Reaction of Grignard reagents with nitriles

Kctonescan be prepared by the reaction of Grignard reagents with nitriles. The initial product is a ketimine, which does not react further with the Grignard reagent, thereby preventing formation of the tertiary alcohol. Subsequent hydrolysis gives the ketone (Scheme 10.8). 

Much improved yields of ketones, formed by reaction of Grignard reagents with nitriles 33, have been obtained when reactions were performed in benzene containing 1 Eq of diethyl ether, rather than in diethyl ether alone [51]. Under the modified conditions, it is postulated that reaction occurs through a species in which the nitrile has displaced a diethyl ether solvent molecule from a dimeric Grignard species. 

FIGURE 14.62 Mechanism of reaction of Grignard reagents with nitriles. 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

Reactions of either Grignard or organolithium reagents with most aldehydes, ketones, or esters produce alcohols. Reactions of organolithium reagents with carboxylic acids, or of Grignard reagents with nitriles, produce ketones. 

The final area that can be discussed involves the kinetics and mechanism of reactions of Grignard reagents with ketones, nitriles, Schiff bases, and weak acids. This area is intimately tied to the problem of the structure of the organomagnesium reagent itself and this in turn centers around the values of the equilibrium constants for the processes... 

Reductions in reaction yields by PEG and 18-crown-6 were observed by Yamazaki and coworkers for borohydride reductions of aldehydes and ketones in tetrahydrofuran and for the reaction of Grignard reagents with ketones and nitriles in benzene. The deleterious effect on the borohydride reductions was especially interes- 2 ting because of previous observations of enhancement by crown ethers. Yamazaki and coworkers found 18-crown-6 and PEG to have comparable... 

Contrary to benzo[b]thiophen, benzo[b]selenophen is acylated at position 2. 2-Bromobenzo[b]selenophen, prepared from the 2-lithium derivative and bromine, is acylated at position 3, and from this derivative the 3-isomers could be synthesized. A large number of 2- and 3-aroylbenzo[b]seleno-phens were synthesized, either by Friedel-Crafts reaction of benzo-[bjselenophencarboxylic acid chlorides and benzenes or from benzol bjselenophens and benzoic acid chlorides. Also the reaction between Grignard reagents and nitriles was used for the synthesis of aroylbenzo[b]selenophens. 4,S-Diaminobenzo[b]selenophen has been synthesized via nitration of 5-aminobenzo[b]selenophen or via the reaction of the diazonium salt derived from the S-amino-derivative with p-sulphanilic acid. From the diamino-derivative, several fused benzo[b]selenophens, e.g. (525), (526), and (527), were prepared. Reaction of the phenyl-... 

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