Synthesis of 2-Aminobenzothiazoles via Oxidative C-H Functionalization

Significance

Reported is the synthesis of 2-aminobenzothiazoles from N-arylthioureas via an intramolecular C-S bond formation and C-H functionalization process. Many palladium sources and co-oxidants were screened and, unexpectedly, the combination of Pd(PPh₃)₄ with the activated MnO₂ as co-oxidant was revealed to be the best condition for this oxidative cyclization. However, the role of MnO₂ remains unclear. A potential mechanism was suggested involving σ-bond ­metathesis, wherein an anionic peroxo/peroxide-palladium aids in proton abstraction. Para- and meta-substituted aryl thioureas underwent chemoselective cyclization in reasonable yields. However, the reaction was found to be very sensitive to steric effects at the ortho-position adjacent to the C-H bond undergoing functionalization. Further, the reaction was sensitive to the nature of the group ortho to the thiourea group, for example, with halogen substituent competitive reductive cyclization to the dehalogenated cyclized product was observed.