Synthesis of 4,6-Disubstituted 2-Thioxo-1,2-dihydropyridine-3-carbonitriles by the Reaction of Acetylenic Ketones with Cyanothioacetamide

Russian Journal of General Chemistry - The reaction of acetylenic ketones with cyanothioacetamide in the presence of morpholine yields 4,6-disubstituted...     

New example of acyl cleavage of benzoyl-1,1,1-trifluoroacetone in a three-component synthesis of 4-aryl-2-thioxo-6-phenyl-1,2-dihydropyridine-3-carbonitriles

A three-component condensation of aromatic aldehydes, cyanothioacetamide, and benzoyl-1,1,1-trifluoroacetone, involving the acyl cleavage of the latter, results in 4-aryl-2-thioxo-6-phenyl-1,2-dihydropyridine-3-carbonitriles. Their alkylation was studied.     

Synthesis of Heterocycles via 2-Thioxo-1,2-dihydropyridine-3-carbonitrile Derivative

The present study aimed to investigate the synthetic potentiality and chemical reactivity of 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative 1. This goal performed via its reaction with each of 1-chloroacetone and iodomethane to afford the corresponding 2-alkylthio derivatives 3 and 9, respectively. Compound 3 underwent intramolecular cyclization to afford the corresponding thieno[2,3-b]pyridine derivative 4 which in turn, reacted with dimethylformamide/dimethylacetal followed by hydrazine hydrate and nitrous acid to afford the corresponding pyridothienopyrimidine and pyridothienopyridazine derivatives 6 and 8, respectively. On the other hand, Compound 9 reacted with hydrazine hydrate to give 3-aminopyrazolo[3,4-b]pyridine derivative 10, which diazotized with nitrous acid to give the corresponding diazonium salt 11. Compound 11 coupled with several active –CH₂-containing reagents to synthesize the corresponding pyridopyrazolo-triazines 15, 24, 29, and 31. The formulas of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, ¹H NMR, Mass spectral data, as well as data from elemental analyses.     

Synthesis of 4-aryl-6-phenyl-2-thioxo-1,2-dihydropyridine-3-carbonitriles by three-component condensation of aromatic aldehydes with cyanothioacetamide and 4,4,4-trifluoro-1-phenylbutane-1,3-dione

4-Aryl-6-phenyl-2-thioxo-1,2-dihydropyridine-3-carbonitriles were synthesized by three-component condensation of aromatic aldehydes with cyanothioacetamide and 4,4,4-trifluoro-1-phenylbutane-1,3-dione. The reaction involved initial formation of Michael adducts which underwent acyl cleavage.     

Synthesis and structure of new substituted 2-dicyanomethylene-1,2-dihydropyridines

The synthesis of substituted 2-dicyanomethylene-1,2-dihydropyridines 3b-c and 2-dicyanomethylene-2,3,4,5-tetrahydropyridine 4 is accomplished from malononitrile dimer and propenenitriles 2 . All structures were determined by nmr techniques; however to put our structural assignment for 6-amino-3-cyano-5-ethoxycarbonyl-2-dicyanomethylene-1,2-dihydropyridine 3d on a firm and unequivocal basis we decided to perform X-ray diffraction analysis of this compound.     

Ionic liquid-assisted carboxylation of amines by CO2: a mechanistic consideration

The catalytic roles of ionic liquids (ILs) in the syntheses of 1,3-disubstituted ureas from the carboxylation of amines by CO(2) were experimentally and theoretically investigated. The carboxylation reaction of n-butylamine was greatly facilitated by the presence of an IL and the catalytic activity of the IL was strongly affected by the nucleophilicity of the anion. Computational study on the mechanistic aspects of the carboxylation with methylamine with or without the presence of an IL, 1-ethyl-3-methylimidazolium chloride, implies that the activation energies of the transition states and the intermediate ionic species could be lowered significantly through the multi-interactions of the carbonyl group of CO(2) with both cations and anions of the ILs.     

Reaction of cis-3-bromo-1,2-dibenzoylpropene with amines

The reaction of cis-3-bromo-1,2-dibenzoylpropene (1) with amines proceeds by means of a substitution-rearrangement attack to give the 2-(α-aminoacetophenonyl)acrylophenones ( 2 ). Like similar structures, 2 undergoes further substitution-rearrangement by amines to give 3-benzoyl-5-phenylpyrroles ( 5 ) and an enaminoketone, α-acetophenonyl-β-aminoacrylophenone ( 3 ). Competitive with substitution-rearrangement, amine addition to 2 followed by loss of hydrogen and then water leads to formation of the 3-benzoyl-4-amino-5-phenylpyrroles ( 4 ). The enaminoketones ( 3 ) by contrast with 2 are quite stable. Structure 2 when in polar solvents or in the presence of amines undergoes substitution-rearrangement to give 3 , which can be induced to give the pyrroles ( 5 ) when exposed to acid conditions. When neat or in solvents of low polarity, 2 undergoes intermolecular substitution-rearrangement-dehydration to give 5 almost exclusively. A novel addition reaction of 3-benzoyl-5-phenylfuran involving attack by isopropyl- or cyclohexylamine provides a quantitative method of synthesizing the appropriate N-substituted examples of 3 and an efficient method of deriving the corresponding pyrroles ( 5 ).     

