SolutionsProtection of carboxyl groups
Exercise 1
Why is the tert-butyl ester cleaved by trifluoroacetic acid at room temperature but not the methyl ester? And why is the methyl ester hydrolysed by LiOH whereas the tert-butyl ester hardly is?
In acid, the tert-butyl ester is protonated and the O–C(CH3)3 bond breaks, giving the stable tert-butyl cation (AAL1 mechanism); methyl cannot form a cation. In base, hydrolysis begins with attack of hydroxide on the carbonyl, which the tert-butyl group hinders sterically.
Exercise 2
Propose the synthesis of 4-(1-hydroxy-1-methylethyl)benzoic acid from 4-bromobenzoic acid.
The carboxyl must be protected in a way compatible with an organometallic: it is converted into the 4,4-dimethyloxazoline (with 2-amino-2-methylpropan-1-ol, or via the acid chloride and amide, and cyclization with SOCl2). Then Mg in THF (or n-BuLi at −78 °C) and acetone give the tertiary alcohol. Acid hydrolysis of the oxazoline releases the acid; it must be mild, or the benzylic tertiary alcohol dehydrates.