reactions of enolates with carbonyl compounds

Reactions of Enolates with Carbonyl Compounds(The Aldol and Claisen reactions)

By Vijay Kumar Maurya

IntroductionFormation of enolates or enols by base or acid and then nucleophillic attack by enols and enolates on carbonyl group of aldehyde and ketone or acylating agents

A brief discussion on:• Explanation of reactions through mechanism• Specific names of reaction• Reaction conditions• Regio-selectivity• Control of the reaction• Uses of it

MechanismThe simplest available enolisable is acetaldehyde i.e. CH3CHO and when it is reacted with a small amount of NaOH,

As the final product contains aldehyde and alcohol group, so it is named as aldol

MechanismThe same reaction occurs with ketones(say )

But with more base, further reaction occurs because aldol product dehydrated rather easily under the reaction conditions to give stable conjugated unsaturated carbonyl compounds

Depending upon the reactions conditions base catalysed reaction gives sometime elimination product and sometimes aldol(i.e. high temperature, strong base long time will favor the elimination product

MechanismAcid catalyzed mechanism, enols are less nucleophilic than enolates, and the reactions occurs because the electrophilic carbonyl is protonated(i.e. the carbonyl carbon is activated)

MechanismIf there are two different carbonyl compounds, then it is called Cross Condensation reactions. This reaction to work well two conditions are there:• One partner only must be capable of enolisation• The other partner must be incapable of enolisation and be more

electrophilic than the other enolisable partner

If cross condensation reaction happens between acetaldehyde and formaldehyde, then

Reaction between acetaldehyde and formaldehyde

Why do we need to control the reaction?When a mixture of two carbonyl compounds(A and B) is taken both of them having α- hydrogen atom and treated with a base, then four aldol products can be formed, i.e.• If A acts as both electrophile and nucleophile• If B acts as both electrophile and nucleophile• If A acts as both electrophile and B as nucleophile• If B acts as both electrophile and A as nucleophile

To overcome this situation some specific enol equivalent can be used to control the reactions, like, lithium enolates, silyl enols ethers, etc

Control of the reactionUsing lithium enolates, prepared at low temperature(-78 ˚C ) in THF

Control of the reactionUsing silyl enols ethers, prepared in weak base such as tertiary amine and for trapping the enolate Me3SiCl.

UsesIn preparation of alcohol,

2 CH3CHO CH3CH(OH) CH2CHO CH3CH=

CHCHO

CH3CH2CH2CH2OHIn synthesis of vitamin A ,

In aldol condensation of glycol-aldehyde gives monosaccharides.

3 CH2(OH)CHO C6H12O6 ( Formose )

OH- H2O Δ

H2/Ni

NaOH

BF3

AcOH

Citral

References• A Guidebook to Mechanism in Organic Chemistry, by Peter

Sykes.

• Organic Chemistry: Jonathan Clayden, Nick Greeves and Stuart Warren.

A lot of interesting things are out there to be explored, so let us keep our eyes open.

A very thank to all …