Synthesis of 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1<Emphasis Type="Italic">H</Emphasis>-4,5-dihydrofuran-3-carboxylic acids derivatives by recyclization of 5-arylfuran-2,3-diones under the action of cyanoacetic acid derivatives

Recyclization of 5-arylfuran-2,3-diones under the action of ethyl cyanoacetate or of malonic acid dinitrile resulting in the corresponding esters or nitriles of 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1Н-4,5-dihydrofuran-3-carboxylic acids was investigated.     

Polyfunctional imidazoles: III. Synthesis of 1-aryl-2,4-dihalo-1<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carboxylic acids and their derivatives

1-Aryl-4-chloro(2,4-dichloro)-1H-imidazole-5-carbaldehydes reacted with N-bromosuccinimide affording bromides of 1-aryl-2-bromo(2,4-dichloro)-1H-imidazole-5-carboxylic acids which were converted into the corresponding acids, esters, and amides.     

Synthesis of New 2-Aminopyrrole Derivatives by Reaction of Furan-2,3-diones 3-Acylhydrazones with CH-Nucleophiles

Recyclization of furan-2,3-diones acylhydrazones under the action of esters, amides and nitriles of cyanoacetic acids gave the corresponding esters, amides and nitriles of 2-amino-1-R-4-oxo-5- (2-oxo-2-aryl/tert-butylethylidene)-4,5-dihydro-1H-pyrrole-3-carboxylic acids.     

Synthesis and properties of 5-ferrocenyl-1H-pyrazole-3-carbaldehydes

New ferrocene derivatives - ethyl esters of 1-aryl-5-ferrocenyl-1H-pyrazole-3-carboxylic acids were synthesized. The corresponding aldehydes were obtained from acid esters in two steps. The reductive amination reaction of 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehyde was studied. Several of these compounds were investigated by cyclic voltammetry. All of them exhibited a reversible one-electron oxidation-reduction wave owing to the ferrocene-ferricinium redox couple with a positive shift (0.51-0.69 V) compared with that of ferrocene (0.46 V). The X-ray crystal structure of the ethyl ether 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-pyrazole-3-carboxylic acid is also presented.     

The application of (Z)-3-aryl-3-haloenoic acids to the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones

Studies directed at the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones from (Z)-3-aryl-3-haloenoic acids are described. The successful strategy relies on the preparation of (Z)-3-aryl-3-haloenoic acids from acetophenones through the corresponding (Z)-3-aryl-3-haloenals and the conversion of the (Z)-3-aryl-3-haloenoic acids to (Z)-5-benzylidene-4-aryl-5H-furan-2-ones. The furanones were subsequently treated with primary amines and dehydrated to the corresponding (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones.     

A simple and convenient synthesis of 3-[5-(trifluoromethyl)-1,2,3-triazol-4-yl]cinnamic acids from 4-aryl-6-(trifluoromethyl)-2H-pyran-2-ones and sodium azide

4-Aryl-6-(trifluoromethyl)-2H-pyran-2-ones and ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates react with sodium azide to produce highly functionalized CF₃-1,2,3-triazoles: 3-[5-(trifluoromethyl)-1,2,3-triazol-4-yl]cinnamic acids and monoethyl esters of [5-(trifluoromethyl)-1,2,3-triazol-4-yl]arylmethylidene malonic acids.     

Tetracarbonyl Systems: VII. Reactions of 1,3,4,6-Tetracarbonyl Compounds with o-Aminothiophenol in the Synthesis of Regioisomeric 3(2)-Aroylmethylene-1,4-benzothiazin-2(3)ones

In reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with o-aminothiophenol (3Z)-3-aroylmethylene-3,4-dihydro-2H-1,4-benzothiazin-2-ones were obtained in a preparative yield. In solution of the latter compounds an enamine-imine tautomerism was observed. In reaction of ethyl esters or amides of 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acids with the o-aminothiophenol regioisomeric 2-aroylmethylene-2H-1,4-benzothiazin-3(4H)-ones were formed.     

4-aryl-2-hydroxy-4-oxobut-2-enoic acids <Emphasis Type="Italic">N</Emphasis>-(2-pyridyl)amides in reactions with diazo compounds

Reactions of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides with diazomethane, diazoethane, diaryldiazomethanes, and diazofluorene lead to the formation of 2-alkoxy-4-aryl-4-oxobut-2-enoic acids N-(2-pyridyl)amides, 3-aroyl-5-methylpyrazole-4-carboxylic acids N-(2-pyridyl)amides, and 3-alkoxy-3-(2-aryl-2-oxoethyl)-2,3-dihydro-2-oxoimidazo[1,2-a]pyridines. The composition and structure of compounds obtained depend on the nucleophilic nature of the diazo compound and on the character of substituents in the aryl and pyridine parts of the substrate.     

