Isobutyraldehyde Hydrazon

The coupling of enamines with aromatic diazonium salts has been used for the syntheses of monoarylhydrazones of a-diketones (370,488-492) and a-ketoaldehydes (488,493). Cleavage of the initial enamine double bond and formation of the phenylhydrazone of acetone and acetophenone has been reported with the enamines of isobutyraldehyde and 2-phenylpropionalde-hyde. Rearrangement of the initial coupling product to the hydrazone tautomer is not possible in these examples. 

Crooks and Robinson have used this method to prepare 2,3-dimethyl-5-azaindole in 14.5% yield from isobutyraldehyde 4-pyridylhydrazone, obtaining none of the expected 3,3-dimethyl-5-azaindolenine. The ethyl methyl ketone hydrazone gave the same azaindole in 51.5% yield. These authors also suggest that the 3,3-dimethyl-7-azaindolenine reported by Kelly and Parrick is in fact the rearranged product 2,3-dimethyl-7-azaindole. There is no evidence to date to support either structure. 

Table I, examination of which provides ample support for the generality of the process. It is noteworthy that increased branching at the carbon a to the imine function leads to decreased yields of the desired adducts (12) the reason for this failure has not been addressed, but reversion by retroaldolization is one likely possibility. The base that was typically employed to effect the deprotonation of the intermediate aldimines was lithium diisopropylamide, since alkyllithiums were found to add to the carbon-nitrogen double bond of the aldimines. Wittig observed in a number of instances that the overall yields of a,3-un-saturated carbonyl compounds obtained according to this procedure were better than by the corresponding classical Wittig reaction. Interestingly, the anion derived from the r-butylimine of isobutyraldehyde reacts with selected a,3-unsaturated ketones to give 1,4-adducts, whereas the corresponding hydrazone anions add to such ketones to provide the 1,2-adducts. ...

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