<P> Esters can undergo a variety of reactions with carbon nucleophiles . As with acid halides and anhyrides, they will react with an excess of a Grignard reagent to give tertiary alcohols . Esters also react readily with enolates . In the Claisen condensation, an enolate of one ester (1) will attack the carbonyl group of another ester (2) to give tetrahedral intermediate 3 . The intermediate collapses, forcing out an alkoxide (R'O) and producing β - keto ester 4 . </P> <P> Crossed Claisen condensations, in which the enolate and nucleophile are different esters, are also possible . An intramolecular Claisen condensation is called a Dieckmann condensation or Dieckmann cyclization, since it can be used to form rings . Esters can also undergo condensations with ketone and aldehyde enolates to give β - dicarbonyl compounds . A specific example of this is the Baker--Venkataraman rearrangement, in which an aromatic ortho - acyloxy ketone undergoes an intramolecular nucleophilic acyl substitution and subsequent rearrangement to form an aromatic β - diketone . The Chan rearrangement is another example of a rearrangement resulting from an intramolecular nucleophilic acyl substitution reaction . </P> <P> Because of their low reactivity, amides do not participate in nearly as many nucleophilic substitution reactions as other acyl derivatives do . Amides are stable to water, and are roughly 100 times more stable towards hydrolysis than esters . Amides can, however, be hydrolyzed to carboxylic acids in the presence of acid or base . The stability of amide bonds has biological implications, since the amino acids that make up proteins are linked with amide bonds . Amide bonds are resistant enough to hydrolysis to maintain protein shape and structure in aqueous environments, but are susceptible enough that they can be broken when necessary . </P> <P> Primary and secondary amides do not react favorably with carbon nucleophiles . Grignard reagents and organolithiums will act as bases rather than nucleophiles, and will simply deprotonate the amide . Tertiary amides do not experience this problem, and react with carbon nucleophiles to give ketones; the amide anion (NR) is a very strong base and thus a very poor leaving group, so nucleophilic attack only occurs once . When reacted with carbon nucleophiles, N, N - dimethylformamide, or DMF, can be used to introduce a formyl group . </P>

Protonation in the absence of a good nucleophile