21.6: Chemistry of Esters (2023)

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Goals

After completing this section, you should be able to do so

1. Discuss the widespread occurrence of esters in nature and their important commercial applications by giving an example of an ester bond in nature and an example of a commercially important ester.
2. Write an equation to describe the hydrolysis of an ester under acidic or basic conditions.
3. identify the products formed upon hydrolysis of a given ester.
4. Identification of reagents that can be used for ester hydrolysis.
5. Identify the structure of an unknown ester from the products of its hydrolysis.
6. Write down the mechanism of hydrolysis of alkaline esters.
7. Write down the mechanism of hydrolysis of acid esters.
8. Write an equation describing the reduction of an ester with lithium aluminum hydride.
9. Identify the product formed from the reduction of a specific ester (or lactone) with lithium aluminum hydride.
10. Identify the ester, reagents, or both that must be used to produce a specific primary alcohol.
11. Write a detailed mechanism for the reduction of an ester by lithium aluminum hydride.
12. Identify diisobutylaluminum hydride as a reagent for reducing an ester to an aldehyde and write an equation for such a reaction.
13. Write an equation to describe the reaction of an ester with a Grignard reagent.
14. Identify the product formed by the reaction of a specific ester with a specific Grignard reagent.
15. Identify the ester, Grignard reagent, or both needed to produce a specific tertiary alcohol.
16. 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.

• Milk
• Verseifung
study notes

Many esters have distinctive aromas and flavors. Some examples are listed below.

basic structure:

Table 21.1 Characteristic structures and odors of selected esters
IUPAC-Name R R' Aroma
Octylethanat CH3 CH3(CH2)6CH2 orange
Propylethanoat CH3 CH3CH2CH2 pera
2-Methylpropylpropanoat CH3CH2 (CH3)2CHCH2 Ron
Methylbutanoat CH3CH2CH2 CH3 Apple
Ethylbutanoat CH3CH2CH2 CH3CH2 Pina

A "lactone" is a cyclic ester and has the general structure

Again, by realizing that the steps involved in acid hydrolysis of an ester are exactly the same as in a Fischer esterification (but in reverse order!), you can minimize the amount of memorization. The details of both mechanisms can be deduced from the knowledge that both reactions involve 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, novacaine, oil of wintergreen, and aspirin.

Ester compounds are often the source of the pleasant flavors found in many fruits.

Esters are also present in a number of important commercial and synthetic applications. For example, polyester molecules make excellent fibers and are used in many fabrics. Woven polyester tubing, 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 water bottles and other beverages. It is also formed into sheets called Mylar, which are used in balloons. Synthetic arteries can be made from PET, polytetrafluoroethylene (PTFE), and other polymers.

The lactones, cyclic esters, have a similar reactivity as the acyclic esters.

production of esters

The most versatile method for preparing esters is the nucleophilic substitution of the acyl of an acid chloride with 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 treating it with a primary alkyl halide using an SNorte2 Reaction.

ester reactions

Esters are one of the most useful functional groups. Due to their low reactivity, they are easy to process and they are stable enough to be used as solvents in organic reactions (e.g. ethyl acetate). Esters are still reactive enough to undergo hydrolysis to form carboxylic acids, alcoholysis to form various esters, and aminolysis to form amides. In addition, they can react with Grignard reagents to form 3ÖAlcohols and hydride reagents to form 1Öalcohols or aldehydes.

Conversion of esters to carboxylic acids: hydrolysis

Esters can be cleaved back to a carboxylic acid and an alcohol by reaction with water and a catalytic amount of strong acid. This reaction is 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. In ester hydrolysis, the equilibrium is shifted towards carboxylic acid formation by using a large excess of water in the reaction.

