Pyridines cyanopyridine

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). 

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... 

Yield % (reaction time h) [a] Anhydrous H202 in MluOH. [b] Aqueous H202 (30%), [c] Pyridine and 3-cyanopyridine (6 mol% of each). 

A major improvement regarding epoxidation of terminal olefins was achieved upon exchanging pyridine for its less basic analogue 3-cyanopyridine (p Krl pyridine = 5.4 pKa 3-cyanopyridine = 1.9) [105]. This improvement turned out to be general for a number of different terminal olefins, irrespective of the existence of steric hindrance at the a-position of the olefin or the presence of other functional groups in the substrate (Scheme 6.13 and Table 6.9). 

Heterocyclic N-oxides such as pyridine, quinoline, or isoquinoline N-oxides can be converted into a mixture of 2- and some 4-cyanopyridines, 2- or 4-cyanoquino-lines, or 1-cyanoisoquinolines, in 40-70% yield, in a Reissert-Henze reaction, by activation of the N-oxide function by O-acylation [1] or O-alkylation [2, 3] followed by treatment with aqueous alkali metal cyanide in H2O or dioxane. 

In two publications [36, 37] and a subsequent review [38], a closely related alternative procedure for conversion of pyridine-N-oxides into cyanopyridines was reported in 1983. This used a combination of the mild Lewis acid Me2NCOCl and trimethylsilyl cyanide 18 for the cyanation of pyridine N-oxides such as 860, affording, in CH2CI2, via 932 and 933, 2-cyanopyridine 862 in 94% yield and apparently no 4-cyanopyridine 864 [36-38] (Scheme 7.13). With 3-substituted pyridine N-oxides such as methyl nicotinate N-oxide a mixture of 40% methyl 2-cyanonico-tinate and 60% methyl 6-cyanonicotinate is obtained. 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl- and 2 4-dimethyl-dicarbethoxy-pyrrole (V,12-V,13) 2-amino- and 2 4-dimethyl-thiazole (V,1 V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylpyridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanopyridine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi ox3depidine (V,29). 

A convenient and easily accessible way to quantify hydrophobicity is the determination of the octanolAvater partition coefficient (log P) and we have determined the hydrophobicity of 13 selected ruthenium-arene complexes (71). As expected, hydrophobicity increases with an increase of the size of the coordinated arene ring, but decreases significantly when the chloride is replaced by neutral ligands such as pyridine and 4-cyanopyridine. The latter observation is somewhat counter intuitive at first inspection, but correlates with replacement of anionic chloride to yield a dicationic complex. The hydrophobicity... 

The equilibrium between radical-anion and dimer for pyridine and quinoline has been examined in a number of aprotic solvents. Radical-anions of pyridine dimer-ise rapidly in liquid ammonia in tire presence of alkali metal ions [15] In hex-amethylphosphoramide with alkali metal counter ions, the monomer is detectable in an equlibrium concentration [16], The monomeric species can be stabilised by substituents and 2- or 4-cyanopyridines give radical-anions which persist in liquid ammonia while 3-cyanopyridine radical-anion dimerises with a rate constant of 2 x 10 [17], Quinoline radical-anion is stable in hexamelhylphosphoramide [16] but in liquid ammonia it dimerises irreversibly [18]. 

The cobalt-catalyzed synthesis enables 2,2 -dipyridyl to be prepared directly from 2-cyanopyridine and acetylene in a 72% yield with a cyanopy-ridine conversion of 21%. The pyridine benzene ratio in the product is 2.7 1 [Eq.(18)]. 

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... 

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