Question

How would I synthesize m-isopropylbenzoic acid from benzene? My initial thought was to do alkylation and treat with KMnO to produce the carboxylic acid and then do alkylation to produce the isopropyl at the meta position. But that wouldn’t work, because alkylation and acylation do not occur in the presence of strong or moderate deactivators.

Answer 1

Yes, Friedel Craft Alkylation and Acylation cannot be carried out on deactivated rings. So we use an alternate method for alkylation.

These will be the two basic steps required.

Step 1: Formation of Benzoic Acid (Since it is a meta directing group, this group should be attached first)

Reagents required: a) We can either use the method you told in your question, ie, oxidation of toluene using KMnO₄

b) We can also use mono-bromination, followed by formation of Grignard Reagent and attack on Carbon dioxide followed by hydrolysis.

Step 2: Second step is the alkylation of Benzoic acid, which cannot be carried out by Friedel Craft's alkylation/acylation. So we use alternate reagents will lead to the generation of isopropyl carbocation.

Reagents to be used: a) Isopropyl alcohol + H⁺

b) Propene + H⁺

  c) Isopropyl alcohol + BF₃

All these reagents will lead to the formation of Isopropyl carbocation, which will act as an electrophile and hence substitute at the meta position of benzoic acid.