Methyl esters
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 372-381, 383-387,
728-731.
Stability
| H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
| Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
| Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
| Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
| Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
| Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
Protection
A convenient and efficient sonochemical method for methyl esterification of
carboxylic acids is catalyzed by polymer-supported triphenylphosphine in the
presence of 2,4,6-trichloro-1,3,5-triazine and Na2CO3.
Methyl esters of various carboxylic acids bearing reactive hydroxyl groups as
well as acid- or base-labile functionalities could be rapidly prepared within
short times in good to excellent yields in high purities without column
chromatography.
S. Jaita, W. Phakhodee, M. Pattarawarapan,
Synlett, 2015, 26, 2006-2008.
Sc(OTf)3 catalyses a direct transesterification of carboxylic esters
in boiling alcohols. Methyl, ethyl, isopropyl, and allyl esters were prepared
from various substrates in high yields. The application of microwave irradiation
led to significantly reduced reaction times.
N. Remme, K. Koschek, C. Schneider, Synlett, 2007,
491-493.
A copper-catalyzed O-methylation of carboxylic acids using dimethyl sulfoxide
(DMSO) as the methyl source exhibits a broad substrate scope and excellent
functional group tolerance. Mechanistic studies indicate that a methyl radical
is generated from dimethyl sulfoxide.
J. Jia, Q. Jiang, A. Zhao, B. Xu, Q. Liu, W.-P. Luo, C.-C. Guo,
Synthesis, 2016, 48, 421-428.
A highly effective synthesis of methyl esters from benzylic alcohols, aldehydes,
or acids via copper-catalyzed C-C cleavage from tert-butyl hydroperoxide
is easily accessible and practical and offers an alternative to the traditional
way.
Y. Zhu, H. Yan, L. Lu, D. Liu, G. Rong, J. Mao, J. Org. Chem., 2013,
78, 9898-9905.
Dimethylcarbonate is a nontoxic and green methylating reagent. A base-catalyzed
methyl transfer from dimethylcarbonate to carboxylic acids offers high
selectivity for esterification and mild reaction conditions, that enable
conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling
studies suggest a mechanism via direct methyl transfer from dimethylcarbonate to
the substrate.
Y. Ji, J. Sweeney, J. Zoglio, D. J. Gorin, J. Org. Chem., 2013,
78, 11606-11611.
A Cu-catalyzed nondecarboxylative methylation of carboxylic acids with
methylboronic acid proceeds in air as sole oxidant and offers a strategy for
replacing toxic, electrophilic alkylating reagents. An isotope-labeling study
supports an oxidative cross-coupling mechanism, in analogy to that proposed for
Chan-Lam arylation.
C. E. Jacobson, N. Martinez-Muņoz, D. J. Gorin, J. Org. Chem.,
2015,
80, 7305-7310.
Other Syntheses of Methyl Esters
A readily accessible catalyst system consisting of Pd/charcoal in combination
with bismuth(III) nitrate and tellurium metal enables an efficient aerobic
oxidative methyl esterification of primary alcohols, exhibits a broad substrate
scope, and is effective with both activated and unactivated alcohols bearing
diverse functional groups. The Bi and Te additives significantly increase the
reaction rate, selectivity, and overall product yields.
A. B. Powell, S. S. Stahl, Org. Lett., 2013,
15, 5072-5075.
Deprotection
N,N-diarylammonium pyrosulfate efficiently catalyzes the hydrolysis of
esters under organic solvent-free conditions. This reverse micelle-type method
is successfully applied to the hydrolysis of various esters without the
decomposition of base-sensitive moieties and without any loss of optical purity
for α-heterosubstituted carboxylic acids.
Y. Koshikari, A. Sakakura, K. Ishihara, Org. Lett., 2012,
14, 3194-3197.
Aluminum powder and iodine in anhydrous acetonitrile mediate a one-pot
deprotecting of alkyl carboxylates under nonhydrolytic conditions. Cleavage of
lactones affords the corresponding ω-iodoalkylcarboxylic acids. This method
enables the selective cleavage of alkyl carboxylic esters in the presence of
aryl esters.
D. Sang, H. Yue, Y. Fu, J. Tian, J. Org. Chem., 2021, 86,
4254-4261.
