Another way to the synthesis of 1,2,3-triazoles

Article abstract of DOI:10.1002/jhet.1095

The reactions of α-bromoacetophenones with methylhydrazine in refluxing acetic acid generated 2-methyl-4-aryl-2H-[1,2,3]triazoles in good yields. The method was developed by the reactions of α-bromoacetophenones with phenylhydrazines in the presence of cu

Full text of DOI:10.1002/jhet.1095

Month 2013
Another Way to the Synthesis of 1,2,3‐Triazoles
a
b
*
Beihua Xu and Yongzhou Hu
aZhejiang Pharmaceutical College, Ningbo 315100, People’s Republic of China
bZhejiang University, Department of Medicinal Chemistry, School of Pharmacy, Hangzhou 310006,
People’s Republic of China
*
E-mail: xubh@mail.zjpc.net.cn
Received April 15, 2011
DOI 10.1002/jhet.1095
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
The reactions of α‐bromoacetophenones with methylhydrazine in refluxing acetic acid generated 2‐methyl‐4‐
aryl‐2H‐[1,2,3]triazoles in good yields. The method was developed by the reactions of α‐bromoacetophenones
with phenylhydrazines in the presence of cupric ion, leading to 2,4‐diary‐2H‐[1,2,3]triazoles. The structures
were established on the basis of corresponding IR, 1H NMR, and elemental analysis data.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
order to investigate this reaction, a series of substituted
α‐bromoacetophenones were applied in the same reaction
condition, and the corresponding 2‐methyl‐4‐aryl‐2H‐
[1,2,3]triazoles (4‐10) (Table 1) were obtained in moderate
to high yields (Scheme 1).
The possible mechanism is proposed here (Scheme 2).
In this scheme, C1 and C2 of α‐bromoacetophenone(2)
underwent nucleophilic attack of methylhydrazine, respec-
tively, which afforded intermediate (a). The loss of an amino
moiety from intermediate (b) gave rise to intermediate (c).
Then, C2 of (c) underwent nucleophilic attack of another
methylhydrazine, with the result of methylimino group being
replaced by methyl hydrazono group. Further loss of a
proton from intermediate (d) led to the intermediate (e).
In the end, through the loss of methylamine under thermal
condition, compound 3 was obtained.
1,2,3‐Triazoles have a broad range of biological activity, and
there are numerous examples in the literature including
antibacterial activity [1, 2], antiviral activity [3], anti‐convulsant
[4], selective β3‐adrenergic receptor agonism [5], and so on. A
few methods for the preparation of 1,2,3‐triazole derivatives
have been developed. Among them, 1,3‐dipolar cycloaddition
between an azide and an alkyne is the classical and extensively
used method [6–8], leading to the 1H‐[1,2,3]triazole
derivatives. Other methods, such as the reaction of
nitriles with CH2N2 [9] and the intramolecular condensation
of bisarylhydrazones [10–12], have not been developed further.
The strict reaction conditions or monotonous products may be
responsible for their unpopularity today. Herein we report a
one‐pot synthesis of 2,4‐disubstituted‐2H‐[1,2,3]triazoles via
the coupling of α‐bromoacetophenones with hydrazines.
To extend the utility of this method, phenylhydrazine
was employed as the starting material to react with α‐
bromoacetophenone in refluxing acetic acid. The reaction
appeared to be limited. Little triazole, but bisphenylhydrazone
(12), was obtained in low yield. To obtain the desired
product, an addition of catalyzer was necessary. Some
catalysts were tried, and cupric ion was found to be
more efficient to promote the cyclization than the
others. Therefore, 2,4‐diaryl‐2H‐[1,2,3]triazoles (13‐30)
(Table 2) were prepared by cupric ion mediated
RESULTS AND DISCUSSION
We studied the reaction of N‐phenacylisoquinolinium
bromide (1) with methylhydrazine in refluxing acetic acid.
Unexpectedly 2‐methyl‐4‐phenyl‐2H‐[1,2,3]triazole (3) was
obtained. Then α‐bromoacetophenone (2), a more simple
material than the quaternary salt (1), was employed to react
with methylhydrazine, yielding the same product (3). In
© 2013 HeteroCorporation

B. Xu and Y. Hu
Vol 000
Table 1
Analytical and spectroscopic data for compounds 3-10.
