Chemistry of N-Heterocyclic Sulfur Compounds. Reaction of 2,5-Dimercapto-1,3,4-thiadiazoles with 1,ω-Dibromoalkanes. Synthesis of Tetrathia(2,5)-1,3,4-thiadiazolophanes and Dithia(3,5)-1,3,4-thiadiazolinophanedithiones

Article abstract of DOI:10.1021/jo00379a017

The base-catalyzed reaction of 2,5-dimercapto-1,3,4-thiadiazole (1) with 1,ω-dibromoalkanes Br(CH2)nBr (n=1-4) has been investigated.Model experiments on the alkylation of 2-mercapto-5-(methylthio)-1,3,4-thiadiazole (3) with 1,ω-dibromoalkanes and 2,5-bis<(chloroalkyl)thio>-1,3,4-thiadiazoles, as well as on the dialkylation of 1 with 2-<(chloroalkyl)thio>-5-(methylthio)-1,3,4-thiadiazoles, have shown that both 3 and 1 undergo regioselective S-alkylation under basic conditions.However, the heterocyclization of 1 with 1,ω-dibromoalkanes and 2 equiv of KOH, carried out in EtOH under high dilution conditions, not only gave the expected S,S-bridgehead 2:2 macrocycles 2a (m=1; n=1,2,4), i.e., tetrathia<(n + 2).(n + 2)>(2,5)-1,3,4-thiadiazoles, but also the S,N-bridgehead 2:2 macrocycles 2b (m=1; n=2,3), i.e., dithia<(n + 1).(n + 1)>(3,5)-1,3,4-thiadiazolinophanedithiones.Furthermore, the high-dilution reaction of 1 with CH2Br2 and triethylamine gave 1,3,9,11,17,19-hexathia<3.3.3>(2,5)-1,3,4-thiadiazolinophane (19) (2a: m=2; n=1), while the use of 1 equiv of KOH under moderate dilution resulted in the formation of the macrocyclic isomer 1,8,15-trithia<2.2.2>(3,5)-1,3,4-thiadiazolinophane-4,11,18-trithione (20) (2b: m=2; n=1).The product distribution appears to be strongly dependent on the experimental conditions used, the nature and amount of base, the length of the dibromide, and its strength as an electrophilic agent.Several competing mechanisms have been ascertained to occur in the base-catalyzed heterocyclization of 1 with 1,ω-dibromoalkanes.The proposed reaction pathways gain support from the study of appropriate model reactions and from the isolation and identification of the involved key intermediates. 13C NMR spectroscopy has been extensively used to firmly establish the structures of the compounds obtained.