“Zero VOC” Synthetic Strategy – Aromatic Amination Reactions in Deep Eutectic Solvents

Abstract

Rising concern for environment hazards resulting from the use of volatile organic compounds (VOCs) is prompting many chemists to use “green” solvents like water, polyethylene glycol, ionic liquids and deep eutectic solvents (DES). With a few notable exceptions, many of these processes still need to use volatile organic solvents for the workup and isolation of products. In the present report, we demonstrate a “zero VOC” protocol which eliminates the need to use organic solvents for any stage of the reaction. As a proof of concept, nucleophilic aromatic substitution reactions of 1‐halo‐2,4‐dinitrobenzene with secondary amines were carried out in deep eutectic solvents. The reaction workup involved the addition of water for separating the product from the DES. Evaporation of water led to recovery of the DES, which exhibited good recyclability. The reaction in deep eutectic solvents was much faster than that in many other solvents, as confirmed by the kinetic studies. An attempt was made to elucidate the origin of this rate enhancement based on analysis activation parameters and correlation with the polarity parameters. The results show that use of deep eutectic solvents can take chemists a step closer towards the “zero VOC” synthetic strategy.

Aromatic nucleophilic substitution (snar) reactions of halo‐substituted dinitrobenzene in liposome reaction media: Effect of reaction medium and role of halogen leaving group

“…[15] The high yields of S N Ar reaction in nanomicelles indicated the possible role of aqueousorganic interface towards enhancing the reactivity. In continuation with our previous efforts towards developing an environmentally sustainable synthetic strategy for S N Ar reactions, [14,16] further exploration of S N AR reactions in microheterogeneous media such as liposomes (or vescicles) was relevant and logical extension of the previous attempts.…”

“…[9,10] However, the general reactivity of substrates in organic solvents and aqueous media has observed to be low, thus hampering extensive application of this class of reactions. The sluggish nature of nucleophilic substitution reactions (coupled with concern over the environmental hazards of conventional organic solvents) has prompted the use of numerous unconventional reaction media such as ionic liquids, [11][12][13] deep eutectic solvents, [14] and nanomicelles. [15] The high yields of S N Ar reaction in nanomicelles indicated the possible role of aqueousorganic interface towards enhancing the reactivity.…”

Solvent‐Controlled Regioselectivity in Nucleophilic Substitution Reactions of 1‐X‐2,4‐Difluorobenzenes with Morpholine Using Deep Eutectic Solvents

“…[21] Recently, our group demonstrated the use of "zero VOC" synthetic strategy for SNAr reactions of 1-halo-2,4-dinitrobenzene with secondary amines using deep eutectic solvents as reaction media. [22] The products could be obtained almost in stoichiometric yield, in very short time. The use of water as the only solvent for workup allowed the DES medium to be recycled for up to four times with negligible loss of reactivity.…”

“…These solvents have shown great potential as reaction media with improved yields, shorter reaction times and better selectivity [21] . Recently, our group demonstrated the use of “zero VOC” synthetic strategy for SNAr reactions of 1‐halo‐2,4‐dinitrobenzene with secondary amines using deep eutectic solvents as reaction media [22] . The products could be obtained almost in stoichiometric yield, in very short time.…”