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Base-catalyzed nucleophilic addition of carbon nucleophiles to the exocyclic double bond of 2-(5-aryl-4-methyl-2-oxo-1,2-dihydro-3H-pyrrol-3-ylidene)malononitriles afforded spiro-fused pyrrole derivatives, 7-amino-3-aryl-4-methyl-1-oxo-8-oxa-2-azaspiro[4.5]deca-3,6,9-triene-6-carbonitriles. The products can be regarded as rare structural analogs of biologically active spirans based on isatin.

An environmentally friendly method has been developed for the preparation of 5H-chromeno[2,3-b]pyridine derivatives in an aqueous medium under ultrasound irradiation.

Successive treatment of 3-acylcyclopropane-1,1,2,2-tetracarbonitriles with sodium hydrogen carbonate and alkylmercaptan in water environment results in the formation of 2-(5-amino-2-aryl-2-alkyl-sulfanyl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles.

A procedure has been developed for the synthesis of polyfunctional pyrano[3,4-c]pyrrole derivatives via intramolecular cyclization involving vicinal cyano and carboxamide groups on a pyran ring. 3-Amino-1-oxo-1,3a,4,7a-tetrahydropyrano[3,4-c]pyrrole-3a,7a-dicarbonitrile thus obtained react with organic amines to give stable ammonium salts and undergo hydrolysis to 1,3-dioxo-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-3a,7a-dicarbonitriles in the presence of sulfuric acid.

Reaction of 2-chloropyridine-3,4-dicarbonitriles with primary amines in the presence of potassium carbonate in ethanol results in the fusion of pyrrole cycle and the formation of N 1-substituted 4-halo-1H-pyrrolo-[3,4-c]pyridine-1,3(2H)-diimines.

In reaction of tetracyanoethylene with ketones and HCl in 1,4-dioxane at 30–40°? 6-hydroxy-2-chloro-1,4,5,6-tetrahydropyridine-3,4,4-tricarbonitriles are formed.

N-Aryl- and N,N-diethyl-3-oxobutanamides reacted with salicylaldehyde and N-phenylthiourea in ethanol in the presence of sodium hydrogen sulfate as catalyst to give the corresponding N-substituted 2-methyl-3-phenyl-4-sulfanylidene-3,4,5,6-tetrahydro-2H-2,6-methano-1,3,5-benzoxadiazocine-11-carboxamides.

The reaction of potassium 2-(2,2-dimethylpropanoyl)-1,1,3,3-tetracyanopropenide with an equimolar amount of 2-sulfanylethanol afforded 2-{5-amino-2-(tert-butyl)-4-cyano-2-[(2-hydroxyethyl)sulfanyl]- 2,3-dihydrofuran-3-ylidene}propanedinitrile, whereas 4-amino-1-(tert-butyl)-1,6-bis[(2-hydroxyethyl)- sulfanyl]-3-imino-1,3-dihydrofuro[3,4-c]pyridine-7-carbonitrile was obtained in the reaction with excess 2-sulfanylethanol.

Annulation of 2-chloropyridine-3,4-dicarbonitriles with hydrazine hydrate and N,N-dimethylhydrazine afforded 3-aminopyrazolo[3,4-b]pyridine-4-carbonitriles and 3-amino-1-methylpyrazolo[3,4-b]pyridine- 4-carbonitriles, respectively.

A procedure has been developed for the synthesis of methyl 6-alkyl-3-cyano-2-halopyridine-4-carboxylate by three-component reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles with hydrogen halides in methanol.

5-Oxoalkane-2,2,3,3-tetracarbonitriles have been synthesized by reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles with methyl iodide in dimethyl sulfoxide.

4-Aryl-2-aminobuta-1,3-diene-1,1,3-tricarbonitriles (benzylidene derivatives of malononitrile dimer) reacted with bromo(cyano)acetic acid amide and esters to give the corresponding 2-amino-6-aryl-5-cyano-4-(dicyanomethylidene)-3-azabicyclo[3.1.0]hex-2-ene-1-carboxylic acid amides and esters.

