Ester

Structure and bonding

Esters derived from carboxylic acids and alcohols contain a carbonyl group C=O, which is a divalent group at C atom, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, carboxylic acid esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. The pK_a of the alpha-hydrogens on esters of carboxylic acids is around 25 (alpha-hydrogen is a hydrogen bound to the carbon adjacent to the carbonyl group (C=O) of carboxylate esters).

Many carboxylic acid esters have the potential for conformational isomerism, but they tend to adopt an S-cis (or Z) conformation rather than the S-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.

Physical properties and characterization

Esters derived from carboxylic acids and alcohols are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.

Characterization and analysis

Esters are generally identified by gas chromatography, taking advantage of their volatility. IR spectra for esters feature an intense sharp band in the range 1730–1750 cm⁻¹ assigned to ν_C=O. This peak changes depending on the functional groups attached to the carbonyl. For example, a benzene ring or double bond in conjunction with the carbonyl will bring the wavenumber down about 30 cm⁻¹.

Applications and occurrence

Esters are widespread in nature and are widely used in industry. In nature, fats are, in general, triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Several billion kilograms of polyesters are produced industrially annually, important products being polyethylene terephthalate, acrylate esters, and cellulose acetate.

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 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 flavor industry. Ester bonds are also found in many polymers.

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 dehydrating agent:

RCO₂H + R'OH ⇌ RCO₂R' + H₂O

The equilibrium constant for such reactions is about 5 for typical esters, e.g., ethyl acetate. 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 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.

Another method for the dehydration of mixtures of alcohols and carboxylic acids is the Mitsunobu reaction:

RCO₂H + R'OH + P(C₆H₅)₃ + R₂N₂ → RCO₂R' + OP(C₆H₅)₃ + R₂N₂H₂

Carboxylic acids can be esterified using diazomethane:

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:

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 chlorides and acid anhydrides to give esters:

RCOCl + R'OH → RCO₂R' + HCl

(RCO)₂O + R'OH → RCO₂R' + RCO₂H

The reactions are irreversible simplifying work-up. Since acyl chlorides and acid anhydrides also react with water, anhydrous conditions are preferred. The analogous acylations of amines to give amides are less sensitive because amines are stronger nucleophiles 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:

RCO₂H + (CH₃)₃OBF₄ → RCO₂CH₃ + (CH₃)₂O + HBF₄

Although rarely employed for esterifications, carboxylate salts (often generated in situ) react with electrophilic alkylating agents, such as alkyl halides, to give esters. Anion availability can inhibit this reaction, which correspondingly benefits from phase transfer catalysts or such highly polar aprotic solvents as 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:

RCO₂R' + CH₃OH → RCO₂CH₃ + R'OH

Like the hydrolysation, transesterification is catalysed by acids and bases. The reaction is widely used for degrading triglycerides, 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:

n (C₆H₄)(CO₂CH₃)₂ + 2n C₂H₄(OH)₂ → [(C₆H₄)(CO₂)₂(C₂H₄)]_n + 2n CH₃OH

A subset of transesterification is the alcoholysis of diketene. This reaction affords 2-ketoesters.

(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:

H₂C=CH₂ + ROH + CO → CH₃CH₂CO₂R

A preparation of methyl propionate is one illustrative example.

H₂C=CH₂ + 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:

CH₃OH + CO → HCO₂CH₃

Addition of carboxylic acids to alkenes and alkynes

In hydroesterification, alkenes and alkynes insert into the O−H bond of carboxylic acids. Vinyl acetate is produced industrially by the addition of acetic acid to acetylene in the presence of zinc acetate catalysts:

HC≡CH + CH₃CO₂H → CH₃CO₂CH=CH₂

Vinyl acetate can also be produced by palladium-catalyzed reaction of ethylene, acetic acid, and oxygen:

2 H₂C=CH₂ + 2 CH₃CO₂H + O₂ → 2 CH₃CO₂CH=CH₂ + 2 H₂O

Silicotungstic acid is used to manufacture ethyl acetate by the alkylation of acetic acid by ethylene:

H₂C=CH₂ + CH₃CO₂H → CH₃CO₂CH₂CH₃

From aldehydes

The Tishchenko reaction involves disproportionation of an aldehyde in the presence of an anhydrous base to give an ester. Catalysts are aluminium alkoxides or sodium alkoxides. Benzaldehyde reacts with sodium benzyloxide (generated from sodium and benzyl alcohol) to generate benzyl benzoate. The method is used in the production of ethyl acetate from acetaldehyde.

Other methods

• Favorskii rearrangement of α-haloketones in presence of base
• Baeyer–Villiger oxidation of ketones with peroxides
• Pinner reaction of nitriles with an alcohol
• Nucleophilic abstraction of a metal–acyl complex
• Hydrolysis of orthoesters in aqueous acid
• Cellulolysis via esterification
• Ozonolysis of alkenes using a work up in the presence of hydrochloric acid and various alcohols.
• Anodic oxidation of methyl ketones leading to methyl esters.
• Interesterification exchanges the fatty acid groups of different esters.

Reactions

Esters are less reactive than acid halides and anhydrides. As with more reactive acyl derivatives, they can react with ammonia and primary and secondary amines to give amides, although this type of reaction is not often used, since acid halides give better yields.

Transesterification

Esters can be converted to other esters in a process known as transesterification. Transesterification can be either acid- or base-catalyzed, and involves the reaction of an ester with an alcohol. Unfortunately, because the leaving group is also an alcohol, the forward and reverse reactions will often occur at similar rates. Using a large excess of the reactant alcohol or removing the leaving group alcohol (e.g. via distillation) will drive the forward reaction towards completion, in accordance with Le Chatelier's principle.

