Thermal and microwave assisted reactions of 2,5-disubstituted thienosultines with [60]fullerene: non-Kekulé biradicals and self-sensitized oxygenation of the cycloadduct

Refluxing an o-dichlorobenzene solution of 2,5-disubstituted thienosultines 10a-f with [60]fullerene for 2-24 h gave both 1:1 and 2:1 cycloadducts in 37-79% isolated yields. The reaction was highly accelerated by microwave irradiation giving comparable yields of cycloadducts. Sultines 10a-f underwent cheletropic extrusion of SO₂ to form the corresponding non-Kekulé biradical intermediates 11a-f, which were subsequently trapped by [60]fullerene to form corresponding cycloadducts. The activation energy barriers (ΔG_c^≠) determined for the boat-to-boat inversion of these 4′,5′,6′,7′-tetrahydrobenzo[c]thieno-[5′,6′:1,2][60]fullerene adducts 12a-f were found to be in the range of 13.5-14.8 kcal/mol. Unexpectedly, one of the monoadduct 12a was found to be labile when kept in air under ambient light. Two new products 15 (a sulfine-enone) and 16 (an endione) were isolated from the decomposed 12a and were found to derive from self-sensitized singlet oxygen reaction on the 2,5-dimethylthieno moiety of 12a.     

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.     

Synthesis of substituted methyl aryl ketone pyrimidinyloximes and their reactions with nucleophiles

Chloropyrimidines react readily with the sodium salts of alkyl aryl ketoximes to give acetophenone O-(2,4-dimethylpyrimidin-6-yl)- and O-(4,6-dimethylpyrimidin-2-yl)oximes, the oximino-groups in which readily undergo nucleophilic substitution.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1644–1648, December, 1989.     

Synthesis of 3-halo-2,5-disubstituted furans via CuX mediated cyclization-halogenation reactions

The Cu(I) halide (X = I, Br, Cl) mediated reactions of Cbz-protected cis-2-phenylethenyl-3-hydroxypyrrolidine gave novel 3-halo-2,5-trisubstituted furans in good yields, via a cyclization-halogenation, ring-opening reaction sequence. In contrast, the reactions with CuCN gave mainly the corresponding 3-cyanofuro[3,2-b]pyrrole formed from a cyclization-cyanation reaction.     

Synthesis of anthra[9,1-cd]isothiazolium derivatives and their reactions with nucleophiles

The methylation of 9-methyl-4-methylamino-5H-anthra[1,9,8-bcde]-1,10⁴-dithia-9-azapentalen-5-one takes place at the S₍₁₎, atom and leads to a 2-methyl-7-methylamino-10-methylthio-6-oxo-6H-anthra[9,1-cd]isothiazolium salt, while protonation is directed to the N₍₉₎ atom to give a 5,10-bis(methylamino)-6-oxo-6H-anthra [1,9-cd]dithiolium salt. Depending on their nature, substitution of the hydrogen atom in the 5 or 3 position, reversible addition of a hydroxide ion in the 10b position, demethylation, or opening of the heteroring occurs in the reaction of the anthraisothiazolium cation with nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 256–263, February, 1992.     

Electronic structure of organylthiochloroacetylenes and their reactions with O-containing nucleophiles

Conclusions Reactivity of organylthiochloroacetylenes toward O-containing nucleophiles was studied. It was established that phenolate anions attack the acetylenic C atom bound to the Cl atom and alcoholate anions attack the carbon atom bound to the S atom, which corresponds with the data of quantum chemical calculations.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya No. 3, pp. 612–616, March, 1988.     

Diisophorone and related compounds. Part 12 Synthesis of 4-bromodiisophorones and their reactions with nucleophiles

4-Bromodiisophor-2(7)-en-1-ol-3-one (2) is accessible by the action of hydrobromic acid on 2,7-epoxydiisophoran-1-ol-3-one (1), and is convertible into the corresponding 1-carboxylic acid (9) by theKoch-Haaf reaction. Nucleophilic substitution displaces the halogen in both the 4-bromoketol (2) and the 4-bromoketo-acid (9). Amongst the products thus obtained, 4-hydroxy-1-carboxydiisophor-2(7)-en-3-one (11) is of special interest as a source of the 3,4-diketo-1-carboxylic acid (13).

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Diisophoron und verwandte Verbindungen, 12. Mitt.: Synthese von 4-Bromdiisophoronen und ihre Reaktion mit Nucleophilen

Zusammenfassung 4-Bromdiisophor-2(7)-en-1-ol-3-on (2) ist durch Einwirkung von Bromwasserstoffsäure auf 2,7-Epoxydiisophoran-1-ol-3-on (1) erhältlich und wird mittels derKoch-Haaf-Reaktion zur entsprechenden 1-Carbonsäure (9) umgesetzt. Durch nucleophile Reagenzien wird das Halogen sowohl im 4-Bromketol (2) als auch in der 4-Bromoketosäure (9) substituiert. Unter den so erhältlichen Produkten ist das 4-Hydroxy-1-carboxydiisophor-2(7)-en-3-on als Ausgangsmaterial für die 3,4-Diketo-1-säure (13) von zusätzlichem Interesse.

