Reaction of 3-aryl-1-(2-methyloxiran-2-yl)prop-2-en-1-ones with tosylhydrazine

Article abstract of DOI:10.1007/s10593-005-0309-y

It was established that the reaction of 3-aryl-1-(2-methyloxiran-2-yl)prop- 2-en-1-ones with tosylhydrazine leads to 3-[(E)-2-arylvinyl]-4-methyl-1-tosyl- 1H-pyrazoles and 3-aryl-1-(2-methyloxiran-2-yl)-3-tosylpropan-1-ones. The latter are formed as a result of rearrangement of the intermediate hydrazino alcohols and/or addition of p-toluenesulfinic acid during reductive degradation of the tosylhydrazine. It was shown that the reaction of 3-aryl-1-(2-methyloxiran-2-yl) -3-tosylpropan-1-ones with an excess of tosylhydrazine leads to 3-(2-aryl-2-tosylethyl)-4-methyl-1-tosyl-1H-pyrazoles. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-005-0309-y

Chemistry of Heterocyclic Compounds, Vol. 41, No. 10, 2005
REACTION OF 3-ARYL-1-(2-METHYLOXIRAN-2-YL)PROP-
2-EN-1-ONES WITH TOSYLHYDRAZINE
T. A. Koval'chuk, N. M. Kuz'menok, and A. M. Zvonok
It was established that the reaction of 3-aryl-1-(2-methyloxiran-2-yl)prop-2-en-1-ones with
tosylhydrazine leads to 3-[(E)-2-arylvinyl]-4-methyl-1-tosyl-1H-pyrazoles and 3-aryl-1-(2-methyloxiran-
2-yl)- 3-tosylpropan-1-ones. The latter are formed as a result of rearrangement of the intermediate
hydrazino alcohols and/or addition of p-toluenesulfinic acid during reductive degradation of the
tosylhydrazine. It was shown that the reaction of 3-aryl-1-(2-methyloxiran-2-yl)-3-tosylpropan-1-ones
with an excess of tosylhydrazine leads to 3-(2-aryl-2-tosylethyl)-4-methyl-1-tosyl-1H-pyrazoles.
Keywords: hydrazone, α,β-unsaturated epoxy ketone, pyrazole, tosylhydrazine, β-tosyl ketone,
p-toluenesulfinic acid.
As shown earlier, the reaction of α,β-unsaturated epoxy ketones with hydrazine includes attack by the
nitrogen-containing nucleophile in the enone system of the substrate followed by disproportionation of the
intermediate 3-oxiranyl-4,5-dihydro-1H-pyrazoles to 3-β-hydroxyalkanoyl-1H-pyrazoles. At the same time, the
introduction of phenyl-substituted hydrazine into the reaction under these conditions leads to 1-phenyl-3-styryl-
1H-pyrazoles, formed as a result of cyclization of the intermediate hydrazones at the oxirane ring [2]. In a
continuation of these investigations and in order to synthesize 1-tosyl-substituted pyrazoles in the present work
we studied the reaction of a series of unsaturated epoxy ketones with tosylhydrazine. Aryl-substituted pyrazoles
are of interest as specific ligands of cannabinoid receptors and are being studied intensively as potential products
in the fight against alcoholism and drug addiction [3-5].
It was found that the reaction of 3-aryl-1-(2-methyloxiran-2-yl)propan-2-en-1-ones 1a-e with
tosylhydrazine, boiled in isopropyl alcohol for 3-6 h in the presence of acetic acid, leads to the formation of
3-[(E)-2-arylvinyl]-4-methyl-1-tosyl-1H-pyrazoles 2a-e and 3-aryl-1-(2-methyloxiran-2-yl)-3-tosylpropan-1-
ones 3a-e as the main products with overall yields of 52-68% (Table 1). The tosyl ketones 3a-e are formed as
two diastereomers, differing in the relative configuration of the chirality centers, in equal proportions. The initial
enones were detected in the reaction mixture with control by TLC irrespective of the duration of the reaction,
and increase in the reaction time or heating temperature did not lead to their disappearance but gave rise to the
appreciable formation of resinous products. If a 1.4-1.5 excess of the tosylhydrazine was used in the reaction
with the monoepoxides 1a-e, the formation of 3-(2-aryl-2-tosylethyl)-4-methyl-1-tosyl-1H-pyrazoles 4a-e with
yields of up to 21% was observed in addition to the main products.
