Alkylpyridines reduction

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

The reductive cleavage of the C—O bond in 2- and 4-substituted hydroxy-methylpyridines was mentioned in Part I. The optically active l-(4-pyridyl)-alkanols are reduced in good yield to the optically inactive alkylpyridine, whereas the 2-substituted derivatives were reduced in lower yield to the optically active alkylpyridine (and some tetrahydropyridine derivatives).384,385 The difference in behavior was explained by orientation of the adsorbed pro-tonated pyridine, allowing contact between the electrode and the 2-substituent, but not the 4-substituent. This model was used in later work however, not excluded was the possibility that the higher stability of the p-quinonoid dihydropyridine intermediate, compared to the o-quinonoid dihydropyridine, played a role in the relative ease of reduction of the 4- and 2-substi-tuted pyridines. 

Ferles et al. have studied the reduction of alkylpyridines and reported the yields of piperidines and 3-piperideines. For instance, reduction of either 2-picoline (15) or 3-picoline (16) gave predominantly the respective piperidines it also gave significant amounts of the piperideines 17 and 18, respectively (Scheme 5) (Table I).3i Other isomeric piperideines were not formed, and the... 

Very little work has been done on reduction of hydroxyalkylpyridines, although the approach can be an excellent way to make alkylpyridines from the carbinols. Work done points up once again how variable the products of a given transformation can be with seemingly small changes in experimental conditions. 

Reduction of optically active pyridylcarbinols showed interesting behavior. The 2-isomer (39) retained chirality in the product alkylpyridine, whereas the 4-isomer (40) did not (Table V) (Scheme 13).59 A mechanism was proposed previous to this work to account for the retention of chirality in 39.60... 

The larger part of the work on ketones concerns the reduction of the isomeric acetylpyridines (48). The products were the carbinols (49) and pina-cols (50) (Scheme 17) there are no reports of alkylpyridine products, as were seen in carbinol reductions (see Section II,D). In acidic media, reduction of 2-(48) gave almost exclusively 2-(49) and little dimer.69 What dimer was formed was mostly meso and the proportion of it increased as pH increased. 

The procedure can also be applied in the case of substrates 87 and 88 bearing different chains. This is the case for the synthesis of the asymmetrical bis-pyridinium macrocycle, a precursor of haliclamine A [50]. As illustrated in Fig. (34), the 3-alkylpyridine derivatives 93 and 94, obtained by the commercially available thiophene 92, lead to the dimeric macrocycle via the Zincke procedure, which affords obtaining haliclamine A (49) by reduction. 

Several routes to substituted heterocyclic systems have been devised that feature the reactions of unsaturated imine anions formed by reduction of the corresponding aromatic nitrogen heterocycles (Schemes 11 and 12). Dehydration of the intermediate adducts gives the alkyl-substituted aromatic heterocycles. These procedures provide useful entries to 3-alkylpyridines (25 15-77% overall yields) and 4-alkylisoquinolines (26 25-65% overall yields). ... 

Finally, pyridine derivatives can be reduced by metals. Piperidine is obtained from pyridine with sodium in alcohols Ladenburg reaction) piperidines, as well as tetrahydropyridines, are obtained from 4-alkylpyridines. A -Alkylpyridinium ions are converted into 7V-alkylpiperidines by metals such as Zn or Sn in an acidic medium, or by electrochemical reduction (122 - 125, see p 293). 

Reductions—Gases of the reduction of pyridine nuclei in which side chains are also saturated have been mentioned. It is possible, however, to saturate the double bonds of alkylpyridines without modifying the nucleus. For this purpose have been used hydriodic acid a also widi phosphorus , sodium amalgam , Raney alloy and alkali , and various forms of catalytic hydrogenation . Benzyl alcoholic potash can evidently reduce stilbazoles (p. 336). 

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