Amines, preparation from ketones

Originally, a C-20 amine (prepared from a bisnorcholanic acid) was converted into its 7V-chloro derivative, dehydrohalogenated to the imine, converted into the A-acetylenanime, reacted with perbenzoic acid, then hydrolyzed to the 17a-hydroxy-20-ketone ... 

Amines, preparation from isothiocyanates, 18, 5 from ketones, 17, 76 m-Aminobenzaldehyde, 13, 28... 

Treatment of the azepinone ring with TMS tiiflate followed by amination affords piperazine 83 (Scheme 16, Section 2.1.1.5 (2005JMC1705)). Likewise, benzothiazepines 374 can be prepared from ketones 373 with N-alkylpiperazines and N-methylhomopiperazine in the presence of trimethylsilyl tiiflate (Scheme 76, Section 5.1.1 (2002JMC344, 2004JMC143)). 

Platinum oxide (0.2 g) is suspended in water (10 ml) and reduced by hydrogen, then the ketone (0.3 mole), ammonium chloride (20 g, 0.37 mole), saturated methanolic ammonia solution (225 ml), and aqueous ammonia (25 ml) are added, and the mixture is hydrogenated at 1-3 atm. The following are among the amines prepared from the corresponding ketones, in the yields stated, by this method 4-methyl-2-pentanamine (57-65%), 4-heptanamine (40 to 60%), 2,4-dimethyl-3-pentanamine (55%), and (x-methylbenzylamine (69%).1002... 

Methylenation. 2-(Phenylthio)ethanols (2), prepared from ketones (1) and phenylthiomethylhthium, undergo reductive /3-ehmination to give 1-alkenes when treated with the black reagent prepared from TiCU and L1A1H4 in the presence of a tertiary amine [ 1,8-bis(dimethylamino)naphthalene or tri-n-butyl-amine]. Benzene-dioxane is used as solvent for the elimination (4 hr. reflux). ... 

Enamines are an important class of uncharged synthetic intermediates that exhibit carbanion-like reactivity. They are typically prepared from ketones with one or more a-hydrogens and a secondary amine under acid catalysis ... 

In the present case, only one amide is formed, because benzophenone is a symmetrical ketone. Because the oximes are prepared from ketones, the reaction was often used, before the advent of modern spectroscopic techniques, to determine the structure of the starting ketone. This structure determination was accomplished by the subsequent identification of the acid and amine obtained upon hydrolysis of the amide product of the rearrangement. 

A general one-step method for preparation of primary and secondary nitroparaffins from amines by oxidation with y -chloroperbenzoic acid in 1,2-dichloroethane has been reported (68). This method is particularly useful for laboratory quantities of a wide variety of nitroparaffins because a large number of amines are readily available from ketones by oxime reduction and because the reaction is highly specific for nitroparaffins. 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

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

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. 

A reagent more reactive than tris(dimethylamino)arsine employed by Weingarten and White 39) was tetrakis(dimethylamino)titanium (145). With this compound it was possible to prepare N,N-dimethyl(l-isopropyl-2-methylpropcnyl)amine (147) from diisopropyl ketone. Weingarten and White 39) have suggested a possible mechanism for this reaction (see p. 88). If benzaldehyde 39,111), formaldehyde 111), or acetaldehyde 39) is used, the corresponding gem diamine or aminal (143) is formed. 

Methyl vinyl ketone 2 tends to polymerize, especially in the presence of a strong base the yield of annulation product is therefore often low. A methyl vinyl ketone precursor, e.g. 6, is often employed, from which the Michael acceptor 2 is generated in situ, upon treatment with a base. The quaternary ammonium salt 6 can be obtained by reaction of the tertiary amine 5, which in turn is prepared from acetone, formaldehyde and diethylamine in a Mannich reaction. 

Draw the following molecule as a line-bond structure, and show how it can be prepared from a ketone and an amine. 

Primary amines can be prepared from alkyl halides by the use of hexamethylenetetramine followed by cleavage of the resulting salt with ethanolic HCl. The method, called the Delepine reaction, is most successful for active halides such as allylic and benzylic halides and a-halo ketones, and for primary... 

This is the most common method for the preparation of enamines and usually takes place when an aldehyde or ketone containing an a hydrogen is treated with a secondary amine. The water is usually removed azeotropically or with a drying agent, but molecular sieves can also be used. Stable primary enamines have also been prepared.Enamino-ketones have been prepared from diketones and secondary amines using microwave irradiation on silica gel. ° Secondary amine perchlorates react with aldehydes and ketones to give iminium salts (2, p. 1178). Tertiary amines can only give salts (12). 

Primary amines have been prepared from many aldehydes with at least five carbons and from many ketones by treatment with ammonia and a reducing agent. 

For the preparation of enamines or imines from ketones, see Section 356 (Amine-Alkene). 0 1. CFsSOsSiMes, MeCN S... 

D. S. Treybig and R. G. Martinez. Compositions prepared from hydrocarbyl substituted nitrogen-containing aromatic heterocyclic compounds, an aldehyde and/or ketone and an amine. Patent US 4871848, 1989. 

One of the potentially most useful aspects of the imine anions is that they can be prepared from enantiomerically pure amines. When imines derived from chiral amines are alkylated, the new carbon-carbon bond is formed with a bias for one of the two possible stereochemical configurations. Hydrolysis of the imine then leads to enantiomerically enriched ketone. Table 1.4 lists some examples that have been reported.118... 

Titanium enolates can be prepared from lithium enolates by reaction withatrialkoxy-titanium(IV)chloride,suchasfra-(isopropoxy)titaniumchloride.21 Titanium enolates are usually prepared directly from ketones by reaction with TiCl4 and a tertiary amine.22 Under these conditions, the Z-enolate is formed and the aldol adducts have syn stereochemistry. The addition step proceeds through a cyclic TS assembled around titanium. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

The addition-elimination reaction of hetero-atom-substituted nitroalkenes provides functionalized derivatives of unsaturated nitro compounds.26 Nitroenamines are generally prepared from a-nitro ketones and amines (see Chapter 5 regarding acylation of nitro compounds).26... 

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