Reactions of Quinoxaline

Some typical examples of recently reported reactions of unsubstituted quinoxaline, hydroquinoxalines, or simple A -alkylquinoxalinium salts are mentioned here. 

Quinoxaline and acetaldehyde gave 2-acetylquinoxaline (Bu OaH, FeS04, H2SO4-H2O, 10°C, 50 min 78%) benzaldehyde similarly gave 2-benzoyl-quinoxaline (55%) and several substituted benzoyl derivatives were made likewise. (See also Section 7.7.1.) 

Quinoxaline with the carbanion of (chloromethyl)sulfonylbenzene (PI1SQ2 CH2CI) gave the diannulated adduct, l,8-bisphenylsulfonyl-l,8,8a, 8b-tetra-hydrobisazirino[l,2-a 2, l -c]quinoxaline (7) [KOH, Me2SO, 20°C, 5h 

Quinoxaline with dimethyl sulfone or sulfoxide gave l,3,3a,4,9,9a-hexahydro-thieno[3,4-Z7]quinoxaline 2.2-dioxide (8, n = 2) [Me2S02, BuLi, THF, 20°C, 30 min then quinoxaline, 20°C, 4h 82%) or the corresponding 2-oxide (8, 

In a somewhat similar way, quinoxaline with A -benzylmethanesulfonamide gave a separable mixture of l-benzyl-l,3,3a,4,9,9a-hexahydroisothiazolo[3,4-bjquinoxaline 2.2-dioxide (9) and 2-(Af-benzylsulfamoylmethyl)-l,2-dihydro-quinoxaline (10) (MeS02NHPh, BuLi, THF, 20°C, 1 h then quinoxaline, 20°C, 2h 66% and 15%, respectively) the latter product was oxidized to 2-(Af-benzylsulfamoylmethyl)quinoxaline (11) by passing through a column of 

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Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

The formation of quinoxaline quaternary salts is often difficult. However, reaction of quinoxaline with ethyl iodide in boiling acetonitrile gives ethyl quinoxalinium iodide in 76% yield, and treatment of the parent base with methyl toluene-p-sulfonate at room temperature gives methyl quinoxalinium toluene-p-sulfonate in quantitative yield. ... 

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

This chapter covers recent information on the preparation, physical properties, and reactions of quinoxaline and its C-alkyl, C-aryl, iV-alkyl, and A-aryl derivatives as well as their respective ring-reduced analogs. In addition, it includes methods for introducing alkyl or aryl groups (substituted or otherwise) into quinoxalines already bearing substituents and the reactions specific to the alkyl or aryl groups in such compounds. For simplicity, the term alkylquinoxaline in this chapter is intended to include alkyl-, alkenyl-, alkynyl-, and aralkylquinoxalines likewise, arylquino-xaline includes both aryl- and heteroarylquinoxalines. 

Some aspects of the deoxidative C-substitution of quinoxaline N-oxides (see Section 4.6.2.2 for cross-references) and the photoinduced rearrangement of quinoxaline dioxides into quinoxalinediones (see Section 4.5.1) have been discussed already. The remaining reactions of quinoxaline A -oxides are covered in the following subsections. 

Some minor reactions of quinoxaline A -oxides are illustrated in the following classified examples. 

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. 

Another interesting example of a reaction of quinoxalines is the preparation of phenazines 173 from quinoxaline 172 which was covered in Section 6.2.8.1. 

Quinoxaline derivatives (36), and not the expected sydnones, were obtained from the Af-nitroso derivatives of 3-arylamino-l-aryl-pyrrolidine-2,5-diones (35). The precise nature of this rearrangement has not so far been determined.40 The derived quinoxaline-2,3-dicarboxylic acid mono-jV-arylamides (37) were obtained in 40-60% yield. The latter compounds were also made by the conventional reaction of quinoxaline 2,3-dicarboxylic anhydride and an amine.40... 

Quinoxaline and 2-methylquinoxaline form 1 1 adducts (111) with diphenylcyclopropenone,122 and an analogous pyrrolo[l,2-a]quin-oxaline has been isolated from the reaction of quinoxaline with di-phenylcyclopropenethione.123... 

Studies of the reactions of quinoxaline N-oxides under Reissert reaction conditions have led to some very interesting and unusual results. Thus, treatment of quinoxaline IV-oxide with PhCOCl/KCN in methanol or water under standard Reissert conditions gave 6-chloroquinoxaline as the major product (ca. 45%), and only small amounts of the desired 2-cyanoquinoxaline. Use of 3 equivalents of TMSCN in place of KCN and dichloromethane as solvent, however, gave 2-cyanoquinoxaline in 72% yield. When 2,3-diphenylquinoxaline iV-oxide was treated with 1 equivalent of PhCOCl in the presence of 3 equivalents of either KCN or TMSCN a mixture of products was always obtained irrespective of the solvent used. The most interesting of these products was the ring cleaved compound 1. 

Reaction of Quinoxaline with Perfluoro-n-butyl Iodide and Cyclohexene (12) [18] (Eq.15)... 

Reaction of quinoxaline with DMAD furnished tetramethyl -6aH-pyrido-[l,2-a]quinoxaline-7,8,9,10-tetracarbox ylate (72MI1). 

Synthesis and thermal and photochemical reactions of quinoxaline 1,4-dioxides and phenazine 9,10-dioxides 93H(35)1503. 

Mild oxidation of 3-substituted quinoxalin-2-ones, formed by reaction of quinoxalin-2(l//)-ones and Grignard reagents, with potassium hexacyanoferrate(III) or hydrogen peroxide gives aromatic systems. ... 

Dialkylated quinoxalines are accessible by reaction of quinoxalines with reactive trialkylox-onium (Meerwein) salts. ... 

The reaction of quinoxaline with aldehydes in the presence of a redox system affords alkyl and aryl quinoxalin-2-yl ketones. When saturated solutions of iron(II) sulfate and tert-butyl hydroperoxide are added to an aldehyde and quinoxaline, 2-acylquinoxalines are formed. 

Similarly, the reaction of quinoxaline 1,4-dioxides with formamide affords quinoxalinecarbox-amide derivatives. 

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