Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts

Abstract

A novel atom-economic three-component one-pot reaction of a primary amine, an S-alkylisothiouronium salt and a Michael receptor is reported, which affords a guanidinium salt and thioether simultaneously.The guanidine moiety is involved in catalyzing the conjugated Michael addition of the mercaptan. The reaction proceeds under ambient conditions using a non-toxic EtOH-H 2 O mixture as the solvent, and the two products can be very easily purified. Complete atom economy is achieved by fully utilizing the S-alkylisothiouronium salt and converting the previously wasted mercaptan by-product into the valuable thioether.

Cu‐catalyzed vinylamination of S‐alkylisothiouronium salts with maleimide and alkylamines

“…[ 10,11 ] For example, Li reported a metal‐free three‐component thia‐Michael addition and guanidination of amines, S ‐alkylisothiouronium salt, and Michael acceptor to generate guanidinium salts and thioether (Scheme 1A). [ 12 ] Despite these impressive advancements have been made to expand the application of S ‐alkylisothiouronium salts, to the best of our knowledge, the new transformation of S ‐alkylisothiouronium salts in oxidative‐coupling/multi‐component cascade reactions remains underexplored.…”

An efficient synthesis of 2-thio-5-amino substituted benzoquinones via KI catalyzed cascade oxidation/Michael addition/oxidation starting from hydroquinone

“…To achieve this goal, a model reaction of hydroquinone (1, 1 mmol), cyclohexylamine (2a, 2 mmol) and S-allylisothiouronium bromide (3a, 1 mmol) was carried out using triethylamine (Et 3 N, 1 mmol) as base, tetrabutylammonium bromide (TBAB) as catalyst in CH 2 Cl 2 /H 2 O in an open atmosphere at room temperature referring to our previous work. 28,29 To our delight, the expected product 2-allylthio-5-cyclohexylamino-1,4-benzoquinone (4aa) was obtained in 19% yield (entry 1, Table 1). To nd the optimized reaction conditions, different solvent systems and bases were rst screened (entries 2-9, Table 1).…”

“…[25][26][27] In the meantime, S-alkylisothiouronium salts have been successfully used to replace the thiols in the thia-Michael addition in our previous work to avoid the foul smell and toxicity of thiols (Scheme 2, eqn (1)). 28,29 Considering the continues of our work and the advantages of MCRs, we envisaged that the 2-thio-5-amino substituted benzoquinones would be prepared using S-alkylisothiouronium salts as equivalents of thiols and starting from hydroquinone via cascade oxidation/Michael addition/oxidation strategy (Scheme 2, eqn (2)). To achieve this goal, a model reaction of hydroquinone (1, 1 mmol), cyclohexylamine (2a, 2 mmol) and S-allylisothiouronium bromide (3a, 1 mmol) was carried out using triethylamine (Et 3 N, 1 mmol) as base, tetrabutylammonium bromide (TBAB) as catalyst in CH 2 Cl 2 /H 2 O in an open atmosphere at room temperature referring to our previous work.…”