The structure of the synthesized substances was proved on the basis of data from elemental analysis, IR
and H NMR spectroscopy (Table 1), and an alternative synthesis of compound 3a by reaction of the
1
monoepoxide 1a with p-toluenesulfinic acid.
__________________________________________________________________________________________
Belarus State Technological University, Minsk, Belarus; e-mail: kovtatale@bstu.unibel.by. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1481-1489, October, 2005. Original article submitted
October 28, 2003.
0009-3122/05/4110-1237©2005 Springer Science+Business Media, Inc.
1237

1238

TABLE 1. The Characteristics of the Synthesized Compounds
Found, %
——————
Calculated, %
Com-
pound*
Empirical
formula
Yield,
%*2
mp, °С
С
H
N
53
2а
2b
2c
2d
2e
3а
С19H18N2O2S
С19H17ClN2O2S
С19H17BrN2O2S
С20H20N2O3S
С26H24N2O3S
С19H20O4S
67.32
67.43
61.01
61.20
54.74
54.68
65.08
65.20
5.44
5.36
4.73
4.60
4.24
4.11
5.64
5.47
8.19
8.28
7.36
7.51
6.47
6.71
7.43
7.60
151-152
120-121
140-141
105-107
136-138
139-143
39
41
10
37
15
70.16
70.25
5.59
5.44
6.56
6.30
66.13
66.26
5.98
5.85
3b
3с
3d
3e
С19H19ClO4S
С19H19BrO4S
C20H22O5S
158-160
157-162
130-133
Oil
18
24
42
30
60.15
60.23
5.26
5.05
53.74
53.91
4.37
4.52
64.04
64.15
6.12
5.92
C26H26O5S
69.28
69.31
5.98
5.82
4a
4b
4c
4d
4e
C26H26N2O4S2
C26H25ClN2O4S2
C26H25BrN2O4S2
C27H28N2O5S2
C33H32N2O5S2
63.01
63.14
59.31
59.02
54.32
54.45
61.59
61.81
5.51
5.30
4.94
4.76
4.56
4.39
5.49
5.38
5.36
5.66
5.00
5.29
5.28
4.88
5.03
5.34
180-183
155-157
Oil
10
7
21
2
Oil
65.73
65.98
5.16
5.37
4.52
4.66
185-189
4
_______
* Compounds 3a-d were isolated as mixtures of diastereomers.
*2 The yields of compounds 2e, 3c,e, and 4a,c-e were determined from the
1H NMR spectrum of the reaction mixture.
In contrast to the initial enones, there are no absorption bands for the carbonyl group at 1680 cm-1 in the
IR spectra of compounds 2a-e. A characteristic feature of the 1H NMR spectra of the styrylpyrazoles 2a-e is the
presence of a doublet signal for the protons of the methyl group of the pyrazole ring at 2.05-2.17 ppm with spin–
spin coupling constant J = 1.0 Hz and a quartet associated with it in the region of 7.80-7.85 ppm, corresponding
to the signals of the C(5)–H protons of the azole ring. The signals of the vicinal protons at the multiple bond are
observed downfield in the form of an AB system with JAB = 16.6 Hz. The presence of the tosyl fragment in
compounds 2a-e and also in the simultaneously formed tosyl ketones 3a-e is confirmed by the presence of
absorption bands for the symmetrical and asymmetrical stretching vibrations of the sulfonyl S=O bonds at
1195-1140 cm-1 and 1375-1300 cm-1 [6] in the IR spectra of these compounds and by the data from the 1H NMR
spectra, in which singlets in the region of 2.4 ppm and a downfield AB spin system with JAB = 8.3 Hz
correspond to absorption of the protons of the CH3 group and the p-substituted aromatic ring. In the mass
spectrum of the styrylpyrazole 2a there is a molecular ion peak with m/z 338, the low intensity of which is due to
the ease of elimination of the tosyl group with the formation of a peak for a fragment ion with m/z 183, which
corresponds to a major part of the ion current.