One-pot synthesis of alkyl 3-aryl-2-(4-phenyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)propanoates

Reaction of 3-aryl-2-bromopropanoic acids esters, products of the Meerwein arylation, with sodium azide afforded alkyl 2-azido-3-arylpropanoates. The latter react with ethyl acetoacetate and phenylacetylene to form 1,2,3-triazole derivatives. A one-pot method for the synthesis of 3-aryl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-propanoic acid esters via a tricomponent reaction of alkyl 2-bromo-3-arylpropanoates, sodium azide, and phenylacetylene in the presence of CuI was developed.     

Synthesis of 6-Acyl-7-aryl-4,7-dihydrotetrazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-5-carboxylic acids and their methyl esters

6-Acyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylic acids and methyl 6-acyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylates were synthesized by fusion of 4-aryl-2,4-dioxobutanoic acids and their methyl esters, respectively, with 1H-tetrazol-5-amine and aromatic aldehydes. The reaction of methyl 2,4-dioxopentanoate with 1H-tetrazol-5-amine and 2-fluorobenzaldehyde in boiling acetic acid gave methyl 6-acetyl-5-hydroxy-7-(2-fluorophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine-5-carboxylate.     

Synthesis and microbial transformation of β-amino nitriles

Rhodococcus equi A4, Rhodococcus erythropolis NCIMB 11540 and Rhodococcus sp. R312 were investigated towards their ability to produce β-amino amides and acids from β-amino nitriles. The microorganisms show comparable trends: five-membered alicyclic 2-amino nitriles were transformed significantly faster than the six-membered compounds and the products of trans-2-amino nitriles (amides and acids) were formed considerably faster than the cis-counterparts (amides). The trans-five membered nitriles gave the amides (1b, 5b) in excellent enantiomeric excess (94-99%), the biotransformation of trans-six membered substrates resulted in the formation of the acid (3c, 7c) in excellent ee (87-99%). The ee's of the cis-compounds were throughout lower. Fifteen new substances were synthesized and characterized in the course of this work.     

Synthesis of 1-Aryl-1H-pyrazolecarbonitriles and related derivatives

The synthesis of 1-aryl-5-cyano-1H-pyrazole-4-carboxylic acid, ethyl esters 1 is described. Subsequent chemistry led to relatively simple and unique pyrazole derivatives. Most important of these are 1-aryl-5-(aminocarbonyl)-1H-pyrazole-4-carboxylic acids 2, which are chemical hybridizing agents in wheat and barley. The regioselective hydrolysis of 1-(3-chlorophenyl)-1H-pyrazole-4,5-dicarboxylic acid, dimethyl ester (7b) and subsequent chemistry is also described.     

Nitrile biotransformation for highly enantioselective synthesis of 3-substituted 2,2-dimethylcyclopropanecarboxylic acids and amides

Biotransformations of differently configured 2,2-dimethyl-3-substitued-cyclopropanecarbonitriles were studied using a nitrile hydratase/amidase-containing Rhodococcus sp. AJ270 whole-cell catalyst under very mild conditions. Although all of the cis-3-aryl-2,2-dimethylcyclopropanecarbonitriles appeared inert toward the biocatalyst, a number of racemic trans-isomers efficiently underwent a highly enantioselective hydrolysis to produce (+)-(1R,3R)-3-aryl-2,2-dimethylcyclopropanecarboxylic acids and (-)-(1S,3S)-3-aryl-2,2-dimethylcyclopropanecarboxamides in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of 1R-enantioselective nitrile hydratase and amidase, with the later being a dominant factor. The influence of the substrates on both reaction efficiency and enantioselectivity was discussed in terms of steric and electronic effects. Coupled with chemical transformations, biotransformations of nitriles provided convenient syntheses of optically pure geminally dimethyl-substituted cyclopropanecarboxylic acids and amides, including chrysanthemic acids, in both enantiomeric forms.     

