Sustainable Chemical Derivatization of Hydroxycinnamic Acids

Green solvents like ethyl acetate and acetone convert hydroxycinnamic acids into natural and unnatural derivatives such as amides, esters, and other valuable synthetic intermediates. Employing as protection-activation a system based on an alkyl chloroformate and N-methyl morpholine, ethyl acetate emerges as an excellent solvent for coupling O-carbonate-protected mixed anhydrides in acylation reactions of C-protected amino acids, amines, and catalyzed acylation of alcohols. This results in high yields of O-protected phenolic amides and esters. Acetone is preferred for acyl nucleophilic substitution reactions involving ionic species like free amino acids, sodium azide, and sodium hydroxide, all added in water. This approach releases the resultant O-protected acylation products. Free phenolic compounds are promptly obtained on demand through carbonate deprotection. This synthetic method offers a simplified procedure and employs low-cost reagents to prepare natural and unnatural hydroxycinnamic acid derivatives.