Substitution Reactions of Carboxylic Acid Derivatives

Nucleophilic Acyl Substitution Reactions of Carboxylic Acid Derivatives (Chapter21)... 

We don t expect you to be satisfied with the bland statement that tetrahedral intermediates are formed in these reactions of course, you wonder how we know that this is true. The first evidence for tetrahedral intermediates in the substitution reactions of carboxylic acid derivatives was provided by Bender in 1951. 

Using pKaH to predict the outcome of substitution reactions of carboxylic acid derivatives... 

We don t expect you to be satisfied with the bland statement that tetrahedral intermediates are formed in these reactions of course, you wonder how we know that this is true. The first evidence for tetrahedral intermediates in the substitution reactions of carboxylic acid derivatives was provided by Bender in 1951. He made carboxylic acid derivatives RCOX that had been labelled with an isotope of oxygen, 0. This is a non-radioactive isotope that is detected by mass spectrometry. He then reacted these derivatives with water to make labelled carboxylic acids. By any reasonable mechanism, the products would have one i 0 atom from the labelled starting material. Because the proton on a carboxylic acid migrates rapidly from one oxygen to another, both oxygens are labelled equally. 

This chapter will discuss methods for the preparation of esters, acid chlorides, anhydrides, and amides from carboxylic acids, based on acyl substitution reactions. Acyl substitution reactions of carboxylic acid derivatives will include hydrolysis, interconversion of one acid derivative into another, and reactions with strong nucleophiles such as organometallic reagents. In addition, the chemistry of dicarboxylic acid derivatives will be discussed, as well as cyclic esters, amides, and anhydrides. Sulfonic acid derivatives will be introduced as well as sulfate esters and phosphate esters. Finally, nitriles will be shown to be acid derivatives by virtue of their reactivity. 

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