Microwave (MW), Ultrasound (US) and Combined Synergic MW-US Strategies for Rapid Functionalization of Pharmaceutical Use Phenols.

Anna Pawełczyk,Dorota Olender,Lucjusz Zaprutko,Katarzyna Sowa-Kasprzak

doi:10.3390/molecules23092360

Anna Pawełczyk, Dorota Olender + Show 2 more

Open Access

https://doi.org/10.3390/molecules23092360

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Abstract

Increasingly stringent regulations aimed at protection of the natural environment have stimulated the search for new synthetic methodologies in organic and medicinal chemistry having no or minimum harmful effect. An interesting approach is the use of alternative activation factors, microwaves (MW) or ultrasounds (US) and also their cross-combination, which has been tested in the fast and efficient creation of new structures. At present, an easy and green hybrid strategy (“Lego” chemistry) is generally recommended for the design of new substances from different chemistry building blocks. Often, selected biologically active components with specific chemical reactivities are integrated by a suitably designed homo- or heterodifunctional linker that modifies the functionality of the starting structure, allowing easy covalent linkage to another molecule. In this study, a fast introduction of heterodifunctional halogenoacidic linker to selected mono-, di- and triphenolic active substances, allowing their functionalization, was investigated. Nucleophilic substitution reaction was chosen to produce final ethers with the reactive carboxylic group from phenols. The functionalization was performed using various green factors initiating and supporting the chemical reactions (MW, US, MW-US). The benefits of the three green supporting methods and different conditions of reactions were analyzed and compared with the results of the reaction performed by conventional methods.

Highlights

The concept of green chemistry, referring to processes not harmful to the natural environment, was first used in a scientific publication in 1990 [1,2], and in 1998, Anastas and Warner [3] systematized and published 12 principles of green chemistry. These principles describe the methods of implementation of green ideas
They contain guidelines for the interdisciplinary pursuit of economical and prudent management of chemical and energy raw materials, using non-classical synthesis methods based on alternative reaction media such as water, supercritical fluids or ionic liquids
The reactions assisted with ultrasound, microwaves and above all their combination are characterized by a unique and specific synergy of action

Summary

Introduction

The concept of green chemistry, referring to processes not harmful to the natural environment, was first used in a scientific publication in 1990 [1,2], and in 1998, Anastas and Warner [3] systematized and published 12 principles of green chemistry These principles describe the methods of implementation of green ideas (prevent waste, atom economy, design for energy efficiency, chemical engineering, less hazardous synthesis, design of safer chemicals, design for degradation, safer solvents and auxiliaries, renewable feedstock, catalysis, reduce derivatives, pollution and accident prevention). They contain guidelines for the interdisciplinary pursuit of economical and prudent management of chemical and energy raw materials, using non-classical synthesis methods based on alternative reaction media such as water, supercritical fluids or ionic liquids.

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