Acid derivatives acyl substitution

Among the various carboxylic acid derivatives, acyl chlorides are especially useful because they are readily converted to acid anhydrides, esters, and amides by nucleophilic acyl substitution (Table 19.1). Yields are high and the reaction rates are much... 

Amines are nitrogen nucleophiles. They react with the carbonyl group of carboxylic acid derivatives (acyl halides, anhydrides, and esters) by nucleophilic acyl substitution (Sec. 10.11). 

There is one last reaction to consider. Remember the reaction of a carboxylic acid such as butanoic acid with a base such as NaOH or NaOCHg described in Chapter 6 (Section 6.2). Sodium methoxide is a good base (Chapter 12, Section 12.1), but as seen in Chapter 11 (Section 11.3.2), methoxide is also a good nucleophile. What happens when butanoic acid reacts with sodium methoxide in ether The answer is that the acid-base reaction dominates indeed, the acid-base reaction is much faster than the acyl substitution reaction. Therefore, sodium methoxide reacts with butanoic acid to give the sodium salt of butanoic acid (76, the conjugate base) and methanol (the conjugate acid). If a potential nucleophile is a potent base, the acid-base reaction will dominate with carboxylic acids. Nucleophilic acyl substitution reactions dominate with acid derivatives, with some exceptions that are discussed in Chapter 22. 

When acid derivative 2 reacts with sulfuric acid, the oxygen atom is the base and the conjugate acid product of this acid-base reaction is oxocarbenium ion 3, which is resonance stabilized. When 2 is an acid chloride, anhydride, ester, or amide, a heteroatom is attached to the positive carbon in 3. As in Chapter 18 (Section 18.1), the acid-base reaction of the carbonyl unit in 2 to give 3 facilitates reactions with nucleophiles. The reaction of intermediate 3 with a nucleophile ( Y) gives tetrahedral intermediate 4 contrary to acyl addition, reaction 4 contains an X group that can function as a leaving group. Loss of X leads to the final product of this reaction 5. If the nucleophile ( Y) is hydroxide, compormd 5 is the carboxylic acid (X = OH). If the nucleophile Y is an alcohol, the product 5 is an ester, and if Y is an amine, the product 5 is an amide. This first reaction is therefore the acid-catalyzed acyl substitution reaction of acid derivatives. 

MECHANISM OF NUCLEOPHILIC ACYL SUBSTITUTION Acid-Catalyzed Acyl Substitution Reactions Base-Catalyzed Acyl Substitution Reactions Relative Reactivity of Acyl Derivatives... 

CARBOXYLIC ACID DERIVATIVES NUCLEOPHILIC ACYL SUBSTITUTION... 

Carboxylic Acid Derivatives Nucleophilic Acyl Substitution... 

Both stages involve more than one step and these steps differ in detail among the various carboxylic acid derivatives and for different reaction conditions This chapter is organized to place the various nucleophilic acyl substitutions into a common mechanis tic framework and to point out the ways m which individual classes differ from the rest... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

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