Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders.

A strategy to industrialize microwave synthesis from the perspectives of process optimization, scale up and reactor design was devised for the synthesis of glycerol carbonate (GC). The strategy is based on the application of absorbed energy density (AED) and absorbed power density (APD) parameters. Here, the microwave synthesis was conducted using a constant-power heating mode. The mapping of microwave heating characteristics based on heating power, reaction temperature and AED was first performed for the microwave system. Then, the optimization of APD and AED was conducted and the intensive optimum conditions at 175 J/g AED and 1.9 W/g APD was used to scale up the microwave synthesis from 0.3 mol (27 g) to 3 mol (267 g). The resulting syntheses were highly reproducible and consistent. Based on APD and AED, the thermal and non-thermal microwave effects can be characterized and they are useful in the design of continuous-flow microwave reactor.

Strategy to scale up microwave synthesis with insight into the thermal and non-thermal effects from energy-based perspective

Microwave radiation is a proven technology to enhance the efficiency of organic synthesis. The selective absorption of radiation by polar compounds and conversion of electromagnetic energy into heat by dielectric losses forms the basis of the nonconventional microwave dielectric heating. This technology facilitates the acceleration of the reaction rate and enhancement in the product yields through uniform and selective heating thereby; it aids in the development of cleaner and greener synthetic routes. The initial part of the chapter is more comprehensive and discusses the theoretical background, microwave mechanisms, and role of microwaves in different organic reactions. The latter part of the chapter discusses briefly the types of microwave reactors, current challenges in microwave-assisted synthesis regarding energy efficiency, and scale-up of organic transformations.

Microwave catalysis in organic synthesis

Chromones is a family of oxygen heterocyclic compounds whose synthetic versatility and broad spectrum of bioactive properties has been widely reported over the past decade. The increasing number of publications related to the synthesis of this heterocyclic system highlights diverse synthetic approaches, using different starting materials, with novel and efficient synthetic details, applying alternative heating conditions, that provides a huge number of polyfunctionalized 4 H -chromen-4-one derivatives. The purpose of this chapter is to present a comprehensive survey of the methodologies developed for the synthesis of 2,3-unsubstituted, 2- and 3-substituted and 2,3-disubstituted 4 H -chromen-4-ones, focusing on the literature since 2012, in nearly 450 publications. 

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Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

In this work liquid phase one-step synthesis of acacetin from ethyl 3-(4-methoxyphenyl)-3-oxopropionate and phloroglucinol using PEG 1000 as solvent was examined. Heating of the reaction mixture was done with 915 MHz and 2.45 GHz microwaves at atmospheric pressure. The demethylation of the obtained acacetin using HBr at reflux led to the formation of apigenin. In view of a possible scale-up, the reaction conditions under 915 MHz microwaves were optimized to obtain high yields of acacetin. The energy required to convert phloroglucinol in acacetin was also estimated and used to calculate the total microwave power required for scaling up the process by a factor of 100. This method is an easier and cleaner synthesis for large scale preparation of flavones with good yields and purity.

Dominique Chantreux

Papers

Scale-up of one-step synthesis of acacetin and apigenin using 915 MHz microwaves