Yanina V. Burgart

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.

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.

Synthesis of fluoroalkyl-containing 2-oxyimino-1,3-dicarbonyl compounds and their reaction with hydrazine hydrate

Abstract Reaction of fluoroalkyl-containing 1,3-keto esters and 1,3-diketones and their copper chelates with sodium nitrite gives the corresponding 2-hydroxyiminosubstituted ligands and chelates. 1,1,1-Trifluoro-3-hydroxyimino-4-pheny1-2,4-butanedione reacts with hydrazine hydrate with the formation of 4-hydroxyiminopyrazole. The 1,3-keto ester with a nonafluorobutyl substituent gives the stable 3-nonafluorobutyl-3-dihydroxy-4-hydroxyiminopyrazolidone-5. The similar reaction of ethyl trifluoroacetoacetate oxime leads to a pyrazolidone-5 (which can be dehydrated to 4-oxyiminopyrazolinone-5) and the hydrazide of 4,4,4-trifluoro-2-hydroxyimino-3-dihydroxybutanoate.

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles.

Summary The interaction of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole is an efficient synthetic approach to novel azaheterocycles. 2-Ethoxymethylidene-3-oxo esters bearing alkyl substituents react with 5-aminotetrazole to form ethyl 2-azido-4-alkylpyrimidine-5-carboxylates which are capable of subsequent nucleophilic substitution. The use of diethyl 2-ethoxymethylidenemalonate in this reaction resulted in ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate, while ethyl 2-ethoxymethylidenecyanoacetate yielded 5-[2,6-diamino-3,5-bis(ethoxycarbonyl)pyridinium-1-yl]tetrazol-1-ide through an alternative pathway. Ethyl 2-benzoyl-3-ethoxyprop-2-enoate reacted with 5-aminotetrazole by two reaction routes to form ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-enoate and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate.

The selective ortho-methoxylation of pentafluorobenzoic acid – a new way to tetrafluorosalicylic acid and its derivatives

Abstract A simple and efficient preparation of tetrafluorosalicylic acid has been developed which involves a selective substitution of fluorine in pentafluorobenzoic acid with methoxyl group by magnesium methoxide. The synthesis of 2,6-dimethoxy-3,4,5-trifluorobenzoic acid, 4,5,6-trifluororesorcinol and its dimethoxy ether is described.

Alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates as new effective and selective inhibitors of carboxylesterase.

A series of alkyl 2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates was synthesized and their inhibitory activity with respect to porcine liver carboxylesterase (CaE, EC 3.1.1.1), human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), and horse serum butyrylcholinesterase (BChE, EC 3.1.1.8) was studied. The molecular docking method was used to study the binding mode of the compounds in the active site of CaE. It was found that compounds containing the trifluoromethyl group in the third position of carbonyl chain are highly effective and selective inhibitors of CaE with nanomolar IC50 values, which agrees well with the results of molecular docking.

Transformations of 4-Hydroxy-5,6,7,8-tetrafluorocoumarin Derivatives with Monoamines

The 4-hydroxy-5,6,7,8-tetrafluorocoumarin reacts with the monoamines to form salts under the mild conditions or the 4-alkyl(aryl)aminocoumarins on refluxing in o-xylene. The 3-acetyl-4-hydroxy-5,6,7,8-tetrafluorocoumarin reacts with the strong basic amines in the polar solvents to give salts that can be transformed into the 3-alkylaminoethylidene-5,6,7,8-tetrafluorobenzopyran-2,4-diones. The latter can be obtained by reaction of the 3-acetylcoumarin with different amines. The reactions of the 3-acetylcoumarin with the strong basic amines in dimethyl sulfoxide lead to the 7-alkylamino-3-alkylaminoethylidene-5,6,8-triflurobenzopyrandiones. The 3-acetimidoyl-4-hydroxy-5,6,7,8-tetrafluoro-coumarin affords the 3-alkylaminoethylidenebenzopyrandiones with the monoamines, but in dimethyl sulfoxide the 7-substituted 3-acetimidoyl-5,6,8-trifluorobenzopyrandiones or the 7-alkylamino-3-alkylaminoethylidene-5,6,8-triflurobenzopyrandiones can be obtained.

RECYCLIZATION OF 7-FLUOROALKYL- 4,7-DIHYDROAZOLO(5,1-c)(1,2,4)TRIAZINES INTO 5-(PYRAZOLINYLHYDRAZONO)AZOLES IN THE REACTIONS WITH HYDRAZIDES AND THIOSEMICARBAZIDE

7-Fluoroalkyl-4,7-dihydroazolo[5,1-c][1,2,4]triazines react with hydrazides and thiosemicarbazide to form 5-(5-hydroxy-5-polyfluoroalkyl-2-pyrazoline-4-ylhydrazono)azoles as a result of triazine ring opening at bond C-7-N-8 and followed by regio-selective condensation.

Fluorine-containing 2-functionalized 1,3-dicarbonyl compounds for heterocyclic synthesis

Data on the synthesis and chemical transformations of 2-functionalized fluoroalkyl-containing 1,3-dicarbonyl compounds are reviewed. Reactions giving fluorinated heterocycles are discussed. The heterocyclization of non-substituted fluoroalkylated 1,3-dicarbonyl compounds with the same dinucleopiles is considered for the sake of comparison.

Reaction of perfluoropenten-2 with polyamines

Abstract The formation of fluorocontaining azaheterocycles on the base of perfluoropenten-2 has been studed. Perfluoropenten-2 reacts with ethylenediamine to give 5,7-trifluoromethyl -6-fluoro-1H-1,4-diazepine The same reaction of perfluoropenten-2 with diethylenetriamine and triethylenetetraamine yieldes fluorinated polyazamacrocycles