Nucleophilic acyl substitution general mechanism

Hydrazine cleaves amide bonds to form acylhydrazides according to the general mechanism of nucleophilic acyl substitution discussed in Chapter 20... 

Both in the laboratory and in living organisms, the reactions of carbonyl compounds take place by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, and carbonyl condensation. These... 

General mechanism of a nucleophilic acyl substitution reaction. 

Conversion of Acid Chlorides into Alcohols Reduction Acid chlorides are reduced by LiAJH4 to yield primary alcohols. The reaction is of little practical value, however, because the parent carboxylic acids are generally more readily available and can themselves be reduced by L1AIH4 to yield alcohols. Reduction occurs via a typical nucleophilic acyl substitution mechanism in which a hydride ion (H -) adds to the carbonyl group, yielding a tetrahedral intermediate that expels Cl-. The net effect is a substitution of -Cl by -H to yield an aldehyde, which is then immediately reduced by UAIH4 in a second step to yield the primary alcohol. 

From a chemical point of view, amide and ester bonds have comparable structural and spectroscopic features and are hydrolyzed by the same general mechanism, i.e., a nucleophilic acyl substitution involving an addition-elimination sequence (see Chapt. 3). However, in a given structure, the amide... 

Acid derivatives differ in the nature of the nucleophile bonded to the acyl carbon —OH in the acid, —Cl in the acid chloride, —OR in the ester, and —NH2 (or an amine) in the amide. Nucleophilic acyl substitution is the most common method for interconverting these derivatives. We will see many examples of nucleophilic acyl substitution in this chapter and in Chapter 21 ( Carboxylic Acid Derivatives ). The specific mechanisms depend on the reagents and conditions, but we can group them generally according to whether they take place under acidic or basic conditions. 

Nucleophilic acyl substitutions are also called acyl transfer reactions because they transfer the acyl group from the leaving group to the attacking nucleophile. The following is a generalized addition-elimination mechanism for nucleophilic acyl substitution under basic conditions. 

The general mechanism for nucleophilic acyl substitution is a two-step process nucleophilic attack followed by loss of the leaving group, as shown in Mechanism 22.1. 

Q> j Mechanism 22.1 General Mechanism—Nucleophilic Acyl Substitution... 

The mechanism for this reaction has the usual two steps of the general mechanism for nucleophilic acyl substitution presented in Section 22.7—addition of the nucleophile followed by loss of a leaving group—plus an additional step involving proton transfer (Mechanism 22.9). 

Similar experiments have indicated the reversible formation of tetrahedral intermediates in hydrolysis of other esters, amides, anhydrides, and acid chlorides, and are the basis of the general mechanism we have shown for nucleophilic acyl substitution. 

Most reactions of carbonyl groups occur by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, am carbonyl condensation. These mechanisms have many variations, just a alkene electrophilic addition reactions and 8 2 reactions do, but the varia tions are much easier to learn when the fundamental features of the mechanisms are understood. Let s see what the four mechanisms are and what kinds of chemistry carbonyl groups undergo. 

Section 17.7 General Mechanism for Nucleophilic Acyl Substitution Reactions... 

The net result of this process is substitution of the —OR group of the alcohol for the —OH group of the acid. Hence the reaction is referred to as nucleophilic acyl substitution. But the reaction is not a direct substitution. Instead, it occurs in two steps (1) nucleophilic addition, followed by (2) elimination. We will see in the next and subsequent sections of this chapter that this is a general mechanism for nucleophilic substitutions at the carbonyl carbon atoms of carboxylic acid derivatives. 

The add chlorides prepared in this fashion are often not isolated and purified, but rather are used directly in a subsequent reaction. This is possible because both of the side products, HCl and SO2, are gases and readily lost or removed from the mixture. For example, if an amide is the desired product, then the crude acid chloride is simply allowed to react with an excess of an amine. An excess of the amine is used to neutralize the HCl that is generated during the preparation of the acid chloride (Eq. 20.7) and by the reaction of the acid chloride with the amine (Eq. 20.6). Like 18, acid chlorides are highly reactive, and they tend to undergo nucleophilic acyl substitution according to the general mechanism shown in Equation 20.2. 

This type of reaction is called a nucleophilic acyl substitution, and the rest of this chapter will be dominated by various examples of this type of reaction. The general mechanism has two core steps (Mechanism 21.1). 

The general mechanism for nucleophilic acyl substitution is a two-step process nucleophilic... 

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