Investigations in the imidazole series

The catalytic dechlorination of 1-alkyl-5-chloro-, 1-alkyl-4-chloro-, and 1-alkyl(aralkyl)-2-alkyl(aryl)-5-chloroimidazoles in the presence of Raney nickel, which makes it possible to simplify the synthesis of a number of 1-alkyl- and 1-alkyl(aralkyl)-2-alkyl(aryl)imidazoles, was investigated.See [1] for communication LXXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 820–822, June, 1972.     

Synthesis and Properties of 3-Alkyl(aryl)-5-chloromethylisoxazoles

3-Chloro-2-isothiocyanato-1-propenyl alkyl(aryl) ketones react with hydroxylamine hydrochloride to give 3-alkyl(aryl)-5-chloromethylisoxazole. Treatment of the latter with dimethylamine and ammonium thiocyanate leads to formation of previously unknown 3-alkyl(aryl)-5-dimethylamino(or isothiocyanato)- methylisoxazoles.     

Heterocyclization of Derivatives of 4-Oxoalkanoic Acids to 1,5-Disubstituted Pyrrolin-2-ones

Conditions were developed for the synthesis and production of 1-aryl-5-alkyl(aryl)-3H- and 1-aryl-5-alkyl(aryl)-5H-pyrrolin-2-ones from the amides and esters of 4-oxoalkanoic acids. It was established that the yield and ratio of the 3H and 5H isomers depend on the substrate employed in the reaction.     

Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones

The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d were obtained from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 1, 2a-d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one ring.     

Amidrazones. 6 . Synthesis of 1,2,4-thiadiazoles by thermolysis of N3-thiocarbamoylamidrazone ylides

Reaction of N³-unsubstituted amidrazone ylides ( 1a and 1b ) with alkyl or aryl isothiocyanates gives N³-thiocarbamoylamidrazone ylides ( 2 ). Thermolysis of 2 gives 3-alkyl(or aryl)-5-alkyl(or aryl)amino-1,2,4-thiadiazoles ( 3a-i ).     

Facile synthesis of 4-alkyl (and aryl)-2-aryl-6-diazo-4h- thieno[3,2-b]pyridine-5,7-diones

Treatment of 3-[3-alkyl (and aryl)amino-5-arylthieno-2-yl]-2-diazo-3-oxopropanoates 8 with TMSOTf (3 equiv) in the presence of Et(3)N (6 equiv) in CH(2)Cl(2) for 1 h at room temperature afforded 4-alkyl (and aryl)-2-aryl-6-diazo-4H-thieno[3,2-b]pyridine-5,7-diones 14 in excellent yields. On heating of 14 in the presence of a catalytic amount of Rh(2)(CF(3)CF(2)CF(2)CO(2))(4) in PhH for 4-10 h at reflux, corresponding ring contraction products, 4-alkyl (and aryl)-5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones 16, were produced in good to excellent yields.     

Reaction of 3-alkyl(aryl)-5-chloromethylisoxazoles with nucleophilic reagents

Previously unknown 3-alkyl(aryl)isoxazoles containing various functional groups in the 5-position were synthesized by reactions of 3-alkyl(aryl)-5-chloromethylisoxazoles with nucleophiles (2-aminoethanol, methylamine, sodium acetate, and sodium methoxide).     

Polyfunctional imidazoles: I. Synthesis of 1-substituted 4-chloro-1<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbaldehydes by Vilsmeier-Haack reaction

2-[Alkyl(aryl)amino]acetamides in reaction with Vilsmeier-Haack reagent afforded 1-alkyl(aryl)-4-chloro-1H-imidazole-5-carbaldehydes.     

Researches on imidazoles

A number of 1-alkyl (1, 2-dialkyl)-4-nitro-5-alkyl (aryl, dialkyl) aminoimidazoles are synthesized by reacting 1-alkyl (1, 2-dialkyl)-4-nitro-5-chloroimidazoles with aliphatic, aromatic, and heterocyclic amines. Hydrogenation of 1-ethyl-2-methyl-4-nitro-5-(N-morpholino) imidazole in acetic anhydride gives 1-ethyl-2-methyl -4-diacetylamino-5-(n-morpholino) imidazole, characterized as its picrate.Paper presented at the All-Union Conference on the Chemistry of Five-Membered Heterocyclic Rings, Rostovon-Don, 1962.     

New oxidative cyclizations of 1,3,4,6-tetraketones. Synthesis and structure of (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxaspiro[2.4]hept-5-en-7-ones

Iodosobenzene diacetate oxidation of 1,3,4,6-tetraketones 1a-c yielded (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxa-spiro[2.4]hept-5-en-7-ones (4a-c) in addition to 2-acyl-6-alkyl(aryl)-3-hydroxy-4-pyrones (3a-c). The structure of new spiro-heterocycles 4 was inferred from chemical and spectroscopic data, and the stereochemistry was fully defined by a single-crystal X-ray analysis. Alternative cyclization pathways can be rationalized as proceeding through carbocation intermediates derived from both forms of the ring-chain tautomerism of 1,3,4,6-tetraketones 1.     

Novel synthesis of monofluorocyclobutanes by the ring expansion- fluorination of cyclopropylmethanols with an amine-metal fluoride pyridinium poly(hydrogen fluoride)-complex

Various new 1-fluoro-1-alkyl(or aryl)-2-substituted cyclobutanes were synthesized stereoselectively from 1-alkyl(or aryl)cyclopropyl carbinols by the ring expansion-fluorination using (ⁱPr)₂-KHF₂-(HF)_n·Py, and 2-hydroxymethyl-1-fluorocyclobutanes were synthesized via a new rearrangement of (1-alkyl(or aryl)cyclopropyl) ethylene oxides.     