Calculated (found) (%)
No
R
H
Yield %
60
m.p./_C
56
IR(KBr)/m (cm_1)
3035,1476, 1457,
1H NMR: (deuteriochloroform): d
C
H
N
3
7.81(s,1H), 7.78–7.76(m,2H),
7.45–7.41(m,2H), 7.36–7.32(m,1H),
4.23(s,3H)
7.79(s,1H), 7.70(dd,2H, J = 2.0,6.7 Hz),
7.39(dd,2H, J = 2.0, 6.7 Hz), 4.23(s,3H) (55.69) (4.01) (21.45)
7.80(s,1H), 7.65-7.63(m,2H),
7.57-7.54(m,2H), 4.23(s,3H)
7.77(s,1H), 7.65(d, 2H, J = 8.1 Hz),
7.23(t, 2H, J = 8.0 Hz),
67.91
5.70
26.40
1385, 764, 691
1471,1377, 829
(68.12) (5.65) (26.60)
55.83 4.16 21.70
4
5
6
4-Cl
4-Br
47
41
56
96–98
120–122
64–66
1473, 1379, 832
45.40
(45.16) (3.43) (17.46)
69.34 6.40 24.26
(69.01) (6.17) (24.04)
3.39
17.65
4-CH3
3035,1485,1385,821
4.21 (s,3H), 2.37 (s,3H)
7
4-CH3O
73
104–106
1613,1578,1483,
1383, 837
7.74(s,1H), 7.71-7.68(m,2H),
63.48
5.86
22.21
6.97-6.94(m,2H), 4.21(s,3H), 3.84(s,3H) (63.34) (5.99) (21.98)
8
9
4-OH
81
58
126–128 3195,1617,1591,1492,
7.75(s,1H), 7.65-7.62(m,2H), 6.91-6.87
(m, 2H), 4.22(s,3H)
61.70
(61.52) (5.23) (23.85)
60.27 5.94 19.18
(60.02) (5.98) (19.05)
5.18
23.99
1452, 843
3,4-(MeO)2
94–96
1607,1590,1500,1380,
862, 841
7.76(s,1H),7.34(d,1H, J = 1.8 Hz),
7.31-7.27(m,1H), 6.92(d,1H, J ¼ 8.3 Hz),
4.23(s,3H), 3.97(s,3H), 3.92(s,3H)
7.95(s,1H), 7.86(d, 1H, J ¼ 8.5 Hz),
6.59-6.54(m,2H), 4.21(s,3H),
3.90(s,3H), 3.84 (s,3H)
10
2,4-(MeO)2
58
80
1615,1581,1384, 834
60.27
5.94
19.18
(60.12) (5.85) (19.07)
cyclization of phenylhydrazines and α‐bromoacetophenones
(Scheme 3).
Scheme 1. The synthesis of 2-methyl-4-aryl-2H-[1,2,3]triazoles (3-10).
A possible mechanism for the reaction of α‐
bromoacetophenone with phenylhydrazine was offered
here (Scheme 4). After α‐bromoacetophenone underwent a
similar process to Scheme 2, bisphenylhydrazone (12) was
obtained. However, (12) was not active enough to undergo
intramolecular cyclization as the radical intermediate (d). It
is assumed that the bulk, electron‐attracting phenyl ring
rendered its neighboring nitrogen harder to attack imino‐
nitrogen of phenylhydrazono residue on C1. Therefore,
Scheme 2. The possible mechanism for the synthesis of 2-methyl-4-phenyl-2H-[1,2,3]triazole (3).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Another Way to the Synthesis of 1,2,3‐Triazoles
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Xu and Y. Hu
Vol 000
Scheme 3. The synthesis of 2,4-diaryl-2H-[1,2,3]triazole derivatives (13-30).
