One-Pot, Three-Component Synthesis of 5-Sulfenyl-2-iminothiazolines by Cross-Dehydrogenative C–S Coupling Using I₂/DMSO in Open Air

Abstract

A one-pot, three-component, transition-metal-free regioselective sulfenylation of 2-iminothiazoline through the cross-dehydrogenative coupling strategy via sp2 C–H functionalization has been developed employing iodine as a catalyst and dimethyl sulfoxide as an oxidant. Utility of this sulfenylation technique has been well depicted through participation of various aryl and heterocyclic thiols. Significant features of this C–H functionalization strategy include metal-free open air reaction conditions, which offer a mild and efficient method for sulfenylation to achieve diversely substituted 5-sulfenyl-2-iminothiazoline derivatives.

Convenient Multicomponent One‐Pot Synthesis of 2‐Iminothiazolines and 2‐Aminothiazoles Using Elemental Sulfur Under Aqueous Conditions

“…Presumably the significant difference between the pK a values of benzylamine and 2,6dimethylaniline enables the regioselective preparation of 5 a. [14,36,37] The nucleophilic character of aliphatic amines such as phenethylamine, or benzylamine [63] are able to activate sulfur that might provide 3 a and then 5 a in the absence of external bases. The reaction of 1 a, 2 a and the aqueous polysulfide solution made of 1.0 M PMDTA and 0.4 M sulfur at 80°C provide the thiourea 3 a in 89 % yield in 0.5 hour in water (Table 1, entry 1, see ref.…”

“…Although the ring‐closure may lead to the regioisomer 5a’ , we did not observed its formation in the reaction. Presumably the significant difference between the p K a values of benzylamine and 2,6‐dimethylaniline enables the regioselective preparation of 5 a [14,36,37] …”

“…The regioselectivity is driven by the pK a values of the NH protons, particularly the more basic nitrogen participates in the formation of the heterocycle. [14,36,37] Several variant of the original synthetic method have been developed, like solid supported synthesis [14,38] base-catalyzed and aqueous methods. [39][40][41] Considering green chemistry principles and synthetic efficiency, we focused on one-pot and multicomponent approaches that have been designed by the in situ synthesis of thioureas or αhaloketones.…”

“…Unsubstituted and N ‐monosubstituted thioureas lead to 2‐aminothiazoles while N,N’ ‐disubstituted ones lead to 2‐iminothiazolines. The regioselectivity is driven by the p K a values of the NH protons, particularly the more basic nitrogen participates in the formation of the heterocycle [14,36,37] . Several variant of the original synthetic method have been developed, like solid supported synthesis [14,38] base‐catalyzed and aqueous methods [39–41] .…”

Recent Advances in Multicomponent Reactions with Organic and Inorganic Sulfur Compounds

“…Pramanik's research group recorded a metal‐free three component cross‐dehydrogenative coupling strategy to generate 5‐sulfenyl‐2‐iminothiazolines 99 giving 38 examples in good yields (62 %–82 %) under air atmosphere conditions (Scheme 25). [66] …”