New synthesis and properties of 3-alkyl-, 3-chloroalkyl-, 3-perfluoroalkyl-, and 3-aryl-1-methyl-(5-halo)pyrazoles from chloro(bromo) vinyl ketones and N,N-dimethylhydrazine

Article abstract of DOI:10.1023/A:1022564707537

A new regioselective heterocyclization was revealed in the reaction of 2-chloro- and 2,2-dichloro-(bromo)vinyl ketones with N,N-dimethylhydrazine to afford 3-substituted 1-methyl(5-halo)pyrazoles. The reaction is accompanied by elimination of methyl halide and formation of up to 90% of N,N,N-trimethylhydrazinium halide as the second product.

Full text of DOI:10.1023/A:1022564707537

Russian Journal of Organic Chemistry, Vol. 38, No. 10, 2002, pp. 1501 1506. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 10, 2002,
pp. 1554 1559.
Original Russian Text Copyright
2002 by Levkovskaya, Bozhenkov, Larina, Mirskova.
New Synthesis and Properties of 3-Alkyl-, 3-Chloroalkyl-,
3-Perfluoroalkyl-, and 3-Aryl-1-methyl-(5-halo)pyrazoles
from Chloro(bromo)vinyl Ketones and N,N-Dimethylhydrazine
G. G. Levkovskaya, G. V. Bozhenkov, L. I. Larina, and A. N. Mirskova
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
fax: (3952)396046; e-mail: ggl@irioch.irk.ru
Received November 7, 2001
Abstract A new regioselective heterocyclization was revealed in the reaction of 2-chloro- and 2,2-dichloro-
(bromo)vinyl ketones with N,N-dimethylhydrazine to afford 3-substituted 1-methyl(5-halo)pyrazoles. The
reaction is accompanied by elimination of methyl halide and formation of up to 90% of N,N,N-trimethyl-
hydrazinium halide as the second product.
Pyrazoles, especially those having a halogen atom
in position 5, are promising initial compounds for
the synthesis of drugs, dyes, fluorescent compositions,
insecticides, insectoacaricides, and other biologically
active substances [1 8]. For example, 5-chloro-1,3-
dimethylpyrazole is used as starting compound for
the preparation of a novel antiacaricide agent, Fen-
pyroximate [2, 3]. A series of pyrazolodiazocines
and pyrazolodiazepines exhibiting antidepressant
activity was obtained from 3-alkyl-5-chloro-5-methyl-
pyrazoles [6, 7]; acylation of the latter gives the
corresponding 4-acyl derivatives as components of
fungicide compositions [8]. We can conclude that
development of preparative procedures for synthesis
of pyrazoles, specifically halogen-substituted pyra-
zoles, from accessible starting compounds is an im-
portant problem.
[4, 9 11]. 5-Chloro(bromo)pyrazoles are usualy ob-
tained by reactions of acylacetic esters or those
derived from alkylacetylenecarboxylic acids with
hydrazine or methylhydrazine; 5-pyrazolones thus
formed are treated with phosphorus halides [4, 9 11].
However, the reaction of methylhydrazine with acetyl-
acetic esters gives 3-substituted 1-methylpyrazol-5-
ones in low yield, and the process is accompanied
by formation of isomeric products. It should also be
noted that the possibilities for preparation of 3-alkyl-
1-methylpyrazol-5-ones from methylhydrazine and
methyl alkylacetylenecarboxylates are limited by
difficulties in the synthesis of appropriate alkyl-
acetylenecarboxylic acids.
We previously proposed a procedure for prepara-
tion of 1,3-disubstituted pyrazoles from 2-chlorovinyl
ketones and arylhydrazines [12]. On the other hand,
2,2-dichlorovinyl ketones which are also fairly acces-
sible products [12 14] failed to react with phenyl- or
dinitrophenylhydrazine to give pyrazole derivatives;
The known methods for synthesizing halopyrazole
derivatives are laborious, they include a number of
steps, and the yields of the final products are poor
Scheme 1.