Scheme 4. The possible mechanism for the synthesis of 2,4-diphenyl-2H-[1,2,3]triazole (13).
was added slowly to the solution of α‐bromoacetophenone
(1.2 g, 6 mmol) in acetic acid (2 mL).The mixture was
heated to reflux over an oil bath for about 3 hours. After
being cooled to room temperature, the reaction mixture was
neutralized with 20% NaOH solution and then extracted
twice with chloroform. The combined organic extracts were
washed with water and dried over anhydrous Na2SO4. The
solution was concentrated under reduced pressure, and the
residue was purified by column chromatography on silica
gel using ethyl acetate: petroleum ether (1:15) as eluant
to afford 2‐methyl‐4‐phenyl‐2H‐[1,2,3]triazole (3) (60%
yield) as white solid. mp 56°C (Lit. [9] 58°C); IR(KBr)/ν
the oxidation agent was needed to promote this cycli-
zation. The mechanism proposed here was quite similar
to the report by K.S. Balachandran [11]. It was said
that the oxidation agent abstracts a proton from
bisphenylhydrazone (12), giving rise to a radical interme-
diate (f). Further loss of a proton leads to the bis‐azoolefin
(g). And it is proved that bis‐azoolefin can exist in the
mesoionic form, which can be converted to 1,2,3‐triazole,
through the loss of phenylnitrene, both under thermal and
photochemical conditions. In the absence of any catalysts,
the intermediate (12) was the main product of the reac-
tion of α‐bromoacetophenone(2) with phenylhydrazine
(11) in the acetic acid, which appeared as a kind of
bright yellow solid. mp: 148°C (Lit. [12] 148°C), m/z 314
(calculated m/z 314).
(cm−1
)
3035, 1476, 1457, 1385, 764, 691; 1H NMR:
7.81(s, 1H), 7.78–7.76(m, 2H),
(deuteriochloroform):
δ
7.45–7.41(m, 2H), 7.36–7.32 (m, 1H), 4.23 (s, 3H); Anal.
Calcd. for C9H9N3: C, 67.92; H, 5.66; N, 26.42. Found: C,
68.12; H, 5.65; N, 26.60.
4‐(4‐Chloro‐phenyl)‐2‐methyl‐2H‐[1,2,3]triazole (4). Yield
1
(%) 47; m.p. 96–98°C; IR/ν (cm−1) 1471, 1377, 829; H NMR:
EXPERIMENTAL
δ 7.79 (s, 1H), 7.70 (dd, 2H, J = 2.0, 6.7 Hz), 7.39 (dd, 2H, J = 2.0,
6.7 Hz), 4.23 (s, 3H); Anal. Calcd. for C9H8N3Cl: C, 55.83;
H, 4.14; N, 21.71. Found: C, 55.69; H, 4.01; N, 21.45.
General procedure for the reaction of α‐bromoacetophenones
with methylhydrazine, yielding 2‐methyl‐4‐aryl‐2H‐
[1,2,3]triazoles(3‐10). Methylhydrazine (1.7 mL,30 mmol)
4‐(4‐Bromo‐phenyl)‐2‐methyl‐2H‐[1,2,3]triazole (5). Yield
(%) 41; m.p. 120–122°C; IR/ν (cm−1) 1473, 1379, 832; 1H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Another Way to the Synthesis of 1,2,3‐Triazoles
1
NMR: δ 7.80 (s, 1H), 7.65–7.63 (m, 2H), 7.57–7.54 (m, 2H), 4.23
(s, 3H); Anal. Calcd. for C9H8N3Br: C, 45.40; H, 3.36; N, 17.65.
Found: C, 45.16; H, 3.43; N, 17.46.
764, 692; H NMR: δ 8.12 (d, 2H, J = 8.4 Hz), 7.98 (s, 1H),
7.51–7.45 (m, 3H), 7.41 (d, 1H, J = 8.4 Hz), 7.35–7.31 (m, 1H),
6.94 (d, 1H, J = 8.4 Hz), 3.98 (s, 3H), 3.92 (s, 3H); Anal.
Calcd. for C16H15N3O2: C, 68.33; H, 5.34; N, 14.95. Found:
C, 68.49; H, 5.07; N, 14.82.
2‐Methyl‐4‐p‐tolyl‐2H‐[1,2,3]triazole (6). Yield (%) 56; m.p.
1
64–66°C; IR/ν (cm−1)3035, 1485, 1385, 821; H NMR: δ 7.77
(s, 1H), 7.65 (d, 2H, J = 8.1 Hz), 7.23 (t, 2H, J = 8.0 Hz), 4.21
(s, 3H), 2.37 (s, 3H); Anal. Calcd. for C10H11N3: C, 69.36; H,
6.36; N, 24.28. Found: C, 69.01; H, 6.17; N, 24.04.
