Ya. V. Burgart

Biginelli condensations of fluorinated 3-oxo esters and 1,3-diketones

Abstract Condensation of fluorinated 3-oxo esters or 1,3-diketones with benzaldehyde and (thio)urea results in the diastereoselective formation of 4-fluoroalkyl-4-hydroxy-2-oxo(thioxo)-6-phenyl-hexahydropyrimidine-5-carboxylates from which by dehydration under acidic conditions the corresponding 6-fluoroalkyl-2-oxo(thioxo)-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates were obtained. Under the same conditions, hexafluoroacetylacetone furnishes 4,6-dihydroxy-4,6-di(trifluoromethyl)-hexahydropyrimidin-2-one. Some further reactions of these pyrimidine derivatives leading to fused heterocycles are described.

Synthesis of 7-Alkyl(aryl)-6-alkoxycarbonyl-5-fluoroalkyl-1,2,4-tri(tetr)azolo[1,5-a]pyrimidines

Fluorinated 3-oxo esters react with aldehydes and 3-amino-1,2,4-triazoles and 5-aminotetrazoles to give, respectively, 7-alkyl(aryl)-6-alkoxycarbonyl-5-fluoroalkyl-1,2,4-triazolo[1,5-a]pyrimidines and -tetra-zolo[1,5-a]pyrimidines. The same heterocyclic products can be obtained by reaction of 2-benzylidene-2-fluoroacyl esters with the corresponding aminoazoles.

Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl)hydrazones of 1,2,3-triketones and their derivatives

Abstract1,2,3-Triketone 2-(antipyrin-4-yl)hydrazones were synthesized via the azo-coupling reactions of 1,3-diketones with 2-(antipyrin-4-yl)diazonium chloride. The fluoroalkyl-containing hetarylhydrazone enters into cyclocondensation with hydrazines at the 1,3-dicarbonyl fragment to yield 3-tetrafluoroethyl derivatives of pyrazole. It was found that 1,2,3-triketone 2-(antipyrin-4-yl)hydrazones and N-(2-hydroxyethyl)-substituted pyrazole exhibit analgesic activity comparable with that of their structural analog analgin (metamizole sodium), but do not possess antipyretic properties. In contrast, N-phenyl-substituted pyrazole did not exhibit analgesic properties but produced a certain antipyretic effect four hours after pyrogenic administration. Fluoroalkyl-containing compounds are less toxic substances than nonfluorinated 2-(antipyrin-4-yl)hydrazone and analgin.

Synthesis and Structure of 2-Ethoxy- and 2-Aminomethylidene- 3-fluoroalkyl-3-oxopropionates

Condensation of ethyl 3-polyfluoroalkyl-3-oxopropionates with excess triethyl orthoformate gave ethyl 3-polyfluoroalkyl-2-ethoxymethylidene-3-oxopropionates which reacted with primary aliphatic, aromatic, and heterocyclic amines to form ethyl 2-alkyl(aryl, hetaryl)aminomethylidene-3-polyfluoroalkyl-3-oxopropionates. According to the X-ray diffraction and IR data, the latter exist in the crystalline state as the corresponding E isomers, while in solution (NMR data), as mixtures of Z and E isomers. Condensation of ethyl 2-ethoxymethylidene-3-oxopropionates with secondary heterocyclic amines (morpholine and pyrrolidine) led to the formation of 2-morpholino(pyrrolidin-1-yl)methylidene-3-fluoroalkyl-3-oxopropionates which were shown to exist as Z isomers both in the crystalline state and in solution.

Fluorocontaining 1,3-Dicarbonyl Compounds in the Synthesis of Pyrimidine Derivatives

Hexafluoroacetylacetone reacts with urea (thiourea) to yield respectively 4,6-bis(hydroxy)-4,6-bis(trifluoromethyl)hexahydropyrimidin-2-one(thione). The dehydration of the products and also reaction of nonsymmetrical fluoroalkyl-containing 1,3-diketones with urea (thiourea) afford substituted pyrimidines. The condensation of fluorinated 3-oxoesters and 1,3-diketones with benzaldehyde and urea (thiourea) results in 5-alkoxycarbonyl(acyl)-4-hydroxy-2-oxo(thioxo)-6-phenyl-4-fluoroalkylhexahydropyrimidines that on dehydration furnish 5-alkoxycarbonyl(acyl)-2-oxo(thioxo)-4-phenyl-6-fluoroalkyltetrahydropyrimidines. Ethyl 7-nonafluorobutyl-5-phenyl-2,3-dihydrothiazolo[3,2-a]pyrimidine-6-carboxylate hydrobromide forms in reaction of dibromoethane with ethyl ether of 2-thioxo-4-phenyl-6-nonafluorobutyltetrahydropyrimidine.

