4402
A. de la Hoz et al. / Tetrahedron 57 42001) 4397±4403
a saturated solution of sodium carbonate. Evaporation of
solvent yielded the products 19a±19c.
7t, J2.2 Hz, 1H, Ar-H2), 7.2 7t, J7.8 Hz, 1H, Ar-H5), 7.69
7d, J1.7 Hz, 1H, pyrazole-H3), 7.88 7d, J2.4 Hz, 1H,
pyrazole-H5). 13C NMR 7CDCl3) d 106.01 7Ar-C2), 107.28
7pyrazole-C4), 108.91 7Ar-C6), 113.04 7Ar-C4), 126.75
7pyrazole-C5), 130.14 7Ar-C5), 140.74 7pyrazole-C3),
141.15 7Ar-C1), 147.54 7Ar-C3).
4.1.1. 1-/2-Nitrophenyl)pyrazole /19a). o-Nitrophenyl-
hydrazine 77.65 g, 50 mmol) in ethanol plus some drops of
sulfuric acid until acid pH. The mixture was re¯uxed 4 h.
Yield 7.4 g 777%), mp 87±888C 7ethanol). Lit. mp 88±
898C;36 IR 7KBr) 1536, 1523, 1394, 1366 cm21 7nNO2 and
nAr). 1H NMR 7CDCl3) d 6.51 7dd, J2.5 Hz and J1.8 Hz,
1H, pyrazole-H4), 7.48±7.71 7m, 3H, Ar-H), 7.72 7d,
J2.5 Hz, 1H, pyrazole-H5), 7.75 7d, J1.7 Hz, 1H, pyra-
zole-H3), 7.88 7dd, J8.1 Hz and J1.5 Hz, 1H, Ar-H3).
4.2.3. 1-/4-Aminophenyl)pyrazole /20c). Yield 3.4 g
771%), mp 47±488C. Lit. mp 42±448C.38 IR 7KBr) 3297,
1
3196, 1525 cm21 7nNH2 and nAr). H NMR 7CDCl3) d 3.72
7s, 2H, NH2), 6.41 7t, J2.1 Hz, 1H, pyrazole-H4), 7.67 7d,
J1.7 Hz, 1H, pyrazole-H3), 7.78 7d, J2.3 Hz, 1H,
pyrazole-H5), 6.75 7AA0BB0 system, J8.5 Hz, 4H, Ar-H3
and Ar-H5), 7.45 7AA0BB0 system, J8.5 Hz, 4H, Ar-H2
and Ar-H6). 13C NMR 7CDCl3) d 106.76 7pyrazole-C4),
115.43 7Ar-C3 and C5), 121.07 7Ar-C2 and C6), 126.63
7pyrazole-C5), 140.20 7pyrazole-C3), 145.13 7Ar-C4).
4.1.2. 1-/3-Nitrophenyl)pyrazole /19b). From m-nitro-
phenylhydrazine. The mixture was re¯uxed 1 h. Yield 8 g
784%), mp 96±988C 7ethanol). Lit. mp 94±958C;36 IR 7KBr)
1
1532, 1392, 1349, 1316 cm21 7nNO2 and nAr). H NMR
7CDCl3) d 6.55 7t, J2.16 Hz, 1H, pyrazole-H4), 7.65 7t,
J8.1 Hz, 1H, Ar-H5), 7.78 7d, J1.6 Hz, 1H, pyrazole-
H3), 8.03 7d, J2.6 Hz, 1H, pyrazole-H5), 8.12 7td, J
8.0 Hz and J2.1 Hz, 2H, Ar-H4 and H6), 8.57 7t, J
2.2 Hz, 1H, Ar-H2).
4.3. Synthesis of cyanopyrazoles
4.3.1. 1-Phenyl-3-cyanopyrazole /14). Prepared according
to the procedure described in Ref. 28. Yield 713.1 g, 81%),
mp 60±628C. IR 7KBr) 2241, 1600, 1508 cm21 7nCN and
nAr).
4.1.3. 1-/4-Nitrophenyl)pyrazole /19c). From p-nitro-
phenylhydrazine The mixture was re¯uxed 1 h. Yield 8 g
784%), mp 176±1778C 7ethanol). Lit. mp 169±1708C;29 IR
1
7KBr) 1596, 1516, 1392, 1334 cm21 7nNO2 and nAr). H
4.3.2. 1-Phenyl-4-cyanopyrazole /18). Prepared according
to the procedure described in Ref. 29. Yield 71.1 g, 42%),
mp 97±998C. IR 7KBr) 2240, 1551, 1501 cm21 7nCN and
nAr).
