Reaction of Aldehydes and Ketones with Nitrogen Nucleophiles

Condensation Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles 

There are two opposing substituent effects on this reaction. Electron-attracting aryl substituents favor the deprotonation but disfavor the elimination step. The observed substituent effects are small, and under some conditions the Hammett plots are 

The mechanistic pattern of hydration and alcohol addition reactions of ketones and aldehydes is followed in reactions of carbonyl compounds with amines and related nitrogen nucleophiles. These reactions involve addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid catalyzed or base catalyzed. The rates of the reactions are determined by the energy and reactivity of the tetrahedral intermediates. With primary amines, C=N bond formation ultimately occurs. These reactions are reversible and the position of the overall equilibrium depends on the nitrogen substiments and the structure of the carbonyl compound. 

Addition, Condensation and Substitution Reactions of Carbonyl Compounds 

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Section 18.6 Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles 751... 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the carbon-oxygen double bond of aldehydes and ketones Strongly basic nucleophiles such as Gngnard reagents however do react with nitriles in a reaction that IS of synthetic value... 

An iron-catalyzed multicomponent reaction of aldehyde 4a, acetophenone, acetyl chloride and acetonitrile, which was used as the solvent, gave P-amino ketones such as 32 (Scheme 8.11) [41]. It was assumed that the sequence starts with an aldol reaction of aldehyde and ketone and then proceeds further with a displacement of a P-acetoxy group by the nucleophilic nitrile-nitrogen. 

Reactions at the carbon-nitrogen double bond of iminium salts are analogous to nucleophilic reactions at the carbonyl group of aldehydes and ketones. This is why free enamines do not react with nucleophilic reagents, whereas their salts can undergo such reactions. 

The condensation of aldehydes or ketones with secondary amines leads to enamines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nucleophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d2-reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

Nucleophilic Reactions of (Silylamino)phosphines. The reactions of (silylamino)phosphines with simple aldehydes and ketones proceed via nucleophilic attack by phosphorus followed by a [1,4] silyl migration from nitrogen to oxygen to yield new N-silylphosphinimines ( 3). With a,B-unsaturated carbonyl compounds, 1,4-addi-... 

Reactions of selenoamides and selenoureas with aldehydes or ketones proceed via a nucleophilic attack of the selenium atom and lead to the formation of selenium- and nitrogen-containing heterocycles.419-424 The reaction of selenourea with 1,3-dicarbonyl compounds in the presence of potassium hydroxide leads to the formation of selenouracil 212 425 its biological activity has also been tested (Scheme 65).426... 

The reaction of selenoamides and selenourea with aldehydes and ketones has been known to take place via the nucleophilic attack of the selenium atom and end up in the formation of a variety of selenium- and nitrogen-containing heterocycles [99]. For example, selenourea was treated with j0-keto ester in the presence of KOH to give selenouracil (Eq. 27) [100], and its biological activity has been tested [100b]. Very recently, Lewis acid mediated addition of primary selenoamides to a, -unsaturated ketones has been reported to give 1,3-selena-zines (Eq. 28) [99 f]. 

Ammonia and amines of the general formula RNH2 are nitrogen analogs of water and alcohols. They are more nucleophilic than water and alcohols and react faster with carbonyl groups of aldehydes and ketones. In these reactions, a nitrogen analog of a hemiacetal, called a hemiaminal, forms. 

There are many important [5 + 1] two-bond formation heterocyclic syntheses and in certain instances this approach constitutes the method of choice for the preparation of particular classes of heterocycle. Where a carbon atom constitutes the one-atom fragment it is almost invariably present in the form of an electrophilic species such as an aldehyde, carboxylic acid, ketone, ester, acid chloride, urea, etc., and fundamentally condensation consists of reaction of this electrophilic species with a 1,5-dinucleophilic reagent. Where the one-atom fragment is either nitrogen, oxygen or sulfur then the heteroatom may function either as a nucleophile or, in the case of nitrogen and sulfur, also as an electrophile. Almost... 

The reaction of primary amines with aldehydes and ketones do not give the products expected from nucleophilic addition alone. This is because of the further reaction taking place once nucleophilic addition occurs, e.g. consider the reaction of acetaldehyde (ethanal) with a primary amine methylamine (Following fig.). The product contains the methylamine skeleton, but there is no alcohol group and there is a double bond between the carbon and the nitrogen. This product is known as imine or a Scbiffbase. 

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