Том 55, № 3 (2019)

A three-step procedure has been developed for the synthesis of 2-oxo-2,3-dihydro-1H-imidazo-[1,2-a]indole-6,7-dicarbonitriles from substituted 2-amino-1-hydroxy-1H-indole-5,6-dicarbonitriles.

The reaction of Finland trityl with tertiary aliphatic alcohols containing a terminal tertiary amino group, followed by quaternization of the amino groups, afforded new highly polar tri- and hexacationic derivatives. The obtained compounds are characterized by a sharp singlet signal in the EPR spectrum and are soluble in water over a wide pH range.

Pentacyclic heterocyclic compounds containing a 1,2,4-triazole ring have been synthesized from [5-(2-methylpropyl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c]isoquinolin-8-yl]hydrazine. The synthesized [1,2,4]triazolo[4,3-c]pyrimidine derivatives have been found to undergo Dimroth rearrangement in both acidic and basic media.

Study of the intramolecular cyclization of [3-(4-bromo(or methyl)phenylprop-2-yn-1-yl](3-phenylprop-2-en-1-yl)ammonium bromides has shown that the presence of a bromine atom or methyl group in the para position of the aromatic ring inhibits the process. 6-Bromo(or methyl)-4-phenyl-2,3,3a,4-tetrahydro-1H-benzo[f]isoindol-2-ium bromides undergo cleavage in aqueous alkaline medium at both N²-C³ and C¹-N² bonds, whereas cleavage of 6-methyl-4-phenyl-1,3,3a,4-tetrahydrospiro[benzo[f]isoindole-2,4′-morpholin]-2-ium bromide follows only the latter path. An accessible method has been developed for the synthesis of 6-bromo(or methyl)-4-phenyl-2,3,3a,4-tetrahydro-1H-benzo[f]isoindol-2-ium bromides, isomeric N-[7-bromo-2(3)-methyl-1-phenylnaphthalen-3(2)-ylmethyl]piperidines and -morpholines, and their 7-methyl-substituted analogs.

Three of the four possible diastereoisomeric thia-Michael addition products of the reaction of methyl (5-methylidene-4-oxo-cyclopent-2-en-1-yl)acetate with ethanethiol have been isolated and characterized. The major diastereoisomer is all-trans, while the overall fraction of the minor cis,trans and trans,cis isomers does not exceed 30%. The diastereoisomer structure has been determined on the basis of characteristic coupling constants of CH protons of the cyclopentane ring in the ¹H NMR spectra.

Reformatsky reaction of methyl 1-bromocyclopentanecarboxylate with 1-aryl-3-(2-hydroxyphenyl)-prop-2-en-1-ones afforded 6-substituted 4-(2-aryl-2-oxoethyl)-2H,4H-spiro[chromene-3,1′-cyclopentan]-2-ones. A probable reaction mechanism was proposed on the basis of DFT/TZVP quantum chemical calculations.

Oxidative condensation of N,N-bis(prop-2-yn-1-yl)trifluoromethanesulfonamide in DMSO involved only one ethynyl group, whereas in aqueous methanol 1,8-bis(trifluoromethanesulfonyl)-1,8-diazacyclotetradeca-3,5,10,12-tetrayne was obtained. N,N′-(Hexa-2,4-diyn-1,6-diyl)bis(trifluoromethanesulfonamide) in hexane solution was unexpectedly converted to diphenyldiacetylene, presumably, as a result of annulation of highly unsaturated carbon chains in the initial polyacetylene molecule and elimination of trifluoromethanesulfonamide and trifluoromethanesulfonamidomethyl residues.

Base-catalyzed low-temperature transformation of alkyl [(buta-2,3-dienimidoyl)sulfanyl]acetates [1-aza-1,3,4-trienes generated from lithiated alkoxy(or 1H-pyrrol-1-yl)allenes, isothiocyanates, and alkyl 2-bromoacetates] to tetrasubstituted thiophenes has been studied by B3LYP/6-311+G(d,p) quantum chemical calculations. Structural reorganization of 1-aza-1,3,4-trienes to thiophene derivatives involves deprotonation of the SCH₂ group, followed by intramolecular addition of the resulting carbanion to the β-carbon atom of the allene fragment. Gradient paths leading to sulfur heterocycles have been analyzed assuming participation of most stable 1-aza-1,3,4-triene isomers with trans-gauche orientation of the N=C and C=C=C fragments that are conformationally favorable for thiophene ring closure. The nature of substituents on the allene carbon atom and nitrogen atom is the main factor responsible for the ability of 1-aza-1,3,4-trienes to rearrange to thiophene derivatives. In going from 3-methoxy- to 3-(1H-pyrrol-1-yl)-1-aza-1,3,4-triene, the barrier to the cyclization decreases more than twice (from 5.6 to 2.5 kcal/mol). A comparable effect is observed on replacement of methyl group on the nitrogen atom by phenyl: the barrier decreases from 5.6 to 3.1 kcal/mol. Change of substituent in the allene fragment from methoxy to ethoxy group reduces the barrier by 1.0 kcal/mol (from 5.6 to 4.6 kcal/mol). Variation of the alkyl group in the ester moiety almost does not affect the cyclization barrier.