Hydrolysis and saponification

Acid-catalyzed hydrolysis of esters is also an equilibrium process – essentially the reverse of the Fischer esterification reaction. Because an alcohol (which acts as the leaving group) and water (which acts as the nucleophile) have similar pK_a values, the forward and reverse reactions compete with each other. As in transesterification, using a large excess of reactant (water) or removing one of the products (the alcohol) can promote the forward reaction.

Basic hydrolysis of esters, known as saponification, is not an equilibrium process; a full equivalent of base is consumed in the reaction, which produces one equivalent of alcohol and one equivalent of a carboxylate salt. The saponification of esters of fatty acids is an industrially important process, used in the production of soap.

Esterification is a reversible reaction. Esters undergo hydrolysis under acidic and basic conditions. Under acidic conditions, the reaction is the reverse reaction of the Fischer esterification. Under basic conditions, hydroxide acts as a nucleophile, while an alkoxide is the leaving group. This reaction, saponification, is the basis of soap making.

The alkoxide group may also be displaced by stronger nucleophiles such as ammonia or primary or secondary amines to give amides (ammonolysis reaction):

RCO₂R' + NH₂R″ → RCONHR″ + R'OH

This reaction is not usually reversible. Hydrazines and hydroxylamine can be used in place of amines. Esters can be converted to isocyanates through intermediate hydroxamic acids in the Lossen rearrangement.

Sources of carbon nucleophiles, e.g., Grignard reagents and organolithium compounds, add readily to the carbonyl.

Reduction

Compared to ketones and aldehydes, esters are relatively resistant to reduction. The introduction of catalytic hydrogenation in the early part of the 20th century was a breakthrough; esters of fatty acids are hydrogenated to fatty alcohols.

RCO₂R' + 2 H₂ → RCH₂OH + R'OH

A typical catalyst is copper chromite. Prior to the development of catalytic hydrogenation, esters were reduced on a large scale using the Bouveault–Blanc reduction. This method, which is largely obsolete, uses sodium in the presence of proton sources.

Especially for fine chemical syntheses, lithium aluminium hydride is used to reduce esters to two primary alcohols. The related reagent sodium borohydride is slow in this reaction. DIBAH reduces esters to aldehydes.

Direct reduction to give the corresponding ether is difficult as the intermediate hemiacetal tends to decompose to give an alcohol and an aldehyde (which is rapidly reduced to give a second alcohol). The reaction can be achieved using triethylsilane with a variety of Lewis acids.

Claisen condensation and related reactions

Esters can undergo a variety of reactions with carbon nucleophiles. They react with an excess of a Grignard reagent to give tertiary alcohols. Esters also react readily with enolates. In the Claisen condensation, an enolate of one ester (1) will attack the carbonyl group of another ester (2) to give tetrahedral intermediate 3. The intermediate collapses, forcing out an alkoxide (R'O⁻) and producing β-keto ester 4.

Crossed Claisen condensations, in which the enolate and nucleophile are different esters, are also possible. An intramolecular Claisen condensation is called a Dieckmann condensation or Dieckmann cyclization, since it can be used to form rings. Esters can also undergo condensations with ketone and aldehyde enolates to give β-dicarbonyl compounds. A specific example of this is the Baker–Venkataraman rearrangement, in which an aromatic ortho-acyloxy ketone undergoes an intramolecular nucleophilic acyl substitution and subsequent rearrangement to form an aromatic β-diketone. The Chan rearrangement is another example of a rearrangement resulting from an intramolecular nucleophilic acyl substitution reaction.

Other ester reactivities

Esters react with nucleophiles at the carbonyl carbon. The carbonyl is weakly electrophilic but is attacked by strong nucleophiles (amines, alkoxides, hydride sources, organolithium compounds, etc.). The C–H bonds adjacent to the carbonyl are weakly acidic but undergo deprotonation with strong bases. This process is the one that usually initiates condensation reactions. The carbonyl oxygen in esters is weakly basic, less so than the carbonyl oxygen in amides due to resonance donation of an electron pair from nitrogen in amides, but forms adducts.

As for aldehydes, the hydrogen atoms on the carbon adjacent ("α to") the carboxyl group in esters are sufficiently acidic to undergo deprotonation, which in turn leads to a variety of useful reactions. Deprotonation requires relatively strong bases, such as alkoxides. Deprotonation gives a nucleophilic enolate, which can further react, e.g., the Claisen condensation and its intramolecular equivalent, the Dieckmann condensation. This conversion is exploited in the malonic ester synthesis, wherein the diester of malonic acid reacts with an electrophile (e.g., alkyl halide), and is subsequently decarboxylated. Another variation is the Fráter–Seebach alkylation.

Other reactions

• Esters can be directly converted to nitriles.
• Methyl esters are often susceptible to decarboxylation in the Krapcho decarboxylation.
• Phenyl esters react to hydroxyarylketones in the Fries rearrangement.
• Specific esters are functionalized with an α-hydroxyl group in the Chan rearrangement.
• Esters with β-hydrogen atoms can be converted to alkenes in ester pyrolysis.
• Pairs of esters are coupled to give α-hydroxyketones in the acyloin condensation.

Protecting groups

As a class, esters serve as protecting groups for carboxylic acids. Protecting a carboxylic acid is useful in peptide synthesis, to prevent self-reactions of the bifunctional amino acids. Methyl and ethyl esters are commonly available for many amino acids; the t-butyl ester tends to be more expensive. However, t-butyl esters are particularly useful because, under strongly acidic conditions, the t-butyl esters undergo elimination to give the carboxylic acid and isobutylene, simplifying work-up.

List of ester odorants

Many esters have distinctive fruit-like odors, and many occur naturally in the essential oils of plants. This has also led to their common use in artificial flavorings and fragrances which aim to mimic those odors.