Reaction of organozinc reagents prepared from bromomalonic acid esters and zinc with 3-aryl-2-cyanopropenoic acid primary amides

Organozinc compounds prepared from bromomalonic acid esters and zinc react with 3-aryl-2-cyanopropenoic acid primary amides giving a single diastereomer of the corresponding 1-R′-4-aryl-2,6-dioxo-5-cyanopiperidine-3-carboxylic acid esters, or 3-R′-6-aryl-2,4-dioxo-5-cyano-3-azabicyclo[3.1.0]hexene-1-carboxylic acid esters.     

3-methylthio-1,2-dithiolylium salts : Reaction with 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxycoumarin

The reaction of 4- and 5-aryl-3-methylthio-1,2-dithiolylium iodides with 4-hydroxy-6-methyl-2$\text{H}$-pyran-2-one and 4-hydroxycoumarin has been studied. 4-Substituted salts yielded 3-aryl-7-methyl-2-thioxo-2$\text{H}$,5$\text{H}$-pyrano [3,2-c]pyran-5-ones and 3-aryl-2-thioxo-2H,5H-pyrano[3,2-c]benzo[e]pyran-5-ones, respectively, whereas 5-substituted salts gave rise to 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-6-methyl-2$\text{H}$-pyran-2,4-diones and 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-2$\text{H}$-benzo [b]-pyran-2,4-diones.     

Heterocyclization of Derivatives of 4-Oxoalkanoic Acids to 1,5-Disubstituted Pyrrolin-2-ones

Conditions were developed for the synthesis and production of 1-aryl-5-alkyl(aryl)-3H- and 1-aryl-5-alkyl(aryl)-5H-pyrrolin-2-ones from the amides and esters of 4-oxoalkanoic acids. It was established that the yield and ratio of the 3H and 5H isomers depend on the substrate employed in the reaction.     

The reactions of aroylpyruvic acids and their derivatives witho-aminophenyldiphenylmethanol

Aroylpyruvic acids and their methyl esters react witho-aminophenyldiphenylmethanol to form 4-aryl-2-[2-(1-hydroxydiphenylmethyl)phenylamino]-4-oxobut-2-enoic acids and their esters. The α-enamino acids obtained undergo intramolecular heterocyclization in the presence of Ac₂O to affort substituted 4,5-dihydrobenzo[e][1,4]oxazepin-3(1H)-ones. The reaction of 5-arylfuran-2,3-diones witho-aminophenyldiphenylmethanol leads to products of decyclization, 2-(1-hydroxydiphenylmethyl)phenylamides of 4-aryl-2-hydroxy-4-oxobut-2-enoic acid, which upon heating in AcOH or Ac₂O yield 3-aroylacetyl-1,1-diphenyl-1H-benzo[d][1,3]oxazines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2317–2319, November, 1998.     

Synthesis and transformations of derivatives of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acid

On the basis of methyl esters of 2-aryl-5-hydrazino-1,3-oxazole-4-carboxylic acids the earlier unknown methyl esters of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acids as well as their functional derivatives were synthesized. The latter were used for further transformations, in particular, for introducing the residues of highly basic aliphatic amines into the 5 position of oxazole, and the oxazol-2-yl moiety into the 4 position of the oxazole ring.     

Reactions of Ethyl 2-Amino-5-(2-aryl-2-oxoethylidene)- 4-oxo-4,5-dihydrofuran-3-carboxylates and 2-Amino-5-(2-aryl- 2-oxoethylidene)-4-oxo-4,5-dihydrofuran-3-carbonitriles with Alcohols

Ethyl 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylates and 2-amino- 5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carbonitriles reacted with alcohols in the presence of a catalytic amount of concentrated aqueous HCl to give the corresponding 5-alkoxy-2-amino-5-(2-aryl-2- oxoethyl)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic acid derivatives. A probable reaction mechanism was proposed on the basis B3LYP/6-311G(d) quantum chemical calculations.     

Reactions of 4-acyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones with nucleophilic reagents

4-Acetyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones reacted with amines to give 1-alkoxyaryl-5-aryl-4-(1-R-aminoethylidene)pyrrolidine-2,3-diones. Reactions of amines with 4-benzoyl-substituted analogs involve nucleophilic attack on the C³ atom in the heteroring to produce the corresponding 3-R-amino-1-alkoxyaryl-5-aryl-4-benzoyl-2,5-dihydro-1H-pyrrol-2-ones. Reactions of the title compounds with hydrazine hydrate, regardless on the substituent on C₄, afforded 4-aryl-3-methyl(phenyl)-5-[2(4)-methoxyphenyl]-4,6-dihydropyrrolo[3,4-c]pyrazol-6-ones.