1239

TABLE 2. The IR Spectra of Compounds 2-4
Compound
ν, cm-1
Compound
ν, cm-1
2а
1594 (arom.), 1373 (S=O),
1191 (S=O), 965 (=СН)
3с
1715 (C=O), 1596 (arom.),
1304 (S=O), 1146 (S=O)
2b
2c
1594 (arom.), 1374 (S=O),
1191 (S=O), 967 (=СН)
3d
4a
1710 (C=O), 1611 (arom.),
1312 (S=O), 1147 (S=O)
1594 (arom.), 1375 (S=O),
1192 (S=O), 967 (=СН)
1596 (arom.), 1378 (S=Opyr.,),
1301 (S=O), 1192 (S=Opyr.),
1141 (S=O)
2d
2e
3а
3b
1605 (arom.), 1372 (S=O),
1174 (S=O), 963 (=СН)
4b
4c
4e
1596 (arom.), 1386 (S=Opyr.),
1303 (S=O), 1178 (S=Opyr.),
1142 (S=O)
1595 (arom.), 1374 (S=O),
1192 (S=O), 972 (=СН)
1596 (arom.), 1386 (S=Opyr.),
1302 (S=O), 1178 (S=Opyr.),
1143 (S=O)
1708 (C=O), 1596 (arom.),
1315 (S=O), 1145 (S=O)
1597 (arom.), 1373 (S=Opyr.),
1311 (S=O), 1188 (S=Opyr.),
1145 (S=O)
1714 (C=O), 1596 (arom.),
1306 (S=O), 1145 (S=O)
In the IR spectra of the products 3a-e the bands for the stretching vibrations of the carbonyl C=O bond
appear in the form of absorption bands in the region of 1704-1708 cm-1. The structure of the β-tosyl ketones 3a-e
is also confirmed by the presence of an ABX system of coupled protons in the form of three groups of doublets
with JAB = 18.2-18.4, JAX = 7.6-9.7, and JBX = 4.1-5.9 Hz in the region of 3.0-4.9 ppm and also by the retention
of the A'B' spin system of the signals for the geminal protons of the oxirane ring in the region of 2.7-3.3 ppm
with JA'B' = 4.9 Hz.
In the IR spectra of compounds 4a-e the absorption bands of the symmetric and asymmetric stretching
vibrations of the S=O bonds appear at 1386-1373 and 1178 cm-1, which corresponds to the tosyl substituent of
the pyrazole ring, and at 1311-1302 and 1145-1142 cm-1, corresponding to the tosyl fragment in the aliphatic
part. In the 1H NMR spectra of these compounds the above-mentioned ABX system for the protons of the β-aryl-
β-tosylethyl fragment is retained, and there is an A'3X' system for the protons of the methyl-substituted pyrazole
ring.
The pyrazoles 2a-e and β-tosyl ketones 3a-e are probably formed through the intermediate adducts 5,
which are the result of nucleophilic addition of the reagent at the carbonyl group of the initial enones.
Subsequent transformation of the adducts 5 to the hydrazones 6 and intramolecular cyclization of the latter with
participation of the oxirane ring lead to the pyrazoles 2a-e. At the same time the intermediate hydrazino alcohols
5 can decompose under the reaction conditions with release of the diimide, migration of the tosyl group to the
β-carbon atom, and the formation of the β-tosyl ketones 3a-e. In the case of the p-methoxy-substituted enone 1d
this direction is preferred. Such transformation is characteristic of unsaturated hydrazones and can be realized
through a six-center cyclic transition state by concerted transfer of electrons [7]. The intermediate hydrazino
alcohols 5 and hydrazones 6 were not isolated in individual form. However, signals for the protons of the methyl
groups at 1.76 and 1.91 ppm were recorded in the NMR spectra of the reaction mixture of the enone 1a with the
tosylhydrazine after boiling for 2 h. After boiling for 5 h they disappear, and there is a simultaneous increase in
the signals for the protons of the methyl groups of the pyrazole 2a and β-tosyl ketones 3a, indicating the possible
formation of such intermediates. Compounds 3a-e may also be formed by nucleophilic addition to the enones
1a-e of p-toluenesulfinic acid, the appearance of which we detected in a separate experiment by heating
tosylhydrazine in isopropyl alcohol in the presence of acetic acid, although according to published data in
alcohols this process only becomes appreciable at temperatures above 100°C [8].
