Amide, sodium ketones

Aldehyde 20 is reduced by NaBH4 to the alcohol in presence of the amide. Sodium borohydride is one of the weakest hydride donors available. The fact that it can be used in water is evidence of this, as more powerful hydride donors such as LiAlH4 react violently with water. Sodium borohydride does not usually react with carbonyl compounds other than aldehydes and ketones. 

Thermodynamic control. Note that it is also possible for the aldolate adduct to revert to aldehyde and enolate, and equilibration to the thermodynamic product may afford a different diastereomer (the anti aldolate is often the more stable). The tendency for aldolates to undergo the retro aldol addition increases with the acidity of the enolate amides < esters < ketones (the more stable enolates are more likely to fragment), and with the steric bulk of the substituents (bulky substituents tend to destabilize the aldolate and promote fragmentation). On the other hand, a highly chelating metal stabilizes the aldolate and retards fragmentation. The slowest equilibration is with boron aldolates, and increases in the series lithium < sodium < potassium, and (with alkali metal enolates) also increases in the presence of crown ethers. ... 

Sodium hydrogen carbonate a,j -Ethylene-j -halogenocarboxylic acid amides from ketones via immonium salts... 

In order to prepare an acid, a dioxan solution of the diazo ketone is added slowly to a suspension of silver oxide in a dilute solution of sodium thiosulphate Iftheco)iversion to the acid yields unsatisfactory results, it is usually advisable to prepare the ester or amide, which are generally obtained in good yields hydrolysis of the derivative gives the free acid. 

Several triazinyl ketones isomerize to 4-acetamidopyrimidines. TTiis is seen in the C-acylation of 2,4,6-trimethyl-l,3,5-triazine (708) with benzoyl chloride in the presence of sodium amide to give the ketone (709) which undergoes a Dimroth-like rearrangement in boiling water to afford A-(2-methyl-6-phenylpyrimidin-4-yl)acetamide (710) it can be seen that the acylating agent determines the identity of the 6-substituent 64JHC145). 

HALLER - BAUER Ketone Cleavage Cleavage ol ketones, lacking a-hydrogen, with sodium amide. 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

On treatment with a strong base such as sodium hydride or sodium amide, dimethyl sulfoxide yields a proton to form the methylsulfinyl carbanion (dimsyl ion), a strongly basic reagent. Reaction of dimsyl ion with triphenylalkylphosphonium halides provides a convenient route to ylides (see Chapter 11, Section III), and with triphenylmethane the reagent affords a high concentration of triphenylmethyl carbanion. Of immediate interest, however, is the nucleophilic reaction of dimsyl ion with aldehydes, ketones, and particularly esters (//). The reaction of dimsyl ion with nonenolizable ketones and... 

These constitutions have recently received support from the work of A. Haller. If they are correct, then thujone should be capable of yielding trialkyl substitution products, whilst isothujone should not be able to go beyond the dialkyl stage. By alkylation with the assistance of sodium amide, triallylthujone could be prepared, but no higher substitution product than dimethylisothujone could be prepared from isothujone. In the course of his work, Haller prepared the following alkyl derivatives of the two ketones —... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

Ester enolates are somewhat less stable than ketone enolates because of the potential for elimination of alkoxide. The sodium and potassium enolates are rather unstable, but Rathke and co-workers found that the lithium enolates can be generated at -78° C.69 Alkylations of simple esters require a strong base because relatively weak bases such as alkoxides promote condensation reactions (see Section 2.3.1). The successful formation of ester enolates typically involves an amide base, usually LDA or LiHDMS, at low temperature.70 The resulting enolates can be successfully alkylated with alkyl bromides or iodides. HMPA is sometimes added to accelerate the alkylation reaction. 

This is an example of a general reaction by which haloesters are condensed with ketones by means of sodium,2 sodium ethox-ide,3 4 or sodium amide.5 6 1... 

There are several new methodologies based on the Julia olefination reaction. For example, 2-(benzo[t/Jthiazol-2-ylsulfonyl)-j -methoxy-i -methylacetamide 178, prepared in two steps from 2-chloro-iV-methoxy-jV-methylacetamide, reacts with a variety of aldehydes in the presence of sodium hydride to furnish the ajl-unsaturated Weinreb amides 179 <06EJOC2851>. An efficient synthesis of fluorinated olefins 182 features the Julia olefination of aldehydes or ketones with a-fluoro l,3-benzothiazol-2-yl sulfones 181, readily available from l,3-benzothiazol-2-yl sulfones 180 via electrophilic fluorination <06OL1553>. A similar strategy has been applied to the synthesis of a-fluoro acrylates 185 <06OL4457>. 

In contrast to the oxidation of prochiral esters and amides, which induces only moderate ee, sodium enolates of ketones give high stereoselectivity with (+)-147 or (—)-147 as the oxidant (Scheme 4-56 and Table 4-21). The highest stereoselectivity has been observed in the oxidation of the sodium enolate of deoxybenzoin 150, in which benzoin 149 can be obtained in over 95% optical purity. 

Caubere et al. [64, 65] also employed enolates as nucleophiles to intercept the intermediates produced from 32a and the mixture of sodium amide and a sodium enolate. Scheme 6.12 illustrates the results obtained by using the enolates of cyclohexanone and cyclopropyl methyl ketone. The former furnished only the ketone 43 in hexamethylphosphoric triamide as solvent, but almost exclusively the cyclobuta-... 

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