Tetrabromomethane-mediated desulfurization for synthesis of isothiocyanates from amines

Abstract

Isothiocyanate considered as an important building block for pharmaceutical industry. Traditional methods for preparation of isothiocyanate involved the desulfurization of dithiocarbamate salt from amine using oxidizing agent. Although those methods are efficient, however, all of them require the use of toxic reagent, strong oxidizing agent, multiple step synthesis, harsh condition and large amount of metal catalyst. Therefore, in this research, we develop two mild methods to synthesize isothiocyanates from amines using low toxic reagent. For the first process, we were able to demonstrate the use of photocatalyst, safranin O to convert dithiocarbamate salt of 4-bromoaniline into 4-brophenyl isothiocyanate in 48% yield in one-pot under white LED irradiation. For the second process, commercially and low toxic CBr4 was used for desulfurization process. Based on our optimize investigation, we found that the use of CBr4 1.5 equivalences in the presence of 3.0 equivalences of DBU as base in acetonitrile give the optimized condition. Under this condition, we were able to synthesize 32 examples of isothiocyanates in moderate to excellent yields. Moreover, we were able to extend this methodology to prepare unsymmetrical thioureas via the in situ generation of isothiocyanate in one-pot. The synthesis of isothiocyanates and unsymmetrical thioureas were able to prepare a one-gram scale in good yields. The mechanistic study revealed that CHBr3 and sulfur were detected by NMR and SEM/EDX. This evidence suggests that CBr4 act as an electrophile to induce the desulfurization process. The benefit of this reaction includes one-pot synthesis, open air condition and low toxic desulfurizing agent.