D. B. Rubinov

Synthesis of benzimidazolone derivatives based on 2-acylcyclohexane-1,3-diones alkoximes

Abstract2-(1-Alkoxyiminoalkyl)cyclohexane-1,3-diones undergo at heating Beckmann rearrangement to give 6,7-dihydro-1,3-benzoxazol-4(5H)-one derivatives that under treatment with amines in acid medium are converted into 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones. In reaction of 6,7-dihydro-1,3-benzoxazol-4(5H)-ones with O-ethylhydroxylamine 4-ethoxyimino derivatives were obtained that treated with hydrochloric acid formed the corresponding N-ethoxybenzimidazolones.

4-Acyl-2H-thiopyran-3,5(4H,6H)-diones: Synthesis, Oxidation, and Reaction with Amines

Acylation of 2H-thiopyran-3,5(4H,6H)-dione and 2-methyl-2H-thiopyran-3,5(4H,6H)-dione with acetyl chloride or propionyl chloride afforded the corresponding 4-acyl-2H-thiopyran-3,5(4H,6H)-diones. Oxidation of 4-acetyl-2H-thiopyran-3,5(4H,6H)-dione with m-chloroperoxybenzoic acid gave 4-acetyl-2H-thiopyran-3,5(4H,6H)-dione 1-oxide. 4-Acyl-2H-thiopyran-3,5(4H,6H)-diones and 4-acetyl-2H-thiopyran-3,5(4H,6H)-dione 1-oxide reacted with pyrrolidine, allylamine, and p-anisidine, resulting in formation of the corresponding 4-aminomethylene derivatives.

Synthesis of 1,6-disubstituted 2,4-pyridinediones from 5-acetoacetyl-2,2-dimethyl-1,3-dioxane-4,6-dione

Abstract5-Acetoacetyl-2,2-dimethyl-1,3-dioxane-4,6-dione reacts with aliphatic amines and p-methoxy-aniline to afford the corresponding 5-[3-alkyl(or aryl)amino-2-butenoyl] derivatives. Heating of the latter in boiling toluene gives 86–90% of N-substituted 6-methylpyridine-3-carboxylic acids which undergo decarboxylation in diethylene glycol dimethyl ether at 160°C, leading to N-substituted 6-methyl-1,2,3,4-tetrahydro-pyridine-2,4-diones in high yields.

Synthesis of exo- and endocyclic enamino derivatives of 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones

Condensation of 2-acetylcyclohexane-1,3-diones with aromatic aldehydes in the presence of piperidine, pyrrolidine, hexamethyleneimine, or morpholine gave the corresponding 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones as the major products and 2-[3-aryl-1-cycloalkylaminoprop-2-en-1-ylidene]cyclohexane-1,3-diones as minor ones. Endocyclic enamino derivatives were synthesized in two steps through enol methyl ethers which reacted with amines. Endocyclic enamino derivatives of 2-(3-arylprop-2-enoyl)cyclohexane-1,3-diones containing an aryl group on the nitrogen atom readily underwent cyclization to 1,2,3,4,5,6,7,8-octahydroquinoline-4,5-dione derivatives.

Reaction of Nitromethane with Cinnamoyl Derivatives of Cyclic β-dicarbonyl Compounds. Application to the Synthesis of 2(3)-(4-aryl-pyrrolidin-2-ylidene)-1,3(2,4)-diones*

We have shown that reaction of nitromethane with cinnamoyl derivatives of five- and six-membered carbo- and heterocylic β-dicarbonyl compounds in the presence of 1,1,3,3-tetramethylguanidine proceeds according to the mechanism of 1,4-conjugate addition to the enone fragment of cinnamoyl moiety to give 2(3)-( 3-aryl-4-nitrobutanoyl)-substituted cyclic 1,3- or 2,4-diones in good to excellent yields. Chemoselective reduction of nitro function of the latter leads to synthetically useful and biologically interesting 2(3)-(4-arylpyrrolidin-2-ylidene) derivatives.