A New Version of Multicomponent Synthesis of 4,6-Diaryl-2-sulfanylidene-1,2-dihydropyridine-3-carbonitrile Derivatives

Multicomponent condensation of aromatic aldehydes with acetophenones, cyanothioacetamide, and alkylating agents has been shown to provide synthetic routes to various pyridine and thienopyridine derivatives. The structure of some of the synthesized heterocycles has been confirmed by X-ray analysis.     

Synthesis of Ethyl 5-(Arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates

Russian Journal of Organic Chemistry - A one-step procedure has been developed for the synthesis of previously unknown ethyl 5-(arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates by...     

Cyclization of secondary aromatic amines with formaldehyde and cyclopentanone

Secondary aliphatic-aromatic and aromatic amines react with formaldehyde and cyclopentanone in the presence of perchloric acid to form cyclopenta[c]quinolinium salts in good yields. The yields of the cyclization conditions as a function of reagent ratio and reaction time and temperature were studied, and procedures for isolation and purification of the target compounds were developed.     

Simple one-pot multicomponent approach to polyfunctionalized 2-amino-1-methyl-6-(methylthio)-5-nitro-4-aryl-1,4-dihydropyridine-3-carbonitriles

A series of polyfunctionalized 2-amino-1-methyl-6-(methylthio)-5-nitro-4-aryl-1,4-dihydropyridine-3-carbonitriles have been prepared using a multicomponent condensation reaction between aromatic aldehydes, malononitrile, and (Z) N-methyl-1-(methylthio)-2-nitroethenamine in the presence of Et₃N in acetonitrile.     

Gold-catalyzed 1,2-/1,2-bis-acetoxy migration of 1,4-bis-propargyl acetates: a mechanistic study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2-/1,2-bis-acetoxy migration in 1,4-bis-propargyl acetates to form 2,3-bis-acetoxy-1,3-dienes. In this way, (1Z,3Z)- or (1Z,3E)- and (1E,3Z)-1,3-dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one-pot synthesis of quinoxaline heterocycles and tandem Diels-Alder processes have also been devised.     

Synthesis of 2-thioxo-6-trifluoromethyl-1,2-dihydropyridine-3-carbonitrile and ethyl 5-cyano-6-thioxo-1,6-dihydropyridine-2-carboxylate by the S<Subscript>N</Subscript>Vin reaction

Ethyl 5-cyano-6-thioxo-1,6-dihydropyridine-2-carboxylate and 2-thioxo-6-trifluoromethyl-1,2-dihydropyridine-3-carbonitrile were obtained by the S_NVin reaction. The latter compound was used in the synthesis of 2-alkylsulfanyl-6-trifluoromethylpyridin-3-carbonitriles, 3-amino-5-trifluoromethylthieno[2,3-b]pyridin-2-carboxamide, and 7-thifluoromethyl-2-spirocyclopentane-1,2,3,4-tetrahydropyrido[2′,3′:2,3]thieno[4,5-d]pyrim-idin-4-one.     

Regioselective hydrodehalogenation of 3,5-dihaloisothiazole-4-carbonitriles: synthesis of 3-haloisothiazole-4-carbonitriles

3,5-Dibromoisothiazole-4-carbonitrile 1 treated with Zn or In dust (5 equiv) and HCO₂H undergoes regioselective hydrodebromination to give 3-bromoisothiazole-4-carbonitrile 3 in 70-74% yield. Similarly, 5-bromo and iodo 3-chloroisothiazole-4-carbonitriles 8 and 9 give 3-chloroisothiazole-4-carbonitrile 4 in 77 and 85% yields, respectively. Also hydrodeamination of 5-amino-3-chloroisothiazole-4-carbonitrile 7 using isoamyl nitrite gives the latter in 95% yield. The dibromoisothiazole 1 reacts with Zn dust in either DCO₂D or HCO₂D to give 3-bromo-5-deuterioisothiazole-4-carbonitrile 10 in 71 and 58% yields, respectively. The 3-bromoisothiazole 3 reacts with cyclic dialkylamines to give the corresponding 2-(dialkylaminomethylene)-malononitriles and not the expected 3-dialkylaminoisothiazole-4-carbonitriles. Finally, the 3-bromoisothiazole 3 is readily converted into both 3-bromoisothiazole-4-carboxamide 19 and the carboxylic acid 20. All products are fully characterized.     

Photocycloaddition of 2-Oxopyran-3-carbonitriles to 2,3-Dimethylbut-2-ene

On acetone-sensitized irradiation in the presence of 2,3-dimethylbut-2-ene, α-cyano-α,β-unsaturated δ-lactone 5 is converted both to cyclopentapyrans resulting from stepwise addition of the alkene to the olefinic C(β)- and the nitrile C-atom of triplet excited 5 , and cyclobutapyranes, i.e., [2+2] cycloadducts. Similarly, direct irradiation of 1-benzopyran-3-carbonitrile 6 in the presence of the same alkene affords cyclobutabenzopyran 13 and cyclopentabenzopyran 14 , the latter resulting from an upper excited triplet state of 6 .