2.3- Dimethyl-6- quinoxaline

The benzoquinone adduct is a 2 1 molecular complex of 2,3-dimethylquinoxaline and quinol, and is readily prepared by crystallizing quinol from toluene in the presence of excess of 2,3-dimethyl-quinoxaline. 2,3-Dimethylquinoxaline and A -phenylmaleimide undergo Michael addition to form the quinoxalinylmethyl-A -phenylsuccinimide... 

Bis[(4,4 -bipyridinio)methyl]quinoxaline dibromide (120) gave 2,3-dimethyl quinoxaline (121) (Na2S204, H2O, briefly 93%). °... 

Dimethyl-6-quinoxalinamine (121, R = H) gave 6-formamido-2,3-dimethyl-quinoxaline (121, R = CHO) [HCO2H (large excess), AC2O, 20°C, 75 min 78%] the isomeric 6-formamido-3,8-dimethylquinoxaline (70%) was made similarly. ... 

The influence of substituents in mono- and disubstituted 2,3-dimethyl-quinoxalines and their conjugate acids on the UV and NMR spectra have been correlated with a,196 while stretching frequencies of the carbonyl group of 6-substituted quinazolinediones and their half-neutralization potentials have been related to ctp.197... 

Phenyl- and 2,3-diphenyl-quinoxalines in methanol with DMAD give 1 1 1 adducts (453),410 whereas 2-methyl- and 2,3-dimethyl-quinoxalines in acetonitrile form as major products cyclobutapyrroles (454),337 earlier described432 as azepines. By-products in the last two cases are, respectively, the r-7a,(-9,e-9a-isomer of 454 and a compound analogous to that formed from 2,3,5,6-tetramethylpyrazine. 

Table 4 Electrochemical data of QDO, 2-methylquinoxaline 1,4-dioxide, 2,3-dimethyl-quinoxaline 1,4-dioxide, 1,2,3,4-tetrahydrophenazine 5,10-dioxide, and PDO...

Quinoxaline 1,4-dioxide (Quindoxin) has higher antibacterial activity under in vivo than under in vitro conditions. It has been shown that its in vitro activity is enhanced 10 to 100-fold under anaerobic conditions. Derivatives of 3-methylquinoxaline 2-carboxaldehyde 1,4-dioxide such as the N-methylnitrone 86 also have higher in vivo activity than would be expected from in vitro tests. The high in vivo activity of 2,3-dimethyl-quinoxaline 1,4-dioxide is due to the formation of active metabolites, the mono- and dihydroxymethyl derivatives 87 and 88. However the hydroxymethyl derivative of 86 did not show the expected enhanced activity. Compound 88 is referred to in the literature as Dioxidine, and 2,3-bis(acetoxymethyl)quinoxaline 1,4-dioxide is known as Quinoxidine. The trade name for the 2-carboxaldehyde 1,4-dioxide derivative (89) is Car-badox. Of the numerous quinoxaline 1,4-dioxide derivatives patented in... 

Oxidation of quinoxaline with aqueous nitric acid and 2,3-dimethyl-quinoxaline with 20% nitric acid yields 6-nitroquinoxaline-2,3-dione. Quinoxalinediones are also isolated when quinoxalines are oxidized with peracids. Electronegative substituents such as nitro and cyano in the... 

A 1,5-dihydro-l-oxo derivative (47) of pyrrolo[l,2-a]quinoxaline has been shown to be the product of a supposed Diels-Alder reaction between 2,3-dimethylquinoxaline (46) and maleic anhydride. 2-Methylquinoxaline and 2-methyl-3-phenylquinoxaline give the corresponding derivatives 48. " The reaction between 2,3-dimethyl quinoxaline and maleic anhydride proceeds in 80% yield when the reactants are fused together. " ... 

Fig. 6.—The Dependence on pH, and Curves Obtained with the Kalousek Switch, of 2,3-Dimethylquinoxaline in Acetate-Phosphate Buffers. (500 fiM 2,3-Dimethyl-quinoxaline. The pH values of the medium are given on the curves. The auxiliary potentials were 1 and 2, —l.OV 3 and 4, —1,1V and 5, —1.6 V. The frequency used was 6.25 Hz. The curve registrations were 1, 2, and 3, —0.2 V 4, —0.4 V and 5, —0.8 V versus saturated mercurous sulfate electrode.)...

B. Reaction of 2-Phenyl- and 2,3-Diphenyl-quinoxaline with Dimethyl Acetylenedicarboxylate.221... 

Condensation of o-phenylenediamine or xV-methyl-o-phenylcne-diamine with alloxan (8) in neutral solution gives the ureides (9) and (10), respectively However, reaction of o-phenylenediamine with 1,3-dimethylalloxan (13) yields quinoxalin-3-one-2-carboxymethyl-amide (14), rather than the dimethyl ureide. Methylation of (9) in acetone in the presence of potassium carbonate gives the spiro-hydantoin (11). 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

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 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. 

