Ya. S. Kayukov

Three-component synthesis of 2-chloropyridine-3,4-dicarbonitriles

According to published data, tetracyanoethylene reacts with ketones in the presence of a catalytic amount of hydrochloric acid to give 4-oxoalkane1,1,2,2-tetracarbonitriles [1, 2]. It is also known that concentrated hydrochloric acid reacts with 4-oxoalkane-1,1,2,2-tetracarbonitriles to produce 2-chloropyridine-3,4-dicarbonitriles [3]. These data suggest that 2-chloropyridine-3,4-dicarbonitriles could be prepared via one-pot procedure, i.e., without isolation of 4-oxoalkane-1,1,2,2-tetracarbonitriles, which should make their preparation simpler and less expensive.

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides: II. Synthesis of 2-[2-(alkylsulfanyl)-5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidenepropanedinitriles by reaction with thiols

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.

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides: I. Synthesis of 2-[5-amino-2-aryl-2-chloro-4-cyanofuran-3(2H)-ylidene]-propanedinitriles by reaction of potassium 2-aroyl-1,1,3,3-tetracyanopropenides with concentrated hydrochloric acid

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.

Reaction of tetracyanoethylated cyclohexanones with water in acidic medium

It was reported earlier that 4-oxoalkane-1,1,2,2tetracarbonitriles depending on different factors react with hydrohalic acids to form 2-halopyridine-3,4dicarbonitriles [1–3], 2-halo-6-hydroxy-5,6-dihydroxypyridine-3,4,4(1Н)-tricarbonitriles [4], pyrrolo[3,4-c] pyrrole-1,3,4,6(2H,3аH,5H,6аH)-tetraones [1], 3-halo6-oxo-2,7-diazabicyclo[3.2.1]oct-3-ene-4,5-dicarbonitriles [5]. At the same time the influence of the structure of 4-oxoalkane-1,1,2,2-tetracarbonitriles on the reaction with aqueous sulfuric acid was not studied. Only reaction of 50% sulfuric acid with 3-methyl-4oxopentane-1,1,2,2-tetracarbonitrile to afford 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3,4-dicarbonitrile in 10% yield has been reported [3].

Synthesis of 2,2,3,3-tetracyanocyclopropyl ketones and their reactions with oxygen-centered nucleophiles

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.

Reaction of 4-aryl-2-aminobuta-1,3-diene-1,1,3-tricarbonitriles with CH-nucleophiles. I. Synthesis of 5-aryl-2,4-diamino-8,8-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-chromeno-[2,3-b]pyridine -3-carbonitriles

Abstract5-Aryl-2,4-diamino-8,8-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-chromeno[2,3-b]pyridine-3-carbonitriles were synthesized from 4-aryl-2-aminobuta-1,3-diene-1,1,3-tricarbonitriles and dimedone.

Reaction of 2,2,3,3-tetracyanocyclopropyl ketones with sodium and potassium hydroxides

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.

Synthesis of diethylammonium 3,4-dicyano-5,6,7,8-tetrahydroquinolin-2-olates

4-Oxoalkane-1,1,2,2-tetracarbonitriles are products of addition of tetracyanoethylene to ketones. Their molecules possess several electrophilic centers capable of reacting with nucleophiles. However, studies on reactions of these compounds with nitrogen-centered nucleophiles are very few in number. It was reported that reactions of 4-oxoalkane-1,1,2,2-tetracarbonitriles with aqueous ammonia lead to formation of isonicotinic acid derivatives [1] and 2,7-diazabicyclo[3.2.1]oct-3-enes [2].

Synthesis of a new organic anion by reaction of 4-aryl(hetaryl)-4-oxobutane-1,1,2,2-tetracarbonitriles with ammonia

