Imine salts hydrolysis

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

Nitriles can be reduced to amines by lithium aluminum hydride. An imine salt is an intermediate product if the reaction is carried out under the proper conditions, this salt is the major product and provides an aldehyde on hydrolysis (see Section 16-4C) ... 

We met enamines as specific enol equivalents in the last chapter and they are particularly good at conjugate addition. The pyrrolidine enamine from cyclohexanone 41 adds to acrylic esters 42 in conjugate fashion and the first-formed product 43 gives the enamine 44 by proton exchange.4 Acid hydrolysis via the imine salt 45 gives the 1,5-dicarbonyl compound 46. 

Nitriles A Grignard or organolithium reagent attacks the electrophilic cyano group to form the salt of an imine. Acidic hydrolysis of the salt (in a separate step) gives the imine, which is further hydrolyzed to a ketone (Section 18-9). 

Stork enamine reaction The reaction of an enamine with an alkyl halide that results in the alkylation of the (P-carbon. Usually followed by hydrolysis of the resultant imine salt to give a carbonyl functionality at the a-carbon. 

Several new syntheses of 2,5-disubstituted oxazoles have been reported. The reaction of allyl zinc bromides with )V-cyanomethylimidates (136) leads to 2-alkyl- or aryl-5-allyloxazoles in 50-65% yields after hydrolysis of intermediate imine salts (137) <91SC1501>. The allyl zinc reagents add to the nitrile, in contrast to organolithium and magnesium reagents, which are too basic (Scheme 62). 

Interaction of 3-chloro-4-fluoroaniline with diethyl ethoxy-methylene malonate yields the corresponding imine salt, which on being thermally cyclized gives rise to the formation of ethyl-7-ehloro-6-fluoro-4-hydroxyquinoline-3-carboxylate. The resulting produet on being subjected to N-alkalation, followed by the nucleophilic displacement of the 7-chloro moiety with N-methylpiperazine, and finally hydrolysis of the ester yields the desired product ofloxacin. 

Diisobutylaluminium hydride (DIBAL-H or DIBAL, BU2AIH) is a very useful derivative of aluminium hydride and is available commercially as a solution in a variety of solvents. At ordinary temperatures, esters and ketones are reduced to alcohols, nitriles give amines and epoxides are cleaved to alcohols. However, it is particularly useful for the preparation of aldehydes. At low temperatures, esters and lactones are reduced directly to aldehydes (or lactols) nitriles and carboxylic amides give imines which are readily converted into the aldehydes by hydrolysis (7.79-7.81). The lack of further reduction of the aldehyde lies in the relative stability of the intermediate hemiacetal (or imine salt), which hydrolyses to the aldehyde only upon work-up. 

Treatment of t-alkyl nitriles with alkali metals gives imine salts which on hydrolysis furnish ketones. The method is well suited to the synthesis of highly hindered symmetric ketones [equation (9)]. ... 

It is well-established, that the addition of the Grignard reagents to nitriles results in a formation of the imine salts which, upon hydrolysis, yield ketones. However, if a good leaving group, for example a halide or a mesyl ester, is present in the molecule, the reaction can proceed via a different route. Namely, an intramolecular Sf,2 reaction takes place providing a cyclic imine. Despite the simplicity and the synthetic potential... 

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

Starting from the benzylidene diimine 24 (Scheme 15) and only one equivalent of TosMlC, the same reaction afforded the imidazole-imine derivative and then, after alkylation, the corresponding salt 25. After hydrolysis, an... 

The tetrachloroferrate or tetralluoroborate salts of alkylated alkyl- or aryl-nitriles (nitrilium ions) are reduced to imines with triethylsilane. Subsequent hydrolysis of the intermediate imines leads to aldehydes in good yields, thus providing an excellent overall route to aldehydes from nitriles (Eq. 338).28,562... 

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