Pyridine bromo-ethoxy-, amination

Pyridine JV-oxide, amino-, 133-134 2-bromo-4-ethoxy-, amination of, 137 2-chloro-, animation of, 133 electron densities, experimental, 161-162... 

When 3-chloro- or 3-bromopyridine is heated with lithium piperidide and piperidine in boiling ether, 156 is formed, which reacts further with piperidine to give a mixture of 3- and 4-piperidinopyridine in the ratio of 48 52. No 2,3-pyridyne intermediate is apparently produced under these conditions.388 Such an intermediate is probably involved in the reaction of potassium amide in liquid ammonia with 3-bromo-4-ethoxypyridine, which gives 2-amino-4-ethoxypyridine (55-60%). The reaction is, however, complicated by the fact that 2-amino-5-bromo-4-ethoxypyridine (15-20%) and 4-ethoxypyridine (25%) are also obtained.387 The formation of these two by-products may proceed by the preliminary disproportionation of some 3-bromo-4-ethoxy-pyridine to 3,5-dibromo-4-ethoxypyridine and 4-ethoxypyridine.388 The remarkable observation that both 2-amino-6-ethoxypyridine (157) (85%) and 4-amino-2-ethoxypyridine (158) (15%) are formed during the amination of 2-bromo-6-ethoxypyridine367 still requires explanation. No such rearrangement is observed with lithium piperidide.3880... 

When the reaction with propargyl alcohol is run in an amine solution at elevated temperature, the alkynylated product first formed is further transformed by a cyclization reaction with the pyridine nitrogen 3-piperidinoindolizine (35) is formed (36% yield) in piperidine at 80°C. Corresponding cyclization products result from the reaction with 1-bromoisoquinoline or 2-bromoquinoline with propargyl alcohol (80BCJ3273). Alkynylation (38) of 2-chloro-, 3-bromo-, and 4-iodopyrimi-dines, which are vicinally substituted by a cyano, carbamoyl, or ethoxy-carbonyl group, has been effected with phenylacetylene by heating the... 

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