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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Zaitsev et al.
5.8 mmol) in acetonitrile (25 mL). The reaction mixture was
refluxed for 20 h, cooled to ~20 °C, and then poured into 2%
HCl (100 mL) and extracted with ethyl acetate (2×30 mL); the
organic layers were combined, washed with water to neutral pH,
and dried with Na2SO4. The solvent was removed under reduced
pressure, the residue was chromatographed on silica gel (CHCl3).
White crystalline compound 4 was obtained (0.82 g, 58%). M.p.
66—68 °С. Found (%): C, 39.69; H, 4.03; N, 23.16. C8H10N4O5.
Calculated (%): C, 39.67; H, 4.16; N, 23.13. 1Н NMR
((CD3)2SO), δ: 4.76 (t, 2 H, NCH2, J = 6.6 Hz); 3.15 (t, 2 H,
CH2CO, J = 6.6 Hz); 2.53 (s, 3 H, 4ꢀMe); 2.14 (s, 3 H, COMe).
13С NMR ((CD3)2SO), δ: 205.64 (CO); 150.66 (C(3)); 144.21
(C(5)); 114.25 (C(4)); 48.88 (NCH2); 41.04 (CH2CO); 29.76
(CH3CO); 9.65 (4ꢀMe). IR, ν/cm–1: 1720 (CO); 1520, 1336
(NO2). MS, m/z: 242 [M]+.
7b, i.e., hydrolysis of the SCH2CONHPh group accomꢀ
panies removal of the CH2OMe group.
Thus, one can state that the methoxymethyl group can
be successfully used as a protecting group in the synthesis
of some Nꢀunsubstituted 5ꢀRꢀ4ꢀmethylꢀ3ꢀnitropyrazoles.
Experimental
1
H and 13C NMR spectra were recorded on Bruker ACꢀ300
(300.13 MHz) and Bruker DRXꢀ500 (125 MHz) spectrometers,
respectively, at 295 K (unless other temperature is indicated).
Chemical shifts for 1H and 13C are given relative to Me4Si.
IR spectra were recorded on a Specord Mꢀ80 in KBr pellets.
Mass spectra were obtained on a Kratos MSꢀ30 spectrometer
(direct inlet, electron impact, ionization energy 70 eV). The
course of the reactions and purity of compounds were monitored
by TLC on Silufol UVꢀ254 plates, CHCl3—Me2CO (10 : 1).
Elemental analysis was carried out on a Perkin—Elmer Series II
2400 apparatus.
2ꢀ[(3ꢀOxobutyl)thio]acetanilide (5). Potassium carbonate
(0.138 g, 1.0 mmol) was added to a solution of thioglycolanilide
(0.167 g, 1.0 mmol) in acetonitrile (20 mL), the mixture was
stirred for 10 min, then compound 4 (0.242 g, 1.0 mmol) was
added. The reaction mixture was refluxed for 4 h (TLC), cooled
to ~20 °C, poured into water (80 mL) acidified with HCl pH 2—3,
extracted with ethyl acetate (2×20 mL), the organic layers were
combined, washed with water to neutral pH, and dried with
Na2SO4. The solvent was removed under reduced pressure, the
residue was chromatographed on silica gel (CHCl3—Me2CO
(20 : 1)). Compound 5 was obtained in the form of lightꢀyellow
oil (0.178 g, 75%); the yield of compound 1 was (white crystals)
0.077 g (65%). Compound 5. Found (%): C, 60.58; H, 6.30;
N, 5.59; S, 13.42. C12H15NO2S. Calculated (%): C, 60.73; H, 6.37;
N, 5.90; S, 13.51. 1Н NMR ((CD3)2SO), δ: 10.00 (s, 1 H, NH);
7.57 (d, 2 H, oꢀH, Ph, J = 8.1 Hz); 7.30 (t, 2 H, mꢀH, Ph,
J = 8.1 Hz); 7.05 (t, 1 H, pꢀH, Ph, J = 7.3 Hz); 3.30 (s, 2 H,
SCH2СО); 2.78 (br.s, 4 H, COCH2CH2); 2.09 (s, 3 H, Me).
1Н NMR (CDCl3), δ: 8.97 (s, 1 H, NH); 7.62 (d, 2 H, oꢀH, Ph,
J = 8.1 Hz); 7.33 (t, 2 H, mꢀH, Ph, J = 7.7 Hz); 7.12 (t, 1 H, pꢀH,
Ph, J = 7.3 Hz); 3.38 (s, 2 H, SCH2СО); 2.81 (m, 4 H,
COCH2CH2); 2.17 (s, 3 H, Me). 13С NMR (CDCl3), δ: 206.97
(COMe); 167.64 (CONH); 137.39 (ipsoꢀC, Ph); 129.04 (mꢀC,
Ph); 124.85 (pꢀC, Ph); 120.16 (oꢀC, Ph); 42.64 (COCH2CH2);
4ꢀMethylpyrazole,7 methoxymethyl chloride,8 and thioglyꢀ
colanilide9 were prepared as described.
