What is an alpha-carbon reaction?

The position next to the ketone or aldehyde functional group is termed as alpha position and the reaction which occurs at alpha position is called alpha substitution reaction. In an alpha substitution reaction, the alpha proton atom is substituted by an electrophile by the formation of an enol intermediate or enolate ion intermediate. Most of the carbonyl compounds go through an alpha substitution reaction.

Reactions at alpha carbon

Substitution reactions at α carbon can be catalyzed by both acid & base. An acid is formed as one of the products during halogenation of the reaction and is thus autocatalytic. As in the 2^nd illustration if the compound has a chiral center alpha carbon; the results of halogenation reaction and isotopic exchange reaction are racemic. Not all carbonyl mixtures show these characteristics, the 3^rd ketone is an illustration.

Two significant conclusions might be drawn from the above examples.

• In the first example, these substitutions are restricted to carbon atoms α to the carbonyl group. The first ketone is cyclohexanone which has 2 alpha carbons & 4 $\alpha$-hydrogen. Based on the reaction conditions, one or each of the 4 hydrogens might be substituted. The ketone at second example affirms that only alpha-carbon is goes through substitution, regardless of the presence of numerous various sites.
• Second, the substitutions are restricted to hydrogen atoms. This is exhibited convincingly by the ketone in the third example, which has similar structure as the second ketone however there is no alpha-hydrogen in the 3^rd ketone.

The aldol reaction

The aldol reaction is one more illustration of electrophilic substitution reaction at alpha carbon in enols or enolate anions. Three instances of aldol reaction in which base acts as a catalyst are displayed in the below diagram, and the corresponding acid-catalyzed reactions additionally happen. The basic change in the aldol condensation reaction is the dimerization of a carbonyl group to a β-hydroxy carbonyl group by alpha C-H the addition to the double bond of -CHO (aldehydes) or C=O( ketone) of a 2^nd reactant atom.

If the reaction takes place under an acid or base catalyst this reaction is reversible, and the products of beta-hydroxy carbonyl might return to the initial carbonyl compounds. If there is no such catalyst the products of this condensation reaction are completely steady and isolable mixtures. The yield of products is recognized with their general thermodynamic steadiness because of the reversibility. If the reactants contain an aldehyde functional group (-CHO) as in above reactions 1 and 2, the aldol reaction is unassumingly exothermic & the yields are acceptable. But, the aldol reactions in which reactants contain ketone functional group (-C=O) is less ideal, for example, the above reaction 3. A smart method of defeating this hindrance has been found. A similarly unsolvable base barium hydroxide is utilized to catalyze the aldol condensation reaction of acetone , and the product is taken out from this base by filtration and distribution of the acetone.

Mixed aldol condensation reactions

Aldol condensation between different carbonyl reactants is known as crossed or mixed reactions. Mixed aldol reactions occur under certain specific conditions. The base-catalyzed reaction continues utilizing an enolate anion donor species and dynamically protons are detached from the less substituted alpha-carbon while the acid-catalyzed aldol continues utilizing the enol tautomer, and the steadier of the 2 enol tautomers is that with the high substituted double bond.

These crossed aldol reactions are completed because of two variables. To begin with, -CHO is a highly reactive electrophile than –C=O, and formaldehyde is highly reactive than other aldehydes. Second, -CHO lacking α-hydrogen can act as acceptor reactants, and this diminishes the number of products significantly.

Claisen-Schmidt reaction

In the Claisen-Schmidt reaction, ketones undergo aldol condensation with aryl aldehydes to give α, β-unsaturated derivatives. The reaction continues when a solid base is available and the result of the response is a beta-keto ester or a beta-diketone. For these condensation reactions, at least one reagent should have an alpha proton and can form an enolate-like anion upon deprotonation and the reaction additionally requires the base which avoids nucleophilic substitution reaction or nucleophilic addition with carbon having a place with the carbonyl group. An ideal base for this reaction is the sodium alkoxide which is the form base of the alcohol to be formed since it is recovered. Another necessity is that the alkoxy portion of the ester should act as a good leaving group, on account of ethyl and methyl esters.

