第十章第四军医大学药学.pptVIP

Acidity Compared to Alcohols Carboxylic acids are better proton donors than are alcohols (The pKa of ethanol is ~16, compared to ~5 for acetic acid) ? In an alkoxide ion, the negative charge is localized on oxygen while in a carboxylate ion the negative charge is delocalized over two equivalent oxygen atoms, giving resonance stabilization Acidity Constant and pKa Carboxylic acids transfer a proton to water to give H3O+ and carboxylate anions, RCO2?, but H3O+ is a much stronger acid The acidity constant, Ka, is about 10-5 for a typical carboxylic acid (pKa~ 5) Substituent Effects An electronegative group will drive the ionization equilibrium toward dissociation, increasing acidity ? An electron-donating group destabilizes the carboxylate anion and decreases acidity Alkyl groups have little effect. The ionization constants of all acids that have the general formula CnH2n+1CO2H are very similar to one another and equal approximately 10 ?5 (pKa ~5). An electronegative substituent, particularly if it is attached to the α carbon, increases the acidity of a carboxylic acid. Monohaloacetic acids is about 100 times more acidic than acetic acid. Multiple halogen substitution increases the acidity even more; trichloroacetic acid is 7000 times more acidic than acetic acid! Substituent Effects on Acidity Substituent Effects on Acidity Electronegative substituents promote formation of the carboxylate ion Examples of Inductive Effects on Acidity Fluoroacetic, chloroacetic, bromoacetic, and iodoaceticacids are stronger acids than acetic acid Multiple electronegative substituents have synergistic effects on acidity Inductive effects depend on the electronegativity of the substituent and the number of bonds between it and the affected site. As the number of bonds increases, the inductive effect decreases Acidity of Substituted Benzoic Acids Benzoic acid itself is a somewhat stronger acid than acetic acid. Carbon becomes more electron-withdrawing as its s character