Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

Synthesis and some conversions of 6-methyl- and 1,6-dimethyl-5-nitro-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidines

Using a modification of the Biginelli reaction, we have synthesized 6-methyl- and 1,6-dimethyl-5-nitro-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidines. We have studied some of their chemical conversions involving the methyl group on the C₍₆₎ atom, the nitrogen atoms of the pyrimidine ring, and the phenyl substituent.Translated from Khimiya Geterosiklicheskikh Soedinenii, No. 3, pp. 388–392, March, 1993.     

Radical-anions in the vicarious C-amination reactions of N-substituted nitrotriazoles

The vicarious nucleophilic substitution of hydrogen in symmetrical and vicinal nitrotriazoles by 1,1,1-trimethylhydrazinium iodide in t-BuOK/DMSO was studied by ESR. In the ESR monitoring of the reactions the primary radical-anions of 4-nitro-2-phenyl-1,2,3-triazole and 1-methyl-3-nitro-1,2,4-triazole were detected and characterized. It was shown by NMR that the amination of 4-nitro-2-phenyl-1,2,3-triazole takes place exclusively in the triazole ring with the formation of 5-amino-4-nitro-2-phenyl-1,2,3-triazole. 1-Methyl-3-nitro-1,2,4-triazole, like 3-nitro-1,2,4-triazole, does not form amination products. A possible mechanism for the vicarious C-amination of nitrotriazoles and the formation of the radical-anions of the substrates is discussed. Dedicated to Academician M. G. Voronkov on his 85th birthday. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1662–1670, November, 2006.     

Nickel-catalyzed multi-component connection reaction of isoprene, aldimines (lactamines), and diphenylzinc

Ni(acac)₂ catalyzes the four-component connection reaction of diphenylzinc, isoprene, aromatic aldehydes, and aromatic amines in this order and provides stereochemically homogeneous (E)-1-arylamino-1-aryl-3-methyl-5-phenyl-3-pentenes (1) in excellent yields. Aliphatic aldehydes react similarly and give (E)-1-arylamino-1-alkyl-3-methyl-5-phenyl-3-pentenes (1) in slightly reduced yields. When the alkyl groups are bulky, in addition to 1 are formed (E)-1-arylamino-1-alkyl-4-methyl-5-phenyl-3-pentenes (1′) as the minor products. Lactamines prepared in situ from five- and six-membered lactols and aromatic amines are more reactive than alkyl aldehyde aldimines and furnish (E)-4-arylamino-6-methyl-8-phenyl-6-octen-1-ols (4) and (E)-5-arylamino-7-methyl-9- phenyl-7-nonen-1-ols (5), respectively, in good yields with excellent E-stereoselectivity.     

Preparation of 4-bromo-1-hydroxypyrazole 2-oxides by nitrosation of α-bromo-α,β-unsaturated ketoximes

Nitrosation of the oximes of 3-bromo-3-penten-2-one, 3-bromo-4-phenyl-3-buten-2-one, and 2-bromo-1,3-diphenyl-2-propen-1-one using sodium nitrite in acetic acid gave low yields of 4-pyrazolone 1,2-dioxides. Nitrosation using butyl nitrite in the presence of copper(II) sulfate and pyridine in aqueous ethanol produced insoluble copper complexes from which 3,5-dimethyl-, 3-methyl-5-phenyl-, and 3,5-diphenyl-4-bromo-1-hydroxypyrazole 2-oxides could be liberated by treatment with dilute potassium hydroxide, filtration, and acidification of the filtrate. High yields were obtained with the first two oximes, but, presumably due to unfavorable stereochemistry of the oxime, the diphenyl derivative gave a lower yield of the complex, accompanied by 4-bromo- and 4-nitro-3,5-diphenylisoxazole and 4-oximino-3,5-diphenyl-4,5-dihydroisoxazole.     

