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O
References and Notes
160 °C, MW
NHNH2
+
NHNHCOR
R
NH2
(1) Shivarama, H. B.; Veerendra, B.; Shivananda, M. K.; Poojary, B.
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250 psi, 230 W
10 min
1a
4a,b
5a R = Me, 54%
5b R = Ph, 61%
Scheme 2 Reaction of phenyl hydrazine with acetamide and benz-
amide
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Based on the experimental observations and literature
reports, the probable pathway for the reaction is shown in
Scheme 3. It is believed that initially transamidation of
aryl/alkyl hydrazine 1 results in the formation of formohy-
drazide 6 that, upon condensation with formamide 2, gives
1,2,4-triazole 3. The presence of a peak at m/z = 192.96 cor-
responding to molecular formula C11H17N2O+ ion in the ESI-
MS of the reaction mixture of 1f (R = 4-t-BuC6H4) with for-
mamide along with a molecular ion peak at m/z = 201.96
was an indication of the formation of formohydrazide 6 (R =
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R
NHNH2
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MW
HCONH2
N
1
O
H
irradiation
2
N
+
R
NHNH
N
MW
irradiation
HCONH2
2
6
R
3
Scheme 3 Probable reaction pathway
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In summary, we have developed a simple, efficient, and
mild method for the synthesis of substituted 1,2,4-triazoles
from substituted hydrazines and formamide under micro-
wave irradiation. The reactions proceed smoothly in the ab-
sence of a catalyst and have excellent functional-group tol-
erance. Short reaction times, excellent yields, and catalyst-
free conditions are salient features of this method. Reaction
of phenyl hydrazine with acetamide and benzamide under
these conditions resulted in the formation of N′-phenylace-
tohydrazide and N′-phenylbenzohydrazide, respectively.
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(20) Experimental Procedure for the Synthesis of 3a
To a dried microwave tube was added phenylhydrazine (108
mg, 1 mmol) and formamide (0.82 mL, 20 mmol). The tube was
sealed with a plastic microwave septum and then placed into
Acknowledgment
The authors gratefully acknowledge the financial support provided by
DST-FIST (CSI-174/2008) for purchase of a focused microwave and
FTIR and the Natural Sciences and Engineering Research Council of
Canada (NSERC) to conduct this research. G.S. is thankful to CSIR, New
Delhi for a Senior Research Fellowship.
Supporting Information
Supporting information for this article is available online at
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 404–407