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. ... 

Reaction of 10-bromo-iV,l,3-trimethyl-7-oxo-2,3-dihydro-7//-pyrido [ 1,2,3-i/e]quinoxaline-6-carboxamide with 2,6-dimethyl-4-(tributylstannyl)-pyridine in the presence of (Ph3P)2Pd(II)Cl in boiling toluene gave 10-(2,6-dimethyl-4-pyridyl) derivative (OOMIPIO). 

Benzenediamine (288) and the unstable oxamide equivalent (289), prepared in situ by chlorination of bis(dimethylamino)acetylene, gave 2,3-bis(dimethyl amino)quinoxaline (290) (no details). ... 

The second type is examplified in the condensation of 1,2-benzenediamine with dimethyl 3-bromo-3//-azirine-2,3-dicarboxylate to give dimethyl 2,3-quinoxaline-dicarboxylate (347) (Me2NCHO, 20°C, ultrasound, 2 h 69%) analogs were made likewise. 

The unlikely transformation of a pyrimidine into a quinoxaline has, indeed, been reported. Thus 4,5-dimethyl-1,2-benzenediamine (402) and alloxan (403, R = H) under acidic conditions gave 6,7-dimethyl-3-ureidocarbonyl-2(17/)-quinoxalinone (404, R = H) ( 30% see original for details) A(-methylalloxan (403, R = Me) likewise gave 6,7-dimethyl-3-(A(-methylureido)carbonyl-2(17/)-quinoxalinone (404, R = Me) in 50% yield.Such condensations gave improved yields under solid-state conditions. 

Only one procedure has been reported recently within this category. Thus 7-chloro-l-methyl-5-phenyl-2,3-dihydro-lH-benzodiazepin-2-one 4-oxide (437) with dimethyl acetylenedicarboxylate in methylene chloride at 20° C for 3 days gave a separable mixmre of the primary tricyclic adduct, dimethyl lO-chloro-6-oxo-llb-phenyl-5,6,7, 1 lb-tetrahydroisoxazolo[2,3-t/] [ l,4]benzodiazepine-1,2-dicarboxylate (438), and its rearrangement product, 6-chloro-4-(2-methoxalyl-2-methoxycarbonyl-l-phenylvinyl)-l-methyl-3,4-dihydro-2(lT0-quinoxalinone (439) each product afforded 6-chloro-l-methyl-2(l//)-quinoxalinone (440) on refluxing in ethanol (see also Section 1.7.13). However, the final quinoxaline (440) was best obtained in 75% yield) by simply heating the initial substrate (437) and dimethyl... 

Dimethyl-1,5-benzodiazepine, formulated as its 3H tautomer (445), underwent vapor-phase pyrolysis (850°C, 0.02 mmHg, 15 min) to give a mixmre from which three quinoxalines were isolated 2,3-dimethyl- (446, R = Me) (7%), 2-ethyl-3-methyl- (446, R = Et) (10%), and 2-methyl-3-vinylquinoxa-line (447) (1%). ... 

Although derivatives of 2,1,3-benzoxadiazole have been used extensively to make quinoxalines (see Section 1.6.7), the corresponding selena and thia systems have been paid scant attention for that purpose. However, 5-chloro-4-nitro-2,l,3-benzoselenadiazole (456) has been used as a convenient source of 4-chloro-3-nitro-1,2-benzenediamine (457) (HCl + HI, 20°C, 2 h 88%), which was then converted into 6-chloro-5-nitro-2,3(l//,4//)-quinoxalinedione (458) (oxalic acid, 2M HCl, reflux, 2.5 h 23%). ° In addition, irradiation of 2,1,3-benzoselenadiazole (460, X = Se) or 2,1,3-benzothiadiazole (460, X = S) with dimethyl acetylenedicarboxy-late afforded, among other products, dimethyl 2,3-quinoxalinedicarboxylate (459)... 

Benzoxadiazole 1-oxide (481) with 3-acetyltetrahydro-2-furanone (2-acetyl-butyrolactone 482) gave 2-(2-hydroxyethyl)-3-methylquinoxaline 1,4-diox-ide (483) (KOH, MeOH-HaO, 20°C, 24 h 50%) but with 2-acetylacetaldehyde dimethyl acetal (484), in the presence of morpholine as base, it gave 2-(2-morpholinovinyl)quinoxaline 1,4-dioxide (485) (PhH, reflux, water separation, 9 h 47%) ... 

Dimethyl 4-(A -p-bromobenzylidene-A-methylhydrazino)-8-chloro-3aH-isoxa-zolo[2,3-fl]quinoxaline-2,3-dicarboxylate (568) in refluxing dimethylformamide for 10 h afforded 2-(A -p-bromobenzylidene-A-methylhydrazino)-6-chloroquinoxa-line (569) in 17% yield." ... 

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