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Goals
After completing this section, you should be able to
- Discuss the wide occurrence of esters in nature and their important commercial uses, giving an example of an ester linkage in nature and an example of a commercially important ester.
- Write an equation to describe the hydrolysis of an ester under acidic or basic conditions.
- identify the products formed from the hydrolysis of a given ester.
- identify reagents that can be used to cause ester hydrolysis.
- Identify the structure of an unknown ester given the products of its hydrolysis.
- Write the hydrolysis mechanism for alkaline esters.
- Write the hydrolysis mechanism for acid esters.
- Write an equation to describe the reduction of an ester with lithium aluminum hydride.
- Identify the product formed by the reduction of a given ester (or lactone) with lithium aluminum hydride.
- identify the ester, reagents, or both, that must be used to prepare a given primary alcohol.
- Write a detailed mechanism for the reduction of an ester by lithium aluminum hydride.
- Identify diisobutylaluminum hydride as a reagent for reducing an ester to an aldehyde and write an equation for such a reaction.
- Write an equation to describe the reaction of an ester with a Grignard reagent.
- Identify the product formed by the reaction of a given ester with a given Grignard reagent.
- identify the ester, Grignard reagent, or both needed to prepare a given tertiary alcohol.
- Write a detailed mechanism for the reaction of an ester with a Grignard reagent.
key terms
Make sure you can define and use the following key terms in context.
- lactona
- saponification
study notes
Many esters have characteristic aromas and flavors. Some examples are listed below.
basic structure:
| IUPAC name | R | R' | Aroma |
|---|---|---|---|
| octyl ethanoate | CH3 | CH3(CH2)6CH2 | orange |
| propyl ethanoate | CH3 | CH3CH2CH2 | pera |
| 2-methylpropyl propanoate | CH3CH2 | (CH3)2CHCH2 | Ron |
| methyl butanoate | CH3CH2CH2 | CH3 | litter |
| ethyl butanoate | CH3CH2CH2 | CH3CH2 | piña |
A "lactone" is a cyclic ester and has the general structure
By recognizing that the steps in acid hydrolysis of an ester are exactly the same as in Fischer esterification (but in reverse order!), you can again minimize the amount of memorization required. The details of both mechanisms can be deduced from the knowledge that both reactions are acid-catalyzed nucleophilic acyl substitutions.
Esters are present in many biologically important molecules that have a wide range of effects, including fats, waxes, vitamin C, cocaine, nocaine, oil of wintergreen and aspirin.
Ester compounds are often the source of the pleasant aromas of many fruits.
Esters are also present in several important commercial and synthetic applications. For example, polyester molecules make excellent fibers and are used in many fabrics. A woven polyester tube, which is biologically inert, can be used in surgery to repair or replace diseased sections of blood vessels. The most important polyester, polyethylene terephthalate (PET), is made from terephthalic acid and ethylene glycol monomers. PET is used to make bottled water and other beverages. It is also formed into films called Mylar that are used in balloons. Synthetic arteries can be made from PET, polytetrafluoroethylene (PTFE) and other polymers.
Lactones, cyclic esters, have a reactivity similar to that of acyclic esters.
ester preparation
The most versatile method for preparing esters is the nucleophilic acyl substitution of an acid chloride by an alcohol. Acid hydrides and carboxylic acids can also react with alcohols to form esters, but both reactions are limited to the formation of simple esters. Esters can also be formed by deprotonating a carboxylic acid to form a carboxylate and then reacting it with a primary alkyl halide using an Snorte2 reaction.
ester reactions
Esters are one of the most useful functional groups. Their low reactivity makes them easy to work with and they are stable enough to use as solvents in organic reactions (e.g. ethyl acetate). Esters are still reactive enough to undergo hydrolysis to form carboxylic acids, alcoholysis to form different esters, and aminolysis to form amides. Furthermore, they can react with Grignard reagents to form 3oalcohols and hydride reagents to form 1oalcohols or aldehydes.
