Esterification of Carboxylic Acids with Dimethyl Carbonate and DBU 137
In Summary
DMC is an efficient methylating agent of carboxylic acids in the presence of
DBU. The reaction pathway involves initial N-acylation of DBU to form a carbamate intermediate. This carbamate reacts with the carboxylate anion (0alkylation) to afford the methyl ester. DBU not only is the base that forms the carboxylate anion but is also the nucleophile catalyst of the process.
Questions
The addition of methanol decreases the rate of the esterification of carboxylic
acids with DMC-DBU. Without the added methanol methyl benzoate 2 is quantitatively obtained within 3 h, but with extra methanol added, methyl benzoate formation is still not complete after 24 h. Could you explain why?
Answer to the Question
Anion solvation by protic solvents like methanol takes place preferably through
hydrogen bonding. The carboxylate anion will be highly solvated by methanol and
hence its nucleophilicity will be reduced under these conditions, causing a decrease in the reaction rate.
Additional Comments
This prob1em is based on the work by Shieh W-C, Dell S, Repic O (2002) J. Org.
Chem. 67:2188-2191.
Subjects of Revision
Detection ofintermediates. Labeling experiments. Nucleophile catalysis.
In Summary
DMC is an efficient methylating agent of carboxylic acids in the presence of
DBU. The reaction pathway involves initial N-acylation of DBU to form a carbamate intermediate. This carbamate reacts with the carboxylate anion (0alkylation) to afford the methyl ester. DBU not only is the base that forms the carboxylate anion but is also the nucleophile catalyst of the process.
Questions
The addition of methanol decreases the rate of the esterification of carboxylic
acids with DMC-DBU. Without the added methanol methyl benzoate 2 is quantitatively obtained within 3 h, but with extra methanol added, methyl benzoate formation is still not complete after 24 h. Could you explain why?
Answer to the Question
Anion solvation by protic solvents like methanol takes place preferably through
hydrogen bonding. The carboxylate anion will be highly solvated by methanol and
hence its nucleophilicity will be reduced under these conditions, causing a decrease in the reaction rate.
Additional Comments
This prob1em is based on the work by Shieh W-C, Dell S, Repic O (2002) J. Org.
Chem. 67:2188-2191.
Subjects of Revision
Detection ofintermediates. Labeling experiments. Nucleophile catalysis.