An evaluation of credentials of a multicomponent reaction for the synthesis of isothioureas through the use of a holistic CHEM21 green metrics toolkit

Abstract

Multicomponent reactions (MCRs) are considered green and material efficient methods for the synthesis of organic compounds, however very few studies have investigated the metrics of the upstream processes involved to achieve the starting materials used in these reactions.

A more sustainable and highly practicable synthesis of aliphatic isocyanides

“…[24][25][26][27] Nowadays, the commonly used reagent is POCl 3 due to its suitability for different structural motifs. [28][29][30][31][32] Generally, isocyanide synthesis still heavily relies on laboratory preparation, since the number of commercially available isocyanides is limited to a few examples, and even small amounts are relatively expensive. 33 Bienaymé, Bossio and Armstrong focused their isocyanide synthesis work on feasible derivatisation routes, which eventually led to more easily accessible isocyanides.…”

Catalyst‐ and Solvent‐Free Synthesis of N‐Acylhydrazones via Solid‐State Melt Reaction

“…To evaluate the green credentials of our developed method, a variety of green chemistry metrics [62][63][64][65][66][67][68][69][70][71] were calculated for a gram scale synthesis of 3 a and 5 a (Table 5). Atom economy (AE) is the simplest metric used for assessing the efficiency and greenness of a reaction.…”

Novel Access to Known and Unknown Thiourea Catalyst via a Multicomponent‐Reaction Approach

“…Thus, highly toxic reagents and substrates were avoided, since the toxicity of isocyanides and amines is generally considered lower than the otherwise used reagents. [55][56][57] It is noted that the synthesis of isocyanides commonly entails the use of toxic reagents as well, for instance phosgene and its surrogates [58][59][60][61] or phosphorus oxychloride (POCl 3 ), [62][63][64][65] but we recently introduced a more sustainable route using p-toluenesulfonic acid chloride (p-TsCl) obtaining non-sterically demanding aliphatic isocyanides in good yields. [66] Results and discussion…”