3-Pentanones, enamines

Scheme 33 illustrates the difference in reactivity between triazolines obtained from cyclohexanone and cyclo-pentanone enamines. Thus, the reactions of azidophosphonates 239 with cyclohexanone enamines produce unstable aminotriazolines 240 that cannot be isolated due to their spontaneous elimination of amines to provide triazoles 241. Contrary to that, triazolines 242, derived from cyclopentanone enamines, are isolated in good yield (76-88%) and cannot be converted to the corresponding triazoles even by thermolysis <1995H(40)543>. Probably, introduction of a double bond between two five-membered rings would involve too much molecular strain. 

Mimk and Kim (60) have reported the preparation of the enamines of several acyclic ketones by refluxing the ketone with the amine for 66 hr to 76 days. For example the morpholine enamine of 2-pentanone was found to consist only of 121. 

Problem 17.11 Use enamines in the following conversions (a) cyclohexanone to (i) 2-allylcyclohexanone and (ii) 2-acetylcyclohexanone, and (f>) 3-pentanone to 2-methyl-l-phenyl-3-pentanone. <... 

Cyclic ketones react faster than the aliphatic ketones in the order cyclo-pentanone > cyclohexanone > higher-membered cyclic ketones. a-Substi-tuted ketones give the less substituted enamines, which in turn could be alkylated to put a substituent on this position of the ketone [51] (Eq. 11). 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

Alkaloids 164a and 164b have been prepared accordingly from 2 and the pyrrolidine enamines of 2-pentanone and 2-heptanone <1998CPB332>, and a series of 2-arylquinoline and 2-arylquinol-4-one alkaloids have been prepared from 2 and its 6-methoxy derivative with suitably designed enamines <1999CPB1038>. 

Condensation between the Schiffbase of furfural and the ethylene acetal of 5-nitro-2-pentanone in HO Ac gave (452) after deacetalization. The morpholine enamine of (452) rapidly cyclized under the reaction conditions, and hydrolysis of the enamine group gave (453). 

Aldehydes and ketones react with primary amines to give imines. The imin-ium salt intermediate 80 immediately precedes the imine product, and it has an acidic proton that is lost from the nitrogen to form the imine. When a secondary amine (HNR2) reacts with an aldehyde or a ketone, rather than a primary amine, the course of the reaction is identical until the iminium salt intermediate is formed. In a typical experiment, 3-pentanone (69) reacts with the secondary amine diethylamine (Et2NH) and an acid catalyst however, the isolated product is not an imine with a C=N unit, but rather a mixture of compounds that have an amine group attached to a C=C unit. Such products are enamines, and 83 is formed in 86% yield along with 14% of 84. Note that enamine 83 is an E-isomer and 84 is a Z-isomer. 

For the Michael addition between 3-pentanone and nitrostyrene a report by Patil and Sunoj points out a key limitation of the standard enamine derived transition state model when a polar protic reaction medium is employed (Scheme 17.10) [42]. The unassisted transition state inclusive of continuum solvent effects failed to predict the correct stereochemical outcome of the reaction as compared to the experimental observations. The predicted lowest energy transition state has been identified as leading to an incorrect configuration of the newly formed chiral centers as well as the wrong diastereomer. Further refinements to the transition state models were carried out with inclusion of explicit solvent molecules in view of the fact that the reaction being modeled has been conducted in methanol as the solvent. After examining several microsolvated transition states with varying... 

Now let s draw the forward scheme. Ethylene oxide is treated with methyl magnesium bromide, followed by water work-up to give 1-propanol. This alcohol is then oxidized to an aldehyde with PCC, and the resulting aldehyde is then treated with ethyl magnesium bromide, followed by water work-up, to give 3-pentanol. Oxidation with chromic acid gives 3-pentanone, which is then converted to the corresponding enamine upon treatment with dimethylamine and acid catalysis (with removal of water) ... 

Now let s draw the forward scheme. Dehydration of the amide with thionyl chloride produces a nitrile. Subsequent reaction with ethyl magnesium bromide, followed by aqueous acidic work-up, yields 3-pentanone, which can be converted to the desired enamine via an acid-catalyzed reaction with dimethylamine, as shown. 

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