2- Fluoro-5-bromopyridine

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

The stabilities of pyridine-2- and -4-diazonium ions resemble those of aliphatic rather than benzenoid diazonium cations. Benzenediazonium ions are stabilized by mesomerism which involves electron donation from the ring, but such electron donation is unfavorable in 2- and 4-substituted pyridines. On formation, pyridine diazonium cations normally immediately react with the aqueous solvent to form pyridones. However, by carrying out the diazotization in concentrated HC1 or HBr, useful yields of chloro- and bromopyridines 752 can be obtained. Iodinated pyridines can be obtained in good yield using the Sandmeyer reaction. Aminopyridazines and -pyrazines, 2- and 4-aminopyrimidines, and amino-1,2,4-triazines behave similarly. Nucleophilic fluorination via the BalzSchiemann reaction of diazonium fluoroborates yields fluoropyridines, including 2-fluoropyridines. Fluoroborates can also be converted into fluoro compounds by ultraviolet irradiation. 

The rate and activation parameters have been determined for the reaction of potassium methanethiolate with various 2-fluoro- and bromo-pyridines. Although an ortAo-methyl group did not activate the 2- position in 2-bromo- or 2-fluoro-pyridine towards attack by the methanethiolate ion, deactivation of the ortho rather than the para position was observed. At 110°C for the bromo-compounds Ao-Me Xp-Me = 3-9, while Ao-Br A -Br = 2-2. The results have been compared with those obtained using methoxide and benzenethiolate anions in methanol. The relative rates observed in HMPA are the same as those in methanoP . Thio-phenol reacts faster than its anion with a bromopyridine, in methanol, due to a rapid acid-base pre-equilibrium in which the pyridine is protonated. An o-MeO substituent accelerates the replacement of Br, and a small increase is also noted on going from MeOH to DMSO as solvenpii. 

As mentioned already (p. 204), the formation of 4-phenacylpyridine and 4-aminopyridine from S-bromopyridine, acetophenone and sodamide in liquid ammonia led Levine and Leake to postulate the occurrence of 3,4-pyridyne as an intermediate in the reaction. The results of other reactions in which a 3,4-pyridyne plays a part are collected in Table 5,23. 3-Fluoro-... 

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