Bromination of pyridine

Bromopyridine has been made by direct bromination of pyridine - from N-methyl-2-pyridone with phosphorus penta-bromide and phosphorus oxybromide from 2-aminopyridine by diazotization with amyl nitrite in 20% hydrobromic acid from sodium 2-pyridinediazotate by solution in concentrated hydrobromic acid and from 2-aminopyridinc by diazotization in the presence of bromine and concentrated hydrobromic acidd The method described here is essentially that of Craig. 

Bromination of pyridine is much easier than chlorination. Vapour phase bromination over pumice or charcoal has been studied extensively (B-67MI20500) and, as with chlorination, orientation varies with change in temperature. At 300 °C, pyridine yields chiefly 3-bromo-and 3,5-dibromo-pyridine (electrophilic attack), whilst at 500 °C 2-bromo- and 2,6-dibromo-pyridine predominate (free radical attack). At intermediate temperatures, mixtures of these products are found. Similarly, bromination of quinoline over pumice at 300 °C affords the 3-bromo product, but at higher temperatures (450 °C) the 2-bromo isomer is obtained (77HC(32-1)319). Mixtures of 3-bromo- and 3,5-dibromo-pyridine may be produced by heating a pyridine-bromine complex at 200 °C, by addition of bromine to pyridine hydrochloride under reflux, and by heating pyridine hydrochloride perbromide at 160-170 °C (B-67MI20500). 

Chlorination and bromination of pyridine and some alkylpyridines in the (3-position can be effected in the liquid phase at 100°C using excess AlCl3as catalyst. -Bromination of pyridine and 2- and 4-picoline is conveniently effected in oleum at 80-120°C. Bromination kinetics using HOBr in aqueous HC104 indicate that the partial rate factor for bromination of the pyridinium cation is 10 13, comparable to that for nitration. 

Chlorination and bromination of pyridines have been studied under a variety of conditions, particularly in the gas phase. The positional substi-... 

Concluding these reactions with halopyridines, 3-bromopyridine (99), which is readily available by bromination of pyridine at 2I5°C (36CBI534), is converted by ammonia at the relatively low temperature of I40°C in the presence of cupric sulfate to 3-aminopyridine (100) (36CBI534,... 

Electrophilic nitration and bromination of pyridine iV-oxides can be controlled to give 4-substituted products by way of attack on the free A-oxide. ° Under conditions where the A-oxide is 0-protonated, substitution follows the typical pyridine/pyridinium reactivity pattern thus, in fuming sulfuric acid, bromination shows P-regioselectivity. Mercuration takes place at the a-position, however mercuric-catalysed sulfonation produces the 3-sulfonic acid. ... 

Treatment of pyridine with fuming sulfuric acid yields pyridine-3-sulfonic acid which is converted to 3-cyanopyridine by distillation of its sodium salt with potassium cyanide . Better yields are claimed by initial bromination of pyridine in the 3-position and subsequent treatment with cuprous cyanide . The 3-cyanopyridine is then hydrolyzed to nicotinic acid. 

Extensive studies have been made of the vapour-phase bromination of pyridine. At 300 , over pumice or charcoal, bromine converts pyridine mainly into 3-bromo- and 3,5-dibromo-pyridine, whilst at 500 2-bromo-and 2,6-dibromo-pyridine resulti , loi. At 400 a mixture results from which 3,5- and 2,6-dibromopyridine were isolated. More complete examination of the reaction at 300 showed that besides the main products there were also formed 2-bromo-, 2,3-, 2,5-, 2,6- and 3,4-dibromo-, 2,3,5- and 3,4,5-tribromo-, but no 2,4-dibromo-pyridine. The main results of the vapour-phase brominations of pyridine and the bromopyridinesi i" are summarized in Figure 5,2. 

To 2,A. Electrophilic Substitutiori] Bromination of pyridine homologues in fuming sulphuric acid gives excellent yields of 3-bromopyridinesi24i,... 

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