Reactions of 3-nitro-1,2,4-triazoles with alkylating agents. 6*. Alkylation of a neutral heterocycle by alcohols in acid media*

Reaction of 3-nitro-1,2,4-triazole and 5-methyl-3-nitro-1,2,4-triazole with secondary and tertiary alcohols in conc. H₂SO₄ takes place at the N(2) atom. Alkylation by 2-propanol occurs regioselectively to form the 1-isopropyl-3-nitro-and 1-isopropyl-3-methyl-5-nitro-1,2,4-triazoles. As a consequence of isomerization the alkylation using cyclohexyl or tert-butyl alcohols gives respectively a mixture of regioisomers substituted at atom N(1) (1-cyclohexyl-3-nitro-and 1-cyclohexyl-5-methyl-3-nitro-1,2,4-triazoles) and at atom N(2) (5-nitro-1-cyclohexyl-and 1-cyclohexyl-3-methyl-5-nitro-1,2,4-triazoles) and, in the second case, to 1-tert-butyl-3-nitro-1,2,4-triazole. * For Communication 5 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1680–1687, November, 2008.     

Nitropyrazoles: XII. Transformations of the 4-Methyl Group in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization of the Transformation Products

A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl- (dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitropyrazol- 4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl- 3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K₂CO₃ to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K₂CO₃ in acetonitrile; in the reaction with K₂CO₃ in ethanol, the 5-nitro group was replaced by ethoxy.     

Nitropyrazoles

A method for the synthesis of 1-methyl-3,5-dinitropyrazole-4-carbonitrile from 1,4-dimethyl-3,5-dinitropyrazole was developed. Nucleophilic substitution in 1,4-dimethyl-3,5-dinitropyrazole, 1-methyl-3,5-dinitropyrazole-4-carboxamide, and 1-methyl-3,5-dinitropyrazole-4-carbonitrile involves solely the 5-NO₂-group in the ring. 1-Methyl-3,5-dinitropyrazole-4-carbonitrile reacts with thioglycolic acid phenylamide and potassium carbonate to give 4-amino-1-methyl-3-nitro-N-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide. The use of glycolic acid phenylamide instead of thioglycolic acid N-phenylamide under analogous conditions resulted in 5-anilino-1-methyl-3-nitro-1H-pyrazole-4-carbonitrile. An explanation for the regiospecificity of the nucleophilic substitution of the 5-NO₂ group in 4-R-1-methyl-3,5-dinitropyrazoles is given. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2004–2014, October, 2007.     

金属氯化物对硼氢化钠还原α-氯代苯乙酮的影响

以芳醛、麦氏酸和3-甲基-1-苯基-5-氨基吡唑为原料, 经微波辐射一步得到4-芳基-3-甲基-6-氧代-1-苯基-4,5,6,7-四氢吡啶并[2,3-c]吡唑衍生物, 反应2～6 min完成, 产率高. 产物结构通过红外、核磁共振、元素分析及单晶X射线分析确证.     

Reactions of 4,5-diamino-3-methyl-1-phenylpyrazole with aromatic haloketones

Reaction of 4,5-diamino-3-methyl-1-phenylpyrazole with -bromoacetophenones yields pyrazolo[4,5-b]pyrazines. A side product is 1-phenyl-3-methyl-5-imino-4-[(1-phenyl-3-methyl-4-aminopyrazol-5-yl)imino]-2-pyrazoline obtained by dimerization of the starting diaminopyrazole with loss of ammonia and a molecule of hydrogen.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–790, June, 1988.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

One-pot three-component process for the synthesis of substituted pyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazoles catalyzed by nanostructured FSM-16-SO<Subscript>3</Subscript>H

A three-component process for the one-pot synthesis of 6-amino-4-aryl-5-cyano-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazoles by the reaction of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, and malononitrile in the presence of FSM-16-SO₃H as an efficient mesoporous catalyst. The FSM-16-SO₃H was prepared and characterized by SEM, XRD, BET, and FT-IR techniques. The advantages of the presented method are high yields, short reaction times, easy purification of products, easy work-up, and reusability of the catalyst.     

Über die Einwirkung von Ammoniak auf 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon

Zusammenfassung 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon (6 b) reagiert mit flüss. NH₃ zu 6-Chlor-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (7), mit NH₃ in absol. Alkohol zu 6-Chlor-4-hydroxy-3-jod-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (9). Der Mechanismus dieser Reaktionen wird diskutiert.

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The reaction of ammonia with 5-Chloro-2-(N-methyl-iodo-methanesulfonamido)-benzophenone

The reaction of 5-chloro-2-(N-methyl-jodomethanesulfon-amido)-benzophenone (6b) with liquid or absol. alcoholic ammonia leads to 6-chloro-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (7) and 6-chloro-4-hydroxy-3-jodo-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (9) resp. The mechanism of these reactions is discussed.