I, R = Me; II, R = Et; III, R = Pr; IV, R = i-Pr; V, R = CH2Cl; VI, R = CF3; VII, R = Ph; VIII, R = 4-MeC6H4; IX, R =
4-MeOC6H4; X, 4-BrC6H4; XI, R = 4-ClC6H4; XII, R = 4-NO2C6H4; XIII, R = 3-NO2C6H4.
1070-4280/02/3810-1501$27.00 2002 MAIK Nauka/Interperiodica

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LEVKOVSKAYA et al.
Table 1. Yields, physical properties, and elemental analyses of pyrazoles I XVI
bp,
(p, mm)
[mp, C]
C
Found, %
Cl
Calculated, %
Cl
d240
(n2D0)
Comp. Yield,
Formula
no.
%
C
H
N
C
H
N
Ia
64
71
157.5 158
40 (1)
1.1400 45.89 5.63 29.95 21.65 C5H7ClN2
(1.4855)
1.1808 50.03 6.14 24.44 19.60 C6H9ClN2
(1.4848)
45.99 5.40 27.15 21.45
49.84 6.27 24.52 19.37
IIa
IIIa
IV
V
77
70
77
45
67 (2)
(1.4832) 53.00 6.99 22.35 17.66 C7H11ClN2
52.79 7.23 22.49 17.54
52.79 7.23 22.49 17.54
36.39 3.66 42.97 16.97
32.54 2.18 19.21 15.18
76 (17 18) (1.4833) 53.68 7.12 21.98 17.57 C7H11ClN2
[33 33.5]
140 141
36.38 3.69 43.10 16.84 C5H6Cl2N2
1.4927 32.39 2.12 18.97 15.33 C5H4ClF3N2
(1.4184)
VIb
VIIa
VIII
IX
X
XI
XII
XIII
XIVc
XVa
62
89
69
66
89
65
87
70
64
[60 62]
[98.5 100.5]
[74 77]
[103 106]
[89 91]
[160 161]
[105 106.5]
145
62.81 5.00 18.71 14.27 C10H9ClN2
63.33 5.11 17.75 15.39 C11H11ClN2
59.03 4.77 16.04 12.59 C11H11ClN2O 59.33 4.98 15.92 12.58
62.35 4.71 18.40 14.54
63.93 5.36 17.15 15.55
44.13 3.09
9.59 C9H8BrClN2
44.23 2.97 13.06 10.32
52.89 3.55 31.22 12.34
53.00 3.45 30.98 12.38 C10H8Cl2N2
51.04 3.22 14.87 17.97 C10H8ClN3O2 50.54 3.39 14.92 17.68
50.45 3.31 14.82 17.47 C10H8ClN3O2 50.54 3.39 14.92 17.68
(1.5210) 26.34 1.79
1.4674 62.03 8.06
(0.9626)
12.43 C5H4BrF3N2
29.19 C5H8N2
26.22 1.76
12.23
136
62.47 8.29
29.14
XVI
70
146 148
1.5275 45.78
5.24
21.47 C5H7ClN2
45.99 5.40
21.45
a
b
c
Compounds I III, VII, and XV were described previously (see Experimental).
Found, %: F 29.89. Calculated, %: F 30.88.
Found, %: Br 34.89; F 24.89. Calculated, %: Br 34.62; F 25.00.
the corresponding pyrazole was obtained only by
heating of dichlorovinyl phenyl ketone 2,4-dinitro-
phenylhydrazone at the melting point [15]. We also
described a single example [16] of the isolation of
a 3-methylpyrazole derivative in the reaction of
methyl 2,2-dichlorovinyl ketone with excess hydra-
zine; however, this result has not received further
confirmation.
While performing the present study, we have found
that alkyl, aryl, chloroalkyl, and perfluoroalkyl 2,2-di-
chlorovinyl ketones react with 1,1-dimethylhydrazine
to afford the corresponding 3-substituted 5-chloro-1-
methylpyrazoles I XIII (Scheme 1) in good yields.