     

Stereoselective synthesis of cis-2,5-disubstituted pyrrolidines via Wacker-type aerobic oxidative cyclization of alkenes with tert-butanesulfinamide nucleophiles

Palladium(II)-catalyzed aerobic oxidative cyclization of alkenes with tethered tert-butanesulfinamides furnishes enantiopure 2,5-disubstituted pyrrolidines, originating from readily available and easily diversified starting materials. These reactions are the first reported examples of metal-catalyzed addition of sulfinamide nucleophiles to alkenes.     

Synthesis and antiviral evaluation of new 2,5-disubstituted 1,3,4-oxadiazole derivatives and their acyclic nucleoside analogues

Abstract  

A number of new 5-[(naphthalen-1-yloxy)-methyl]-1,3,4-oxadiazole derivatives were synthesized. Sugar 2-[5-[(naphthalen-1-yloxy)methyl]-1,3,4-oxadiazol-2-ylthio]acetohydrazones were prepared by condensation of the hydrazide with the corresponding monosaccharides. Cyclization of the sugar hydrazones with acetic anhydride afforded the substituted oxadiazoline derivatives. The synthesized compounds displayed different degrees of antiviral activities or inhibitory actions against HCV and HIV viruses.     

Synthesis of 2,5-disubstituted tetrahydrofurans from organozinc halides and lactones

<正>2,5-Disubstituted tetrahydrofurans were obtained from lactones and organozinc halides in moderate to high yield in the presence of Lewis acids.     

Synthesis of aminomethylazetidines regioselective reactions of mesyloxymethylazetidinones with nucleophiles II

Two efficient methods have been developed for the synthesis of variously substituted 2‐aminomethylazetidine derivatives 5 by regioselective nucleophilic substitution of 4‐mesyloxymethylazetidin‐2‐ones 3 followed by reduction or by reduction of the appropriate 4‐oxo‐azetidine‐2‐carboxamides 7 . A novel ring transformation of 4‐oxoazetidine‐2‐carboxamides 7 into tetrahydroquinolines 16 by reaction with lithium aluminium hydride/aluminium trichloride has been investigated.     

Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from trichloromethylarenes and acylhydrazines

A preparative synthesis of 2,5-disubstituted 1,3,4-oxadiazoles by the reaction of trichloromethylarenes with hydrazides of carboxylic acids of the aliphatic, aromatic and heteroaromatic series in methanol or ethanol in the presence of pyridine was developed.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–692, May, 1994. Original article submitted April 8, 1994.     

Synthesis of 3-R-2-aryl-4,6-dinitroindoles and specific features of their reactions with anionic nucleophiles

Reaction of different anionic S-nucleophiles with 3-R-2-aryl-4,6-dinitroindoles led to a regiospecific nucleophilic substitution of the nitro group in position 4 with 6-NO₂ group remaining intact. The representatives of some peri-annulated polycyclic systems were synthesized on the basis of the substitution products. Dedicated to Academician V. A. Tartakovsky in honor of his 75th anniversary. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1543–1547, August, 2007.     

Synthesis of 2,5-disubstituted tetrazoles as possible antiinflammatory agents

Several 2-(1-acetoxy-3-substituted carbamido)-5-phenyltetrazoles were synthesized as possible antiinflammatory agents. Nmr spectroscopy was used as a tool in assigning the structure of the. Positional isomers of these substituted phenyltelrazoles. Compounds possessing antiinflammatory activity (100 mg./kg., i.p.) provided 11–41% protection against carrageenin-induced edema in rats. Seven of these substituted phenyltelrazoles possessed antiproteolytic activity and the in vitro inhibition of trypsin activity during hydrolysis of bovine serum albumin ranged from 9–66%.     

Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles containing benzothiazolylthiol grouping

A series of 2,5-substituted 1,3,4-oxadiazoles containing 2-benzothiazolylthiomethyl grouping has been synthesized by condensing derivatives of (2-benzothiazolylthio)acetic acid with imino ester hydrochlorides and hydrazides of carboxylic acids, by the cyclodehydration of N-acyl-N-(2-benzothiazolylthioacetyl)hydrazines under the action of POCl, and also by the reaction of 2-mercaptobenzothiazole with 2-chloromethyl-1,3,4-oxadiazoles in the presence of sodium methylate.I. M. Gubkin Russian State University for Petroleum and Gas, Moscow 117917. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 249–255, February, 2000.     

Perfluoroalkylsulfone reactions with nucleophiles

Perfluorodialkylsulfones were found to react readily with metal hydroxides in water or alcohol solution and with ammonia to form fluorinated sulfonic acid derivatives.     

Synthesis,antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles

In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, ¹H-NMR, ¹³C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250–7.8 µg mL^?1 against the tested microorganisms. Among the newly synthesized derivatives 3–22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than standard drugs ampicillin trihydrate and rifampicin against Pseudomonas aeruginosa and its gentamicin-resistant isolate. The 2D-QSAR (Quantitative Structure–Activity Relationship) analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) was also performed by using multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.     

Synthesis of 2,5-disubstituted pyrroles by the reaction of ketoximes with 1,2-dibromopropane

Conclusions The reaction of ketoximes with 1,2-dibromopropane in the KOH-DMSO system gave 2,5-disubstituted pyrroles in 21–56% yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2175–2177, September, 1988.