Question

How would you prepare p-ethylbenzylamine from a carboxylic acid, using both Hofmann and Curtius rearrangements?

Answer 1

Hofmann rearrangement involves the conversion of an amide into an amine via an isocyanate intermediate while Curtius rearrangement is the thermal decomposition of an acyl azide to an amine again through an isocyanate intermediate.

In Hofmann rearrangement, the amide is subjected to bromine in alkaline conditions to form a N-bromoamide by proton abstraction from the amide nitrogen by the base. This bromoamide then rearranges to the isocyanate intermediate through amide-imido tautomerism with the cleavage of bromide. Later, upon treatment with water of due to the water present in the medium, the isocyanate forms its respective carbamic acid which gets decarboxylated due to its instability to yield the final amine.

In Curtius rearrangement, the isocyanate formation is driven by the extrusion of a highly inert species - nitrogen gas, from the acyl azide, again generating an amido-imido tautomerism which is similar to the N-bromoamide in Hofmann rearrangement after the leaving of bromide.

Therefore, it can be surmised that to converted a carboxylic acid to p-ethylbenzylamine, the respective acid - p-ethylbenzyl carboxylic acid, which is then converted to an acyl chloride for the ease of that species' transformation into an acyl azide or amide. Then, the respective substrates are subjected to the conditions corresponding to the rearrangements to yield the desired product.

Hofmann Rearrangemt:

Curtius Rearrangement: