Acid-catalyzed cyclization of acyldithiocarbazates 1.02, readily available from 1.01, affords 2-methylthio-1,3,4-thiadiazolium salts 1.05. Reaction of 1.05 with nucleophiles such as amino derivatives Z-NH2 or active methylene compounds CH2Z2 leads to 2-imino- or 2-methylene-1,3,4-thiadiazolines 1.06 and 1.07, respectively. If aldoximes (R’CH=NOH) are used as nucleophiles, the reaction with 1.05 in basic medium (Et3N) allows dehydration to nitriles, and thiadiazolone 1.08 is obtained as side product. This compound undergoes easy thionization (1.09) and S-methylation by the Meerwein’s reagent to afford 1.05. Softer nucleophiles such as halides attack the softer electrophilic S-methyl C atom performing demethylation to 1.09, as supported theoretically [pub022]. By using di- or tricarboxylic acid derivatives in the formation of 1.02, or α,ω-diamino derivatives in the reaction with 1.05, several di- and tripodands were obtained, as well as macrocycles incorporating the 1,3,4-thiadiazole subunit.
When cyclization of 1.02 is performed in basic conditions, 1,3,4-oxadiazolin-2-thiones 1.10 are obtained and can be converted into 2-methylthio-1,3,4-oxadiazolium salts 1.04 by S-methylation.
Functionalization at C-5 in 1.09 with amino-substituents has been effected by reaction of 1.01 with isothiocyanates (or isocyanates followed by thionization) [pub006]. A special case was found in the reaction of 1.01 with CS2 that yields 5-methylthio-1,3,4-thiadiazolin-2-thione 1.09 (R: MeS) by initial formation of the mesoionic 2-methilthio-1,3,4-thiadiazolium-5-thiolate 1.05 (R: S–) followed by isomerization involving double intermolecular S,S-transmethylation, as ascertained by QC calculations [pub055].
An alternative route for functionalization at C-5 is by generation of iminophosphorane 1.03 (by the Kirsanov method) and reaction with CS2 or isocyanates leading to mesoionic 2-methylthio-1,3,4-thiadiazolium-5-thiolate or -5-aminide 1.05 (R: S– or R’N–, respectively) [pub006, pub007]