Synthesis of (4-arylpyrrolidin-2-ylidene) derivatives of cyclic β-dicarbonyl compounds from cinnamoyl precursors

Abstract1,4-Conjugate Michael addition of nitromethane to the enone fragment of cinnamoyl derivatives of carbo- and heterocyclic β-dicarbonyl compounds provided the corresponding nitromethyl derivatives. The chemoselective reduction of the nitro group in the latter afforded 4-arylpyrrolidin-2-ylidene derivatives of β-dicarbonyl compounds in high yield. The reaction products with the heterocyclic β-dicarbonyl fragment are formed as equilibrium mixture of E- and Z-rotamers in which the E-rotamer predominates.

Synthesis of Enol Methyl Ethers of 3-Acetyl-6,6-dimethyltetrahydrothiopyran-2,4-dione and Their Reactions with Amines

The reaction of 3-acetyl-6,6-dimethyltetrahydrothiopyran-2,4-dione with diazomethane furnishes a mixture of 3-acetyl-6,6-dimethyl-4-methoxy-5,6-dihydro-2H-thiopyran-2-one and 3-acetyl-6,6-dimethyl- 2-methoxy-5,6-dihydro-2H-thiopyran-4-one in 2:3 ratio, whereas in reaction with dimethyl sulfate in the presence of potassium carbonate forms a mixture of the same products in 9:1 ratio. In both reactions the overall yield of ethers amounts to 50%. Treating of regioisomeric enol methyl ethers with pyrrolidine, o-toluidine, and allylamine provides the corresponding endocyclic enaminodiketones.

Annelation of 3,4-Dihydroisoquinolines with 3-Acylthiotetronic Acids: Synthesis and Properties of 8-Aza-16-thiagona-12,17-diones and 3,4-Dihydroisoquinolinium 3-Acetylthiotetronate

Abstract8-Aza-16-thiagona-12,17-diones have been obtained by the annelation of C(1)-unsubstituted 3,4-dihydroisoquinolines with 3-acylthiotetronic acids on refluxing in glacial acetic acid. The condensation of 1-methyl-3,4-dihydroisoquinoline with 3-acetylthiotetronic acid stopped at the salt formation stage. From the results of H/D isotopic exchange of 3,4-dihydroisoquinolinium 3-acetylthiotetronate it follows that a tautomeric equilibrium is established for the anion of 3-acetylthiotetronic acid, involving the protons of the acetyl group and the C(5) methylene group of the thiolactone ring in isotopic exchange.

Chemical Transformations of 5,5-Dimethyl-2-(3-aryl-4-nitrobutanoyl)cyclohexane-1,3-diones. Synthesis of 6,7-Dihydrobenzo[d]isoxazol-4(5H)-ones and 6,7-Dihydro-1H-indazol-4(5H)-ones with Isoxazole and Isoxazoline Fragments in the Side Chain

By reaction of 5,5-dimethyl-2-(3-aryl-4-nitrobutanoyl)cyclohexane-1,3-diones with hydroxylamine and hydrazine hydrate 6,7-dihydrobenzo[d]isoxazol-4(5H)-ones and 6,7-dihydro-1H-indazol-4(5H)-ones were prepared containing a nitromethyl substituent in the side chain. Basing on the nitromethyl group of the latter nitrile oxide intermediates were generated that were brought into reaction of 1,3-dipolar addition with phenylacetylene, styrene, and vinyl ethyl ether with the formation of the corresponding isoxazole and isoxazoline derivatives.

Synthesis and keto-enol tautomerism of 6-alkyl-1-alkoxypyridine-2,4-diones

Reactions of 2,2-dimethyl-5-(3-oxoalkanoyl)-1,3-dioxane-4,6-diones with alkoxyamines proceed regioselectively at the β′-keto group of the side acyl chain affording the corresponding tricarbonyl imines whose boiling in toluene leads to the formation of products of intramolecular cyclization, N-alkoxy-2,4-dioxopyridine-3-carboxylic acids. The decarboxylition of the obtained pyridine-3-carboxylic acids in mesitylene at 160–165°C gives in the preparative yield N-alkoxypyridine-2,4-diones. Proceeding from the IR and NMR spectra the problems of the keto-enol and imine-enamine tautomerism were discussed for the series of 5-acyl derivatives of the Meldrum acid and the obtained N-alkoxypyridine-2,4-diones.