4‐(4‐Methoxy‐phenyl)‐2‐methyl‐2H‐[1,2,3]triazole (7).
Yield (%) 73; m.p. 104–106°C; IR/ν (cm−1)1613, 1578,
1483, 1383, 837; 1H NMR: δ 7.74 (s, 1H), 7.71–7.68
(m, 2H), 6.97–6.94 (m, 2H), 4.21 (s, 3H), 3.84 (s, 3H);
Anal. Calcd. for C10H11N3O: C, 63.49; H, 5.82; N, 22.22.
Found: C, 63.34; H, 5.99; N, 21.98.
4‐(2‐Methyl‐2H‐[1,2,3]triazol‐4‐yl)‐phenol (8). Yield (%)
81; m.p. 126–128°C; IR/ν (cm−1); 3195, 1617, 1591, 1492,
843; 1H NMR: δ 7.75 (s, 1H), 7.65–7.62 (m, 2H), 6.91–6.87
(m, 2H), 4.22 (s, 3H); m/z: 175(M)+; Anal. Calcd. for
C9H9N3O: C,61.71; H, 5.14; N, 24.00. Found: C, 61.52;
H, 5.23; N, 23.85.
4‐(2,4‐Dimethoxy‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole
(16). Yield (%) 46; m.p. 75–76°C; IR/ν (cm−1)1613, 1594,
1483, 1461, 758, 701; 1H NMR: δ 8.23 (s, 1H), 8.15 (dd,
2H, J = 1.0, 8.6 Hz), 8.08 (d, 1H, J = 8.4 Hz), 7.52–7.49
(m, 2H), 7.37–7.33 (m, 1H), 6.65 (dd, 1H, J = 2.4, 8.4 Hz),
6.59 (d, 1H, J = 2.8 Hz), 3.97 (s, 3H), 3.89 (s, 3H); Anal.
Calcd. for C16H15N3O2: C, 68.33; H, 5.34; N, 14.95.
Found: C, 68.28; H, 5.16; N, 15.08.
2‐Phenyl‐4‐p‐tolyl‐2H‐[1,2,3]triazole (17). Yield (%) 51; m.p.
64–66°C; IR/ν (cm−1) 1596, 1496, 1460, 821, 753, 703; 1H
NMR: δ 8.14–8.12 (m, 2H), 8.02 (s, 1H), 7.79 (d, 2H, J = 8.1
Hz), 7.51–7.47 (m, 2H), 7.36–7.34 (m, 1H), 7.28–7.25 (m, 2H),
2.40(s, 3H); Anal. Calcd. for C15H13N3: C, 76.60; H, 5.53; N,
17.87. Found: C, 76.44; H, 5.42; N, 17.72.
4‐(4‐Chloro‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (18).
Yield (%) 48; m.p. 98–100°C; IR/ν (cm−1)1597, 1499, 1460,
4‐(3,4‐Dimethoxy‐phenyl)‐2‐methyl‐2H‐[1,2,3]triazole (9).
Yield (%) 58; m.p. 94–96°C; IR/ν (cm−1) 1607, 1590, 1500,
1
827, 753, 687; H NMR: δ 8.14–8.11 (m, 2H), 8.03 (s, 1H),
1
1380, 862, 841; H NMR: δ 7.76 (s, 1H), 7.34 (d, 1H, J = 1.8
7.83 (dd, 2H, J = 2.0, 6.7 Hz), 7.50 (t, 2H, J = 7.9 Hz), 7.44
(dd, 2H, J = 2.0, 6.7 Hz), 7.38–7.36 (m, 1H); Anal. Calcd.
for C14H10N3Cl: C, 65.77; H, 3.91; N, 16.44. Found: C,
65.85; H, 3.73; N, 16.25.
Hz), 7.31–7.27 (m, 1H), 6.92 (d, 1H, J = 8.3 Hz), 4.23 (s, 3H),
3.97 (s, 3H), 3.92 (s, 3H); Anal. Calcd. for C11H13N3O2: C,
60.27; H, 5.94; N, 19.18. Found: C, 60.02; H, 5.98; N, 19.05.