The second reaction product is trimethylhydrazinium
chloride. The reactions were carried out in an organic
solvent: hexane, benzene, lower alcohols, diethyl
ether, or acetonitrile; the reactant ratio was 1:2. The
process was accompanied by heat evolution, and the
products were isolated by standard techniques.
the dimethylamino group on the -carbon atom of
the vinyl group. N,N-Dimethylpyrazolium chloride
thus formed undergoes demethylation to give the final
product (Scheme 1).
The structure of pyrazoles I XIII was proved by
spectral methods and elemental analysis (Tables 1 3).
The second product, 1,1,1-trimethylhydrazinium
chloride, is a crystalline water-soluble substance [17]
from which dimethylhydrazine can be regenerated. On
the other hand, trimethylhydrazinium chloride itself
may be utilized in other chemical processes or used
in medicine and agriculture [17, 18].
It is known [19, 20] that 1,1-dimetylhydrazine
reacts with carbonyl compounds, including unsaturated
ones, to give the corresponding hydrazones. Elokhina
et al. [21] reported on the formation of a quaternary
dimethylhydrazinum salt, 1-[1-bromo-2-benzoyl(2-
thenoyl)vinyl]-1,1-dimethylhydrazinium bromide in
the reaction of 1,1-dimethylhydrazine with bromo-
acetylenic ketones. According to the authors, this is
the result of reaction of intermediate 2,2-dibromo-
vinyl phenyl(thienyl) ketones with 1,1-dimethyl-
The reaction mechanism is likely to involve initial
formation of 2-chlorovinyl ketone dimethylhydrazone
and subsequent intramolecular nucleophilic attack by
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

NEW SYNTHESIS AND PROPERTIES OF 3-ALKYL-, 3-CHLOROALKYL-
1503
hydrazine. Contrastingly, by reaction of dimethyl-
Table 2. IR spectra of pyrazoles I XIV and XVIa
hydrazine with 2,2-dibromovinyl trifluoromethyl
ketone [22] we obtained 5-bromo-1-methyl-3-tri-
fluoromethylpyrazole (XIV) (Tables 1 3). The reac-
tion was also accompanied by heat evolution and
formation of 1,1,1-trimethylhydrazinium bromide.
Comp.
no.
C Cl
C C N CH3 (R = Alk)
C H
I
II
770
770
770
775
1510
1510
1510
1500
2950
2925
2860, 2920, 2950
2860 2950
2940, 2975
2960
3125
3120
3120
3120
3130
3150
3127,
3060,
3030
3145
3130
III
IV
V
VI
VII
770, 790 1505
790
780
1480
1490
2940
Likewise, while studying the reaction of chloro-
vinyl ketones with dimethylhydrazine we discovered
a new route to 3-substituted 1-methylpyrazoles.
2-Chlorovinyl methyl ketone and 2-chlorovinyl
chloromethyl ketone reacted with 1,1-dimethylhydra-
zine to give the corresponding 1-methylpyrazoles XV
and XVI in up to 70% yield and 1,1,1-trimethylhydra-
zinium chloride (Scheme 2). It should be emphasized
that the reaction between equimolar amounts of mono-
or dihalovinyl ketones with dimethylhydrazine also
gives pyrazoles and trimethylhydrazinium halides,
but unreacted initial ketone remains in the reaction
mixture. This may be due to partial deactivation of
dimethylhydrazine as a result of quaternization with
liberated methyl chloride; on the other hand, de-
methylation of dimethylpyrazolium salts can also be
effected by dimethylhydrazine which is thus converted
into inactive hydrazinium halide.
VIII
IX
780
790
1490
2920
1500, 2840, 2910, 2940,
1600
1500
1500
2950
2950
2950
X
XI
790
790
3130
3135,
3060,
3090
3140,
3100,
3080,
3050
3100,
3130,
3050,
3070
3145
3130
XII
770
760
1510,
1600
2940
2940
XIII
1500
XIV
XVI
1470
1510
2950
2930, 2950
760
a
Prior to our present study, 3-methyl-, 3-ethyl-,
3-propyl-, and 3-phenyl-5-chloro-1-methylpyrazoles
have already been reported [4, 10, 11], but their
chemical and physical properties have been studied
poorly; in some cases only the boiling points are
available [4]. We have examined the IR and NMR
spectra of pyrazoles I XIV and XVI, and studies of
their chemical transformations (such as acylation,
nitration, sulfonation, etc.) are now in progress.
