Nghiên cứu tổng hợp và chuyển hóa một số 4 acetylsydnone tetra o acetyl β d galactopyranosyl thiosemicarbazon thế

u tng ht s 4-
acetylsydnone tetra-O-acetyl--D-
galactopyranosyl thiosemicarbazon th


 H


i hc Khoa hc T 
Lu ThS.  ; : 60 44 27
ng dn: PGS.TS. Nguy
o v: 2012


Abstract. Tng hp cht 3-(R-  


 -(R-  -nitroso-N-(R-  ng.
Chuyp cht 4-acetyl-3-(R-n xut 4-bromacetyl-3-
(R-ng. Tng hp cht 2--(tetra-O-acetyl-
-D-galactopyranosyl-amino)]-5--arylsydnone)-6H-1,3,4-  u
c  h c  p cht 2--(tetra-O-acetyl--D-
galactopyranosylamino)]-5--arylsydnone)-6H-1,3,4-
sinh hc cng hc.

Keywords. ; Hp cht h; Hoc


Content
p cht u hoc bit
 c th-thiadiazin  ho

hc 


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p chng chim v  c h
 p nh kh  n
cng, c ch s n hoc dit tr c dnh.
 

-oxadiazoli-5-


                 



 





ng. 
thiadiazin     thiosemicarbazid 

thiadiazin, 
“         -acetylsydnone tetra-O-acetyl--D-
” 
 
N-phenyl sydnone




. 
 



-carbon(C
4

  

C
4
- 

~1730cm
1

O
N
N
O
Ph
O
N
N
O
Ph

O
N
N
O
Ph
O
N
N
O
Ph
1.52
1.37
1.64
1.64
1.41
1.64
-0.88
+0.19
+0.03
+0.03
-0.34
+0.73
-0.71
+0.24
+0.11
+0.21
-0.43
+0.57
-0.35
+0.08

+0.01
+0.35
-0.14
+0.3
2 3
4
5

Hình 1.1. Biểu diễn điện tích trong vòng sydnone.
-
3




3

4

4,
O
1,
O
6

5

 
3



5-Aryl-1,3,4-thiadiazin 
.
-thiadiazin  
 2-Morpholino-5-phenyl-
6H-1,3,4-thiadiazin 
-thiadiazin-diethyldipyrazolyl disulfide

    .        -
dimethylamino-5-phenyl-6H-1,3,4-thiadiazin-6-5500.08 


 N,N-dimethyl-5-phenyl-1,3,4-thiadiazol-2-amin
 
N
N
S
Ph
O
N
S
N
NMe
2
Ph
550 °C, 0.008 Torr
-CO
+ +
Me
2

N-CN
PhCN
9

1-(Benzensulfonyl)-3-phenylnaphtho[2,3-e]1,3,4-thiadiazin-5,10-diol (10)   
-(benzensulfonyl)-3-phenyl-1H-benzo[f]indazole-4,9-un

N
N
S
O
O
SO
2
Ph
Ph
O
O
N
N
SO
2
Ph
Ph
t°, toluen
-S
10
11

1,3,4-thiadiazin    (20)  

1
=H, MeEt, Ar, COOEt, Ac; R
2
=H, Alk,Ar;
R
3
=NHAlk, NHAr, NMe
2

(21) 
-thiadiazin

1,3,4-thiadiazin
     -thiadiazin        

N
N
S
R
1
R
2
R
3
N
H
N
R
1
R

2
R
3
H
+
-S
20
21

     - -3-methyl-2,3-dihydro-6H-1,3,4-thiadiazin(22)
(23)
     -phenyl-  -ethoxycarbonyl-6H-1,3,4-thiadiazin(20)
(R
2

H-1,3,4-thiadiazin
-40% 5-imino-1,2-


N
N
S
Ph
NR
Me N
N
Ph
NHR
Me
H

+
-S
22
23

N
N
S
Ph
NMe
Me
Me
N
N
Ph
NMe
Me
Me
H
+
-S
24
25


        -carboxy6-phenyl-2-phenylimino-
6H-1,3,4-thiadiazin(26) 
(27)     -diphenyl-2,7-diphenylimino-1H,6H-dipyrazolo[1,5--
d]pyrazin (28).
NH

