Editing Ester (section)

== Preparation ==
Esterification is the general name for a [[chemical reaction]] in which two reactants (typically an alcohol and an acid) form an ester as the [[product (chemistry)|reaction product]]. Esters are common in organic chemistry and biological materials, and often have a pleasant characteristic, fruity odor. This leads to their extensive use in the [[fragrance]] and [[flavoring|flavor]] industry. Ester bonds are also found in many [[polymer]]s.

===Esterification of carboxylic acids with alcohols===
The classic synthesis is the [[Fischer esterification]], which involves treating a carboxylic acid with an alcohol in the presence of a [[Dehydration reaction|dehydrating]] agent:
:{{chem2|RCO2H + R'OH ⇌ RCO2R' + H2O}}
The equilibrium constant for such reactions is about 5 for typical esters, e.g., ethyl acetate.<ref>{{cite journal | last1=Williams | first1=Roger J. | last2=Gabriel | first2=Alton | last3=Andrews | first3=Roy C. | year=1928 | title=The Relation Between the Hydrolysis Equilibrium Constant of Esters and the Strengths of the Corresponding Acids | journal=Journal of the American Chemical Society | volume=50 | issue=5| pages=1267–1271 | doi=10.1021/ja01392a005| bibcode=1928JAChS..50.1267W }}</ref> The reaction is slow in the absence of a catalyst. [[Sulfuric acid]] is a typical catalyst for this reaction. Many other acids are also used such as [[Dowex|polymeric sulfonic acids]]. Since esterification is highly reversible, the yield of the ester can be improved using [[Le Chatelier's principle]]:
* Using the alcohol in large excess (i.e., as a solvent).
* Using a dehydrating agent: sulfuric acid not only catalyzes the reaction but sequesters water (a reaction product). Other drying agents such as [[molecular sieves]] are also effective.
* Removal of water by physical means such as [[distillation]] as a low-boiling [[azeotrope]] with [[toluene]], in conjunction with a [[Dean-Stark apparatus]].

Reagents are known that drive the dehydration of mixtures of alcohols and carboxylic acids. One example is the [[Steglich esterification]], which is a method of forming esters under mild conditions. The method is popular in [[peptide synthesis]], where the substrates are sensitive to harsh conditions like high heat. DCC ([[dicyclohexylcarbodiimide]]) is used to activate the carboxylic acid to further reaction. [[4-Dimethylaminopyridine]] (DMAP) is used as an acyl-transfer [[catalyst]].<ref>{{OrgSynth | author=B. Neises | author2=W. Steglich |name-list-style=amp | title=Esterification of Carboxylic Acids with Dicyclohexylcarbodiimide/4-Dimethylaminopyridine: ''tert''-Butyl ethyl fumarate | collvol=7 | collvolpages=93 | prep=cv7p0093}}</ref>
:[[File:Steglich-1.svg|300px]]

Another method for the dehydration of mixtures of alcohols and carboxylic acids is the [[Mitsunobu reaction]]:
:{{chem2|RCO2H + R'OH + P(C6H5)3 + R2N2 → RCO2R' + OP(C6H5)3 + R2N2H2}}

Carboxylic acids can be esterified using [[diazomethane]]:
:{{chem2|RCO2H + CH2N2 → RCO2CH3 + N2}}
Using this diazomethane, mixtures of carboxylic acids can be converted to their methyl esters in near quantitative yields, e.g., for analysis by [[gas chromatography]]. The method is useful in specialized organic synthetic operations but is considered too hazardous and expensive for large-scale applications.

===Esterification of carboxylic acids with epoxides===
Carboxylic acids are esterified by treatment with [[epoxides]], giving β-hydroxyesters:
:{{chem2|RCO2H + RCHCH2O → RCO2CH2CH(OH)R}}
This reaction is employed in the production of [[vinyl ester resin]] from [[acrylic acid]].

=== Alcoholysis of acyl chlorides and acid anhydrides ===
Alcohols react with [[acyl chloride]]s and [[acid anhydride]]s to give esters:
:{{chem2|RCOCl + R'OH → RCO2R' + HCl}}
:{{chem2|(RCO)2O + R'OH → RCO2R' + RCO2H}}

The reactions are irreversible simplifying [[work-up (chemistry)|work-up]]. Since acyl chlorides and acid anhydrides also react with water, anhydrous conditions are preferred. The analogous acylations of amines to give [[amide]]s are less sensitive because amines are stronger [[nucleophile]]s and react more rapidly than does water. This method is employed only for laboratory-scale procedures, as it is expensive.

