Salt effects on an ion-molecule reaction--hydroxide-catalyzed hydrolysis of benzocaine.
OBJECTIVE
This work investigates the effect of various salts on the rate of a reaction involving a neutral species (benzocaine alkaline hydrolysis).


METHODS
Benzocaine hydrolysis kinetics in NaOH solutions in the presence of different salts were studied at 25 degrees C. Benzocaine solubility in salt solutions was also determined. Solubility data were used to estimate salt effects on benzocaine activity coefficients, and pH was used to estimate salt effects on hydroxide activity coefficients.


RESULTS
Salts either increased or decreased benzocaine solubility. For example, solubility increased with 1.0 M tetraethylammonium chloride (TEAC) approximately 3-fold, whereas solubility decreased approximately 35% with 0.33 M Na2SO4. Salt effects on hydrolysis rates were more complex and depended on the relative magnitudes of the salt effects on the activity coefficients of benzocaine, hydroxide ion, and the transition state. As a result, some salts increased the hydrolysis rate constant, whereas others decreased it. For example, the pseudo-first-order rate constant decreased approximately 45% (to 0.0584 h(-1)) with 1 M TEAC, whereas it increased approximately 8% (to 0.116 h(-1)) with 0.33 M Na2SO4.


CONCLUSIONS
Different salt effects on degradation kinetics can be demonstrated for a neutral compound reacting with an ion. These salt effects depend on varying effects on activity coefficients of reacting and intermediate species.
Al-Maaieh
Ahmad
A
Division of Pharmaceutics, School of Pharmacy, The University of Iowa, Iowa City, Iowa, 52242, USA. al-maaieh_ahmad@lilly.com
Flanagan
Douglas R
DR
D000779:Anesthetics, Local / Q000737:chemistry*; D001566:Benzocaine / Q000737:chemistry*; D004355:Drug Stability; D006868:Hydrolysis; D008956:Models, Chemical; D010472:Perchlorates / Q000737:chemistry; D012492:Salts / Q000737:chemistry*; D017670:Sodium Compounds / Q000737:chemistry; D012972:Sodium Hydroxide / Q000737:chemistry; D012995:Solubility; D013431:Sulfates / Q000737:chemistry; D019789:Tetraethylammonium / Q000737:chemistry
D000779:Anesthetics, Local; D010472:Perchlorates; D012492:Salts; D017670:Sodium Compounds; D013431:Sulfates; C012036:sodium sulfate; D012972:Sodium Hydroxide; D019789:Tetraethylammonium; C031068:sodium perchlorate; D001566:Benzocaine