Pyridines, 3-substituted, pressure amination

Fluoroaromatics are produced on an industrial scale by diazotization of substituted anilines with sodium nitrite or other nitrosating agents in anhydrous hydrogen fluoride, followed by in situ decomposition (fluorodediazoniation) of the aryldiazonium fluoride (21). The decomposition temperature depends on the stabiHty of the diazonium fluoride (22,23). A significant development was the addition of pyridine (24), tertiary amines (25), and ammonium fluoride (or bifluoride) (26,27) to permit higher decomposition temperatures (>50° C) under atmospheric pressure with minimum hydrogen fluoride loss. 

The reaction of furans with ammonia and its derivatives is of considerable synthetic utility (B-73MI31 too). Substituted furan-2-carbaldehydes and 2-acylfurans on heating with ammonia and ammonium salts, often under pressure, yield 3-hydroxypyridines. The mechanism of this reaction is thought to involve nucleophilic attack of ammonia at the 2-position. Ring opening affords an amino aldehyde or ketone and thence, by reclosure, the 3-hydroxy-pyridine (Scheme 29). A wide range of substitutents is tolerated. Primary amines with furan-2-carbaldehydes yield A-substituted pyrroles, the closure of the intermediate... 

Butylamination of 3-picoline is shown in Scheme 35. The ratio of the 2-amino-5-isomer (89) to the 2-amino-3-isomer (90) was 16 L The yield of both isomers was 72%, which is about the same as obtained with sodium amide. The predominance of 89 is due most likely to steric hindrance caused by the bulkiness of the aminating agent. The situation is similar to the amination with sodium amide of 3-substituted pyridines at atmospheric pressure, in which the bulk of the 3-substituent directs the amount of 2-amino-5-isomer formed (Section IV), except that in this case, it is the size of the aminating group that decides the ratio of isomers. Additional alkylaminations of 3-substituted pyridines are shown in Table III. 

The hydrogenation of various aryl ketones in MeCN under H2 at high pressure is catalysed efficiently by the neutral complex (52) or its three cationic variants (53) (X = PFg, BF4, OTs) in the absence of a base, whereas the arene-substituted complexes (54) under similar conditions required an amine as a base (pyridine and Et3N were most effective). The Sulfo-Binepine ligand (55) proved to be less effective. " ... 

---