NMR 7CDCl3) d 6.57 7t, J2.0 Hz, 1H, pyrazole-H4),
7.80 7d, J1.5 Hz, 1H, pyrazole-H3), 8,04 7d, J2.6 Hz,
1H, pyrazole-H5), 7.90 7AA0BB0 system, J9.2 Hz, 2H,
Ar-H2 and Ar-H6), 8.35 7AA0BB0 system, J9.2 Hz, 2H,
Ar-H3 and Ar-H5).
4.4. General procedure for the syntheses of 1-/cyano-
phenyl)pyrazoles
4.2. General procedure for the reduction of nitro-
pyrazoles to aminopyrazoles.
The amine 70.75 g, 5 mmol) was dissolved in water 77 mL)
containing hydrochloric acid 71.56 g, 15 mmol), and the
solution was cooled in ice. The temperature was maintained
at 0±58C and a saturated aqueous solution of sodium nitrite
70.41 g, 6 mmol) was added portionwise, after allowing
15 min. for reaction, until the mixture show an excess of
nitrous acid on testing with a starch-iodide paper. The solu-
tion of the diazonium salt was neutralized with sodium
carbonate maintaining a constant stirring and was added
to an aqueous solution 725 mL) of copper 7I) cyanide
70.45 g, 5 mmol) potassium cyanide 70.97 g, 15 mmol) in
excess and heated at 808C. Then the mixture was heated
at 608C during 20 min with constant stirring. The solution
was ®ltered and the ®ltrate was extracted with diethyl ether
73£25 mL). The combined extracts were dried with anhy-
drous magnesium sulfate. Evaporation of the solvent
yielded the cyanoderivatives.
Prepared following a procedure similar to that described in
Ref. 30. Palladium-carbon catalyst 710%) was added
portionwise during 5±10 min to a hot solution of the appro-
priate nitropyrazole 75.6 g, 30 mmol) in ethanol 750 mL)
containing hydrazine hydrate 77.5 mL, 150 mmol). The
mixture was heated under re¯ux for 1 h. The hot solution
was ®ltered through a Whatman paper to remove Pd, the
solution was ®ltered through silica gel 710 g) and the solvent
was evaporated. The amino derivatives 20a±20c were used
without further puri®cation.
4.2.1. 1-/2-Aminophenyl)pyrazole /20a). Yield 4.4 g
793%), bp 1408C 7ball-to-ball)/0.5 mmHg. Lit. mp: 498C.37
1
IR 7KBr) 3450, 3346, 1620 cm21 7nNH2 and nAr). H NMR
7CDCl3) d 4.62 7s, 2H, NH2), 6.44 7t, J2.4 Hz, 1H, pyra-
zole-H4), 6.71±6.86 7m, 2H, Ar-H3 and H5), 7.1±7.2 7m, 2H,
Ar-H4 and H6), 7.71 7d, J2.4 Hz, 1H, pyrazole-H5), 7.74
7d, J1.5 Hz, 1H, pyrazole-H3). 13C NMR 7CDCl3) d
106.35 7pyrazole-C4), 117.24 7Ar-C3), 118.02 7Ar-C5),
126.47 7Ar-C1), 124.11 7Ar-C6), 128.46 7Ar-C4), 129.83
7pyrazole-C5), 140.48 7pyrazole-C3), 141.03 7Ar-C2).
4.4.1. 1-/2-Cyanophenyl)pyrazole /21a). The product was
puri®ed by distillation under reduced pressure using a
Kugelrohr apparatus. Yield 70.53 g, 63%), bp 1258C 7oven
temperature)/0.5 mmHg. IR 7neat) 2227, 1600, 1522 cm21
7nCN and nAr). Anal. Calcd for C10H7N3: C, 70.99; H, 4.17;
N, 24.83. Found: C, 71.07; H, 4.28; N, 24.81.
4.2.2. 1-/3-Aminophenyl)pyrazole /20b). Yield 3.2 g
768%), bp 1508C 7ball-to-ball)/0.5 mmHg. IR 7KBr) 3346,
4.4.2. 1-/3-Cyanophenyl)pyrazole /21b). The product was
puri®ed by column chromatography on silica gel 7hexane/
ethyl acetate 8:2). Yield 70.54 g, 64%), mp 53±558C. IR
7KBr) 2228, 1586, 1522 cm21 7nCN and nAr). Anal. Calcd
1
3221, 1608 cm21 7nNH2 and nAr). H NMR 7CDCl3) d 3.82
7s, 2H, NH2), 6.43 7t, J2.4 Hz, 1H, pyrazole-H4), 6.59 7dm,
J8.0 Hz, 1H, Ar-H4), 7.0 7dm, J8.0 Hz, 1H, Ar-H6), 7.09