Ester

The organic compound contributing to the flavours and even at times aromas in fruits and flowers are esters. Natural flavours and aromas are produced as a result of complex mixtures of many compounds, with esters being as a primary component. For example, the natural orange aroma is composed of 30 different esters which include 10 carboxylic acids, 34 alcohols, 34 aldehydes and ketones, and 36 hydrocarbons. The food industry always tries to mimic natural flavours by formulating artificial component. Even artificial flavours though are composed of multiple complex mixtures, yet they are not as complicated as their natural counterparts. For example, an artificial pineapple mixture has 7 esters, 3 carboxylic acids, and 7 essential oils (other natural extracts). In some cases, even an individual ester may have a similar smell to a natural aroma. Some examples include chocolate, honey, vanilla etc.

Structurally, an ester is an organic compound with an alkoxy (OR) group attached to the carbonyl group.

R may be Hydrogen, alkyl or aryl, while R’ may be alkyl or aryl only. 

Effect of Structure 

The rate of esterification of various alcohols and acids and their extent of the equilibrium reactions depends on the structure of the molecules and the nature of the functional substituents of the alcohol and the acids. In the process of making of acetate esters, the primary alcohols get esterified most rapidly and completely. So, the highest yield is achieved from methanol in the least time. The reaction rate is almost the same in the case of Ethyl, n-propyl, and n-butyl alcohols. But under similar conditions, the reaction rate is slower for secondary alcohols. However, wide variations are found among various members of the same series. For tertiary alcohols, the reaction rate is slow and the conversions are also nominal (1-10% at equilibrium).

The esterification of acids with straight chains like acetic, propionic, and butyric acids and others like phenylacetic and β-phenyl propionic acid happen quickly with isobutyl alcohol at 155°C. The rate of esterification is low for acids with branched chain acids as the branches are responsible for the greater retarding effect. But the formation of ester products from these substituted acids is higher than normal straight-chain ones. On the other hand, aromatic acids, benzoic and p-toluic have high equilibrium conversions though the reaction rate is slow. a nitrile group on an aliphatic acid inhibits the esterification rate. In the case of chloroacetic acids, increased chlorination results in decreasing velocity. Even double bonds retard the rate of esterification. It has been found that the esterification of that α,β-unsaturated acids are a bit complicated and time-consuming than their saturated analogues. The effect of triple bond in α,β position is similar to that of the double bonds. Both retards the process. 

Even if the double bond is removed as in erucic and brassidic acids, no such effect is found. In fact, conjugated double bonds in the α,β-position produce a greater retarding effect. 

The esterification of Cis-substituted unsaturated acids is way easier than their trans-isomers.

Synthesis of Esters 

The reaction of carboxylic acids, acid chlorides and acid anhydrides with alcohols result in the formation of esters. 

Alcohol reacts with a carboxylic acid in the presence of a mineral acid catalyst, such as sulfuric acid to result in esterification. 

Since these reactions result in an equilibrium mixture of both products and reactants, the reaction conditions must be deployed accordingly in order to produce a reasonable yield. In the starting mixture, a large excess of one of the reactants can be used or the alternate way could be the removal of one of the products by distillation as the reaction proceeds. This will shift the equilibrium to the right. 

Various other synthetic methods to manufacture esters are also there. The reaction of acid chlorides and alcohol also gives an ester and hydrochloric acid. To neutralize the resulting acid, a small amount of pyridine can be added to the reaction mixture. Alcohols reacting with acid anhydrides also yields an ester. But unlike the reaction involving carboxylic acid, these two reactions don't give an equilibrium mixture.

I. Acid-Catalysed Esterification of a Carboxylic Acid and an Alcohol

The reaction of carboxylic acids and alcohols in the presence of an acid catalyst produces esters. Typically, strong inorganic (mineral) acid such as H₂SO₄, HCl and H₃PO₄ are used in a catalytic amount. Strong organic acids such as benzenesulphonic or p-toluenesulphonic acid are actually better preferred as they are soluble in the typical organic solvents used in organic reactions and on top of that, they can be used as catalyst without introducing any additional amount of water in the reaction equilibrium.