1240

TABLE 3. The 1H NMR Spectra of Compounds 2-4
Com-
pound*
Chemical shifts, δ, ppm. (J, Hz)
1
2
2а
2b
2c
2.17 (3Н, d, J = 1.0, СН3); 2.40 (3Н, s, СН3); 6.98 (1Н, d, J = 16.6, СН=);
7.29 (1Н, d, J = 16.6, СН=); 7.81 (1Н, br. s, H-5); 7.26-7.91 (9Н, m, arom.)
2.17 (3Н, d, J = 1.0, СН3); 2.30 (3Н, s, СН3); 6.90 (1Н, d, J = 16.6, СН=);
7.00-7.40 (7Н, m, arom., СН=); 7.81 (1Н, br. s, H-5); 7.88 (2H, d, J = 8.3, С6Н4)
2.11 (3Н, d, J = 1.0, СН3); 2.34 (3Н, s, СН3); 6.85 (1Н, d, J = 16.6, СН=);
7.20 (1Н, d, J = 16.6, СН=); 7.15-7.40 (6Н, m, arom.); 7.77 (1Н, br. s, H-5);
7.83 (2H, d, J = 8.3, С6Н4)
2d
2e
2.16 (3Н, d, J = 1.0, СН3); 2.39 (3Н, s, СН3); 2.81 (3Н, s, OСН3);
6.83 (1Н, d, J = 16.6, СН=); 6.87 (2Н, d, J = 8.6, С6Н4–OCH3);
7.21 (2Н, d, J = 8.5, С6Н4–CН3); 7.41 (2Н, d, J = 8.6, С6Н4–OСН3);
7.80 (1Н, br. s, H-5); 7.87 (2Н, d, J = 8.5, С6Н4–CН3)
2.07 (3H, d, J = 1.0, CH3); 2.39 (3H, s, CH3); 5.11 (2H, s, CH2);
6.94 (1H, d, J = 8.1, С6H4); 6.96 (1H, t, J = 7.6, С6H5); 7.10 (1H, d, J = 16.9,
CH=); 7.22 (1Н, m, C6H4); 7.27 (2Н, d, J = 8.3, С6H4); 7.29-7.40 (3Н, m, arom.);
7.43 (2Н, m, C6H5); 7.54 (1Н, m, C6H4); 7.61 (1Н, d, J = 16.9, СН=);
7.78 (1H, br. s, H-5); 7.86 (2Н, d, J = 8.3, С6Н4)
3а
3b
3с
3d
1.41 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.91 (1Н, d, J = 4.9, СН2–O);
3.16 (1Н, dd, J = 7.7, J = 18.2, СН2–CН); 3.22 (1Н, d, J = 4.9, СН2–O);
3.46 (1Н, dd, J = 5.9, J = 18.2, СН2–CН); 4.74 (1Н, dd, J = 5.9, J = 7.7, СН–CН2);
7.06 (2Н, d, J = 8.5, С6Н4); 7.32 (2Н, d, J = 8.5, С6Н4); 7.13-7.30 (5Н, m, arom.)
1.40 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.77 (1Н, d, J = 4.9, СН2–O); 2.79 (1Н, d,
J = 4.9, СН2–O); 3.13 (1Н, dd, J = 9.7, J = 18.2, СН2–CН); 3.44 (1Н, dd, J = 4.1,
J = 18.2, СН2–CН); 4.68 (1Н, dd, J = 4.1, J = 9.7, СН–CН2); 7.10 (2Н, d, J = 8.5,
С6Н4); 7.30 (2Н, d, J = 8.5, С6Н4); 7.15-7.30 (5Н, m, arom.)
1.41 (3Н, s, СН3); 2.40 (3Н, s, СН3); 2.91 (1Н, d, J = 4.9, СН2–O); 3.12 (1Н, dd,
J = 8.1, J = 18.1, СН2–CН); 3.20 (1Н, d, J = 4.9, СН2–O); 3.41 (1Н, dd, J = 5.6,
J = 18.1, СН2–CН); 4.68 (1Н, dd, J = 5.6, J = 8.1, СН–CН2); 7.03 (2Н, d, J = 8.6,
С6Н4); 7.36 (2Н, d, J = 8.6, С6Н4); 7.15-7.25 (5Н, m, arom.)
