Aldol Reaction - Condensation & Intramolecular Reactions

In this article we will learn about Aldol Reaction - Condensation & Intramolecular Reactions in organic chemistry.

Aldol reaction is well-known named reaction in organic chemistry for the synthesis of β-hydroxyaldehyde or β-hydroxyketone.

Key words: Aldol reaction, Named reaction, Enol, Enolate, β-hydroxy carbonyl compound.

Introduction

It is a reaction in organic chemistry in which an enol or an enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone. This reaction is discovered separately by Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in the year 1872. The reaction was developed by using two aldehyde compounds and the product of reaction is known as “aldol” because final compound consists of aldehyde and alcohol. In general aldol reactions are simple to perform and provide high yields of the products. Hence it is used in industries for large scale productions of β-hydroxy carbonyl compounds.

Mechanism of Aldol Reaction

Aldol reaction can be done by using base or acid catalyst. It proceeds through two different mechanisms.

1.    Base catalyzed mechanism

Base catalyzed mechanism consists of three steps:

a)      Step 1: A base takes proton from the carbon which is adjacent to the carbonyl carbon to form enolate ion. It is also known as “enolic donar”.

b)    Step 2: The enolate acts as a nucleophile and attacks on another carbonyl carbon (also known as “electrophilic acceptor”) to form alkoxide ion.

c)      Step 3: Protonation of the alkoxide ion to form alcohol functional group. Final outcome of the reaction is b-hydroxy carbonyl compound.

Figure 1: Base catalyzed mechanism of Aldol Reaction

2.    Acid catalyzed mechanism

Acid catalyzed mechanism consists of four steps:

a)      Step 1: Protonation of carbonyl oxygen

b)      Step 2: Deprotonation of alpha carbon to produce enol intermediate

c)     Step 3: Nucleophilic addition of enol on to another carbonyl group to form alcohol

a)      Step 4: Deprotonation of carbonyl oxygen to give b-hydroxy carbonyl compound.

Figure 2: Acid catalyzed mechanism of Aldol Reaction

In general aldol product further undergoes dehydration to give enone. This is known as Aldol Condensation Reaction.

Figure 3: Aldol Condensation Reaction

Example:

Reaction of benzophenone with aqueous sodium hydroxide gives b-hydroxy ketone compound and further dehydration produces a,b-unsaturated ketone compound.

Figure 4: Reaction of benzophenone with aqueous sodium hydroxide

An aldol reaction in general gives mixture of products based on the number of different alpha protons. For example, reaction of acetone and acetaldehyde gives mixture of aldol products. Here both the carbonyl compounds can act as enolic donar and electrophilic acceptor. 

Figure 5: Crossed Aldol Reaction

Mechanism:

Figure 6: Mechanism of Crossed Aldol Reaction

Intramolecular Aldol Reaction

If two carbonyl groups present in the molecule, then there is possibility of intramolecular Aldol reaction.

Example:

Adipaldehyde is di-carbonyl compound which undergoes intramolecular aldol reaction. In the first step there is formation of enolate ion. Then enolate donar attacks on electrophilic carbonyl carbon to for alkoxide ion. Finally alkoxide takes proton from water molecule to produce aldol product. Further dehydration of the alcohol gives a,b-unsaturated carbonyl compound.

Figure 7: Intramolecular Aldol Reaction

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