Nitriles from dimethylhydrazones

Potassium salts of hydrazones are also available by other procedures. Potassium amide has been used to generate potassium salts of monoaryl ketone hydrazones. The reactive intermediate generated in these cases is a dianion. Highly dispersed forms of potassium have also been reported to generate potassium salts from. -dimethylhydrazones at -60 C. The use of K/AI2O3 in metalation of aldehyde hydrazone anions produces m est yields of alkylated products in THF suspension. In hexane suspension, side reactions believed to include nitrile formation lead to lower synthetic yields of hydrazone piquets. 

Quaternary hydrazonium salts (derived from aldehydes) give nitriles when treated with OEt or DBU (p. 488, 1337) as do dimethylhydrazones RCH— NNMe2 when treated with Et2NLi and HMPA. All these are methods of converting aldehyde derivatives to nitriles. For the conversion of aldehydes directly to nitriles, without isolation of intermediates, see 16-21. 

Nitriles. Elimination of dimethylamine from A,(V-dimethylhydrazones of aldehydes occurs on exposure to ClCOOMe. 

Side reactions can occur in formation of hydrazone anions and limit the thermal stability of these anions. Most commonly these side reactions involve addition at the carbonyl carbon or elimination of a dialkylamide anion and nitrile formation. Normant has described both problems and has suggested that nitrile formation also occurs slowly in cases where HMPA has been added to azaallyllithium reagents derived from /V,N-dimethylhydrazones. These problems are exacerbated in the case of aldehyde hydrazones when there is branching at the carbon a or p to the carbonyl carbon. 

Still another powerful method for the regeneration of carbonyl compounds from dialkylhydrazones is copper-catalyzed hydrolysis. The reagents that have been tested for this purpose are 2% aqueous cop-per(II) acetate solution at pH 4, copper(II) chloride in 0.05M phosphate buffer and 75% tetrahydrofu-ran/water, and copper(II) sulfate pentahydrate . Under the conditions of the hydrolysis, no reaction is observed in the absence of the copper(II) ion. Typical yields are 85-100%. Other functional groups like a-dicarbonyl, a-tricarbonyl, acetal and aldehydic formyl groups were not affected by this hydrolysis procedure. Nitrile formation in the case of aldehyde dimethylhydrazones was not a significant side reaction. However, reaction times ranged from 1 to 15 h. The reaction is believed to be nonoxidative in nature rather, the copper is believed to activate the C=N bond and catalyze hydrolysis. The dimethylhydrazine produced during hydrolysis also complexes irreversibly with the copper(II) ion to drive the reaction to completion. 

A secondary amide is obtained by selective oxidation of a tertiary carbon center in adamantane with NaI04 in the presence of iron(III) perchlorate in acetonitrile (eq 18). Dimethylhydra-zones undergo periodate induced hydrolysis, at pH 7, to give carbonyl compounds in high yields (eq 19). However, these conditions are unsuitable for the hydrolysis of dimethylhydrazones derived from aromatic or a,unsaturated aldehydes because mixtures of aldehydes and nitriles are formed. 

Methacrolein dimethylhydrazone adds to acrylic derivatives (ester, nitrile, methyl vinyl ketone) in the absence of solvent, under sonication with pulsed irradiation (Eq. 13).Compounds inaccessible conventionally were prepared in good yields. Direct comparison with thermal conditions is not feasible since the latter were made in solution. From maleic and fumaric esters, the same trans diester forms in 99% yield by sonication for 48 h at 50°C (Eq. 14). The absence of stereospecificity is an argument frequently invoked against a concerted mechanism. With these substrates, relatively long irradiation times are required. 

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