1.41 (3Н, s, СН3); 2.40 (3Н, s, СН3); 2.77 (1Н, d, J = 4.9, СН2–O); 2.79 (1Н, d,
J = 4.9, СН2–O); 3.05 (1Н, dd, J = 9.8, J = 18.1, СН2–CН); 3.43 (1Н, dd, J = 4.4,
J = 18.1, СН2–CН); 4.63 (1Н, dd, J = 4.4, J = 9.8, СН–CН2); 7.10 (2Н, d, J = 8.6,
С6Н4); 7.45 (2Н, d, J = 8.6, С6Н4); 7.15-7.25 (5Н, m, arom.)
1.41 (3Н, s, СН3); 2.40 (3Н, s, СН3); 2.92 (1Н, d, J = 4.9, СН2–O); 3.13 (1Н, dd,
J = 7.8, J = 18.1, СН2–CН); 3.21 (1Н, d, J = 4.9, СН2–O); 3.42 (1Н, dd, J = 5.6,
J = 18.1, СН2–CН); 4.69 (1Н, dd, J = 5.6, J = 7.8, СН–CН2); 7.0 (2Н, d, J = 8.5,
С6Н4); 7.35 (2Н, d, J = 8.5, С6Н4); 7.17-7.22 (5Н, m, arom.)
1.41 (3Н, s, СН3); 2.40 (3Н, s, СН3); 2.78 (1Н, d, J = 4.9, СН2–O); 2.80 (1Н, d,
J = 4.9, СН2–O); 3.07 (1Н, dd, J = 10.0, J = 18.1, СН2–CН); 3.43 (1Н, dd, J = 4.2,
J = 18.1, СН2–CН); 4.65 (1Н, dd, J = 4.2, J = 10.0, СН–CН2); 7.06 (2Н, d, J = 8.5,
С6Н4); 7.43 (2Н, d, J = 8.5, С6Н4); 7.18-7.23 (5Н, m, arom.)
1.41 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.91 (1Н, d, J = 4.9, СН2–); 3.13 (1Н, dd,
J = 7.7, J = 18.2, СН2–CН); 3.21 (1Н, d, J = 4.9, СН2–); 3.40 (1Н, dd, J = 5.9,
J = 18.2, СН2–CН); 3.76 (3Н, s, ОСН3); 4.68 (1Н, dd, J = 5.9, J = 7.7, СН–CН2);
6.73 (2Н, d, J = 8.6, С6Н4–OСН3); 6.98 (2Н, d, J = 8.6, С6Н4–OСН3); 7.17 (2Н, d,
J = 8.5, С6Н4); 7.34 (2Н, d, J = 8.5, С6Н4)
1.40 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.76 (1Н, d, J = 4.9, СН2–); 2.79 (1Н, d,
J = 4.9, СН2–); 3.09 (1Н, dd, J = 9.7, J = 17.9, СН2–CН); 3.38 (1Н, dd, J = 4.1,
J = 17.9, СН2–CН); 3.75 (3Н, s, ОСН3); 4.64 (1Н, dd, J = 4.1, J = 9.7, СН–CН2);
6.75 (2Н, d, J = 8.6, С6Н4–OСН3); 7.04 (2Н, d, J = 8.6, С6Н4–OСН3); 7.19 (2Н, d,
J = 8.5, С6Н4); 7.42 (2Н, d, J = 8.5, С6Н4)
3e
1.42 (3Н, s, СН3); 2.34 (3Н, s, СН3); 2.77 (1Н, d, J = 4.9, СН2–); 2.84 (1Н, d,
J = 4.9, СН2–); 3.17 (1Н, dd, J = 7.8, J = 18.3, СН2–CН); 3.47 (1Н, dd, J = 3.9,
J = 18.3, СН2–CН); 5.10 (2Н, s, O–CН2); 5.61 (1Н, dd, J = 3.9, J = 7.8, СН–CН2);
6.60-7.47 (13Н, m, arom.)
1.43 (3Н, s, СН3); 2.34 (3Н, s, СН3); 2.90 (1Н, d, J = 4.9, СН2–); 3.22 (1Н, dd,
J = 9.7, J = 18.3, СН2–CН); 3.23 (1Н, d, J = 4.9, СН2–); 3.50 (1Н, dd, J = 5.9,
J = 18.3, СН2–CН); 5.03 (2Н, s, O–CН2); 5.56 (1Н, dd, J = 5.9, J = 9.7, СН–CН2);
6.60-7.47 (13Н, m, arom.)
