2-Hydroxy-6-chloropyridine, reaction

Due to the abundance of halopyridines, Suzuki reactions in which they serve as electrophiles have been used to synthesize a plethora of arylpyridines and heteroarylpyridines [39, 40]. 6-Phenyl-2-nitro-3-methylpyridine (55) was obtained via the reaction of 6-bromo-2-nitro-3-methylpyridine (54) and phenylboronic acid [39]. Not surprisingly, 3-chloropyridine was virtually inert under such conditions in contrast to 2-chloro- and 4-chloropyridine. The Suzuki coupling of 2-hydroxy-6-bromopyridine failed as well, possibly because 2-hydoxypyridines exist almost entirely in the keto form. 

Arnoldi et al.2S0 have described a reaction in which a dichlorocarbene reacts with 2-chloropyridine by first complexing at the nitrogen atom, thereby increasing the ability of a hydroxy group to displace the chlorine in position 2. 

Aminomethylfurans are converted into 3-hydroxypyridines by acid and an oxidizing agent, e.g. (219) —+ (220). 2-Hydroxymethylfurans with chlorine in aqueous methanol give 3-hydroxy-4-pyrones. 3-Hydroxypyridines can conveniently be prepared by reaction of 2-acylfurans with ammonia (Scheme 75). Pyrrole and dichlorocarbene give some 3-chloropyridine (Section 3.3.1.7.1). 

Pyrithione (zinc salt of) is used as a component of antidandruff shampoos and as a bactericide in soap and detergent formulations. This compound (2-mercaptopyridine N-oxide) exists in equilibrium with N-hydroxy-2-pyridinethione and is a fungicide and bactericide, prepared by reaction of 2-chloropyridine N-oxide with sodium hydrosulfide and sodium sulfide. This compound is also known as Omadine, Its formula is shown below. 

When the blocking group is other than a halogen atom or a keto group, only tars are formed. 8-Hydroxy- 1,7-naphthyridine61 is obtained from 3-amino-2-hydroxypyridine, and 1,5-naphthyridine is obtained from the 2-halo-3-aminopyridines when they are subjected to the Skraup reaction. 3-Aminopyridine 1-oxide aifords the parent 1,5-naphthyridine,62 and both 3-amino-6-hydroxypyridine and 3-amino-6-chloropyridine give 2-hydroxy-l,5-naphthyridine.63 Hart64 has applied the Skraup synthesis to 3-amino-4-hydroxypyridine and has obtained the expected 4-hydroxy-l,5-naphthyridine. 

Syntheses. The structure (LXXXI) of ricinine has been confirmed by several sjmtheses. The anhydride of 2,3-dicarboxy-4-chloropyridine, obtained by the oxidation of 4-chloroquinoline, is converted by means of ammonia to the monoamide (LXXXII). This is converted by the Hofmann reaction to the amine (LXXXIH) from which the hydroxy compound (LXXXIV) is obtained by diazotization. The action of phosphorusi oxychloride and phosphorus pentachloride on the hydroxy compound... 

Hydroxypyridine has been converted into 3-chloropyridine by reaction with phosphorus pentachloride in a sealed tubeS30 and 3-hydroxy-2,6-dinitropyridine also reacts with phosphorus pentachloride , but there can be no doubt that, in general, 2- and 4-hydroxypyridines are more reactive than 3-hydroxypyridines (see below). 2- and 4-Hydroxypyridine i 28, 44i, 83i give good yields of 2- and 4-chloropyridine. 

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