J. Chem. Research (S), 1997, 40–41 J. Chem. Research (M), 1997, 0336–0343 Synthesis of Novel Spiro and Fused Cyclopenta[c]-pyrazole and -pyrimidine Derivatives Hassan A. Albar,* Mohammed S. I. Makki and Hassan M. Faidallah Department of Chemistry, University of King Abdulaziz, Jeddah 21413, Saudi Arabia Condensation of diarylmethylidenecyclopentanes with hydrazine, hydroxylamine and thiourea derivatives afford the corresponding fused pyrazoles, oxazoles and pyrimidines. Nitrile imides are well known 1,3-dipoles and their reactions with a,b-unsaturated carbonyl compounds,1–4 4-arylmethylideneoxazolones5,6 and 3-arylmethylidene lactones7 have been extensively investigated.On the other hand, it has been reported that 2-substituted 5-methylidenecyclopentan- 2-ones are useful as intermediates for the synthesis of cyclopentenoid antibiotics and anticancer agents.8 For these reasons some new fused cyclopentapyrazole, cyclopentapyrimidine and spiropyrazoline derivatives have been synthesized either by the 1,3-dipolar addition of nitrile imides to arylmethylidenecyclopenta[c]pyrazole derivatives 2–6 or by other methods, with the two-fold objective of preparing compounds of biological importance and studying the regiochemistry of the cycloaddition process.The condensation of substituted hydrazines with the diarylmethylidenecyclopentanones 1a,b afforded 2,3-disubstituted 6-arylmethylidenecyclopenta[1,2-c]pyrazoles 2–6. Mild oxidation of 2, 3 and 5 with bromine water gave the corresponding pyrazoles 7, 8 and 9 respectively.Condensations of hydroxylamine with a,b-unsaturated ketones usually yield the corresponding isoxazolines, but in some cases the product was found to be the isoxazole derivative.9 However, in our case the reactions of 1a,b with hydroxylamine yielded the corresponding isoxazole derivatives 10a,b (Scheme 1). In view of the usefulness of 2-sulfanyl-1,4-dihydropyrimidines as vulcanizing accelerator agents and photographic stabilizers,10 we prepared some new pyrimidine derivatives 11 and 12 from the condensation of 1a with thiourea and methylthiourea.The reaction of 11 with bromoesters afforded the thioesters 13 and 14, while reaction with hydrazine hydrate afforded the 2-hydrazino derivative 15 which on condensation with acetylacetone in refluxing ethanol gave the triazolo derivative 16 (Scheme 1). The reactions of the nitrile imides 17, generated in situ by treatment of the corresponding hydrazonoyl chlorides 18 with triethylamine, with arylmethylidenecyclopentanes 2 and 4c were carried out in refluxing toluene.TLC analysis of the reaction mixture on silica gel with a mixture of light petroleum and ethyl acetate (5 :1 v/v) as eluent showed the formation of only one product. This was confirmed by 1H NMR analysis of the crude reaction product, in which only one methine singlet signal was observed. These findings indicate that the reactions studied are regiospecific, yielding one of the two possible regioisomers 19 and 19p.Techniques used: 1H NMR, MS, IR, elemental analysis References: 12 Table 1: Physical and elemental analytical data for pyrazoline and pyrazole derivatives Table 2: 1H NMR spectral data for the prepared compounds 40 J. CHEM. RESEARCH (S), 1997 Scheme 1 Reagents: i, NH2OH; ii, RNHNH2; iii, Br[CH2]nCO2Et; iv, (CH3CO)2CH2 Scheme 2 *To receive any correspondence.Received, 16th February 1996; Accepted, 29th October 1996 Paper E/6/01146b References cited in this synopsis 1 G.Bianchi, R. Gandolfi and C. DeMicheli, J. Chem. Res., 1981, (S) 6; (M) 0135. 2 S. T. Ezmirly, A. S. Shawali and A. M. Bukari, Tetrahedron, 1988, 44, 1743. 3 A. S. Shawali, B. E. Elanadouli and H. A. Albar, Tetrahedron, 1985, 41, 1877. 4 H. A. Albar, J. Chem. Res., 1996, (S) 316; (M) 1756. 5 N. G. Argypoulos and E. C. Argyropoulou, J. Heterocycl. Chem., 1984, 21, 1397. 6 E. C. Argyropoulou, N. G. Argypoulos and E. Thessalonikeos, J. Chem. Res., 1990, (S) 202; (M) 1557. 7 A. S. Shawali, A. M. Farag, M. S. Algharib and H. A. Albar, J. Chem. Res. (S), 1993, 80. 8 Narasaka Koichi, Jpn. Kokai Tokkyo Appt., 91/331,066, 1991 (Chem. Abstr., 1993, 119, 270683m). 9 A. R. Katritzky, Adv. Heterocycl. Chem., 1963, 2, 370. 10 J. Willems and A. Vandenberghe, C. R. Congr. Int. Chim. Ind., 1958, 31, 476 (Chem. Abstr., 1960, 54, 22657). J. CHEM. RESEARCH (S), 1997 41