The IR spectra of compounds I IV, VI, XIV, and XVI were
recorded from samples prepared as thin films, and of V and
VII XIII, from samples pelleted with KBr.
belongs to stretching vibrations of the C4 H bond.
The corresponding frequency increases in going to
3-arylpyrazoles VII XIII and those having an elec-
tron-acceptor group on C3 (compounds V, VI, and
XIV). Absorption of the endocyclic C C bond
1
appears at 1480 1510 cm .
The IR spectra of 5-bromo-, 5-chloro-, and 5-un-
substituted 1-methylpyrazoles are characterized by
1
In the H NMR spectra of pyrazoles I XIII, reson-
1
absorption in the region 3120 3150 cm , which
ance signals of the 4-H proton are observed in the
Scheme 2.
XV, R = Me; XVI, R = CH2Cl.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

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LEVKOVSKAYA et al.
Table 3. 1H, 13C, 15N, and 19F chemical shifts ( , ppm) and coupling constants (J, Hz) in the NMR spectra of pyrazoles
I XIV and XVI in CDCl3
1H
15N
13C
C5
Comp.
no.
NCH3
5-H
3-R
N2
N1
C3
C4
NCH3
others
I
II
III
3.72
3.73
3.74
5.94 2.19
148.13
103.87 127.16 35.66 13.80 (CH3)
5.92 0.91 t, 2.45 q
5.97 0.93 t, 1.61 m,
2.51 t
5.99 1.20 d, 2.89 m
6.24 4.48
78.4
188.2
183.8
152.95
103.10 127.09 35.84 22.79, 30.69, 13.86
(C3H7)
IV
V
VIa
3.73
3.78
3.88
74.4
74.3
118.40
103.97 127.86 35.99 38.61 (CH2Cl)
6.46
178.5 141.80 q 103.40 128.88 36.78 121.69 q (CF3)
(2JCF (1JCF = 169.1)
38.7)
150.94 101.84 128.00 36.34
=
VII
VIII
3.81
3.85
6.44 7.29 7.64 m
6.44 2.34 (CH3),
7.17 d, 7.59 d
(8.1)
6.39 3.82 (CH3O),
6.89 d, 7.63 d
(8.8)
81.6
82.8
184.8
150.96 101.63 128.09 36.30 125.28, 130.10,
129.43, 137.92
IX
3.79
185.3
150.75
101.30 128.05 36.20 55.34 (OCH3);
126.65, 114.13,
132.78, 159.68
X
3.85
3.81
3.90
6.44 7.48 d, 7.57 d
(8.4)
6.40 7.28 d, 7.19 d
(8.7)
6.58 7.87 d, 8.23 d
(8.7)
80.3
81.6
76.8
183.2
184.8
180.0
149.54
149.81
148.45
101.66 128.26 36.24 131.69, 121.86,
126.76
101.86 128.00 36.42 133.91, 131.45,
128.95, 126.66
102.83 129.11 36.66 124.05, 124.18,
125.78, 139.04,
XI
XIIb
147.40
XIIIb 3.90
6.58 7.55 d.d (8.0),
8.13 d (8.0),
78.0
181.3
148.51
102.31 129.73 36.63 120.30, 122.68,
128.85, 131.00,
8.06 d.d (8.0,
134.72, 148.65
1.8), 8.51 d
(1.8)
3.91 6.54
XIV
142.57 q 107.13 114.62 38.19 120.67 q (1JCF
=
(2JCF = 39.1)
6.27 d 4.58 (CH2Cl);
(1.6) 7.32 d (4-H, 1.6)
268.7)
XVI
3.86
74.8
181.2
148.37
105.08 130.97 38.62 76.83
a
F(CF3) 63.4 ppm (relative to CCl3F).
