AUTHOR=Valentini Francesca , Galloni Pierluca , Brancadoro Diana , Conte Valeria , Sabuzi Federica 

TITLE=A Stoichiometric Solvent-Free Protocol for Acetylation Reactions

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.842190

DOI=10.3389/fchem.2022.842190

ISSN=2296-2646

ABSTRACT=Considering the remarkable relevance of acetylated derivatives of phenols, alcohols, 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 here proposed. Acetylation reactions are classically performed using excess of acetic anhydride (Ac2O) in solvent-free conditions, or 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, that 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, aryl and alkyl thiols. Remarkably, a further improvement has been achieved replacing Ac2O with its greener alternative, isopropenyl acetate (IPA).