Conversion of esters to carboxylic acids: hydrolysis
Esters can be cleaved back into a carboxylic acid and an alcohol by reaction with water and a catalytic amount of strong acid. This reaction represents the reverse of the acid-catalyzed esterification of a carboxylic acid and an alcohol discussed in Section 21.3. Both ester formation and cleavage reactions are part of an equilibrium that can be manipulated using Le Chatelier's principle. For ester hydrolysis, the equilibrium is shifted towards carboxylic acid formation using a large excess of water in the reaction.
general reaction
Example
Mechanism
Acid catalysis is required during ester hydrolysis because water is a weak nucleophile. Protonation of the carbonyl ester increases the partial positive charge on the carbonyl carbon, increasing its electrophilicity. After protonation, water adds to the carbonyl carbon, causing the formation of a tetrahedral alkoxide intermediate. A proton is then transferred to the –OR group, increasing its ability to act as a leaving group. Reforming the carbonyl double bond causes the removal of an alcohol (HOR) as a leaving group, creating a protonated carboxylic acid. In the last step of the mechanism, water acts as a base, eliminating a hydrogen, to form a carboxylic acid and regenerate the acid catalyst.
1) Carbonyl protonation
2) Nucleophilic attack by water
3) proton transfer
4) Abandon group removal
5) Deprotonation
lactone hydrolysis
Lactones (cyclic esters) undergo typical ester reactions, including hydrolysis. Hydrolysis of the lactone under acidic conditions creates a hydroxy acid.
Conversion of esters to carboxylic acids: saponification
Esters can also be split into a carboxylate and an alcohol by reaction with water and a base. The reaction is commonly called saponification from the Latin sapo, meaning soap. This name comes from the fact that soap used to be made by hydrolyzing fatty esters.
The saponification reaction uses a better nucleophile (hydroxide) and is generally faster than an acid-catalyzed hydrolysis. The carboxylation ions produced by saponification are negatively charged and very unreactive towards further nucleophilic substitution, making the reaction irreversible.
general reaction
Example
Mechanism
Base-promoted hydrolysis of an ester follows the typical mechanism of nucleophilic acyl substitution. One full equivalent of hydroxide anion is used, so the reaction is called base-promoted and not base-catalyzed. The ester saponification mechanism begins with the nucleophilic addition of a hydroxide ion to the carbonyl carbon to give a tetrahedral alkoxide intermediate. The carbonyl bond is reformed along with the removal of an alkoxide leaving group (-OR), producing a carboxylic acid. The alkoxide base deprotonates the carboxylic acid to obtain a carboxylate salt and an alcohol as products.
The last deprotonation step essentially removes the carboxylic acid from equilibrium, leading to the completion of saponification. Since the carboxylic acid is no longer part of the equilibrium, the reaction is effectively irreversible.
1) Nucleophilic attack by hydroxide
2) Abandon group removal
3) deprotonation
This mechanism is supported by experiments performed with isotopically labeled esters. When the ether-type oxygen of the ester was labeled with18Or, labeled oxygen appeared in the alcoholic product after hydrolysis.
An alternative mechanism would be if the hydroxide participates in an Snorte2 reaction to create the carboxylate product. If this were to happen, the reaction product of the alcohol would not contain the labeled oxygen.
Saponification of esters in biological systems, called hydrolytic acyl substitution reactions, are common. In particular, acetylcholinesterase, an enzyme present in the synapse, catalyzes the hydrolysis of the ester group of acetylcholine, which is a neurotransmitter that triggers muscle contraction. Like many other hydrolytic enzymes, the acetylcholinesterase reaction occurs in two stages: first, a covalent enzyme-substrate intermediate is formed when the acyl group of acetylcholine is transferred to an active site on serine on the enzyme (a transesterification reaction). A water nucleophile then attacks this ester, removing the acetate and completing the hydrolysis.
Conversion of esters into different esters: transesterification
Transesterification is a reaction in which an ester is converted to a different ester through reaction with an alcohol. Since there is typically very little difference in stability between the two esters, the equilibrium constant for this reaction is usually close to one. Using a large excess of reagent alcohol or removing the by-product alcohol can push the reaction equilibrium towards products according to Le Chatelier's principle. Transesterifications also show that great care must be taken when using an ester-containing compound in a reaction involving an alcohol.
general reaction
Example
Mechanism in Basic Conditions
The reaction follows the basic mechanism of a nucleophilic acyl substitution. The alkoxide leaving group of the ester is replaced by an alkoxide nucleophile which enters creating a different ester.
1) Nucleophilic attack by an alkoxide
2) Abandon group removal
Mechanism in acidic conditions
Protonation allows the reactive alcohol to add to the carbonyl ester. The transfer of protons to the ester's alkoxy group increases its ability to act as a leaving group. Reform of the C=O carbonyl bond removes the leaving group and subsequent deprotonation with water forms the ester product.
1) Carbonyl protonation
2) Nucleophilic attack on the carbonyl.
