A series of new spiro[cyclopropane-1,4'-pyrazol-3-one] derivatives 3a h were synthesized by the reaction of 4-arylidene-3H-pyrazol-3-one 1 with secondary and tertiary carbanions derived from a methylene and methine group bearing both a leaving group and electron-withdrawing group, e.g. methyl chloroacetate, ethyl chloroacetate, isopropyl chloroacetate, tert-butyl chloroacetate, chloroacetonitrile, 2-chloro-N,N-diethylacetamide, methyl 2-chloropropionate and 2-chloropropionitrile, in the presence of sodium hydride. All the synthesized compounds 3a h were active against Candida albicans with MIC 25 μg/mL in vitro.

An approach to pyrano [2,3-c]pyrazoles starting from spirocyclopropanepyrazoles via a ring-opening/ cyanomethylation and intramolecular cyclization is described. Reactions of spirocyclopropanepyrazoles 1a-d with chloroacetonitrile in the presence of sodium hydride gave the corresponding cyanomethoxypyrazoles 4a-d. Treatment of 4a-d with sodium hydride at room temperature caused intramolecular Michael addition reaction to afford the corresponding pyrano[2,3-c]pyrazoles 5a-d.

Pyran derivatives R 0340Ring Transformation of Spirocyclopropanepyrazoles into Pyrano[2,3-c]pyrazoles.-Instead of a one-pot reaction the conversion can be carried out stepwise with isolation of the intermediates. In this case the overall yield is generally lower. The reaction mechanism is discussed. -(MARUOKA*, H.; MASUMOTO, E.; EISHIMA, T.; OKABE, F.; NISHIDA, S.; YOSHIMURA, Y.; FUJIOKA, T.; YAMAGATA, K.; J. Heterocycl. Chem. 46 (2009) 4, 782-787; Fac. Pharm. Sci., Fukuoka Univ.,

Pyrazole derivatives R 0180Synthesis and Antifungal Activity of Spiro[cyclopropane-1,4'-pyrazol-3-one] Derivatives. -The spiro compounds (III) are constructed by reaction of pyrazolone (I) with secondary and tertiary carbanions derived from a methylene and methine group possessing both a leaving and electron-withdrawing group. The spiro-cyclopropanepyrazoles (III) display moderate or week antifungal activity in vitro against C. albicans and S. cerevisiae. -(MARUOKA*, H.; KASHIGE, N.; EISHIMA, T.; OKABE, F.; TANAKA, R.; FUJIOKA, T.; MIAKE, F.; YAMAGATA, K.; J.