Methyl aroylpyruvates reacted with 4-amino-N-carbamimidoylbenzene-1-sulfonamide in acetic acid–ethanol (1: 1) to give methyl 4-aryl-2-{[4-(carbamimidoylsulfamoyl)phenyl]amino}-4-oxobut-2-enoates which were found to exist in solution as mixtures of Z and E isomers.

2-Oxocycloalka[b]pyridine-3,4-dicarbonitriles reacted with nitric acid in the presence of potassium nitrate to give α-gem-dinitro derivatives of cycloalka[b]pyridines.

Reactions of 2-aroyl-1,1,3,3-tetracyanopropenides with hydrogen halides in solvents of low dielectric permittivity result in the formation of 6-amino-2-aroyl-2-halopyridine-3,5-dicarbonitriles. 2-Acyl-1,1,3,3-tetracyanopropenides under similar conditions afford 2-(2-alkylidene-5-amino-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles. In solvents of high dielectric permittivity the result of the reaction depends on the nature of the hydrogen halide and the acyl(aroyl) substituent: With HCl and HBr 2-aroyl-1,1,3,3-tetracyanopropenides form 2-(5-amino-2-aryl-2-halo-4-cyano-2,3-dihydrofuran-3-ylidene)-propanedinitriles, and 2-acyl-1,1,3,3-tetracyanopropenides give 2-(2-alkylidene-5-amino-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles; with HI depending on the reaction conditions and the structure of the acyl substituent 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles, 2-(5-amino-4-cyano-2,3-dihydrofuran-3-ylidene) propane-dinitrile, 2-amino-4-(dimethoxybenzyl)-6-iodo-5-cyanonicotinamide, 4-amino-6-iodo-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-7-carbonitrile, or 4-amino-6-iodo-3-oxo-1-ethylidene-1,3-dihydrofuro[3,4-c]pyridine-7-carbonitrile are obtained.

Reaction of arylmethylidene derivatives of malononitrile dimer with 1,3-cyclohexanediones in anhydrous methanol in the presence of sodium methylate as catalyst affords 4-amino-5-aryl-2-methoxy-6-oxo-5,6,7,8,9,10-hexahydrobenzo[b][1,8]naphthyridine-3-carbonitrile. In the presence of strong electron-donor substituents in the benzene ring the reaction takes another route resulting in 4-amino-2-aryl-6-methoxypyridine-3,5-dicarbonitriles.

Reaction of methyl 6-aryl-5-acetyl-3,6-dihydrotetrazolo[1,5-a]pyrimidine-4-carboxylates with ammonia and aliphatic amines results in 7-aryl-6-methylene-3,7-dihydropyrrolo[3,4-d]tetrazolo[1,5-a]-pyrimidine-4-ones and their 5-alkyl derivatives.

Reactions of 3-amino-8-hydroxy-1,6-dioxo-2,7-diazaspiro[4.4]non-3-ene-4-carbonitriles with aqueous hydrohalic acid led to the formation of alkyl-substituted pyrrolo[3,4-c]-pyrrole-1,3,4,6-tetraones.

Acid-catalyzed hydrolysis of 3,4-dialkyl-substituted 8-amino-1-imino-6-morpholin-4-yl-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles under mild conditions led to the formation of 8-amino-6-morpholin-4-yl-1-oxo-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles, and their acylation afforded N-(8-amino-9-cyano-6-morpholin-4-yl-2-oxa-7-azaspiro-[4.4]nona-3,6,8-trien-1-ylidene)acetamides. The NMR spectra of compounds synthesized in contrast to the spectra of initial N-unsubstituted imins contained no doubled proton and carbon signals.

Reactions of 2-acyl(aroyl)-1,1,3,3-tetracyanopropenides with hydrazine hydrate followed by neutralization led to the formation of 2-amino-4-[hydrazono(aryl)methyl]-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles.