4ꢀMethylꢀ3,5ꢀdinitropyrazole (1). Oleum (41%, d = 1.963 g
cm–3, 12.0 mL) was added to 92.5% sulfuric acid (30.0 mL,
d = 1.826 g cm–3) at a temperature of 30—40 °C; at this temperꢀ
ature, 4ꢀmethylpyrazole (2) (2.00 mL, 24.2 mmol) and then fumꢀ
ing nitric acid (d = 1.5 g cm–3) (3.1 mL, 73.8 mmol) were added
dropwise. The reaction mixture was heated at 100—105 °C for
2 h, cooled to ~20 °C, poured onto ~300 g of crushed ice; air was
passed for 3ꢀ4 h through the suspension thus obtained until total
removal of nitrogen oxides. The precipitate was filtered off, washed
with water and dried in air. White crystalline product 1 (2.22 g)
was obtained. The aqueous layer was extracted with ethyl aceꢀ
tate (2×40 mL), the organic layers were combined, washed with
water to neutral pH, and dried with Na2SO4. The solvent was
removed under reduced pressure, the residue was crystallized
from ethanol. The target product (0.92 g) was obtained additionꢀ
ally. The total yield of compound 1 is 3.14 g (75%), m.p.
211—213 °С. Found (%): C, 27.84; H, 2.18; N, 32.26. C4H4N4O4.
Calculated (%): C, 27.92; H, 2.34; N, 32.56. 1Н NMR ((CD3)2SO),
δ: 2.57 (s, Me). 13C NMR ((CD3)2SO), δ: 149.14 (C(3)); 112.55
(C(4)); 9.13 (Me). IR, ν/cm–1: 3164 (NH); 1548, 1336 (NO2).
MS, m/z: 172 [M]+.
37.15 (SCH2CO); 30.10 (Me); 26.40 (CH2CH2S). IR, ν/cm–1
:
3308 (NH); 1716 (COMe); 1668 (CONH). MS, m/z: 237 [M]+.
1ꢀMethoxymethylꢀ4ꢀmethylꢀ5(3)ꢀ[(4ꢀmethylphenyl)thio]ꢀ
3(5)ꢀnitropyrazole (6a). Potash (0.75 g, 5.4 mmol) was added to
a solution of dinitropyrazole 3 (1.00 g, 5.8 mmol) and pꢀtoluꢀ
enethiol (0.80 g, 6.4 mmol) in acetonitrile (40 mL). The reaction
mixture was refluxed for 15 h in a flow of argon (TLC), cooled to
~20 °C, poured into water (150 mL), extracted with ethyl acetate
(2×30 mL), the organic layers were combined and dried with
Na2SO4. The solvent was removed under reduced pressure, the
residue was chromatographed on silica gel (CCl4, then CHCl3).
Solid yellow compound 6a was obtained (0.79 g, 58%). M.p.
45—47 °С. Found (%): C, 53.62; H, 5.15; N, 13.24; S, 10.16.
C13H15N3O3S. Calculated (%): C, 53.23; H, 5.15; N, 14.32;
S, 10.93. 1Н NMR ((CD3)2SO), δ: 7.16 (d, 2 H, оꢀH, C6H4Meꢀp,
J = 8.1 Hz); 7.12 (d, 2 H, mꢀH, C6H4Meꢀp, J = 8.1 Hz); 5.59
(s, 2 H, CH2); 3.25 (s, 3 H, OMe); 2.27 (s, 3 H, Me), 2.26
(s, 3 H, Me). 13С NMR ((CD3)2SO), δ: 153.41 (C(3)); 136.93
(C(4´)); 134.00 (C(5)); 130.15 (C(2´)); 129.28 (C(1´));
128.01 (C(3´)); 120.36 (C(4)); 80.45 (CH2); 56.58 (OMe); 20.33
(CH3C6H4); 9.79 (4ꢀMe). IR, ν/cm–1: 1560, 1516, 1348 (NO2).
MS, m/z: 293 [M]+.
1ꢀMethoxymethylꢀ4ꢀmethylꢀ3,5ꢀdinitropyrazole (3). Potasꢀ
sium carbonate (4.5 g, 32.6 mmol) and methoxymethyl chloride
(2.4 mL, 31.6 mmol) were added to a solution of dinitropyrazole
1 (5.0 g, 29.1 mmol) in acetonitrile (100 mL). The reaction
mixture was stirred for 1 h (TLC) and then poured into water
(300 mL), extracted with ethyl acetate (2×60 mL), dried with
Na2SO4, and the solvent was removed under reduced pressure.
White crystalline product 3 was obtained (6.1 g, 97%). M.p.
78—80 °С. Found (%): C, 33.38; H, 3.51; N, 25.94. C4H8N4O5.
Calculated (%): C, 33.34; H, 3.73; N, 25.92. 1Н NMR
((CD3)2SO), δ: 5.83 (s, 2 H, CH2); 3.34 (s, 3 H, OMe); 2.57 (s, 3 H,
1
CMe). Н NMR (CDCl3), δ: 5.90 (s, 2 H, CH2); 3.41 (s, 3 H,
OMe); 2.70 (s, 3 H, CMe). 13С NMR ((CD3)2SO), δ: 151.51
(C(3)); 143.63 (C(5)); 115.34 (C(4)); 84.18 (CH2); 57.14 (OMe);
9.60 (Me). IR, ν/cm–1: 1528, 1336 (NO2). MS, m/z: 216 [M]+.
4ꢀ(4ꢀMethylꢀ3,5ꢀdinitropyrazolꢀ1ꢀyl)butanꢀ2ꢀone (4). Methꢀ
yl vinyl ketone (0.50 mL, 6.2 mmol) and potash (0.16 g,
1.2 mmol) were added to a solution of dinitropyrazole 1 (1.00 g,