Structure and Reactivity of Carboxylic Acid Derivatives

The number of reactions in this chapter is quite large and keeping track of them all can be difficult—or it can be manageable. The key to making it manageable is the same as always  

This difference in reactivity, especially toward hydrolysis, has an important result. We ll see in Chapter 25 that the structure and function of proteins are critical to life itself. The bonds mainly responsible for the structure of proteins are amide bonds, which are about 100 times more stable to hydrolysis than ester bonds. These amide bonds are stable enough to maintain the structural integrity of proteins in an aqueous environment, but susceptible enough to hydrolysis to be broken when the occasion demands. 

What structural features are responsible for the reactivity order of carboxylic acid derivatives Like the other carbonyl-containing compounds that we ve studied, they all have a planar arrangement of bonds to the carbonyl group. Thus, all are about the same in offering relatively unhindered access to the approach of a nucleophile. They differ in the 

Electron release from the substituent X stabilizes the carbonyl group and makes it less electrophilic. 

The order of reactivity of carboxylic acid derivatives toward nucleophilic acyl substitution can be explained on the basis of the electron-donating properties of substituent X. The greater the electron-donating powers of X, the slower the rate. 

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Section 20 2 The structure and reactivity of carboxylic acid derivatives depend on how well the atom bonded to the carbonyl group donates electrons to it... 

Relative Reactivities, Structures, and Spectra of Carboxylic Acid Derivatives Comparisons of physical properties. 

RELATIVE REACTIVITIES, STRUCTURES, AND SPECTRA OF CARBOXYLIC ACID DERIVATIVES... 

At this point we want to consider the relative reactivity of carboxylic acid derivatives and other carbonyl compounds in general terms. We return to the subject in more detail in Chapter 7. Let us first examine some of the salient structural features of the carbonyl compounds. The strong polarity of the C=0 bond is the origin of its reactivity toward nucleophiles. The bond dipole of the C-X bond would be expected increase carbonyl reactivity as the group X becomes more electronegative. There is another powerful effect exerted by the group X, which is resonance electron donation. 

We begin with a comparison of the structures, properties, and relative reactivities of carboxylic acid derivatives. We then explore the chemistry of each type of compound. Halides and anhydrides are valuable reagents in the synthesis of other carbonyl compounds. Esters and amides are enormously important in nature for example, the esters include common flavoring agents, waxes, fats, and oils among the amides we find urea and penicillin. The alkanenitriles, RC=N, are also freated here because they have similar reactivity. 

Asymmetric alkylation of carboxylic acid derivatives has been studied intensively for about 20 years. [1] Numerous auxiliaries, tailor-made structures with high steric demands for effective RelSi face differentiation, have been synthesized and their efficiency tested. [1, 2] In recent years besides the preparative aspects of enolates, physico-chemical investigations into their structure-reactivity relationships have gained interest. [3] Crystal structure analyses, osmometric measurements, and NMR studies in solution are helpful in the investigation of the factors that may control enolate reactions. [3-5]... 

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