7036
H.A. Ioannidou, P.A. Koutentis / Tetrahedron 65 (2009) 7023–7037
until no starting material remained (TLC). The reaction mixture was
then allowed to cool to ca. 20 ꢀC, poured onto crushed ice (50 g) and
extracted with EtOAc (3ꢁ50 mL). The organic extracts were com-
bined, dried and adsorbed onto silica. Chromatography (hexane/
EtOAc, 1:1) gave the title compound 70 (9.4 mg, 20%, based on re-
covered starting material) as colourless needles, mp 200–202 ꢀC
(lit.,95 208 ꢀC) (from EtOH); Rf (hexane/EtOAc, 1: 1) 0.18; nmax/cmꢂ1
3229w, 3211w, 3192w, 3055w, 2955w, 2924w, 2853w, 1730w,
1607m, 1587w, 1495m, 1458m, 1439m, 1364w, 1315w, 1294w,
1287w, 1221w, 1177m, 1074m, 1026m, 953s, 914m, 765s; dH
(300 MHz; DMSO-d6) 12.78 (1H, s, NH), 7.76–7.32 (10H, m, Ph CH),
4.0 (2H, s, NH2); m/z (EI) 235 (Mþ, 100%), 220 (8), 132 (17), 117 (6),
104 (81), 77 (50), 51 (19), identical to an authentic sample.
1533m, 1499m, 1479w, 1448w, 1428w, 1396w, 1314w, 1285w,
1248w, 1153w, 1078w, 1030w, 1002w, 931w, 896w, 854w, 779m,
771m, 741w, 715w, 700s; dH (300 MHz; CDCl3) 7.52–7.43 (5H, m, Ph
CH), 4.07 (2H, s, NH2), 3.68 (3H, s, CH3); dC (75 MHz; CDCl3) 155.9,
148.0, 130.1 (Ph CH), 129.1 (Ph CH), 128.8 (Ph CH), 126.9 (Ph C),
114.35 (C^N), 79.1 (CC^N), 37.2 (CH3); dC (75 MHz; DEPT-135,
CDCl3) 130.1 (Ph CH), 129.1 (Ph CH), 128.8 (Ph CH); m/z (EI) 198 (Mþ,
100%), 183 (1), 170 (5), 155 (9), 143 (2), 128 (17), 115 (2), 101 (5), 88
(2), 77 (C6Hþ5 , 15), 63 (3), 51 (9).
Acknowledgements
The authors thank the Cyprus Research Promotion Foundation
(Grant No. DRASI/TEXNO/1104/04) and the following organisations
in Cyprus for generous donations of chemicals and glassware: the
State General Laboratory, the Agricultural Research Institute and
the Ministry of Agriculture. Furthermore we thank the A.G. Leventis
Foundation for helping to establish the NMR facility in the Uni-
versity of Cyprus.
4.44. 5,50-Diphenyl-1H,10H-3,30-bipyrazole-4,40-dicarbo-
nitrile 79
A mixture of 5,50-diphenyl-3,30-biisothiazole-4,40-dicarbonitrile
78 (50 mg, 0.14 mmol) and anhydrous hydrazine (2 mL) was stirred
at ca. 110 ꢀC until no starting material remained (TLC). The reaction
mixture was then allowed to cool to ca. 20 ꢀC, poured onto crushed
ice (50 g) and extracted with EtOAc (3ꢁ50 mL). The organic extracts
were combined, dried and adsorbed onto silica. Chromatography
(hexane/EtOAc, 7:3) gave the title compound 79 (29.5 mg, 65%) as
a pale yellow powder, mp >300 ꢀC (from EtOH); Rf (hexane/EtOAc,
References and notes
1. Mulhall, J. Br. J. Urol. 1997, 79, 363.
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04, p 167.
9. Elguero, J. (eds. in Chief: Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.). In
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Academic: New York, NY, 1976; p 55.
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18. Claisen, L. Chem. Ber. 1909, 42, 59.
7:3) 0.18; lmax (t-BuOMe)/nm 206 (log
3 4.43), 241 (4.32), 263
(4.32); nmax/cmꢂ1 3191m, 3119w, 3026w (Ph CH), 2952w, 2924w,
2237s (C^N), 1636w, 1559w, 1491w, 1475m, 1398w, 1368w, 1300w,
1279w, 1076m, 1039m, 1015m, 956s, 914w, 799m, 765m, 707m; dH
(300 MHz; DMSO-d6) 7.92–7.90 (4H, m, Ph CH), 7.66–7.59 (6H, m,
Ph CH); dC (75 MHz; DMSO) 149.55, 146.5, 131.4 (Ph CH), 130.3 (Ph
CH), 127.6 (Ph CH), 127.3 (Ph C), 115.5 (C^N), 87.1 (CC^N); m/z (EI)
336 (Mþ, 60%), 307 (4), 280 (6), 251 (4),194 (3),177 (8),149 (18),127
(9), 104 (10), 89 (6), 77 (C6Hþ5 , 36), 64 (9), 57 (11) [Found: Mþ,
336.1134. C20H12N6 requires M, 336.1123].
4.45. Reaction of 3-chloro-5-phenylisothiazole 1 with
methylhydrazine
A
mixture of 3-chloro-5-phenylisothiazole-4-carbonitrile 1
(50 mg, 0.23 mmol) and methylhydrazine (1 mL) was stirred at ca.
