Nitrile acyl-substituted

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Michael reaction, 894-895 mutarotation. 986 nitrile hydrolysis, 768-769 nucleophilic acyl substitution reaction. 790... 

Reactions of Amides Because amides are the most stable acid derivatives, they are not easily converted to other derivatives by nucleophilic acyl substitution. From a synthetic standpoint, their most important reaction is the reduction to amines, which is one of the best methods for synthesizing amines. Amides are hydrolyzed by strong acid or strong base. Just as nitriles can be hydrolyzed to amides, amides can be dehydrated to nitriles. 

Chapter 22 continues the study of carbonyl compounds with a detailed look at nucleophilic acyl substitution, a key reaction of carboxylic acids and their derivatives. Substitution at sp hybridized carbon atoms was introduced in Chapter 20 with reactions involving carbon and hydrogen nucleophiles. In Chapter 22, we learn that nucleophilic acyl substitution is a general reaction that occurs with a variety of heteroatomic nucleophiles. This reaction allows the conversion of one carboxylic acid derivative into another. Every reaction in Chapter 22 that begins with a carbonyl compound involves nucleophilic substitution. Chapter 22 also discusses the properties and chemical reactions of nitriles, compounds that contain a carbon-nitrogen triple bond. Nitriles are in the same carbon oxidation state as carboxylic acids, and they undergo reactions that form related products. 

A rhodium-catalyzed decomposition of a-diazoacetophenones in benzonitrile gives an intermediate acyl-substituted nitrile ylide (157) that cyclizes to the oxazole or may be trapped with DMAD to produce a pyrrole (Scheme 73) <92CL2197>. Ethyl cyanoformate and ethyl 3,3,3 trifluoro-... 

This chapter also explores how the mechanistic principles governing nucleophilic acyl substitution apply to many of the reactions of nitriles, compounds of the type R—C=N . 

Carbon monoxide, hydrogen cyanide, and nitriles also react with aromatic compounds in the presence of strong acids or other Friedel-Crafts catalysts. These reactions are quite useful for synthetic purposes, since the products are formyl- or acyl-substituted aromatics. These electron-withdrawing groups retard any further electrophilic substitutions. Detailed mechanistic studies have not been carried out, but the general outlines of the mechanism of these reactions are given below ... 

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. 

Another FGI that gives carboxylic acid products is the hydrolysis of carboxylic acid derivatives, such as esters and nitriles. Such hydrolysis reactions can either be acid catalyzed (H3O+) or base promoted (1. NaOH, H2O 2. H3O ) and involve an acyl substitution mechanism (addition-elimination) that replaces any acyl leaving group with a hydroxyl group. The synthesis of carboxylic acids via nitriles is especially noteworthy since the introduction of the cyano group via Sn2 with CN involves the formation of a new C-C bond (adds one new carbon to the alkyl halide carbon chain). 

Nucleophilic acyl substitution includes many useful synthetic methods and is a major participant in numerous biosynthetic processes. Its mechanism, which constitutes a major portion of this chapter, has been thoroughly studied and provides a framework for organizing what might otherwise be a collection of isolated facts, details, and observations. Similar principles apply to the reactions of nitriles and are included as well. 

Closely related to the carboxylic acids and nitriles discussed in the previons chapter are the carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or snbstituent that can act as a leaving group in the nucleophilic acyl substitution reaction that we saw briefly in the Preview of Carbonyl Chemistry ... 

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