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Question 145

p-cresol reacts with chloroform in alkaline medium to give the compound A which adds hydrogen cyanide to form, the compound B. The latter on acidic hydrolysis gives chiral carboxylic acid. The structure of the carboxylic acid is

Solution

The sequence involves three well-known reactions of aromatic aldehydes and ketones.
Step-1 : Reimer-Tiemann formylation of a phenol.
Step-2 : Cyanohydrin formation (nucleophilic addition of $$HCN$$).
Step-3 : Acidic hydrolysis of the nitrile group to a carboxylic acid.

Step 1 : Preparation of compound A
In the Reimer-Tiemann reaction, phenols treated with $$CHCl_3$$ and aqueous $$KOH$$ are ortho-formylated:

$$\require{mhchem}$$ $$\ce{p-CH_3-C_6H_4-OH\ (p\text{-cresol})\xrightarrow[H_2O]{CHCl_3/KOH} \ 2-HO-3-CH_3-C_6H_3-CHO}$$

Because the para position is blocked by $$CH_3$$, the formyl group enters the ortho position relative to $$OH$$. Thus, compound A is $$2\text{-hydroxy-5-methylbenzaldehyde}$$ (also called 4-methyl-salicylaldehyde).

Step 2 : Formation of compound B
An aldehyde adds hydrogen cyanide across the $$C=O$$ bond to give a cyanohydrin:

$$ \ce{2-HO-5-CH_3-C_6H_3-CHO + HCN \longrightarrow 2-HO-5-CH_3-C_6H_3-CH(OH)-CN}\quad(\text{compound B}) $$

The carbon that was originally the aldehydic carbon now bears four different groups ($$H$$, $$OH$$, $$CN$$, and the aryl group), so B already possesses a chiral centre.

Step 3 : Acidic hydrolysis of B
On heating the cyanohydrin with dilute mineral acid, the $$-CN$$ group is converted into $$-COOH$$ without affecting the adjacent $$OH$$ group:

$$ \ce{2-HO-5-CH_3-C_6H_3-CH(OH)-CN \xrightarrow[\Delta]{H_3O^+} 2-HO-5-CH_3-C_6H_3-CH(OH)-COOH} $$

The product is $$2\text{-hydroxy-2-(2-hydroxy-5-methylphenyl)acetic acid}$$, commonly described as a 5-methyl-mandelic acid analogue. The $$\alpha$$-carbon (the one bearing $$OH$$ and $$COOH$$) remains attached to four different groups, hence the acid is chiral, exactly as stated in the problem.

The structure corresponds to Option B.

Answer : Option B which is 2-hydroxy-2-(2-hydroxy-5-methylphenyl)acetic acid.

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