Benzyl esters
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 372-381, 415-419,
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 of carboxylic acids
Triethylamine mediates esterification reactions between 2-benzyloxy-1-methylpyridinium
triflate and carboxylic acids. Alcohols, phenols, amides, and other sensitive
functionality are not affected; a dual role for triethylamine as a promoter and
a scavenger is postulated.
J. Tummatorn, P. A. Albiniak, G. B. Dudley, J. Org. Chem., 2007,
72, 8962-8964.
A simple 2,2'-biphenol-derived phosphoric acid catalyst promotes a
dehydrative esterification from an equimolar mixture of carboxylic acids and
primary or secondary alcohols in toluene at 100 °C without the necessity to
remove water. This reaction was also successfully conducted at the gram scale.
M. Hatano, C. Nishioka, A. Mimura, R. Kimura, Y. Okuda, T. Yamada, K. Sakata, Synlett, 2023,
34,
2508-2514.
A benzyne-mediated esterification of carboxylic acids and alcohols provides
products under mild conditions via a selective nucleophilic addition of
carboxylic acid to benzyne in the presence of alcohol followed by a
transesterification with alcohol. Benzyne can also be used to promote
lactonization and amidation reactions.
J. Zhao, J. Shi, Y. Li, Org. Lett., 2021, 23,
7274-7278.
A direct benzylation of carboxylic acids with toluene via palladium-catalyzed
C-H acyloxylation under 1 atm of oxygen demonstrates good functional group
tolerance and high yields. The method provides a facile, atom-economic, and
efficient synthesis of benzyl esters.
H. Liu, G. Shi, S. Pan, Y. Jiang, Y. Zhang, Org. Lett., 2013,
15, 4098-4101.
An esterification of primary benzylic C-H bonds with carboxylic acids using di-tert-butyl
peroxide as an oxidant is catalyzed by novel ionic iron(III) complexes
containing an imidazolinium cation. The reaction offers a broad generality and
tolerates sterically hindered starting materials.
B. Lu, F. Zhu, H.-M. Sun, Q. Shen, Org. Lett.,
2017, 19, 1132-1135.
Other Syntheses of Benzyl esters
A catalytic transesterification is promoted by a tetranuclear zinc cluster. The
mild reaction conditions enabled the reactions of various functionalized
substrates to proceed in very good yield. A large-scale reaction under
solvent-free conditions offers high environmental and economical advantages.
T. Iwasaki, Y. Maegawa, Y. Hayashi, T. Ohshima, K. Mashima, J. Org. Chem., 2008,
73, 5147-5150.
Copper(II) catalyzes a cross dehydrogenative coupling (CDC) reaction of
aldehydes with alkylbenzenes in the presence of TBHP to yield benzylic esters.
S. K. Rout, S. Guin, K. K. Ghara, A. Banerjee, B. K. Patel, Org. Lett., 2012,
14, 3982-3985.
Deprotection
In situ generation of molecular hydrogen by addition of triethylsilane to
palladium on charcoal results in rapid and efficient reduction of multiple bonds,
azides, imines, and nitro groups, as well as deprotection of benzyl and allyl
groups under mild, neutral conditions.
P. K. Mandal, J. S. McMurray, J. Org. Chem.,
2007,
72, 6599-6601.
In situ preparation of an active Pd/C catalyst from Pd(OAc)2 and
charcoal in methanol enables a simple, highly reproducible protocol for the
hydrogenation of alkenes and alkynes and for the hydrogenolysis of O-benzyl
ethers. Mild reaction conditions and low catalyst loadings, as well as the
absence of contamination of the product by palladium residues, make this a
sustainable, useful process.
F.-X. Felpin, E. Fouquet, Chem. Eur. J., 2010,
12440-12445.
Ammonia, pyridine and ammonium acetate were extremely effective
as inhibitors of Pd/C catalyzed benzyl ether hydrogenolysis. While olefin, Cbz,
benzyl ester and azide functionalities were hydrogenated smoothly, benzyl ethers
were not cleaved.
H. Sajiki, Tetrahedron Lett., 1995,
36, 3465-3468.
Benzyl esters of various acids can be chemoselectively cleaved on treatment with
nickel boride in methanol at ambient temperature to give the parent carboxylic
acids in high yields. Esters such as methyl, ethyl, tert-butyl, and
trityl esters as well as benzyl ethers, tert-butyl ethers, and N-benzylamides
remain unaffected under these conditions.
J. M. Khurana, R. Arora, Synthesis, 2009,
1127-1130.