Reaction of Ethyl 6-Alkyl(aryl)-4-chloromethyl-2-methylpyridine-3-carboxylates with Ammonia and Primary Amines

Ethyl 6-alkyl(aryl)-4-chloromethyl-2-methylpyridine-3-carboxylates react with ammonia andprimary amines to give 6-substituted 3-alkyl(aryl)-1-methyl-1'2-dihydropyrrolo[3'4-c]pyridin-7-ones.The reactions with 4-aminopyridine yield ethyl 6-alkyl(aryl)-2-methyl-4-(4-pyridylaminomethyl)pyridine-3-carboxylates.     

Synthesis and GIAO NMR calculations for some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives: comparison of theoretical and experimental 1H and 13C chemical shifts

Four novel 3-alkyl(aryl)-4-(4-methoxycarbonylbenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with methyl 4-formylbenzoate and characterized by elemental analyses and IR, 1H NMR, 13C NMR and UV spectral data. In addition, isotropic 1H and 13C nuclear magnetic shielding constants of 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound was optimized using the 6-311G basis set.     

Reactions of amidines with oxalyl chloride. II

Unsubstituted, N-alkyl(aryl)- and N-chloroamidines react with oxalyl chloride to form imidazolidine-4, 5-diones. The hydrochlorides of 1-aryl-2-alkyl(aryl)imidazolidine-4, 5-diones decompose thermally to give N-arylimidoyl isocyanates which change immediately to 4-quinazolones.     

Bromination of 5-Substituted 3H-Furan-2-ones and 3H-Pyrrol-2-ones

The bromination of 5-alkyl(aryl)-3H-furan-2-ones and 5-alkyl(aryl)-3H-pyrrol-2-ones and also their derivatives takes place at the ethylene bond with the formation of 4-monobromo derivatives. N-Phenyl-3H-pyrrol-2-ones are brominated simultaneously at the ethylene bond of the heterocycle and at the phenyl substituent at the nitrogen atom.     

Interaction of 1,5-disubstituted 3-methyl-2-oxo-2,3-dihydro- 1<Emphasis Type="Italic">H</Emphasis>-imidazole-4-carbonitriles with hydrogen sulfide

The reaction of 1-alklyl(aryl)-5-alkyl(aryl)amino-3-methyl-2-oxo-2,3-dihydro-1H-imidazole-4-carbo-nitriles with hydrogen sulfide was investigated. Unexpectedly, this led, after treatment of the reaction products with triethyl orthoformate, to 1,2,4-dithiazol-5-ylidene-5-thioxoimidazolidin-2-one derivatives.     

Substituierte 5-Hydroxypyrimidine und ihre O,O-Diethylphosphorsäure-, O,O-Diethylthiophosphorsäure-und N,N-Dimethylcarbamidsäureester

4-Alkyl (or aryl)-6-chloro-5-hydroxy-2-methylpyrimidines5a–5e, 4-alkyl (or aryl)-5-hydroxy-2-methyl-1H-pyrimidin-6-ones5g–5k and 6-alkyl (or aryl)-5-hydroxy-1H,3H-pyrimidin-2,4-diones5l–5n were prepared and converted into O,O-diethylphosphoric acid esters7a–7e, O,O-diethylphosphorothioic acid esters7f–7i and N,N-dimethylcarbamic acid esters8.

     

A novel synthesis of 4,5-diaryl-6-arylamino-2,3-benzo-1,3a,6a-triazapentalenes

Treatment of N-alkyl- and N-aryl-imines of 2,3-diaryl- and 2-alkyl-3-aryl-3-(benzotriazol-1-yl)propenals with trifluoroacetic anhydride in THF at room temperature gave 5-alkyl-4-aryl-6-[N-alkyl (and aryl)-N-trifluoroacetyl]amino-2,3-benzo-1,3a,6a-triazapentalenes in moderate to good yields. On heating triazapentalenes having R²=aryl in MeOH at reflux, detrifluoroacetylation of triazapentalene occurred to give title compounds in good yields. However, the same treatment of triazapentalenes having R²=alkyl did not give the corresponding detrifluoroacetylation product. The title compounds and 5-alkyl-4-aryl-6-(N-alkyl-N-trifluoroacetyl)amino-2,3-benzo-1,3a,6a-triazapentalenes were found to be good precursors for the synthesis of 1-(o-aminophenyl)-3-arylamino-4-alkyl (and aryl)-5-arylpyrazoles and 1-(o-aminophenyl)-3-(N-alkyl-N-trifluoroacetyl)amino-4-alkyl (and aryl)-5-arylpyrazoles, respectively.     

双－（3－烷基／芳基）－7H－1，2，4－三唑并[3,4-b]-1,3,4-噻二嗪类化合物的合成及波谱性质

利用1，4－二溴丁二酮（1）分别与3－烷基／芳基－4－氨基－5－巯基－1， 2，4－三唑（2a-2n）反应，合成了14种新的双－（3－烷基／芳基）－7H－1，2， 4－三唑并[3,4-b]－1，3，3-噻二嗪类化合物（3a-3n），并利用EA、IR，~1H NMR和MS确定了其结构。     

Synthesis and non-aqueous medium titrations of some new 4-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

The synthesis of 3-alkyl(aryl)-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3 from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2 with 3-ethoxy-4-hydroxybenzaldehyde is described.The acetylation and methylation reactions of the compounds 3 giving compounds of type 4 and 5, respectively, were investigated. The newly synthesized compounds were characterized using elemental analyses and IR, (1)H-NMR, (13)C-NMR and UV spectral data.In addition, to investigate the effects of solvents and molecular structure upon acidity,compounds 3 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide). The half-neutralization potential values and the corresponding pKa values were determined for all cases.