Synthesis and structure of 1-tert-butyl-substituted 3(5)-alkylpyrazoles from 2-chlorovinyl ketones

Abstract

Reactions of alkyl, halomethyl 2-chlorovinyl ketones with tert-butylhydrazine in the presence of triethylamine afford unsymmetrical 1-(tert-butyl)-3-and -5-disubstituted pyrazoles. The reaction direction is governed by the ketone ability of the nucleophilic substitution of chlorine and of the dehydrochlorination leading to acetylene ketones. 2-Chlorovinyl ketones react with tert-butylhydrazine along two routes giving mixtures of 1-(tert-butyl)-3-and -5-alkylpyrazoles. The content of 3-alkyl-1-(tert-butyl)pyrazole in the formed isomers mixture grows up to 73% with growing length of the alkyl chain of the ketone and up to 87 and 94% at introducing halogen atom in the alkyl fragment of the chloroenone.Pyrazole and its derivatives attract attention due to the widest range of their pharmacologic activity [1][2][3][4][5], versatile specific agrochemical properties [6][7][8][9]. The high interest in this class of heterocyclic compounds originates as well from their large potential in modern technologies of dyes in cosmetics, photography and production of fluorescent substances and stabilizers [1][2][3][4][5]. Compounds of the pyrazole series find application both in the large-scale and fine organic synthesis [1][2][3][4][5], in the supramolecular [10] and polymer chemistry [11, 12], as liquid crystls [13], ligands for metal complex catalysis [14][15][16], in designing complexes with uncommon magnetic properties [17,18].The practical utilization of pyrazoles and the extension of their application fields requires not only development of synthetic procedures for new pyrazole derivatives, but mainly the solution of an important task of working out directional procedures for preparation of individual isomers of unsymmetrically substituted pyrazoles. The analysis of the known approaches shows the especially promising application of haloenones as initial reagents for pyrazole synthesis [19][20][21][22][23], in particular, of their individual isomers. The systematic investigation of the reactivity of versatile haloenones [24][25][26][27][28][29] demonstrated that the reactions of 2,2-dihalovinyl ketones with unsymmetrical dialkylhydrazines, alkyl-, arylhydrazines under various condition resulted in the chemo-and regiospecific formation of 1-alkyl(aryl)-5-halo-3-alkyl(aryl)(haloalkyl)pyrazoles. Therewith the hydrazine character does not considerably affect the process direction.The preparation of 1,3-disubstituted pyrazoles with no halogen atoms in the ring from 2-chlorovinyl ketones is governed by the hydrazine structure. The regioselective synthesis of 1,3-disubstituted pyrazoles from 2-chlorovinyl ketones occurs at the use of 1,1-dialkyl-and arylhydrazines [29][30][31]. At the same time no formation of two isomers was observed in the reactions of 2-chlorovinyl ketones with hydrazines containing a long alkyl chain [32].In extension of the research on the development of syntheses of dialkyl-substituted pyrazoles we studied the reactions of a number of 2-chlorovinyl ketones with tert-butylhydrazine. The goal of the work consiste...

The Structure of Biologically Active Functionalized Azoles: NMR Spectroscopy and Quantum Chemistry

“…The known methods for obtaining these practically important substances are complex and multi-stage, while the yields of the final products are low [100,101]. As a result of the search for new ways of recycling rocket fuel, as mentioned above, we have proposed an original method for the formation of functionally substituted pyrazoles or isoxazoles using heptyl (or hydroxylamine) or other reagents [102][103][104][105][106][107][108][109][110][111][112].…”