N(NO2) 11.2 (XII), 11.1 ppm (XIII) (relative to CH3NO2).
b
region 5.6 6.9 ppm. In going from 3-alkylpyrazoles
I IV to derivatives containing electron-acceptor (CF3,
XV and XVI, the 5-H signal appears in a much
weaker field than 4-H (Table 3).
CH2Cl) or aryl group on C3, the 4-H signal shifts
downfield. An analogous but less distinct tendency is
observed for signals from the NCH3 protons. The 4-H
signal of 5-bromo-1-methyl-3-trifluoromethylpyrazole
(XIV) is also displaced slightly downfield relative
to the corresponding signal of its 5-chloro analog VI.
The positions of the C4 and C5 signals in the 13C
NMR spectra of compounds I XIII change only
slightly (
3 ppm) on variation of the substituent
C
on C3. Their chemical shifts fall into the same regions
as those found for 1-methylpyrazole ( 105.7 and
128.7 ppm, respectively) [23]. Naturally, Cthe chemical
1
In the H NMR spectra of 5-unsubstituted pyrazoles
shift of C3 changes over a wider range (
35 ppm;
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

NEW SYNTHESIS AND PROPERTIES OF 3-ALKYL-, 3-CHLOROALKYL-
1505
Table 3). Variations of the N1 and N2 chemical shifts
in the 15N NMR spectra of 5-chloropyrazoles I XIII
are about 10 and 8 ppm, respectively. Electron-
acceptor substituents in position 3 induce a downfield
shift of the N1 signal (Table 3). It is known that
shielding of the pyrrole-type nitrogen atom in azoles
is much stronger, as compared to the pyridine-type
nitrogen atom [24]. In fact, the chemical shifts of N1
fall into the range from 178 to 188 ppm, while the
N2 signals are displaced downfield by 100 ppm.
Pyrazoles I XI and XIV XVI are colorless liquids
or crystalline powders having a specific mould odor
which is typical of pyrazole and its derivatives. Nitro-
phenyl-substituted pyrazoles XII and XIII are light
orange powders. The products are readily soluble in
organic solvents and insoluble in water.
Thus the proposed procedure for preparation of
3-alkyl-, 3-aryl-, 3-chloroalkyl-, and 3-perfluoroalkyl-
5-chloro-1-methylpyrazoles and [5-chloro(bromo)]-1-
methyl-3-trifluoromethylpyrazoles utilizes readily
accessible initial compounds or those produced on
a large scale; it requires neither special equipment nor
catalyst and is simple; therefore, it can be applied
for large-scale syntheses. We are now studying the
scope of application of this procedure. It seems
important to examine the effect of ketone conforma-
tion, dialkylhydrazine structure, and nature of the
halogen atom in initial halovinyl ketones on the reac-
tion direction.
H 10.03; Cl 32.06; N 25.33. The filtrate was distilled
to obtain 8.36 g of pyrazole I. bp 156 157.5 C;
published data [10, 11]: bp 158 C, n1D7.6 = 1.4841,
d147.6 = 1.1367.
When the reaction of N,N-dimethylhydrazine with
2,2-dichlorovinyl methyl ketone (reactant ratio 2:1)
was performed in benzene, ether, acetonitrile, or lower
alcohols (metanol, ethanol, or 2-propanol), other
conditions being equal, pyrazole I was obtained in
63 68% yield. Pyrazoles II XIV were synthesized in
a similar way (Tables 1 3).
5-Chloro-3-ethyl-1-methylpyrazole (II) was syn-
thesized from 7.54 g (0.125 mol) of N,N-dimethyl-
hydrazine and 8.72 g (0.0627 mol) of 4,4-dichloro-3-
penten-2-one. 1,1,1-Trimethylhydrazinium chloride,
8.85 g (80%), was isolated. Yield of pyrazole II 6.4 g;
published data [4]: bp 82 83 C (28 mm).