II. Acid-Catalysed Esterification of a Carboxylic Acid and an Alcohol in Excess

Methyl salicylate, the major component in the oil of wintergreen is produced by many plants of the wintergreen family. Methyl salicylate can be used as a flavouring agent (responsible for the mint flavour in chewing gum) or a fragrance. It is also a component in liniments (rubbing ointments).

III. Esters produced from an Acid Chloride and an Alcohol

The reaction between acid chlorides and alcohols in the presence of a weak base such as pyridine or Na₂CO₃ results in the formation of esters. The weak base manages to trap or neutralize the HCl formed in the course of the reaction. The reaction mechanism is shown as follows 

IV. Esterification using an Acid Anhydride and an Alcohol or a Phenol

Acid anhydrides undergo nucleophilic acyl substitution reaction with alcohols to yield esters. In the reaction, either a strong acid (H₂SO₄) or a weak base (pyridine) can be used as a strong catalyst or it may be effected by heating.

Acetylsalicylic acid, or aspirin, is one of the most widely used and versatile drugs in today’s pharma world. Charles von Gerhardt was the first one to synthesize it in 1853 and was later patented by a German dye chemist named Friedrich Bayer in 1893. The later one identified its potential as an analgesic (pain reliever). 

Salicylic acid is a component of willow and poplar bark. This had been used as a pain killer for centuries, but due to its highly acidic property, it caused irritation of the mucous membranes of the mouth and throat and even resulted in uncomfortable gastric pain. By transformation of the acidic phenol functionality into an ester group, the compound can retain its analgesic properties but have lost some of its irritating side effects. Apart from acting as a pain reliever, aspirin acts also as an antipyretic (fever reducer) and an anti-inflammatory agent (used for arthritis). But if taken in large quantities (several grams per day), it may result in gastric problems. Its use has been used in Reyes syndrome, a brain disorder affects people under the age of 18. 

Some people may be highly allergic to aspirin as well. The aspirin interferes with platelets affecting normal blood clotting that leads to haemorrhage in extreme cases. However, its anticoagulant properties make it ideal for preventing blood clots in the arteries. As per the recent studies, the consumption of one-half of an aspirin tablet per day can help the prevention of heart attacks and strokes. If acetic anhydride is used as a reactant, instead of acetic acid, it will result in rapid and irreversible conversion of salicylic acid to acetylsalicylic acid.

V. Reaction Mechanism of Aspirin Synthesis in the presence of Acid Catalyst

VI. Reaction Mechanism of Aspirin Synthesis in Neutral Media

Reaction of Esters 

As compared to acid chlorides, the reactivity of the esters are less.

Reaction Sites on a Carboxylic Group on Esters

The nucleophilic acyl substitution reaction is the most common reaction where esters react with a nucleophile. 

I. Hydrolysis of Esters in Basic Media

Unlike the acid chlorides that gets hydrolysed readily in water, esters do not undergo hydrolysis readily in water. The hydrolysis of esters can occur only in the presence of an acid or base catalyst. The products of the hydrolysis vary depending on whether the reaction is conducted in a basic media or an acidic media.

Hydrolysis of esters in basic media results in the formation of a carboxylate salt and alcohol, which on acidification produces a carboxylic acid and an alcohol.

Mechanism of Hydrolysis of Esters in Basic Media

Although hydrolysis is the breaking down by water, in a basic environment, the salt of water (NaOH or KOH) acts as a stronger nucleophile than that of the water molecule itself. Thus the former is the effective nucleophile in this alkaline or basic media.

For historical reasons, the hydrolysis of ester in aqueous hydroxide (KOH or NaOH) is known as saponification because it was used in the manufacture of soap by reacting oils or fats like triesters or triglycerides with lye that contains mainly KOH.

II. The reaction of Esters with Ammonia and Amines

Ester undergoes a nucleophilic substitution reaction with ammonia and amines. The substitution happens at carbonyl carbon to produce amides. The nucleophilic nature of amines and ammonia is stronger than that of water and alcohols. Even the presence of water and alcohol can help proceed with the reaction. 

Hydroxamate for Esters 

Just like other amines are more nucleophilic than alcohols and therefore displaces alcohols from esters, hydroxylamine is no different. It also undergoes the same mechanisms to provide hydroxamic acids. Hydroxamic acids result in highly coloured complexes that are reddish blue/ magenta in colours in ferric chloride solutions.