4-Cyanopyridines

P-Cyanopyridine. Mix 25 g. of powdered nicotinamide with 30g. of phosphoric oxide in a 150 ml. distilling flask by shaking. Immerse the flask in an oil bath and arrange for distillation under a pressure of about 30 mm. Raise the temperature of the oil bath rapidly to 300°, then remove the oil bath and continue the heating with a free flame as long as a distillate is obtained. The nitrile crystallises on cooling to a snow-white solid. Redistil the solid at atmospheric pressure practically all of it passes over at 201° and crystallises completely on cooling. The yield of p-cyanopyridine, m.p. 49°, is 20 g. 

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

Vinylpyridine (23) came into prominence around 1950 as a component of latex. Butadiene and styrene monomers were used with (23) to make a terpolymer that bonded fabric cords to the mbber matrix of automobile tires (25). More recendy, the abiUty of (23) to act as a Michael acceptor has been exploited in a synthesis of 4-dimethylaminopyridine (DMAP) (24) (26). The sequence consists of a Michael addition of (23) to 4-cyanopyridine (15), replacement of the 4-cyano substituent by dimethylamine (taking advantage of the activation of the cyano group by quatemization of the pyridine ring), and base-cataly2ed dequatemization (retro Michael addition). 4-r)imethyl aminopyri dine is one of the most effective acylation catalysts known (27). 

Cyanopyridines are usually manufactured from the corresponding picoline by catalytic, vapor-phase ammoxidation (eq. 7) in a fixed- or fluid-bed reactor (28). 3-Cyanopyridine (25) is the most important nitrile, as it undergoes partial or complete hydrolysis under basic conditions to give niacinamide... 

Hydrogenation of 3-cyanopyridine (25) in the presence of ammonia gives 3-pico1ylamine [3731 -52-0] (29) however, hydrogenation in the presence of hydrogen chloride affords the corresponding 3-carbinol (30) (31). 

Pyridinecarbonitriles, -carboxamides, and -carboxylic Acids. 3-Cyanopyridine (25) is used for the production of niaciu (27), or vitamin 4-Cyanopyridine (15) is used for making the antitubercular dmg isonia2id (31) (101). 

Cyanopyridine [100-54-9] M 104.1, m 50 , pK 1.38. Crystd to constant melting point from o-xylene/hexane. 

The Reissert-Henze reaction offers a method to prepare cyanopyridines and extends the Reissert and Kaufmann reactions in the quinoline and isoquinoline series. 

The cyano group in 2-chloro-4-cyanopyridine does, however, appear to... 

The pyridine-N-oxide 245 was converted into the cyanopyridine 246 and its isomer (Scheme 80). Grignard reaction, Fischer s indole synthesis, and N-protection gave a pyridinyl indole 247. Selenium dioxide selectively oxidized the methyl group to give the isonicotinic acid. The synthesis of Flavocarpine (244) was finally accomplished by a set of standard reactions as outlined in Scheme 80 (87TL5259). 

Tetraazaphthalocyanines are cyclization products of pyridine-2,3-dicarboni-triles,296-457 pyridine-2,3-dicarboxylic acid,459 or 2-cyanopyridine-3-carboxamide.295... 

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