Intramolecular nucleophilic assistance in reactions of acetals

Abstract

The hydrolyses of 4-aminobutyraldehyde diethyl acetal, 2-pyridylmethylaminoacetaldehyde diethyl acetal, succinaldehydic acid dimethyl acetal, and D-threo-teturonic acid dimethyl acetal are not appreciably faster than those of analogous acetals without the potential neighbouring groups, which indicates that there is no intramolecular nucleophilic assistance in the former reactions. The cyclisation of 2-carboxybenzaldehyde diethyl acetal to 3-ethoxyphthalide is about three times faster than the hydrolysis of terephthalaldehydic acid diethyl acetal in aqueous buffers, which also indicates the absence of significant nucleophilic assistance. In 82% w/w aqueous dioxan the pH*–rate profile for the cyclisation of 2-carboxybenzaldehyde diethyl acetal at 60° is sigmoid and at pH* 9·46 the rate is 3000 times that for the hydrolysis of terephthalaldehydic acid diethyl acetal. Therefore under these conditions the carboxylate group provides nucleophilic assistance for the acid-catalysed rupture of the acetal bond.

Hydrolysis of 2-(o-carboxyphenyl)-1,3-dioxolan proceeds via an intermediate, probably 3-(2-hydroxyethyl)-1,3-dioxolan, in aqueous solution at a rate approximately ten times that for the hydrolysis of 2-(p-carboxyphenyl)-1,3-dioxolan. Hydrolysis of 3-(2-hydroxy-1,1,2,2-tetramethylethoxy)phthalide is too fast for it to be detectable as an intermediate in the hydrolysis of 2-(o-carboxyphenyl)-4,4,5,5-tetramethyl-1,3-dioxolan. In water the latter reaction is about ten times faster than hydrolysis of the para-isomer and in 50% w/w aqueous dioxan it is about fifty times faster. Under these conditions the reaction probably involves intramolecular nucleophilic catalysis.

The hydrolyses of o-carbamoylbenzaldehyde diethyl acetal and 2-(o-carbamoylphenyl)-1,3-dioxolan yield 3-hydroxyphthalimidine. These reactions proceed via an intermediate which was tentatively identified as o-carbamoylbenzaldehyde.