A microdroplet-accelerated Biginelli reaction: mechanisms and separation of isomers using IMS-MS

Abstract

Electrospray ionization (ESI) combined with ion mobility spectrometry (IMS) and mass spectrometry (MS) techniques is used to examine the Biginelli reaction in an ensemble of ions generated from droplets.

Accelerated microdroplet synthesis of benzimidazoles by nucleophilic addition to protonated carboxylic acids

“…Factors of similar magnitude have been reported for the Biginelli reaction where similar temperature effects are associated with the last step of a reaction. 52…”

Identifying reactive intermediates by mass spectrometry

“…43 The organocatalytic reactions are oen used for stereoselective reactions. 44 Here, product 4 is formed as R or S stereoisomer at the a-carbon atom of the aldehyde. The stereochemistry is predetermined by the conguration of the key enamine intermediate 5.…”

“…Increasing the concentration can also substantially accelerate some reactions. 13,44,57 Hence, processes that are important at high concentrations can be selectively detected, although they do not play a role at standard conditions in solution. The concentration of the solution during the spray process accelerates all condensation reactions and it has been even tested as an alternative approach for bulk synthesis.…”

Similarity and Competition between Biginelli and Hantzsch Reactions: an Opportunity for Modern Medicinal Chemistry

“…[53][54][55] The Biginelli reaction was ultimately exploited in material chemistry as direct, convergent and easy reaction for the development of functional materials such as polymers, dyes or adhesives. [56] Modern approaches to the Biginelli reaction, such as biocatalytic, [57] microwave-assisted, [58] high pressure assisted [59,60] and microdroplet accelerated reactions [61] have also been reported with excellent results. Due to the problems connected with the insolubility of urea and DHPM product in cold organic solvents, there are few examples of the Biginelli reaction in a continuous-flow.…”