A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur

Abstract

Isothiocyanates were snythesized in a more sustainable manner by sulfurization of isocyanides with elemental sulfur using catalytic amounts of DBU (down to 2 mol%).

Recent Advances in the Synthesis of Isothiocyanates Using Elemental Sulfur

“…The convenient activation of sulfur by nucleophilic additives, such as aliphatic amines and hydroxyl, sulfide and cyanide anions [40], and the corresponding significantly milder conditions compared to thermal activation support the notion that a switched mechanism also exists, involving a nucleophilic sulfur anion (S x − ) and the carbene of the isocyanide (5) acting as an electrophile (Scheme 2). The experimental findings from the research of Al-Mourabit et al and Meier et al and those found by our research group also support this latter presumption [41][42][43][44][45][46]. The exact number or the distribution of sulfur atoms in the forming anions was investigated experimentally and theoretically as well, suggesting that it depends on the reaction conditions and reactants [47].…”

“…To circumvent the toxicity of chalcogens, Stalke and co-workers introduced a base-free approach using a molybdenum catalyst, which they already applied in the episulfidation of alkenes and allenes with sulfur [69,74,75]. The reaction of isocyanides (41) and sulfur in the presence of catalyst 42 required 3 days in refluxing acetone, resulting in ITCs (43) in good to excellent yields (Scheme 9A) [69]. The first step of the reaction might be the sulfuration of 42 providing the molybdenum disulfur complex 44, which acts as the active sulfurtransferring agent.…”

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

“…[53] Certain nucleophiles, such as aliphatic amines are able to activate sulfur, generating open-chain ionic polysulfide anions which can be used in the atom efficient sulfuration of isocyanides leading to isothiocyanates. [54][55][56][57] Recently, we have published the preparation of aqueous solutions of sulfur that we applied in the chromatography-free and continuous flow synthesis of thioureas starting from isocyanides and both aliphatic and aromatic amines. [54,56] These methodologies enable the synthesis of symmetric or asymmetric thioureas from the isothiocyanate precursor isocyanides and the isolation of the pure products by a simple filtration.…”

“…Although plenty of sulfurating reagents are available, the application of elemental sulfur is considered to the most atom economical approach [53] . Certain nucleophiles, such as aliphatic amines are able to activate sulfur, generating open‐chain ionic polysulfide anions which can be used in the atom efficient sulfuration of isocyanides leading to isothiocyanates [54–57] . Recently, we have published the preparation of aqueous solutions of sulfur that we applied in the chromatography‐free and continuous flow synthesis of thioureas starting from isocyanides and both aliphatic and aromatic amines [54,56] .…”

One‐Pot Synthesis of Thiocarbamates

“…[24,25] Alternatively, more sustainable routes to isocyanates were published in the last years and some of them have already been employed in the synthesis of thiocarbamates. [11,21] Recently, it was shown that also isothiocyanates can be obtained rather sustainably utilizing isocyanides as starting material, [26] which, if applied, would allow for a more benign synthesis of Oorganyl or dithiocarbamates by functionalization with an alcohol or thiol. On this basis, S-organyl thiocarbamates are theoretically accessible through the Newman-Kwart rearrangement by isomerization of the O-thiocarbamates, [27] yet a direct synthetic route is more favorable.…”