Question

How would you convert benzene into 4-bromocyclohexanecarboxylic acid?

Answer 1

How about benzene → toluene → 4-bromotoluene → 4-bromobenzoic acid → 4-bromocyclohexanecarboxylic acid?

Explanation:

Let's do a retrosynthetic analysis.

4-Bromocyclohexanecarboxylic acid

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.

4-Bromobenzenoic acid

We can form a benzoic acid by permanganate oxidation of an alkyl group on the ring.

We could use 4-bromotoluene.

4-Bromotoluene

We could either brominate toluene or do a Friedel-Crafts alkylation of bromobenzene.

The direct bromination of toluene looks better, because `"Br"` is a deactivating group.

Toluene

This is easy: a Friedel-Crafts alkylation of benzene.

The synthetic steps in review:

1. Benzene to toluene (Friedel-Crafts alkylation)
2. Toluene to 4-bromotoluene (electrophilic aromatic substitution)
3. 4-Bromotoluene to 4-bromobenzoic acid (`"MnO"_4^-` oxidation of side-chain)
4. 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 (`"Sn/HCl"` reduction)

3a. 4-Methylaniline to 4-methylbenzenediazonium chloride (diazotization with `"NaNO"_2"/HCl"` at 0 °C)
3b. 4-Methylbenzenediazonium chloride to 4-methylbenzonitrile ( Sandmeyer reaction, `"CuCN/KCN"`)
3c.. 4-Methylbenzonitrile → 4-methylbenzoic acid (acid- or base-catalyzed hydrolysis)