5-Chloro-1-methyl-3-propylpyrazole (III) was
synthesized from 12 g (0.2 mol) of N,N-dimethyl-
hydrazine and 16.7 g (0.1 mol) of 1,1-dichloro-1-
hexen-2-one in 50 ml of 2-propanol. Yield 13 g.
Published data [4]: bp 78 79 C (10 mm).
5-Chloro-3-isopropyl-1-methylpyrazole (IV) was
obtained from 12 g (0.2 mol) of N,N-dimethylhydra-
zine and 16.7 g (0.1 mol) of 1,1-dichloro-4-methyl-1-
penten-3-one in 100 ml of diethyl ether. Yield 12.7 g.
5-Chloro-3-chloromethyl-1-methylpyrazole (V)
was synthesized from 12 g (0.2 mol) of N,N-dimethyl-
hydrazine and 17.3 g (0.1 mol) of 1,4,4-trichloro-3-
buten-2-one in 100 ml of benzene. Yield 13 g.
5-Chloro-1-methyl-3-trifluoromethylpyrazole
(VI) was synthesized from 7.44 g (0.1238 mol) of
N,N-dimethylhydrazine and 10.97 g (0.0619 mol) of
4,4-dichloro-1,1,1-trifluoro-3-buten-2-one in 40 50 ml
of anhydrous acetonitrile. Yield 5.46 g.
5-Chloro-1-methyl-3-phenylpyrazole (VII) was
synthesized from 12 g (0.2 mol) of N,N-dimethyl-
hydrazine and 20.2 g (0.1 mol) of 3,3-dichloro-1-
phenyl-2-propen-1-one in 100 ml of dry diethyl ether.
Yield 5.46 g. mp 60 62 C [9].
EXPERIMENTAL
The 1H, 13C, 15N, and 19F NMR spectra were
recorded on Bruker DPX-400 (400.6, 100.61, 40.56,
and 376 MHz, respectively) and Jeol FX-90Q instru-
1
ments (90 MHz for H and 84 MHz for 19F). Hexa-
methyldisiloxane was used as internal reference for 1H
and 13C NMR spectra. The IR spectra were measured
on a Specord 75IR spectrometer.
5-Chloro-1,3-dimethylpyrazole (I). 4,4-Dichloro-
3-buten-2-one, 13.9 g (0.1 mol), was slowly added in
a dropwise manner to a solution of 12.0 g (0.2 mol) of
N,N-dimethylhydrazine in 50 100 ml of dry hexane.
When the exothermic reaction was over, the mixture
was stirred for 1 2 h, and the precipitate of 1,1,1-tri-
methylhydrazinium chloride was filtered off and dried
under reduced pressure over P2O5. Yield 9.68 g
(88%). mp 261 262 C; published data [17]: mp 245 C
5-Chloro-1-methyl-3-(4-tolyl)pyrazole (VIII) was
synthesized from 12 g (0.2 mol) of N,N-dimethyl-
hydrazine and 21.1 g (0.1 mol) of 3,3-dichloro-1-
(4-tolyl)-2-propen-1-one in 100 ml of anhydrous
diethyl ether. Yield 18.39 g, mp 60 62 C [9].
5-Chloro-3-(4-methoxyphenyl)-1-methylpyrazole
(IX) was synthesized from 12 g (0.2 mol) of N,N-di-
methylhydrazine and 22.9 g (0.1 mol) of 3,3-dichloro-
1-(4-methoxyphenyl)-2-propen-1-one in 100 ml of
anhydrous ether. Yield 15.36 g.
1
(decomp.; from EtOH EtOAc). IR spectrum, , cm :
3200, 3100, 3005, 2700 (N H); 2950 (CH3); 1480,
1
1630 (C N). H NMR spectrum (CD3OD), , ppm:
3.41 (NMe). Found, %: C 32.58; H 10.24; Cl 31.97;
N 25.37. C3H11ClN2. Calculated, %: C 32.58;
3-(4-Bromophenyl)-5-chloro-1-methylpyrazole
(X) was synthesized from 12 g (0.2 mol) of N,N-di-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

1506
LEVKOVSKAYA et al.
methylhydrazine and 27.9 g (0.1 mol) of 1-(4-bromo-
phenyl)-3,3-dichloro-2-propen-1-one in 100 ml of
anhydrous ether. Yield 17.92 g.
