Regioselective synthesis of 1,5-diaryl-1H-imidazoles by palladium-catalyzed direct arylation of 1-aryl-1H-imidazoles

[reaction: see text] A variety of 1,5-diaryl-1H-imidazoles have been regioselectively synthesized by direct coupling of 1-aryl-1H-imidazoles with aryl iodides or bromides in DMF in the presence of CsF as the base and a catalyst precursor consisting of a mixture of Pd(OAc)2 and AsPh3. The data obtained in this synthetic study support a reaction mechanism involving an electrophilic attack of an arylpalladium(II) halide species onto the imidazole ring. Interestingly, some imidazole derivatives synthesized in this study have been found to exhibit significant cytotoxic activity against human tumor cell lines.     

Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole

Highly selective, practical, and efficient protocols for the preparation of 4(5)-aryl-1H-imidazoles 2, 2,4(5)-diaryl-1H-imidazoles 3, and 4,5-diaryl-1H-imidazoles 1 are described. A key step of these protocols is the regioselective synthesis of 5-aryl-1-benzyl-1H-imidazoles 9 by Pd-catalyzed direct C-5 arylation of commercially available 1-benzyl-1H-imidazole (8) with aryl halides. The three-step synthesis of compounds 3 from 8 also involves the Pd-catalyzed and Cu-mediated direct C-2 arylation of imidazoles 9 with aryl halides under base-free and ligandless conditions. On the other hand, the four-step synthesis of imidazoles 1 from 8 also involves the regioselective bromination of compounds 9 and a Suzuki reaction of the resulting 5-aryl-1-benzyl-4-bromo-1H-imidazoles 11 with arylboronic acids 5 under phase-transfer conditions, followed by N-debenzylation.     

Synthesis of New 1H-indazole derivatives

Reactions of 3-aryl-1-phenyl-2-propen-1-ones IIa-d with ethyl phenylacetate (I) in the presence of sodium ethoxide under reflux for one hour gave only the corresponding 3,5-diaryl-2,4-dibenzoyl-6-phenyl-cyclo-hexanones IIIa-d. The reaction of these compounds with hydrazine hydrate afforded the corresponding 5-benzoyl-4,6-diaryl-3,7-diphenyl-1,4,5,6,7-pentahydro-1H-indazole IVa-d. The structures of the products were established by spectroscopic (ir, uv, nmr and mass spectra), single-crystal X-ray analysis and chemical evidence.     

Polyfunctional imidazoles: VI. Synthesis of 2-amino-1-aryl-4-chloro-1H-imidazole-5-carboxylic acids derivatives

Aryl-2,4-dichloro-5-formylimidazoles by a successive treatment with hydroxylamine and thionyl chloride were converted into 1-aryl-2,4-dichloroimidazole-5-carbonitriles which by the action of sodium azide and tin(II) chloride were transformed into 2-amino-1-aryl-4-chloroimidazole-5-carbonitriles. The consecutive reactions of 2-azido-1-aryl-4-chloro-5-formylimidazoles with N-bromosuccinimide, methanol, or amides led to the formation of methyl esters and amides of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids. The reduction of the latter with tin(II) chloride resulted in the corresponding derivatives of 2-amino-1-aryl-4-chloroimidazole-5-carboxylic acids, and the reduction of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids was accompanied with decarboxylation and yielded 2-amino-1-aryl-4-chloroimidazoles.     

Polyfunctional imidazoles: VIII. 1-Aryl-4-chloro-5-[R-sulfanyl(sulfonyl)methyl]-1H-imidazoles

Alkylation of (1-aryl-4-chloro-1H-imidazol-5-yl)methanethiols with alkyl halides, propargyl bromide, or chloroacetic acid gave 1-aryl-5-(R-sulfanylmethyl)-4-chloro-1H-imidazoles. 1-Aryl-4-chloro-5-(methylsulfanylmethyl)-1H-imidazoles and [(1-aryl-4-chloro-1H-imidazol-5-yl)methylsulfanyl]acetic acids were oxidized to the corresponding sulfones with potassium permanganate.     

