Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

Abstract

Many scientists are working hard to find green alternatives to classical synthetic methods. Today, state-of-the-art ultrasonic and grinding techniques already drive the production of organic compounds on an industrial scale. The physicochemical and chemical behavior of cyclodextrins often differs from the typical properties of classic organic compounds and carbohydrates. The usually poor solubility and complexing properties of cyclodextrins can require special techniques. By eliminating or reducing the amount of solvent needed, green alternatives can reform classical synthetic methods, making them attractive for environmentally friendly production and the circular economy. The lack of energy-intensive synthetic and purification steps could transform currently inefficient processes into feasible methods. Mechanochemical reaction mechanisms are generally different from normal solution-chemistry mechanisms. The absence of a solvent and the presence of very high local temperatures for microseconds facilitate the synthesis of cyclodextrin derivatives that are impossible or difficult to produce under classical solution-chemistry conditions. Although mechanochemistry does not provide a general solution to all problems, several good examples show that this new technology can open up efficient synthetic pathways.

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

“…Besides traditional synthetic methods, alternative techniques, such as ultrasound and microwave irradiation [21], as well as mechanosynthesis [22,23] for the functionalizations, such as tosylation or azidation of CDs have been also described [24,25].…”

Characterization, Preparation, and Promotion of Plant Growth of 1,3-Diphenylurea/β-Cyclodextrin Derivatives Inclusion Complexes

“…Inclusion complexes are prepared by grinding mixtures, a chemical reaction in mechanochemistry, with the application of mechanical forces to induce drug–drug interactions, leading to the inclusion of the guest drug in the CD cavity . The advantage of this method is that inclusion complexes can be formed without using organic solvents and are therefore unaffected by oxidation, reduction, or hydrolysis .…”

“…20 Inclusion complexes are prepared by grinding mixtures, a chemical reaction in mechanochemistry, with the application of mechanical forces to induce drug−drug interactions, leading to the inclusion of the guest drug in the CD cavity. 21 The advantage of this method is that inclusion complexes can be formed without using organic solvents and are therefore unaffected by oxidation, reduction, or hydrolysis. 22 Additionally, the three-dimensional mixed grinding method uses two rotational axes, allowing the entire inner surface of the spherical container to be utilized, which overcomes the disadvantages of two-dimensional mixed grinding methods, such as the heat produced during grinding and unevenness in mixing.…”