The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.     

Reaction of halothane with carbonyl compounds in the presence of bases

The reaction of halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane (1), with aldehydes and ketones in the presence of bases was found to give 1-alkyl- or 1-aryl-2-bromo-2-chloro-3,3,3-trifluoropropanols (2) or 2-chloro-3,3-difluoro-2-propenols (3) selectively in good to moderate yields depending on the bases and reaction conditions.     

Syntheses Based on 4-Chloro-1-[3,5-di(trifluoromethyl)phenyl]-, 4-Chloro-1-(2,4-difluorophenyl)-5-formyl-3-methyl-6,7-dihydroindazoles,and 4-Chloro-5-formyl-3-methyl-1-(2-pyridyl)-6,7-dihydroindazoles

Vilsmeier formylation of 1-[3,5-di(trifluoromethyl)phenyl]- and 1-(2,4-difluorophenyl)-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles gave the corresponding 1-aryl-4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles. Reaction of the latter with amidines, o-phenylenediamine, hydrazine, or hydroxylamine gave a series of 1-aryl-3-methyl-6,6-dihydroindazoles annelated at positions 4 and 5. The reaction of 4-chloro-5-formyl-3-methyl-1-(2-pyridyl)-6,7-dihydroindazole with substituted anilines gave 5-arylaminomethylene-4-oxo- or 5-arylaminomethylene-4-arylimino-3-methyl-1-(2-pyridyl)-4,5,6,7-tetrahydroindazoles depending on the molar ratio of reagents and the nucleophilicity of the amines.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 740–750, May, 2005.     

Synthesis of 3-aminomethyl-2-aryl- 8-bromo-6-chlorochromones

[reaction: see text] An efficient synthetic route to Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones has been developed. 3-Aryl-1-(3-bromo-5-chloro-2-hydroxyphenyl)-2-propen-1-one or 2-aryl-8-bromo-6-chlorochroman-4-one could be reacted under Mannich conditions yielding 2-aryl-8-bromo-6-chloro-3-methylenechroman-4-one, which was further converted to the target compound via an aza-Michael reaction followed by an SeO(2) oxidation. This procedure represents a new method to introduce a primary aminomethyl group at the 3-position of a 2-arylchromone scaffold. The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics.     

Synthesis of 1-aryl-5-arylazo-3-phenylsulfonylpyrazol-4-ols from 1-chloro-3-phenylsulfonyl-2-propanone

Treatment of 1-chloro-3-phenylsulfonyl-2-propanone (2) with arenediazonium chlorides gave 1-arylhydrazono-3-chloro-1-phenylsulfonyl-2-propanones 4 , which were cyclized in the presence of sodium acetate to 1-aryl-3-phenylsulfonylpyrazol-4-ols 5B. Further treatment of 5B with arenediazonium chlorides yielded 1-aryl-5-arylazo-3-phenylsulfonylpyrazol-4-ols.     

A study of nitrogen- and sulfur- containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with phenacyl halides has been studied, and a number of 3-aryl-7-chloro-2H-pyrido-[2,3-b]-1,4-thiazines have been synthesized. Two types of intermediate compounds have been isolated: 2-amino-6-chloro-2-phenacyl-thiopyridines and 3-aryl-7-chloro-3-hydroxy-1,2-dihydropyrido[2,3-b]-1,4-thiazines.     

A study of nitrogen- and sulfur- containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with phenacyl halides has been studied, and a number of 3-aryl-7-chloro-2H-pyrido-[2,3-b]-1,4-thiazines have been synthesized. Two types of intermediate compounds have been isolated: 2-amino-6-chloro-2-phenacyl-thiopyridines and 3-aryl-7-chloro-3-hydroxy-1,2-dihydropyrido[2,3-b]-1,4-thiazines.For part VI, see [3].     

Lewis acid-mediated reactions of 1-cyclopropyl-2-arylethanone derivatives with allenic ester, ethyl acetoacetate, and methyl acrylate

TMSOTf-mediated reactions of 2-aryl-1-(1-phenylcyclopropyl)ethanones 1 with allenic esters afford a novel method for the synthesis of 6-methyl-3a,7-diaryl-3,3a-dihydro-2H-benzofuran-4-one derivatives 2 in moderate yields. In addition, we also found that TMSOTf-mediated reactions of 1-cyclopropyl-2-arylethanones with ethyl acetoacetate can provide the corresponding 2,3-dihydrobenzofuran-4-ol and dihydrofuro[2,3-h]chromen-2-one in moderate yields via a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H2O, one intermolecular aldol type reaction and two intramolecular aldol type reactions, a cyclic transesterification, dehydration, and aromatization. Moreover, by using methyl acrylate to replace allenic ester, the corresponding 7-aryl-3,5,6,7-tetrahydro-2H-benzofuran-4-one and 5-aryl-3,5,6,7-tetrahydro-2 H-benzofuran-4-one can be formed in moderate to high yields in the presence of Bi(OTf)2Cl. Plausible reaction mechanisms have also been provided on the basis of control experiments.     

