Blue Light induced Coupling of N- Hydroxysulphonamides: An efficient and green Approach to Access Symmetrical Thiosulfonates

The visible light induced, highly efficient, and green protocol has been demonstrated for the synthesis of symmetrical S-Phenyl benzene thiosulfonates by irradiation of NHydroxy sulphonamides in the presence of ethanol solvent. The adopted method shows significant advantages such as eco-friendly procedures, short reaction time, cost effectiveness, operational simplicity, excellent yields and use of blue light which is a ubiquitous, making it a genuinely green protocol.


Introduction
Organosulfur compounds have attracted great attention due to their potent antimicrobial and fungicidal activities, with considerable attention to agrochemical area in recent years [1]. among them, thiosulfonates are of particular interest in pharmaceutical, clinical, together with their wide range of industrial applications [2].
Because of the widespread application of thiosulfates, considerable effort has been made in the development of synthetic methods for such compounds. The frequently employed methods involve the oxidation of symmetrical and unsymmetrical disulfides.
There are numerous approaches for the synthesis of thiosulfonates including selective reduction of sulfonyl chlorides [3], reaction of thiosulfonates with diaryliodonium salts [4], reaction of thiols with sulfonic acid using cyanuric chloride [5], iodine/bromine oxidative sulfenylation of sulfonates with disulfides [6], and oxidation of disulfides or thiosulfinates [7]. From disulfides or thiols [8]. In general, the traditional preparation involves the sulfone-sulphur bond formation, which mainly based on the sulfenylation of sodium sulfinates with disulfides in the presence of AgNO3, or halogen-based oxidants [9]. Notably, the coupling of thiols with sulfonyl chlorides has been less studied due to the rapid formation of disulfides via the nucleophilic substitution of 3 thiosulfonates by thiols [10] Currently, the copper-or iron mediated oxidative coupling of thiols with sodium sulfinates has also been developed [11]. Therefore, the development of a convenient and practical protocol for the synthesis of thiosulfonates is still a significant issue. In the past few years, sulfonyl hydrazides have been widely used as convenient sulphur electrophiles or nucleophiles in the presence of (TBHP) tert-butyl hydroperoxide and molecular iodine, copper and iron salts, which have been considered to be ideal and useful sulfonylation or sulfenylation agents. [12]. Recently, the cross-coupling reaction of sulfonyl hydrazides with thiols (or sodium sulfinates with disulfides) has been developed for the preparation of thiosulfonates with the help of transitional metal catalysts [13], Sodium sulfinates [14] and sulfoxides [15] are also important organosulfur compounds. Alternatively, thiosulfonates can be obtained by thiosulfonate exchange reactions of sulfenamides, by the reaction of potassium thiosulfonates with diaryliodonium salts [16]. Most of the existing methods involve the use of a stoichiometric number of oxidants, such as diazenecarboxamides [17], claysupported ferric nitrate [18], silica sulfuric acid/sodium nitrite [19], and peroxynitrite [20]. Many of these methods suffer from long reaction times, laborious isolation procedures, difficult preparation, or, drastic reaction conditions, costly reagents, unsatisfactory yields, tedious workup procedures, and co-occurrence of several side reactions. In short, for the synthesis of thiosulfonates in the reported methods, some special additives as catalyst (oxidants or reductants), toxic reagents (e.g., RSH), or harsh conditions are still demanded for these transformations. The safety of the environment and consciousness about the reduction in global warming inspires the use of renewable energy resources and minimization of waste products. In the past several years, the development of a sustainable, eco efficient energy source for the construction of biologically important organic compounds has become an important 4 research area in the field of synthesis. Visible light induced synthesis has evoked the interest of chemists and researchers due to the easy availability of visible radiation. In addition, cost effective radiation is useful and harmless to human beings [21]. Light is a perfect reagent for the environmentally benign, green organic synthesis of scaffolds because it activates organic molecules, facilitating a smooth completion of the chemical reaction [22]. In recent years, visible light catalysis has emerged as a powerful tool for realizing novel organic transformations under mild reaction conditions. Therefore, in this article we carried out the visible light-induced catalysed transformations of N-Hydroxysulphonamides to symmetrical thiosulfonates derivatives as bioactive molecules in of ethanol which is observed as a green medium for synthesis. With the optimized reaction conditions in hand, a series of N-hydroxy sulphonamide were applied in the reaction to establish the scope and generality of this protocol (

Reagents
All the chemicals including iodine, hydroxylamine hydrochloride, potassium carbonate, sulfonyl chloride derivatives and other chemicals were procured from Sigma Aldrich and Alfa Aesar and were used as received.

Result and Discussion
To investigating our model reaction and to find the optimal reaction condition, Nhydroxyphenylsulfonamide was stirred at room temperature in ethanol using blue LED as visible light source. Initially, reactant was stirred in the absence of any catalyst and no product was observed even after 3 hour of stirring (table 1 entry 8). Knowing the ability of photocatalysts to promote organic reactions in visible light, we subsequently used eosin Y as a photocatalyst for our reaction. We observed that no product formation was occurring in the presence of eosin Y after 12 hours (table 1 entry 1).
Next, we took rhodamine and rosebengal as the photocatalysts but no progress of reaction was observed in the 12 hour stirring time (

Conclusion
In summary, we have developed a simple, yet highly efficient, visible light activated, 'real' green synthetic strategy to symmetrical thiosulfonate derivatives by N-Hydroxysulphonamides. A visible light assisted, metal free and easy workup procedure are some of the prime advantages of our reaction. To the best of our knowledge, the reported conditions are the first ever reported visible light mediated, synthesis of symmetrical thiosulfonate derivatives. Due to the mild reaction conditions, a wide range of substrates can be tolerated. The visible light as catalyst, short reaction