S. A. Soldatova

Synthesis and molecular structure of 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives and dimethyl 4-cyano-2,3,6,7-tetrahydro-1H-3-benzazonine-5,6-dicarboxylate

A study was carried out on the direction of 1,2,3,4-tetrahydroisoquinolinium quaternary salt rearrangements by the action of base with or without dimethyl acetylenedicarboxylate. These quaternary salts containing a methylene group at the nitrogen atom, are converted in the presence of base through intermediate N-ylides into the Stevens rearrangement products, namely, tetrahydro-3-benzazepines. Upon the addition of dimethyl acetylenedicarboxylate as an electrophilic trap, this diester adds at the carbanion site of the ylide with subsequent recyclization of the piperidine fragment to give a 2-benzazonine derivative with an unusual 4,5-positioning of the olefin bond in the nine-membered heterocycle. An X-ray structural analysis established the molecular structures of 2-cyano-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and dimethyl 4-cyano-2,3,6,7-tetrahydro-1H-3-benzazo-nine-5,6-dicarboxylate.

Synthesis and molecular structure of bis(benzo)aza-14-crown-4 ethers with 7-azabicyclo[3.3.1]nonane and homologous fragments

By condensation of cycloalkanes with 2-{2-[2-(2-formylphenoxy)ethoxy]ethoxy}benzaldehyde and ammonium acetate by Petrenko-Kritchenko method first representatives of new heterocyclic systems, bis(benzo)-aza-14-crown-4 ethers containing a 7-aza-bicyclo[3.3.1]nonane or its homologous fragment, were obtained in 6–15% yield. With growing cycle of the initial cycloketone the yield of the azacrownophane considerably grew. By means of XRD analysis the molecular structure was established of four synthesized macrocycles, the relative configuration of asymmetrical atoms was determined, and the size of the internal cavities of the azacrown part was estimated.

Dimethyl 2-[23-oxo-22,24-diphenyl-8,11,14-trioxa-25-aza­tetra­cyclo­[19.3.1.02,7.015,20]penta­cosa-2,4,6,15(20),16,18-hexaen-25-yl]but-2-enedioate

The title compound, C39H37NO8, is a product of the Michael addition of the cyclic secondary amine subunit of aza-14-crown-4 ether to dimethyl acetylenedicarboxylate. The piperidinone ring exhibits a distorted chair conformation and the dimethyl acetylenedicarboxylate fragment has a cis configuration with a dihedral angle of 56.61 (5)° between the two carboxylate groups. The crystal packing is stabilized by the weak C—H⋯O hydrogen bonds.

Conversion of 3-benzoyl-1-methyl-4-phenyl-γ-piperidol by arylamines and arylhydrazines. Synthesis of 3-arylamino-1-oxo-1-phenylpropanes and 1,3-diarylpyrazoles and their fragmentation under electron impact

It has been established that on heating, 3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidine is ring-opened in the presence of arylamines by a type of retroaldol reaction, with subsequent transamination of the intermediate Mannich base and the formation of 3-arylamino-1-oxo-1-phenylpropanes. When using arylhydrazines this γ-piperidol is recyclized with the formation of 1,3-diarylpyrazoles and their 4,5-dihydro derivatives. The mass spectral behavior of a series of 3-arylamino-substituted 1-phenylpropanones has been studied.

Rearrangements of N-ethoxycarbonylmethyl-1,2,3,4-tetrahydroquinolinium halogenalkylates effected by sodium hydride. Synthesis of 2,3,4,5-tetrahydro-1H-3-benzazepines

Quaternary salts obtained from N-alkyl-1,2,3,4-tetrahydroisoquinolines and ethyl haloacetates or diethyl bromomalonate under the action of sodium hydride in boiling 1,4-dioxane were converted into N-alkyl-N-ethoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepines in 49–60% yield. From the reaction mixture by column chromatography products of β-elimination by Hofmann reaction, 2-(N-methyl-N-ethoxycarbonylmethyl)-aminomethylstyrenes were also isolated (yield 0.6–16%).

