3-Cyanopyridine-2 -ones

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). 

A number of routes are available for the synthesis of 2,2 -bipyridines where one of the pyridine rings is built up from simpler entities. For example, condensation of 2-(aminomethyl)pyridine (31) with acetaldehyde or acetylene over a silicon-alumina catalyst at 450°C gives 2,2 -bipyridine, ° whereas 2-cyanopyridine reacts with acetylene at 120°C in the presence of a cobalt catalyst to afford 2,2 -bipyridine in 95% yield.2-Acetylpyridine with acrolein and ammonia gives 2,2 -bipyridine in the presence of dehydrating and dehydrogenating catalysts, and related condensations afford substituted 2,2 -bipyridines. ° In a similar vein, condensation of benzaldehyde with 2 mol of 2-acetylpyridine in the presence of ammonia at 250°C affords 2,6-di(2-pyridyl)-4-phenylpyridine, ° and related syntheses of substituted 2,2 6, 2"-terpyridines have been described. Likewise, formaldehyde with two moles of ethyl picolinoylacetate and ammonia, followed by oxidation of the product and hydrolysis and decarboxylation, affords a good... 

Like 2,2 - and 2,3 -bipyridines, 2,4 -bipyridine is formed by a number of reactions where one of the pyridine rings is built up from simpler components. Thus 4-(aminomethyl)pyridine with acetylene or acetaldehyde at 450"C affords 2,4 -bipyridine and 4-cyanopyridine reacts with acetylene at 120 C under pressure in the presence of a cobalt catalyst to give 2,4 -bipyridine in over 90% yield. 4-Acetylpyridine with acrolein and ammonia in the presence of dehydrating and dehydrogenating catalysts also gives 2,4 -bipyridine. A number of minor routes to 2,4 -bipyridine are worthy of... 

Note the key role of the 2-cyanopyridine ion in promoting the course of the subsequent fragmentation. Proximity effects in 2-substituted pyridines are often instrumental in dictating the nature of decomposition on electron impact, for example in 2-dimethylaminopyridine (68TL3689,73CS(3)139,74JOC285) and in other amino, chloro, and -one derivatives (68JHC647). 

In most of the reactions studied, the appearance of biphasic kinetics showed that the full oxidation process is achieved through the stepwise oxidation of one of the metal centers, rendering a mixed-valence species which is further oxidized to the final product. The question arises in Eq. (35) as to the alternative first oxidation of iron or ruthenium. The stoichiometry of the first oxidation step with bridging 4- and 3-cyanopyridines (with the N-atom of py binding to... 

Condensation of 2-chloro-3-cyanopyridines 6 (X = Cl) with hydrazines yields 3-aminopyrazolo[3,4-fe]pyridines 7. The majority of workers9-15 report 1 -H derivatives but 1-substituted compounds have also been prepared.9,16 17 In one instance9 a hydrazinopyridine (6 R2 = H, R3 = CN,... 

Cyanopyridine (pAfa 1.45) yields a trace of tetramethyl 9-cyano-9a77-quinolizine-l,2,3,4-tetracarboxylate (cf. 5) with DMAD the only product isolable from the 4-cyano isomer was the trimethyl 7-cyanoin-dolizine-l,2,3-tricarboxylate (cf. 35), whereas 2-methoxypyridine yielded 9 and ll.238 Cyclization in one direction to give 8 followed by a [1,5] sigmatropic shift, and pericyclic ring opening would lead to 9. The alternative cyclization to 10, followed by ionization and recombination, or a [1,5] shift, gives a second product 11, which has also been obtained from the quinolizinium salt 12. 

Among these methods, Thorpe isomerization of substituted 2-alkylthio-3-cyanopyridines is of considerable interest. The advantages of this approach are that the starting 3-cyanopyridine-2(l //)-thiones (7) are readily accessible, diverse 3-cyanopyridine-2(l //)-thiones can be used, one-pot procedures can be employed, and the final products are prepared in high yields. The mechanism of this transformation can be represented by the Scheme (1985MI1, 1989MI2) ... 

Examples of the synthesis of thieno[2,3-Z>]pyridines according to method C are scarce. In this case, the synthesis of the starting 3-cyanopyridine-2(l //)-thione, its -alkylation, and cyclization of an intermediate occur as a multicomponent one-pot process. For example, the reaction of thioamides 28 with l-(4-morpho-lino)cyclohexene (29) in anhydrous ethanol followed by treatment with a twofold excess of KOH and then with a-bromo ketones produced thienoquinolines 30 (1997KGS1384). 

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