Journal of the American Chemical Society, Vol.121, No.19, 4598-4607, 1999
Equilibrium formation of anilides from carboxylic acids and anilinesin aqueous acidic media
The formations of formanilide, p-methoxyformanilide, p-nitroformanilide, and acetanilide from their corresponding carboxylic acids and anilines in aqueous acidic media have been investigated at temperatures between 60 and 100 degrees C under a variety of conditions such as pH, D2O, added phosphate, and added ethanol. In each case, the pseudo-first-order rate constants for the establishment of equilibrium (k(obs)), from both the hydrolysis and formation directions, and the conditional equilibrium constant (K' = [anilide]/[aniline](total)) were determined in excess formate. From K', and knowledge of how the pK(a) values of RCOOH and anilinium ion depend on the various conditions, is derived a corrected equilibrium constant, K'(eq), defined as [anilide]/ ([aniline] [RCOOH]). In the case of formanilide, the K' value is found to be invariant with temperature reductions, although the K'(eq) value increases. In D2O media, the K' value drops slightly, but after correcting for the medium induced changes in [aniline] and [RCOOH], the K'(eq) value is the same as in water. In the presence of added KH2PO4, the rate of establishment of equilibrium increases but the K' and K'(eq) values do not change relative to their values without phosphate. Added ethanol is found to increase both the rate of establishment of equilibrium and the K' equilibrium constants, but reduces K'(eq). The mechanism of formation of anilides in water under acidic conditions is discussed.