===Alkylation of carboxylic acids and their salts===
[[Trimethyloxonium tetrafluoroborate]] can be used for [[esterification]] of carboxylic acids under conditions where acid-catalyzed reactions are infeasible:<ref>{{cite journal 
|first1=Douglas J.|last1=Raber|first2=Patrick |last2=Gariano, Jr|first3=Albert O. |last3=Brod|first4=Anne L. |last4=Gariano|first5=Wayne C.|last5=Guida|doi=10.15227/orgsyn.056.0059 |title=Esterification of Carboxylic Acids with Trialkyloxonium Salts: Ethyl and Methyl 4-Acetoxybenzoates |journal=Organic Syntheses |date=1977 |volume=56 |page=59}}</ref>
:{{chem2|RCO2H + (CH3)3OBF4 -> RCO2CH3 + (CH3)2O + HBF4}}
Although rarely employed for esterifications, carboxylate salts (often generated ''in situ'') react with [[electrophilic]] [[alkylating agent]]s, such as [[alkyl halide]]s, to give esters.<ref name=Ullmann/><ref>{{Cite journal|last1=Matsumoto|first1=Kouichi|last2=Shimazaki|first2=Hayato|last3=Miyamoto|first3=Yu|last4=Shimada|first4=Kazuaki|last5=Haga|first5=Fumi|last6=Yamada|first6=Yuki|last7=Miyazawa|first7=Hirotsugu|last8=Nishiwaki|first8=Keiji|last9=Kashimura|first9=Shigenori|date=2014|title=Simple and Convenient Synthesis of Esters from Carboxylic Acids and Alkyl Halides Using Tetrabutylammonium Fluoride|url=http://jlc.jst.go.jp/DN/JST.JSTAGE/jos/ess13199?lang=en&from=CrossRef&type=abstract|journal=Journal of Oleo Science|language=en|volume=63|issue=5|pages=539–544|doi=10.5650/jos.ess13199|pmid=24770480|issn=1345-8957|doi-access=free}}</ref> Anion availability can inhibit this reaction, which correspondingly benefits from [[phase transfer catalyst]]s or such highly polar [[aprotic solvent]]s as [[Dimethylformamide|DMF]]. An additional iodide salt may, via the [[Finkelstein reaction]], catalyze the reaction of a recalcitrant alkyl halide. Alternatively, salts of a coordinating metal, such as silver, may improve the reaction rate by easing halide elimination.

===Transesterification===
[[Transesterification]], which involves changing one ester into another one, is widely practiced:
:{{chem2|RCO2R' + CH3OH → RCO2CH3 + R'OH}}
Like the hydrolysation, transesterification is catalysed by acids and bases. The reaction is widely used for degrading [[triglyceride]]s, e.g. in the production of fatty acid esters and alcohols. [[Poly(ethylene terephthalate)]] is produced by the transesterification of [[dimethyl terephthalate]] and ethylene glycol:<ref name=Ullmann/> 
:{{chem2|''n'' (C6H4)(CO2CH3)2 + 2''n'' C2H4(OH)2 → [(C6H4)(CO2)2(C2H4)]_{''n''} + 2''n'' CH3OH}}

A subset of transesterification is the alcoholysis of [[diketene]]. This reaction affords 2-ketoesters.<ref name=Ullmann/>
:{{chem2|(CH2CO)2 + ROH → CH3C(O)CH2CO2R}}

===Carbonylation===
Alkenes undergo [[carboalkoxylation]] in the presence of [[metal carbonyl]] catalysts. Esters of [[propanoic acid]] are produced commercially by this method:
:{{chem2|H2C\dCH2 + ROH + CO → CH3CH2CO2R}}
A preparation of [[methyl propionate]] is one illustrative example. 
:{{chem2|H2C\dCH2 + CO + CH3OH → CH3CH2CO2CH3}}

The carbonylation of [[methanol]] yields [[methyl formate]], which is the main commercial source of [[formic acid]]. The reaction is catalyzed by [[sodium methoxide]]:
:{{chem2|CH3OH + CO → HCO2CH3}}