Synthesis and reactions of 1-(4-chloro-, 3-chloro-, 2-chloro-, 2,4-dichloro-, and 2,4-difluorophenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles

Reaction of the potassium salt of 2-formyldimedone with hydrochlorides of 4-chloro-, 3-chloro-, 2-chloro-, 2,4-dichloro-, and 2,4-difluorophenylhydrazines gave the corresponding 2-arylhydrazinomethylene-dimedones which cyclized in acid media to 1-substituted 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles. Oxidation of the latter with selenious acid gave the corresponding 4,5-dioxo-4,5,6,7-tetrahydroindazoles which were further converted into 3-aryl-5,5-dimethyl-4,5-dihydro-3H-pyrazolo[4,3-a]phenazines and 2,6-diaryl-4,4-dimethyl-4,5-dihydro-1H(3H)-indazolo[4,5-g]imidazoles.Riga Technical University, Riga LV-1658, Latvia; e-mail: marina@osi.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 533–539, April, 2000.     

Heterocyclization of functionalized heterocumulenes with C,N-, C,O, and C,S-binucleophiles: IX. Reaction of 1-aryl-1-chloro-2,2,2-trifluoroethyl isocyanates with sulfanylacetic acid esters as a convenient synthetic route to 2-aryl-2-trifluoromethyl-4-oxo-1,3-thiazolidine-5-carboxylates

1-Aryl-1-chloro-2,2,2-trifluoroethyl isocyanates reacted with methyl and ethyl sulfanylacetates to give the corresponding alkyl 2-aryl-2-trifluoromethyl-4-oxo-1,3-thiazolidine-5-carboxylates.     

Synthesis of 3-aryl-5-dichloromethyl-1H-pyrazole-1-carboxamides from 1-aryl-3,4,4-trichlorobut-3-en-1-ones

The reaction of 1-aryl-3,4,4-trichlorobut-3-en-1-ones with semicarbazide hydrochloride in the presence of sodium acetate is accompanied by prototropic allylic rearrangement, leading to the formation of two isomeric products, semicarbazones of the initial ketones and 1-aryl-3,4,4-trichlorobut-2-en-1-one semicarbazones. The latter undergo heterocyclization in the presence of triethylamine to give the corresponding 3-aryl-5-dichloromethyl-1H-pyrazole-1-carboxamides.     

An investigation of nitrogen- and sulfur-containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with ortho-substituted phenacyl halides has been investigated. Two types of intermediate compounds have been isolated: 3-amino-6-chloro-2-(phenacylthio)pyridines and 2-aryl-2-hydroxy-1,2-dihydro-3H-pyrido[2,3-b][1,4]thiazines. Boiling 3-amino-6-chloro-2-mercaptopyridine with ortho-substituted phenacyl halides in ethanol has given 2-aryl-3H-pyrido[2,3-b][1,4]thiazines.For Communication XXVII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1262–1265, September, 1973. Original article submitted March 15, 1972,     

A Novel Route to the Synthesis of 3-Pyridine Carboxaldehydes by Vilsmeier Reagent

2-Chloro-5-aryl-3-pyridine carboxaldehydes are obtained by Vilsmeier reaction of 4-aryl-3-buten-2-one oxime. The suspected intermediate N-(2-arylethenyl)acetamides also give the same 2-chloro-5-aryl-3-pyridine carboxaldehydes under identical reaction condition.     

Unusual reductive cleavage of 3-aryl-2,3-epoxyamides by using samarium diiodide. Synthesis of 3-aryl-3-deuterio-2-hydroxyamides with total regioselectivity

Ring-opening of 3-aryl-2,3-epoxyamides 1 was achieved by using samarium diiodide and D₂O, yielding 3-aryl-3-deuterio-2-hydroxyamides 2 with total regioselectivity. The starting compounds 1 were easily prepared by reaction of the corresponding lithium or potassium enolates of α-chloroamides with aldehydes or ketones. When the reaction was carried out in the presence of H₂O instead of D₂O, the corresponding 3-aryl-2-hydroxyamides were isolated. The treatment of enantiopure 3-aryl-2,3-epoxyamides afforded optically active 3-aryl-2-hydroxyamides.     

Synthesis of heterocycles on the basis of arylation products of unsaturated compounds. 19.* Arylation of 2-acetylthio- phene and the synthesis of 2-(5-aryl-2-thien- yl)-4-quinolinecarboxylic acids

The reaction of 2-acetylthiophene with acetylthiophene with arenediazonium chlorides in the presence of cupric chloride as catalyst gives 2-acetyl-5-arylthiophenes. These products react with 5-chloro- and 5-bromoisatins to give 6-chloro- and 6-bromo-substituted 2-(5-aryl-2-thienyl)-4-quinolinecarboxylic acids.     

