Synthesis of (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles via three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole

Three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole under mild conditions is described, which generates the desired (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles in moderate to good yields. This reaction proceeds smoothly with high selectivity. The tandem condensation, nucleophilic addition, and 5-exo-cyclization may be involved in the process.     

An organocatalytic rearrangement of 2-(N-alkyl-/aryl-)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde

2-(Arylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 4-oxo-4H-1-benzopyran-3-carbanilide when treated with glycine in the presence of formalin, but under similar conditions 2-(alkylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 3-alkylaminomethylenechroman-2,4-dione.     

Reaction of 3-(alken-1-yl)-4,5-dihydro-3H-pyrazoles with sodium nitrite in acetic acid

3-Vinyl-4,5-dihydro-3H-pyrazole reacted with sodium nitrite in acetic acid to give 3-vinyl-1-nitroso-4,5-dihydro-1H-pyrazole, whereas 3-isopropenyl-4,5-dihydro-3H-pyrazole under analogous conditions was unexpectedly converted into a nitro derivative, 3-(1-methyl-2-nitrovinyl)-4,5-dihydro-1H-pyrazole.     

Synthesis of 6-substituted 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones using the Vilsmeier reaction

The reaction of 6-amino-1,3-dimethyluracil with equimolar amounts of arylalkanone Mannich bases under optimized reaction conditions leads to 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines in a yield of 50-80%. Functionalization of these dihydropyridopyrimidine(1H,3H)-2,4-diones with the Vilsmeier reagent affords, depending on the reaction conditions, either 6-dimethylaminomethylidene substituted 5H-pyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones or the corresponding pyridopyrimidine(1H,3H)-2,4-diones bearing a carboxaldehyde function in position 6 of the heterocycle. Some further transformations of the aldehyde function demonstrate the synthetic potential of the synthesized structures, introducing pharmacologically relevant basic substituents into the side chain of these pyrido[2,3-d]pyrimidine derivatives.     

Unprecedented InCl3-catalyzed formation of cis-fused perhydrofuro[2,3-b]oxepines

2-Methylindole and its N-substituted derivatives react smoothly with 2,3-dihydrofuran (DHF) in the presence of a catalytic amount of InCl₃ under mild conditions to afford the corresponding 2-methyl-3-perhydrofuro[2,3-b]oxepin-4-yl-1H-indole derivatives in fairly good yields with high diastereoselectivity, while 3,4-dihydro-2H-pyran (DHP) affords exclusively 5,5-di(1H-3-indolyl)-1-pentanol derivatives in high yields under similar reaction conditions.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

AlCl3-mediated tandem Friedel-Crafts reactions of vinylidenecyclopropanes with acyl chlorides: a facile synthetic method for the construction of 1-[2-(2,2-diarylvinyl)-1-phenyl-3H-inden-5-yl]ethanone derivatives

AlCl₃-mediated tandem Friedel-Crafts reaction of vinylidenecyclopropanes with acyl chlorides produced the corresponding 1-[2-(2,2-diarylvinyl)-1-phenyl-3H-inden-5-yl]ethanone derivatives in moderate to good yields under mild conditions within short reaction time.     

A facile synthesis of new 3-(2-benzimidazolyl)-2-alkyl-4-(3H)-quinazolinones under microwave irradiation

Preparation of 2-amino-N-(1-H-benzimidazol-2-yl)benzamide and a variety of new 3-(2-benzimidazolyl)-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters under microwave irradiation are described.     

A facile synthesis of novel 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones using microwave heating

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (7a–w) have been synthesized by the Knoevenagel condensation reaction of 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (3a–d) with suitably substituted 2-(1H-indol-3-yl)2-oxoacetaldehydes (6a–g) under microwave conditions. The thioxothiazolidin-4-ones were prepared from the corresponding aryl/alkyl amines (1a–d) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a–g) were synthesized from the corresponding acid chlorides (5a–g) using HsnBu₃.     

Dy(OTf)3 as a versatile catalyst for the synthesis of 3-pyrrolyl-indolinones and pyrrolyl-indeno[1,2-b]quinoxalines

Dysprosium(III) triflate is found to catalyze efficiently the coupling of 4-hydroxyproline with indeno[1,2-b]quinoxalin-11-one and isatin derivatives under mild conditions to produce 11-(1H-pyrrol-1-yl)-11H-indeno[1,2-b]quinoxalin-11-one and 3-(1H-pyrrol-1-yl)indolin-2-one derivatives, respectively, in excellent yields in short reaction times. A comparative study with both InCl₃ and Dy(OTf)₃ is described.     

Diels-Alder cycloaddition of electrophilic 2H-azirines with 3-(3-(tert-butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-ones. Treatment of the cycloadducts under acidic conditions

3-(3-(tert-Butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-one was reacted with several electrophilic 2H-azirines to give the expected cycloadducts in moderate to good yields. Treatment of the cycloadducts under acidic conditions gave six-membered ring aminoenones and aziridine derivatives. In the case where anilinium fluoride was used an inversion at the C-2 stereogenic center was observed forming an isomer of the former cycloadduct. The chiral (R)-3-(3-(tert-butyldimethylsiloxy)buta-1,3-dienyl)-4-phenyloxazolidin-2-one was also reacted with an electrophilic 2H-azirine. The reaction showed no diastereoselectivity, but both diastereoisomers were fully isolated by chromatography.     

