Cyanopyridines reduction

The hydrogenolysis of halopyridines can be convenient when carried out with 15% aqueous TiCl in presence of acetic acid. Aqueous titanium trichloride quantitatively removes cyano group from cyanopyridines. Reductive dehalogenation is also catalysed by Sml -... 

FIGURE 2.30. Redox catalysis induction of Srn1 reactions. Cyclic voltammetry in liquid ammonia + 0.1 M KC1 at —40°C of (a) redox catalyis of the reductive cleavage of 2-chlorobenzonitrile, RX, by 4-cyanopyridine, P. The dotted reversible cyclic voltammogram corresponds to P in the absence of RX. The solid line shows the catalytic increase of the current, (b) Transformation of the voltammogram upon addition of the nucleophile PhS. Adapted from Figure 1 in reference 23, with permisison from the American Chemical Society. 

Fig. 3 Electrochemical and homogeneous standard free energies of activation for self-exchange in the reduction of aromatic hydrocarbons in iV.A -dimethylformamide as a function of their equivalent hard sphere radius, a. 1, Benzonitrile 2, 4-cyanopyridine 3, o-toluonitrile 4, w-toluonitrile 5, p-toluonitrile 6, phthalonitrile 7, terephthalonitrile 8, nitrobenzene 9, w-dinitrobenzene 10, p-dinitrobenzene 11, w-nitrobenzonitrile 12, dibenzofuran 13, dibenzothiophene 14, p-naphthoquinone 15, anthracene 16, perylene 17, naphthalene 18, tra 5-stilbene. Solid lines denote theoretical predictions. (Adapted from Kojima and Bard, 1975.)...

The reduction of 2- and 4-cyanopyridine to the aminomethylpyridine was mentioned in Part I. 3-Aminomethylpyridine has been prepared from 3-cyanopyridine in an electrocatalytic reduction in aqueous hydrochloric acid solution, using an electrode consisting of a thinly deposited layer of palladium black on graphite. The reduction proceeds with electrolytically generated hydrogen not via an electron transfer to the substrate.418... 

Cyanopyridines undergo titanium-mediated reductive cyclopropanation to give pyridylcyclopropylamines in good yield <20030L753>. Both 2- and 3-cyanopyridine react with the titanium species 81 formed from diethylzinc and methyltriisopropyloxytitanium in the presence of lithium isopropoxide to give the cyclopropylamine product in 80% and 82% yield, respectively (Equation 55). 

The reduction of 2- and 4-cyanopyridine (253) exhibits special features (Fig. 10). In acid solution the protonated species is reduced in... 

The more flexible tether embodied in bispyridocarbazoles 321 and 322 was synthesized by Roques and colleagues (779) as shown in Scheme 50. The bischloro tether 319 was prepared from 4-bromopyridine (316) by halogen-metal exchange, condensation with 4-cyanopyridine, and Wolff-Kishner reduction of the resulting ketone 317. Catalytic hydrogenation, chlorination, and then alkylation of 320 with 319 gave the desired bispyridocarbazoles (321, 322). An important discovery in this research is that the methosulfate salts impart excellent water solubility to the bispyridocarbazoles. 

The reduction of cyanopyridines exhibits special features. In acid solution the protonated species is reduced in a four-electron reaction [457 61] to the pyridylmethylamine, but in alkaline medium the carbon-carbon bond is cleaved with formation of pyridine and cyanide ion [447, 462] (Chapter 23). 3-Cyanoquinoline is reduced to the 1,4-dihydro derivative [463] in slightly alkaline solution. 

For the reduction of cyanopyridines to the aminomethylpyridines, a lead cathode in dilute sulfuric acid containing FeS04 has been recommended [460]. 

The reduction of 3-cyanopyridine (20) in ethanol leads mainly to the tetrahydropyridine 22. Reduction in pyridine or diglyme however, produces 1,4-dihydropyridine (21) as the major product. Minor amounts of the 3-pyridylmethylamine 23 are also obtained with ethanol, and the aprotic solvents prevent further ring reduction. 