4-Oxoalkane-1,1,2,2-tetracarbonitriles are known to react with concentrated aqueous ammonia to produce compounds of two types. Adducts of tetracyanoethylene and cyclic ketones (such as cyclopentanone and cyclohexanone) give rise to 2,7-diazabicyclic compounds [1], whereas from aliphatic tetracyanoethylated ketones isonicotinic acid derivatives are formed [2]. There are no published data on reactions of aqueous ammonia with tetracyanoalkanones derived from methyl aryl(hetaryl) ketones. When such reactions were carried out under the conditions reported in [1, 2], strong tarring occurred, and no individual products were isolated. By varying the conditions of this reaction we succeeded in obtaining ammonium 4-aryl1,1,2,2-tetracyano-4-oxobutan-1-ides IIa–IIc by mixing ketones Ia–Ic with a freshly prepared solution of ammonia in ethyl acetate at reduced temperature. Structures analogous to IIa–IIc but having singly charged metal cations were reported in [3, 4]. Compounds IIa–IIc turned out to be unstable in the solid state: on exposure to air they lost hydrogen cyanide with formation of ammonium 4-aryl-1,1,2-tricyano-4oxobut-2-en-1-ides IIIa–IIIc that are derivatives of a new organic anion. Intermediate formation of ammonium salts IIa–IIc is confirmed by their transformation into initial ketones Ia–Ic by the action of dilute hydrochloric acid immediately after isolation. Some structural similarity of salts IIIa–IIIc to betaines described in [5] may be noted. The latter were synthesized from tetracyanoethylene and pyridinium ylides. The structure of compounds IIIa–IIIc was confirmed by their IR, H NMR, and mass spectra and elemental analyses. The synthesis of salts III is an example of new reaction pathway of 4-oxoalkane1,1,2,2-tetracarbonitriles with ammonia. Ammonium 1,1,2-tricyano-4-(4-methoxyphenyl)4-oxobut-2-en-1-ide (IIIa). 4-(4-Methoxyphenyl)-4oxobutane-1,1,2,2-tetracarbonitrile (Ia), 0.139 g (0.5 mmol), was added to 2 ml of a freshly prepared solution of ammonia in ethyl acetate, cooled to –10°C, and the mixture was vigorously stirred until it became homogeneous. After several minutes, a solid separated and was filtered off, washed with cold ethyl acetate, and kept for 5–7 days on exposure to air. Yield 0.115 g (86%), mp 84–85°C. IR spectrum, ν, cm: 2230, 2199 (C≡N); 1667 (C=O). H NMR spectrum, δ, ppm: 3.81 s (3H, OCH3), 6.51 s (1H, CH), 7.01 d (2H, Harom), 7.07 br.s (4H, NH4), 7.79 d (2H, Harom). Mass spectrum: m/z 251 (Irel 49%) [M – NH3]. Found, %: C 62.51; H 4.77; N 20.95. C14H12N4O2. Calculated, %: C 62.68; H 4.51; N 20.88. Compounds IIIb and IIIc were synthesized in a similar way. Ammonium 1,1,2-tricyano-4-oxo-4-(2-thienyl)but-2-en-1-ide (IIIb). Yield 0.096 g (79%), mp 85– 87°C. IR spectrum, ν, cm: 2221, 2196 (C≡N); 1672 (C=O). H NMR spectrum, δ, ppm: 6.41 s (1H, CH), 7.16 d.d (1H, Harom), 7.19 br.s (4H, NH4), 7.65 d.d (1H, R = 4-MeOC6H4 (a), 2-thienyl (b), 3,4-(MeO)2C6H3 (c). ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 597–598.

One-step transformation of tetracyanocyclopropyl ketones into pyrrolo[3,4-c]pyridine derivatives

Tetracyanocyclopropyl ketones obtainable via modified Wideqvist reaction are accessible and convenient precursors of a number of heterocyclic systems [1–3]. Reactions of cyclopropyl ketones Ia–Ic with alkoxides give rise to 2-[2-alkoxy-5-amino-4-cyano-2-phenylfuran-3(2H)-ylidene]malononitriles [3]. We anticipated that replacement of the ketone acetal fragment in the latter by more labile semiacetal moiety should facilitate recyclization of the furan ring into pyrrole. Such transformation could be promoted using hydroxide ion instead of alkoxide in reactions with cyclopropyl ketones Ia–Ic. The above assumption was verified by studying the reaction of cyclopropyl ketones Ia–Ic with aqueous sodium hydroxide. We found that this reaction involves not only expected recyclization of furan ring into pyrrole but also annelation of pyridine ring. The structure of compounds IIa–IIc isolated by neutralization of the reaction mixture with a solution of sulfuric acid was confirmed by the H NMR and mass spectra. The H NMR spectra contained singlets at δ 7.12– 7.69 and 8.78–9.02 ppm, which were assigned to the hydroxy and NH protons, respectively, in the pyrrole ring. The NH proton in the pyridine ring resonated as