Hydrogenations substituted pyridines

Cyclopropyl methanols when treated with a combination of hydrogen fluoride, pyridine, potassium hydrogen fluoride, and diisopropylamine undergo fluonnation and rearrangement to give excellent yields of homoallylic fluorides Chlorobenzene substituted cyclopropyl methanols at low temperatures leads to ring expansion to give... 

Closely related to the basicity of pyridine is its hydrogen-bonding ability two indices of this property have been measured for a very short series of substituted pyridines and are very well correlated by CT-values. ... 

Shindo studied the hydrogen-bonding ability of a fairly long series of substituted pyridine 1-oxides with methanol in chloroform solution and found that the OH frequency of the hydrogen-bonded OH group in methanol is well correlated with the <7-values. For four compounds, the intensity of the same band is also well correlated. In a similar study the OH frequencies of phenol vary monotonically with the CT-values, but not in a linear fashion. 

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. 

The scope of reactions involving hydrogen peroxide and PTC is large, and some idea of the versatility can be found from Table 4.2. A relatively new combined oxidation/phase transfer catalyst for alkene epoxidation is based on MeRe03 in conjunction with 4-substituted pyridines (e.g. 4-methoxy pyridine), the resulting complex accomplishing both catalytic roles. 

We now turn to substituent-sensitive tautomerism. Johnson and Rumon studied a series of solids derived by cocrystallizing substituted benzoic acids and substituted pyridines (108). Their IR evidence indicated, as expected, that when the benzoic acid is a strong acid and the pyridine a strong base, salts 50a are formed. For a weak acid and a weak base, hydrogen-bonded pairs of neutral molecules,... 

It may have been the dramatic 1964 publication of E.S. Lewis and L. Funderburk that forced the question of hydrogen tunneling in complex solution reactions near room temperature into the consciousness of a larger scientific public, particularly in physical-organic chemistry. This article presented isotope effects for proton abstraction from 2-nitropropane by a series of substituted pyridines, and the values rose sharply as the degree of steric hindrance to the reaction increased (Fig. 1). AU the observed H/D isotope effects, from 9.6 to 24, were larger than expected from the simplest version of the so-called semiclassical theory of isotope effects (Fig. 2). 

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. 

Commercial development of a range of cycloalkene-cobalt homogeneous catalysts has prompted their application in the synthesis of pyridine and 2-substituted pyridines. Thus, bis(cyclopentadienyl)cobalt catalyzes the reaction of acetylene with hydrogen cyanide, acetonitrile or acrylonitrile to yield pyridine, 2-methylpyridine and 2-vinylpyridine respectively (Scheme 4 R = H, Me or CH=CH2) (76S26, 78AG(E)505, 75BEP846350). The high cost of the catalyst has so far limited full commercial realization of this route. Acrylonitrile... 

Fluoro-l-haloalka-l,3-dienes are prepared in a similar manner by treatment of substituted 2,2-(dihalocyclopropyl)methanols with a hydrogen fluoride/pyridine/diisopropylamine/ sodium fluoride system to give compound 2, followed by dehydrohalogenation with potassium /< r/-butoxide.80... 

Moreover, interesting ring-formation reactions to give 7 have also been reported for substituted mclhoxyallenyl(cyclopropyl)methanols using 70% hydrogen fluoride/pyridine in combination with sodium fluoride or potassium hydrogen fluoride.82... 

The procedures discussed for aromatics can readily be adopted for the efficient preparation of fluoro-substituted heteroaromatics.141,143,149 150 Fluorodediazoniations of 2-ainino-, 3-amino-, 4-amino- and 2.6-diamino-substituted pyridines and some of the chloro or bromo derivatives have been carried out in liquid hydrogen fluoride with anhydrous sodium nitrite. About 1.2 equivalents of nitrite are used per amino group, and ammonium hydrogen fluoride has also been added. The corresponding fluoropyridines or their hydrochlorides have been obtained in 49-89% yield.150 For example, the reported synthesis150 is suitable for the preparation of larger quantities of 4-fluoropyridine hydrochloride (54% yield mp 100 C) examples are given by the formation of 5-7.150... 

Substituted 2//-azirines are readily transformed into 2,2-difluoroethylamines160168 by treatment with hydrogen fluoride/pyridine to give the products in moderate yield. Depending on the substituents, a-fluoro ketones are also formed in some cases.160169 Increased yields are obtained under similarly mild conditions with a weakened hydrogen fluoride system from 30% hydrogen fluoride/pyridine plus triethylamine.169... 

Halofluorinations take place, as a rule, regioselectively (Markovnikov addition), the olefinic carbons can be substituted with a variety of substituents ranging from alkyl or aryl groups to different electron-withdrawing functions see for example refs 31 and 178-180. Bromo-fluorination of 4-/m-butyl-l-methylcyclohexene with /V-bromosuccinimide in 70% hydrogen fluoride/pyridine gave two stereoisomers 1 and 2.181... 

Comparison of bromofluorinations of six substituted ethyl cinnamates using A-bromosuccin-imide with hydrogen fluoride/pyridine and hydrogen fluoride/tetrahydrofuran (several molar ratios) also shows a Markovnikov-type regioselectivity. The stereoselectivity depends on several factors 184... 

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