chat luang tu flavon di tir hidroxiquinolin
TT

xeton

wrc)

%N

Hieu

R.

Ptid turngoai

Phd hdng ngoai (cm^)

su^

X^(nm)(l9E)

hnt)

Tim

V.i,

{%)

Fo,

Fo,
Fo,

(FQI,^)

Vux;

VMI

Ql

191-192

0,49

7a,

8.9

9.1

1634

1124;1242

3167

241(4.58); 256(4.48); 294(3.94)

Q2

180-181

0.43

80

8.6

8.2

1635

1160.124?

3266

241(4.46); 263(4.31); 300(4.45)

Q3

251 252

0.42

69

1621

1 U 5 . 1245

3128

-; 256(4.62); 312(4.35)

04

102-103

0.46

72

1661

1174;1244

-

242(4.48);-; 298(4,40)

/.o

7.2

6.9

7.1

Bdng 12: Cdc hap chdt titang tu flavon di tir axit dehidroaxetic (Ff),f^ ,.12)
TT.

1 Xeton

1 urc)

1 ^

%N

HI6u

nm

rmh

(%)

Pttd tiong rejoai (cm')

Phd I I ; ngoai
>_(«m)(tg,:)

Vco

Vcoc

*lH4t

DHAl

258-260

0,40

73

4.81

5.03

1695; 162a

1244

221(4.?^). 263(4.64); 284(3.76); 432(4,33)

^BHA2

DHA2

208-210

0.47

75

4 . M j 4.31

1695; 1528

1244

210(4.56); 244(4^:5); 302(4.21). 452{?,53)

^0HA3

DHA3

212-m

0,56

55

3.81

4.19

1716; 1647

1224

-; 239(4.33): 3 0 : (4.19); 446(4,40)

FoHA4

\)\\M

2/4-2/5

0.4/

4.59

4.32

1714.1041

1180

22/(<.12): 28'l{:i.r)9), ;-;i6(3.62); 431(4.46)

FBHAS

DHA5

207-209

0.54

92

3.67

4.01

1713; irvt?

1242

22/(4.27). 235(3.73): 32a(3.G9); 432(4.42)

FBHAS

DHA6

215-216

0.42

71

-

-

1722.1060

1263

2 0 9 : 2 4 1 ; - ; 383

1 ^BNA7

DHA7

247-248

0.5C

P^

1718. 1540

1249

209; 255; -; 381

'^OHAM

0HA8

259-260

0.57

C3

3.a3

3,97

1720:1660

1253

209;251;35G;;«'.9

FBHAS

DHA9

185-186

0,59

78

-

-

1685; 1666

1233

210; 23a. 317;-

'DHA1$

DHA10

173-174

0.44

69

1728; 1640

1245

201; 248;-; 393

1718; 1641

1252

201.225:308:364

1719-154((

1253

201; 2 3 1 ; - ; 356

83

-

'BHAIt

DHA11

119-120

0.35

GO

*BHAt2

DHA12

158-159

0.65

47

_

-

•

4.81 1 4.65

• 1 -

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.

Xeton

ticTC)

Phd hdng ngoai

%N

Ht^suat

R,

(%)

Tnh

Tim

Vc^cm')

Phd tur ngoai: A^(nrn) (Ige)

PE.

El

158-160

0.71

74

9.93

9,64

3358

225(4.45); 305(4.41); 341(4.55)

PD

E2

166-168

0.65

61

9.61

9,33

3378

224(4.19); 266(4.10); 300(4,07)

PE3

E3

138-140

0.83

55

8,42

8.25

3395

-; 254(4.36): 306(4.09)

Pw

E4

114-116

0,77

75

8.22

8.50

3296

-; 302(4.32); 341(4.52)

P..