N
H
S
HOOC
NPh
Ph
N
H
N
HOOC
NHPh
26
27
PPA
-S
N
N
N
H
N
H
O
O
Ph
PhN NPh
Ph
28

      -thiadiazin       -
         -thiadiazin   

          -imino-  -alkylimino-5-methyl-6H-1,3,4-
thiadiazin-amino- -[alkyl(aryl)amino]-4-methyl-2,3-
dihydro-1,3-thiazole (30).
NH
N
S
R
1
NH
2
+
R
2
H
29
N
S
R
1
NH
2
NH
2
+
R
2
30

5-Methyl-6H-1,3,4-thiadiazin(31) (R
1


  -nitrobenzaldehyd (R
2
=H, NO
2
 
acid, thu  -(benzylideN-  -[(4-nitrobenzylidene)hydrazino]thiazole
(32).
NH
N
S NH
2
+
R
1
H
CH
3
31
N
S
CH
3
NH
2
NH
R
1
N
CH

C
6
H
4
-4-R
2
32

2-Amino- -alkylamino-5-phenyl-6H-1,3,4-thiadiazin(33) 
   -alkylimino-3-methyl-4-phenyl-2,3-dihydro-6H-1,3,4-thiadiazin(34) 
 --2-imino-5-methyl-2,3-dihydro-6H-1,3,4-thiadiazin    -amino-5-
methyl-6H-1,3,4-thiadiazin 

N
N
S NHR
2
R
1
Ph
33
N
N
S
Ph
CH
3
NR
2
R

1
34
Mel, Me
2
CO
t°, 10h

2-Dialkylamino-5-aryl-6H-1,3,4-thiadiazin
1,3,4-thiadiazin        -dialkylamino-6H-1,3,4-
thiadiazin            dimethyl sulfoxide
-pyrrolidino- -cyclohexylamino-5-phenyl-6H-1,3,4-thiadiazin
-dialkylamino-
5-phenyl-6H-1,3,4-thiadiazin
N
N
S
Ph
R
1
N
N
+
S
Ph
R
1
R
2
35
X

-
Me
2
CO
MeSO
3
F or
EtOBF
4
t°, 0.5-6h

6H-1,3,4-thiadiazin-2(3H)-   
2
   -thiadiazoles (36).

+
N- 

2
.

NH
N
S
R
2
O
R
1
N

N
S
R
2
R
1
36
ButOCl,DMF, 0 °C
-CO
2

 6H-1,3,4-thiadiazin-2-amin (37) -halogen keton cho 2H-
imidazo[2,1-b]6H-1,3,4-thiadiazin(38) (R
1
=Ar; R
2
=H).
N
N
S
Ph
NH
2
+
R
2
Br
O
R
1

-HBr, -H
2
O
N
N
S
N
Ph
R
2
R
1
37
38


N
N
H
S CH
3
Ph
CH
3
MeCOOC
N
S
HOOC
Ph

NH
NHAc
N
S
MeCOOC
Ph
NH
NH
2
N
S
MeCOOC
Ph
NH
N
CH
3
CH
3
N
N
S
MeOOC
Ph
NH
2
HCl
Me
2
CO

CF
3
CO
2
H
55
-
60 °C
60
61


- 
 



   phn ng v  n xut ca acid thiocarbamic cho
ng.




4


- 




 

2


2
, phm 1956[21]. 
-mercapto-1,3,4-thiadiazol. Ph
sau:



 DMF, d




  

 
               


              

       

 




  
-

1

Năng lượng photon vi sóng
trong vùng tần số này (0,0016 eV), quá yếu để phá vỡ liên kết hoá học và cũng thấp hơn năng
lượng của chuyển động Brownn
 hiệu ứng nhiệt của các vật liệu
nhờ hiệu ứng nhiệt điện môi vi sóng
 
 sự làm phân cực và sự truyền ion.


