Carbonyl derivatives RCOX

A quite different and complimentary approach is to assume that addition of a nucleophile to an acyl derivative (RCOX) would follow the linear free energy relationship for addition of the nucleophile to the corresponding ketone (RCOR, or aldehyde if R=H) if conjugation between X and the carbonyl could be turned off, while leaving its polar effects unchanged. This can be done if one knows or can estimate the barrier to rotation about the CO-X bond, because the transition state for this rotation is expected to be in a conformation with X rotated by 90° relative to RCO. In this conformation X is no longer conjugated, so one can treat it as a pure polar substituent. Various values determined by this approach are included in the tables in this chapter. 

As can be seen from equations 2-5, the formation of A -acylenamines proceeds from derivatives of carboxylic acids (having an oxidation level equal to three ), namely anhydrides or add halides RCOX or amides RCONH2, on the one hand, and from carbonyl compounds or their derivatives (oxidation level equal to two ), namely enamines 3, acetylenes 5, or vinyl ethers 6, on the other. Indeed, the acetylenes 5, being the dehydration products of enols, may be regarded as having a masked carbonyl functionwhile the enamines 3 rank with vinyl ethers, vinyl esters and enols, as the heteroanalogs of these carbonyl derivatives (see Section IV). 

Carbonyl compounds will be taken in this chapter to mean any organic compound that contains at least one carbon-oxygen double bond where we limit the substitution to only saturated aliphatic, saturated alicyclic and aryl hydrocarbyl groups. Carbonyl compounds with a variety of unsaturated substituents have earlier been discussed within the context of enones4. Non-hydrocarbyl substituents, X , may be directly attached to the carbonyl and elsewhere in the molecule. The first type of species, RCOX, is alternatively identified as acyl derivatives such as carboxylic acids and their esters, halides and amides and have already been discussed in a recent Patai thermochemistry... 

The characteristic reaction of an acyl (carboxyl) com-poimd RCOX is cleavage of the C-X bond. The reactions of carbonyl compounds, such as aldehydes RCHO and ketones R2CO, do not involve cleavage of the C-R or C-H bonds. Many drugs are derivatives of carbonyl compounds, though their parentage may not be obvious. 

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