Pyridine catalytic hydrogenation

The low yields of 6,6 -disubstituted-2,2 -bipyridincs recorded in Table I are probably the result of steric retardation of the adsorption of 2-substituted pyridines. This view is supported by the observation that 2-methylpyridine is a much weaker poison for catalytic hydrogenations than pyridine. On the other hand, the quinolines so far examined (Table II) are more reactive but with these compounds the steric effect of the fused benzene ring could be partly compensated by the additional stabilization of the adsorbed species, since the loss of resonance energy accompanying the localization of one 71-electron would be smaller in a quinoline than in a pyridine derivative. 

Piperidine is obtained commercially by the catalytic hydrogenation of pyridine over a nickel catalyst at about 200 C. A-Substituted derivatives are formed by reduction of the corresponding pyridinium salts. 

Catalytic hydrogenation of pyridine 2-isoxazolones gives, surprisingly, a mixture of [l,8]naphthyridine and [l,8]tet-rahydronaphthyridine, the exact ratio depending upon the solvent used to perform the hydrogenation (Scheme 25) <2003T9887>. 

Pipendine. the hydrogenation product of pyridine, is used as an intermediate for drugs and for making rubber-vulcanization accelerators, e.g., piperidinium pentamechylenedithiocarbamate (also known as Accelerator 552 ). On a commercial scale, piperidine (hexahydropyridine) is prepared by the catalytic hydrogenation of pyridine, e.g., with nickel catalysts at from 68 to 136 atmospheres pressure and at l50-20C,c,C. or under milder conditions with noble-metal catalysts. Pyridine derivatives can be similarly reduced to substitute piperidines. See formulas below. 

Application of Spectrophotometry to the Study of Catalytic Systems H. P. LeftinandM. C, Hobson,Jr. Hydrogenation of Pyridines and Quinolines Morris Freifelder Modern Methods in Surface Kinetics Flash, Desorption, Field Emission Microscopy, and Ultrahigh Vacuum Techniques Gert Ehrlich... 

Oxidative reactions of pyridines are commercially more interesting than reductive ones because catalytic hydrogenation of pyridines is a generally useful method, whereas catalytic oxidation is not. In contrast, anodic oxidation of pyridines is widely applicable and can replace methods that use expensive oxidants such as permanganate salts or chromic oxide. Consider, as an example, oxidation of a methylpyridine to produce 1 kg of the pyr-idinecarboxylic acid this process would consume about 3 worth of potassium permanganate at 100% efficiency and would produce 0.7 kg of byproduct Mn02 for disposal or recycle. The same anodic reaction would consume only 0.30 of electrical power (for oxidation) and would not produce a significant amount of material for disposal. 

Piperidine-type metacyclophane alkaloids have four chiral carbon atoms C-3, C-5, C-9, and C-ll. With 96 in hand, Fujita et al. hydrogenated its pyridine ring over Adams catalyst and Raney nickel in order to define the relative stereochemistry of C-5 and C-9. They obtained a single crystalline hexahydro derivative in quantitative yield. Catalytic hydrogenation of substituted pyridines generally results in cis products. Therefore, one can assume the cis relationship of C-5 and C-9 hydrogens in the foregoing... 

The pyridine co-catalyst performs three important functions. Firstly, it accelerates the catalytic turnover, secondly, it prevents decomposition of the epoxide product and finally, in sufficient concentration, the pyridine increases the lifetime of the catalyst. Table 3.3 illustrates some of the substrates which have been epoxidized using the MTO/hydrogen peroxide/pyridine system. 

Catalytic hydrogenation may be used in the preparation of 3-piperideines only exceptionally, e.g., in the case of some 4-substituted pyridines as the starting compounds, since usually the catalytic hydrogenation of pyridine, its homologs, derivatives, and quaternary salts leads to the hexahydro compounds. 1-Methyl-4-methoxycarbon-yl-3-piperideine hydrohalide (110), however, was obtained by hydrogenation of methyl isonicotinatemethiodide109, 110ormethobromide110 over platinum dioxide in methanol. 

The main side reactions occurring during the catalytic hydrogenation of pyridines consist of the following ... 

Piperidine is a colourless liquid, miscible with water, and of an unpleasant smell with a bp of 106°C. It has properties typical of a secondary amine and is a stronger base (pKa = 11.2) than pyridine pKa = 5.2). It is produced commerically by catalytic hydrogenation of pyridine. 

The hydrogenation of pyridine to piperidine is difficult to perform both catalytically and electrochemically. However a study of the electrolytic reduction of pyridine at a Raney Ni cathode at atmospheric pressure resulted in near theoretical rates and good yields (90%), ... 

Heterocyclic Compounds. - The largest electrochemical reduction in this category is the production of piperidine from pyridine by Robinson Brothers. The 120 tonne p.a. produced by this method is supplementary to the bulk of the production which is produced by catalytic hydrogenation of pyridine. The electrochemically produced piperidine is believed to contain fewer by-products and can be produced from pyridine which contains sulphur. 

The metal-free highly enantioselective catalytic hydrogenation of pyridines, especially 2,6-disubstituted pyridines, which are inert to hydrogenation, has been achieved with H2 in toluene by using catalysts generated in situ by hydroboration of alkenes with HB(C6F5)2 a broad range of piperidines has been formed in 44-99% yields with 90 10 0 to 99 1 cis trans ratio. 0... 

---