Carboxyl derivatives reactivity trend

Two new sections on the protection of phosphates and the alkyne-CH are included. All other sections of the book have been expanded, some more than others. The section on the protection of alcohols has increased substantially, reflecting the trend of the nineties to synthesize acetate- and propionate-derived natural products. An effort was made to include many more enzymatic methods of protection and deprotection. Most of these are associated with the protection of alcohols as esters and the protection of carboxylic acids. Here we have not attempted to be exhaustive, but hopefully, a sufficient number of cases are provided that illustrate the true power of this technology, so that the reader will examine some of the excellent monographs and review articles cited in the references. The Reactivity Charts in Chapter 10 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first introduced. No attempt was made to update these Charts, not only because of the sheer magnitude of the task, but because it is nearly impossible in... 

The relative reactivity of a-haloacetates toward protein functional groups is sulfhydryl > imidazolyl > thioether > amine. Among halo derivatives the relative reactivity is I > Br > Cl > F, with fluorine being almost unreactive. The oc-haloacetamides have the same trend of relative reactivities, but will create a terminal amide group not a terminal carboxylate. 

When differences in hybridization are removed, the relative trends in the donor ability of lone pairs correlate well with the electronegativity of heteroatoms. In a textbook example, reactivity of carboxylic acid derivatives increases in the following order amide < ester < acyl fluoride due to decrease in n,j interaction (X=N>0>F). Lower importance of negative conjugation leads to increased positive charge and electrophi-licity of the carbonyl carbon (see Chapter 6 for further discussion). 

The four carboxylic acid derivatives that are the focus of this chapter have the relative reactivity toward nucleophilic acyl substitution as follows. The differences in this trend are dramatic. For example, at common ambient temperatures and neutral pH, acid halides will react with water within seconds to minutes, while anhydrides will do so over minutes to hours. Esters, however, do not... 

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