Use of Substituted Acetamides for the Synthesis of 3-Substituted 2-Aminoquinolines

Recent Advances in the Friedländer Reaction

“…71 N-Acetylated 2-amino benzaldehydes have been combined with amides to give 2-amino-3-hydroxy quinoline derivatives in moderate yields. 72 The base-catalyzed intramolecular condensation of 2-acetamido aceto or benzophenones is known as the Camps quinoline synthesis. 73 As one might expect, most of the reported cases of Camps quinoline synthesis involve reactions in which only one of the carbonyl groups is enolizable, affording quinolin-2-ols or quinolin-4-ols, thus eliminating the regioselectivity problem.…”

“…A modified Friedla ¨nder condensation for the synthesis of 3-hydroxyquinoline-2-carboxylates employs the readily accessible O-methyloximes, which are sufficiently reactive to condense selectively with 2-amino benzaldehydes, without undergoing self-condensation, on treatment with an ethanolic solution of potassium hydroxide at reflux (eq 24). 92a Esters or lactones 93 and amides 72 are not common carbonyl partners in Friedla ¨nder-type condensations. Amides have been combined with N-acetylated 2-amino benzaldehydes to give 2,3-disubstituted quinolines (eq 25).…”

“…Amides have been combined with N-acetylated 2-amino benzaldehydes to give 2,3-disubstituted quinolines (eq 25). 72 Diethyl 1,3-allenedicarboxylate has been used as the masked carbonyl partner in an interesting Friedla ¨nder-type synthesis of 2,3,4-trisubstituted quinolines (eq 26). 28 Thus, the Michael adducts obtained by addition of the 2-carbonylsubstituted aniline to the allene in chlorobenzene at 80 °C gives the corresponding quinolines in good yields when treated with t-BuOK at 0 °C.…”

“…Esters or lactones and amides are not common carbonyl partners in Friedländer-type condensations. Amides have been combined with N -acetylated 2-amino benzaldehydes to give 2,3-disubstituted quinolines (eq ) …”