4‐(2,4‐Dimethoxy‐phenyl)‐2‐methyl‐2H‐[1,2,3]triazole (10).
Yield (%) 58; m.p. 80°C; IR/ν (cm−1) 1615, 1581, 1384, 834;
1H NMR: δ 7.95 (s, 1H), 7.86 (d, 1H, J = 8.5 Hz), 6.59–6.54
(m, 2H), 4.21 (s, 3H), 3.90 (s, 3H), 3.84 (s, 3H); Anal. Calcd.
for C11H13N3O2: C, 60.27; H, 5.94; N, 19.18. Found: C,
60.12; H, 5.85; N, 19.07.
4‐(3,4‐Dichloro‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (19).
Yield (%) 39; m.p. 108–110°C; IR/ν (cm−1)1595, 1496, 1454,
1
762, 697; H NMR: δ 8.10 (d, 2H, J = 8.4 Hz), 8.00 (d, 2H, J
= 11.6 Hz), 7.69 (dd, 1H, J = 2.2, 8.2 Hz), 7.52–7.48 (m, 3H),
7.36 (t, 1H, J = 7.2 Hz); Anal. Calcd. for C14H9N3Cl2: C,
57.95; H, 3.10; N, 14.49. Found: C, 57.83; H, 3.02; N, 14.38.
4‐(2,4‐Difluoro‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (20).
Yield (%) 59; m.p. 82–84°C; IR/ν (cm−1)1597, 1500, 1459,
General procedure for the reaction of α‐bromoacetophenones
with phenylhydrazines, yielding 2,4‐diaryl‐2H‐[1,2,3]triazoles
(13‐30). Cupric chloride (0.2 g 1.5 mmol) was added to
the mixture solution of α‐bromoacetophenone (0.30 g 1.5
mmol) and phenylhydrazine (0.71 mL 6 mmol) in acetic
acid (4 mL). The above mixture was heated to reflux over
an oil bath for about 2 hours. After being cooled to room
temperature, the reaction mixture was filtered by cotton,
washed with dichloride methane until only the insoluble
solid was left. The filtered solution was neutralized by 20%
NaOH solution, then extracted, washed with NaCl saturated
water, and dried over anhydrous Na2SO4. The solution was
concentrated and the residue was purified by column
chromatography on silica gel using ethyl acetate: petroleum
ether = 1:30 as eluant, affording 2,4‐diphenyl‐2H‐[1,2,3]
triazole (13) (50 % yield) as light yellow solid. m.p. 36°C
(Lit. [12] 40°C); IR/ν (cm−1) 3035, 1598, 1497, 1457, 757,
693; 1H NMR: δ 8.14 (d, 2H, J = 8.2 Hz), 8.05 (s, 1H),
7.90 (dd, 2H, J = 1.0, 8.2 Hz), 7.52–7.45 (m, 4H), 7.41–7.34
(m, 2H); Anal. Calcd. for C14H11N3: C,76.02; H, 4.98; N,
19.00. Found: C, 75.88; H, 4.90; N, 19.14.
1
749, 702; H NMR: δ 8.17–8.13 (m, 4H), 7.53 (t, 2H, J = 7.6
Hz), 7.39 (t, 1H, J = 7.2 Hz), 7.08–6.95 (m, 2H); Anal. Calcd.
for C14H9N3F2: C, 65.37; H, 3.50; N, 16.34. Found: C, 65.19;
H, 3.62; N, 16.49.
4‐(4‐Bromo‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (21).
Yield (%) 52; m.p. 100–102°C; IR/ν (cm−1) 1599, 1500,
1461, 825, 751, 687; 1H NMR: δ 8.13 (d, 2H, J = 7.7 Hz),
8.04 (s, 1H), 7.78 (d, 2H, J = 8.4 Hz), 7.60 (d, 2H, J = 8.4
Hz), 7.51 (t, 2H, J = 8.0 Hz), 7.37(t, 1H, J = 7.4 Hz); Anal.
Calcd. for C14H10N3Br: C, 56.02; H, 3.33; N, 14.00. Found:
C, 55.86; H, 3.25; N, 14.11.
