Dipotassium 1,3,4-thiadiazole-2,5-bis(thiolate) as a new S-donor for direct synthesis of symmetrical disulfides

In this research, a simple, efficient and novel protocol is eveloped for the direct synthesis of symmetrical disulfides using dipotassium 1,3,4-thiadiazole-2,5-bis(thiolate) as a new, low toxicity, inexpensive, stable solid and free of foul-smelling thiols for synthesize symmetric diaryl/dialkyl disulfides from aryl and alkyl halides in presence of MOF-199 and CuO nanoparticles. Significantly, using this method results in obtaining a variety of symmetrical disulfides in moderate to excellent yields (up to 98%).


Results and discussion
The FT-IR spectrum of MOF-199 indicated three peaks at 3440 cm −1 , 1642 cm −1 and 1446 cm −1 which belong to H 2 O, EtOH molecules in the cavities of the matter, carbonyl group of the benzene tricarboxylic acid and the double bond of the benzene ring, respectively (Fig. 2). Regarding the FT-IR of Cuo nanoparticles, the stretching vibrations at 477 cm −1 , 522 cm −1 and 603 cm −1 can be related to the Cu-O band (Fig. 3).
One of the best approaches to determine of elements present in nanoparticles and the purity of nanoparticles is energy-dispersive X-ray spectroscopy (EDS). The EDX spectra of the MOF-199 and CuO NPs approve the presence of Cu and O elements in the structure of the catalysts and also confirm the fact that the nanoparticles have been successfully synthesized (Figs. 6,7).    www.nature.com/scientificreports/ X-ray diffraction (XRD) was used in order to investigate the structure of MOF-199 and CuO NPs. Regarding the XRD pattern of MOF-199, the biggest peak (222) is at 2θ = 11.76°. Considering the peaks observed in the region of 2θ = 10°-20° indicate the crystal structure of the MOF-199 metal-organic framework, which is consistent with the pattern presented in previous studies. (Fig. 8). Moreover, it is worth mentioning that 2θ = 34.45°, 37.30° for the CuO NPs confirms the structure of the catalyst (Fig. 9).
After the synthesis and characterization of MOF-199 and CuO NPs, the sulfur-transfer of 1,3,4-thiadiazole-2,5-bis(thiolate) was investigated in the synthesis of disulfides. In order to reach optimum conditions, iodobenzene and 1,3,4-thiadiazole-2,5-bis(thiolate) were used as a sulfur source in presence of different parameters including solvent, temperature and amounts of MOF-199 (method a) and CuO (method b). Based on the results of Table 1, the best results were obtained in dimethylformamide as a solvent using 4 mg MOF-199 and 5 mg CuO at 100 °C.
After obtaining the optimum conditions, a large number of symmetrical diaryl (alkyl) disulfides (1a-1l) was synthesized using 1,3,4-thiadiazole-2,5-bis(thiolate) in presence of MOF-199 and CuO NPs, the results of which are shown in Table 2. As can be seen, aryl iodides were more reactive than aryl bromides. Also based on  www.nature.com/scientificreports/ results in Table 2, both catalysts have a good to excellent yields, but MOF-199 has more activity and efficiency for the synthesis of diaryl and dialkyl disulfides. In most cases, the yield of the reactions was higher with shorter reaction times in the presence of MOF-199. The possible mechanism for the synthesis of disulfides is shown in Fig. 10 21 . The mechanism of this reaction is similar to Ullmann's reaction. The first step is the oxidative addition of copper to the aryl halide, which the organocopper intermediate (I) is formed. Consequently, it reacts with 1,3,4-thiadiazole-2,5-bis(thiolate) and finally converts to intermediate (II). Afterwards, intermediate (III) is produced using CuO extraction.    Subsequently, 10 g PEG was solved in 10 ml distillated water and, then, it was added to the reaction mixture dropwise and sonicated for 1 h. Finally, the product was separated using centrifugation process and, then, dried at 45 °C in oven.
General procedure for the synthesis of disulfides using CuO NPs. A mixture of aryl or alkyl halide (1 mmol), 1,3,4-thiadiazole-2,5-bis (thiolate) (2 mmol) and CuO (5 mg) in PEG (2 ml) was stirred at 100 °C. After completion of the reaction, the reaction mixture was cooled to room temperature and, then, the product was separated using H 2 O and EtOAc. The analysis of some compound contain 1H NMR and13C NMR spectrum are available in supplementary information.

Conclusion
In conclusion, an effective method was reported for the synthesis of symmetric diaryl (dialkyl) disulfides from aryl and alkyl halides. The salient features of the present protocol include: being more economic, comprehensive and environmentally friendly than previous methods. Moreover, dipotassium 1,3,4-thiadiazole-2,5-bis(thiolate) was introduced as a new sulfur source for the synthesis of symmetric disulfides from aryl and alkyl halides in presence of MOF-199 and CuO nanoparticles. Dipotassium 1,3,4-thiadiazole-2,5-bis(thiolate) has great potential as a sulfur-transfer reagent and possesses some specific advantages such as: low toxicity, water-solubility, www.nature.com/scientificreports/ stability and being odorless. Therefore, this strategy provides a new method for the direct synthesis of symmetrical disulfides.

Data availability
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Received: 8 July 2022; Accepted: 16 September 2022 Figure 10. A possible mechanism for the synthesis of disulfides.