Reaction of 2,2,3,3-tetracyanocyclopropyl ketones with water solution of sodium hydroxide after neutralization with sulfuric acid leads to the formation of 4-amino-1-hydroxy-3,6-dioxo-2,3,5,6-tetrahydro-1Hpyrrolo[3,4-c]pyridine-7-carbonitriles. Pivaloyltetracyanocyclopropane reacts in another way and is converted into sodium 6a-tert-butyl-3,4-dicyano-5-oxo-1,5,6,6a-tetrahydropyrrolo[2,3-b]pyrrol-2-olate. 1-Benzoyl-1-methylcyclopropane-2,2,3,3-tetracarbonitrile reacts with the sodium hydroxide with the retention of the threemembered ring and the formation of 11-methyl-4-phenyl-3,5,9-triazatetracyclo[5.3.1.01,7.04,11]undecane-2,6,8,10-tetraone.

The reaction of sodium 2-acyl(aroyl)-1,1,3,3-tetracyanopropenides with hydroiodic acid at heating led to the formation of 1-alkyl(aryl)-4-amino-6-iodo-3-oxo-1,3-dihydrofuro[3,4-c]pyridine-7-carbonitriles.

3-Benzoylcyclopropane-1,1,2,2-tetracarbonitrile reacted with water to give 2-benzoyl-1,3-dicyanocyclopropane-1-carboxamide as a result of hydrolysis of the cyano group in the trans position with respect to the carbonyl group and subsequent decarboxylation. The reaction of 3-benzoyl-3-methylcyclopropane-1,1,2,2-tetracarbonitrile with water involved heterocyclization with participation of the carbonyl group and cis-cyano groups, leading to 8-methyl-3,6-dioxo-1-phenyl-2,7-diazatricyclo[3.2.1.04,8]octane-4,5-dicarbonitrile. Hydrolysis of 3-alkylcyclopropane-1,1,2,2-tetracarbonitrile followed both reaction paths to produce mixtures of products, including 7-alkyl-4-amino-7-hydroxy-1,9-dioxo-3,8-diazatricyclo[4.3.0.01,5]non-3-ene-5-carbonitriles. In all cases, the three-membered ring was retained.

The reaction of 5,6-dialkyl-2-halopyridine-3,4-dicarbonitriles with alcoholic ammonia under elevated pressure gave 5,6-dialkyl-2-aminopyridine-3,4-dicarbonitriles as a result of nucleophilic replacement of the halogen atom by amino group. 6,7-Dialkyl-4-halo-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diimines were formed in analogous reaction at room temperature in the presence of potassium carbonate.

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides reacted with hydrogen halides along two concurrent pathways with formation of furan or pyridine derivatives. The reaction in butan-2-ol afforded 2-amino-4-acyl-(aroyl)-6-halopyridine-3,5-dicarbonitriles, whereas the major products in the reactions with HCl and HBr in aqueous solution were the corresponding 2-(5-amino-2-aryl-2-chloro(bromo)-4-cyano-2,3-dihydrofuran-3-ylidene)malononitriles. The reaction with aqueous hydrogen iodide was accompanied by reductive deiodination and produced 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)malononitriles.

Reactions of 2-aroyl-1,1,3,3-tetracyanopropenides with thiols in acid medium led to the formation of the corresponding 2-alkylsulfanyl-substituted 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles.

The reaction of 2,2,3,3-tetracyanocyclopropyl ketones with hydrazine involved the addition at the carbonyl and cyano groups and resulted in the formation of previously unknown polycyclic systems whose common feature was the presence in the structure of a pyridazine ring. In the general case 3-substituted 6-amino-8-oxo-4,5,7-tptriazatricyclo[4.3.0.02.9]-non-3-ene-1,9-dicarbonitriles were obtained. The reaction with 3-pivaloylcyclopropane-1,1,2,2-tetracarbonitrile took another route with the opening of the three-membered ring and the formation of 3-amino-7a-tert-butyl-6-oxo-5,6,7,7a-tetrahydro-4aH-pyrrolo[2,3-c]pyridazine-4,5-dicarbonitrile.

