Reactivity of nitro groups in a pyrazole ring
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2083
N, 23.06. C9H10N4O5. Calculated (%): C, 51.83; H, 3.68;
N, 23.25. 1H NMR ((CD3)2SO), δ: 10.33 (s, 1 H, NH); 7.55 (d,
2 H, oꢀPh, J = 10 Hz); 7.32 (t, 2 H, mꢀPh, J = 7.5 Hz); 7.09 (t,
1 H, pꢀPh, J = 7.5 Hz); 5.28 (s, 2 H, CH2); 3.82 (s, 3 H, Me).
13C NMR ((CD3)2SO), δ: 164.11 (CONH); 156.72 (C(5));
150.92 (C(3)); 138.02 (ipsoꢀPh); 128.86 (mꢀPh); 123.98 (pꢀPh);
119.67 (oꢀPh); 110.34 (CN); 72.46 (C(4)); 70.66 (OCH2); 35.84
(Me). IR, ν/cm–1: 3332 (NH); 3304 (NH); 2244 (C≡N); 1716
(C=O); 1524 (NO2); 1344 (NO2). MS, m/z: 301 [M]+.
5ꢀAnilinoꢀ1ꢀmethylꢀ3ꢀnitropyrazoleꢀ4ꢀcarbonitrile (11). Poꢀ
tassium carbonate (0.025 g, 0.18 mmol) was added to a solution
of product 10 (0.048 g, 0.16 mmol) in acetonitrile (10 mL) and
the mixture was refluxed for 4 h, cooled, poured into water
(100 mL), acidified with dilute HCl to рH 5—6, extracted with
ethyl acetate (2×20 mL), and washed with brine. The solvent
was removed in vacuo to give 0.035 g (90%) of product 11,
m.p. 235—236 °C. Found (%): C, 54.49; H, 4.01; N, 28.54.
C11H9N5O2. Calculated (%): C, 54.32; H, 3.73; N, 28.79.
1H NMR ((CD3)2SO), δ: 9.25 (s, 1 H, NH); 7.32 (t, 2 H, mꢀPh,
J = 7.5 Hz); 7.05 (m, 3 H, oꢀPh + pꢀPh); 3.80 (s, 3 H, Me).
13C NMR ((CD3)2SO), δ: 152.01 (C(3)); 148.98 (C(5)); 139.66
(ipsoꢀPh); 129.20 (mꢀPh); 123.01 (pꢀPh); 118.81 (oꢀPh); 110.63
(CN); 76.12 (C(4)); 37.09 (Me). IR, ν/cm–1: NH (3364); 2232
(C≡N); 1536 (NO2); 1348 (NO2). MS, m/z: 243 [M]+.
5ꢀAzidoꢀ1ꢀmethylꢀ3ꢀnitropyrazoleꢀ4ꢀcarbonitrile (12). Soꢀ
dium azide (0.120 g, 1.8 mmol) was added to a solution of
nitrile 2 (0.336 g, 1.7 mmol) in acetonitrile (35 mL), the mixture
was refluxed for 10 min and cooled, and water (150 mL) was
added. The aqueous solution together with the precipitate was
extracted with ethyl acetate (2×35 mL), the extract was dried
with Na2SO4, and the solvent was removed in vacuo to give
0.223 g of product 12 (68%), m.p. 131—133 °C. Found (%):
C, 31.52; H, 1.55; N, 49.79. C5H3N7O2. Calculated (%):
C, 31.10; H, 1.57; N, 50.77. 1H NMR ((CD3)2SO), δ: 3.75
(s, Me). 13C NMR ((CD3)2SO, δ: 151.69 (C(3)); 143.90 (C(5));
109.42 (CN); 79.65 (C(4)); 36.80 (Me). IR, ν/cm–1: 2244 (C≡N);
2148 (N3); 1512 (NO2); 1352 (NO2). MS, m/z: 193 [M]+.
5ꢀAminoꢀ1ꢀmethylꢀ3ꢀnitropyrazoleꢀ4ꢀcarbonitrile (13).