Dihydropyridines generated from pyridinium salts carrying electron-withdrawing substituents at the 3 position by borohydride reduction are generally resistant to further reduction. The dihydro derivatives of 1-methyl-3-cyanopyridine, 68, 69, and 70, were recovered unchanged when treated with borohydride in water. Only 1,2-dihydro-l-methyl-3-cyano-pyridine (68) was converted to the tetrahydropyridine 71 when trimethyl borate was added to the reaction medium. Diborane/water achieved the same conversion, while added boric acid returned the starting materials. ... 

Helv. Chim. Acta 24- supplemental issue in honor of Gadient Engi, p 26E (1941) by lithium aluminum hydride reduction of ethyl nicotinate Rosenmund- Zymalkowski, Ber, 85, 156 0952) Cohen, U.S, pat, 2,520.037 (1950) Mosher- Tessieri-J. Am. Chem, Soc, 73t 4926 (1951) of methyl nicotinate Bohlmann, Ber. 86, 1423 (1953). From 3 -cyanopyridine Chase, U.S. pat. 2,615,896 (1952 to Hoffmann-La Roche) from 3-aminomethylpyridine Schlapfer. U.S- pat, 2,547,048 (1951 to Hoffmann-La Roche) frnm thionicotinic acid S-methyl ester- Ruzicka, Prelog. UJS. pet. 2,509,171 (1950 to Ciba). 

NaBH4 does not react with pyridine. However, if the pyridine ring contains electron-attracting substituents, reduction with NaBH4 leads to di- and tetrahydropyridines. 3-Cyanopyridine, for instance, yields 120 and 121 ... 

Ruthenium(II) A range of complexes of the type [Ru(L)(NH3)j] + (e.g. L = pyridine, pyridazine, pyrazine, pyrimidine,triazine, 2-cyanopyridine, 3-cyanopyridine, 4-cyan-opyridine, 2-, 3- and 4-RC(0)-substituted pyridines (R = CHMe2, CH2Et, CHjPr, OMe, NH2, OH, H, Ph ), IV-methylpyrazine, 4,4 -bipyridine, l,2-bis(4 -pyridyl)ethylene," hyp-oxanthine, guanine, xanthine,4-dimethylaminopyridine" ) have been prepared by reaction of [RuCl(NH3)j]Cl2 with a Ag" salt (AgOjCCF3 is often used) followed by zinc amalgam reduction... 

Two competing processes have been reported for the photoreaction of 2-cyanopyridine in the presence of methanol and ethanol. The products formed are the ethers 382 by attack on the pyridine ring and the hydroxyalkyl derivatives 383 by reaction at the cyano group h Reductive decyanation occurs on irradiation of the pyrazines 384 in the presence of secondary or tertiary amines. It is likely that a SET process is involved. SET processes are also involved in the reactions of 9-cyanophenanthrene in the presence of amines. Using non-polar solvents affords the diethylaminyl radical exclusively and the products 385 (principal product), 386 and 387 are obtained. In acetonitrile, however, the... 

A new s3rnthesis of coniine has been reported (55). 2-Cyanopyridine with ethyl magnesium bromide gave 2-propionylpyridine which was transformed to coniine by Wolff-Kishner reduction followed by catalytic hydrogenation. Clemmensen reduction of the 2-propionylp5rridine gave... 

Cyanopyridines have been reduced to aminoethylpyridines by a variety of methods, 2- And 4-cyanopyridine are reduced with sodium borohydride to 2-and 4-aminomethylpyridine, respectively. In acidic solutions, the polaro-graphic reduction of 4-cyanopyridine yields 4-aminomethylpyridine. Hydrogenation of 6-chloro-5-cyano-4-methoxymethyl-3-nitro-2-picoline over palladium-charcoal in aqueous hydrochloric acid gives 3-amino-5-aminomethyl-4-methoxymethyl-2-picoline hydrochloride. 3-Amino-5-aminomethyl-2,4-lutidine is prepared in good yield by the catalytic reduction (Pd—C in methanol) of 6-chloro-3-cyano-2,4-dimethyl-3-nitropyri-dine. The hydrogenation of 3-( S-pyridylmethoxy)propionitrile over Raney Nickel yields 3-[(3-aminopropoxy)methyl] pyridine. ... 

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