E5

177-179

0.56

78

-

^

3385

205(4.17); 225(4.28); 250.280.
305(vai); 340(4.77)

PE«

E6

107-109

0,53

72

-

-

3285

202; 225(4,64); 235; 283;
305(vai); 340(394)

Ddng 14: Cdc pirazolin chda hgp phdn resoxinol (Pjf,,^ vd PoRf,.9)
TT.

xeton

W(°C)

Rf

Hi6usuat

%N

Phd hdng ngoai

Phd ttf ngoai:

(%)

TWi

Tim

V^Jon')

^™.('wn)Ogi:)

PRI

Rl

173-174

0,56

74

11.38

11.10

3432. 3381

220(3,85);-; 338(3.56)

P.«

R2

144-145

0.67

72

10.97

10.85

3118,3380

225(3,55); -; 344(3.67)

Pm

R3

237-238

0.74

51

9.44

9,30

3150.3138

-

Pw

R4

170-171

0.71

46

10.97

11,17

3311

-

PRS

R5

139-140

0.78

60

9,15

9.33

4448.3312

250(4.05);-; 340(4.21)

PD«

DR6

165-166

0.57

65

13.38

13.12

3400.3388

230(3.69); 291P.36); 337(3,52)

• t«7

DR7

199-200

0.62

73

12.80

12.50

3417. 3379

230(3,66); 266(3.24); 346(3.33)

Pt«l

DR8

277-278

0.66

40

-

-

3448

-

PDTS

DR9

171-172

0,75

'' 1

1^50

3448

223(3,48); 291(3,11); 365(3.15)

112,80

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
TT.

Xeton

wrc)

Phd hdng ngoai

%N

Hteusu^

R,

(%)

Tffih

Tim

Vc^cm')

(PEI.6)

Phd lu ngoai: Kmknm) (Ige)

PE.

El

158-160

0.71

74

9.93

9.64

3358

225(4,45); 305(4.41); 341(4.55)

PK

E2

166-168

0.65

61

9.61

9.33

3378

224(4.19); 266(4.10); 300(4,07)

PB

E3

138-140

0.83

55

8,42

8.25

3395

-; 254(4,36): 306(4.09)

PB4

E4

114-116

0.77

75

8,22

8,50

3296

-; 302(4.32); 341(4.52)

P.^

E5

177-179

0.56

78

-

3385

205(4,17); 225(4,28); 250.280,
305(vai); 340(4,77)

PE«

E6

107-109

0.53

72

-

3285

202; 225(4.64); 235; 283;

-

305(vai); 340(394)

Bdng 14: Cdc pirazolin chda hgp phdn resoxinol (Pf^,,^ vd
TT.

xelon

tncTC)

R,

%N

Hi6usuat

Phd hdng ngoai 1

PDR^-V)

Phd hjr ngoai:

(*)

Vnt\

Tim

V.„{rm')

A„Jnm)(Igc)

PR.

Rl

173-174

0.56

74

11.38

11.10

3432. 3381

220(3.85);-; 338(3.56)

P.U

R2

144-145

0.67

72

10.97

10.85

3418,3380

225(3.55); -; 344(3.67)

PR3

R3

237-238

0.74

51

9,44

9.30

3150,3138

-

PR*

R4

170-171

0.71

46

10.97

11.17

3311

-

P«.

R5

139-140

0.78

60

9.15

9.33

4448.3312

250(4.05);-: 340(4.21)

Ptw

DR6

165-166

0.57

65

13.38

13.12

3400.3388

230(3.69). 291P.36); 337P.52)

"vm

DR7

199-200

0.62

73

12.80

1Z50

3417. 3379

230(3.66); 266(3.24); 346(3.33)

PpB.

