= Solution
\b[Aqueous base selectively converts the <methyl ester> to a <carboxylate>, and brief acidification gives the corresponding monoacid while retaining the <tert-Butyl ester>.] At the methyl-ester end, a hydroxide <lone pair> attacks the acyl <carbon> and the <carbonyl> pi pair moves to <oxygen>. The tetrahedral intermediate collapses as the <oxygen> anion reforms C=O and the acyl C–OMe bond breaks to <methoxide>. <proton transfer> then gives the <carboxylate> and <methanol>. <carboxylate> formation makes the net <saponification> effectively irreversible under the basic conditions; <protonation> protonates that <carboxylate>.
The <tert-Butyl ester> reacts more slowly under these conditions because its bulky alkoxy group hinders acyl attack, and <tert-butoxide> is a stronger base and poorer <leaving group> than <methoxide>. The <selectivity> is kinetic, not an assertion that tert-butyl <esters> can never undergo base hydrolysis. The work-up should be sufficiently mild and brief to avoid the separate acid-labile pathway.
\b[Anhydrous <trifluoroacetic acid> instead removes the tert-butyl group, leaving the <methyl ester>.] <protonation> activates the <ester>; in a useful reactive <protonation> form the alkoxy <oxygen> bears the <proton>. The O–C(tert-butyl) bond then cleaves with its electron pair going to <oxygen>, producing the <carboxylic acid> and a tert-butyl-cation-like fragment. Loss of a methyl <proton> gives 2-methylpropene and regenerates the acid catalyst. Carbonyl-oxygen <protonation> and charge delocalization can precede cleavage; drawing alkoxy-oxygen <protonation> is a transparent way of tracking the bonds broken. The key distinction is \b[alkyl–oxygen cleavage] here versus \b[acyl–oxygen cleavage] in the base reaction. Methyl-cation formation is strongly unfavourable, and without water ordinary acid-catalysed methyl-ester hydrolysis is not available. No water is required to account for the tert-butyl deprotection or its <alkene> by-product.
\Image[/past-exam-of-the-chemistry-course-of-the-year-1-of-the-natural-sciences-course-of-the-university-of-cambridge/2023/paper-1-ester-deprotection.png]
{title=Original mechanisms contrasting tetrahedral acyl substitution with acid-promoted tert-butyl alkyl–oxygen cleavage}
Back to article page
