Functional Derivatives of Carboxylic Acids

Compounds such as acid chlorides, amides, esters and anhydrides are collectively called carboxylic acid derivatives, because each differs from a plain carboxylic acid only in WHICH group or atom has replaced the acid's own -OH -- an acid chloride replaces -OH with -Cl, an amide replaces it with -NH2, an ester replaces it with -OR', and an anhydride replaces it with -OOCR (i.e. it is 'capped' by a second acyl group rather than a simple substituent). All four derivative classes share the same underlying reaction pattern -- nucleophilic ACYL substitution, in which an incoming nucleophile adds to the carbonyl carbon and then expels the original leaving group -- so their reactivities differ mainly in how good a leaving group that original substituent is. This is captured by the RELATIVE REACTIVITY order: acid chloride > acid anhydride > ester > acid amide (R-COCl > (RCO)2O > R-COOR' > R-CONH2). Two independent factors explain this order together. (i) BASICITY of the leaving group: a WEAKER base is a BETTER leaving group, so a derivative whose leaving group is a weaker base breaks its C-L bond more readily and is therefore MORE reactive; the basicity order of the relevant leaving groups is H2N: > :OR > RCOO: > :Cl, so reactivity runs in the exact REVERSE of that order. (ii) RESONANCE effect: the LESS electronegative the leaving-group atom, the MORE strongly its lone pair can donate back into the carbonyl by resonance, and that resonance donation stabilises (and so deactivates) the carbonyl -- the electronegativity of the leaving-group atom itself follows -Cl > -OCOR > -OR > -NH2, so …