Quinoxaline, 2-chloro-, reaction with

Chloroquinoxaline undergoes facile nucleophilic displacement reactions with amines and aryloxides to give the corresponding 2-substituted quinoxalines. With diamines, besides the 2-amino derivatives, bis(quinoxalinyl)alkylenediamines are produced. When 2-chloro-quinoxaline is treated with a sodium aryloxide in an excess of the corresponding phenol, a mixture of the expected 2-aryloxyquinoxaline and the corresponding benzofuro[2,3-6]quinoxaline (144) is obtained. 2-Aryloxyquinoxalines are readily cyclized with polyphosphoric acid to benzofuro[2,3-6]quinoxalines. 2-Arylfuro[2,3-h]quinoxalines (146) result from cyclization of 2-phenacyl-3-quinoxalinones (145). ... 

Oxidation of the parent base with hydrogen peroxide in formic acid gives a high yield of mono-N-oxide and a little di-N-oxide N-Oxidation is assumed to proceed preferentially at the less hindered 4-nitrogen. A number of substituted benzo[/]quinoxaline 4-oxides have been prepared, the majority by oxidation of the appropriate benzo[/]quinoxaline with peracids. " Treatment of benzo[/]quinoxaline 4-oxide with phosphoryl chloride gives mainly 3-chlorobenzo[/]quinoxaline. An isomeric mono-chloride, m.p. 104-104.5°, is also isolated from this reaction which is shown by independent synthesis not to be the 2-chloro derivative. A dichloro derivative, m.p. 187-188°, of unknown structure is obtained by treatment of the parent base with chlorine in glacial acetic acid. A disubstitution product of unknown orientation and m.p. 288° is obtained by nitration of... 

A variety of pyrrolo[l,2-a]quinoxaline derivatives 406 were synthesized in good to excellent yields when pyrrole-2-carboxamides 405 were used instead of a-amino acid derivatives in reactions with 1-fluoro- (383) and chloro- (404) -2-nitrobenzenes under a mild transition metal-free process (Scheme 2.73) (Huang et al. 2011). 

Scheme 3.20 Reaction of 3-[a-chloro(p-nitrobenzyl)] quinoxalin-2-one with acetylacetone...

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, ... 

Likewise, when 98 was refluxed with aqueous KOH in dioxane, the corresponding 2-phenylfurono[2,3-6]quinoxaline was produced in 67% yield [52], The Sonogashira reactions of chloro- and dichloroquinoxalines and trimethylsilylacetylene (56, 57] or but-3-yn-2-ol [58] have also been documented. 

Lund and coworkers [131] pioneered the use of aromatic anion radicals as mediators in a study of the catalytic reduction of bromobenzene by the electrogenerated anion radical of chrysene. Other early investigations involved the catalytic reduction of 1-bromo- and 1-chlorobutane by the anion radicals of trans-stilhene and anthracene [132], of 1-chlorohexane and 6-chloro-l-hexene by the naphthalene anion radical [133], and of 1-chlorooctane by the phenanthrene anion radical [134]. Simonet and coworkers [135] pointed out that a catalytically formed alkyl radical can react with an aromatic anion radical to form an alkylated aromatic hydrocarbon. Additional, comparatively recent work has centered on electron transfer between aromatic anion radicals and l,2-dichloro-l,2-diphenylethane [136], on reductive coupling of tert-butyl bromide with azobenzene, quinoxaline, and anthracene [137], and on the reactions of aromatic anion radicals with substituted benzyl chlorides [138], with... 

Reaction of quinoxaline with the fluorine-iodine-triethylamine system gives 2-fluoroquinoxaline 40 and 2,3-difluoroquinoxaline 41, whose yields depend on the fluorine usage (Equation 6) <1999J(P1)803>. Using 6-chloro-quinoxaline or 6,7-dichloroquinoxaline as the substrate, the monofluoro product is predominantly formed regardless of the amount of fluorine used. It is suggested that the reaction proceeds via attack of the fluoride ion on the a-carbon of an intermediate A -iodo quinoxalinium species followed by elimination of hydrogen iodide with triethylamine. 

Nucleophilic displacement of 2-chloro-3-phenylquinoxaline with methylamine at 100°-150° and with sodium phenoxide in excess of phenol of 100° gives the expected 2-methylamino- and 2-phenoxy-3-phenylquinoxalines.155 2-Chloroquinoxaline and its 3-phenyl derivative undergo ring closure with aminoacetaldehyde dimethylacetal to an imidazo[l,2-a]quinoxaline.136 Nucleophilic substitution of 2-chloro-quinoxaline with hydroxide ion in water is accelerated by cationic micelles and retarded by anionic micelles. These results were correlated with reactions of l-chloro-2,4-dinitrobenzene, and the characteristics of their transition states were discussed.137... 

Reactions of 2-chloro- and 2,3-dichloroquinoxalines with carbanions give 2-quinoxalinyl ketones and 3-chloro-2-quinoxalinyl ketones, respectively e.g., 2-quinoxalinylacetophenone (151) from acetophenone anion.161 However, 2,3-dimethoxy- and 2,3-diethoxy-quinoxaline with methyl ethyl ketone and sodamide in anhydrous benzene give 2-amino derivatives rather than ketones.162... 

Chloro derivative 291 was obtained from dioxo derivative 70 by treatment of phosphoryl chloride in dimethylformamide at 100°C for 2 hours (80CPB3537). The treatment of chloro derivative 291 with methylhydra-zine in a mixture of ethanol and chloroform under reflux gave 2H-pyrido[ 1,2-a]pyrimidin-2-one 295 and rearranged pyridazino[3,4-6]-quinoxaline 296 in 4.8% and 78% yields, respectively (Scheme 21) (80CPB3537). 3,4-Dihydroquinoxalinone 70 could not be rearranged into pyridazino[3,4-6]quinoxaline 296 by treatment with methylhydrazine. When hydrazine hydrate was employed instead of methylhydrazine, tricyclic ethyl ester 297 (R1 = Et) was obtained. The latter reaction gave methyl ester 297 (R1 = Me) when carried out in a mixture of methanol and chloroform (80CPB3537). 

The pyridazino[3,4-6]quinoxaline (89) is synthesized by the 1,3-dipolar cycloaddition reaction of 6-chloro-2-(l-methylhydrazino)quinoxaline 4-oxide (88) with DMAD (Equation (10)) <91JHC199>. 

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