Synthesis of 5-polyfluoroalkyl-4-(p-tolyl-sulfonyl)pyrazoles and 4-polyfluoroalkyl-5-(p-tolylsulfonyl)pyrimidines from 1-dimethylamino-2-(p-tolylsulfonyl)-polyfluoro-1-alken-3-ones

Abstract

Keywords: 1-arylsulfonyl-1,1-dihydropolyfluoro-2-alkanone, enaminone, pyrazole, pyrimidine, Vilsmeier-Haack-Arnold reaction, X-ray diffraction structural analysis.Fluoropyrazoles and fluoropyrimidines display a variety of strong biological activities [1][2][3][4][5], which has led to work to develop new methods for the synthesis of such heterocyclic compounds.The synthetic approaches for the heterocyclic pyrazole system have been studied extensively. The most common approach involves a reaction, in which the three-carbon fragment of a β-dicarbonyl compound or its synthetic equivalent is condensed with the diatomic N-N fragment of hydrazine or its derivative. A problem with this approach is the regioselectivity of the reaction using asymmetric starting compounds since a mixture of N-substituted pyrazoles is formed in most cases [6]. The similar reaction of β-dicarbonyl compounds with a binucleophile possessing an N-C-N fragment leads to the formation of pyrimidines and is also frequently used for the design of these heterocycles [7].In the present work, we studied the feasibility of using 1-dimethylamino-2-(p-tolylsulfonyl)-polyfluoro-1-alken-3-ones 2a,b, which are the synthetic equivalents of a new type of β-dicarbonyl compounds, namely, 1-arylsulfonyl-2-oxopolyfluoroalkanals 1a,b for the regioselective synthesis of fluoropyrazoles and fluoropyrimidines. Monoenamines of various 1,3-dicarbonyl compounds (amide vinylogs) have found common use in the synthesis of many heterocyclic systems [8].

The crystal structure of ethyl 1-(4-nitrophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate, C13H10F3N3O4

“…As a part of our ongoing interest on the synthesis, physico-chemical and structural properties of the pyrazole based coordination compounds [12,13] we examined the crystal structure of the title pyrazole ligand. The bond lengths and angles within the Nphenylpyrazole core are comparable with those reported for the similar pyrazole ligands [14][15][16][17][18]. The C1-N1 bond [1.436(2) Å] allows a rotation of the phenyl relative to the pyrazole ring, thus the dihedral angle between the corresponding ring planes is 49.26(6)°.…”

One-Pot, Two-Step Conversion of Aldehydes to Phosphonyl- and Sulfonylpyrazoles Using Bestmann–Ohira Reagent

“…The general methods for the synthesis of pyrazoles are 1,3-dipolar cycloaddition of diazo compounds with alkenes or alkynes (Pechmann synthesis) and the cyclocondensation between hydrazines and 1,3-difunctional compounds (Knorr synthesis) . These approaches were employed for the synthesis of various functionalized phosphonyl- and sulfonylpyrazoles as well. − Recently, we and Smietana et al have employed α-diazo-β-ketophosphonate (Bestmann–Ohira reagent, BOR) 3a as a diazomethyl phosphonate precursor in the 1,3-dipolar cycloaddition with various electron-deficient alkenes (e.g., 2 , Scheme a) for the regioselective synthesis of phosphonylpyrazoles (e.g., 4 ). We also extended this strategy to the synthesis of sulfonylpyrazoles 5 using α-diazo-β-ketosulfone 3b as a 1,3-dipole precursor …”