ester

A carboxylic acid ester. R and R' denote any alkyl or aryl group

Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol.^[1] Esters are usually derived from an inorganic acid or organic acid in which at least one -OH (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. That is, esters are formed by condensing an acid with an alcohol.

Esters are ubiquitous. Most naturally occurring fats and oils are the fatty acid esters of glycerol. Esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Phosphoesters form the backbone of DNA molecules. Nitrate esters, such as nitroglycerin, are known for their explosive properties, while polyesters are important plastics, with monomers linked by ester moieties.

Nomenclature

Etymology

The word 'ester' was coined in 1848 by German chemist Leopold Gmelin.^[2]], probably as a contraction of the german Essigäther - acetic ether.

IUPAC nomenclature of Esters

Ester names are derived from the parent alcohol and the parent acid, where the latter may be an organic or an inorganic acid. Esters derived from the simplest carboxylic acids are commonly named according to the more traditional, so-called "trivial names" e.g. as formate, acetate, propionate, and butyrate, as opposed to the IUPAC nomenclature methanoate, ethanoate, propanoate and butanoate. Esters derived from more complex carboxylic acids are, on the other hand, more frequently named using the systematic IUPAC name, based on the name for the acid followed by the suffix -oate. For example the ester hexyl octanoate, also known under the trivial name hexyl caprylate, has the formula CH₃(CH₂)₆CO₂(CH₂)₅CH₃.

The chemical formulas of organic esters are typically written in the format of RCO₂R', where R and R' are the hydrocarbon parts of the carboxylic acid and alcohol, respectively. For example butyl acetate, derived from butanol and acetic acid would be written CH₃CO₂C₄H₉. Alternative presentations are common including BuOAc and CH₃COOC₄H₉.

Cyclic esters are called lactones, regardless of whether they are derived from an organic or an inorganic acid. One example of a (organic) lactone is gamma-valerolactone.

Orthoesters

An uncommon class of organic esters are the orthoesters, which have the formula RC(OR')₃. Triethylorthoformate (HC(OC₂H₅)₃) is derived, in terms of its name (but not its synthesis) from orthoformic acid (HC(OH)₃) and ethanol.

"Inorganic esters"

A phosphoric acid ester

Ester is a general term for the product derived from the condensation of an acid and an alcohol. Thus, the nomenclature extends to inorganic oxo acids, e.g. phosphoric acid, sulfuric acid, nitric acid and boric acid. For example, triphenyl phosphate is the ester derived from phosphoric acid and phenol. Organic carbonates, such as ethylene carbonate, are derived from carbonic acid and ethylene glycol.

Structure and bonding

Esters contain a carbonyl center, which gives rise to 120°C-C-O and O-C-O angles. Unlike amides, 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.^[3] The pKa of the alpha-hydrogens on esters is around 25.^[4]

Physical properties and characterization

Esters 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.^[3]

Characterization and analysis

Esters are usually 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 conjugation 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.^[5] Esters are responsible for the aroma of many fruits, including apples, pears, bananas, pineapples, and strawberries.^[6] Several billion kilograms of polyesters are produced industrially annually, important products being polyethylene terephthalate, acrylate esters, and cellulose acetate.^[7]

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 characteristic pleasant, 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

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.^[8] but 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 azeotropes 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. DMAP (4-dimethylaminopyridine) is used as an acyl-transfer catalyst.^[9]

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 expensive for large scale applications.

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 carboxylate salts

Although not widely employed for esterifications, salts of carboxylate anions can be alkylating agent with alkyl halides to give esters. In the case that an alkyl chloride is used, an iodide salt can catalyze the reaction (Finkelstein reaction). The carboxylate salt is often generated in situ. In difficult cases, the silver carboxylate may be used, since the silver ion coordinates to the halide aiding its departure and improving the reaction rate. This reaction can suffer from anion availability problems and, therefore, can benefit from the addition of phase transfer catalysts or highly polar aprotic solvents such as DMF.