Synthesis, structure, and biological activity of [2.2]paracyclophanes. 7. Synthesis of 2-([2.2]paracyclophan-4-yl)pyridines,-tetrahydroquinolines, and-benzo[h]quinolines based on condensation of 4-(β-dimethylaminopropionyl)[2.2]paracyclophane with primary amines

Condensation of 4-(β-dimethylaminopropionyl)paracyclophane with aliphatic aldehydes or cyclohexanones in the presence of hydroxylamine gave 2-([2.2]paracyclophan-4-yl)pyridines and-5,6,7,8-tetrahydroquinolines respectively. Reaction of these salts with α-naphthylamine gives a mixture of paracyclophanyl substituted 1,2,3,4-tetrahydrobeno[h]quinoline and benzo[h]quinoline.

Synthesis of pyrrolidines and tetrahydro-1H-azepines from 4-aryl-1-benzoyl(ethoxycarbonyl)methyl-1-methyl-1,2,3,6-tetrahydropyridinium halides

Abstract4-Aryl-1,2,3,6-tetrahydropyridinium quaternary salts which have a benzoylmethyl or ethoxycarbonylmethyl group on atom N-1 generate N-ylides when heated in the presence of NaH and they can rearrange in situ with contraction or expansion of the six-membered heterocycle to give substituted pyrrolidines (as a result of a [2,3]-sigmatropic rearrangement) or 1H-tetrahydroazepine derivatives (via Stevens rearrangement). The presence of an aryl substituent at position C-4 in the tetrahydropyridine ring allows to avoid the formation of elimination products and changes the direction of the reaction towards the preparation of the tetrahydroazepines.

Indolopyridines with a bridging heteroatom

Reaction of 2-acetylpyridine with 4-[2.2]paracyclophanyllithium or 4-acetyl[2.2]paracyclophane with 2-pyridllithium gives 1-([2.2]paracyclophan-4-yl)-1-(2-pyridyl)ethanol. Its molecular and crystalline structures have been studied by x-ray analysis. It was found that heating this alcohol in acid medium causes dehydration and heterocyclization to give 1-paracyclophanyl-1-pyridylethylene and 10-methyl[2.2]paracyclophano[4,5-bindolizine.

Synthesis, structure, and biological activity of [2.2]paracyclophanes. 6. Synthesis of 2-([2.2]paracyclophan-4-yl)(benzo[g])indoles

Cyclocondensation of 2-([2.2]paracyclophan-4-yl)-2-oxoethyltriethylammonium bromide with aniline and α-naphthylamine gives 2-(paracyclophan-4-yl)indoles and benzo[g]indole respectively.

Synthesis, structure, and biological activity of derivatives of [2,2]-para-cyclophane. 2. 4-Hydroxymethyl(acyloxymethyl, alkenyl)-[2,3]-para-cyclophanes

With the goal of studying the structure and biological activity of new compounds of the [2,2]-para-cyclophane (PCP) series (I), based on its 4-acyl derivatives (II) we synthesized 4-hydroxymethyl-, 4-acyloxymethyl-, and 4-alkenyl-substituted para-cyclophanes (Ill-VII). The starting 4-acetylPCP (IIa) was obtained as in [4]. We synthesized 4-benozoylPCP (IIb) in good yield (70%) by benzoylation of PCP I with benzoyl chloride in the presence of A1C13 at -35~ in dichloromethane. Earlier [5], compound lib was obtained in four steps through 4-PCP carboxylic acid (= 50% yield). Based on ketone IIa, we obtained three new imines: the semicarbazone, the thiosemicarbazone, and the 2,4-dinitrophenylhydrazone (IIIa-c respectively; the characteristics and PMR spectra of the compounds are presented in Table 1 and 2). By reduction of ketones II by sodium borohydride, we obtained methyl(IVa) and phenyl(IVb) {[2,2]-paracyclophane-4-yl}carbinols having an asymmetric center and a plane of asymmetry for the monosubstituted para-cyclophane moiety. According to the PMR spectral data, mixtures of diastereomeric racemic alcohols IVa are obtained in an 1:2 ratio. The major diastereomer, which according to the Cremer rule [3] should have the S configuration relative to the alcohol C-atom, was isolated by crystallization from hexane (m.p. 99-101~ Its 1H and 13C NMR spectra are presented in Table 2 and in the Experimental section.