Reaction with Primary Amines Imines

W-substituted imines are sometimes called Schiff s bases, after Hugo Schiff, a German chemist who described their formation in 1864. 

Both the addition and the elimination phase of the reaction are accelerated by acid catalysis. Carefnl control of pH is essential, since sufQcient acid must be present to give a reasonable eqnilibrinm concentration of the protonated form of the aldehyde or ketone. Too acidic a reaction medinm, however, converts the amine to its protonated form, a form that is not nncleophilic, and retards reaction. 

PROBLEM 17.11 Write the structure of the carbinolamine intermediate and the imine product formed in the reaction of each of the following  

SAMPLE SOLUTION The carbinolamine is formed by nucleophilic addition of the amine to the carbonyl group. Its dehydration gives the imine product. 

A number of compounds of the general type H2NZ react with aldehydes and ketones in a manner analogous to that of primary amines. The carbonyl group (C=0) is converted to C=NZ, and a molecule of water is formed. Table 17.4 presents examples of some of these reactions. The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones. 

Acetal formation is a characteristic reaction of aidehydes and ketones, but not of carboxylic acids. Use retrosynthetic analysis to show you could use a cyclic acetal protecting group in the following synthesis, then write equations for the procedure showing the necessary reagents. 

Like acetal formation, the reaction of aldehydes and ketones with primary amines— compounds of the type RNH2 and ArNHj—is a two-stage process. Its first stage is nucleophilic addition of the amine to the carbonyl group to give a hemiaminal. The second 

Chapter 17 Aldehydes and Ketones Nucleophilic Addition to the Carbonyl Group 

Stage is a dehydration and yields an imine as the isolated product. Imines from aldehydes are called aldimines, those from ketones are ketimines. 

Mechanism 17.5 presents the mechanism for the reaction between benzaldehyde and methylamine given in the first example. The first two steps lead to the carbinolamine the 

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Reaction with Primary Amines Imines 746 Imines in Bioiogicai Chemistry 749... 

Reaction with primary amines (Section 17 10) Isolated product is an imine (Schiff s base) A carbinolamine inter mediate is formed which undergoes de hydration to an imine... 

Oxoalkyl)phosphonic diesters, through their reactions with primary amines, yield imine derivatives. The reaction between the (oxoalkyl)phosphonate, benzylamine and... 

II. Imine formation reaction with primary amines... 

Reaction of primary amines with aldehydes and ketones (Section 17.10) Imines are formed by nucleophilic addition of a primary amine to the carbonyl group of an aldehyde or a ketone. The key step is formation of a carbinolamine intermediate, which then dehydrates to the imine. 

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

The reductive alkylation of a primary amine with ketone leads to the formation of a stable imine. In the presence of hydrogen and a hydrogenation catalyst, the imine is reduced to a secondary amine. Similarly, a diamine reacts stepwise to form dialkylated secondary amines. However, several side reactions are possible for these reactions as outlined by Greenfield (12). The general scheme depicting the reaction between primary amine or diamine to yield secondary amine through a Schiff base is shown in Figure 17.1. 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

Reaction of A,A-dimcthylsullamoyl aziridines 323 and 325 with primary amines furnishes substituted 1,2,5-thiadiazolidine 1,1-dioxides 324 and 326, respectively, in a regioselective manner <06SL833>. Aziridine 325 is made from ( I /t,6,S ,Z)-bicyclo[4.2. l]non-3-en-9-one in two steps /V,/V-dimethylsulfamoyl imine formation using dimethylsulfamide and subsequent reaction with trimethylsulfoxonium ylide. The product from the reaction with 4-methoxy-benzyl amine can be subsequently manipulated (debenzylation and derivatization) to give the alternative nitrogen substitution pattern in a controlled manner. 

Reaction of the carbaldehyde 242 with primary amines afforded the imines 243 and 244, and with ethyl cyanoacetate, in the presence of piperidine/AcOH, gave the acrylates 245 <2004T11511>. 

In sharp contrast, amination of diphenylacetylene with primary amines induced by dimethyltitanocene596 or the reaction of terminal acetylenes with various primary amines in the presence of [Ru3(CO)i2]597 results in the formation of the corresponding imines ... 

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