Concerted Bimolecular Substitution Reactions of Acetal Derivatives of Propionaldehyde and Benzaldehyde

The propionaldehyde acetal derivatives 1-acetoxy-1-methoxy-3-(4-methoxyphenyl)propane, 1-methoxy-3-(4-methoxyphenyl)-1-(4-nitrophenoxy)propane, and 1-azido-1-ethoxypropane undergo concerted bimolecular substitution reactions with anionic nucleophiles. The products are unstable adducts that break down to the corresponding aldehydes. The observed rate constants follow Swain–Scott correlations withs values of 0.1-0.2, which indicate a low sensitivity to the attacking nucleophile and are consistent with an “exploded” transition state. Water shows a small negative deviation from these plots but reacts through a stepwise mechanism with a highly unstable oxocarbenium ion intermediate. Similarly, an acetal derivative of benzaldehyde, azidomethoxyphenylmethane, undergoes rapid concerted bimolecular substitution with good nucleophiles. The unexpectedly larges value of 0.4 is similar to that observed for a 4-nitrobenzyl system but, remarkably, the reactivity toward thiocyanate is >10⁵-fold greater than that of benzyl azide and ˜100-fold greater than that of 1-azido-1-ethoxypropane, which provides evidence for a benzylic effect. Water exhibits a positive deviation of ˜30-fold from the Swain–Scott correlation for anionic nucleophiles, and hydrolysis of this compound occurs by a concurrent stepwise mechanism with a diffusionally equilibrated oxocarbenium ion intermediate. The consequences of these results for reactions of glycosyl derivatives are discussed.