Secondary amines ketones

Many impurities are present in commercial caprolactam which pass into the liquid wastes from PCA manufacture from which caprolactam monomer may be recovered. Also, the products of die thermal degradation of PCA, dyes, lubricants, and other PCA fillers may be contained in the regenerated CL. Identification of die contaminants by IR spectroscopy has led to the detection of lower carboxylic acids, secondary amines, ketones, and esters. Aldehydes and hydroperoxides have been identified by polarography and thin-layer chromatography. 

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

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Secondary amines are compounds of the type R2NH They add to aldehydes and ketones to form carbmolammes but their carbmolamme intermediates can dehydrate to a stable product only m the direction that leads to a carbon-carbon double bond... 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Reaction of secondary amines with aldehydes and ketones (Section... 

With secondary alkanolamines, aldehydes in the presence of K CO yield di-tertiary amines, which, on distillation, break down into a,P unsaturated amines and secondary amines. With a mono- or dialkanolamine, an alkaU metal cyanide, and an aldehyde or ketone, aminoacetonitriles are formed. 

CH3)3Si)2N]2U(CH2Si((CH3)2)N(Si(CH3)3)) Generally, uranium metaUacycles are quite reactive inserting a host of organics, ie, CO, secondary amines, nitriles, isonitriles, aldehydes, ketones, and alcohols. 

Hydroxyl Group. The OH group of cyanohydrins is subject to displacement with other electronegative groups. Cyanohydrins react with ammonia to yield amino nitriles. This is a step in the Strecker synthesis of amino acids. A one-step synthesis of a-amino acids involves treatment of cyanohydrins with ammonia and ammonium carbonate under pressure. Thus acetone cyanohydrin, when heated at 160°C with ammonia and ammonium carbonate for 6 h, gives a-aminoisobutyric acid [62-57-7] in 86% yield (7). Primary and secondary amines can also be used to displace the hydroxyl group to obtain A/-substituted and Ai,A/-disubstituted a-amino nitriles. The Strecker synthesis can also be appHed to aromatic ketones. Similarly, hydrazine reacts with two molecules of cyanohydrin to give the disubstituted hydrazine. 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Secondary amines react smoothly with 3-ketones to give enamines and good selectivity is achieved in the presence of 7-, 12-, 17- and 20-ketones. With pyrrolidine the reaction takes place under very mild conditions and no catalyst is usually required. Hydrolysis occurs by simply heating in ethanol. 

Acid hydrolysis of (i-perfluoroalkylvinylamines, prepared from secondary amines and perfluoroalkylacetylenes, yields p-aminovinyl perfluoroalkyl ketones as the major products [79] (equation 20)... 

Enamine (Section 17.11) Product of the reaction of a secondary amine and an aldehyde or a ketone. Enamines are characterized by the general structure... 

Enamines from the Condensation of Aldehydes and Ketones with Secondary Amines. ... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

This innovation was exploited by Stork and his co-workers (6-8) for a study of enamine formation from a variety of ketones and secondary amines. 

The secondary amines used in the preparation of enamines have been primarily simple dialkylamines or cyclic amines of five- or higher-membered rings. Azetidine (4) yields a stable enamine with cyclopentanone (28). No simple enamines formed by condensation of ethylenimine (5) or a substituted ethylenimine with an aldehyde or ketone have been reported. 

If a molecule contains both a ketonic and aldehydic carbonyl group, a secondary amine will react with the aldehydic carbonyl group to give a -enamino ketone (15). This has been shown not only for 2-formylcyclo-hexanone (14) (32,33) but also in steroidal systems when the aldehyde and ketone groups are in five- or six-membered rings (34). 

The intermediacy of an aminal in the formation of enamines from ketones and secondary amines is not usually proposed. The only direct evidence for this is the infrared spectra of the reaction mixtures produced when dimethyl-or diethylamine was allowed to react with cyclohexanone or cyclopentanone... 

The only kinetic data reported are in a Ph.D. thesis (41). Integral order kinetics were usually not obtained for the reaction of a number of ketones with piperidine and a number of secondary amines with cyclohexanone. A few of the combinations studied (cyclopentanone plus piperidine, pyrrolidine, and 4-methylpiperidine, and N-methylpiperazine plus cyclohexanone) gave reactions which were close to first-order in each reactant. Relative rates were based on the time at which a 50% yield of water was evolved. For the cyclohexanone-piperidine system the half-time (txn) for the 3 1 ratio was 124 min and for the 1 3 ratio 121 min. It appears that an... 

Ternary iminium complex salts can be prepared by direct combination of an aldehyde or ketone with a secondary amine complex salt (95). An adaptation of this procedure employing the perchlorate salts of secondary amines provides a simple method for the preparation of the readily crystallized and nonhydroscopic ternary iminium perchlorates (96), Eq. (10). 

They found that a stoichiometric mixture of titanium tetrachloride, secondary amine, and aldehyde or ketone produeed enamines directly and rapidly [Eq. (11)]. 

The reaction of a secondary amine with a ketone or with an open-chain aldehyde gives a mixture of isomers 164 and 165 (R = H, alkyl, or aryl). No consistent policy has been established as to which isomer is considered... 

The initial investigation of the reaction of aldehydes and ketones with complex secondary amine salts was that of Lamchen et al. (11). A few salts had been observed before by Zincke and Wiirker (24), but the reaction was not examined in detail. Lamchen et al. prepared a number of compounds that were presumed to be iminium salts. The amine salts were halostannates, halobismuthates, haloantimonates, and hexahaloplatinates. Among the reported products were N-ethylidenepiperidinium (13) and N-cinnamili-denetetrahydroisoquinolinium (14) salts. 

A recent adaptation of the procedure employing perchlorate and fluoro-borate salts has been reported by Leonard and Paukstelis (J5). This report includes proof of structure by direct comparison to iminium salts prepared by protonation of enamines. The general reaction reported was that of a ketone or aldehyde with a secondary amine perchlorate to give iminium salts. A large structural variety of carbonyl compounds and several amine... 

It has been shown (140) that enamines react as well, if not better, under the conditions of the Leuckart-Wallach reaction to give amines than do ketones in the presence of ammonia, primary amines, or secondary amines. This implies that in the Leuckart-Wallach reaction the pathway may be through the enamine and, of course, the iminium salt. The Leuckart-Wallach reaction has been reviewed (141). Examples of enamines reduced under the conditions of the Leuckart-Wallach reaction are listed in Table 12. 

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