Ester Hydrolysis and Nitrosative Deamination of Novocaine in Aqueous Solutions

Abstract

In aqueous solutions, the kinetic features of both the hydrolysis reaction of the ester function of novocaine in alkaline medium and the nitrosation reaction of the primary amine group of novocaine in mild acid medium were investigated by UV/vis spectroscopy. The ester hydrolysis shows first-order kinetics with respect to both the drug and the nucleophile, OH-, concentrations, thus following a typical S(N)2 (Ac) mechanism. The rate of the reaction decreases strongly with the polarity of the reaction media, analyzed for both dioxane-water and Me2SO-water mixtures. The effect of the presence of cationic micelles of tetradecyltrimethylammonium bromide, TTABr, was abnormal in that it inhibits the rate of the reaction throughout the analyzed concentration range of the surfactant. The same pattern of behavior is observed in the presence of anionic micelles of sodium dodecyl sulfate (SDS); however, the effect is more pronounced. The rate equation obtained in the kinetic study of the nitrosation reaction of novocaine in mild acid medium contains first- and second-order terms with respect to [nitrite], which correspond with the two parallel reaction paths due to nitrosation via both NO+ and N2O3, respectively; the rate of the reaction also increases with both the [H+] and the total acetic acid-acetate buffer concentration. In contrast to the ester hydrolysis, the nitrosation reaction is accelerated in aqueous micellar solutions of both cationic and anionic surfactants of TTABr and SDS, respectively.

Protonation Constants of Procaine in Different Salts

“…Procaine or novocaine has been used as a local anesthetic for a long time. The dissociation equilibria of this substance are important to understand its behavior; therefore, it has been considered of interest to study the variation of its acid−base equilibrium constants with salt concentration in different ionic media at 25 °C.…”

Reactions of Carboxylic, Phosphoric and Sulfonic Acids and their Derivatives

“…74 The rate of alkaline hydrolysis of the local anaesthetic novocaine (diethylaminomethyl 4-aminobenzoate) was reported. 75 Kinetic studies of the reactions of polyalkylamines with aryl acetates and aryl methyl carbonates at pH 7-11.5 showed that concerted mechanisms operate. 76 The hydrolysis of glycine methyl ester, CH 2 (NH 2 )CO 2 Me, and methionine methyl ester, MeSCH 2 CH 2 CH(NH 2 )CO 2 Me, was catalysed with high effectiveness by the Cu(II) complex of N ,N ,N ,N -tetramethylethylenediamine, the observed catalytic enhancement being 10 4 -fold.…”

Investigation of physico-chemical behaviour of local anaesthetics in aqueous SDS solutions

“…As an example, in the case of TCA the input values of A a ¼ 0.025-the absorbance reading at the lowest pH-and A b ¼ 0.924-the absorbance reading at the highest pH-gave the optimized pK a1 ¼ 2.27 AE 0.02 reported in Table 1, along with the pK a1 measured for the other anaesthetics. 18 (See Fig. S1 of ESIw.…”