Pyridine, hydrogenation, side reactions

Several side reactions have also been observed, and, for the present purpose, all reactions leading to products other than 2,2 -bipyridines will be considered under this heading. Some of these undoubtedly involve hydrogen derived from the catalyst, but no attempt will be made adequately to review the field of reactions involving pyridines, metal catalysts, and hydrogen. 

Reductive alkylation by alcohol solvents may occur as an unwanted side reaction 22,39), and it is to avoid this reaction that Freifelder (20) recom mends ruthenium instead of nickel in pyridine hydrogenation. Alkylation by alcohols may occur with surprising ease 67). Reduction of 18 in ethanol over 10% palladium-on carbon to an amino acid, followed bycyclization with /V,/V-dicyclohexylcarbodiimide gave a mixture of 19 and 20 wiih the major product being the /V-ethyl derivative 49,50). By carrying out the reduction in acetic acid, 20 was obtained as the sole cyclized product 40). 

The pyridine nucleotide dehydrogenase reactions fall into two large groups those which transfer hydrogen from or to the A (or pro R) side of the 4 position of the nicotinamide ring, and those which use the B (or pro S) side 1.64,65),... 

More convenient for the formation of aryl fluorides 4 is the decomposition of triazenes with hydrogen fluoride/pyridine (70 30 w/w) mixture, easier to handle than pure hydrogen fluoride. In this case, decomposition is performed at a lower temperature (18-50°C) and acetic acid, for example, is a suitable solvent.299 However, radical side reactions can be more pronounced, especially with bromo-, iodo-, nitro- or 2-methoxy-subslituted substrates. 

Secondary chlorides of propane and butane can be made without side reactions from isopropyl alcohol and s-butyl alcohol by treatment with HCl and ZnCl, in the cold however, treatment of the next higher homolpg 3-pentanol under the same conditions gives a mixture of chloropentanes. The 2- and 3-chloropentanes are best obtained by the SOClj-pyridine procedure. The corresponding bromo derivatives have been obtained using hydrogen bromide at a low temperature however, care must be taken to avoid isomerization. 

None of the catalysts tested quaternary ammonium salts, N,N-dimethylamino pyridine (DMAP), 1-methyl imidazole, tertiary amines, Michler s ketone, quinoline etc. performed as well as pyridine. For the preparation of 1-fluoroalkyl carbonate, the best catalytic system found was the KF/18-crown-6 complex. To avoid side reactions, only aldehydes without hydrogen at C-2 should be used in this case. 

The temperatures necessary for successful conversion of many pyridines under high pressure conditions with most catalysts (except ruthenium) also favor side reactions. Indeed, in the hydrogenation of pyridine with copper chromite at 220° and 100-150 atm (6) only 50% of piperidine was obtained along with an equal amount of a high boiling condensation product. Reduction, therefore, under more moderate conditions is desirable. 

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

Self condensation of products of reduction or interaction between resultant piperidines and starting materials or intermediates in the course of hydrogenation may take place under moderate conditions, but are favored under more forceful conditions. Adkins (20) points out that conditions necessary for successful conversion of many pyridines with nickel catalysts also favor side reactions (1), (2), and (3). They are noted with other catalysts where temperature and pressure conditions are high. 

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