Transesterification

Transesterification, which involves changing one ester into another one, is widely practiced:

RCO₂R' + CH₃OH → RCO₂CH₃ + R'OH

Like the hydrolysction, 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(ethyleneterephthalate) is produced by the transesterification of dimethyl terephthalate and ethylene glycol:^[7]

(C₆H₄)(CO₂CH₃)₂ + 2 C₂H₄(OH)₂ → 1/n {(C₆H₄)(CO₂)₂(C₂H₄)}_n + 2 CH₃OH

Carbonylation

Alkenes undergo "hydroesterification" in the presence of metal carbonyl catalysts. Esters of propionic acid are produced commercially by this method:

C₂H₄ + ROH + CO → C₂H₅CO₂R

The carbonylation of methanol yields methyl formate, which the main commercial source of formic acid. The reaction is catalyzed by sodium methoxide:

CH₃OH + CO → CH₃O₂CH

Addition of carboxylic acids to alkenes

In the presence of palladium-based catalysts, ethylene, acetic acid, and oxygen react to give vinyl acetate:

C₂H₄ + CH₃CO₂H + 1/2 O₂ → C₂H₃O₂CCH₃ + H₂O

Direct routes to this same ester are not possible because vinyl alcohol is unstable.

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.

Reactions

Esters react with nucleophiles at the carbonyl carbonyl carbon. The carbonyl is weakly electrophilic but is attacked by strong nucleophilies (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 is weakly basic (less so than in amides) but forms adducts.

Addition of nucleophiles at carbonyl

Esterification is a reversible reaction. Esters undergo hydrolysis under acid 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:

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.^[10]

Claisen condensation and related reactions

As for ketones and 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.

Other reactions

• 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.

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 isobutene, simplifying work-up.

List of ester odorants

Many esters have distinctive fruit-like odors, which has led to their commonplace use in artificial flavorings and fragrances.

Ester Name	Formula	Odor or occurrence
Allyl hexanoate		pineapple
Benzyl acetate		pear, strawberry, jasmine
Bornyl acetate		pine
Butyl butyrate		pineapple
Ethyl acetate		nail polish remover, model paint, model airplane glue
Ethyl butyrate		banana, pineapple, strawberry
Ethyl hexanoate		pineapple, waxy-green banana
Ethyl cinnamate		cinnamon
Ethyl formate		lemon, rum, strawberry
Ethyl heptanoate		apricot, cherry, grape, raspberry
Ethyl isovalerate		apple
Ethyl lactate		butter, cream
Ethyl nonanoate		grape
Ethyl pentanoate		apple
Geranyl acetate		geranium
Geranyl butyrate		cherry
Geranyl pentanoate		apple
Isobutyl acetate		cherry, raspberry, strawberry
Isobutyl formate		raspberry
Isoamyl acetate		pear, banana (flavoring in Pear drops)
Isopropyl acetate		fruity
Linalyl acetate		lavender, sage
Linalyl butyrate		peach
Linalyl formate		apple, peach
Methyl acetate		glue
Methyl anthranilate		grape, jasmine
Methyl benzoate		fruity, ylang ylang, feijoa
Methyl butyrate (methyl butanoate)		pineapple, apple, strawberry
Methyl cinnamate		strawberry
Methyl pentanoate (methyl valerate)		flowery
Methyl phenylacetate		honey
Methyl salicylate (oil of wintergreen)		Modern root beer, wintergreen, Germolene and Ralgex ointments (UK)
Nonyl caprylate		orange
Octyl acetate		fruity-orange
Octyl butyrate		parsnip
Amyl acetate (pentyl acetate)		apple, banana
Pentyl butyrate (amyl butyrate)		apricot, pear, pineapple
Pentyl hexanoate (amyl caproate)		apple, pineapple
Pentyl pentanoate (amyl valerate)		apple
Propyl acetate		pear
Propyl hexanoate		blackberry, pineapple, cheese, wine
Propyl isobutyrate		rum
Terpenyl butyrate		cherry

See also

• Cyanate ester
• Oligoester
• Polyolester
• Transesterification
• Transamidification

References

External links

• An introduction to esters
• Molecule of the month: Ethyl acetate and other esters
• An example of esters commercial application