Jivani S G, Stella V J
J Pharm Sci. 1985 Dec;74(12):1274-82. doi: 10.1002/jps.2600741207.
The rate of decarboxylation of p-aminosalicylic acid (1) in aqueous solutions was studied at 25 degrees C (mu = 0.5) as a function of pH and buffer concentration. A pH-rate profile was generated by using the rate constants extrapolated to zero buffer concentration. The profile was bell-shaped, with the maximum rate of decarboxylation near the isoelectric pH. The rate constants obtained in buffered solutions indicated general acid catalysis. Bronsted behavior appeared to be adhered to. The two ionization constants of 1 were determined spectrophotometrically at 25 degrees C and at an ionic strength of 0.5. An HPLC method was used to characterize the degradation products of the reaction. Kinetic solvent deuterium isotope effects were studied to further confirm the mechanism of decarboxylation. Below pH 7.0, the mechanism of 1 decarboxylation is the rate controlling proton attack on the carbon-alpha to the carboxylic acid group of 1 anion and the ampholyte, followed by the rapid decarboxylation of the formed intermediate.
在25℃（μ = 0.5）下，研究了对氨基水杨酸（1）在水溶液中的脱羧速率与pH值和缓冲液浓度的关系。通过将速率常数外推至零缓冲液浓度来生成pH-速率曲线。该曲线呈钟形，在等电点pH附近脱羧速率最高。在缓冲溶液中获得的速率常数表明存在一般酸催化作用。似乎符合布朗斯特行为。在25℃和离子强度为0.5的条件下，通过分光光度法测定了1的两个电离常数。采用高效液相色谱法对反应的降解产物进行了表征。研究了动力学溶剂氘同位素效应以进一步证实脱羧机理。在pH 7.0以下，1脱羧的机理是速率控制质子对1阴离子和两性离子羧酸基团α位碳原子的进攻，随后形成的中间体迅速脱羧。