4-BROMOACETYL-3-(R-PHENYL)SYDNONE
-bromoacetyl-3-(R-phenyl)sydnone em 
-acetyl-3-(R-phenyl)
acetyl
-  N-(R-
oacetat.
- N-(R-
 N-nitroso-N-(R-phenyl)glycine.
- -(R-N-nitroso-N-(R-phenyl)glycine

-   -(R-phenyl)sydnone   

2
O
5


  -        -acetyl-3-(R-phenyl)sydnone  
percloric HClO
4
510C.
- bromo

N-(R-phenyl)glycine
N-(R-phenyl)glycine em N-
 
Phương pháp 1:N-(R-phenyl)



 N-(R-phenyl)glycine
 
 N-(R-phenyl)glycine.
Phương pháp 2;





Phương pháp 3:            


N-(R-phenyl)glycine
N-nitroso-N-(R-phenyl)glycine
N-nitroso-N-(R-phenyl)glycine
N-(R-phenyl)glycine 

th-
2-N-(R-phenyl)glycine 
 
 



-(R-phenyl)sydnone
    
  N-nitroso-N-(R-phenyl)  
anhyd




 
  3-(R-phenyl)sydnone.

 


  

-acetyl-3-(R-phenyl)sydnone.
-acetyl-3-(R-phenyl)sydnone 
     “phương pháp nóng”
“phương pháp lạnh”
Phương pháp nóng         
2
O

5
   

 acetic 


m 96
0

Phương pháp lạnh
10
4

 
15
30-

em 

   
2
O
5

c 


dunn-hexan : ethy
-bromoacetyl-3-(R-phenyl)sydnone
           bromo   


 20 . 



 =


2






 10 
 15-20 . 
2
, 























 



, 


. 



  




2







 , cho 
 , 







 , 






.
      --(tetra-O-ACETYL--D-
GLACTOPYRANOSYLAMINO)-5--ARYLSYDNONE)-6H-1,3,4-THIADIAZIN
 

 


 
-79




 
o

 
n-hexan 
        2-3     
 


.4.

Bảng kết quả tổng hợp và dữ kiện vật lý của 2-(2’,3’,4’,6’-(tetra-O-acetyl-β-D-
galactopyranosylamino)-5-(3”-arylsydnone)-6H-1,3,4-thiadiazin
N
R
Màu sắc
Hiệu suất(%)
Đ
nc
(°C)
7a
H

75
107,2-108,1
7b
4-Me


80
123,7-124,5
7c
2-Me

78
158,2-158,9
7d
4-MeO

72
124,4-124,6
7e
4-Cl

75
161,3-161,8
7f
4-Br

76
130,9-131,3

V    P CHT --(TETRA-O-ACETYL--D-
GALACTOPYRANOSYLAMINO)-5--ARYLSYDNONE)-6H-1,3,4-THIADIAZIN
- Phổ hồng ngoại.

Phổ hồng ngoại của 2-(2
’

,3
’
,4
’
,6
’
-tetra-O-acetyl-β-D-galactopyranosylamino)-5-[3
’’
-(4-
bromophenyl)sydnone]-6H-1,3,4-thiadiazin.

Bảng băng sóng hấp phụ phổ IR của các hợp chất2-(2
’
,3
’
,4
’
,6
’
-tetra-O-acetyl-β-
D-galactopyranosylamino)-5-(3
’’
-arylsydnone)-6H-1,3,4-thiadiazin
N
0

R

NH


C=O (ester)

C
-O-
C (ester)

C=C

C=N
7a
H
3321
1748
1222, 1058
1505, 1520
1600
7b
4

-Me
3328
1746
1228, 1053
1512, 1470
1630
7c
2

-Me
3376

1747
1227, 1056
1573, 1498
1600
7d
-MeO
3324
1744
1223, 1059
1515, 1490
1605
7e
4

