Level 2 - Case 20
Esterification of Carboxylic Acids with
Dimethyl Carbonate and DBU
Key point: Nucleophile catalysis. lsotope labe/ing
o
+ H 3 C, 0
~
0
,CH 3
Ba se
DMC
Esterification of Carboxylic Acids with Dimethyl
Carbonate and DBU
Dimethyl carbonate (DMC) bas attracted considerable attention in the last years as
a nontoxic alternative to the traditional methylating agents methyl iodide or dimethyl sulfate. Although this reagent efficiently methylates carboxylic acids, phenols, anilines and activated methylenes, generally its use requires high temperatures and very frequently high pressures (Scheme 20.1).
o
RC02H
11
- - - - H3c . . . . o . . . . . . . . . . . . . . o . . . . cH3
ArOH
DMC
~ 2 CN
ArCH(CH 3 )CN
Scheme 20.1
Among the diverse mechanistic studies directed to prevent the use of high temperatures dming the process, the esterification of benzoic acid 1 with DMC, at
90°C, in the presence of a variety of amine bases (l equiv) was investigated
(Scheme 20.2). Although different types of bases were studied, (e.g. N-methylmorpholine (NMM), tributylamine, 4-dimethylaminopyridine (DMAP), ammonium hydroxide) only 1,8-diazabicyclo[5 .4.0]undec-7-ene (DBU) yielded methyl
benzoate 2 in quantitative yield. With the rest of the amines tested, the ester 2 was
not obtained even after prolonged reaction times.
Esterification of Carboxylic Acids with
Dimethyl Carbonate and DBU
Key point: Nucleophile catalysis. lsotope labe/ing
o
+ H 3 C, 0
~
0
,CH 3
Ba se
DMC
Esterification of Carboxylic Acids with Dimethyl
Carbonate and DBU
Dimethyl carbonate (DMC) bas attracted considerable attention in the last years as
a nontoxic alternative to the traditional methylating agents methyl iodide or dimethyl sulfate. Although this reagent efficiently methylates carboxylic acids, phenols, anilines and activated methylenes, generally its use requires high temperatures and very frequently high pressures (Scheme 20.1).
o
RC02H
11
- - - - H3c . . . . o . . . . . . . . . . . . . . o . . . . cH3
ArOH
DMC
~ 2 CN
ArCH(CH 3 )CN
Scheme 20.1
Among the diverse mechanistic studies directed to prevent the use of high temperatures dming the process, the esterification of benzoic acid 1 with DMC, at
90°C, in the presence of a variety of amine bases (l equiv) was investigated
(Scheme 20.2). Although different types of bases were studied, (e.g. N-methylmorpholine (NMM), tributylamine, 4-dimethylaminopyridine (DMAP), ammonium hydroxide) only 1,8-diazabicyclo[5 .4.0]undec-7-ene (DBU) yielded methyl
benzoate 2 in quantitative yield. With the rest of the amines tested, the ester 2 was
not obtained even after prolonged reaction times.