MODIFICATION OF REACTIVITY OF SOME CARBOXYLIC ACID DERIVATIVES BY COMPLEXATION . EFFECTS ON SOME INTERMOLECULAR AND INTRAMOLECULAR REACTIONS

The kinetic method for studying organic complexes utilizes measurements of the reaction rate of a substrate as a function of ligand concentration to establish the stability constant for the substrate-ligand interaction product (the complex) and to determine the chemical reactivity of the complex, which is expressed as q11, the fractional decrease in reactivity of the complex relative to the uncomplexed substrate. Reactions studied include the intramolecular general base catalyzed hydrolysis of trans-cinnamoylsalicylic acid anion (CSA anion); intermolecular hydroxide ion catalyzed hydrolysis of CSA anion; sulfite addition to the olefinic double bond of CSA anion; intermolecular nucleophilic reactions of p-nitrophenyl benzoate with the nucleophiles hydroxide ion, hydrogen peroxide anion, hydroxylamine, hydrazine, and sulfite; intermolecular reactions of N-trans-cinnamoyl-imidazole with water and acetate; and intramolecular catalyses of the hydrolyses of phthalamic acid, p-nitrophenyl glutarate, and me hyl hydrogen phthalate. The ligands included theophylline and its anion; the anions of 8-chloro-, 8-bromo-, and 8-iodotheophyllines; caffeine; 8-methoxycaffeine; and 7-(2,3-dihydroxypropyl)-theophylline. Solubility and spectral studies of complex stability were employed for supporting evidence of interaction. All studies were in aqueous solution. Hydroxide attack at the ester function of cinnamate-xanthine and benzoate-xanthine complexes is essentially completely inhibited (q11= 1). Sulfite addition to the cinnamate double bond also gives q11 = 1. These results are interpreted to mean that, in the complex, the ligand is physically near these sites in the substrate. A series of nucleophiles reacting with the p-nitrophenyl benzoate-theophylline complex gave q11 values ranging from 0.6 to 1. It is suggested that complex formation can result in both lowering of initial-state energy and raising of transition-state energy, with the extent of the transition-state effect (and therefore q11) depending on the fractional displacement of the transition state along the reaction coordinate. Intramolecular catalyses were not significantly inhibited by complex formation. The kinetic method for studying complexes is a useful probe into complex structure. © 1969, American Chemical Society. All rights reserved.