Nucleophilic substitution and ring closure reactions of 4‐chloro‐3‐nitro‐2‐quinolones

Abstract

4‐Chloro‐3‐nitro‐2‐quinolones 3 obtained from the 4‐hydroxy quinolones 1 by nitration and chlorination, reacted with sodium azide to the 4‐azido derivatives 4 which cyclized on thermolysis to yield the furoxanes 5. Nucleophilic substitution reactions of 3 led to the 4‐amino‐, 4‐fluoro‐ and 4‐alkoxy‐3‐nitroquinolones 7, 8 and 9, respectively. With thiols either 4‐thio‐3‐nitro‐ 10 or 3,4‐dithioquinolones 11 were obtained depending on the basic catalyst.

4-Hydroxyquinol-2-ones. 86. Synthesis of Methyl (Ethyl) Esters of 1-Substituted 4-Amino-2-oxoquinoline-3-carboxylic Acids

“…However ammonia does not react, after passing dry gaseous ammonia into a solution of chloro-substituted ester 8 in alcohol or DMF for 5 h only the starting material was isolated. At atmospheric pressure such a replacement was successfully effected only for the highly reactive 4-chloro-3-nitroquinol-2-ones [14], while in the remaining cases treatment with ammonia in an autoclave is necessary [8]. This is not acceptable for the synthesis of amino esters 1 due to the inevitable amidation of the alkoxycarbonyl group.…”

Thermal Cyclization of 3-Acyl-4-azidopyridines to Isoxazolo[4,3-c]pyridines

“…Also the use of bases such as triethyl amine during the chlorination, a method previously employed successfully in similar systems [9] gave no results. However, tosylation of the sodium salts of 1 [1,3a,d,e] furnished the reactive intermediates 2.…”

Nucleophilic substitution and ring transformation reactions with 4-chloro-6-ethyl-3-nitropyrano[3,2-c]quinoline-2,5(6H)-dione

“…25 We herein report for application of a known modification under substantial milder conditions, at room temperature using sodium nitrite as catalyst. 17 Roschger et al 17 had applied this methodology in similar case of 4-hydroxyquinolin-2-ones, and according to this modification, catalytic effect of the nitrite was attributed to an initial nitrosation at position 3 and subsequent in situ oxidation of the nitroso intermediate to the The substitution of the chlorine by an azide group was achieved by the reaction of compound 3 with sodium azide, in N-methylpyrrolidone, at room temperature (Scheme 2). The IR spectrum of the product 4 showed characteristic absorption band at 2150 cm -1 attributed to the azido group.…”

“…Organic azides with suitable ortho substituents are known to undergo thermal cyclization with loss of N 2 gas. 17,26,27 Ring closure to the fused furoxan 5 was achieved by thermolysis of the azide 4 in refluxing nitrobenzene (Scheme 2). The IR spectrum of furoxan 5 showed characteristic absorption bands at 1448 cm -1 assigned to the C=N-O, while the stretching vibration of the fragment O-N→O was seen at 1301 cm -1 (as the recently reported for furoxan ring 28 ).…”

“…15,16 The chemistry of nucleophilic reactions involving ring opening-ring closure (RORC) of 4-chloro-3-nitropyrano[3,2-c]quinolinone 3 attracted our attention due to the expected higher reactivity of the o-chloronitro heterocycles and to the paucity of their literature reports. [17][18][19] On the other hand, the combination of a pyrazole and/or pyrimidine nucleus with the quinoline moiety in one molecular framework is reported to confer biological activity. [20][21][22] Herein we report the synthesis of the novel 4-chloro-6-ethyl-3-nitropyrano[3,2-c]quinoline-2,5-dione (3) and a study of its chemical behavior towards some nitrogen, sulfur and carbon nucleophiles to obtain a new series of 4-substituted-3-nitropyranoquinolinediones.…”