Electrophilic Properties of Carboxylic Acid Derivatives

Carboxylic acid derivatives, CH3C(=0)Z, are similar to aldehydes and ketones in that they contain a polar carbonyl group. Therefore, nucleophiles should add to the carbonyl carbon, although the rate of addition may depend on the Z group. 

One way to investigate the electrophilic properties of these molecules is to examine the orbital that each uses to accept electrons from a nucleophile. This orbital is the lowest-unoccupied molecular orbital (LUMO). Examine the LUMO for methyl acetate (Z=OCH3), acetaldehyde (Z=H), N,N-dimethylacetamide (Z=N(CH3)2) and acetyl chloride (Z=C1) (acetaldehyde is not a carboxylic acid derivative, but is included here for comparison). What is the shape of the LUMO in the region of the carbonyl group Is it a o or 7U orbital Is it bonding or antibonding What other atoms contribute to the LUMO Which bonds, if any, would be weakened when a nucleophile transfers its electrons into the LUMO  

A molecule with a low energy LUMO can accept electrons more readily than a molecule with a higher energy LUMO. The LUMO energies (in au) for the above molecules ai e 0.192 (methyl acetate), 0.161 (acetaldehyde), 0.212 (N,N-dimethylacetamide), and 0.132 (acetyl chloride). Order these molecules from most electrophilic to least electrophilic. 

LUMO of methyl acetate reveals the likely site of nucleophilic attack. 

Chapter 10 Carboxylic Acid Derivatives. Nucleophilic Substitution 149 

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Cyanoformamidines, exhibiting nucleophilic and electrophilic properties in the 1,3-positions, react with hexafluoroacetone forming five-membered heterocycles (86CB2127). This ability to form five-membered heterocycles is the major characteristic of hexafluoroacetone, which is also inherent in some perfluorinated and partially fluorinated ketones, aldehydes, and imines in their reactions with a-functional derivatives of carboxylic acids, as well as w-amino, a-N-alkylamino,... 

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