20 ꢀC until no starting material remained (TLC). The reaction mix-
ture was then poured onto crushed ice (50 g) and extracted with
EtOAc (3ꢁ50 mL). The organic layer was separated, dried and
adsorbed onto silica. Chromatography (hexane/EtOAc, 1:1) gave 3-
(1-methylhydrazinyl)-5-phenylisothiazole-4-carbonitrile 83 (22 mg,
42%) as yellow needles, mp 129.5–131 ꢀC (from cyclohexane); Rf
(hexane/EtOAc, 1:1) 0.83; [Found C, 57.4; H, 4.2; N, 24.3. C11H10N4S
19. Scho¨ttle, J. Chem. Ber. 1912, 45, 2340.
20. Cusmano, S. Gazz. Chim. Ital. 1939, 69, 594.
21. Cusmano, S. Gazz. Chim. Ital. 1940, 70, 86.
22. Cusmano, S. Gazz. Chim. Ital. 1940, 70, 227.
23. Cusmano, S. Gazz. Chim. Ital. 1940, 70, 235.
24. Cusmano, S. Gazz. Chim. Ital. 1940, 70, 240.
25. Bell, F. J. Chem. Soc. 1941, 285.
26. Musante, C. Gazz. Chim. Ital. 1942, 72, 537.
requires C, 57.4; H, 4.4; N, 24.3%]; lmax (DCM)/nm 275 (log 3 2.88),
332 (2.19); nmax/cmꢂ1 3324w (NH), 3219w, 3061w (Ph CH), 2975w,
2940w, 2222m (C^N), 1629m, 1536s, 1502m, 1457w, 1446w,
1430w, 1404m, 1386w, 1337w, 1272m, 1249w, 1195w, 1180w,
1120m, 1080w, 1041m, 1030m, 1001w, 968w, 933m, 915w, 855s,
820m, 755s, 722s; dH (300 MHz; CDCl3) 7.73–7.70 (2H, m, Ph CH),
7.51–7.49 (3H, m, Ph CH), 4.02 (2H, br s, NH2), 3.32 (3H, s, CH3); dC
(75 MHz; CDCl3) 176.3, 168.9, 131.1 (Ph CH), 129.3 (Ph CH), 128.7 (Ph
C), 127.5 (Ph CH), 115.2 (C^N), 94.8 (CC^N), 43.0 (CH3); dC
(75 MHz; DEPT-135, CDCl3) 131.1 (Ph CH), 129.3 (Ph CH), 127.5 (Ph
CH), 43.0 (CH3); m/z (EI) 230 (Mþ, 100%), 214 (22), 201 (4), 187 (11),
159 (5), 153 (8), 128 (15), 121 (60), 114 (5), 104 (12), 77 (C6Hþ5 , 20).
Further elution (EtOAc, 100%) gave 3-amino-1-methyl-5-phenyl-
1H-pyrazole-4-carbonitrile 84 (12 mg, 27%), as colourless needles,
mp 158–159 ꢀC (lit.,78 158 ꢀC) (from EtOH); Rf (EtOAc) 0.55; [Found
C, 66.7; H, 5.1; N, 28.3. C11H10N4 requires C, 66.65; H, 5.1; N, 28.3%];
27. Musante, C. Gazz. Chim. Ital. 1943, 73, 355.
28. Gardner, T. S.; Smith, F. A.; Wenis, E.; Lee, J. J. Org. Chem. 1956, 21, 530.
29. Musante, C.; Fatutta, S. Gazz. Chim. Ital. 1958, 88, 879.
30. Fatutta, S. Gazz. Chim. Ital. 1959, 89, 964.
31. Adembri, G.; Camparini, A.; Ponticelli, F.; Tedeschi, P. J. Chem. Soc., Perkin Trans. 1
1977, 971.
32. Adembri, G.; Camparini, A.; Donati, D.; Ponticelli, F.; Tedeschi, P. Tetrahedron
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35. Musante, C.; Stener, A. Gazz. Chim. Ital. 1959, 89, 1579.
36. Alberola, A.; Antolı´n, L. F.; Cuadrado, P.; Gonza´lez, A. M.; Laguna, M. A.; Pulido,
F. J. Synthesis 1988, 203.
37. Zelenin, K. N.; Lagoda, I. V. Russ. J. Gen. Chem. 2000, 70, 1887.
38. Shaw, G. J. Chem. Soc. 1952, 3428.
39. Ponzio, G.; Carta-Satta, G. Gazz. Chim. Ital. 1930, 60, 150.
40. Boulton, A. J.; Roe, D. E.; Tsoungas, P. G. Gazz. Chim. Ital. 1981, 111, 167.
41. Knorr, L.; Reuter, B. Chem. Ber. 1894, 27, 1169.
42. Landesberg, J. M.; Olofson, R. A. Tetrahedron 1966, 22, 2135.
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lmax (EtOAc)/nm 252 (log
3213w (NH), 3034w (Ph CH), 2946w, 2220m (C^N),1638m,1557m,
3
2.95); nmax/cmꢂ1 3381m, 3311w (NH2),