NaI•2H2O (1.013 g, 5.5 mmol) and then FeCl3•6H2O (0.246 g,
0.9 mmol) were added to a solution of azide 12 (0.117 g,
0.6 mmol) in acetonitrile (20 mL), the mixture was stirred for
15 min, and chloroform (50 mL) was added. The solution was
washed with dilute solution of Na2S2O3 and brine and dried with
Na2SO4, and the solvent was removed in vacuo to give 0.066 g
(65%) of product 13, m.p. 218—220 °C. Found (%): C, 35.82;
H, 3.19; N, 42.15. C5H5N5O2. Calculated (%): C, 35.93; H, 3.02;
N, 41.90. 1H NMR ((CD3)2SO), δ: 7.29 (s, NH2); 3.65 (s, Me).
13C NMR ((CD3)2SO, δ: 154.15 (C(5)); 151.89 (C(3)); 112.42
(CN); 68.74 (C(4)); 36.40 (Me). IR, ν/cm–1: 3432 (NH2); 3344
(NH2); 3256 (NH2); 3216 (NH2); 2236 (C≡N); 1524 (NO2);
1348 (NO2). MS, m/z: 167 [M]+.
N, 19.17; S, 10.97. 1H NMR ((CD3)2SO), δ: 7.91 (s, 1 H, NH2);
7.82 (s, 1 H, NH2); 7.34 (m, 3 H, Ph); 7.17 (m, 2 H, Ph); 4.17
(s, 2 H, CH2); 3.40 (s, 3 H, Me). 13C NMR ((CD3)2SO), δ:
162.25 (CONH2); 149.92 (C(3)); 137.23 (ipsoꢀPh); 135.14
C((5)); 128.83, 128.71 (oꢀPh + mꢀPh); 127.71 (pꢀPh); 120.91
(C(4)); 40.47 (Me); 37.28 (Me). IR, ν/cm–1: 3400 (NH2);
1688 (C=O); 1672 (C=O); 1528 (NO2); 1364 (NO2). MS,
m/z: 292 [M]+.
Methyl (4ꢀcarbamoylꢀ1ꢀmethylꢀ3ꢀnitropyrazolꢀ5ꢀyl)thioꢀ
acetate (15). A solution of K2CO3 (0.330 g, 2.4 mmol) in water
(1 mL) was added with stirring to a solution of amide 6 (0.300 g,
1.4 mmol) in DMF (5 mL). Then a solution of methyl thioꢀ
glycolate (0.15 g, 1.4 mmol) in DMF (2 mL) was added dropwise.
The reaction mixture was stirred for 3 h, kept for 16 h, and
poured in ice. The precipitate was filtered off, washed with
several portions of ice water, and recrystallized from water to
give 0.210 g (55%) of product 15, m.p. 133—135 °C (from waꢀ
ter). Found (%): C, 34.89; H, 3.94; N, 20.09; S, 11.47.
C8H10N4O5S. Calculated (%): C, 35.04; H, 3.68; N, 20.43;
1
S, 11.69. H NMR ((CD3)2SO), δ: 7.87 (s, 1 H, NH2); 7.64 (s,
1 H, NH2); 4.04 (s, 3 H, NMe); 3.94 (s, 2 H, CH2); 3.63 (s, 3 H,
OMe). 13C NMR ((CD3)2SO), δ: 169.09 (COOMe); 161.85
(CONH2); 150.01 (C(3)); 134.82 (C(5)); 120.19 (C(4));
52.44 (OMe); 38.08 (NMe); 37.16 (CH2). IR, ν/cm–1: 3396
(NH2); 3308 (NH2); 3208 (NH2); 1704 (C=O, COOCH3); 1668
(C=O, CONH2); 1532 (NO2); 1328 (NO2). MS, m/z: 243
[M – OCH3]+.