     

Configuration and isomerization of 2,4,5-substituted 1,3,2-dioxaborinanes

Reaction of esters of isobutylboronic acid with 2-methyl-1-phenyl-1,3 propanediol and 2-benzyl-1,3-butanediol gave 2-isobutyl-5-methyl-4-phenyl- and 4-methyl-5-benzyl-1, 3, 2-dioxaborinanes respectively, with a preponderance of the cis-isomers in the mixtures. Cis-2-isobutyl-5-methyl-4-phenyl-1, 3, 2-dioxaborinane was converted to thetrans isomer on heating to 150°C with a catalytic amount of ZnCl₂.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1291–1294, September, 1995.     

Synthese der isomeren 3, 4-Dimethyl-4-phenyl-3, 4-dihydro-carbostyrile

Cyclisation of 2-methyl-3-phenyl-but-3-en-anilide (III) with polyphosphoric acid gave cis-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (VII) in 61% yield together with a small amount of 2, 3-dimethylindenone (VIII), whereas with AlCl₃ a phenyl group was split off to give 3, 4-dimethylcarbostyril (VI). The anilide III isomerises to cis- and trans-2, 3-dimethyl-cinnam-anilide (IV resp. V) under basic conditions. The anilides IV and V gave only small yields of the dihydrocarbostyril VII with polyphosphoric acid. Chlorination of VII in position 3 using PCl₅ yielded IX which, on splitting out HCl, gave 3-methylene-4-methyl-4-phenyl-3, 4-dihydro-carbostyril (X). X was converted to trans-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (XI) by catalytic hydrogenation.     

Some Features of the Reactions of 3-Nitro-6-phenylhexa-3,5-dien-2-one with Thiophenols

The reaction of 3-nitro-6-phenylhexa-3,5-diene-2-one with 4-methyl- and 4-chlorothiophenols yields 1,4- and 1,6-addition products at conjugated dienone system. By the example of the 1,4-addition adduct of 4-methylthiophenol, its conversion in solution to the 1,6-addition product was shown. 4-Methyl-3-nitro-2-styryl-2,3-dihydrobenzo[b][1,4]thiazepine was synthesized by reacting 3-nitro-6-phenylhexa-3,5-dien-2-one with o-aminothiophenol.     

Synthesis of 2-acyl-3-methylthiofurans from 3-methylthio-2-pentene-1,5-dione enolates

2-Acyl-3-methylthiofurans 3 are obtained in fair yields from 3-methylthio-2-pentene-1,5-dione enolates 1 by reaction with iodine. In a similar reaction 1-phenyl-3-methylthio-4-nitro-2-buten-1-one gave 3-methylthio-2-nitro-5-phenylfuran 11. In the crystalline state the 2-benzoyl-3-methylthio-5-phenylfuran 3b showed a non-bonded sulfur-oxygen interaction as inferred from an X-ray diffraction determination, with a S····O distance of 2.871(5)Å.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations of N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction of N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh₃)₄ gave a mixture of 2-allyl-4-methyl-5-nitroisoquinolin-1-one and 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly gave 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one and 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products are not interconvertible. A deuterium-labelling study indicated that the isomers were formed by different pathways: a π-allyl-Pd route and the classical Heck route. The corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide and N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide gave good yields of the required 4-methyl- and 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh₃)₄, Et₃N, Bu₄NCl, 150 °C, rapid heating). Hydrogenation of the nitro groups gave 4-methyl- and 4-benzyl-5-aminoisoquinolin-1-ones, which were potent inhibitors of PARP-1 activity.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VI. Synthesis of ethyl or methyl 1,5-disubstituted 1H-pyrazole-4-carboxylates

Reaction of ethyl or methyl 3-oxoalkanoates with N,N-dimethylformamide dimethyl acetal gave, generally in excellent yields, a series of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates II which reacted with phenylhydrazine to afford the esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids III in high yields. Esters III were hydrolyzed to the relative 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles in excellent yields. Reaction of II with methylhydrazine afforded in general a mixture of 3- and 5-substituted ethyl 1-methyl-1H-pyrazole-4-carboxylates with the exception of IIg , which gave in high yield methyl 5-benzyl-1-methyl-1H-pyrazole-4-carboxylate, which was hydrolyzed to the relative pyrazolecarboxylic acid. This afforded by heating 5-benzyl-1-methyl-1H-pyrazole in quantitative yield.