Ketones with derivatives of ammonia

TABLE 17.4 Reaction of Aldehydes and Ketones with Derivatives of Ammonia RCR + H2NZ... 

Table 16.2 summarizes the reactions of aldehydes and ketones with derivatives of ammonia. 

TABLE 16.2 REACTIONS OF ALDEHYDES AND KETONES WITH DERIVATIVES OF AMMONIA... 

Aldehydes and ketones can be differentiated from noncarbonyl compounds through their reactions with derivatives of ammonia (Section 16.8B). 2,4-Dinitrophenylhydrazine and hydroxylamine react with aldehydes and ketones to form precipitates. Oximes are usually colorless, whereas 2,4-dinitrophenylhydrazones are usually orange. The melting points of these derivatives can also be used in identifying specific aldehydes and ketones. 

In the Fischer synthesis, indoles are prepared from a ketone 40 and a phenylhydrazine derivative 41 (Eq. 15.4.3). The two-step-reaction, starting with a condensation towards a phenylhydrazone 42 and followed by an acid-catalyzed cyclisation with elimination of ammonia, is usually combined in a one-pot procedure (72). 

Aldehydes and ketones are characterized through the addition tortliVcafbony 1 group of nucleophilic reagents, especially derivatives of ammonia (Sec. 19.14). An aldehyde or ketone will, for example, react with 2,4-dinitrophenylhydrazine to form an insoluble yellow or red solid. 

C.iii. Reaction with Nitriles. Nitriles are carboxylic acid derivatives and react with Grignard reagents (also sec, 8.2.C).l Initial attack generates an intermediate iminium salt that can be hydrolyzed (with loss of ammonia) to the corresponding ketone. HO The best yields are obtained with aryl nitriles, and this is illustrated... 

A -Arylhydrazones, derived from enolizable aldehydes or ketones 30, are converted into indoles 31 under Lewis (ZnCl2, BF3) or Bronsted acid (H2SO4, polyphosphoric acid, CH3COOH, HCl in ethanol) catalysis with loss of ammonia Fischer synthesis, E. Fischer 1883) ... 

Table 16.4 lists several other derivatives of ammonia and hydrazine that react with aldehydes and ketones to give imines. 

A class of nitrogen containing compounds that was omitted from the section just dis cussed includes mines and their derivatives Immes are formed by the reaction of aide hydes and ketones with ammonia Immes can be reduced to primary amines by catalytic hydrogenation... 

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

In Robinson s now well-known suggestions, regarding the processes by which alkaloids may be produced in plants, two main reactions are used j the aldol condensation and the similar condensation of carbinol-amines, resulting from the combination of an aldehyde or ketone with ammonia or an amine, and containing the group. C(OH). N., with substances in which the group, CH. CO. is present. By these reactions it is possible to form the alkaloid skeleton, and the further necessary changes postulated include oxidations or reductions and elimination of water for the formation of an aromatic nucleus or of an ethylene derivative. 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis,Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition metals have also been used. Microwave irradiation has been used to facilitate this reaction. Aniline derivatives react with a-diazoketones, in the presence of a... 

Intermolecular N-C-C transfragment replacement occurs less widely than the N-C-N replacement. A synthesis of alkyl(aryl)pyrimidines has been published that was based on the replacement of the N-C-C fragment of the pyrimidine ring by an identical sequence of atoms derived from a ketone in the presence of ammonia [94H(38)249]. Heating a solution of 3-methyl-5-nitropyrimidin-4(3//)-one (120) in acetonitrile with cyclohexanone and ammonia gas in a sealed tube at 100°C for 3 hours gave tetrahy-... 

Pyridine and its derivatives are technically-important fine chemicals. Their isolation from coal tar is decreasing, whereas their manufacture by synthetic methods has increased rapidly. The classical pathways to pyridine have been discussed by Abramovitch (74HC14-1-4). Many of them rely on the reaction of aldehydes or ketones with ammonia in the vapor phase. However, the condensation processes used suffer from unsatisfactory selectivity. Using soluble organocobalt catalysts of the type [YCoL] allows pyridine and a wide range of 2-substituted derivatives to be prepared selectively and in one step from acetylene and the appropriate cyano compound [Eq.(l)]. 

Our own group is also involved in the development of domino multicomponent reactions for the synthesis of heterocycles of both pharmacologic and synthetic interest [156]. In particular, we recently reported a totally regioselective and metal-free Michael addition-initiated three-component substrate directed route to polysubstituted pyridines from 1,3-dicarbonyls. Thus, the direct condensation of 1,3-diketones, (3-ketoesters, or p-ketoamides with a,p-unsaturated aldehydes or ketones with a synthetic equivalent of ammonia, under heterogeneous catalysis by 4 A molecular sieves, provided the desired heterocycles after in situ oxidation (Scheme 56) [157]. A mechanistic study demonstrated that the first step of the sequence was a molecular sieves-promoted Michael addition between the 1,3-dicarbonyl and the cx,p-unsaturated carbonyl compound. The corresponding 1,5-dicarbonyl adduct then reacts with the ammonia source leading to a DHP derivative, which is spontaneously converted to the aromatized product. 

In contrast to laboratory scale operations, four-bond formation processes are of considerable importance as industrial routes to pyridine derivatives and have been investigated in Considerable detail. Vapour phase condensation of aldehydes and ketones with ammonia and amines in the presence of a variety of silica/alumina catalysts containing different promoters (e.g. cobalt(II) chloride) can give excellent yields of substituted pyridines (e.g. equation 151), and the nature of the products formed can be largely controlled by change in the stoichiometry of the reactants and variation of experimental conditions (equation 152). 

Problem 15.28 Write the formula for the solid derivative formed when an aldehyde or ketone reacts with each of the following ammonia derivatives ... 

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