Reaction of 3-Aryl-1-(2-methyloxiran-2-yl)prop-2-en-1-ones with Tosylhydrazine

Abstract

Keywords: hydrazone, α,β-unsaturated epoxy ketone, pyrazole, tosylhydrazine, β-tosyl ketone, p-toluenesulfinic acid.As shown earlier, the reaction of α,β-unsaturated epoxy ketones with hydrazine includes attack by the nitrogen-containing nucleophile in the enone system of the substrate followed by disproportionation of the intermediate 3-oxiranyl-4,5-dihydro-1H-pyrazoles to 3-β-hydroxyalkanoyl-1H-pyrazoles. At the same time, the introduction of phenyl-substituted hydrazine into the reaction under these conditions leads to 1-phenyl-3-styryl-1H-pyrazoles, formed as a result of cyclization of the intermediate hydrazones at the oxirane ring [2]. In a continuation of these investigations and in order to synthesize 1-tosyl-substituted pyrazoles in the present work we studied the reaction of a series of unsaturated epoxy ketones with tosylhydrazine. Aryl-substituted pyrazoles are of interest as specific ligands of cannabinoid receptors and are being studied intensively as potential products in the fight against alcoholism and drug addiction [3][4][5].It was found that the reaction of 3-aryl-1-(2-methyloxiran-2-yl)propan-2-en-1-ones 1a-e with tosylhydrazine, boiled in isopropyl alcohol for 3-6 h in the presence of acetic acid, leads to the formation of 3-[(E)-2-arylvinyl]-4-methyl-1-tosyl-1H-pyrazoles 2a-e and 3-aryl-1-(2-methyloxiran-2-yl)-3-tosylpropan-1ones 3a-e as the main products with overall yields of 52-68% (Table 1). The tosyl ketones 3a-e are formed as two diastereomers, differing in the relative configuration of the chirality centers, in equal proportions. The initial enones were detected in the reaction mixture with control by TLC irrespective of the duration of the reaction, and increase in the reaction time or heating temperature did not lead to their disappearance but gave rise to the appreciable formation of resinous products. If a 1.4-1.5 excess of the tosylhydrazine was used in the reaction with the monoepoxides 1a-e, the formation of 3-(2-aryl-2-tosylethyl)-4-methyl-1-tosyl-1H-pyrazoles 4a-e with yields of up to 21% was observed in addition to the main products.The structure of the synthesized substances was proved on the basis of data from elemental analysis, IR and 1 H NMR spectroscopy (Table 1), and an alternative synthesis of compound 3a by reaction of the monoepoxide 1a with p-toluenesulfinic acid. 6 H 4 , c Ar = 4-BrC 6 H 4 , d Ar = 4-MeOC 6 H 4 , e Ar = 2-PhCH 2 OC 6 H 4 CH=); 7.22 (1Н, m, C6H4); 7.27 (2Н, d, J = 8.3, С6H4); 7.29-7.40 (3Н, m, arom.); 7.43 (2Н, m, C6H5); 7.54 (1Н, m, C6H4); 7.61 (1Н, d, J = 16.9, СН=); 7.78 (1H, br. s, H-5); 7.86 (2Н, d, J = 8.3, С6Н4) 1.41 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.91 (1Н, d, J = 4.9, СН2-O); 3.16 (1Н, dd, J = 7.7, J = 18.2, СН2-CН); 3.22 (1Н, d, J = 4.9, СН2-O); 3.46 (1Н, dd, J = 5.9, J = 18.2, СН2-CН); 4.74 (1Н, dd, J = 5.9, J = 7.7, СН-CН2); 7.06 (2Н, d, J = 8.5, С6Н4); 7.32 (2Н, d, J = 8.5, С6Н4); 7.13-7.30 (5Н, m, arom.) 3а 1.40 (3Н, s, СН3); 2.38 (3Н, s, СН3); 2.77 (1Н, d, J = 4.9, СН2-O); 2.79 (1Н, d, J = 4.9, СН2-O); 3.13 (1Н, dd, J = 9.7, J = 1...

Polyfunctional intermediates for the preparation of liquid-crystalline and anisotropic materials

“…Substituted unsaturated epoxyketones (VI) can be prepared by the epoxydation of 4-substituted 3-buten-2-ones with hydrogen peroxide in an alkaline medium and then by the interaction of 4-substituted 3,4-epoxybutanones with the corresponding aldehydes (Scheme 5) [25][26][27][28].…”