3) proton transfer
4) Elimination of the leaving group
5) Deprotonation
Conversion of ester to amides: Aminolysis
It is possible to convert esters to amides by direct reaction with ammonia or amines. However, these reactions are not commonly used because forming an amide using an acid chloride is a much simpler reaction.
Conversion of esters to 1oAlcohols: Reduction of hydrides
Esters can undergo a hydride reduction with LiAlH4to form two alcohols. The alcohol derived from the acyl group of the ester will be 1oand is normally considered the main product of the reaction. The other alcohol is derived from the alkoxy group of the ester and is normally considered a by-product of the reaction. Observation! Sodium borohydride (NaBH4) is not a sufficiently reactive hydride agent to reduce esters or carboxylic acids. In fact, NaBH4can selectively reduce aldehydes and ketones in the presence of ester functional groups.
general reaction
Predicting the products of a hydride reduction
There are three major bonding changes during this reaction: 1) The -OR leaving group is removed from the ester. 2) The C=O carbonyl bond becomes a C-O-H, an alcohol. 3) Two C-H bonds are formed when two of the hydride nucleophiles add to the original carbonyl carbon of the ester.
Example
Mechanism
The mechanism for the hydride reduction of esters is analogous to the hydride reduction of carboxylic acids. Nucleophilic acyl substitution replaces the -OR leaving group on the ester with a hydride nucleophile to form an aldehyde intermediate. Because aldehydes are more reactive than esters, they rapidly undergo a second nucleophilic hydride addition to form a tetrahedral alkoxide intermediate. An acid treatment protonates the alkoxide to create a 1oalcohol.
1) Nucleophilic attack by the hydride.
2) Exit group removal
3) Nucleopilic attack by the hydride anion
4) The alkoxide is protonated
Conversion of esters to aldehydes: reduction of hydrides
Like acid chlorides, esters can be converted to aldehydes using the weaker reducing reagent diisobutylaluminum hydride (DIBALH). As shown above, an aldehyde intermediate is produced after an ester undergoes nucleophilic acyl substitution with a hydride. When DIBALH is used as a hydride source, the aldehyde does not react further and is isolated as the reaction product. The reaction is normally carried out at -78oC to help isolate the aldehyde product.
general reaction
Example
Conversion of esters to 3oAlcohols: Grignard Reagents
Addition of Grignard reagents converts the esters into two alcohols, a 3oalcohols (main product) and a 1oalcohol (considered a by-product). The Grignard reagent is added to the ester twice, once during a nucleophilic acyl substitution to form a ketone intermediate and again during a nucleophilic addition to form the 3oalcoholic product In general, during this reaction, two C-C bonds are formed on the carbonyl carbon of the ester.
general reaction
Predicting the products of a Grignard reaction
Example
Mechanism
In the first two steps of the mechanism, the OR leaving group of the ester is replaced by the R group of the Grignard reagent via a nucleophilic acyl substitution. This forms a ketone intermediate that is not isolated because ketones, which are more reactive than esters, undergo rapid nucleophilic addition with a second equivalent of Grignard reagent to form an alkoxide intermediate. An acid treatment protonates the alkoxide to form the 3oalcoholic product
1) Nucleophilic attack
2) Abandon group removal
3) Nucleophilic attack
4) Protonation
Example \(\PageIndex{1}\)
How could the following molecule be produced using a Grignard reagent and an ester?
Solution
The main bond breaks for this example are two C-C sigma bonds between the carbonyl carbon and two alpha carbons. Reactions with esters involve a double addition of the Grignard reagent, so the fragments removed must be the same. In this example, the C-C bonds surrounding the two methyl groups are broken. By breaking these bonds, the target molecule is separated into the required starting materials. The fragment containing the alcohol carbon forms a C=O carbonyl bond and gains an –OR to become an ester. The R group of the ester is not very important for the overall reaction and is usually a methyl or ethyl group. The alkyl fragments gain MgBr to form a Grignard reagent. Remember that the Grignard reagent only contains an alkyl fragment.
Exercises \(\PageIndex{1}\)
1) Why is alkaline hydrolysis of an ester not a reversible process? Why does the reaction with a hydroxide ion and a carboxylic acid not produce an ester?
2) Draw the reaction product between the following molecule and LiAlH4, and the product of the reaction between the following molecule and DIBAL.
3) How could you prepare the following molecules from esters and Grignard reagents?
(a)
(b)
(C)
- answers
-
1) The reaction between a carboxylic acid and a hydroxide ion is an acid-base reaction, producing water and a carboxylate ion.
2)
3)
(a)
(b)
(C)