2′-Oxo-1′,2′-dihydrospiro[cyclopropane-1,3′-indole]-2,2,3,3-tetracarbonitriles reacted with oxygencentered nucleophiles to form addition products at the cyano groups with conservation of the three-membered ring. Reactions of the title compounds with alcohols required the presence of base catalyst, and the products, 2-amino-4,4-dialkoxy-2′-oxo-1′,2′-dihydrospiro[3-azabicyclo[3.1.0]hex-2-ene-6,3′-indole]-1,5-dicarbonitriles, were converted into the corresponding 2-imino-2′,4-dioxospiro[3-azabicyclo[3.1.0]hexane-6,3′-indole]-1,5-dicarbonitriles and 2,2′,4-trioxospiro[3-azabicyclo[3.1.0]hexane-6,3′-indole]-1,5-dicarbonitriles by the action of acetic and sulfuric acids, respectively. The reactions with ketone oximes occurred in the absence of a catalyst, yielding 2-amino-4,4-bis(alkylideneaminooxy)-2′-oxo-1′,2′-dihydrospiro[3-azabicyclo[3.1.0]hex-2-ene-6,3′-indole]-1,5-dicarbonitriles. The reactions with thiols, aliphatic amines, and anilines were accompanied by opening of the three-membered ring. In the reactions with triphenylphosphine and thiols 2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)malononitrile was obtained, while morpholine and N,N-dimethylaniline gave rise, respectively, to 3,3-diaryl-and 3,3-dimorpholino-1H-indol-2(3H)-ones and tri- and dicyanoethylene derivatives.

We now propose a new synthetic approach to photochromic diarylethenes, which is based on the reaction of tetracyanoethylene with ketones as key intermediate step. Tetracyanoethylation of ketones has been well documented; however, there are almost no published data on reactions of aryl arylmethyl ketones with tetracyanoethylene. Adducts of tetracyanoethylene with ketones of the general formula R(CO)CH2R′ were used as starting compounds to obtain heterocycles containing an RC=CR′ fragment [4–10]. Analogous reactions with aryl arylmethyl ketones Ar(CO)CH2Ar could give rise to various 1,2-diarylethenes as new potential photochromes. We were the first to react tetracyanoethylene with 1,2-diarylethanones Ia and Ib in the presence of a catalytic amount of hydrochloric acid. As a result, we isolated 3,4-diaryl-4-oxobutane-1,1,2,2-tetracarbonitriles IIa and IIb. The substrates were deoxybenzoin (Ia), the parent compound of the 1,2-diarylethanone series, and 1,2-bis(2,5-dimethylthiophen-3-yl)ethanone (Ib). The latter was selected taking into account that diarylethenes containing thienyl substituents are most promising from the viewpoint of the design of practically useful photochromic devices [1]. Ketone Ib was synthesized in a number of steps starting from hexane2,5-dione [11].

5,5-Dialkyl-2-halo-6-hydroxy-5,6-dihydro-1H-pyridine-3,4,4-tricarbonitriles reacted with morpholine in aprotic solvent to give the corresponding 3,3-dialkyl-4,5-dicyano-6-halo-2-morpholino-1,2,3,4-tetrahydropyridine-4-carboxamides, while analogous reaction in amphiprotic solvent resulted in the formation of 8,8-dialkyl-3-halo-6-oxo-2,7-diazabicyclo[3.2.1]oct-3-ene-4,5-dicarbonitriles.

