Nucleophilic Addition of Amines Imine and Enamine Formation

Nucleophilic Addition of Amines Imine and Enamine Formation 

Primary amines, RNH2, add to aldehydes and ketones to yield itninefl R2C=NR. Secondary amines, R2NH, add similarly to yield enaminefl R2N-CR=CR2 (cne + amine = unsaturated amine). Imines are importani intermediates in many metabolic pathways, and we ll see frequent examples of their occurrence in Chapter 29. 

Imine formation and enamine formation appear different because one leads to a product with a C=N double bond and the other leads to a product with a C=C double bond. Actually, though, the reactions are quite similar. Both are typical examples of nucleophilic addition reactions in which water is eliminated from the initially formed tetrahedral intermediate and a new C=Nu double bond is formed. 

Mechanism of imine formation by reaction of a ketone or aldehyde with a primary amine. The key step is nucleophilic addition to yield a carbinolamine intermediate, which then loses water to give the imine. 

Imines are particularly common as intermediates in many biological pathways, where they are often called Schiff bases. The amino acid alanine, for instance, is metabolized in the body by reaction with the aldehyde pyridoxal phosphate (PLP), a derivative of vitamin Bg, to yield an imine that is further degraded. 

An imine is formed in a reversible, acid-catalyzed process that begins with nucleophilic addition of the primary amine to the carbonyl group, followed by transfer of a proton from nitrogen to oxygen to yield a neutral 

ThomsonNOv Click Organic Primary amines, RNH2, add to aldehydes and ketones to deld imines, R2C=NR. 

Process to view an animation of Secondary amines, R NH, add similarh to yield enamines, R2N—CR=CR2 

Thomson Click Organic Process to view an animation of the addition of an amine to a carbonyl compound to form an 

Mechanism of imine formation by reaction of an aldehyde or ketone with a primary amine. 

I Nucleophilic attack on the ketone or aldehyde by the lone-pair electrons of an amine leads to a dipolar tetrahedral intermediate. 

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NUCLEOPHILIC ADDITION OF AMINES IMINE AND ENAMINE FORMATION... 

I Nucleophilic Addition of Amines Imine and Enamine Formation 737... 

Nucleophilic addition of amines to aldehydes and ketones (Sections 17.10, 17.11) Primary amines undergo nucleophilic addition to the carbonyl group of aldehydes and ketones to form carbinol-amines. These carbinolamines dehydrate under the conditions of their formation to give A/-substituted imines. Secondary amines yield enamines. 

Nucleophilic addition of amine nucleophiles formation of imines and enamines... 

The driving force behind this reaction is the formation of an aromatic ring. The reactions in this problem are nucleophilic addition of a primary amine, followed by elimination of water to yield an imine or enamine. All of the other steps are protonations and deprotonations. 

Aldehydes and ketones can undergo nucleophilic addition reactions. In particular, aldehydes and ketones can react with amines to form imines and enamines, reactions that might compete with formation of amide bonds between amino acids. Because of this reactivity, aldehydes and ketones are unlikely to be found in amino acid side chains. 

Many addition-elimination reactions at carbonyl centers involve a nucleophilic attack on the carbonyl carbon, followed by an elimination that restores the double bond. We first explore addition followed by 1,2-elimination, one of many types of reactions referred to as condensations. Strictly speaking, a condensation occurs when two large molecules combine to create a more complex molecule with the loss of a small molecule, such as water or an alcohol. Therefore, a condensation is a form of substitution. We will also examine condensation reactions that form polymers (see Chapter 13). One of the more complex condensations is the formation of an imine or enamine from a carbonyl and an amine. In both of these cases an oxygen is replaced by a nitrogen with loss of water (Eq 10.105 and 10.106). 

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