Hydrogenation, catalytic epoxy-ketones

Pyrazoles were synthesized in the authors laboratory by Le Blanc et al. from the epoxy-ketone as already stated in Sect. 3.1.1a, Scheme 35 [80]. The synthetic strategy employed by Le Blanc et al. [80] was based upon that the strategy published by Bhat et al. [81] who also described the synthesis of pyrazoles but did not report cytotoxic evaluation on the synthesized compounds. Scheme 48 shows the synthesis of the most active compound (178). Dissolution of the epoxide (179) with a xylenes followed by treatment with p-toluenesulfonic acid and hydrazine hydrate produced the pure nitro-pyrazole 180 in good yield (60%). Catalytic hydrogenation with palladium on activated carbon allowed the amino-pyrazole (178) to be obtained in a pure form. This synthesis allowed relatively large numbers of compounds to be produced as the crude product was sufficiently pure. Yield, reaction time, and purification compared to reported approaches were improved [50, 61, and 81]. Cytotoxicity of these pyrazole analogs was disappointing. The planarity of these compounds may account for this, as CA-4, 7 is a twisted molecule. 

Hydrogenation of the a -epoxy ketone shown in Eq. 365) over platinum in ethyl aoet te was found by Reese1441 to leave the epoxide ring intact. Tetrasubstituted ethylene oxides are notoriously unremaivc toward most reagents, and catalytic reduction proves to be unexceptional in this respect. 

The aluminium species is, however, not directly responsible for the epoxidation of ds-cyclo-octene. Its role is more to generate via a radical pathway peroxo-species from the solvents that are then able to epoxidise the substrate (Scheme 18.28). The Schuchardt group investigated further ot,p-unsaturated ketones with this catalytic system and isolated as major products the corresponding ot,p-epoxy-ketones as shown in Scheme 18.29. The proposed mechanism involves a strong interaction via hydrogen bonds... 

Lower valent tungsten halides are a new class of deoxygenation agents, e.g. for the conversion of carbonyl or epoxy compounds into olefins . A new reagent, generated in situ from iron pentacarbonyl and a small amount of base in moist solvents, selectively and efficiently hydrogenates the ethylenic portion of a,/ -unsaturated carbonyl compounds, such as ketones or lactones, under mild conditions. Aliphatic tert. amides can be easily reduced to alcohols by alkali metals in hexa-methylphosphoramide and a protic cosolvent such as tert-butanol. Aldehydes can be obtained from acids by catalytic reduction of intermediate carboxylic alkoxyformic anhydrides . Sec. nitro compds. are converted into ketones by the joint action of a nitrite ester and NaNOg under mild, non-acidic conditions . 

---