Synthesis of a new series of ditopic proligands for metal salts: differing regiochemistry of electrophilic attack at 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole

An improved synthesis of 3{5}-amino-5{3}-(pyrid-2-yl)-1H-pyrazole (I) is described, which affords the compound on a multi-gram scale. Reaction of I with acid chloride and isothiocyanate electrophiles in MeCN cleanly results in attack at its amino group, yielding N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)amide and N-(3-{pyrid-2-yl}-1H-pyrazol-5-yl)thiourea products. These are good candidates as proligands for the simultaneous complexation of metal cations and anions. However, treatment of I with isocyanates under the same conditions instead yields attack at the pyrazole ring, giving 3-(pyridin-2-yl)-5-aminopyrazole-1-carboxylic acid amides as the only isolable products. The differing regiochemistries of these reactions were confirmed by ¹H NMR and X-ray crystallography.     

Stereoselective synthesis of Z-3-alkoxy-2-[(4′-methoxyphenyl)methylidene]-1(3H)-isobenzofuranones

Photoreorganisation of 2-alkoxy-2-(4′-methoxyphenyl)-1H-indene-1,3(2H)-diones in anhydrous acetone affords exclusively Z-3-alkoxy-3-[(4′-methoxyphenyl)methylidene]-1(3H)-isobenzofuranones. The products were identified by X-ray crystallography of one of them.     

Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives

The superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids by Bronsted superacids (CF₃SO₃H, HSO₃F) or strong Lewis acids AlX₃ (X=Cl, Br) results in the formation of 4-aryl quinolin-2(1H)-ones in quantitative yields. The vinyl triflates or vinyl chlorides may be formed as additional reaction products. The investigated amides in reactions with benzene give 4,4-diaryl 3,4-dihydroquinolin-2-(1H)-ones under the superelectrophilic activation. 4-Aryl quinolin-2(1H)-ones in POCl₃ are converted into 4-aryl 2-chloroquinolines. 4-Fluorophenyl-4-phenyl 3,4-dihydroquinolin-2-(1H)-one give N-formylation products in a yield of 79% under the Vilsmeier–Haack reaction conditions.     

Efficient stepwise and one pot three-component synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles

Environmentally benign conditions have been developed for the synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles (3) starting from 3-acetyl-2H-chromen-2-one (1) through the intermediacy of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)malononitrile (2) using the Knoevenagel condensation followed by the Gewald reaction. Alternatively, 3 could also be prepared in a one pot method by treating equimolar amounts of 1, malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions, easy work-up procedure, and good yields.     

An efficient synthesis of (−)-3-deazaaristeromycin

The coupling reaction of 4-chloro-1H-imidazo[4,5-c]pyridine (6-chloro-3-deazapurine) and (3aS,4S,6R,6aR)-tetrahydro-2,2-dimethyl-6-vinyl-3aH-cyclopenta-[d][1,3]dioxo-4-ol under Mitsunobu reaction conditions provides, after three subsequent straightforward reactions, ready access to the highly biologically active (−)-3-deazaaristeromycin. The versatility of this procedure opens access to a diverse pool of 3-deazapurine carbocyclic nucleosides.     

Synthesis and anticorrosive properties of alkylammonium polyfluoro-3-(ethoxycarbonyl)-2-oxo-2h-chromen-4-olates

Reactions of ethyl polyfluoro-4-hydroxy-2-oxo-2H-chromene-3-carboxylates with amines under mild conditions afforded alkylammonium polyfluoro-3-(ethoxycarbonyl)-2-oxo-2H-chromen-4-olates which efficiently inhibited hydrochloric acid corrosion of mild steel at low concentrations (10^?4-10^?5 M).     

Regioselective synthesis of 3-aryl-5-(1H-indole-3-carbonyl)-4-hydroxyfuroic acids as potential insulin receptor activators

3-Methoxy-4-aryl-furan-2,5-dicarboxylic acid (8) is selectively converted into its C-5 methylester (6) by treatment with methyl chloroformate followed by decarboxylation in one flask. Acylation of the resulting half ester with a 7-substituted indole was performed under mild conditions to afford 3-aryl-5-(1H-indole-3-carbonyl)-4-methoxy-2-furoic acid (11). The synthetic utility of the resulting furoic acids as a skeleton in the synthesis of potential insulin receptor activators is established.     

Chemoselective synthesis of 3H-pyrrolo[2,3-c]quinolin-4(5H)-one derivatives from 3-phenacylideneoxindoles and substituted tosylmethyl isocyanide (TosMIC)

A simple and convenient synthetic approach to access of 3H-pyrrolo[2,3-c]quinolin-4(5H)-one derivatives by the reaction of (Z)-3-(2-oxo-2-ethylidene)indolin-2-one derivatives 1 with functionalized TosMICs under basic conditions has been reported. The desired products were obtained in good to excellent yields (82–94%). The easy accessibility of the starting materials, simple and mild reaction conditions, short reaction time, and good to excellent chemical yields make this methodology highly efficient.     

An expedient route to indoles via a cycloaddition/cyclization sequence from (Z)-1-methoxybut-1-en-3-yne and 2H-pyran-2-ones

The cycloaddition of (Z)-1-methoxybut-1-en-3-yne (2) with 5,6-disubstituted 3-acylamino-2H-pyran-2-ones 1 under microwave-irradiation conditions, with classical heating or at high-pressures (13-15 kbar) affords the benzene derivatives 3 with a strategically positioned 2-methoxyethenyl moiety. In some cases, at high-pressures after long reaction times, 2,2-dimethoxyethyl products 4 were obtained. Adducts 3 and 4 can be cyclized under mild conditions into 1,5,6-trisubstituted indole derivatives 5.