Q52. - Organic Chemistry

Question

Question: (a) Identify intermediates A–C in the following stepwise conversion of p-isobutyl benzaldehyde to the analgesic ibuprofen.

(b) Direct alkylation of D by treatment with one equivalent of LDA and CH3I does not form ibuprofen. Identify the product of this reaction and explain how it is formed.

Step-by-Step Solution

Answer

Answer

 

(a)

 

Intermediate A

Intermediate B

Intermediate C

(b) The product formed by direct alkylation of D by treatment with one equivalent of LDA and CH3I.

 

Strong base LDA abstracts the acidic proton and forms a carboxylate anion which undergoes alkylation with methyl iodide and forms a substitution product.

Step 1: LDA

 

Lithium di-isopropyl amide (LDA) is a non-nucleophilic (harpoon) strong base. It can abstract protons even from a weakly acidic position.

 

Due to its bulkiness, it abstracts the proton from a less crowded position

Step 2: Identification of intermediates

(a)

 

• The compound p-isobutyl benzaldehyde, on treatment with (NaBH₄) sodium borohydride  yields the corresponding alcohol compound A ((4-isobutylphenyl) methanol).

  Reaction of p-isobutyl benzaldehyde to produce compound A

 

 

• (4-isobutylphenyl) methanol reacts with phosphorous tribromide.

          As bromine is a better leaving group, the cyanide displaces the                 bromide to yield the cyano intermediate B.

                 Conversion of compound A to compound B

 

 

• Compound B on treatment with a base LDA abstracts the proton from the alpha carbon to form a carbanion.

          Then the carbanion reacts with methyl iodide to form an alkylated             product C.

                        Conversion of compound B to compound C

 

• Compound C on hydrolysis followed by heating gives ibuprofen.

                                         Conversion of C to ibuprofen

Step 3: Treatment of D with LDA

(b)

 

• Treatment of compound D with a strong base, LDA, followed by reaction with methyl iodide gives the product.

 

• Here a strong base LDA abstracts the acidic proton and forms a carboxylate anion which undergoes alkylation with methyl iodide and forms a substitution product, which is not ibuprofen. 

                                Reaction of compound D with LDA