Mechanism of claisen condensation

Stage 1: The solid base eliminates an α hydrogen atom and produces an enolate particle. This enolate anion is somewhat steady because of the delocalization of the electrons.

The above reaction prompts the arrangement of the enolate ions.

Stage 2: The carbonyl carbon of the second ester reactant is currently the objective of a nucleophilic attack from the enolate anion. This prompts the disposal of the alkoxy group and the recovery of the form base of the alcohol. This alkoxide particle eliminates the formed alpha proton, leading to a new enolate anion which is currently resonance stabilized. The arrangement of this new enolate particle is outlined beneath.

Stage 3: Now, an aqueous acid such as phosphoric acid or sulphuric acid, for instance, is added to neutralize the negative charge on the enolate anion just as any base which is as yet present. This prompts the development of a beta-diketone or a beta-keto ester, which is isolated immediately and the leaving group is eliminated.

Reactions at the alpha carbons of carboxylic acid derivatives

In this segment comparative reactions of carboxylic acid, subsidiaries will be analyzed.

Acid-catalyzed α-chlorination and α-bromination reactions continue all the more leisurely with -COOH (carboxylic acid), RCOOR’(ester) & RCN (nitrile) than with carbonyl group. RCOX ( alkyl halides) and anhydrides are effectively halogenated than RCOOR^' & RCN, likely as a result of their high concentration of enol. This distinction might be utilized to work with the α-halogenation of -COOH ( carboxylic acids). Accordingly, the change of the acid to its acyl chloride subordinate is trailed by α-bromination or chlorination, and the subsequent halogenated acyl chloride is then hydrolyzed to the product of carboxylic acid. This three-venture arrangement can be diminished by utilizing a reactant measure of PBr₃ or PCl₃, as displayed in the below reaction. This basic adjustment functions admirably because the carboxylic acid group and RCOCl exchange help the reaction progress. The result is the α-halogenated acid and the RCOX. This halogenation system is known as the hell-vol hard-Zelinsky reaction.

Context and Applications

This topic is important for both undergraduate and postgraduate courses, particularly for Bachelors and Masters in Chemistry.

Practice Problems

Question 1: Among the subsequent options does not have alpha hydrogen atoms?

A) Formaldehyde

B) Acetaldehyde

C) Dimethyl acetaldehyde

D) Acetone

Answer: Option A is correct.

Explanation: The chemical formula of acetaldehyde, acetone, and phenylacetaldehyde is CH₃CHO, CH₃COCH₃, and PhCH₂CHO respectively while the chemical formula of formaldehyde is HCHO which has a single carbon there is no α-substitution carbon, there is no α hydrogen.

Question 2: The reaction of C₆H₅CHO with (CH₃CO)₂O and CH₃COONa in the occurrence of the base is known as?

A) Claisen condensation

B) Perkin reaction

C) Cannizzaro reaction

D) Aldol condensation

Answer: Option B is correct.

Explanation: The reaction of C₆H₅CHO with (CH₃CO)₂O and CH₃COONa is called perkin condensation.

Question 3: Reactions between aryl aldehydes and ketones is known as?

A) Claisen condensation

B) Perkin reaction

C) Cannizzaro reaction

D) Aldol condensation

Answer: Option A is correct.

Explanation: The aldol condensation of ketones with aryl aldehydes is termed a Claisen-Schmidt reaction.

Question 4: An enol or an enolate intermediate reacts with a compound having a carbonyl functional group to give a β-hydroxy aldehyde or β-hydroxy ketone is recognized as which reaction?

A) Claisen condensation

B) Perkin reaction

C) Cannizzaro reaction

D) Aldol condensation

Answer: Option D is correct.

Explanation: If -CHO compounds having α-hydrogen reacts with a weak base to give β-hydroxy aldehydes is termed as an aldol condensation reaction.

Question 5: The reaction between 2 different –CHO and –C=O groups is known as?

A) Claisen condensation

B) Perkin reaction

C) Mixed aldol condensation

D) Aldol condensation

Answer: Option C is correct.

Explanation: If there is a condensation reaction between 2 different carbonyl compounds is known as crossed or mixed condensation reaction.