4‐Phenyl‐2‐o‐tolyl‐2H‐[1,2,3]triazole (22). Yield (%) 28;
m.p. 73–74°C; IR/ν (cm−1) 2965, 1611, 1514, 1455, 764,
693; 1H NMR: δ 8.08–8.04 (m, 3H), 7.92–7.90 (m, 2H),
7.51–7.47 (m, 2H), 7.42–7.38 (m, 1H), 7.04–7.01 (m, 2H),
3.89 (s, 3H); Anal. Calcd. for C15H13N3: C, 76.60; H,5.53;
N,17.87. Found: C, 76.74; H, 5.50; N, 17.74.
4‐(4‐Methoxy‐phenyl)‐2‐o‐tolyl‐2H‐[1,2,3]triazole (23).
Yield (%) 32; m.p. 64–65°C; IR/ν (cm−1) 2964, 1613, 1580,
1497, 1461, 839, 761; 1H NMR: δ 8.01 (s, 1H), 7.83–7.80
(m, 2H), 7.64–7.62 (m, 1H), 7.36–7.33 (m, 3H), 7.01–6.98
(m, 2H), 3.86 (s, 3H), 2.44 (s, 3H); Anal. Calcd. for
C16H15N3O: C,72.45; H, 5.66; N, 15.85. Found: C, 72.26; H,
4‐(4‐Methoxy‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (14).
Yield (%) 58; m.p. 92–94°C; IR/ν (cm−1) 2966, 1597, 1500,
1
1488, 1464, 835, 762, 693; H NMR: δ 8.12 (dd, 2H, J = 1.0,
8.6 Hz), 7.98 (s, 1H), 7.85–7.82 (m, 2H), 7.51–7.47 (m, 2H),
7.36–7.34 (m, 1H), 7.02–6.99 (m, 2H), 3.86 (s, 3H); Anal. Calcd.
for C15H13N3O: C, 71.71; H, 5.18; N, 16.73. Found: C, 71.66;
H, 5.03; N, 16.65.
5.29; N, 15.68.
4‐(4‐Chloro‐phenyl)‐2‐o‐tolyl‐2H‐[1,2,3]triazole (24).
Yield (%) 35; m.p. 67–69°C; IR/ν (cm−1) 2962, 1496, 824,
1
756; H NMR: δ 8.08 (s, 1H), 7.85–7.83 (m, 2H), 7.65–7.63
4‐(3,4‐Dimethoxy‐phenyl)‐2‐phenyl‐2H‐[1,2,3]triazole (15).
Yield (%) 44; m.p. 96–97°C; IR/ν (cm−1) 1598, 1503, 1464,
(m, 1H), 7.47–7.45 (m, 2H), 7.39–7.37 (m, 3H), 2.46 (s, 3H);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Xu and Y. Hu
Vol 000
Yield
Anal. Calcd. for C15H12N3Cl: C, 66.80; H, 4.45; N, 15.59.
Found: C, 66.87; H, 4.28; N, 15.34.
2,4‐Bis‐(4‐chloro‐phenyl)‐2H‐[1,2,3]triazole (30).
(%) 26; m.p. 134–135°C; IR/ν (cm−1) 1604, 1493, 827; 1H
NMR: δ 8.11–8.08 (m, 3H), 8.05 (s, 1H), 7.86–7.83 (m, 2H),
7.50–7.46 (m, 4H); Anal. Calcd. for C14H9N3Cl2: C, 57.95; H,
3.10; N, 14.49. Found: C, 57.82; H, 2.98; N, 14.58.
4‐Phenyl‐2‐p‐tolyl‐2H‐[1,2,3]triazole (25). Yield (%) 46;
m.p. 74–76°C; IR/ν (cm−1) 3035, 1605, 1510, 1456, 812,
767, 692; 1H NMR:
δ 8.06–8.03 (m, 3H), 7.94–7.91
(m, 2H), 7.51–7.48 (m, 2H), 7.43–7.39 (m, 1H), 7.32 (d,
2H, J = 8.0 Hz), 2.44 (s, 3H); Anal. Calcd. for C15H13N3:
C, 76.60; H,5.53; N,17.87. Found: C, 76.42; H, 5.38; N,
18.03.
REFERENCES AND NOTES
4‐(4‐Methoxy‐phenyl)‐2‐p‐tolyl‐2H‐[1,2,3]triazole (26).