7. FRG Patent no. 2423642, 1974; Chem. Abstr., 1975,
vol. 83, no. 206345.
8. Russian Patent no. 2072991, 1997; Byull. Izobret.,
1997, no. 4.
5-Chloro-3-(4-chlorophenyl)-1-methylpyrazole
(XI) was synthesized from 4.6 g (0.02 mol) of 2,2-
dichlorovinyl 4-chlorophenyl ketone and 2.4 g
(0.04 mol) of N,N-dimethylhydrazine in 50 ml of
anhydrous ether. Yield 4.04 g.
5-Chloro-1-methyl-3-(4-nitrophenyl)pyrazole
(XII) was synthesized from 4.92 g (0.02 mol) of
2,2-dichlorovinyl 3-nitrophenyl ketone and 2.4 g
(0.04 mol) of N,N-dimethylhydrazine in 50 ml of
anhydrous ether. Yield 3.90 g.
5-Chloro-1-methyl-3-(3-nitrophenyl)pyrazole
(XIII) was synthesized from 4.92 g (0.02 mol) of
2,2-dichlorovinyl 3-nitrophenyl ketone and 2.4 g
(0.04 mol) of N,N-dimethylhydrazine in 50 ml of
anhydrous ether. Yield 4.12 g.
9. Michaelis, A. and Dorn, N., Ber., 1907, vol. 23,
p. 179; Michaelis, A. and Dorn, N., Justus Liebigs
Ann. Chem., 1907, vol. 352, p. 169.
10. Auwers, K. and Niemyer, F., J. Prakt. Chem., 1925,
vol. 110, p. 153.
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5-Bromo-1-methyl-3-trifluoromethylpyrazole
(XIV) was synthesized in a similar way from 2.70 g
(9.5 mmol) of 2,2-dibromovinyl trifluoromethyl
ketone and 1.2 g (1.9 mmol) of N,N-dimethylhydra-
zine. Yield 1.5 g. The product was purified by distil-
lation.
1,3-Dimethylpyrazole (XV). Likewise, from 1.2 g
of N,N-dimethylhydrazine and 1.04 g of 4-chloro-
3-buten-2-one in 50 100 ml of anhydrous hexane we
obtained 0.9 g of 1,1,1-trimethylhydrazinium chloride
and 0.84 g (64%) of pyrazole XV. bp 136 138 C,
1993, no. 7Zh108.
19. Kitaev, Yu.P. and Buzykin, B.I., Gidrazony (Hydra-
n2D0 = 1.4674, d240 = 0.9626; published data [25]:
bp 136 C, n1D6.2 = 1.46769, d416.2 = 0.9628.
zones), Moscow: Nauka, 1974, p. 17.
20. Belyaev, E.Yu., N,N-Dimetilgidrazin v organicheskoi
khimii, (N,N-Dimethylhydrazine in Organic Chem-
istry), Krasnoyarsk: Sibirsk. Gos. Tech. Univ., 1999,
p. 7.
21. Elokhina, V.N., Nakhmanovich, A.S., Larina, L.I.,
Shishkin, O.V., Baumer, V.N., and Lopyrev, V.A.,
Izv. Ross. Akad. Nauk, Ser. Khim., 1999, no. 8,
p. 1536.
3-Chloromethyl-1-methylpyrazole (XVI). From
1.20 g of N,N-dimethylhydrazine and 1.39 g of 1,4-di-
chloro-3-buten-2-one in 50 100 ml of anhydrous ether
we obtained 0.96 g (88%) of 1,1,1-trimethylhydrazi-
nium chloride. The filtrate was purified by column
chromatography on silica gel to isolate pyrazole XVI.
Yield 0.91 g.
22. Bozhenkov, G.V., Levkovskaya, G.G., and Mirsko-
va, A.N., Russ. J. Org. Chem., 2002, no. 1, pp. 134
135.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002