Abstract
Considering the remarkable relevance of acetylated derivatives of phenols, alcohols, and aryl and alkyl thiols in different areas of biology, as well as in synthetic organic chemistry, a sustainable solvent-free approach to perform acetylation reactions is proposed here. Acetylation reactions are classically performed using excess of acetic anhydride (Ac2O) in solvent-free conditions or by eventually working with stoichiometric amounts of Ac2O in organic solvents; both methods require the addition of basic or acid catalysts to promote the esterification. Therefore, they usually lead to the generation of high amounts of wastes, which sensibly raise the E-factor of the process. With the aim to develop a more sustainable system, a solvent-free, stoichiometric acetylation protocol is, thus, proposed. The naturally occurring phenol, thymol, can be converted to the corresponding—biologically active—ester with good yields, in the presence of 1% of VOSO4. Interestingly, the process can be efficiently adopted to synthesize other thymyl esters, as well as to perform acetylation of alcohols and aryl and alkyl thiols. Remarkably, a further improvement has been achieved replacing Ac2O with its greener alternative, isopropenyl acetate (IPA).
Highlights
In the framework of organic transformations, acetylation is a common and versatile reaction, extensively used both on laboratory and industrial scale
Thymol and carvacrol acetylation were accomplished with ca. 75% yield, which is in line with the results achieved with Ac2O; octyl, cyclohexyl, and benzyl acetate were obtained in lower amounts, and the reaction performed on aryl and alkyl thiols led to poor yields and lacked in selectivity (Supplementary Table S7)
Thymol has been adopted as model substrate, as its ester derivatives are known for their biological properties
Summary
Francesca Valentini 1, Pierluca Galloni 1,2, Diana Brancadoro 2, Valeria Conte 1 and Federica Sabuzi 1,2*. Considering the remarkable relevance of acetylated derivatives of phenols, alcohols, and aryl and alkyl thiols in different areas of biology, as well as in synthetic organic chemistry, a sustainable solvent-free approach to perform acetylation reactions is proposed here. Acetylation reactions are classically performed using excess of acetic anhydride (Ac2O) in solvent-free conditions or by eventually working with stoichiometric amounts of Ac2O in organic solvents; both methods require the addition of basic or acid catalysts to promote the esterification. They usually lead to the generation of high amounts of wastes, which sensibly raise the E-factor of the process.
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