Reactions of fluorine-containing 3-oxo esters with aldehydes

Abstract Fluoroalkylcontaining 3-oxo esters react with aldehydes to form 2-benzylidene-3-fluoroacyl-esters or 4-aryl(alkyl)-3,5-dialkoxycarbonyl-2,6-dihydroxy-2,6-di(fluoroalkyl)tetrahydropyranes depending on the conditions. Ethyl pentafluorobenzoylacetoacetate with benzaldehyde affords 3,5-diethoxy-carbonyl-4-phenyl-2-pentafluorophenyl-7,8,9,10-tetrafluoro-4,5-dihydrobenzo[b]oxacin-6-one.

One-step solvent-free synthesis of fluoroalkyl-substituted 4-hydroxy-2-oxo(thioxo)hexahydropyrimidines in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate

A convenient procedure has been developed for the synthesis of fluoroalkyl-substituted 6-aryl-4-hydroxy-2-oxo-(thioxo)hexahydropyrimidine derivatives by three-component condensation of fluorinated β-dicarbonyl compounds with aromatic aldehydes and urea or thiourea in the absence of a solvent using 6 mol % of 1-butyl-3-methylimidazolium tetrafluoroborate as catalyst.

Synthesis of fluoroalkyl-containing 1,2,3-triketone 2-hetarylhydrazones and their reactions with hydrazines

Fluoroalkyl-containing 1,2,3-triketone 2-(2,3-dimethyl-5-oxo-1-phenyl-1,2-dihydropyrazol-4-yl)-, 2-(4-ethoxycarbonylpyrazol-3-yl)-, and 2-(1,2,4-triazol-3-yl)hydrazones were synthesized by the azo coupling reactions of fluorinated 1,3-diketones with the corresponding hetaryldiazonium chlorides. The hetarylhydrazones thus synthesized were subjected to cyclocondensation with hydrazines at the 1,3-dicarbonyl fragment to give 3-fluoroalkyl-4-hetarylazopyrazoles.

Features of reactions of polyfluorinated ethyl 4-oxo-2-pnenyl-4H-chromene-3-carboxylates with N-nucleophiles

Ethyl 5,6,7,8-tetrafluoro-4-oxo-2-phenyl-4H-chromene-3-carboxylate in reactions with primary amines is characterized by a chromone-coumarin rearrangement affording 3-[amino(phenyl)methylene]-6,7,8-trifluoro-2H-chromene-2,4(3H)-diones, and ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4H-chromene-3-carboxylate characteristically adds the amine at the C2 site of the flavone furnishing 3-amino-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylates which depending on the substituent at the amino group are capable of intramolecular cyclization into 3-[(alkylamino)(phenyl)methylene]-5,6,7,8-tetrafluoro-2H-chromene-2,4(3H)-dione or in the case of benzylamine substituent, into ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-trifluoro-1,4-dihydroquinoline-3-carboxylate. The main process in the reaction of tri- and tetrafluoroflavones with secondary amine (1-methylpiperazine) is the nucleophilic substitution at the C7 of flavone. In the reaction with 1,2-phenylenediamine 3-[(2-aminophenyl)amino]-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylate was obtained from tetrafluoroflavone and 1H-benzimidazol-2-yl(3,4,5-trifluoro-2-hydroxyphenyl)methanone, from trifluoroflavone.

Synthesis, structure, and complexing ability of fluoroalkyl-containing 2,2′-(biphenyl-4,4′-diyldihydrazono)bis(1,3-dicarbonyl) compounds

New fluoroalkyl-containing 2,2′-(biphenyl-4,4′-diyldihydrazono)bis(1,3-diketones) and 2,2′-(biphenyl-4,4′-diyldihydrazono)bis(3-oxopropionates) were synthesized by azo coupling of the corresponding 1,3-dicarbonyl compounds with biphenyl-4,4′-bis(diazonium) dichloride. Complexing ability of the obtained bis-hydrazones was studied, and new coordination compounds of the general formula M2L2 [where M = Ni(II), Cu(II); L = fluoroalkyl-containing 2,2′-(biphenyl-4,4′-diyldihydrazono)bis(1,3-diketone)] were obtained.