Effect of Substitutes on Hydrogenation

There are disadvantages in carrying out the hydrogenation of pyridines as salts. When the corresponding piperidine bases are desired, isolation of some of them in good yield is difficult because of their extreme water solubility. The isolation of pure piperidinecarboxylic and piperidine-alkanoic acids after reduction as hydrochloride salts is troublesome and often extremely difficult. The reduction of the corresponding pyridine acids now no longer requires the presence of an acid. This will be discussed in a subsequent section. 

Steric effects also play a part in the hydrogenation of the pyridine ring. 

Adkins and co-workers (3) first commented on the favorable effect of substituents in 2- and 6- positions. 2,3-Dicarbethoxypyridine was hydrogenated at a lower temperature and in a shorter reaction period than 3-carbethoxypyridine in the presence of either Raney nickel or nickel on kieselguhr. This suggests physical shielding by a group or groups adjacent to the nitrogen atom. The fact that 2-methylpyridine 

This effect, however, is discounted by Smith (34) who suggests that initial hydrogen pressure, amount of catalyst and type of solvent may have had some influence on reaction time. In some other work by Adkins (35) there was little significant difference between the reduction of 2- and 3-methylpyridines. Similarly, hydrogenation in the presence of a nickel silica gel catalyst shows more rapid conversion for pyridine (5 hr) than for 2-methylpyridine (7 hr) (36) 

On the other hand, comparative reductions of pyridine and 2-methylpyridine in the presence of ruthenium dioxide8 (2% ratio of catalyst to compound) show that the 2-substituted compound is reduced more readily. Indeed, with a lower catalyst ratio the difference is more significant. With a 0.1% ratio of ruthenium dioxide catalyst 2-picoline was completely converted to 2-methylpiperidine in 20 min at 200° and 70 atm pressure. The hydrogenation of pyridine under similar conditions took 90 min. Unpublished work from the same laboratory (37) on the reduction of 2-picoline at room temperature and 2 atm pressure in the presence of a 20% weight ratio of 5% rhodium on alumina shows complete hydrogen uptake in 4 hr as against 6 hr for analytical reagent redistilled pyridine under the same conditions. 

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