Addition nucleophilic: to aldehydes and ketones

The next section explores the mechanism of nucleophilic addition to aldehydes and ketones There we 11 discuss their hydration a reaction m which water adds to the C=0 group After we use this reaction to develop some general principles we 11 then survey a number of related reactions of synthetic mechanistic or biological interest... 

This pattern of increased reactivity resulting from carbonyl group prolonalion has been seen before m nucleophilic additions to aldehydes and ketones (Section 17 6) and... 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds, its central theme is a fundfflnental reaction type, nucleophilic addition to carbonyl groups. The principles of nucleophilic addition to aldehydes and ketones developed here will be seen to have broad applicability in later chapters when transfonnations of various derivatives of carboxylic acids are discussed. 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

Aniline is a primary amine and undergoes nucleophilic addition to aldehydes and ketones to form imines. 

The methoxide ion uses of its lone pairs of electrons to form a bond to the electrophilic carbonyl carbon of the acid chloride. Simultaneously, the relatively weak n bond of the carbonyl group breaks and both of the n electrons move onto the carbonyl oxygen to give it a third lone pair of electrons and a negative charge. This is exactly the same first step involved in nucleophilic addition to aldehydes and ketones. However, with an aldehyde or a ketone, the tetrahedral structure is the final product. With carboxylic acid derivatives, the lone pair of electrons on oxygen return to reform the carbonyl n bond (Step 2). As this happens, the C-Cl o bond breaks with both electrons moving onto the chlorine to form a chloride ion that departs the molecule. 

As was the case for nucleophilic additions to aldehydes and ketones, two mechanisms occur for the reactions in this chapter one under basic conditions and one under acidic conditions. Both of these start in the same manner as the addition reaction mechanisms. The basic conditions mechanism is shown in Figure 19.1. First the nucleophile... 

Q The first step of this mechanism is exactly the same as the first step for nucleophilic addition to aldehydes and ketones under basic conditions (see Figure 18.1). The nucleophile may be uncharged in some cases. 

In Chapter 21 we continue the study of carbonyl compounds with a detailed look at aldehydes and ketones. We will first learn about the nomenclature, physical properties, and spectroscopic absorptions that characterize aldehydes and ketones. The remainder of Chapter 21 is devoted to nucleophilic addition reactions. Although we have already learned two examples of this reaction in Chapter 20, nucleophilic addition to aldehydes and ketones is a general reaction that occurs with many nucleophiles, forming a wide variety of products. 

We begin our study of nucleophilic additions to aldehydes and ketones by briefly reviewing nucleophilic addition of hydride and carbanions, two reactions examined in Sections 20.4 and 20.10, respectively. 

Nucleophilic addition to aldehydes and ketones (25.11) With 1 ° amines ... 

Nucleophilic additions to aldehydes and ketones have two general V) ations, as shown in Figure 19.2 (1) The tetrahedral intermediate can be protonated by water or acid to give an alcohol, or (2) the carbonyl oxygc atotn can be eliminated as HO" or H2O to give a product with a C Nu d, ble bond. 

Thiols will undergo nucleophilic addition to aldehydes and ketones, whereas alcohols only react with aldehydes (Scheme 4). Thiols also react with acid chlorides to yield esters. 

This pattern of increased reactivity resulting from carbonyl group protonation has been seen before in nucleophilic additions to aldehydes and ketones (Section 17.6) and in the mechanism of the acid-catalyzed esterification of carboxylic acids (Section 19.14). Many biological reactions involve nucleophilic acyl substitution and are catalyzed by enzymes that act by donating a proton to the carbonyl oxygen, the leaving group, or both. 

Directionality and Diastereofacial Selection in Nucleophilic Addition to Aldehydes and Ketones... 

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