A procedure for the synthesis of 2,2,3,3-tetracyanocyclopropyl ketones has been developed on the basis of three-component Wideqvist reaction of dihydroxymethyl ketones, 2-bromomalononitrile, and malononitrile. The presence of five electron-withdrawing groups in the resulting cyclopropyl ketones determines high acidity of proton in the cyclopropane ring. Facile deprotonation by the action of bases promotes opening of the three-membered ring with formation of either 1,1,3,3-tetracyanopropenides or (in the presence of alcohols or oximes), [2-alkoxy(aminooxy)-5-amino-4-cyanofuran-3(2H)-ylidene]malononitriles. The reaction with acetone oxime was not accompanied by cleavage of the three-membered ring, and nucleophilic attack was directed at the cyano groups in the trans position with respect to the carbonyl group to give the corresponding (1R*,5S*,6R*)-4-amino-2,2-bis(prop-2-ylideneaminooxy)-3-azabicyclo[3.1.0]hex-3-ene-1,5-dicarbonitriles.

2-(4-Amino-2,5-dihydro-1H-imidazol-4-ylidene)malononitriles were synthesized by three-component reaction of tetracyanoethylene, carbonyl compound, and ammonium acetate. The synthesis can be performed in two steps with intermediate isolation of 2-aminoethene-1,1,2-tricarbonitrile, as well as using preliminarily prepard 2-aminoethene-1,1,2-tricarbonitrile and 1,3,5-trisubstituted 2,4-diazapentadienes.

Hydrolysis of 6,6-dimethyl-4,8-dioxo-5,7-dioxaspiro[2.5]octane-1,1,2,2-tetracarbonitrile in aqueous dioxane in the presence of hydrogen bromide gave a mixture of 2,2,3,3-tetracyanocyclopropane-1-carboxylic acid and ammonium 3-cyano-4-dicyanomethylidene-5-oxo-4,5-dihydro-1H-pyrrol-2-olate. Hydrolysis of the same compound in the presence of sulfuric acid was accompanied by nitrogen migration and led to the formation of (1R*,2S*,3S*)-1,3-dicyanocyclopropane-1,2-dicarboxamide whose structure was proved by X-ray analysis.

In reaction of alkyl 2-amino-5,6-dialkyl-3-cyanopyridine-4-carboxylates with isocyanates formed unstable ureas, and with nitrous acid at 60–70°C alkyl 5,6-dialkyl-2-oxo-1,2-dihydro-4-pyidinecarboxylates were obtained. It was shown for the latter that their reactions with organic acids and amides occurred at the cyano group, and the alkaline hydrolysis involved the ester group.

It was discovered by means of dynamic NMR that the 1-(cis-1-methylprop-1-en-1-yl)-1,2-dimethyl-acenaphthylenonium ion generated under conditions of “long life” for carbocations underwent fast (ΔG#35.8 kJ mol−1 at −103°C) degenerate 1,2-shift of the cis-dimethylvinyl group. Quantum-chemical calculations by DFT method predict lower rate of 1,2-shift for the trans-dimethylvinyl group compared to cis-dimethylvinyl group and dependence on the cations conformation of the rates of these processes and of the rearrangement mechanism into the ions of phenalenyl type.

β,β,γ,γ-Tetracyanoalkanones react with acrolein at a high rate to afford the corresponding 2-substituted 4-formyl-3-cyclopentene-1,1,2-tricarbonitriles in high yields. The reaction occurs under mild conditions and is quite applicable for modification of natural and biologically active compounds possessing an R′CHC(O)CR3 fragment to obtain their derivatives containing three cyano groups.

Reactions of 2,2,3,3-tetracyanocyclopropanecarboxylic acid with potassium, sodium, calcium, strontium, barium, ammonium, N-methylpyridinium, N-methylquinolinium, N,N-dimethyl-1,4-diazabicyclo-[2.2.2]octane-1,4-diium, and N,N-dimethylanilinium iodides afforded the corresponding 3-cyano-4-dicyanomethylidene-5-oxo-4,5-dihydro-1H-pyrrol-2-olates.

