Pyridine 2-cyano-5-methylpyridine

Treatment of 4-amino-3,5-dicyano-2-methylpyridine (509) with ammonium sulfide at 45°C for 10 h gave only 4-amino-3-cyano-2-methyl-5-thiocarbamoylpyridine (510). Oxidation of this thioam-ide (510) with hydrogen peroxide gave the 3-aminoisothiazolo[4,3-c]pyridine (511) in good yield (Scheme 63) <80BRP2074565>. 

Cyano-6-methylpyridine-4-carboxamide (2 g, 12.4 mmol) was treated with 10% aq KOH (30 mL) and freshly prepared 1 M aq NaOCl solution (11 mL). The clear-yellow solution was healed on a steam-bath to 80 C for 30 min. A small amount of gas evolved. The solution was chilled and extracted with Et20. The Et20 solution, when dried and saturated with anhyd HC1, furnished 2-mcthylpyridine-4,5-diamine dihydrochloride yield 5-10% mp > 250 °C (dec.). The cold aqueous solution was neutralized with HOAcand yielded a copious precipitate oITine-yellow needles which were recrystallized from EtOH or pyridine yield 1.53 g (70%) mp > 250°C. 

In the Taylor synthesis of (III.28) [31], aldehyde (HI.32) was obtained by reaction of2-amino-3-cyano-5-(dimethoxymethyl)pyridine and guanidine, followed by cleavage of the acetal with aqueous formic acid. The pyridine aminonitrile was elaborated in a sequence of high-yield steps from 3-cyano-5-methylpyridine-2-thione. These steps consisted of the following (yields in... 

I. 1 g. 2-cyanomethyl-6-methylpyridine and 1.0 g. 2-methylpyridine-6-aldehyde mixed with gentle warming, and allowed to stand at room temp, for ca. 10 min. until the mass solidifies -> 1.53 g. 2-cyano-l,2-di-(6-methyl-2-pyridyl) ethanol.— The pyridine derivatives act as their own basic catalysts. W. Baker et al., Soc. 1958, 3594. 

Lithium aluminium hydride reduces 3-cyanopyridines to the aminomethyl compounds . It has been seen (p. 258) that lithium aluminium hydride can attack the pyridine nucleus in compounds such as 3,5-dicyano- and 3,5-diethoxycarbonyl pyridine, it is reduced (to the dihydro stage) and the substituents remain intact . In the borohydride reduction of quaternary salts (p. 261) the nucleus is reduced and a 3-cyano group left untouched. Controlled reduction with lithium aluminium hydride and with sodium triethoxyaluminium hydride failed to produce more than a trace of aldehyde from 3-cyano-4-methylpyridine , but the second reagent worked well with nicotino- and isonicotino-nitrile . Nicotinonitrile gives good yields of pyridine-3-aldehyde with lithium triethoxyaluminium hydride . 

---