A versatile method for the preparation of substituted 1,2,3,4-tetrahydroquinolines

Article abstract of DOI:10.1021/jo00128a041

N-Alkyl-N-aryl-1H-benzotriazole-1-methanamines 1 react with acetaldehyde to give 4-(benzotriazol-1-yl)-1,2,3,4-tetrahydroquinolines 11 in good yields along with minor amounts of diamines 12. Reactions of 1 with higher enolizable aldehydes R¹CH₂CHO lead to 4-(benzotriazol-1-yl)tetrahydroquinolines with an R¹ substituent at C-3 (17, 18). Condensation of N-methylaniline with two molecules of aldehyde RCH₂CHO and one molecule of benzotriazole produces 4-(benzotriazol-1-yl)-1,2,3,4-tetrahydroquinolines 34 bearing an R substituent at C-3 and RCH₂ on C-2. In all of these products, the benzotriazol-1-yl moiety can be replaced by a hydrogen atom (by reduction with lithium aluminum hydride) or by an alkyl or aryl group (by reaction with a Grignard reagent). Treatment of 11 with sodium alkoxides leads to 4-alkoxy-1,2,3,4-tetrahydroquinolines 10. Elimination of a molecule of nitrogen from the benzotriazole system of 4-(benzotriazol-1-yl)-1,2,3,4-tetrahydroquinolines 17, 18, and 35 by sodium hydride produces the corresponding 4-(phenylamino)1,2-dihydroquinolines 26 (R¹ = alkyl) or 4-(phenylimino)-1,2,3,4-tetrahydroquinolines 27 and 38 (R = Ph), depending on the nature of the substituents at C-3 and the workup conditions.