Multicomponent reactions of amines with aldehydes and H2S as efficient route to heterocycles and thioaza macrocycles

Abstract

Here we provide new experimental results on multicomponent reactions of amines with aldehydes and H(2)S in the directed synthesis of functionally-substituted 1,3-thiazetidines, 1,3,5-dithiazinanes, 1,3,5-thiadiazinanes, 1,5-dithia-3,7-diazacyclooctanes, and thioaza macrocycles. X-ray analysis gave insight into the structure of the synthesized compounds. New kinds of multicomponent reactions (MCR) have been discovered and characterized.

Synthesis of partially hydrogenated 1,3,5-thiadiazines by Mannich reaction

“…37b, 54,57,63,[71][72][73][74][75] As in the case of primary amines, the reaction gave unequivocal results. For example, cyclothiomethylation of the simplest hydrazine (at molar ratio N 2 H 4 : CH 2 O : H 2 S = 1 : 6 : 4) at 0°С without catalysts gave the tetracyclic product 26, at 20°С -its mixture with compound 27, while at 40-60°С the only product isolated was the dithiadiazabicyclooctane 28 (Scheme 9).…”

“…41,55,57,60 When performing the reaction in aqueous alcohol solution at 0°С and the reactant ratio of ArNH 2 : СН 2 О : H 2 S = 2 : 3 : 1, weakly basic nitroanilines formed either 1,3,5-dithiazines 20, or their mixtures with 1,5-dithia-3,7-diazacyclooctanes 22. For o-substituted anilines, generally low degrees of conversion When performing the cyclothiomethylation of p-aminobenzosulfonamides and aminobenzoic acids, 41b α-and β-amino acids, 37 hydroxylamine, and various amino alcohols, 62,63 as well as aminophenols 55,57,63,64 and aminothiophenols 57 with CH 2 O-H 2 S, in none of the cases derivatives of 1,3,5-thiadiazine 13 could be successfully isolated: as a rule, derivatives of 1,3,5-dithiazine 20 or S,N-containing macrocycles were obtained instead.…”

Effective synthesis of N-substituted 1,3,5-dithiazinanes by reactions of N-methyl-1,3,5-dithiazinane and 1,3,5-trithiane with aromatic amines

“…A Schlenk flask equipped with a magnetic stirrer was charged under argon with 11 mmol of 1,3,5-trithiane, 0.5 mmol of FeCl 3 · 6 H 2 O as catalyst, and 10 mmol of the corresponding arylamine in 5 ml of acetonitrile. The mixture was stirred for 6 h at 60°C, and the products (compounds I and V-IX) were purified by column chromatography and identified by comparing with authentic samples [9,13,14].…”

The synthesis of N-substituted N,S-macroheterocycles derived from aromatic carboxylic acid hydrazides

“…There are stereoelectronic interactions between the unshared electrons on the nitrogen and sulfur atoms (for instance, in the dithiazinane [17,18] and dithiazepinane [19] systems), that reduce the energy of the chair conformation and the chair-chair conformation, respectively. However, the macrocycle has a higher conformational mobility, so the number of possible conformations increases.…”