Conversion of enamines, enamides and triazoles by trithiazyl trichloride into 1,2,5-thiadiazoles

Abstract

Trithiazyl trichloride 1 converts primary and secondary enamines, enamides and 1,2,3-triazoles into 1,2,5thiadiazoles. These mild reactions provide one-pot routes to various alkyl, aryl, functional and quaternary 1,2,5-thiadiazoles, in moderate to good yields. The trimer 1 reacts as a 1,2-bis-electrophile adding an N-S unit across C᎐ ᎐ C-N. For primary enamines 15 N-labelling reveals an additional, minor pathway in which N-S-N is added across C᎐ ᎐ C, with elimination of the enamine nitrogen. With N-alkylated enamines the alkyl group is retained in a quaternised thiadiazole, but this can be dealkylated in situ. Enamides react similarly but with spontaneous N-deacylation. 1,2,3-Triazoles with electron withdrawing groups to stabilise their acyclic diazoimine tautomers also give 1,2,5-thiadiazoles, with loss of dinitrogen. Mechanisms are proposed for these new reactions.We have shown that trithiazyl trichloride, (NSCl) 3 , "the trimer" 1 reacts readily with nucleophilic unsaturated substrates, by electrophilic attack or by cycloaddition, to give a useful range of sulfur-nitrogen heterocylic compounds. 1 Thus pyrroles, for example, are converted into isothiazoles or fused 1,2,5thiadiazoles. 2 It seemed that enamines might undergo somewhat analogous reactions, with addition of the trimer across the bisnucleophilic enamine group or across the carbon-carbon double bond, and we now describe these and related reactions. Results and discussion Reactions with primary enaminesWe first treated the stable primary enamines 3-aminocrotononitrile 2a and methyl, ethyl and p-nitrobenzyl 3-aminocrotonates 2b-d with the trimer 1 (1 equiv.

Ring fused 1,2,5-thiadiazoles from oximes and trithiazyl trichloride

“…We have shown that enamines, enamides and 1,2,3-triazoles all react with trithiazyl trichloride 1, the trimer of N᎐ ᎐ ᎐ S-Cl, to form 1,2,5-thiadiazoles by a combination of C-C-N and S-N components. 1 On mechanistic grounds it seemed that the even more readily available oximes of α-methylene ketones might react similarly and we now show, in a limited investigation, that they do. Our initial reactions of oximes with the trimer 1 proved to be relatively complex and not high yielding.…”

Recent Developments in the Synthesis and Applications of 1,2,5-Thia- and Selenadiazoles. A Review

“…Mechanisms were proposed for these transformations. 65 It was found that 1-aryl-2-chloroethanone oximes 56 reacted with tetrasulfur tetranitride in refluxing dioxane to afford 3-aryl-1,2,5-thiadiazoles 57 in good to high yields (Scheme 27). 66 Surprisingly bromo analogs under the same conditions gave a mixture of…”

“…82 1-Unsubstituted or 1-tosylated 1,2,3-triazoles 100, containing the electronwithdrawing 4-nitrophenyl group at position 5, reacted with trithiazyl trichloride in boiling tetrachloromethane for 16 h to give 3-aryl-1,2,5-thiadiazoles 101 in high yields (Scheme 48). 93 It was proposed that the starting triazoles to react by initial ring opening to their acyclic Downloaded by [Laurentian University] at 08:03 25 November 2014…”

Trithiazyl Trichloride

“…11 The reaction of 1 with simple imines provides a new one-pot synthesis of 1,2,4-thiadiazoles (eqs 10 and 11): Reactions with Enamines and Enamides. 12 These mild reactions provide one-pot routes to alkyl, aryl, and functionalized and quaternized 1,2,5-thiadiazoles in modest yields with retention of the enamine nitrogen, the trimer 1 contributing an S-N unit; for example, eqs 12-14: …”

“…When the second ring fusion is not possible, as with indan-1-one oxime (eq 16), the yield of the analogous 1,2,5-thiadiazole (11) was much improved. With benzosuberone oxime (12), the mono-thiadiazole (13) was isolated, but interestingly this did not react further (eq 17). Reactions with Furans.…”