4-Aryl-3-methyl-4-oxobutane-1,1,2,2-tetracarbonitriles reacted with morpholine to give 8-amino-3aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles. Ar = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c). 4-Oxoalkane-1,1,2,2-tetracarbonitriles are extensively studied representatives of the series of polynitrile compounds. Derivatives of 4-oxoalkane-1,1,2,2tetracarbonitriles are known as potential antitumor agents [1] and coordination polymers with interesting topology [2]. We now perform extensive studies on the transformations of 4-oxoalkane-1,1,2,2-tetracarbonitriles by the action of nitrogen-centered nucleophiles [3]. 4-Oxoalkane-1,1,2,2-tetracarbonitriles were reported to react with ammonia and amines to form 3-amino-7oxo-4,6-diazabicyclo[3.2.1]oct-2-ene-1,2-dicarbonitriles [4], 3-amidinio-2-aminopyridine-4-carboxylates [5], diethylammonium 3,4-dicyano-5,6,7,8-tetrahydroquinolin-2-olates [6], and ammonium 4-aryl-4oxo-1,1,2-tricyanobut-2-en-1-ides [7]. We recently showed that the reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles with morpholine leads to 5-amino-2(morpholin-4-yl)-3H-pyrrole-3,4-dicarbonitriles [8, 9] and found that nitrogen-centered nucleophiles preferably add to the β-cyano groups of polyelectrophilic tetranitriles. The resulting compounds are representatives of a poorly explored class of aza heterocycles, 3H-pyrroles, which may be regarded as nitrogen-containing cyclopentadiene analogs. Despite limited published data, some 3H-pyrroles were found to exhibit antimicrobial and antitumor activity [10–12]. With a view to synthesize new functionally substituted 3H-pyrrole derivatives, we extended the series of 4-oxoalkane-1,1,2,2-tetracarbonitrile substrates and examined their reaction with morpholine in more detail. The reactions of 4-aryl-3-methyl-4-oxobutane-1,1,2,2DOI: 10.1134/S1070428013060110

Reactions of aliphatic 2,2,3,3-tetracyanocyclopropyl ketones with aqueous ammonia afforded 4-alkyl- 4-amino-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitriles with conservation of the three-membered ring. Reactions of the same compounds with primary amines were accompanied by opening of the cyclopropane ring, and they led to the formation of 5-amino-6,6a-dimethyl-2-oxo-1,2,6,6a-tetrahydropyrrolo[2,3-b]-pyrrole-3,4-dicarbonitriles as a result of successive heterocyclizations.

Reactions of 2-methylcyclohexanone and menthone with tetracyanoethylene gave 2-(1,1,2,2-tetracyanoethyl)cyclohexanones which underwent quantitative transformation in the solid phase into 3,4-cyanosubstituted 2-aminopyrans in 2-3 days at room temperature. 2-Methyl-2-(1,1,2,2-tetracyanoethyl)cyclohexanone reacted with hydroiodic acid to afford 8a-hydroxy-2-iodo-4a-methyl-1,4,4a,5,6,7,8,8a-octahydroquinoline-3,4,4-tricarbonitrile. The reaction of 2,2'-methylenedi(cyclohexanone) with tetracyanoethylene resulted in formation of 7-imino-4,5-tetramethylene-2'-oxo-6-oxabicyclo[3.2.1]octane-2-spiro-1'-cyclohexane-1,8,8-tricarbonitrile.

Potassium 2-aroyl-1,1,3,3-tetracyanopropenides reacted with concentrated hydrochloric acid to give the corresponding 2-[5-amino-2-aryl-2-chloro-4-cyanofuran-3(2H)-ylidene]propanedinitriles.

3-Amino-4-aryl-1-dicyanomethylidene-1,3a,4,4a-tetrahydrocyclopropa[c]pyrrole-3a,4a-dicarbonitriles were synthesized by reaction of 2-amino-4-arylbuta-1,3-diene-1,1,3-tricarbonitriles (arylmethylidene derivatives of malononitrile dimer) with bromomalononitrile.