Mechanism

Acid catalysis is required during ester hydrolysis since water is a weak nucleophile. Protonation of the carbonyl ester increases the partial positive charge on the carbonyl carbon, increasing its electrophilicity. Upon protonation, water adds to the carbonyl carbon causing the formation of a tetrahedral alkoxide intermediate. A proton is then donated to the -OR group, increasing its ability to act as a leaving group. The reformation of the carbonyl double bond causes the removal of an alcohol (HOR) as a leaving group, resulting in a protonated carboxylic acid. In the final step of the mechanism, the water acts as a base, abstracting hydrogen, forming a carboxylic acid, and regenerating the acid catalyst.

1) Protonation of the carbonyl

2) Nucleophilic attack by water

3) Protonentransfer

4) Cancel group removal

5) deprotonation

(Video) 20.8 Synthesis and Reactions of Esters

Lactonhydrolyse

Lactones (cyclic esters) undergo typical ester reactions, including hydrolysis. Hydrolysis of the lactone under acidic conditions produces a hydroxy acid.

Conversion of esters into carboxylic acids: saponification

Esters can also be cleaved into a carboxylate and an alcohol by reaction with water and a base. The reaction is commonly referred to as 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 usually faster than acid-catalyzed hydrolysis. The carboxylation ions generated by saponification are negatively charged and very unreactive towards further nucleophilic substitution, rendering the reaction irreversible.

Mechanism

Base-promoted hydrolysis of an ester follows the typical mechanism of nucleophilic acyl substitution. A full equivalent of hydroxide anion is used, so the reaction is said to be base-promoted, not base-catalyzed. The ester saponification mechanism begins with the nucleophilic addition of a hydroxide ion at the carbonyl carbon to give a tetrahedral alkoxide intermediate. The carbonyl bond is reformed along with the removal of an alkoxide (-OR) leaving group, giving a carboxylic acid. The alkoxide base deprotonates the carboxylic acid to give a carboxylate salt and an alcohol as products.

The final deprotonation step essentially removes the carboxylic acid from the equilibrium, resulting in complete saponification. Since the carboxylic acid is no longer part of the equilibrium, the reaction is practically irreversible.

1) Nucleophilic attack by hydroxide

2) Cancel group removal

3) deprotonation

This mechanism is supported by experiments performed with isotopically labeled esters. In the case of the ether type, the oxygen of the ester was marked with18Or labeled oxygen appeared in the alcoholic product after hydrolysis.

(Video) Claisen condensation of esters

An alternative mechanism would be when the hydroxide binds to a SNorte2 reaction to generate the carboxylate product. If this were to happen, the alcohol reaction product would not contain the labeled oxygen.

The saponification of esters in biological systems, referred to as hydrolytic acyl substitution reactions, is common. In particular, acetylcholinesterase, an enzyme present in the synapse, catalyzes the hydrolysis of the ester group of acetylcholine, a neurotransmitter that triggers muscle contraction. Like many other hydrolytic enzymes, the acetylcholinesterase reaction occurs in two phases: first, a covalent enzyme-substrate intermediate is formed when the acyl group of acetylcholine is transferred to an active serine site on the enzyme (a transesterification reaction). A water nucleophile then attacks this ester, removing the acetate and completing the hydrolysis.

Conversion of esters into other esters: transesterification

Transesterification is a reaction in which an ester is converted into another ester by reacting it with an alcohol. Because there is usually 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 the reactant alcohol or removing the alcohol by-product can shift the equilibrium of the reaction toward products according to Le Chatelier's principle. Transesterification reactions also show that great care should be taken when using an ester-containing compound in a reaction involving an alcohol.

mechanism in basic conditions

The reaction follows the basic mechanism of a nucleophilic acyl substitution. The ester's alkoxide leaving group is displaced by an incoming alkoxide nucleophile, yielding a different ester.

1) Nucleophilic attack by an alkoxide

2) Cancel group removal

Mechanism under acidic conditions

Protonation allows addition of the reactive alcohol to the carbonyl ester. Proton transfer to the ester's alkoxy group increases its ability to act as a leaving group. Reforming of the C=O carbonyl bond removes the leaving group and subsequent deprotonation with water forms the ester product.