New efficient approach to 2,2-diaryl-1,1-difluoro-1-alkenes and 1,1-difluoro-2-aryl-1,3-dienes via Suzuki coupling of alpha-halo-beta,beta-difluorostyrenes

[reaction: see text] Alpha-halo-beta,beta-difluorostyrenes [ArCX = CF2; X = Br, I; Ar = aryl, heteroaryl; synthesized by the Pd(0)-catalyzed coupling reaction of the corresponding alpha-halo-beta,beta-difluoroethenylzinc reagents (CF2=CXZnCl, X = Br, I) with aryl iodides] were functionalized at the halogen site with arylboronic acids under Pd(0)-catalyzed Suzuki-Miyaura coupling reaction conditions to obtain 2,2-diaryl-1,1-difluoro-1-alkenes (ArAr'C=CF2, Ar' = aryl, heteroaryl) in 51-91% isolated yield. The corresponding reaction with alkenylboronic acids produced 1,1-difluoro-2-aryl-1,3-dienes in 53-80% isolated yield. Alternatively, 2,2-disubstituted-1,1-difluoro-1-alkenes were synthesized in moderate yield by a zinc-insertion reaction at the halogen site of the alpha-halo-beta,beta-difluorostyrenes, followed by Pd(0)-catalyzed cross-coupling of the zinc reagent with aryl or alkenyl iodides.     

On the formation and solvolysis of 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines

The condensation of aryl methyl ketones 6 with acetic anhydride 4a in the presence of the boron trifluoride-acetic acid adduct 7 gives rise to the formation of 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines 8 in satisfactory yields. The stable 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines 8 can be transformed by hydrolysis into the corresponding aroylacetones 9. The reaction was optimized so as to avoid the formation of by-products, such as 2,4-diaryl-6-methylpyrylium tetrafluoroborates 11 or self-condensation products. © 1997 John Wiley & Sons, Inc.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

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.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 3: Syntheses of tri- and tetra-aryl DPPs

Novel synthetic methodologies leading towards 2,3,5-triaryl- and 2,3,5,6-tetraaryl-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-diones (tri- and tetra-aryl-DPPs) and their derivatives have been investigated. Direct arylation of 3,6-diphenyl-DPP was possible using 1-fluoro-2,4-dinitrobenzene. Acylation of ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates with N-arylbenzimidoyl chlorides in the presence of a strong base gives the novel 2,3,6-triaryl-DPPs together with the corresponding uncyclised enamines. A new and simple method for the synthesis of ethyl 1,2-diaryl-4,5-dihydro-5-oxopyrrole-3-carboxylates has led to an alternative route to triaryl-DPPs via reaction with benzonitrile under basic conditions, and combination of this with the benzimidoyl chloride methodology has enabled the synthesis of variously substituted 2,3,5,6-tetraphenyl-DPPs.     

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.     

Massenspektroskopische Untersuchungen an 2,5-Diaryl-1-(arylimino)-1λ4,2,5-thiadia-zolidin-3,4-dionen

The mass spectra of 2,5-diaryl-1-(arylimino)-1λ⁴,2,5-thiadiazolidin-3,4-diones have been examined. Some fragmentations are explained by rearrangement of the title compounds to 1,3-(diarylimino)-5-aryl-1λ⁴,2,5-thioxazolidin-4-ones and 1-oxo-2,5-diaryl-3-(arylimino)-1λ⁴,2,5-thiadiazolidin-4-ones.     

Polyfunctional imidazoles: VII. 1-aryl-4-chloro-5-[hydroxy(halo)methyl]-1H-imidazoles and their derivatives

The reduction of 1-aryl-4-chloro-1H-imidazole-5-carbaldehydes with sodium tetrahydridoborate gave 1-aryl-4-chloro-1H-imidazol-5-ylmethanols which were converted into 5-chloromethyl and 5-fluoromethyl derivatives. 1-Aryl-4-chloro-5-chloromethyl-1H-imidazoles reacted with sodium azide, secondary amines, thiols, and triphenylphosphine to produce the corresponding products of chlorine replacement in the 5-chloromethyl group.     

