Oxalinic acid

Following extraction/cleanup, quinoxaline-2-carboxylic acid can be detected by electron capture, or mass spectrometric techniques, after gas chromatographic separation on capillary or conventional columns. A prerequisite of quin-oxaline-2-carboxylic acid analysis by gas chromatography is the derivatization of the molecule by means of esterification. Esterification has been accomplished with methanol (419, 420, 422), ethanol (421), or propanol (423) under sulfuric acid catalysis. Further purification of the alkyl ester derivative with solid-phase extraction on a silica gel column (422), thin-layer chromatography on silica gel plate (420), or liquid chromatography on Hypersil-ODS, 3 m, column (423), has been reported. 

Similar rearrangements have been observed on irradiation of quin-oxaline mono- (LXXXIII) and di-X-oxides (LXXXI) in dilute aqueous solution or dilute sulfuric acid,169 of a-9-acridyl-JV -phenylnitrone (LXXXV) moistened with acetone,10 and of LXXXVIT178 forming LXXXII, LXXXIV, LXXXVI, and LXXXVIII, respectively. 

Various peracids have been used for the N-oxidation of quinoxalines, but the most convenient reagent for many 2-substituted and 2,3-disub-stituted quinoxalines is 30% aqueous hydrogen peroxide in acetic acid. With this reagent, oxidation has been carried out at temperatures ranging from 20° to 90°.108-112 For example, 2-methyl-3-phenylquin-oxaline (91) when treated with peroxide and acetic acid at 56° for 14 hours yields a mixture of the 1-oxide (92) and the 1,4-dioxide (93).112... 

Peracetic acid oxidation of 2-carbamoylquinoxaline (94) at 20°-25° gives the monoxides 95 and 96, and at higher temperatures the 1,4-dioxide (97) is isolated in 50% yield, together with a small amount of the 1,4-dioxide of 2-amino-3-quinoxalinone.m However, Hayashi and co-workers report the isolation of only 96 from 94 using monoperphthalic acid in ether <10°.109 In their attempt to correlate the nature of 2-substitution with the formation of 1- versus 4-oxides, they examined the behavior of some 2-alkyl substituted quinoxalines 113,114 2-ethylquin-oxaline gives the 1- and 4-oxides and the 1,4-dioxide, 2-isopropylquin-oxaline yields the 4-oxide and the 1,4-dioxide however, 2-f-butylquin-oxaline only furnishes the 4-oxide because of steric hindrance.114 The N-oxidation of 2-phenyl- and 2-alkyl-3-phenyl-quinoxalines with monoperphthalic acid furnishes the products shown in Table 1.114... 

Chlorination of 5-hydroxyquinoxaline 1,4-dioxide in methylene chloride gives the 6,8-dichloro derivative, but reaction with N-chlorosuccinimide yields 8-chloro-5-hydroxyquinoxaline dioxide. Bromination in acetic acid gives the 6,8-dibromo derivative.195 15 Side-chain bromination is observed, however, when 2,3-dimethylquinoxaline 1,4-dioxide reacts with bromine in dioxane 2,3-bis(bromomethyl)quin-oxaline 1,4-dioxide is formed.195c... 

Oxaline (143) was isolated in 1974 by Nagel et al. (183,184) from cultures of the toxicogenic fungus Penicillium oxalicum. The compound may be classified as an indole alkaloid, but it is one of the three indole alkaloids known at present that also contains an imidazole substituent the other indole alkaloids being roquefortine (144) and neoxaline (145). The structure of oxaline was deduced from physicochemical data and confirmed by single-crystal X-ray analysis. It has been suggested that in the biosynthesis of oxaline, nature makes use of the amino acids tryptophan and histidine (184). 

Substituted quinoxalines afford mono-A-oxides, presumably the 1-oxides, and are resistant to further oxidation, though 5-methoxyquin-oxaline is exceptional in forming a 1,4-dioxide. In the case of 6-substituted quinoxalines, as the substituent becomes more electron attracting, the yields of 1,4-dioxide decrease but more of the corresponding 2,3-dioxo compound (41) is formed.50 55 Peracetic acid oxidation of l-methylquinoxalin-2-one (42) at 55°C gives l-methylquinoxaline-2,3-dione (43) in moderate yield, and similar treatment of l,3-dimethylquinoxalin-2-one (44) yields a small quantity of the 4-oxide.56 An improved yield of (43) is obtained by... 

Many other examples of Az-peptides are listed in the literature and suggest that Az-amino acids are usually more stable than the E isomers [76]. However, some dehydropeptides like the neurotoxins roquefortine 11 and oxaline 12, isolated from Penicillium roqueforti and Penicillium oxalicum, respectively, both contain a A His residue (Fig. 13.13) [77]. Phomopsin A 13 (Fig. 13.13), an antimitotic agent produced by Phomopsis leptostromiformis, is also a A -peptide as it contains A Asp and A Ile residues [78,79]. 

Treatment of quinoxaline-2,3-dicarboxylic acid anhydrides, diesters, or dinitriles with hydrazine monohydrate gives pyridazino[4,5-h]quin-oxalines (Scheme 7). ... 

Qui unci 111 n, f-[[(3-Ca rboxy-2-q u i noxa tinyi)car-bonyl]amino]-3,3-dimethyl-7-oxo-4-thia-l-azabicycto-[3.2.0]heptane-2-carboxylic acid 3-carboxy-2-quinoxaliny[-penicillin. C 6Hl6N30,S mol wt 416.42. C 51.92%, H 3.87%, N 13.46%, O 23.05%, S 7.70%. Semi-synthetic antibiotic related to penicillin. Prepd by condensation of quin-oxaline-2,3-dicarboxylic anhydride with 6 -aminopenicillanic acid Richards et at., Nature 199, 354 (1963). 

The incorporation data shown in Table 5 clearly demonstrates that in both cases the pro-S-hydrogen is the one lost. Since the stereochemistry of the dehydroamino acid unit in both roquefortine and oxaline are of the E-configuration, a net syn-elimination of the 3-pro-S hydrogen and H(2) must occur during the biosynthesis of the dehydrohistidine unit (Scheme 28). 

A suspension of 3-amino-2-cyano-5,6-dihydrobenzo[h]quinoxaline 4-oxide in acetic acid containing coned. H2SO4 refluxed 16 hrs. -> 3-amino-2-cyanobenzo[h]quin-oxaline. Y 73%. F. e. s. E. C. Taylor and J. V. Berrier, Heterocycles 6, 449 (1977). 

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