Side-chain nucleophilic reactivity of five-membered heterocyclic rings: base-catalysed reactions of aldehydes with phenylacetonitrile

Abstract

The rates of the sodium methoxide-catalysed condensations of heteroaromatic aldehydes (Ar = C₆H₅, C₆H₄CH₃-p, C₆H₄OCH₃-p, C₆H₄Cl-p, 2-thienyl, 2-furyl, pyrrol-2-yl, N-methylpyrrol-2-yl, 1-naphthyl, 3-pyridyl, 4-pyridyl) with phenylacetonitrile are measured in methanol. The reaction is third order overall, first order in each reactant. The reactivity sequence is pyridine-4-carbaldehyde > furan-2-carbaldehyde > pyridine-3-carbaldehyde > benzaldehyde > thiophene-2-carbaldehyde > naphthalene-1-carbaldehyde > N-methylpyrrole-2-carbaldehyde > pyrrole-2-carbaldehyde. The Hammett treatment of the data shows the variability of the substituent constants for the heteroatoms confirming that they are system-dependent. Apparent substituent constants for the heteroatoms are calculated. The data are well correlated by the Taft–Pavelich equation, indicating that the reactivity of the five-membered rings depends on steric and polar effects.