New method for the annelation of a pyridine ring on derivatives of imidazole and benzimidazole

The interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-substituted (benz)imidazoles in benzene gave (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-imidazolium bromides and (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-benzimidazolium bromides which readily cyclize in the presence of base to form derivatives of 7,9-diarylpyrido[1,2-a]benzimidazole and 6,8-diarylpyrimidazo[1,2-a]pyridine. The effects of the nature of substituents in the benzene ring of the diarylbutenones and the substituent at N(1) in the (benz)imidazoles on the alkylation and cyclization reactions has been studied. The optimum conditions for the synthesis of the 5-R-4-hydroxy-2,4-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]benz-imidazol-10-ium, 5-R-2,4-diaryl-4-hydroxy-4,5-dihydro-3H-pyrido[1,2-a]benzimidazol-10-ium, and 5-R-2,4-diaryl-5H-pyrido[1,2-a]benzimidazol-10-ium have been found.     

A convenient synthesis of 5-aryl- and 5-heteroaryl-2-furaldehydes by the cross-coupling reaction of organozincs

An efficient synthetic route for the preparation of 5-heteroaryl- and 5-aryl-2-furaldehydes has been developed. It has been accomplished by the palladium(0)-catalyzed cross-coupling reaction of heteroarylzinc and arylzinc reagents with 5-bromo-2-furaldehyde under very mild conditions.     

One-pot palladium-catalyzed C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with arylboronic acids

The 2-aryl-3-iodo-4-(phenylamino)quinolines undergo one-pot palladium-mediated C-I and C-H bond activation and subsequent Suzuki-Miyaura cross-coupling with arylboronic acids under anhydrous conditions to afford mixture of 2,3-diaryl-4-(phenylamino)quinolines (minor) and 2-aryl-4-([(1,1′-biaryl)-2-yl]amino)quinoline derivatives (major). The 2,3-diaryl-4-(phenylamino)quinolines were isolated as major products when 2 M K₂CO₃ was used as a base. A plausible mechanism, which implicates a six-membered palladacycle intermediate is proposed for the formation of the observed mixture of products. The prepared compounds were characterized using a combination of spectroscopic and X-ray crystallographic techniques.     

Rhodium(III)-catalyzed oxidative coupling of 5-aryl-1H-pyrazoles with alkynes and acrylates

[RhCp*Cl(2)](2)-catalyzed oxidative coupling of 5-aryl-1H-pyrazoles with alkynes and acrylates has been achieved using Cu(OAc)(2) as an oxidant. Coupling with alkynes afforded six-membered azacycles as a result of C-C and C-N coupling. Coupling with acrylates followed a process of diolefination and a subsequent aza-Michael cyclization.     

Spirobisheterocyclization of 5-(Methoxycarbonyl)-1<Emphasis Type="Italic">H</Emphasis>-pyrrol-2,3-diones by the action of enaminoesters. Crystal and molecular structure of 1,7-diazaspiro[4.4]nonane

1-Aryl-4-aroyl-5-(methoxycarbonyl)-1Н-pyrrole-2,3-diones react with methyl 4-aryl-2-(arylamino)-4-oxobut-2-enoates with the formation of methyl 1,7-diaryl-4,9-diaroyl-3-hydroxy-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-8-carboxylates.     

Synthesis of 4-Hydroxy-3-(1-aryl-2-acetylethyl)-7,8-diaryl-2H-thieno(3,2-h)chromen-2-ones Using Cerium(III) Chloride

A new series of 4-hydroxy-3-(1-aryl-2-acetylethyl)-7,8-diaryl-2H-thieno(3,2-h)chromen-2-ones were synthesized in good yields by reacting 4-hydroxy-7,8-diaryl-2H-thieno(3,2-h)chromen-2-ones with various α,β-unsaturated ketones in presence of cerium(III) chloride in acetonitrile.     

Reaction of 5-Amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile with Hydroxycyclohexanones

Russian Journal of General Chemistry - The reaction of 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile with 3-aryl-5-hydroxy-5- methyl-2,4-di(ethoxycarbonyl)cyclohexanones in acetic acid...