Pyrazole derivatives Pyrazole derivatives R 0180Synthesis of 5-Hydroxy-and 5-Amino-1-tosyl-5-phenyl-3-(2-arylvinyl)-4,5-dihydropyrazoles. -The title compounds are interesting as potential bioreceptor ligands. -(KUZ'MENOK, N. M.; KOVAL'CHUK*, T. A.; ZVONOK, A. M.; Synlett 2005, 3, 485-486; Dep. Org. Chem., Belarus State Univ. Technol., Minsk 220630, Belarus; Eng.) -Jannicke 28-131

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...

The reactions of 5-hydroxy-1-tosyl-2-pyrazolines with amines or with hydrazine have been investigated. We have shown that these compounds are convenient substrates for the synthesis of 5-aminosubstituted pyrazolines and NH-pyrazoles.

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The reaction of b-arylacryloyloxiranes with tosylhydrazine leads to unexpected 5-hydroxysubstituted D 2 -pyrazolines. A series of 3-styryl substituted pyrazoles and 5-amino-D 2 -pyrazolines were synthesized from the 5-hydroxy-D 2 -pyrazolines. The mechanism of this process has been proposed based on current and previous results.The reaction of hydrazine and its derivatives with a,b-unsaturated ketones and a,b-epoxy ketones is one of the preparative methods for the synthesis of pyrazolines and pyrazoles. Pyrazolines are typical products of these reactions, when a,b-unsaturated ketones are used, and 4-hydroxy pyrazolines in the case where a,b-epoxy ketones are applied. 1 Combination of the functionalities of the barylacryloyloxiranes allowed evaluation of the reactivity of the carbonyl group, oxirane ring and conjugated double bond to nucleophilic reagents such as hydrazine. Earlier, we found that the reaction of b-arylacryloyloxiranes with hydrazine gives the oxiranylpyrazoline intermediates, stable enough for isolation. However, in solution these compounds undergo further intramolecular oxidative-reductive transformation to b-hydroxyalkylpyrazoles. 2 These data indicate that hydrazine reacts preferentially with the conjugated double bond of barylacryloyloxiranes. Reaction of phenylhydrazine with b-arylacryloyloxiranes in proton solvents gives b-arylvinylpyrazoles, which shows participation of the oxirane ring in the cyclization process. 3 In this paper, the reaction of b-arylacryloyloxiranes with tosylhydrazine is reported. Pyrazoles and pyrazolines with aromatic substituents are interesting as potential bioreceptor ligands. 4 Although 4-hydroxypyrazolines are the typical products of the reaction of a,b-epoxy ketones with tosylhydrazine 5 and other hydrazines, 1 we found that the reaction of 3-aryl-1-(3-phenyloxiran-2-yl)-prop-2-en-1-ones (1a-f) with tosylhydrazine under acid catalysis leads to formation of 3-(2-arylvinyl)-5-hydroxy-5-phenyl-1-tosyl-2-pyrazolines (2a-f) with 58-83% yield (Scheme 1). Additionally, 3-(2-arylvinyl)-5-phenyl-1-tosyl-1H-pyrazoles (3a-f) were isolated with 7-21% yield by chromatography after crystallization of the major products. 6The structures of 5-hydroxy-3-styrylpyrazolines (2a-f) were determined by IR, 1 H NMR and 13 C NMR spectroscopy. 7 Thus, the hydroxyl, azomethine and vinyl group absorptions were observed in IR spectra, but there was no presence of the carbonyl band. The 1 H NMR spectra indicated the presence of the methylene diastereotopic protons at d = 3.20-3.50 ppm (J = 17.6-17.9 Hz), consistent with 5-hydroxypyrazoline structures. 8,9 The chemical shift of the double bond protons appeared in the range of d = 6.55-6.66 ppm and 6.92-7.14 ppm (J = 16.4-16.7 Hz). Compared to the initial enones, they are displayed at the higher field as an ABsystem. The tosyl group protons are shown in the 1 H NMR spectrum as a characteristic singlet at d = 2.4 ppm (for the methyl group) and AB-system of aromatic protons signals in the low field at the range of d = 7.22 and 7.68 ppm (J = 8.3 ...