Acetic acid esters
Ac-OR, Acetic acid esters, Acetate esters, Acetates
T. W. Green, P. G. M. Wuts, Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 150-160, 712-715.
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
4-(N,N-Dimethylamino)pyridine hydrochloride (DMAP·HCl) was used as a
recyclable catalyst for the acylation of inert alcohols and phenols under
base-free conditions. The catalyst can be reused more than eight times without
loss in activity and works with various acylating reagents.
Z. Liu, Y. Liu, Q. Wang, Org. Lett., 2014,
16, 236-239.
Inexpensive phosphoric acid
(H3PO4) catalyzes a safe and simple acylation of alcohols with acid anhydrides.
In situ-generated diacylated mixed anhydrides are proposed as the active
species - acting as efficient
catalytic acyl transfer reagents. A
23 g scale synthesis of an ester was demonstrated.
H. Hayashi, S. Yasukochi, T. Sakamoto, M. Hatano, K. Ishihara, J. Org. Chem., 2021, 86,
5197-5212.
Bi(OTf)3 catalyzes mild acylations of alcohols with acid
anhydrides. Sterically demanding or tertiary alcohols could be acylated smoothly.
Less reactive acylation reagents such as benzoic and pivalic anhydride are also
activated. Methanolysis of the unreacted anhydrides into easily separable methyl
ester realized quite easy separations of the desired pivaloylated or benzoylated
products.
A. Orita, C. Tanahashi, A. Kakuda, J. Otera, J. Org. Chem., 2001,
66, 8926-8934.
Vanadyl triflate efficiently catalyzes a nucleophilic acyl substitution of
anhydrides with a myriad array of alcohols, amines, and thiols in high yields
and high chemoselectivity. By using mixed-anhydride technique, oleate and
peptide syntheses can be achieved.
C.-T. Chen, J.-H. Kuo, C.-H. Li, N. B. Barhate, S.-W. Hon, T.-W. Li, S.-D. Chao,
C.-C. Liu, Y.-C. Li, I.-H. Chang, J.-S. Lin, C.-J. Liu, Y.-C. Chou, Org. Lett., 2001, 3,
3729-3732.
Phosphomolybdic acid (PMA) is a simple and efficient catalyst for the
acetylation of structurally diverse alcohols, phenols, and amines. Acetylation
reactions with acetic anhydride proceed in excellent yield in the presence of a
catalytic amount of PMA at ambient temperature within a relatively short
reaction time under solvent-free conditions.
S. T. Kadam, S. S. Kim, Synthesis, 2008,
267-268.
Acylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, and it was found that Cu(OTf)2 was very efficient in catalyzing the reaction under mild conditions in CH2Cl2.
K. L. Chandra, P. Saravan, R. K. Singh, V. K. Singh, Tetrahedron, 2002, 58, 1369-1374.
Copper(II) tetrafluoroborate efficiently catalyzes acetylation of structurally
diverse phenols, alcohols, thiols, and amines with stoichiometric amounts of Ac2O
under solvent-free conditions at room temperature. Acid-sensitive alcohols are
smoothly acetylated without competitive side reactions.
A. K. Chakraborti, R. Gulhane, Shivani, Synthesis, 2004,
111-115.
Various alcohols, thiols, phenols, and amines can be acetylated using acetic
anhydride in the presence of catalytic quantity of silver triflate. The method
proceeds under mild conditions, does not involve cumbersome workup, and the
resulting products are obtained in high yields within a reasonable time.
R. Das, D. Chakraborty, Synthesis, 2011,
1621-1625.
A macroporous polymeric acid catalyst enables a direct esterification of
carboxylic acids and alcohols at 50 to 80°C without removal of water to give the
corresponding esters with high yield. Flow esterification for the synthesis of
biodiesel fuel was also achieved by using a column-packed macroporous acid
catalyst under mild conditions.
M. Minakawa, H. Baek, Y. M. A. Yamada, J. W. Han, Y. Uozumi, Org. Lett., 2013,
15, 5798-5801.
Primary and secondary alcohols react with vinyl or isopropenyl acetate at
room temperature in the presence of Y5(OiPr)13O as
catalyst to give the corresponding esters. In selected cases, the yttrium
catalyst promotes a selective O-acylation of amino alcohols without the
formation of the amide.
M.-H. Lin, T. V. RajanBabu,
Org. Lett., 2000, 2, 997-1000.
Benzylidene 1,1-diacetate is a sustainable and efficient acyl donor for
enzymatic acylation of chiral and nonchiral alcohols. Especially, unsaturated
acetates can be converted without E/Z isomerization. The acyl
donor can be recreated and reused. A dynamic kinetic resolution (DKR) protocol
results in chiral acetates in high yields and very high enantiomeric excesses.
D. Koszelewski, A. Brodzka, A. Madej, D. Trzepizur, R. Ostaszewski, J. Org. Chem., 2021, 86,
6331-6342.
An efficient Na2CO3-catalyzed O-acylation of
phenols with alkenyl carboxylates as acyl reagents in MeCN provides aryl
carboxylates in very good yields.
X.-Y. Zhou, X. Chen, Synlett, 2018, 29,
2321-2325.
Molecular iodine catalyzes acetalation and acetylation of sugars with stoichiometric amounts of enol acetates under solvent-free
conditions to give orthogonally
protected sugar derivatives in short time and good yields. At lower
temperature, it is possible to obtain the acetonide acetate as a single product
whereas peracetate is the major product at higher temperature.
D. Mukherjee, B. A. Shah, P. Gupta, S. C. Taneja, J. Org. Chem., 2007,
72, 8965-8969.
Other Syntheses of Acetic Acid Esters
A counterattack protocol for differential acetylative cleavage of
phenylmethyl ether allows the reuse of the phenylmethyl moiety as
benzyl bromide, thus providing advantages in terms of
waste minimization and atom economy. The applicability of this
methodology has been extended for solid phase organic reactions with the
feasibility of reuse of the solid support.
A. K. Chakraborti, S. V. Chankeshwara, J. Org. Chem., 2009,
74, 1367-1370.
The use of 0.2 eq. of TiCl4 and 1.2 eq. of Ac2O
enables a mild direct conversion of THP ethers to acetates.
S. Chandrasekhar, T. Ramachandar, M. V. Reddy, M. Takhi, J. Org. Chem., 2000,
65, 4729-4731.
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.
Acetyl-, benzoyl- and pivoyl-protected alcohols and phenols undergo smooth
deacylation in a two-phase system of powdered NaOH and Bu4NHSO4
in THF or CH2Cl2.
R. D. Crouch, J. S. Burger, K. A. Zietek, A. B. Cadwallader, J. E. Bedison, M.
M. Smielewska, Synlett,
2003, 991-992.
An unprecedented hydroalumination of C=O bonds catalyzed by zirconocene
dichloride enables a site-selective deprotection of peracetylated functional
substrates. A mixed metal hydride, with 1:1 zirconium/aluminum stoichiometry, is
the reductive species.
T. Courant, M. Gavel, R. M. Q. Renard, V. Gandon, A. Y. P. Joosten, T.
Lecourt, J. Org. Chem., 2021, 86,
9280-9288.
A combination of Cp2ZrCl2 and DIBAL-H promotes a
regioselective cleavage of primary acetates on a broad scope of substrates,
ranging from carbohydrates to terpene derivatives, with a high tolerance toward
protecting groups and numerous functionalities found in natural products and
bioactive compounds.
M. Gavel, T. Courant, A. Y. P. Joosten, T. Lecourt,
Org. Lett., 2019, 21, 1948-1952.
