Chemical activation by mechanochemical mixing, microwave and ultrasonic irradiation

The diverse nature of the world of chemical synthesis requires various greener pathways in our quest towards attaining sustainability. The emerging area of green chemistry envisages minimum hazard as the performance criterion when designing new chemical processes. Cleaner processes are being developed as we continue to explore alternatives to conventional chemical syntheses and transformations. One of the thrust areas for achieving this target is to explore alternative efficient reaction conditions and eco-friendly reaction media to accomplish the desired chemical transformations with minimized by-products or waste and without the use of conventional volatile organic solvents, wherever possible. Consequently, several newer strategies have appeared, such as reactions under solvent-free (dry media) conditions,¹ mechanochemical mixing (grinding),^2,3 use of solid-supported reagents and the alternate heating and activation methods that utilize microwave⁴ (MW) and ultrasonic irradiation⁵ for rapid syntheses. These techniques overcome some of the problems associated with excessive or wasteful heating. Ball-mill processing is a solid-state size reduction process that can be easily scaled up and has been used in the paint industry, material science, the pharmaceutical industry, and also for environmental remediation. Mechanochemical solvent-free processing of organic molecules that prevents the usage of toxic metallic species and solvents is gaining popularity.^2,3 While ultrasonic irradiation enhances the chemical reaction and mass transfer via the process of acoustic cavitation,⁵ MW irradiation provides the ‘volumetric core’ and selective heating of polar entities.⁶ The selective absorption of microwaves by polar molecules and intermediates in a multiphase system could also substitute as a phase transfer catalyst without using any phase transfer reagent, thereby providing the observed acceleration, as has been noticed for ultrasonic irradiation.⁷ Experimental observations in several reaction systems have been consistent with the mechanistic postulation wherein the polar transition state of the reaction is favored by MW irradiation with respect to the dielectric polarization nature of MW energy transfer.^6,8

The review in this issue of Green Chemistry (A. Bruckmann, A. Krebs and C. Bolm, Green Chem., 2008, DOI: 10.1039/b812536h) provides an overview of organocatalytic reactions using non-traditional methods. Mechanochemical organocatalytic strategy has demonstrated good stereoselectivity in asymmetric aldol reactions, Baylis–Hillman reactions, and the protection of the heterocyclic amino groups of nucleosides. On the same organocatalytic theme, MW-assisted enantioselective proline-catalyzed α-aminomethylation of ketones has successfully reduced the reaction time and catalyst loading. Several reactions, the Michael addition, Baylis–Hillman and Diels-Alder, have been some of the beneficiaries of exposure to MW and ultrasonic irradiation in terms of shortening the reaction times and reducing the amount of reagents and solvents that are often used in excess.

Eco-friendly advantages of the synthetic alternatives based on unconventional activation via MW or ultrasound irradiation or the use of a mechanochemical approach for ‘neat’ reactions in the absence of any solvent are increasingly becoming apparent and may be adopted by the pharmaceutical industry to reduce or eliminate volatile organic solvents, thus preventing pollution ‘at source’. Synthetic processes using MW/ultrasonic irradiation to shorten the reaction time and eliminate or minimize side product formation are already finding acceptance in the pharmaceutical industry⁹ (combinatorial chemistry) and polymer syntheses, and may pave the way towards a greener and more sustainable approach to chemical syntheses.¹⁰ Newer developments on these themes, especially involving benign reaction media such as water¹¹ and polyethylene glycol (PEG),¹² in conjunction with MW and ultrasonic irradiation and/or ball-milling under solvent-free conditions, may help realize sustainable pathways for chemical synthesis and transformations, including generation of nanomaterials.¹³

References

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