Pyridines 2-methoxy-, bromination

The 4-pyridones behave similarly, with the neutral tautomer reacting below pH 6 and the anion at higher pH. The observation that 4-methoxy-pyridine shows little comparative reactivity over the whole range is evidence that the hydroxy tautomer is not involved in the bromination process. Again, once the first bromine has entered the ring, further bromination occurs more readily because of easier anion formation (83CJC2556). 

A useful method of synthesis of 5-bromo- and 5,8-dibromo-3-methoxy-2-phenylimidazo[ 1,2-a]pyridines has involved quenching the lithium derivatives with bromine (83S987). 

The bromine group in 4-bromo-5-methoxy-2-trifluoromethyl-l,10-phenanthroline has been replaced by lithium with w-butyllithium and the lithio derivative reacted with pyridine 2-aldehyde.215... 

Halogen atoms in pyrones and pyridones e.g. 902) are unreactive toward SAE nucleophilic displacement. 3-Halopyridines are less reactive than the a- and 7-isomers but distinctly more reactive than unactivated phenyl halides. Thus, a bromine atom in the 3-position of pyridine or quinoline can be replaced by methoxy (NaOMe-MeOH, 150°C), amino (NH3-H20-CuS04, 160°C) or cyano (CuCN, 165°C). 5-Halogens in pyrimidines are also relatively unreactive. 

Another substitution reaction that is initiated by photochemical hydrogen abstraction is the replacement of the bromine atom in 2-bromo-8-methoxy-l, 4-naphthoquinone by an acyl group757. Irradiation of a solution in benzene of the quinone, butyraldehyde or capraldehyde and pyridine yields mixtures of acylated quinone and acylated hydro-quinone. In the first step, the excited quinone abstracts the aldehyde hydrogen atom and this is followed by bond formation between the acyl radical and C-2 of the quinone. The radical that is formed after departure of a bromine atom may either lose a hydrogen atom and yield acylated quinone or take up a hydrogen atom and become acylated hydro-quinone. 

On treatment of both quinoline and pyridine /V-oxides with bromine and thallium(iil) acetate, y-bromo-derivatives are formed pyridine JV-oxides are the less reactive substrates/ The reaction of 8-methoxyquinoline iV-oxide with acetic anhydride and methanol yields 84% of 2,8-dimethoxyquinoline. Similarly, the reaction of the 6-methoxy-iV-oxide and ethanol and acetic anhydride gives 2-ethoxy-6-methoxyquinoline, but, under the same conditions, the 7-methoxy-N-oxide is unchanged/ The Reissert compounds (149) derived from substituted quinolines, on treatment with thallium(lll) nitrate and trimethyl orthoformate, undergo either smooth ring-contraction or oxidative debenzoyl-ation, depending on the substitution pattern in the aromatic ring (Scheme 61)/ ... 

Selective bromination of 2-methoxy-6-methylpyridine afforded 5-bromo-2-methoxy-6-methylpyridine <94SC(24)1367). Subsequent deprotonation of the pyridine derivative in the benzilic position, or lithium-bromine exchange, allowed regioselective introduction of various electrophiles. 

Preparation by bromination of 2-hydroxy-4,6-di-methoxy-acetophenone (Xanthoxylin) in chloroform containing 6% of pyridine (96%) [2892]. 

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