1241

TABLE 3 (continued)
1
2
4a
4b
1.86 (3H, d, J = 1.0, CH3); 2.36 (3H, s, CH3); 2.37 (3H, s, CH3); 3.36 (1H, dd,
J = 11.7, J = 15.4, CH2–CH); 3.59 (1H, dd, J = 3.9, J = 15.4, CH2–CH); 4.64 (1H,
dd, J = 11.7, J = 3.9, CH–CH2); 7.03-7.39 (11H, m, arom.); 7.54 (2H, d, J = 8.3,
С6Н4); 7.56 (1H, br. s, H-5)
1.90 (3H, d, J = 1.0, CH3); 2.40 (3H, s, CH3); 2.41 (3H, s, CH3); 3.32 (1Н, dd,
J = 12.0, J = 15.7, СН2–CН); 3.56 (1Н, dd, J = 3.7, J = 15.7, СН2–CН);
4.65 (1Н, dd, J = 3.7, J = 12.0, СН–CН2); 6.96 (2Н, d, J = 8.6, С6Н4);
7.00 (2Н, d, J = 8.6, С6Н4); 7.16 (2Н, d, J = 8.1, С6Н4); 7.21 (2Н, d, J = 8.3,
С6Н4); 7.44 (2Н, d, J = 8.1, С6Н4); 7.50 (2Н, d, J = 8.3, С6Н4); 7.60 (1H, br. s, H-5)
4c
1.90 (3H, d, J = 1.0, CH3); 2.40 (3H, s, CH3); 2.41 (3H, s, CH3); 3.31 (1Н, dd,
J = 12.0, J = 15.7, СН2–CН); 3.56 (1Н, dd, J = 3.7, J = 15.7, СН2–CН); 4.64 (1Н,
dd, J = 3.7, J = 12.0, СН–CН2); 6.91 (2Н, d, J = 8.6, С6Н4); 7.16 (2Н, d, J = 8.6,
С6Н4); 7.17 (2Н, d, J = 8.1, С6Н4); 7.21 (2Н, d, J = 8.3, С6Н4); 7.44 (2Н, d, J = 8.1,
С6Н4); 7.50 (2Н, d, J = 8.3, С6Н4); 7.60 (1H, br. s, H-5)
4d
4e
1.87 (3H, d, J = 0.8, CH3); 2.37 (3H, s, CH3); 2.38 (3H, s, CH3); 3.31 (1Н, dd,
J = 12.0, J = 15.3, СН2–CН); 3.55 (1Н, dd, J = 3.8, J = 15.3, СН2–CН); 3.73 (3H, s,
OCH3); 4.59 (1Н, dd, J = 3.8, J = 12.0, СН–CН2); 6.57-7.55 (12Н, m, arom.);
7.56 (1H, br. кв, J = 0.8, H-5)
1.88 (3H, d, J = 1.0, CH3); 2.33 (3H, s, CH3); 2.35 (3H, s, CH3); 3.44 (1H, dd,
J = 10.2, J = 15.4, CH2–CH); 3.63 (1H, dd, J = 3.9, J = 15.4, CH2–CH); 4.44 (1H,
d, J = 11.7, CH2–O); 4.69 (1H, d, J = 11.7, CH2–O); 5.49 (1H, dd, J = 3.9, J = 10.2,
CH–CH2); 6.54 (1H, d, J = 8.1, C6H4); 6.87 (1H, t, J = 7.6, C6H5); 7.01 (2H, d,
J = 8.3, C6H4); 7.05 (2H, d, J = 8.3, C6H4); 7.13 (1H, m, C6Н4); 7.20 (2H, m, C6H5);
7.30 (6H, m, arom.); 7.49 (2H, d, J = 8.3, C6H4); 7.57 (1H, br. s, H-5)
_______
* Compounds 3a-d were isolated as mixtures of diastereomers.
