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Paper Report about tetrazole derivatives
exhibited antiinflammatory activity.
applied as plant growth regulators to increase tomato yields
and accelerate ripening.
identified as central nervous stimulants.
many reports have emphasized the biological and
pharmacological activities of tetrazoles.
Paper Report about tetrazole derivatives
★ Bond, A.; etc.; Eur. J. Pharmacol. 1999, 380, 91.
★ Nagamatsu, T.; etc.; Eur. J. Pharmacol. 1999, 374, 93.
★ O’Brien, P. M.; etc.; J. of Med. Chem. 1996, 39, 2354.
★ Harfenist, M.; etc.; J. of Med. Chem. 1996, 39, 1857.
★ O’ Brien, P. M.; etc.; Bioorg. & Med. Chem. Lett. 1995,
5, 295.
★ O’ Brien, P. M.; etc.; Bioorg. & Med. Chem. Lett.1995,
5, 289.
R
R
O Ph H
1) n- BuSnN3
C
p-dioxane, reflux
N
CN 2) HCl, Et O
2
H
O Ph H
C
N
H
N
(CH2)11CH3
N
N
N
R
R
O Ph H
C
N
N
H
O Ph H
C
N
H
N
N
N H
N
N
N
O’ Brien, P. M.; etc.; Bioorg. & Med. Chem. Lett. 1995, 5, 295.
O’ Brien, P. M.; etc.; Bioorg. & Med. Chem. Lett.1995, 5, 289.
Gyoung, Y. S.; etc.; Tetrahedron Lett. 2000, 41, 4193.
N
(CH2)11CH3
Syntheses of 5-(3-Arylsydnon-4-yl)tetrazole
Derivatives
OH
N3
Ar
N
N
Cl
OH
Ar
N
N
N
+
N
O
O
O
NaN3
MeOH/H2O
O
1
17
o
0 C
N
N
N
Ar
N
N
OH
N
O
O
18
1a, 17a : Ar = C6H5
1b, 17b : Ar = p-CH3C6H4
1c, 17c : Ar = p-CH3OC6H4
1d, 17d : Ar = p-CH3CH2OC6H4
疊氮型化合物之鏈-環(Ring-Chain)互變異構化
R
R'
R
N
N
+
R'
R'
R
N
N
N
+
N N
N
(B)
(A)
R
N
R'
N
+
N
N
(A')
N
N
N
N
(C)
直鏈結構的氧-取代基-3-芳香基雪梨酮-4-甲
利用Schotten-Baumann方法，在過量的三乙胺存在
下，3-芳香基雪梨酮-4(17)可與各種醯
氯化物(19a~19c)作用，但依舊生成直鏈結構的氧取代基-3-芳香基雪梨酮-4-
直鏈結構的氧-取代基-3-芳香基雪梨酮-4-甲
Ar
+
N
O
Ar
O
N OH
N
O
N3
N3
Et3N
R
Cl
19a : R = CH3
N
19a~19c
19b : R = C2H5
C
O
N
O
O
17a~17d
N
O
20aa~20dc
19c : R = C6H5
R
表3.氧-取代基-3-芳香基雪梨酮-4-甲醯疊氮
(20aa~20dc)之收率
起始物
醯氯化物
產物
收率* (%)
17a ( Ar = C6H5)
19a ( R = CH3)
20aa
45
17a ( Ar = C6H5)
19b ( R = C2H5)
20ab
51
17a ( Ar = C6H5)
19c ( R = C6H5)
20ac
87
17b ( Ar = p-CH3C6H4)
19c ( R = C6H5)
20bc
91
17c ( Ar = p-CH3OC6H4)
19c ( R = C6H5)
20cc
92
17d ( Ar = p-C2H5OC6H4)
19c ( R = C6H5)
20dc
89
*再結晶收率
3-芳香基雪梨酮-4-四唑雜環化合物的合成
N
N3
OH
Ar
N
N
N
Ar
O
O
Cl
R
O
O
N
O
19a~19d
17a~17d
O
21aa~21db
N
N
N
Ar
EtOH
0
50~60 C
N
N
OH
19a : R = CH3
19b : R = C2H5
N
O
O
18a~18d
O
N
N
+
N
N
R
表4. 雪梨酮四唑雜環衍生物(21aa~21db,18a~18d)
之收率
起始物
反應試劑
產物
收率*(%)
17a ( Ar = C6H5)
19 a ( R = CH3)
21aa
76
17b ( Ar = p-CH3C6H4)
19a ( R = CH3)
21ba
67
17c ( Ar = p-CH3OC6H4)
19a ( R = CH3)
21ca
55
17d ( Ar = p-C2H5OC6H4)
19a ( R = CH3)
21da
63
17a ( Ar = C6H5)
19b ( R = C2H5)
21ab
54
17b ( Ar = p-CH3C6H4)
19b ( R = C2H5)
21bb
50
17c ( Ar = p-CH3OC6H4)
19b ( R = C2H5)
21cb
61
17d ( Ar = p-C2H5OC6H4)
19b ( R = C2H5)
21db
65
21aa
EtOH
18a
89
21ba
EtOH
18b
85
21ca
EtOH
18c
80
21da
EtOH
18c
84
*再結晶收率
N
+N
-N
N3
Ar
N
O
OH
+
N
Cl
R
N
O
_ HCl
N
N
O
N
N
H
H
N
H
O
Ar
N
O
H
+
.. :
N
N
O
O
..
N
R
H
N N
N
N
N
Ar
O
N
N
O
O
N
N
R
R
O
O
+
O
O
N
O
O
N
O
O
N
O
Ar
N
N
_
O
+
N
Ar
O
N
R
O
O
N
N
N
N
H+
..
N
+
N
Ar
N
R
O
O
O
+N
+
O
Ar
R
HO
Ar
N
Ar
pyridine
N
EtOH , 0 C
N
O
O
1
H
Ph
N H
HN
O
Ar
O
Ar
N
_
N
PhNHNH2
O
O
H N
N
C
N
o
N
Cl
N
OH
Cl
N
PhNHNH2
N
PhNH2
N
N
O
O
O
H2N
N N
N
H H
N
O
H2N
N O
Ar
O
O
Ph
_
NHPh
Ar
HNO
N
N
N
O
9
O
..
H2N
Ar
C NNHPh
N
N
H
R CHO
O
O
7
+
R CH O H
Ph
N
N
NH CH R
Ar
C
N NHPh
_
N
N
O
+
H
C N
N
H
N
O
O
Ph
N
N
oxidation
Ar
Ar
C
C N
N
N
O
11
O
R
C
O
H
R