New Insight into the Azaenamine Behaviour of N-Arylhydrazones: First Aldol and Improved Mannich Reactions with Unactivated Aldehydes

Abstract

N-Arylhydrazones can be added to various aldehydes in amine solvents to form new Mannich and aldol products. A wide range of hydrazones and aldehydes formally reported as unreactive can now be coupled to give adducts easily converted into azoalkenes. These transformations parallel the aldolisation/crotonisation processes allowing access to novel heterocycles and the design of new multi-component reactions.

Keywords

hydrazones - Mannich bases - azo compounds - cycloadditions

References

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14

Baldwin et al. observed an easy retro-aldolisation process from an azoaldol adduct similar to 5 (see ref. [9] ).

15

These α-ketohydrazones are very easily prepared by diazonium coupling with β-ketoesters followed by decarboxylation (Japp-Klingemann reaction).

16

Hydrogenation of an α-ketohydrazone-formaldehyde adduct has been performed diastereoselectively to form 1-phenyl-2-amino-propandiol-1,3 (see ref. [7] ).

18

Typical experimental procedure for the Mannich process in diethylamine: To a solution of hydrazone 1g (1 mmol) in diethylamine (1 mL) was added benzaldehyde (2 mmol) and the mixture refluxed until completion. Evaporation of the solvent afforded the crude product which was directly treated with 1-dodecanthiol in chlorobenzene (4 h, reflux) to form the new thioether 7 in 56% isolated yield.
Typical experimental procedure for the aldol reaction: To a solution of hydrazone 1g (1 mmol) in diisopropylamine (1 mL) was added benzaldehyde (2 mmol) and the mixture refluxed until completion. Evaporation and separation on silica gel afforded the expected aldol adduct 6a in 70% isolated yield.