Ketones imine formation with primary

Aldehydes and ketones can react with primary and secondary amines to form Schiff bases, a dehydration reaction yielding an imine (Reaction 45). However, Schiff base formation is a relatively labile, reversible interaction that is readily cleaved in aqueous solution by hydrolysis. The formation of Schiff bases is enhanced at alkaline pH values, but they are still not stable enough to use for crosslinking applications unless they are reduced by reductive amination (see below). 

Reductive amination combines an in situ imine formation with a consecutive reduction. If this reduction is carried out in an asymmetric fashion, chiral amines are accessible in one step from the corresponding ketones (Scheme 32.20, route A). Primary amines are available via the p-methoxy-phenyl (PMP)-group that can be removed with cerium ammonium nitrate (CAN) afterward (route B). 

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. 

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

Reaction of an aldehyde or ketone with a secondary amine, R2NH, rather than a primary amine yields an enamine. The process is identical to imine formation up to the iminium ion stage, but at this point there is no proton on nitrogen that can be lost to form a neutral imine product. Instead, a proton is lost from the neighboring carbon (the a carbon), yielding an enamine (Figure 19.10). 

Imine formation is reversible. Show all the steps involved in the acid-catalyzed reaction of an imine with water (hydrolysis) to yield an aldehyde or ketone plus primary amine. 

Imines are formed by condensation of aldehydes or ketones with primary amines, but they form with more difficulty than enamines.84,85 A special case of enamine preparation was described with 20-oxo-steroids.86 Treatment of these ketones with a primary amine gives a 20-ketimine, which is acetylated with acetic anhydride, with migration of the double bond and formation of 20-(A-acetylalkylamino)-J17(20)-pregnene (14) reduction of 14 with lithium aluminum hydride affords the enamine. 

A. 15.1.2.2 Imines and Enamines. Primary amines react with aldehydes and ketones to form the corresponding A-alkyl- or A-aryl-substituted imines (R— CO—R + R"—NH2 R—C=(NR")—R + H2O). Imine formation is a... 

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. 

On treatment of cyclopropanecarbaldehydes and cyclopropyl ketones with hy-droxylamine, ° methoxyamine, semicar-bazide ° and amines,the corresponding oximes, O-methyl-oximes, semicarbazones, and imines, respectively, were obtained, often in excellent yield. For example, formation of imine 4. Vicinal primary diamines may react with both amino... 

The mechanism for enamine formation is exactly the same as that for imine formation, until the last step of the reaction. When a primary amine reacts with an aldehyde or a ketone, the protonated imine loses a proton from nitrogen in the last step of the reaction, forming a neutral imine. However, when the amine is secondary, the positively charged nitrogen is not bonded to a hydrogen. A stable neutral molecule is obtained by removing a proton from the a-carbon of the compound derived from the carbonyl compound. An enamine is the result. 

Aldehydes and ketones react with primary amines to form imines and with secondary amines to form enamines. The mechanisms are the same, except for the site from which a proton is lost in the last step of the reaction. Imine and enamine formation are reversible imines and enamines are hydrolyzed under acidic conditions back to the carbonyl compound and amine. A pH-rate profile is a plot of the observed rate constant as a function of the pH of the reaction mixture. Hydroxide ion and heat differentiate the Wolff-Kishner reduction from ordinary hydrazone formation. 

Like acetal formation, the reaction of aldehydes and ketones with primary amines— compounds of the type RNH2 and ArNH2—is a two-stage process. Its first stage is nucleophilic addition of the amine to the carbonyl group to give a carbinolamine. The second stage is the dehydration of the carbinolamine to yield the isolated product of the reaction, an A-alkyl or A-aryl-substituted imine. 

Notice that enamines are the nitrogen counterpart of enols (p. 448). Now comes an important question Why doesn t the iminium ion formed from primary amines or ammonia (Fig. 16.49) also lose a proton from carbon to give an enamine Why is imine formation preferred when there is a choice (Fig. 16.55) The answer is extraordinarily simple Just as the ketone tautomer is more stable than the enol, the imine is more stable than the enamine and so is preferred when possible. It is only in cases where imine formation is not possible, as when secondary amines are used, that enamines are formed. We hope you have noticed that the imine- and enamine-forming reactions are reversible. The reactions work best under slightly acidic conditions with heat applied to drive off water. If water is added to an imine or enamine, the reverse reaction occurs to yield the carbonyl compound and an amine. 

An aldehyde or a ketone reacts with a primary amine to form an imine (sometimes called a Schiff base). An imine is a compound with a carbon-nitrogen double bond. The reaction requires a trace amount of acid. Notice that imine formation replaces a C=0 withaC=NR. 

Aldehydes and ketones react with ammonia and primary amines to form imines. Reaction with aldehydes yields aldimines, and ketimines arise in reactions with ketones (Figure 8.28). Imines derived from aliphatic carbonyl compounds are generally unstable and are transformed to more stable products, such as amines, diamines and others. Secondary amines react with aldehydes and ketones with the formation of enamines (Figure 8.29). Imines are similarly flavour-active compounds derived from furan-2-carbaldehyde. For example, the aromas of Ar-furfuryl(isobutylidene)amine, N-(furfuryl)isopentyhdeneamine (8-155) and N-(furfurylidene)isobutylamine (8-156) reportedly resemble chocolate. 

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