Nucleophilic acyl substitution reaction kinds

We ve now studied three of the four general kinds of carbonyl-group reactions and have seen two general kinds of behavior. In nucleophilic addition and nucleophilic acyl substitution reactions, a carbonyl compound behaves as an electrophile. In -substitution reactions, however, a carbonyl compound behaves as a nucleophile when it is converted into its enol or enolate ion. In the carbonyl condensation reaction that we ll study in this chapter, the carbonyl compound behaves both as an electrophile and as a nucleophile. 

Thioesters undergo the same kinds of reactions as esters and by similar mechanisms Nucleophilic acyl substitution of a thioester gives a thiol along with the product of acyl transfer For example... 

The net effect of the addition/elimination sequence is a substitution of the nucleophile for the -Y group originally bonded to the acyl carbon. Thus, the overall reaction is superficially similar to the kind of nucleophilic substitution that occurs during an Sn2 reaction (Section 11.3), but the mechanisms of the two reactions are completely different. An SN2 reaction occurs in a single step by backside displacement of the Leaving group a nucleophilic acyl substitution takes place in two steps and involves a tetrahedral intermediate. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Problem 29.8 Look at the entire glycolysis pathway and make a list of the kinds of organic reactions that take place—nucleophilic acyl substitutions, aldol reactions, ElcB reactions, and so forth. 

In this case, from the standpoint of the acid chloride, reaction is acid-catalyzed nucleophilic acyl substitution, of the kind discussed in Sec. 20.4, with the aromatic ring acting as the nucleophile. 

We are in a strange, complex chemical environment here, but in it we recognize familiar kinds of compounds—hemiacetals, esters, anhydrides, carboxylic acids—and familiar kinds of reactions—nucleophilic carbonyl addition, hydride transfer, 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. 

Benzene rings with substituents other than halo, nitro, sulfonic acid, alkyl, and acyl can be prepared by first synthesizing one of these substituted benzenes and then chemically changing the substituent. The kinds of substituents that can be placed on benzene rings are greatly expanded by reactions of arene dia-zonium salts, nucleophilic aromatic substitution reactions, and reactions involving a benzyne intermediate. The relative positions of two substituents on a benzene ring are indicated either by numbers or by the prefixes ortho, meta, and para. 

Notice in Figure 20.12 that the mechanisms of the nucleophilic acyl substitution steps are given in an abbreviated form that saves space by not explicitly showing the formation and subsequent collapse of tetrahedral reaction intermediates. Instead, electron movement is shown as a heart-shaped path around the carbonyl oxygen to imply the full mechanism. Biochemists use this kind of format frequently, and weTl also use it on occasion in the remaining chapters. 

If you were to look at the steps of vitamin B12 biosynthesis, you would see exactly the same kinds of reactions we ve been seeing throughout the text— nucleophilic substitutions, eliminations, aldol reactions, nucleophilic acyl substitutions, and so forth. There are, of course, some complexities, but the fundamental mechanisms of organic chemistry remain the same, whether in the laboratory with smaller molecules or in organisms with larger molecnles. 

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