Pyridinecarbaldehydes, reduction

The quaternization of 2-pyridinecarbaldehyde with 2,3,6-trimethoxy-9-phenanthryl-methyl bromide (183) yielded a salt (184) which, when cyclized, afforded a dibenz[/i,/]acridizinium derivative (185). Reduction of the quinolizinium ring of (185) afforded ( )-cryptopleurine (57JA3287). 

The NAD+-dependent alcohol dehydrogenase from horse liver contains one catalytically essential zinc ion at each of its two active sites. An essential feature of the enzymic catalysis appears to involve direct coordination of the enzyme-bound zinc by the carbonyl and hydroxyl groups of the aldehyde and alcohol substrates. Polarization of the carbonyl group by the metal ion should assist nucleophilic attack by hydride ion. A number of studies have confirmed this view. Zinc(II) catalyzes the reduction of l,10-phenanthroline-2-carbaldehyde by lV-propyl-l,4-dihy-dronicotinamide in acetonitrile,526 and provides an interesting model reaction for alcohol dehydrogenase (Scheme 45). The model reaction proceeds by direct hydrogen transfer and is absolutely dependent on the presence of zinc(II). The zinc(II) ion also catalyzes the reduction of 2- and 4-pyridinecarbaldehyde by Et4N BH4-.526 The zinc complex of the 2-aldehyde is reduced at least 7 x 105 times faster than the free aldehyde, whereas the zinc complex of the 4-aldehyde is reduced only 102 times faster than the free aldehyde. A direct interaction of zinc(II) with the carbonyl function is clearly required for marked catalytic effects to be observed. 

Creighton and co-workers have extended a preliminary study on model dehydrogenase reactions. The ZnCl2-catalysed reduction of l,10-phenanthrolme-2-carbox-aldehyde by iV-propyl-l,4-dihydronicotinamide in acetonitrile was investigated, as well as the metal-catalysed borohydride reduction of 2- and 4-pyridinecarbaldehyde. The results support the view that the zinc in alcohol dehydrogenase serves to polarize the carbonyl group of the substrate aldehyde and to facilitate deprotonation of the alcohol. 

Reduction by a hydridoaluminate is generally applicable. For instance, 3-pyridinecarbaldehyde was obtained in 83% yield by the action of sodium triethoxyhydridoaluminate on 3-pyridinecarbonitrile in tetrahydrofuran for... 

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