Nucleophilic Chlorination of 3-Formyl-4-hydroxy-quinolin-2(1H)-ones

Abstract

Chlorination of 1‐substituted 3‐formyl‐4‐hydroxy‐2‐quinolones (1a, b) with phosphorylchloride leads to 4‐chloro‐3‐dichloromethylquinolones (2), which can be hydrolyzed to 4‐chloro‐3‐formyl‐quinolones (4). From the anilinomethylene quinolinediones (3), at low temperatures the formylquinolones 4 can be obtained directly, whereas at high temperatures cleavage of the tautomeric azomethine moiety followed by subsequent ring closure to the naphthyridines (7) takes place. With 1‐unsubstituted 3‐formyl‐4‐hydroxy‐2‐quinolones (1d) either the 3‐dichloromethylquinolone (2d) or the 2,4‐dichloro‐3‐dichloro‐methylquinoline (10) is obtained depending on the reaction conditions. Similar results are obtained with the 1‐unsubstituted anilinomethylene compounds (3). Attempts to obtain the 3‐formyl‐2,4‐dichloroquinoline (11) were unsuccessful because in all experiments the 2‐chloro‐group was converted to an oxygen function.

4-Hydroxy-2-quinolones 166*. Synthesis, isomerism, and antitubercular activity of 3-arylaminomethylene-quinoline-2,4-(1H,3H)-diones

“…The structure of the Schiff base obtained by reaction of 3-acyl-4-hydroxy-2-oxo-1,2-dihydroquinolines with N-nucleophiles has repeatedly attracted the attention of investigators. As a result they have been reported as a mixture of two tautomers azomethine 3 and enamine 4 with a predominance of the latter [13][14][15][16]. The experiments we have carried out show a somewhat different picture.…”

tert‐Amino effect at a coumarin and a 2‐quinolone system: Synthesis of 1,2 fused 5H‐chromeno[4,3‐b]pyridin‐5‐ones and a 6H‐benzo[h][1,6]naphthyridin‐5‐one

“…To a stirred mixture of 0.54 g (0.62 ml; 6.4 mmol) of piperidine (3a) and 0.50 g (4.4 mmol) of ethyl cyanoacetate (2) in ethanol (5 ml), 700 mg (3.2 mmol) of the 2-oxoquinoline-3-carbaldehyde 1b (prepared as described in the literature [6]) was added. The mixture was stirred at room temperature for 20 min, then poured onto 50 g of ice-water and stirred for further 20 min.…”

4-hydroxy-2-quinolones 165*. 1-R-4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carbaldehydes and their thiosemicarbazones. Synthesis, structure, and biological properties

“…Hence, for a long time, they were prepared by the Reimer-Tiemann method although the yields of the target compounds did not exceed 40% [25]. More efficientl was basic hydrolysis of 3-arylaminomethylenequinoline-2,4-(1H,3H)-diones [32] which, in turn, were prepared also by reaction of 4-hydroxy-2-quinolones with triethylorthoformate and anilines [23,26] or with formamidines [26,27]. However, good yields were only basically achieved in this case in the final stage.…”

“…This was also the basic position in our work related to the synthesis and study of the antitubercular properties of the 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazones 1a-f. The obvious route for the synthesis of the starting 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbaldehydes (4-hydroxy-3-formylcarbostyrils) 2a-f by Vilsmeier formylation of 4-hydroxy-2-quinolones is not successful [23,24]. Hence, for a long time, they were prepared by the Reimer-Tiemann method although the yields of the target compounds did not exceed 40% [25].…”