2-Phenoxypyridines

Zhu, Z., Cameron, B.R. and Skerlj, R.T. (2003) Cycloauration of substituted 2-phenoxypyridine derivatives and X-ray crystal structure of gold, dichloro[2-[[5-[(cyclopentylamino)carbonyl]-2-pyridinyl- N]oxy]phenyl- C]-, (SP-4-3)-. Journal of Organometallic Chemistry, 677, 57. 

Treatment of 2-bromo-6-phenoxypyridine with potassium amide in liquid ammonia gave a mixture of three isomeric compounds which were identified as 2-amino-6-phenoxypyridine (28%), 4-amino-2-phenoxypyridine (9%), and 2-methyl-4-phenoxypyrimidine (50%). 

Pyridones react similarly, but without elimination of the heteroatom bridge. Adducts 313 were obtained in modest yield from A-methyl-2-pyridones 31216 and other iV-alkyl derivatives 1 11. With 312 (Ri = H), however, the major products resulted from benzyne attack at oxygen (i.e. 2-phenoxypyridines) although some 313 (Ri = H) was formed and, in a few instances, A-phenylation also occurred in low yield 16. ... 

Chloro-, 2-ethoxy-, and 2-phenoxypyridine-l-oxides (XII-435) do not rearrange but form 1 -hydroxy-2-pyridones after hydrolysis. However, 2-chloro-4-methylpyridine-1-oxide (XII-436, R = 4-CH3) and 2-chloro-6-methylpyridine-l-oxide (Xn-436, R 6-CH3) give the corresponding acetoxymethyl-2-chloropyri-dines. ... 

Amines and amides as enhancers (chlorphenera-mine, diphenhydramine, 3-phenoxypyridine, nicotine, alkyl n,n-dialkyl amino acetate)... 

For example, A-phenyl-4-pyridinamine is formed in 89% yield when 4-phenoxypyridine is heated with an excess of aniline hydrochloride for 3 h at 180°.1104... 

Since the amide moiety could be totally replaced by aryl or hetaryl ethers and also directly substituted by pyrazol, several new combinations became possible, which led to the discovery of the phenoxypyridine ethers (Section 4.1.4.4). 

Phytoene Desaturase Inhibitors j 197 Table 4.1.2 Structural evolution of phenoxypyridine ethers since 1994. 

Various compounds benzothieno(furano)pyridines [145], 4-cyclopentadienyl-pyridines [146], 4-phenoxypyridines [147], 4-acetylenepyridines [148], furano[2,3-b]pyridines [149], 4-aminopyridines [150], bistetrafluoro-4,4 -pyridine [151] and others practically important pyridines [152-155] were obtained by the reaction of nucleophilic substitution. 

As expected, 4-aryloxy groups in pyridine oxides can be replaced by amines . 4-Alkoxy709 and 4-aryloxy-groups706 in quaternary pyridinium salts are readily replaced. In contrast to 4-phenoxypyridine, 4-phenoxy-pyridine hydrochloride does not react with arylamine hydrochlorides, presumably because of the lowering of the nucleophilic power of the amine... 

Pyridine-carboxylic acids have been prepared by the reaction of the 3-pyridyl Grignard reagent 36a and of 2- and 3-pyridyl lithium with carbon dioxide. Nicotinic acid isotopically labelled in the carboxyl group has been obtained in this way . The reaction is especially useful for preparing pyridine-acetic acids and has been applied to 2-2t t and 4-picolyl lithium i. Under conditions where phenyl lithium adds to the azomethine linkage of 4-picoline, 2-phenylpyridine-4-acetic acid i is produced. 2,6-Lutidine gave 6-methylpyridine-2-acetic acid, but the reaction failed with 2-methyl-6-phenoxypyridine . ... 

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