Quinoxalin-2,3-diones

Oxidation of 4-methylquinoxalin-3-one 2-carboxy-fV -methylamlide (45) with hydrogen peroxide and acetic acid furnishes the 1-oxide but, on removal of either or both of the fV-raethyl groups (giving 46, 47, or 48), oxidation with hydrogen peroxide or with peracetic or perbenzoic acid results in the removal of the carboxyamide groups and the formation of a quinoxaline-2,3-dione. ... 

E. Reactions of Quinoxalin-2-ones and Quinoxaline-2,3-diones (2-Hydroxy- and 2,3-Dihydroxy-quinoxalines) ... 

With diazomethane, quinoxaJin-2-ones and quinoxaline-2,3-diones... 

Quinoxalin-2-one is a very weak base (pK — 1.37) and so the different orientation of substitution in acetic and sulfuric acids may mean that in acetic acid the principal species undergoing nitration is the neutral molecule, and in sulfuric acid, the mono-cation. Treatment of quinoxaline-2,3-dione, or its iViV -dimethyl derivative in sulfuric acid, with 1 equivalent of potassium nitrate, results in nitration at position 6 with 2 equivalents of potassium nitrate, 6,7-dinitro compounds are formed. When quinoxaline is boiled with aqueous nitric acid, 6-... 

Ultraviolet and infrared spectroscopy indicate that quinoxaline-2,3-dione type structures are preferred to tlie tautomeric 3-hydroxy-quinoxalin-2 One or 2,3-dihydroxyquinoxaline forms. The light absorption properties (UV) of quinoxaline-2,3-dione have been compared with those of its NN -, ON-, and OO -dimethyl derivatives (79, 80, and 81), and also its N- and 0-monomethyl derivatives (43 and 82). The parent dicarbonyl compound and its mono- and di-A -methyl derivatives show very strong carbonyl absorption near to 1690 cm split into two peaks. 

Methylthioquinoxaline is oxidized by hydrogen peroxide in acetic acid at room temperature mainly to 2-methylsulfonylquinoxa-line (88) at 55°C, 2-methylsulfonylquinoxaline 4-oxide (89) and quinoxaline-2,3-dione are formed. 

Quinoxaline A-oxides undergo rearrangement under a variety of conditions. Thus on treatment of 2-ethoxy- and 2-methoxy-quinoxa-line 4-oxide with hydrochloric acid, rearrangement and hydrolysis occurs to give quinoxaline-2,3-dione. A possible intramolecular mechanism of rearrangement is shown in Scheme 7. Reaction of 2,3-... 

The lipophilicity (7 m value) and specific hydrophobic surface area of pyrido[l,2-a]pyrazinium-l-olates 342 and -3-olate 343, and l-(4-chlorophe-nyl)-l-hydroxy-l,2-dihydropyrazino[2,l-a]isoquinolinium salt (344) has been measured by reversed-phase thin-layer chromatography (98MI13). Partition coefficient (log/ ) of 9-bromo-5-[(A-phenylaminocarbonyl)-methyl]-l,2,3,5,6,7-hexahydropyrido[l,2,3- fc]quinoxaline-2,3-dione was calculated to be 2.78 (97JMC4053). 

It is of primary interest to avoid corrosive mineral acids in synthetic processes. This can easily be achieved by use of acidic solid supports coupled with microwave irradiation. This has been applied to the preparation of quinolines [53] (Scheme 8.35). This procedure is a safe, green alternative to the use of H2S04 at more than 150 °C. In the same way, quinoxaline-2,3-diones were prepared [54] by use of single-mode irradiation. Previous attempts in solution led to explosions, but the authors successfully used solvent-free conditions with acidic supports or catalysts (the best being p-toluenesulfonic acid) and irradiation times of 3 min (Scheme 8.36). 

The quinoxalinedione derivatives 6-cyano-7-nitroquinoxaline (CNQX), 6,7-dinitro-quinoxaline-2,3-dione (DNQX), and 2,3-dioxo-6-nitro-l,2,3,4-tetrahydrobenzo[f]quinox-aline-7-sulphonamide (NBQX) are potent competitive antagonists of AMPA and kainate receptors. Of these, NBQX shows the most functional selectivity (approximately threefold) for AMPA over KA receptors (45), and has been used in low concentrations (1 pM) to isolate kainate currents in hippocampal interneurons (46). 

Fig. 10.8 SAR by MS applied to the A1061 construct (see text), (a) Structures of key motifs screened against the RNA target. Compound A is a D-amino acid. Compounds B1 and B2 are quinoxalin-2,3-diones. Compound AB is the rigid biaryl linked compound, (b) Binding affinity for the motifs when screened individually as well as binding affinity for motifs when screened in competition experiments are shown. Binding...

Sulfonation of quinoxaline-2,3-dione (58) with fuming sulfuric acid yields the 6-sulfonic acid (59).69 Similarly, if quinoxaline-2,3-dione is... 

Quinoxaline-2,3-dione is converted into 2,3-dichloroquinoxaline by phosphoryl chloride142 or phosphorus pentachloride.143 2,3-Dibromo-quinoxaline is similarly obtained using phosphoryl bromide in dimethyl-aniline.144 Quinoxalin-2-one undergoes ring contraction to 2-methyl-benzimidazole (134) with hydrazine145 however, quinoxaline-2,3-dione gives 3-hydrazino-2-quinoxalinone.145 Quinoxalin-2-one yields a 3-p-dimethylaminophenyl derivative with 7V,N-dimethylaniline (in AcOH, with NH4N03), and a 3-(indol-3-yl) derivative with indole.146... 

Dichloroquinoxaline with anhydrous potassium fluoride at 200° yields 2,3-difluoroquinoxaline, which is readily hydrolyzed to quinoxaline-2,3-dione.158 Treatment of 2,3-dichloroquinoxaline with phosphorus pentachloride at 300° yields hexachloroquinoxaline, which with potassium fluoride at 380° gives predominantly hexafluoro-quinoxaline (148).139... 

Methylquinoxaline-2,3-dione (173) is oxidized with Co(OAc)2 Mn(OAc)2 in HBr/H20 to the 6-carboxylic acid (174),183 which on treatment with thionyl chloride is converted into 2,3-dichloro-quinoxaline-6-carbonyl chloride (175).184 The 6-sulfonyl chloride is obtained from quinoxaline-2,3-dione and chlorosulfonic acid and treatment of the resulting 6-chlorosulfonyl derivative with phosphoryl chloride and pyridine.185 Such derivatives are useful synthetic dye intermediates. 

Synthesis of 14C- and 3H-labelled 6-nitro-7-sulphamoylbenzo[F]quinoxalin-2,3-dione (173)... 

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