Leaving group hydroxide

Most nucleophiles are both more basic and more reactive towards sp -hybridized carbon than is water. Thus catalysis is readily observed wilh those esters which undergo hydrolysis at a significant rate in neutral solution, that is, with esters activated by electron withdrawing substituents in either the acyl or the leaving group. Hydroxide ion, however, is basic enough to attack any ester, and since the mechanism of alkaline hydrolysis appears to be relatively simple this reaction will be discussed first. 

Notice the leaving group in (he secotul step It is tvalt-r, a weak base. Proton ution allows nucleophilic substitution to occur in alcohols because it turns it bad leaving group (hydroxide, a strong base) into a good one (water). This theme will return in Chapter 9. 

As discussed in Section 10.5D, a special value of p-toluenesulfonic (tosylate) and meth-anesulfonic (mesylate) esters is that in forming them, an —OH is converted from a poor leaving group (hydroxide ion) in nucleophilic displacement to an excellent leaving group, the p-toluenesulfonate (tosylate) or methanesulfonate (mesylate) anions. 

In Summary Nucleophilic attack on the carbonyl group of carboxylic acid derivatives is a key step in substitution by addition-elimination. Either acid or base catalysis may be observed. For carboxylic acids, the process is complicated by the poor leaving group (hydroxide) and competitive deprotonation of the acid by the nucleophile, acting as a base. With less basic nucleophiles, addition can occur. 

Part two of the mechanism is conversion of the hemiacetal into an acetal, which requires four steps. First a proton transfer step converts a bad leaving group (hydroxide) into an excellent leaving group (water). Loss of water gives an intermediate that can be attacked by another molecule of the alcohol. The resulting oxonium ion is then deprotonated... 

---