Question

The first widely used herbicide for the control of weeds was 2,4 -dichlorophenoxyacetic acid (2,4-D). Show how this compound might be synthesized from phenol and chloroacetic acid by way of the given chlorinated phenol intermediate.

Short answer

Answer: The synthesis of 2,4-D involves three steps: 1. Synthesis of the chlorinated phenol intermediate (2,4-dichlorophenol) through electrophilic aromatic substitution with phenol and chlorine. 2. Conversion of chloroacetic acid to its active form, chloroacetyl chloride, using thionyl chloride (SOCl₂). 3. Nucleophilic attack of the chlorinated phenol intermediate (2,4-dichlorophenol) on chloroacetyl chloride to form 2,4-dichlorophenoxyacetic acid (2,4-D).

Step-by-step solution

Synthesis of the chlorinated phenol intermediate

To synthesize the chlorinated phenol intermediate, we start with phenol and react it with chlorine. This is an electrophilic aromatic substitution reaction, where chlorine acts as the electrophile and phenol as the nucleophile. The intermediate that we need to synthesize is 2,4-dichlorophenol. Phenol, being an activated aromatic ring, will direct the incoming electrophile to ortho and para positions. Since we need the chlorine atoms at positions 2 and 4, we should provide controlled mono-chlorination followed by ortho-chlorination. Reaction: Phenol + 2 Cl₂ → 2,4-dichlorophenol

Conversion of chloroacetic acid to its active form

In order to react chloroacetic acid with the chlorinated phenol intermediate, we first need to convert it into its more reactive form, thionyl chloride (SOCl₂). This electrophilic substitution reaction converts carboxylic acids into their corresponding acyl chlorides. Reaction: Chloroacetic acid + SOCl₂ → Chloroacetyl chloride + HCl + SO₂

Nucleophilic attack of chlorinated phenol intermediate on chloroacetyl chloride

With the chlorinated phenol intermediate (2,4-dichlorophenol) and chloroacetyl chloride in hand, we can proceed to form the 2,4-dichlorophenoxyacetic acid (2,4-D). In this reaction, the oxygen atom of the phenol group in 2,4-dichlorophenol will act as a nucleophile and attack the carbonyl carbon of chloroacetyl chloride, leading to the formation of an ester linkage between the two molecules. Reaction: 2,4-dichlorophenol + Chloroacetyl chloride → 2,4-dichlorophenoxyacetic acid (2,4-D) In summary, the synthesis of 2,4-dichlorophenoxyacetic acid (2,4-D) involves three steps: (1) synthesis of the chlorinated phenol intermediate, (2) conversion of chloroacetic acid to its active form, and (3) nucleophilic attack of chlorinated phenol intermediate on chloroacetyl chloride.