In the presence of an excess of tosylhydrazine the β-tosyl ketones that are formed then react with
participation of the epoxy ketone fragment, leading to the adducts 4a-e. This fact is confirmed by the isolation of
the pyrazole 4a when compound 3a is heated with tosylhydrazine, whereas the pyrazole 2a does not change
under such conditions. In view of the possibility that p-toluenesulfinic acid is formed during the decomposition
of tosylhydrazine an alternative path for the formation of the pyrazoles 4a-e with the addition of
p-toluenesulfinic acid at the multiple bond of the styrylpyrazoles 2a-e when they are heated together was
considered. The negative result of this experiment indicated that the precursors of the β-aryl-β-ethylpyrazoles
4a-e are the β-tosylepoxy ketones 3a-e.
Thus, the reaction of 2-cinnamoyl-2-methyloxiranes with tosylhydrazine, unlike the reaction with
phenylhydrazine, is complicated by the concurrent formation of β-tosylepoxy ketones as a result of
decomposition of the intermediate hydrazino alcohols and addition of p-toluenesulfinic acid.
EXPERIMENTAL
The chemical reagents used in the work were of pure, analytical, and chemically pure grades. The
1
solvents were prepared and purified by traditional methods [9]. The H NMR spectra were obtained on a Tesla
BS-567A spectrometer (100 MHz) and a Bruker Avance-400 spectrometer (400 MHz) in deuterochloroform
with HMDS as internal standard (δ 0.05 ppm). The mass spectra were obtained on a Shimadzu QP-5000
instrument (70-eV ionizing electrons). The IR spectra were obtained on a Specord IR-75 spectrophotometer in
1242

tablets with potassium bromide. The reaction was monitored by TLC on Silufol plates (Kieselgel 60 F254). The
eluants were 1:1-5:1 mixtures of diethyl ether and hexane, and the developer was iodine vapor or 4% potassium
permanganate solution. Silicagel L 40/100 was use to isolate the individual substances by column
chromatography. The initial unsaturated epoxy ketones 1a-e were obtained by the method in [10] by
condensation of the respective acyloxiranes and aromatic aldehydes in methanol in the presence of a 15%
methanol solution of sodium hydroxide. The physicochemical characteristics and spectral characteristics of the
synthesized compounds are given in Tables 1-3.
3-[(E)-2-Arylvinyl]-4-methyl-1-tosyl-1H-pyrazoles (2a-c) and 3-Aryl-1-(2-methyloxiran-2-yl)-3-
tosylpropan-1-ones (3a-c). A sample of the 3-aryl-1-(2-methyloxiran-2-yl)prop-2-en-1-one 1a-c (5 mmol) was
dissolved in isopropyl alcohol (20 ml), and acetic acid (0.3 ml) and tosylhydrazine were added (6.5 mmol). The
reaction mixture was boiled with a reflux condenser for 3-6 h, while the reaction was monitored by
chromatography. It was then cooled, and the pyrazole 2a-c was filtered off. The remaining part of the reaction
mixture was chromatographed on silica gel with linear gradient elution with petroleum and diethyl ethers and
then with diethyl ether and ethanol as eluants. As a result the pyrazoles 2a-c and tosyl ketones 3a-c were
isolated. Mass spectrum of styrylpyrazole 2a, m/z (Irel, %): 338 [M+] (8), 183 [M+-Ts] (100), 168 (12), 156 (38),
143 (14), 128 (28), 115 (20), 91 (45), 77 (13), 65 (31), 51 (12), 39 (18).
4-Methyl-3-[(E)-2-(4-methoxyphenyl)vinyl]-1-tosyl-1H-pyrazole (2d) and 1-(2-Methyloxiran-2-yl)-
3-(4-methoxyphenyl)-3-tosylpropan-1-one (3d). We dissolved 1-(2-methyloxiran-2-yl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (1d) (0.3 g, 1.38 mmol) in isopropyl alcohol (15 ml) and added acetic acid (0.2 ml) and
tosylhydrazine (0.28 g, 1.52 mmol). The reaction mixture was boiled with a reflux condenser for 5 h, and the
solvent was evaporated. The residue was diluted with water, neutralized with sodium carbonate solution, and
extracted with diethyl ether (3 × 5 ml). The combined fractions were dried over anhydrous sodium sulfate. After
partial evaporation of the solvent the tosyl ketone 3d (0.1 g) was filtered off. The remaining part of the reaction
mixture was submitted to chromatographic separation as described above, and the pyrazole 2d and also
compound 3d were isolated.
