Multicomponent reactions of amino alcohols with CH2O and dithiols in the synthesis of 1,3,5-dithiazepanes and macroheterocycles

A series of new hydroxyl-substituted 1,3,5-dithiazepanes and N,N'-(2-hydroxyethyl)tetrathiadiazacycloalkanes were synthesized by the multicomponent reactions (MCRs) of amino alcohols with formaldehyde and (alpha,omega-dithiols. The MCR with 1,2-dithiol proceeds via a (1+2+1)-cyclocondensation with selective formation of 1,3,5-dithiazepanes. Stereochemisty of the dithiazepane ring was determined by X-ray diffraction. The reaction with higher alpha,omega-dithiols (1,3-propane-, 1,4-butane-, 1,5-pentane-, 1,6-hexanedithiol and 2-[2-(2-sulfanyletoxy)ethoxy]-1-ethanethiol) yielded OH-substituted macroheterocycles as a result of (2+4+2)-cyclocondensation. The structure of the latter was determined by NMR spectroscopy, MALDI-TOF and electrospray ionization methods. The doubly charged ions like [M+2H](2+) are found in the ESI spectra of the macrocycles. (C) 2014 Elsevier Ltd. All rights reserved.