Synthesis of N-Hydroxyalkyl-1,5,3-Dithiazepanes Based on Amino Alcohols

Abstract

Catalytic methods were developed for the synthesis of N-hydroxyalkyl-1,5,3-dithiazepanes by recyclization of 1-oxa-3,6-dithiacycloheptane with amino alcohols and by intermolecular cyclization of 1,2-ethanedithiol with methoxymethylamino alcohols.According to published data [1], one of the methods for the synthesis of N-substituted 1,5,3-dithiazepanes is the three-component condensation of primary amines with formaldehyde and 1,2-ethanedithiol. Another method is based on the catalytic recyclization of 1,3,5-triazin-2-one with 1,2-ethanedithiol [2] or 1-oxa-3,6-dithiacycloheptane with primary amines, as well as using the transamination of N-alkyl-1,5,3-di-thiazepanes with aniline derivatives [3] or aliphatic ,ω-diamines [4]. There are no literature references regarding the preparation of N-hydroxyalkyl-1,5,3-dithiazepanes. The interest in this class of heterocycles is motivated by their possible use as fungicides [5,6].In order to develop an effective catalytic method for the synthesis of N-hydroxyalkyl-1,5,3-dithiazepanes, we studied the recyclization of 1-oxa-3,6-dithiacycloheptane (1) with amino alcohols. The preliminary experiments indicated that the uncatalyzed interaction of 2-amino-2-methylpropane-1,3-diol with equimolar quantity of 1-oxa-3,6-dithiacycloheptane (1) in an EtOH-CHCl 3 solvent mixture at room temperature over 3 h led to the formation of 2-(1,5,3-dithiazepan-3-yl)-2-methylpropane-1,3-diol (2) in a yield not exceeding 20%. For the purpose of optimizing the yield of the heterocycle 2, recyclization of 1-oxa-3,6-dithiacycloheptane (1) with amino alcohol was performed in the presence of catalysts based on salts of transition metals (Cu, Pd, Co, Ni, Zr, Ti) and rare earth metals (Eu, Er, Yb, La, Sm), which have shown high activity in heterocyclization reactions [7,8]. The highest activity in this reaction was observed for the catalysts based on rare earth metal salts, where the yield of 2-(1,5,3-dithiazepan-3-yl)-2-methylpropane-1,3-diol (2) increased in the following order (5 mol% of catalysts were used): EuCl 3 ·6H 2 O (45%), Er(NO 3 ) 3 ·6H 2 O (49%),

New Catalytic Method for the Synthesis of 2,7-Dicycloalkyl-hexaazaperhydropyrenes

“…To achieve a higher yield of the target heterocycle 2, we have performed the reaction of 1,3,5-tricyclopropyl-1,3,5triazine with 1,4,5,8-tetraazadecalin in the presence of the catalysts that showed high activity in the ring transformation reactions [17][18][19]. The highest activity was found for catalysts based on transition metal salts and complexes, the yield of 2,7-dicyclopropyl-2,3a,5a,7,8a,10a-hexaazaperhydropyrene (2) being increased in the series of catalysts (5 mol% toward tetraazadecalin) as follows: The proposed structures were confirmed by the molecular ion peaks present in the positive ion matrix assisted laser desorption ionization tandem time-of-flight mass spectra (MALDI TOF/TOF MS, resolution 0.001 a.u.…”

Efficient catalytic synthesis of N-cycloalkyl-1,5,3-dithiazepanes

“…However, the catalytic recyclization of 1-oxa-3,6-dithiacycloheptane with primary amines allows selective preparation of N-aryl- [3,4] and N-alkyl-1,5,3-dithiazepanes [5,6] which are potential bactericidal, antimicrobial, and fungicidal agents [7,8].…”

“…In continuation of our studies in the field of catalytic synthesis of practically important N-substituted 1,5,3-dithiazepanes [3][4][5][6], in the present work we made an attempt to synthesize previously unknown N-cycloalkyl-1,5,3-dithiazepanes by recyclization of 1-oxa-3,6-dithiacycloheptane (1) with various cycloalkylamines. The reaction of cyclopropanamine with an equimolar amount of 1-oxa-3,6-dithiacycloheptane (1) in a mixture of ethanol with chloroform at room temperature in the absence of a catalyst in 3 h afforded 3-cyclopropyl-1,5,3-dithiazepane (2) in no more than 40% yield.…”

“…The reaction of cyclopropanamine with an equimolar amount of 1-oxa-3,6-dithiacycloheptane (1) in a mixture of ethanol with chloroform at room temperature in the absence of a catalyst in 3 h afforded 3-cyclopropyl-1,5,3-dithiazepane (2) in no more than 40% yield. To improve the yield of 2, the reaction of 1 with cyclopropanamine was carried out in the presence of transition (Cu, Pd, Co, Ni, Zr, Ti) and rare earth metal salts (La, Sm, Eu, Yb) which were used previously to catalyze heterocyclization reactions [3][4][5][6]. The most active were catalysts based on rare earth metals, and the yield of 3-cyclopropyl-1,5,3-dithiazepane (2) Under the optimal conditions (5 mol % of SmCl 3 · 6 H 2 O, EtOH-CHCl 3 , 20°C, 3 h), cycloalkylamines reacted with 1-oxa-3,6-dithiacycloheptane (1) yielding 50-87% of N-cycloalkyl-1,5,3-dithiazepanes 2-4 and 8-11 (Scheme 1).…”