1) Protonation of the carbonyl

2) Nucleophilic attack on the carbonyl.

3) Protonentransfer

4) elimination of the leaving group

5) deprotonation

Conversion of esters to amides: aminolysis

It is possible to convert esters to amides by direct reaction with ammonia or amines. These reactions are not commonly used, however, as forming an amide using an acid chloride is a much simpler reaction.

Conversion of esters to 1ÖAlcohols: Hydride reduction

Esters can undergo hydride reduction with LiAlH4to form two alcohols. The alcohol derived from the acyl group of the ester is 1Öand is usually considered the main product of the reaction. The other alcohol is derived from the ester's alkoxy group and is usually considered a by-product of the reaction. Note! Sodium borohydride (NaBH4) is not a sufficiently reactive hydride agent to reduce esters or carboxylic acids. Indeed, NaBH4it can selectively reduce aldehydes and ketones in the presence of ester functional groups.

Predicting the products of a hydride reduction

During this reaction there are three main changes in the bond: 1) The leaving group -OR 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.

Mechanism

The mechanism of hydride reduction of esters is analogous to hydride reduction of carboxylic acids. The 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. Acid treatment protonates the alkoxide to produce a 1ÖAlcohol.

1) Nucleophilic attack by the hydride.

2) Leave group removal

3) Nucleophylic attack by the hydride anion

4) The alkoxide is protonated

(Video) 21.6 Claisen Condensation Reactions

Conversion of esters to aldehydes: reduction of hydrides

Like acid chlorides, esters can be converted to aldehydes with the weaker reducing agent 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 the hydride source, the aldehyde does not react further and is isolated as a reaction product. The reaction is usually carried out at -78ÖC to aid in isolation of the aldehyde product.

Conversion of esters to 3ÖAlcohols: Grignard reagents

Addition of Grignard reagents converts the esters into two alcohols, a 3rdÖAlcohols (main product) and a 1ÖAlcohol (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 then again during a nucleophilic addition to form 3Öalcoholic product In general, two C-C bonds are formed at the parent carbonyl carbon of the ester during this reaction.

Example

(Video) 21.6a Claisen Condensation Reactions

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 which is not isolated since ketones, being more reactive than esters, readily undergo nucleophilic addition with a second equivalent of Grignard reagent to form an alkoxide intermediate. Acid treatment protonates the alkoxide to the 3rdÖalcoholic product

1) Nucleophilic attack

2) Cancel group removal

3) Nucleophilic attack

4) protonation

Example $$\PageIndex{1}$$

How could the following molecule be made using a Grignard reagent and an ester?

Solution

The key bond breaks for this example are two C-C sigma bonds between the carbonyl carbon and two alpha carbons. Reactions with esters involve double addition of the Grignard reagent, so the fragments removed must be the same. In this example, the C-C bonds involving 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 acquires a -OR to become an ester. The R group of the ester is largely irrelevant to 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 contains only one alkyl fragment.

Exercises $$\PageIndex{1}$$

1) Why is the alkaline hydrolysis of an ester not a reversible process? Why doesn't an ester form when a hydroxide ion and a carboxylic acid react?

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 make the following molecules from esters and Grignard reagents?

(A)

(B)

(C)

1) The reaction between a carboxylic acid and a hydroxide ion is an acid-base reaction that produces water and a carboxylate ion.

2)

3)

(A)

(B)

(C)

(Video) reaction of esters & strong nucleophiles

Videos

1. Section 21.4c
(Crisjoe Joseph)
2. Dieckmann Condensation Reaction Mechanism
(The Organic Chemistry Tutor)
3. 21.7 Malonic Ester Synthesis and Acetoacetic Ester Synthesis
4. Dieckmann condensation of diesters
(Chem Help ASAP)
5. 21.6b Dieckmann Condensation Reactions
6. 21.7b The Malonic Ester Synthesis
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