Catalytic Hydrogenation of Substituted Pyridines with PtO 2 Catalyst

The most powerful catalytic hydrogenation was one of the ways to produce a wide array of important compounds in large quantities using inexpensive and clean hydrogen gas without forming any waste. The hydrogenation of nitrogen containing heterocyclic compounds has been investigated by different catalysts such as palladium, nickel, rhodium, ruthenium and platinum. The hydrogenation of substituted pyridines is of particular interest to scientists as the resulting functionalized piperidines are most important intermediates in the synthesis of both natural products and pharmaceuticals. Mono substituted piperidine derivatives were synthesized by the catalytic hydrogenation of the corresponding pyridines with ruthenium dioxide catalyst at high temperatures and larger atmospheric pressures. Further the lower atmospheric pressures favour the catalytic hydrogenation of pyridines with rhodium on carbon catalyst. The catalytic hydrogenation of pyridines with aryl substituent’s leads to the selective reduction of the heterocyclic ring was desired under acidic conditions. The synthesis of pinacol derivative of pyridines has been achieved by the coupling of selective hydrogenated acetyl pyridines with adams catalyst, PtO2. Partial catalytic hydrogenation of catechol, 4-phenyl pyridine, 4-(3-phenyl propyl) pyridine and N,N-alkyl amino pyridines had done with the mild reducing catalyst PtO2. N-substituted pyridinium salts undergo catalytic hydrogenation with PtO2 afforded piperidine derivatives. The unexpected product piperidine hydrochloride was also obtained by the catalytic hydrogenation of nicotinic acid, 3-hydroxy pyridine hydrochloride, 3-pyridyl diphenyl acetate hydro chloride and 2-methoxy pyridine with PtO2. Catalytic Hydrogenation of Substituted Pyridines with PtO2 Catalyst


INTRODUCTION
The most powerful catalytic hydrogenation was one of the ways to produce a wide array of important compounds in large quantities using inexpensive and clean hydrogen gas without forming any waste. The hydrogenation of nitrogen containing heterocyclic compounds has been investigated by different catalysts such as palladium, nickel, rhodium, ruthenium and platinum. The hydrogenation of substituted pyridines is of particular interest to scientists 1-8 as the resulting functionalized piperidines are most important intermediates in the synthesis of both natural products and pharmaceuticals [9][10][11][12] . Mono substituted piperidine derivatives were synthesized by the catalytic hydrogenation of the corresponding pyridines with ruthenium dioxide catalyst at high temperatures and larger atmospheric pressures 13 . Further the lower atmospheric pressures favour the catalytic hydrogenation of pyridines with rhodium on carbon catalyst 14 . The catalytic hydrogenation of pyridines with aryl substituent's leads to the selective reduction of the heterocyclic ring was desired 15,16 under acidic conditions. The synthesis of pinacol derivative of pyridines has been achieved by the coupling of selective hydrogenated acetyl pyridines with adams catalyst, PtO2 17 . Partial catalytic hydrogenation of catechol, 4-phenyl pyridine, 4-(3-phenyl propyl) pyridine and N,N-alkyl amino pyridines had done with the mild reducing catalyst PtO2 [18][19][20] . N-substituted pyridinium salts undergo catalytic hydrogenation with PtO2 afforded piperidine derivatives 21 . The unexpected product piperidine hydrochloride was also obtained by the catalytic hydrogenation of nicotinic acid, 3-hydroxy pyridine hydrochloride, 3-pyridyl diphenyl acetate hydro chloride and 2-methoxy pyridine with PtO2 [22][23][24] .
cis-Piperidine derivatives were also synthesized by the catalytic hydrogenation of certain pyridine derivatives with acidified PtO2 catalyst 25,26 .
Due to the aromatic nature of pyridine nucleus, the hydrogenation of these heterocyclic moieties often requires the elevated temperatures in combination with significant hydrogen pressures and the survey of literature reveals that most of the pyridine derivatives was not satisfactorily reduced with mild reducing catalyst PtO2 at high temperatures. In this paper we reported one methodology to the synthesis of piperidine derivatives from the catalytic hydrogenation of pyridine substrates with mild reducing catalyst PtO2 at room temperatures only. The catalytic hydrogenation of substituted pyridines by the absorption of three moles of clean hydrogen with PtO2 as catalyst under 50 to 70 bar atmospheric pressure in glacial acetic acid at room temperature then afforded piperidine derivatives (Fig. 1

EXPERIMENTAL
All the starting materials and reagent (PtO2) were purchased from Sigma Aldrich and TCI companies. Solvents were purchased from Merck and used without further purification. The Progress of the reactions were monitored by thin layer chromatography (TLC) with ninhydrin charring. 1 H NMR spectra were recorded on Bruker 300 MHz spectrometer with tetra methyl silane was internal standard. All the chemical shift values are reported in δ units. Mass spectra were performed on direct inlet system or LC by MSD trap SL.
General protocol for the catalytic hydrogenation of substituted pyridines with PtO2: Stirred solution of substituted pyridines (1.0 g) in acetic acid (5 mL) was treated with 5 mol % catalytic amount of PtO2 under H2 gas pressure. After 6-10 h, it was quenched with NaHCO3 then it was extracted with ethyl acetate (3 × 20 mL), filtered through celite and dried on Na2SO4. The solvent was evaporated under reduced to gave residue. Further the purification of residue was done by column chromatography (Silica gel, 60-120 mesh, 5 % EtOAc in pet. ether) to furnish the substituted piperidine derivatives. All the synthesized compounds are colourless liquids.

RESULTS AND DISCUSSION
To optimize the reaction conditions, we had investigated the catalytic hydrogenation of substituted pyridine derivatives with platinum oxide in different solvents like tetrahydrofuran, methanol and ethanol, but this hydrogenation was not preceded. After a small quantity of acetic acid was added to the reaction mixture to enhance the activity of catalyst. At this condition the progress of reaction appears to a small extent, but not significantly. Further the significant progress of the reaction would achieved in better yields with glacial acetic acid was used as a protic solvent. Here the optimized results were given in Table-1.

Conclusion
In conclusion, the catalytic hydrogenation of pyridine derivatives with PtO2 catalyst still remains challenging methodology. The decreasing poisonous character of pyridine derivatives and enhancing the catalytic activity towards PtO2 catalyst then the selection of glacial acetic acid was suitable protic solvent. Further our research work should be concentrated on the catalytic hydrogenation of indoles and pyrroles by the mild reducing catalyst PtO2.