===Addition of carboxylic acids to alkenes and alkynes===
In [[hydroesterification]], alkenes and alkynes insert into the {{chem2|O\sH}} bond of carboxylic acids. [[Vinyl acetate]] is produced industrially by the addition of acetic acid to [[acetylene]] in the presence of [[zinc acetate]] catalysts:<ref>{{Ullmann|doi=10.1002/14356007.a27_419.pub2|title=Vinyl Esters |year=2019 |last1=Bienewald |first1=Frank |last2=Leibold |first2=Edgar |last3=Tužina |first3=Pavel |last4=Roscher |first4=Günter |pages=1–16 |isbn=9783527303854}}</ref>
:{{chem2|HC\tCH + CH3CO2H → CH3CO2CH\dCH2}}

[[Vinyl acetate]] can also be produced by [[palladium]]-catalyzed reaction of ethylene, [[acetic acid]], and [[oxygen]]:
:{{chem2|2 H2C\dCH2 + 2 CH3CO2H + O2 → 2 CH3CO2CH\dCH2 + 2 H2O}}

[[Silicotungstic acid]] is used to manufacture [[ethyl acetate]] by the [[alkylation]] of [[acetic acid]] by ethylene:
:{{chem2|H2C\dCH2 + CH3CO2H → CH3CO2CH2CH3}}

===From aldehydes===
The [[Tishchenko reaction]] involves [[disproportionation]] of an [[aldehyde]] in the presence of an anhydrous base to give an ester. [[Catalyst]]s are aluminium alkoxides or sodium alkoxides. [[Benzaldehyde]] reacts with sodium benzyloxide (generated from [[sodium]] and [[benzyl alcohol]]) to generate [[benzyl benzoate]].<ref name="kamm">{{OrgSynth | last1=Kamm | first1=O. | last2=Kamm | first2=W. F. | title=Benzyl benzoate | collvol=1 | collvolpages=104 | year=1922 | volume=2 | pages=5 | doi=10.15227/orgsyn.002.0005 | prep=cv1p0104}}</ref> The method is used in the production of [[ethyl acetate]] from [[acetaldehyde]].<ref name=Ullmann/>

=== Other methods ===
* [[Favorskii rearrangement]] of α-haloketones in presence of base
* [[Baeyer–Villiger oxidation]] of ketones with peroxides
* [[Pinner reaction]] of [[nitrile]]s with an alcohol
* [[Nucleophilic abstraction]] of a metal–acyl complex
*Hydrolysis of [[orthoesters]] in aqueous acid
*Cellulolysis via esterification<ref name="Synthesis of glucose esters from cellulose in ionic liquids">{{cite journal|last=Ignatyev|first=Igor|author2=Charlie Van Doorslaer |author3=Pascal G.N. Mertens |author4=Koen Binnemans |author5=Dirk. E. de Vos |journal=Holzforschung|year=2011|volume=66|issue=4|pages=417–425|title=Synthesis of glucose esters from cellulose in ionic liquids|doi=10.1515/hf.2011.161|s2cid=101737591|url=http://www.degruyter.com/view/j/hfsg.2012.66.issue-4/hf.2011.161/hf.2011.161.xml|url-access=subscription}}</ref>
* [[Ozonolysis]] of [[alkene]]s using a [[Work-up (chemistry)|work up]] in the presence of [[hydrochloric acid]] and various [[alcohols]].<ref>{{cite journal|last1=Neumeister|first1=Joachim|last2=Keul|first2=Helmut|last3=Pratap Saxena|first3=Mahendra|last4=Griesbaum|first4=Karl|title=Ozone Cleavage of Olefins with Formation of Ester Fragments|journal=Angewandte Chemie International Edition in English|date=1978|volume=17|issue=12|pages=939–940|doi=10.1002/anie.197809392}}</ref>
* [[Electrosynthesis#Anodic oxidations|Anodic oxidation]] of [[Methyl group|methyl]] [[ketones]] leading to methyl esters.<ref>{{cite journal|last1=Makhova|first1=Irina V.|last2=Elinson|first2=Michail N.|last3=Nikishin|first3=Gennady I.|title=Electrochemical oxidation of ketones in methanol in the presence of alkali metal bromides|journal=Tetrahedron|date=1991|volume=47|issue=4–5|pages=895–905|doi=10.1016/S0040-4020(01)87078-2}}</ref>
* [[Fat interesterification|Interesterification]] exchanges the fatty acid groups of different esters.