Synthesis of 2-chloro-2-imidoylaziridines via aza-Darzens-type reaction of 3,3-dichloro-1-azaallylic anions and N-(arylsulfonyl)imines

3,3-Dichloro-1-azaallylic anions, generated by deprotonation of alpha,alpha-dichloroketimines 10 with lithium diisopropylamide, reacted with N-sulfonylaldimines 7 to produce the Mannich-type products N-[2,2-dichloro-3-(N-alkylimino)-1,3-diarylpropyl]benzenesulfonamides 11. The latter stable compounds were hydrolyzed at the imino functionality to afford N-[2,2-dichloro-3-oxo-1,3-diarylpropyl]benzenesulfonamides 12 in excellent yields. N-[2,2-Dichloro-3-(N-alkylimino)-1,3-diarylpropyl]benzenesulfonamides 11 were cyclized to cis-3-aryl-2-chloro-2-imidoylaziridines 19 in 81-99% yield with high diastereoselectivity, representing a novel and readily available class of stable 2-chloroaziridines. Finally, a highly stereoselective entry to 2-(aminomethyl)-2-chloroaziridines 27 (70-98% yield; de > 95-99) was worked out from the reaction of cis-3-aryl-2-chloro-2-imidoylaziridines 19 and sodium cyanoborohydride in the presence of acetic acid. The latter 2-(aminomethyl)aziridines 27 represent stereochemically defined small azaheterocyclic rings which were scarcely reported in the literature.     

Synthesis and reactions of 4-(arylhydrazino)coumarins

The interaction of 4-hydroxycoumarin with phenyl-, 2-chlorophenyl- and 4-bromophenyhydrazine hydrochlorides in the presence of triethylamine led in all cases to the corresponding 4-(arylhydrazino)-coumarins and 1-aryl-3-(2-hydroxyphenyl)-2H-pyrazolin-5-ones. 4-(Arylhydrazino)coumarins reacted with 4-chlorobenzaldehyde in the presence of piperidine acetate to give the corresponding 2-aryl-3-(4-chlorophenyl)[1]benzopyrano[4,3-b]pyrazol-4-ones. The reaction of 4-(4-bromophenylhydrazino)-coumarin with 4-chlorobenzaldehyde in the presence of piperidine acetate and an excess of piperidine gave 2-(4-bromophenyl)-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(piperidinocarbonyl)pyrazole, but the reaction of phenyl- and 4-(2-chlorophenylhydrazino)coumarins with 4-chlorobenzaldehyde gave 1-aryl-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(1-piperidino)carbonyl-4,5-dihydropyrazoles.     

Synthesis,stereochemistry, and isomeric transformations of cis- and trans-1,2-dimethyl-4-aryl-5-aroyl-2-imidazolines

The corresponding trans- and cis-1,2-dimethyl-4-aryl-5-aroyl-2-imidazolines were obtained from complexes of cis- and trans-1-methyl-2-aryl-3-aroylaziridines with BF₃ by heating with acetonitrile. The reaction proceeds with inversion of the configuration of the starting 3-aroylaziridines. In the presence of bases the complexes of cis-1,2-dimethyl-4-aryl-5-aroyl-2-imidazolines readily undergo isomerization to the corresponding trans analogs. The structures of the products were established on the basis of the IR, PMR, and mass spectra and the results of elementary analysis. The configurations of the compounds were determined by means of the Overhauser nuclear effect.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 952–957, July, 1981.     

Efficient synthesis of novel 6-substituted 2-(4-aryl-1,2,3-triazol-1-yl)pyrimidines and 7-deazapurines*

A simple and efficient synthesis of 6-substituted 2-(4-aryl-1,2,3-triazol-1-yl)pyrimidines and 7-deazapurines from readily available 6-chloro-2-methylthiopyrimidine and 6-chloro-2-methylthio-7-deazapurine derivatives is described. The synthetic strategy is based on sequential reactions: substitution of 6-chlorine group with amines or (2-pyridyl)tributylstannane, oxidation of the obtained 6-substituted 2-methylthiopyrimidines, and 7-deazapurines to the corresponding 2-methylsulfonyl derivatives, their conversion to 2-azido derivatives and Cu(I)-catalyzed azide???alkyne cycloaddition reaction with arylethynes.     

1,1,3-Trisubstituted cyclobutanes containing thiazole and thiourea fragments

The synthesis of 1-aryl-3-(2-chloro-1-hydroxyethyl)-1-methylcyclobutanes, 1-aryl-3-(2-chloro-1-oxoethyl)-1-methylcyclobutanes, 2-amino-4-(3-aryl-3-methylcyclobutyl)thiazoles, and N-[4-(3-aryl-3-methylcyclobutyl)thiazole-2-yl]-N′-arylthioureas is reported. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 424–429, March, 2006.