2-Methylpyridine, hydrogenation

Methylpyridine Hydrogen peroxide, iron(II) sulfate, sulfuric acid... 

The standard synthesis method features side-chain chlorination of a methylpyridine (picoline), followed by exchange-fluoriaation with hydrogen fluoride or antimony fluorides (432,433). The fluoriaation of pyridinecarboxyHc acids by sulfur tetrafluoride (434) or molybdenum hexafluoride (435) is of limited value for high volume production operations due to high cost of fluorinating agent. 

In an alternative approach, 2-methylglutaronitrile (8) is hydrogenated and cyclized to give high yields of 3-methylpyridine. The feedstock for this process is produced as a by-product of the production of adiponitrile. Oxidative cyclization of 2-methylglutaronitrile to nicotinonitrile (9) has been described (4). 

Methylpyridine-l-oxide has been prepared by the oxidation of 3-methylpyridine with hydrogen peroxide in glacial acetic acid, with 40% peracetic acid and sodium acetate, and with per benzoic acid in benzene. ... 

Meroquinenine, CgHjjOaN (meroquinene), formed by the oxidation of all four alkaloids and of cinchoninone or quininone and by the hydrolysis of quinenine or cinchenine (p. 489), crystallises from methyl alcohol in needles, m.p. 223-4° (dee.), [ajp -f- 27-5° (H2O). It gives a nitrosoamine, m.p. 67°, and a monoacetyl derivative, m.p. 110°, and can be esterified the ethyl ester hydrochloride has m.p. 165°. When oxidised by chromic acid it yields formic and cincboloiponic acids. On reduction with zinc dust and hydriodic acid, it adds on two atoms of hydrogen forming cincholoipon, CgH jOaN, and when heated with hydrochloric acid at 250-60° gives 3-ethyl-4-methylpyridine ()3-collidine). 

Crabtree, Johnson, and Tebby then showed that the methoxymethylindolizine, originally formulated as (109), on successive treatment with hydrogen iodide and diazomethane gave (110). The methoxymethylindolizine must, therefore, be (111) and a similar compound was obtained from 3-methylpyridine. Attempts to convert corresponding labile (77) and stable adducts (78) into (111) by... 

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. 

Pyridine is added to neutralize small amounts of hydrogen iodide, which is often present in iodotrimethylsilane as a result of hydrolysis by contact with moisture. The amount of by-products, including cyclohexyl iodide, is reduced by the presence of pyridine. Hindered pyridine bases such as 2,6-di-terf-butyl-4-methylpyridine" have also been used for this purpose by the submitters. The pyridine bases do not appear to react with iodotrimethylsilane. 

Methyl methacrylate 4-Methylnitrobenzene 2- Methylpyridine Methylsodium Molybdenum trioxide Naphthalene 2-Naphthol Air, benzoyl peroxide Sulfuric acid, tetranitromethane Hydrogen peroxide, iron(II) sulfate, sulfuric acid 4-Chloronitrobenzene Chlorine trifluoride, interhalogens, metals Chromium trioxide, dinitrogen pentaoxide Antipyrine, camphor, phenol, iron(III) salts, menthol, oxidizing materials, permanganates, urethane... 

Hydrogen peroxide, Iron(II) sulfate, 2-Methylpyridine, Sulfuric acid, 4477 Lead(IV) oxide, Carbon black, Chlorinated paraffin, Manganese(TV) oxide,... 

In nitroamine oxides the nitro group may be reduced preferentially but usually both functions are affected. 5-Ethyl-2-methyl-4-nitropyridine A -oxide is converted quantitatively to 4-amino-5-ethyl-2-methylpyridine by hydrogen over 30% palladium on charcoal in ethanolic solution [737]. The outcome of the hydrogenation of a nitroamine oxide may be influenced by reaction conditions [736]. 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

The electrochemical reduction of oxygen in dimethylformamide generates oxygen radical-anion. This will abstract a hydrogen atom from the methyl group in a methylpyridine, the process finally leading to the pyridinecarboxyUc acid [219],... 

The barrier to methyl rotation in 4-methylpyridine has been measured by means of proton spin lattice relaxation time (74MI20405), and found to be very low, about 0.06 kJ mol-1. This is in line with ab initio calculations using a minimal STO-3G basis set (76JST(32)67), and MINDO/3 MO calculations (79JST(57)209), the second of which also show that the equilibrium position for the methyl group is with one hydrogen atom in the plane of the pyridine ring. 

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... 

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