Mechanisms of Lactone Hydrolysis in Neutral and Alkaline Conditions

• Published in: Journal of organic chemistry Vol. 78; no. 14; pp. 6868 - 6879
• Main Authors: Gómez-Bombarelli, Rafael, Calle, Emilio, Casado, Julio
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19-07-2013
• Subjects: Alkalies - chemistry; Carboxylic Acids - chemistry; Catalysis; Esters - chemistry; Hydrolysis; Lactones - chemistry; Molecular Structure; Water - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo400258w

The neutral and base-catalyzed hydrolysis of nine carboxylic acid esters was studied using a hybrid supermolecule-PCM approach including six explicit water molecules. The molecules studied included two linear esters, four β-lactones, two γ-lactones, and one δ-lactone: ethyl acetate and methyl formate, β-propiolactone, β-butyrolactone, β-isovalerolactone, diketene (4-methyleneoxetan-2-one), γ-butyrolactone, 2(5H)-furanone, and δ-valerolactone. DFT and ab initio methods were used to analyze the features of the various possible hydrolysis mechanisms. For all compounds, reasonable to very good qualitative and quantitative agreement with experimental work was found, and evidence is provided to support long-standing hypotheses regarding the role of solvent molecule as a base catalyst. In addition, novel evidence is presented for the existence of an elimination–addition mechanism in the basic hydrolysis of diketene. A parallel work addresses the acid-catalyzed hydrolysis of lactones.