Synthesis

Green chemistry has become a research hotspot in the field of chemistry in recent years due to its environmental friendliness. In the field of organic synthesis, water usually replaces organic solvents as a green solvent to participate in synthesis reactions. However, some substrates have little water solubility or are insoluble in water, leading to the low efficiency of organic synthesis reactions in aqueous media.

Cyclodextrin (CD) can interact with hydrophobic organic molecules and form host-guest inclusion complexes, which increase the solubility of guest molecules in water, thus allowing organic synthesis to occur effectively in the aqueous phase. The synthesis involving CD is not only environmentally friendly but also improves reaction efficiency to a certain extent. Due to its excellent properties, CD has been used in simple synthetic reactions such as oxidation and addition reactions, as described below.

Oxidation Reaction

Oxidation reaction is a key transformation in organic synthesis, which generally uses anhydrous and oxygen-free conditions and various special oxidants. However, the treatment process is cumbersome, and the ideal yield is rarely achieved. When CD is introduced into the oxidation reaction, the interaction between the host molecule and guest molecule will not only lead to an environmentally friendly reaction but will also minimize the by-products produced by over-oxidation. Besides, CD can also activate the reactant so that the oxidation reaction can proceed under mild conditions.

• Instance

2-Iodoxybenzoic acid (IBX) is an oxidant with relatively high selectivity for alcohol oxidation, but it has poor water solubility. β-CD inclusion complexes of epoxide 1 and aziridine 2 were synthesized in water medium, followed by IBX oxidation to give α-hydroxyketones 3 and α-aminoketones 4, respectively (Fig. 1). As a complexing host, β-CD not only activated epoxides or aziridines but also formed CD-IBX complexes. The formed CD-IBX complex enables IBX to be soluble in water, thereby mediating the oxidation reaction ^[1].

Fig. 1 The oxidation reaction of CD inclusion complexes of epoxide 1 or aziriding 2 with IBX. ^[1].

Addition Reaction

An addition reaction is a kind of organic synthesis where two or more molecules combine to form a larger one. The reactants in addition reactions are often poorly soluble in water which requires organic solvents. Moreover, addition reactions usually require high-temperature reflux and catalysis by strong alkalis or other metal salts. It also has disadvantages, such as long reaction time, low reaction yield, and many by-products. CD can transfer the reactants into the aqueous phase through inclusion complexation to avoid these problems.

• Instance

Narender et al. utilized the host-guest interaction between β-CD and phenacyl bromides to react in situ in water to form inclusion complexes and then added thioamide or thiourea to form thiazole compounds, with a yield of 92% (Fig. 2). The role of CD seems to be to activate and solubilize phenacyl bromide, thereby promoting the reaction and shortening the reaction time. This addition reaction did not produce any by-products or rearrangement products. Without β-CD participating in the reaction, the reaction yield was only 20% after 12 hours ^[2].

Fig. 2 The addition reaction of thiazoles and aminothiazoles from phenacyl bromides and thioamide/thiourea in the presence of β-CD. ^[1].

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