DR8

277-278

0.66

40

-

-

3448

-

1 Pora

[)R9

171-172

0,75

'' 1

12,80

12.50

3448

223(3.48); 291(3,11); 365(3.15)

2J


Bane 15: Cdc pirazolin

n.

xeton

UfC)

Rr

chiia
%N

HiOusuJt
(%)

hgp phdn

hidroquinon

(Pfn-s)

Phd hdng ngoai

Phd hJT ngoai:

linti

Inn

Vo„(an')

A,«("m)(k|c)

PH,

HI

154-155

0.61

66

11.38

11.50

3425. 3383

225(3.93): 310(3.85); 340(3.95)

P«

H2

162-163

0,66

47

10.97

11.20

3414.3372

227(3.48); 316(3.45); 344(3,55)

PH,

H3

140-141

0.46

42

9.44

9.29

3283

-

P«

H4

187-188

0,53

72

10.97

10,78

3314

222(3.90); 294(3.37); 368(3.40)

P«

H5

124-125

0.44

64

9.15

9.00

3288.3230

-

Bang 16: Cdc pirazolin chua hgp phdn axit dehidroaxetic (PouAi-n)
TT.

xeton

W^)

R,

%N

Hi&usuat

Phd hdng ngoai

Phd t u ngoai:

(cm')

^ ( n m ) (lgc)

(%)
Tinh

lim

Vc,,

Vcoc

PewM

DHAl

221-223

0,60

75

7,27

7.32

3400

1240

218(4.48); -; 283(4,20); 424(4.17)

PfHU

DHA2

205-207

0,70

96

7.01

6,70

3381

1244

225(4.41): -; 344(4,36); 434(2,45)

PoHU

0HA3

283-284

0,63

93

6,07

5,68

3450

1246

-: 295(4.17)-; 392(3,85)

' MM

DHA4

224-225

0.66

82

7,01

7.31

3450

1245

220(4.53); 285(4.13); -; 392(3,99)

DHA5

115-117

0.75

87

5.89

6.07

3420

1255

-; -; 287(4.02); 354(3,69)

Pavw

DHA6

80-81

0,69

91

-

-

3433

1253

-: 235: -; 394

Pom;

DHA7

127-128

0.47

87

-

-

3429

1241

202.234; 296; 359

PuM

DHA8

170-171

0.66

82

12,80

12.50

:M65

1265

203; -; 284; 383

POM

DHA9

65-66

0.38

86

-

-

3452

1257

203; -: 284; 381

DWMO

DHA10

ISO-181

0.40

89

-

-

3427

1213

207; -; 293. 308

PflHAn

DHA11

240-241

0,52

72

11,09

10.72

3450

1275

203; 252; -; -

Pn«B

0HA12

179-180

0.50

70

-

-

3348

1253

202; 248; -; 350

Pomu

DHA13

220-221

0.49

73

-

-

3443

1212

201; 251:-; 350

'

22

1


uuriK M. /_.
TT.

xeton

U^)

\.u%. yuu4,olin chita vdng quinolin
%N

Hieu suat

Rr

Phd hong ngoai

Pho tu ngoai

(cm')

X_(nm)(lgr)

(%)
rrtfi

Tim

(PQI^)

Va,

VNH

i:t.9

13,6

3422

3277

221(4.21) -; 340(4.32)

58

13.4

13.2

3416

3281

238(4.81): 303(3,92); 341(3,82)

0.76

64

11.7

11.4

3387

3057

236(4,43); 297(3.92); -

0.61

70

11.3

11.2

3450

-

-: -: 341(4.45)

Pu.

Ql

210-211

0,58

Paz

02

200-201

0.64

Po,

03

111-112

Po*

04

i7&-ieo

*

Bang 18: Cdc pirazolin chUa hgp phdn cumarin (Pci.9)

TT.

*:

xeton

U(^)

R,

Hr^sual

Phd hdng ngoai

(%)

(cm')
Vc.

Vc01ac»on

P*c.

01

258-259

0,66

88

3303

1710

Pc

C2

292-293

0.68

57

3277

1710

Pa

C3

328-329

0.83

67

3211

1700

PM

C4

235-236

0.78

75

3411

1721

P«

05

241-242

0.73

70

3118

1747

Pes

06

277-278

0.82

50

3510

1726

Pa

07

188-189

0.79

53

3482

1726

Pes

08

281-282

0.71

90

3273

1722

P«

09

200-201

0,66

69

3472

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 p h ^ 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