Pyridine ring selective reduction

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

The selective reduction of the D-ring olefin in 106 using a partially poisoned catalyst (Pd/C, 0.25 % pyridine) provided intermediate 107 (83 %), which was epimerized at -78 °C with sodium methoxide (HOAc quench at -78 °C, 89 %) (Scheme 10.9). Deoxygenation by means of tosyl hydrazone 108 and subsequent treatment with catechol borane and tetrabutylammonium acetate gave pentacyclic... 

Free radical attack at the pyridine ring is noted for its low selectivity and substituents have little effect. Arylation takes place at all three positions, but halogen atoms preferentially attack the a-, and alkyl radicals the a- and y-positions. Metals such as sodium and zinc transfer a single electron to pyridine to form anion radicals. These can dimerize by reaction at the a- or y-position to yield dipyridyls by loss of hydride ion. Thus, reduction of pyridine by chemical and catalytic means is easier than reduction of benzene. 

The well-established antiarrhythmic agent disopyramide (57-1) comprises the starting material for a cycUzed version of that drug that is somewhat more potent-than the parent. Catalytic hydrogenation of (57-1) in the presence of an acid results in the selective reduction of the pyridine ring to give the corresponding piperidine. 

The selective reduction of functional groups in the pyridine series over ring hydrogenation is probably due to the effect of the nitrogen atom. It is conceivable that this selectivity could be changed, particularly... 

A comparison of the effect of the 3-benzoyl group and the reported ineffectiveness of the 3-acetyl group, of equally strong electron withdrawing power, on selective reduction of the pyridine ring of pyridine quaternary compounds causes speculation. It would be of interest to determine whether the effect is steric by comparison with a pyridine quaternary salt containing the 3-COC(CH3)3 group. 

Before discussing the reduction of the ring in the presence of other heterocycles it might be of interest to mention the selective reduction of one pyridine ring in the presence of another. McCarthy and his associates (141) hydrogenated a-phenyl-a-(2-pyridyl)-2-pyridine-methanol and obtained a 75% yield of a-phenyl-a-(2-pyridyl)-2-piperi-dinemethanol. 

Selective hydrogenation of quinolines and isoquinolines. Catalytic hydrogenation of quinolines and isoquinolines usually occurs preferentially in the pyridine ring. However, if the hydrogenation is conducted in trifluoroacetic acid, the reverse situation obtains and the benzene ring is reduced more rapidly. The same result can be obtained with mineral acids, but such hydrogenations are much slower. Both 2- and 4-phenylpyiidine can also be reduced preferentially in the benzene ring. Platinum oxide or palladium or rhodium catalysts can be used. Further reduction of 5,6,7,8-tetrahydroquinolines with sodium and ethanol provides a convenient route to rrans-decahydroquinolines. 

Reduction of isoquinoline is carried out by catalytic hydrogenation, by hydride reagents or by metals. Catalytic hydrogenation is controlled by the acidity of the reaction medium selective reduction of the pyridine ring to the 1,2,3,4-tetrahydro compound 26 occurs in CH3CO2H, whereas in coned HCl, the benzene moiety is selectively reduced to afford the 5,6,7,8-tetrahydro compound 25. Further hydrogenation leads to the decahydroisoquinoline 27 (cis/trans mixture) ... 

Selective reduction of either the pyridine or the benzene rings in quinolines and isoquinoline can be achieved the heterocyclic ring is reduced to the tetrahydro level by sodium cyanoborohydride in acid solution,by sodium borohydride in the presence of nickel(II) chloride, by zinc borohydride," or, traditionally, by room temperature and room pressure catalytic hydrogenation in methanol. However, in strong acid solution it is the benzene ring which is selectively saturated " longer reaction times can then lead to decahydro-derivatives. 

Synthesis of anti-malarial reagent enpiroline (17) involved the formation of the pyridine skeleton 206 via the Krdhnke reaction of aroyl acrylic acid 204, acyl pyridinium salt 205, and ammonia acetate. Condensation of the carboxyl group in 206 with 2-lithiopyridine afforded the diaryl ketone 207. The relative higher basicity of the terminal pyridinyl ring allowed selective reduction of this ring via hydrogenation in the presence of an acid and simultaneously reduction of the ketone to the alcohol. The desired isomer was then obtained by fractional crystallization to afford 17. ... 

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