Syntheses of 3-Aminoquinoline- 2,4(1H,3H)-diones

Abstract

Reaction of 3-chloro-(2) and 3-bromoquinoline-2,4(1H,3H)-diones(3) with excess of primary alkyl-or arylamines in dimethylformamide provides the corresponding 3-alkyl-or 3-arylamino derivatives (4).Compounds (4) with the primary amino group at the 3 position were best prepared by reaction of 2 with in situ generated ammonia under anhydrous conditions.An alternative approach to the primary amines (4) via reduction of 3-azidoquinoline-2,4(1H,3H)-diones (5) was investigated.The reduction of 5 with zinc in acetic acid gave moderate to good yields of the desired products, while the reaction with triphenylphosphine afforded exclusively 4-hydroxyquinolin-2(1H)-one (1).Recently, we have demonstrated interesting chemical transformations of 3-hydroxyquinoline-2,4(1H,3H)diones (A, Chart).For example, Wittig olefination of A with ethyl (triphenylphosphoranylidene)acetate proceeded highly stereoselectively to afford E-4-ethoxycarbonylmethylene derivatives (B). 1 In some cases furo[2,3-c]quinoline-2,4(3aH,5H)-diones (C) were obtained, presumably as a result of lactonization of the minor formed Z-4-isomer of B. The structure of C was confirmed by an independent synthesis via the intramolecular Wittig reaction. 2On the other hand, under the same reaction conditions as described for the synthesis of B, 5,8-disubstituted 3-hydroxyquinoline-2,4(1H,3H)-diones (A) underwent a completely different reaction, yielding primarily products of indoline (D) and benzoxazine (E) structural type. 3 Those have been shown to be formed via the complex molecular rearrangement of A. 4,5