V. I. Saloutin

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 FLUORINATED 2(3)-ARYLHYDRAZONES OF 1,2,3-TRI(1,2,3,4-TETRA)CARBONYL COMPOUNDS AND THEIR HETEROCYCLIZATION REACTIONS

Abstract New fluorinated 2-arylhydrazones of 1,2,3-triketones, 2-arylhydrazone-1,2,3-diketo esters and 3-arylhydrazone-1,2,3,4-triketo esters have been prepared by the coupling of fluorine-containing 1,3-keto esters, 1,3-diketones, acyl(aroyl)pyruvic esters and their chelates with aryldiazonium chlorides. The arylhydrazones react with hydrazine hydrate, phenylhydrazine, thiosemicarbazide and hydroxylamine to form the corresponding pyrazole and isoxazole derivatives. Interaction of 3-arylhydrazone-1,2,3,4-diketo esters with o -phenylenediamine results in quinoxaline products. Intramolecular cyclization of the arylhydrazones with pentafluorophenyl substituents leads to cinnolone derivatives.

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.

Interaction of perfluoropent-2-ene and its 2-amino-4-imino derivative with ethylenediamine and with diethylenetriamine

Abstract 5,7-Trifluoromethyl-6-fluoro-2,3-dihydro-1 H -1,4-diazepine has been prepared by the reaction of perfluoropent-2-ene (or 2-amino-4-iminoperfluoropent-2-ene) with ethylenediamine. Both perfluoropent-2-ene and 2-amino-4-iminoperfluoropent-2-ene were found to react with diethylenetriamine to form 1,9-trifluoromethyl-3,4,6,7-tetrahydro-2 H -pyrazino[1,2 a ]pyrazine (established by X-ray study). Some salts and the complex with BF 3 of this bicyclic compound are described.

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.

Synthesis of polyfluoroalkylated 1,4-diazinols and 1,4-oxazinols using polyfluoro-2,3-epoxyalkanes32 + 13

Abstract It has been found that the reactions of polyfluoro-2,3-epoxyalkanes with ethylenediamine and 2-aminoethanol yield 2,3-di(polyfluoroalkyl) 1,5,6-trihydro-1,4-diazin-2-ols and 2,3-di(polyfluoroalkyl) -5,6-dihydro-1,4-oxazin-2-ols, respectively. In the case of unsymmetrical oxiranes mixtures of regioisomeric heterocyclic compounds have been obtained. These reactions were found to give some byproducts—N,N′-bis (polyfluoroacyl)ethylenediamines and N-polyfluoroacyl-2-aminoethanols.

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.

Novel fluorinated chromones

Abstract We report here the autocondensation of ethyl pentafluorobenzoylacetate resulting in the formation of 3-pentafluorophenyl-1H-isopyrono [2,3-b]6,7,8,9- tetrafluorochromone ( 1 ). Hydrolysis of ( 1 ) leads to the formation of 2- pentafluorobenzoylmethyl-5,6,7,8-tetrafluorochromone ( 2 ). Other routes to new fluorinated chromones have been established. Pentafluoroacetophenone reacts with diethyloxalate to form ethyl pentafluorobenzoylpyruvate, which can be converted to 2-ethoxycarbonyl-5,6,7,8-tetrafluorochromone ( 3 ). It has been shown that intramolecular cyclization of ethyl 2-ethoxymethylenepentafluorobenzoylacetate also results in the formation of 3-ethoxycarbonyl- 5,6,7,8-tetrafluorochromone ( 3 ).