5ꢀ[(2ꢀAminoꢀ2ꢀoxoethyl)thio]ꢀ1ꢀmethylꢀ3ꢀnitropyrazoleꢀ4ꢀ
carboxamide (16). Aqueous ammonia (20 mL) was added to
product 15 (0.500 g, 1.8 mmol). The resulting solution was
stirred for 4 h and kept for 16 h. The precipitate was filtered off
and the solvent was removed in vacuo. The portions of the prodꢀ
uct were combined and recrystallized from water to give 0.383 g
(81%) of product 16, m.p. 202—204 °C. Found (%): C, 32.15;
H, 3.73; N, 27.09; S, 12.21. C7H9N5O4S. Calculated (%):
C, 32.43; H, 3.50; N, 27.01; S, 12.37. 1H NMR ((CD3)2SO), δ:
7.93 (s, 1 H, NH2); 7.70 (s, 1 H, NH2); 7.53 (s, 1 H, NH2); 7.15
(s, 1 H, NH2); 4.03 (s, 3 H, NMe); 3.62 (s, 2 H, CH2). 13C NMR
((CD3)2SO), δ: 169.39 (CH2CONH2); 161.97 (CONH2); 150.24
(C(3)); 135.45 (C(5)); 120.04 (C(4)); 39.03 (CH2); 38.21 (Me).
IR, ν/cm–1: 3516 (NH2); 3400 br (NH2); 3388 br (NH2); 3200
(NH2); 1696 (C=O); 1672 (C=O); 1556 (NO2); 1332 (NO2).
MS, m/z: 243 [M – NH2]+.
2ꢀ[(1,4ꢀDimethylꢀ3ꢀnitropyrazolꢀ5ꢀyl)thio]ꢀNꢀphenylacetꢀ
amide (17). Thioglycolic acid Nꢀphenylamide (0.460 g,
2.8 mmol) and potassium carbonate (0.390 g, 2.8 mmol) were
added to a solution of 1,4ꢀdimethylꢀ3,5ꢀdinitropyrazole (1)
(0.500 g, 2.7 mmol) in acetonitrile (30 mL) (or Nꢀmethylꢀ
pyrrolidone) and the mixture was stirred at reflux (or heated at
100 °C) for 70 h (or 5 h). The mixture was cooled, poured in
water, and acidified with HCl to рH 2—3. The precipitate was
filtered off, washed with several portions of water, dried, and
recrystallized from toluene to give 0.230 g (28%) (0.340 g (41%))
of product 17, m.p. 172—175 °C (from toluene). Found (%):
C, 50.83; H, 4.46; N, 17.97; S, 10.24. C13H14N4O3S. Calcuꢀ
lated (%): C, 50.97; H, 4.61; N, 18.29; S, 10.47. 1H NMR
((CD3)2SO), δ: 9.99 (s, 1 H, NH); 7.46 (d, 2 H, oꢀPh, J =
7.5 Hz); 7.29 (t, 2 H, mꢀPh, J = 7.5 Hz); 7.05 (t, 1 H, pꢀPh, J =
7.5 Hz); 3.99 (s, 3 H, NMe); 3.56 (s, 2 H, CH2); 2.27 (s,
3 H, CMe). 13C NMR ((CD3)2SO), δ: 166.11 (CONH);
151.92 (C(3)); 138.54 (ipsoꢀPh); 134.31 (C(5)); 128.76 (mꢀPh);
5ꢀBenzylthioꢀ1ꢀmethylꢀ3ꢀnitropyrazoleꢀ4ꢀcarboxamide (14).
A solution of K2CO3 (0.580 g, 4.2 mmol) in water (1 mL) was
added with stirring to a solution of amide 6 (0.500 g, 2.3 mmol)
in DMF (7 mL), and then a solution of benzylmercaptan
(0.280 g, 2.3 mmol) in DMF (3 mL) was added dropwise. The
reaction mixture was stirred for 3 h, kept for 16 h, and poured
in ice. The precipitate was filtered off, washed with several porꢀ
tions of ice water, and dried to give 0.665 g (98%) of product 14,
m.p. 194—197 °C. Found (%): C, 49.20; H, 4.44; N, 18.95;
S, 11.00. C12H12N4O3S. Calculated (%): C, 49.31; H, 4.14;