Synthesis of Some Fused Pyrazoles and Isoxazoles

The α-keto methylene group in 3,5-diaryl-2-cyclohexenones 2 and 3,5-diarylcyclohexanones 8 have been used to obtain fused pyrazoles and isoxazoles. The new compounds were characterized by IR and 1H-NMR spectral data.


Introduction
The exploitation of a simple molecule with different functionalities for the synthesis of heterocycles is a worthwhile contribution in the chemistry of heterocycles.In fact, the 6-carbethoxy-3,5diarylcyclohexenone has been used as an effective synthon in some projected syntheses of benzoselenadiazoles/thiadiazoles [1], spirocyclohexanones [2], carbazole derivatives [3], fused isoxazoles and pyrazoles [4].In the present communication the former has been chosen as a promising starting material to develop pyrazole and isoxazole rings.Earlier we have reported various fused and spiro isoxazoles and pyrazoles by 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines to activated olefins [5].The formation of isoxazoles from open chain α-hydroxymethylene ketones and hydroxylamine is well known [6].The generality of this reaction is extended to cyclohexanone derivatives also [7].In this communication preparations of a new class of fused pyrazoles and isoxazoles from 3,5-diarylcyclohexenones are reported.

Conclusions
The α-keto methylene group in substituted cyclohexenones has been utilized to get pyrazoles and isoxazoles via Claisen like condensation with ethyl formate followed by cyclocondensation with hydrazine hydrate and hydroxylamine hydrochloride.

isoxazoles (11)
A solution of 3/9 (10 mmol) in glacial acetic acid (25 mL) was stirred with hydroxylamine hydrochloride (12 mmol) for 6-8 hours at 70-80 o C. The solvent was removed under reduced pressure.The viscous mass was diluted with water and extracted with ether.The organic layer was washed successively with saturated NaHCO 3 solution, water and brine solution.It was dried (Na 2 SO 4 ) and the solvent was removed.Recrystallization of the crude substance from ethanol afforded pure 5/11.

Oxidation of 4 and 5
A 1:1.5 molar mixture of 4/5 and DDQ in dry benzene (20 mL) was heated at reflux temperature for 2 hours under nitrogen atmosphere.The precipitated DDQ-H 2 was filtered off and the filtrate was subjected to column chromatography on silica gel (60-120 mesh), BDH to obtain 6/7.

Table 1 .
Physical data of compounds 3