Mechanochemical Thiocyanation of Aryl Compounds via C–H Functionalization

Abstract

Aryl thiocyanate compounds are important building blocks for the synthesis of bioactive compounds and intermediates for several functional groups. Reported thiocyanation reactions via C−H functionalization have limited substrate scope and low RME. The ball-milling method reported here uses ammonium persulfate and ammonium thiocyanate as reagents and silica as a grinding auxiliary. It afforded aryl thiocyanates with moderate to excellent yields for a wide variety of aryl compounds (36 examples, 8−96% yield), such as anilines, phenols, anisoles, thioanisole, and indole, thus tolerating substrates with sensitive functional groups. New products such as benzo [d][1,3]oxathiol-2-ones were obtained with C-4 substituted phenols. Thus, to our knowledge, we report, for the first time, aryl thiocyanation reaction by ball-milling at room temperature and solvent-free conditions, with short reaction times and no workup. Analysis of several mass-based green metrics indicates that it is an efficient greener method.

Fe(III)‐Mediated para‐Selective Nucleophilic Thiocyanation and Oxidation Reactions, Access to Thiocyanated Amidophenols and Amidoquinones

“…Preliminary attempts indicated that 3.0 equivalents of the oxidants were feasible for the transformation at ambient temperature, yielding 35 % of the para ‐selective thiocyanated product 2 a (Table 1, entries 1–3). Taking the solvent‐free mechanochemical method as a reference, we carried out the reaction with 3.0 equivalent of ammonium thiocyanate (NH 4 SCN), 3.0 equivalents of ammonium persulfate [(NH 4 ) 2 S 2 O 8 ] and SiO 2 in mortar [12] . Unfortunately, the reaction didn't work though by manual milling for 1 hour (Table 1, entry 4).…”

“…Taking the solvent-free mechanochemical method as a reference, we carried out the reaction with 3.0 equivalent of ammonium thiocyanate (NH 4 SCN), 3.0 equivalents of ammonium persulfate [(NH 4 ) 2 S 2 O 8 ] and SiO 2 in mortar. [12] Unfortunately, the reaction didn't work though by manual milling for 1 hour (Table 1, entry 4).…”

“…[8] Furthermore, radical pathways under harsh conditions, e. g. strong oxidative, [9] acidic ambient, [10] or photocatalytic system [11] have also been realized. Besides, the mechanochemical method [12] and ultrasound-promoted thiocyanation [13] provide optional ideas. Nevertheless, highly selective thiocyanation reactions under mild condition are relatively less reported and worth further study.…”

Green metrics in Mechanochemistry

“…144 In 2020, Malvestiti et al developed a mechanical protocol for the thiocyanation of aryl compounds via C-H functionalization. 145 Ball-mill reactions were all performed on a 0.2 mmol scale, without solvent, in short reaction times. The best conditions found for thiocyanation of orthoand metasubstituted anilines were to grind together anilines (1 equiv), ammonium thiocyanate (1.5 equiv.…”

Green metrics in mechanochemistry

“…172 In 2020, Malvestiti et al developed a mechanical protocol for the thiocyanation of aryl compounds via C-H functionalization. 173 Ball-mill reactions were all performed on a 0.2 mmol scale, without solvent, in short reaction times. The best conditions found for thiocyanation of ortho-and meta-substituted anilines were to grind together anilines (1 equiv.…”