3-[(E)-2-(2-Benzyloxyphenyl)vinyl]-4-methyl-1-tosyl-1H-pyrazole (2e), 1-(2-Methyloxiran-2-yl)-3-
(4-methoxyphenyl)-3-tosylpropan-1-one (3e), and 3-[2-(Benzyloxyphenyl)-2-tosylethyl]-4-methyl-1-tosyl-
1H-pyrazole (4e). We dissolved 3-(4-benzyloxyphenyl)-1-(2-methyloxiran-2-yl)prop-2-en-1-one (1e) (1 g,
3.4 mmol) in isopropyl alcohol (20 ml) and added acetic acid (0.3 ml) and tosylhydrazine (0.85 g, 4.6 mmol).
The reaction mixture was boiled for 3 h, after which the solvent was partly evaporated. After cooling 0.21 g of a
mixture of pyrazoles 2e and 4e was isolated. The tosyl ketone 3e and the pyrazole 2e were isolated by
chromatography.
Boiling of the Tosylhydrazine in Isopropyl Alcohol.We dissolved tosylhydrazine (1.0 g, 5.4 mmol) in
isopropyl alcohol (20 ml) and added acetic acid (0.3 ml). The mixture was boiled with a reflux condenser for 5 h,
and the process was monitored by TLC. After 1 h the formation of p-toluenesulfinic acid was detected by
chromatography. The eluant was 1:4 diethyl ether–ethanol. According to data from the PMR spectrum, the ratio
of tosylhydrazine to p-toluenesulfinic acid after 5 h was 65:10.
3-(2-Phenyl-2-tosylethyl)-4-methyl-1-tosyl-1H-pyrazole (4a). We dissolved 1-(2-methyloxiran-2-yl)-
3-tosyl-3-phenylpropan-1-one (3a) (0.03 g, 0.09 mmol) in isopropyl alcohol (3 ml) and added acetic acid
(0.005 ml) and tosylhydrazine (0.017 g, 0.09 mmol). The mixture was boiled with a reflux condenser for 12.5 h.
The formation of the pyrazole 4a (30%) was detected by means of the PMR spectrum.
1-(2-Methyloxiran-2-yl)-3-tosyl-3-phenylpropan-1-one (3a). To a solution of 1-(2-methyloxiran-2-
yl)-3-phenylprop-2-en-1-one (1a) (0.55 g, 3 mmol) in isopropyl alcohol (15 ml) we added acetic acid (0.25 ml)
and p-toluenesulfinic acid (0.5 g, 3.2 mmol). The reaction mixture was boiled with a reflux condenser for 5 h
and cooled, and 0.41 g of the β-tosyl ketone 3a was filtered off.
1243

REFERENCES
1.
2.
3.
4.
5.
A. M. Zvonok, N. M. Kuz'menok, and L. S. Stanishevskii, Khim. Geterotsikl. Soedin., 633 (1990).
N. M. Kuz'menok and A. M. Zvonok, Khim. Geterotsikl. Soedin., 324 (1996).
A. D. Khanolkar, S. L. Palmer, and A. Makriyannis, Chem. Phys. Lipids, 108, 37 (2000).
R. G. Pertwee, Tocris Reviews, 16, 8 (2001).
M. E. Y. Francisco, H. H. Seltzman, A. F. Gilliam, R. A. Mitchell, S. L. Rider, R. G. Pertwee,
L. A. Stevenson, and B. F. Thomas, J. Med. Chem., 45, 2708 (2002).
D. Barton and W. D. Ollis, Comprehensive Organic Chemistry [Russian translation], Vol. 5, Khimiya,
Moscow (1983), 720 pp.
6.
7.
8.
9.
T. Sato and I. Homma, Bull. Chem. Soc. Jpn., 44, 1885 (1971).
R. S. Dewey and E. E. van Tamelen, J. Am. Chem. Soc., 83, 3729 (1961).
D. D. Perrin, W. L. F. Armarego, and D. R. Perrin, Purification of Laboratory Chemicals, Pergamon
Press, Oxford (1986), 568 pp.
10.
L. S. Stanishevskii, I. G. Tishchenko, and A. Ya. Guzikov, Zh. Org. Khim., 7, 73 (1971).
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