Enolate anions, nitrile, reaction with

C NMR studies of various heteroaromatic nitriles, including 1/7-1,2,3- and 2/7-1,2,3-triazolyl nitriles, reveal a correlation between a value derived from the chemical shifts, cn and c-cn and the reactivity of nitriles in forming the corresponding enaminoketones via reactions with the enolate anion of acetone. Based on the correlation, a new reactivity index y is proposed <82H(l9)22l>. 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. Table 22.1 lists the approximate pKa values of different types of carbonyl compounds and shows how these values compare to other acidic substances we ve seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions. 

Introduction of a cyano group a to the carbonyl group of a ketone can be accomplished by prior formation of the enolate anion with LDA in THF and addition of this solution to p-TsCN at —78°C. The products are formed in moderate to high yields but the reaction is not applicable to methyl ketones. Treatment of TMSCH2N(Me)C=Nf-Bu with iec-butylhthium and R2C=0, followed by iodo-methane and NaOMe leads to the nitrile, R2CH-CN. ... 

The sodium dianions obtained from acids, treated by NaNH2 in liquid ammonia are easily alkylated (refs. 28-30). These dianions have also been used for Michael addition with benzalacetophenone or ethyl cinnamate. A similar Michael addition (ref. 31) is also observed with the enolate of ethyl phenylacetate (Fig. 4). Nitriles can also be deprotonated with NaNH2 in liquid ammonia. The resulting anion was able to give aldol reaction followed by dehydration (ref. 32) or an alkylation reaction (ref. 33). 

On reaction with Grignard reagents, p-keto nitriles are transformed into enamino ketones." The carbonyl group is protected as the enolate anion. To retain the nitrogen atom, a mild workup is required. 

In an extension of quinoline ring formation by reaction of enolate anions with o-trifluoromethylaniline, the enolate anion was replaced with anion of nitrile (44) to give quinoline (45) (Scheme 19) <94TL(35)7597). 

The synthesis begins with an Sn2 reaction (Chapter 10, Section 10.2) of bromide 141 with potassium cyanide to give 144. Note the use of the aprotic solvent DMF to facilitate the 8 2 reaction. A Grignard reaction of the nitrile with methylmagnesium bromide followed by hydrolysis leads to the requisite ketone (see Chapter 20, Section 20.9.3). The final step simply reacts the methyl ketone with LDA under kinetic control conditions to give the enolate anion (143), which is condensed with the ester (142) to give the diketone target, 140 (Section 22.7.2). 

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