-Cl
3479
1746
1231, 1056
1577, 1500
1600
7f
4

-Br
3376
1745
1229, 1060
1571, 1500
1600
- Phổ

1
H NMR và
13
C NMR
2-(2

,3

,4

,6

-tetra-O-acetyl--D-galactopyranosylamino)-
5-(3

-arylsydnone)-6H-1,3,4-thiadiazin 
1
H NMR 
13
C NMR

1

 -            
5,27-3,95 ppm. -
-thiadiazin -

 
13
C NMR,            

135,5--4 -5 
104,7-104,3. 
-61,6ppm. Ba carbon C-5, C---thiadiazin 
   -     
3
    
(CH
3
CO) n--

- Phổ 2D-NMR: COSY, HMBC, HSQC
-NMR: 1,3,4-thiadiazin
7f
1
H NMR 
13
C NMR 
   2-(2

,3

,4

,6

-tetra-O-acetyl--D-galactopyranosylamino)-5-(3

-arylsydnone)-
6H-1,3,4-thiadiazin7a-f.


 
1
H-
1
      
i

1
H-
1

1
H-
1
H COSY ( 3.11
7f 
H-1

(5,27--2

-3

--5

-6

a, H-
6

b(4,02-3,95).

H--6b (3,60)
 
-2(=168.9 ppm)
-6a (=3.72 ppm) -6b ((=3.60 ppm)
  -        -6a (=3.72 ppm)  -6b ((=3.60
ppm), 





 ppm) 





-3-5 ppm).

1
H-
13
C -5

-
roton H- (=4,02- H-=5,24 
1
H-
13
C  


1

13
C 
 .

-6=20,5 ppm,
 H-6a (3,72 ppm), H-
 (=127,6 - (=7,16 ppm);








 3 ppm) 



  , H-
(7,64 
1
H-
13
C 10 
 3.12.
- Phổ khối lượng (MS)


+



V th hom: nh hoc cthiadiazin
b nghi c ch
ti thing 96 mit th nghim bao g
chng: Vi khun gram (-):Vi khun gram (+):Nm si; Nm men
Kt qu c ch ra  bng sau:

Bảng 3.5.1. Kết quả thử hoạt tính kháng khuẩn và kháng nấm của thiadiazin
Kí
hiệu
mẫu
Nhóm thế R
Nồng độ ức chế tối thiểu MIC, µg/ml
Vi khuẩn
gram(-)
Vi khuẩn
gram(+)
Nấm mốc
Nấm men
E. coli
P. aer
B. sub
S. aur
A.nig
F.oxy
S.cer

C.alb
1
2
3
4
5
6
7
8
9
10
7a
H
-
-
100
-
-
-
-
-
7b
4- Me
100
-
100
-
100
-
-

25
7c
2-Me
-
-
-
100
100
-
-
-
7d
4-OMe
-
-
100
-
-
-
-
-
7e
4-Cl
100
-
100
-
-
-
-

-
7f
4-Br
100
-
100
-
100
-
-
100
Nh- Mu 7b 7f biu hin ho
- 7c 7e 
- 7d 7a 
y trong luc sau:
1. - 
- 







N-(R-phenyl)glycine.
- 








N-nitroso-N-(R-phenyl)glycine
- -arylsydnone.
  -           -acetyl-3-

2
O
5

-bromoacetyl-3-

2 --(tetra-O-acetyl--D-galactopyranosyl amino)-5-
-arylsydnone)-6H-1,3,4-    -(tetra-O-acetyl--D-
-bromoacetyl-3-

3. 
1
H NMR,
13
CNMR,

4.          
Gram-(-) Escherichia coli Pseudomolas aeruginosa   -(+) Bacillus
subtillisStaphylococcus aureusAspergillus niger Fusarium oxysporum
men Candida albicansSaccharomyces cerisiae
t 7b 7f 


References
Tài liệu tiếng Việt:
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Tài liệu tiếng Anh:
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Abid and Amir Azam, Assony S. J     
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sydnone
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O



synthesis of 2-amino-1,3,4-J . Org. Chem, 71(25), pp. 9548-9551.
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        Revue
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