Compounds with sulfonyl motif represent an important class of compounds in medicinal chemistry and drug discovery since they display wide range of biological activities. In particular, thiosulfonates are reported as anti-microbial, anti-fungal, insecticidal, cytotoxic and antiviral agents. Also, they have wide spread applications in polymer production, photographic processes, bioanalytical and biomedical fields as biosensors. Besides, they are used as electrophilic sulfenylating reagents in organic synthesis over sulfenyl halides as they are superior with respect to reactivity and stability, with other applications in organic chemistry. In general, symmetric thiosulfonates can be synthesized by the oxidation of thiols or disulfides. Use of different thiols or unsymmetrical disulfides results in the formation of regioisomeric mixture of products. Hence, efficient synthetic methods which would afford thiosulfonates in a highly regioselective fashion are required. Over the years, many approaches are reported for the synthesis of unsymmetrical thiosulfonates including sulfenylation of sodium sulfinates with disulfides in the presence of AgNO3, CuI, halogen or halogen-based oxidants,coupling of thiols with sulfonyl chlorides and oxidative coupling of thiols with sulfinates catalysed by copper and iron. Recently, cross coupling of sulfonyl hydrazides with (a) thiols catalysed CuBr2 in tert-butyl hydroperoxide (TBHP) media (Scheme 1a), (b) disulfides mediated by H2O2 (Scheme 1b) and (c) thiols in NaI/TBHP media (Scheme 1c) are reported. All of these methods suffers from demerits such as use of- transition metal catalysts,  stoichiometric amounts of oxidants elevated temperatures and formation of undesirable side products.Hence, a mild, transition metal-free, oxidant free, green and sustainable synthetic method which overcomes these limitations is in demand.

we have developed a new metal- and oxidant-free method for the synthesis of unsymmetrical thiosulfonates in high yields via sulfonylation of thiols with sulfonyl hydrazides, which overcomes all the limitations of the existing methods. The versatility of the reaction has been demonstrated by using various aryl/heteroaryl/alkyl thiols and aryl/heteroarylsulfonyl hydrazides. The scale up synthesis has highlighted the possible applicability of this method in industries. The reaction proceeds through a radical pathway as evident from radical trapping experiment and cyclic voltammetry studies.

The in vitro cytotoxicities of all compounds against four cancer cell lines were screened by using the MTT assay. The compounds 3ad and 3ah exhibited potent inhibitory activity against tumor cells. Moreover, compound 3ah inhibited cell migration ability and tubulin polymerization in T-24 cells, leading to cell cycle arrest and apoptosis.