New synthesis of 3(5)-methylpyrazole

Full text of DOI:10.1007/s10593-009-0379-3

Chemistry of Heterocyclic Compounds, Vol. 45, No. 8, 2009
LETTERS TO THE EDITOR
NEW SYNTHESIS OF 3(5)-METHYLPYRAZOLE
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1
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1
E. P. Levanova *, V. A. Grabel'nykh , K. A. Volkova , N. V. Russavskaya ,
1
1
1
L. V. Klyba , A. I. Albanov , and N. A. Korchevin
Keywords: hydrazine, 1,4-dichloro-2-butyne, methylpyrazole.
Pyrazole derivatives are the basis of many drugs, pesticides, dyes, and analytical reagents and other
practically important substances [1]. The most important methods for the synthesis of pyrazoles are based on the
condensation of hydrazines with 1,3-dicarbonyl compounds, vinyloxy compounds, or the precursors and
derivatives of vinyloxy compounds [1, 2].
We have found that the reaction of 1,4-dichloro-2-butyne 1 with hydrazine in the presence of potassium
hydroxide leads to 3(5)-methylpyrazole 2 in 43% yield (not optimized).
Me
Me
KOH
KCl
ClCH C
CCH Cl + N H
2 2 4
2
N
HN
–
1
N
N
H
2
b
2
a
The formation of pyrazole 2 probably proceeds through the replacement of one chlorine atom in
dichloride 1 by a hydrazine residue. The second chlorine atom undergoes reductive replacement. Intermediates
such as hydrazine 3 and pyrazoline 4 could not be identified in the reaction mixture.
ClH C
2
H
C
1
+
N H
ClCH C
CCH NHNH2
2
2
4
2
2
–
HCl
HN
CH2
– HCl
3
N
H
4
_
*
______
To whom correspondence should be addressed, e-mail: venk@irioch.irk.ru.
1
A. I. Favorsky Irkutsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of
Sciences, Irkutsk 664033, Russia.
_
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1265-1266, August, 2009.
Original article submitted April 30, 2009.
009-3122/09/4508-1009©2009 Springer Science+Business Media, Inc.
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1009

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The H and C NMR spectra were taken on a Bruker DPX 400 spectrometer at 400 and 106 MHz,
respectively, in CDCl3 with HMDS as the standard. The mass spectrum was taken on a
Shimadzu GCMS-QP5050A mass spectrometer at 70 eV.
3
(5)-Methylpyrazole 2. Dichloride 1 (7.0 g, 57 mmol) was added to a solution of KOH (4.5 g,
5 mmol) in hydrazine hydrate (30 ml) at 25°C. The reaction mixture was stirred for 1 h at 40-50°C, cooled,
and extracted with dichloromethane. Removal of the solvent gave 2.0 g 3(5)-methylpyrazole 2, bp 74-76°C
7
1
(
4.5 mm Hg) (204-205°C (752 mm Hg) [3]). The H NMR spectrum, δ, ppm (J, Hz) showed averaged signals
3
for tautomeric forms 2a and 2b: 2.25 (3H, s, CH ); 6.00 (1H, d, H-4); 7.43 (1H, d, J = 1.5, H-5(3)). The
3
3,4
1
signal for the NH proton was not detected in the H NMR spectrum due to extensive broadening related to the
tautomeric transition. The C NMR spectrum, δ, ppm, consists of two narrow signals at 11.52 (CH ) and 103.89
1
3
3
(
C-4) and two broad signals at 134.41 (C-5(3)) and 142.80 (C-3(5)). The broadening of the two latter carbon
signals is related to the large difference in the chemical shifts of these nuclei in the interconverting tautomers.
+
+
+
+·
Mass spectrum, m/z (I , %): 82 [M] (41.8), 81 [M-H] (27.6), 67 [M-CH ] (1.0), 54 [M-N ] (11.7), 53
rel
3
2
+
[
C H ] (4.7).
4 5
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1
. D. Barton and W. D. Ollis (editors), General Organic Chemistry [Russian translation], Vol. 8, Khimiya,
Moscow (1985).
2
3
. V. I. Ivanskii, Chemistry of Heterocyclic Compounds [in Russian], Vysshaya Shkola, Moscow (1978).
. A. N. Nesmeyanov, N. K. Kochetkov, and M. I. Rybinskaya, Izv. Akad. Nauk SSSR, Otdel. Khim. Nauk,
3
50 (1950).
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010