Quinoxalin-2-one

The predominance of the oxo forms of quinoxalin-2-one (125) and its 3-methyl derivative in aqueous solution was established by Cheese-man using the pK method, only a lower limit beii obtained for Kt (log Kt> 1.6 and 0.9, respectively) because similar cations are... 

This method is widely applicable to the unambiguous synthesis of quinoxalin-2-ones." It involves the intermediate preparation of a l,2,3,4-tetrahydro-2-oxoquinoxaline by the reductive ring closure of the o-nitrophenyl derivative of an a-aminoacid. These derivatives are formed readily from the aminoacid and an o-nitrohalogenobenzene. The final step of oxidation of the tetrahydro- to the dihydro-quinoxa-line is carried out with potassium permanganate or hydrogen peroxide. The preparation of 7-nitroquinoxalin-2-one illustrates the application of this synthesis ... 

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

QuinoxaIin-2-oncs are readily converted into the corresponding 2-chloroquinoxalines by treatment with phosphoryl chloride in the case of the highly insoluble 2,3-diones chlorination is effected conveniently with a mixture of phosphoryl chloride and dimethyl-aniline. The use of phosphorus pcntachloride may lead to side reactions, for example, quinoxalin-2-one (70) is converted into 2,3-... 

Quinoxalin-2 one (70) is in mobile tautomeric equilibrium with 2-hydroxyquinoxaline (71), but physical measurements fail to demonstrate the presence of the hydroxy form (see following). 

The ready conversion of quinoxalin-2-ones into 2-chloroquinoxalines is not chemical evidence for the existence of the hydroxy form. Phen-... 

Treatment of an alkaline solution of quinoxalin-2-one or quinoxa-line-2,3-dione with an alkyl iodide or sulfate results in A-methylation. Thus methylation of 3-aminoquinoxalin-2-one (74) with methyl sulfate and alkali gives 3-amino-l-methylquinoxalin-2-one (75) and not as previously reported the isomeric 0-methyl derivative. ... 

Quinoxalin-2-ones, unlike quinoxaline itself, may be nitrated under mild conditions. Nitration of quinoxalin-2-one in acetic acid gives mainly the 7-nitro derivative in sulfuric acid, the 6-nitro compound is formed (Scheme 6). ... 

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-... 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

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. 

The acidic strength of various quinoxaline derivatives is also listed in Table II. -Methyl groups have an acid-weakening effect and quinoxalin-2-one (2-hydroxyquinoxaline) is, as expected, a weaker acid than quinoxaline-2-thione (2-mercaptoquinoxaline), The marked enhancement of the acidic strength of 5-hydroxyquinoxaline 1-methiodide compared to 5-hydroxyquinoxaline itself, is due to the electron-attracting property of the positively charged nitrogen, ... 

Normal reactions are found again for systems containing C=N double bonds. An unstable triazoline is probably an intermediate product in the reaction of pteridin-7-one (117)to give a mixture of the 8-methyl (118) and 6,8-dimethyl derivatives (119). C-Methylation also occurs in the case of quinoxalin-2-one. ... 

It has been observed that photolysis of the fungicide, 6-methyldithiolo[4,5-fc]-quinoxalin-2-one (quinomethionate 546) in benzene during 8 h afforded not only 6-methyl-2,3(l//,4//)-quinoxalinedione (547) but also the isomeric phenylated products, 6-methyl- (548, Q = H, R = Me) and 7-methyl-3-phenyl-2(l//)-quinox-alinone (548, Q = Me, R = H). 

Brightener structures of only moderate molecular size are of interest for white grounds in the transfer printing of polyester fabrics. Derivatives of 6-acetamidoquinoxaline with an electron-donating substituent (X) in the 2-position (11.48) were prepared by converting quinoxalin-2-one to 2-chloro-6-nitroquinoxaline and condensation with amines (X = RNH), alcohols (X = RO) or phenols (X = PhO), followed by reduction and acetylation (Scheme 11.19). The nitro intermediates (11.49) are also of interest as low-energy disperse dyes for polyester [61]. 

The compound I O.i. I Ob-dihydro-5//, 12//-4b,5,6,12-tetraaza-chrysen-l ] -one 81 <2003JHC357> was prepared through diazotization of the corresponding amine derivative 3-(2-aminophenyl)-l//-quinoxalin-2-one 78. The reaction proceeded through intermediates 79 and 80 (Scheme 4). 

Scheme 7.69 Liquid-phase synthesis of quinoxalin-2-ones.

Kalinski C, Umkehrer M, Ross G, Kolb J, Burdack C, Hiller W (2006) Highly substituted indol-2-ones, quinoxalin-2-ones and benzodiazepin-2, 5-diones via a new Ugi(4CR)-Pd assisted A-aryl amidation strategy. Tetrahedron Lett 47 3423-3426... 

This chapter will give an account of work performed to date in this area, covering solid-phase syntheses of l,5-benzothiazepin-4-ones 2a,b,4 1,6-benzothiazocin-5-ones 3,5 1,5-benzodiazepin-2-ones 4,6,7 4-alkoxy-1,4-thiazin-3-ones 5,5 quinoxalin-2-ones 6,5,8,9 benzimidazolones 7,10 2-alkylthiobenzimidazoles 8," and 2-alkylaminomethylbenzimidazoles 9.12... 

Our approach was based on the observation that it is possible to perform SwAr reactions on solid support with amino acids using a solvent system comprised, in equal parts, of acetone and an aqueous 0.5 M NaHC03 solution at temperatures around 70-75°C. Application of this solvent system to the synthesis of quinoxalin-2-ones 6 from la and a-amino acids is described in Section 3.3.2. With respect to the synthesis of 1,5-ben-zodiazepin-2-ones 4, more than 40 examples of aliphatic and aromatic P-amino acids 35 were found to furnish the desired o-nitro anilines 36, about 80% of which were successfully carried on to eventually afford the ben-zodiazepinone products 4 (Scheme 6). In general, the anthranilic acids required slightly harsher conditions to drive the fluorine displacement to completion (75-80°C, 72 h vs. 70-75°C, 24 h for aliphatic P-amino acids). 

Figure 3.4. Selection of quinoxalin-2-ones synthesized from 1a and a-amino acids 60.

To summarize this section, several research groups have effectively exploited parallels between SwAr strategies leading to [6,7]- and [6,6]-ben-zofused heterocycles and have described complementary reaction protocols suitable for generating diverse combinatorial libraries of benzothiazin-3-ones and quinoxalin-2-ones. 

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... 

The fluorescence spectra of quinoxalin-2-one and 3-substituted quinoxalin-2-ones have been reported and correlated with the absorption spectra.252 253... 

Andronati and co-workers reported a detailed study of the A-basicity of compounds 203 (X = H, Me R1 = H R2 = H, Br, Cl, Me) which contain amide, imine, and amine nitrogens in one molecule. The basicities, obtained from the half-neutralization potentials in potentiometric titrations, showed 203 to be monoacidic bases the basicity varied predictably with substitution and fell between the stronger quinoxaline-2-ones and the weaker l,4-benzodiazepine-2-ones. Ultraviolet spectroscopic studies demonstrated that the amino, not the imino, nitrogen was N-protonated (83CHE337). 

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