An efficient procedure has been developed for the synthesis diarylpropanes containing an urea fragment by acid-catalyzed reaction of N-(3,3-diethoxypropyl)ureas with sesamol. The product structure was proved by spectral data.

Ethyl 3,3,5,5-tetracyano-2-hydroxy-2-methyl-4,6-diphenylcyclohexane-1-carboxylate was synthesized for the first time by three-component condensation of benzaldehyde with ethyl acetoacetate and malononitrile in the presence of trichloroacetic acid. The product structure was proved by X-ray analysis.

Michael addition of various substituted benzylidene- and thiophen-2-ylmethylidenemalononitriles with acetoacetanilide gave the corresponding 5-acetyl-2-amino-4-aryl(hetaryl)-6-oxo-1-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitriles. Treatment of the latter with ethylenediamine in boiling methanol resulted in their rearrangement with elimination of the acetyl group and formation of 2-anilino-4-aryl(hetaryl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles. The product structure was proved by NMR spectroscopy and X-ray analysis.

N-Phenyltrifluoromemanesulfonamide reacted with N,N′-dicyclohexylcarbodiimide in methylene chloride to give exchange products, N-cyclohexyltrifluoromethanesulfonamide and N-cyclohexyl-N′-phenylcarbodiimide. Reaction of the latter with trifluoromethanesulfonamide afforded N-cyclohexyl-N′-phenyl-N″-(trifluoromethanesulfonyl)guanidine. In the reaction of N-phenyltrifluoromethanesulfonamide with N,N′-dicyclohexylcarbodiimide in acetonitrile, substituent exchange was a minor process, whereas the major one was dimerization of N,N′-dicyclohexylcarbodiimide catalyzed by N-phenyltrifluoromethanesulfonamide as NH acid.

Acylpyruvic acids and their esters regioselectively reacted with N-(2-aminophenyl)acetamide to give acyclic enamines, substituted (Z)-2-[(2-acetamidophenyl)amino]-4-oxobut-2-enoates, whose structure was confirmed by X-ray analysis. These compounds were formed as a result of condensation involving the primary amino group of N-(2-aminophenyl)acetamide at the most electrophilic C²=O carbonyl group of acylpyruvic acid or its ester. The obtained enamines underwent thermal heterocyclization to (Z)-3-(2-oxoethylidene)-3,4-dihydroquinoxalin-2(1H)-ones having no substituent on the N¹ atom rather than expected (Z)-1-acetyl-3-(2-oxoethylidene)-3,4-dihydroquinoxalin-2(1H)-ones. The heterocyclization involves intramolecular exchange between the amide and carboxylic acid (ester) fragments. The described transformations occur under mild conditions, require no catalyst or other additives, and therefore conform to the “green chemistry” principles. The products may be interesting from the viewpoints of medicinal chemistry, pharmacology, and fine organic synthesis.

The Diels-Alder reactions of perylene (diene) with 1,2-didehydrobenzene and 4,5-dimethoxy-1,2-didehydrobenzene (dienophiles) generated in situ by two methods were studied. According to the first method, diazonium salts derived from anthranilic acids and stabilized by 4-dodecylbenzenesulfonic acid were treated with potassium fluoride in toluene in the presence of 18-crown-6 on heating. The second method involved generation of arynes directly from substituted anthranilic acids by the action of isoamyl nitrite in toluene on heating. The corresponding Diels-Alder adducts, naphtho[1,2,3,4-ghi]perylene and 10,11-dimethoxynaphtho-[1,2,3,4-ghi]perylene, were isolated in up to 77% yield. The yield was higher when the aryne intermediate was generated from the stabilized diazonium salts. 4,5-Difluoro-1,2-dehydrobenzene and 2,3-dehydronaphthalene generated by both methods failed to react with perylene.