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.

Dichloro-tin (IV) hexadeca-fluoro-phthalocyanine (F16PcSnCl2) thin film on porous silicon layers by ultrasonic spray pyrolysis, for possible application in optoelectronics devices

“…These applications leverage the optical, electrical, and morphological properties of phthalocyanines, which can be adjusted through suitable peripheral substitutions [8][9][10] Furthermore, many of these macrocyclic compounds have had a significant economic impact. For instance, the global annual consumption of phthalocyanine-based pigments is estimated to be between 70,000 to 80,000 metric tons, resulting in a billion-dollar market [11].…”

Exploration of the Conformational Scenario for α-, β-, and γ-Cyclodextrins in Dry and Wet Conditions, from Monomers to Crystal Structures: A Quantum-Mechanical Study

“…The broad applicability of the CD molecule is due to its very versatile properties: it can form 1:1, 2:1, and 2:2 type complexes (even if other ratios are also possible [43]), adapting itself to the size and properties of the guest molecule, by either complexing the guest dimers of small molecules or forming host dimers with large guest molecules [44]. Moreover, hydroxyl groups can be easily functionalized in order to further improve its complexation capabilities; as an example, the derivatization made by the methyl and hydroxypropyl groups improves cyclodextrin solubility [45]. Another relevant feature of CDs is that small molecules with symmetric acidic moieties, such as carbonic, succinic, and citric acid, can be used as cross-linkers, merging the cyclodextrins to one another, to form porous structures like nanosponges and nanogels [46,47].…”

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].…”