How would you convert benzene into 4-bromocyclohexanecarboxylic acid?
How about benzene → toluene → 4-bromotoluene → 4-bromobenzoic acid → 4-bromocyclohexanecarboxylic acid?
Let's do a retrosynthetic analysis.
We must start with benzene, so we should probably hydrogenate 4-bromobenzoic acid.
We will probably need a Raney nickel catalyst, a pressure of 35-40 atm, and a temperature of 200-250 °C.
We can form a benzoic acid by permanganate oxidation of an alkyl group on the ring.
We could use 4-bromotoluene.
We could either brominate toluene or do a Friedel-Crafts alkylation of bromobenzene.
The direct bromination of toluene looks better, because
This is easy: a Friedel-Crafts alkylation of benzene.
The synthetic steps in review:
- Benzene to toluene (Friedel-Crafts alkylation)
- Toluene to 4-bromotoluene (electrophilic aromatic substitution)
- 4-Bromotoluene to 4-bromobenzoic acid (
#"MnO"_4^-#oxidation of side-chain)
- 4-Bromobenzoic acid to 4-bromocyclohexanecarboxylic acid (catalytic hydrogenation)
An alternate synthesis
We could also have used the following scheme:
2a. Toluene → 4-nitrotoluene (aromatic nitration)
2b. 4-Nitrotoluene → 4-methylaniline (
3a. 4-Methylaniline to 4-methylbenzenediazonium chloride (diazotization with
3b. 4-Methylbenzenediazonium chloride to 4-methylbenzonitrile ( Sandmeyer reaction,
3c.. 4-Methylbenzonitrile → 4-methylbenzoic acid (acid- or base-catalyzed hydrolysis)