Yield (%) 58; m.p. 115–117°C; IR/ν (cm−1) 3032, 1614, 1511,
1
[1] Karimkulov, K. M.; Dzhuraev, A. D.; Makhsumov, A. G.;
Amanov, N. Pharm Chem J 1991, 25, 399.
833, 823; H NMR: δ 8.03–8.01 (m, 2H), 7.98 (s, 1H), 7.86–
7.84 (m, 2H), 7.30 (t, 2H, J = 7.6 Hz), 7.03–7.01 (m, 2H), 3.89
(s, 3H), 2.44 (s, 3H); Anal. Calcd. for C16H15N3O: C,72.45; H,
5.66; N, 15.85. Found: C, 72.62; H, 5.54; N, 15.66.
4‐(4‐Chloro‐phenyl)‐2‐p‐tolyl‐2H‐[1,2,3]triazole (27).
Yield (%) 55; m.p. 143–145°C; IR/ν (cm−1) 3036, 1603, 825;
1H NMR: δ 8.03–8.00 (m, 3H), 7.87–7.84 (m, 2H), 7.48–7.44
(m, 2H), 7.32 (d, 2H, J = 8.0 Hz), 2.44 (s, 3H); Anal. Calcd.
for C15H12N3Cl: C, 66.80; H, 4.45; N, 15.59. Found: C, 66.72;
H, 4.30; N, 15.36.
[2] Sheremet, E. A.; Tomanov, R. I.; Trukhin, E. V.;
Berestovitsakaya, V. M. Russ. J. Org Chem 2004, 40, 594.
[3] Diana, D. G.; Nitz, J. J. Eur Patent566199, 1993.
[4] Kelley, J. L.; Koble, C. S.; Davis, R. G.; McLean, E. W.;
Soroko, F. E.; Cooper, B. R. J Med Chem 1995, 38, 4131.
[5] Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore,
M. R.; Cascieri, M. A.; Colwell, L. F.; Deng, L.; Feeney, W. P.;
Forrest, M. J.; Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt,
M. J.; Fisher, M. H.; Weber, A. E. Bioorg Med Chem Lett 2000,
10, 2111.
2‐(4‐Chloro‐phenyl)‐4‐phenyl‐2H‐[1,2,3]triazole (28).
Yield (%) 44; m.p. 112–113°C; IR/ν (cm−1) 1494, 1455, 828,
767, 692; 1H NMR: δ 8.12–8.08 (m, 3H), 7.93–7.90 (m, 2H),
7.52–7.47 (m, 4H), 7.45–7.42 (m, 1H); Anal. Calcd. for
C14H10N3Cl: C, 65.77; H, 3.91; N, 16.44. Found: C, 65.59; H,
3.62; N, 16.25.
[6] Lu, L. H.; Wu, J. H.; Yang, C. H. J Chin Chem Soc 2008,
55, 414.
[7] Journet, M.; Cai, D.; Kowal, J. J.; Larsen, R. D. Tetrahedron
Lett 2001, 42, 9117.
[8] Howell, S. J.; Spencer, N.; Philp, D. Tetrahedron 2001,
57, 4945.
[9] Hoberg, H. Ann Chem 1967, 707, 147.
[10] Latif, N.; Meguid, S. A. J Chem Soc Perkin Trans I 1972,
8, 1095.
[11] Balachandran, K. S.; Hiryakkanavar, I.; George, M. V. Tetrahedron
1975, 31, 1171.
[12] Khadem, H. El.; El‐Sadik, M. M.; Meshreki, M. H. J Chem
Soc (C) 1968, 2097.
2‐(4‐Chloro‐phenyl)‐4‐(4‐methoxy‐phenyl)‐2H‐[1,2,3]
triazole (29). Yield (%) 38; m.p. 144–146°C; IR/ν (cm−1
)
1
2963, 1614, 1494, 459, 837; H NMR: δ 8.10–8.08 (m, 2H),
8.00 (s, 1H), 7.85–7.83 (m, 2H), 7.49–7.46 (m, 2H), 7.03–7.01
(m, 2H), 3.89 (s, 3H); Anal. Calcd. for C15H12N3ClO: C,
63.06; H, 4.20; N, 14.71. Found: C, 63.28; H, 4.12; N, 14.66.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet