2- quinoxaline, with acetal

Other reactions with their counterparts in the pyridine series are also well known. Thus, 2,3-dimethylpyrazine 1,4-dioxide reacts with acetic anhydride to yield 2,3-bis(acetoxy-methyl)pyrazine (S3) in good yield (72KGS1275). Pyrazine 1-oxide also reacts directly with acetic anhydride to yield 2(ljH)-pyrazinone by way of the intermediate acetate (Scheme 22). The corresponding reaction in the quinoxaline series is not so well defined and at least three products result (Scheme 23) (67YZ942). 

Treatment of 2,3-dimethylquinoxaline dioxides and monoxides with acetic anhydride yield 2,3-bis(acetoxymethyl)quinoxalines and 2-acetoxymethylquinoxalines, respectively.112,208 Under alkaline conditions these derivatives are hydrolyzed to the corresponding hydroxy-methylquinoxalines. Thus, 2-methyl-3-phenylquinoxaline-1,4-dioxide... 

In aprotic medium (acetonitrile), quinoxalino[2,3-b]quinoxaline (231) undergoes two reversible reductions to an anion-radical and further to a dianion.367 In 1 1 H20-DMF 231 gives a two-electron wave followed by a four-electron wave. The first reduction leads to 5,12-dihydroquinoxa-lino[2,3-h]quinoxaline (232), whereas the second reduction in a four-electron reaction leads to the 5,5a,6,11,1 la,12-hexahydro derivative (233). On heating with acetic anhydride a triacetyl derivative (234) is obtained367 [Eq. (128)]. 

A third alkaloid contained sulfur (a rare feature in higher plant nitrogen heterocycles) and was shown to be 4-methylthiocanthin-6-one (XIV) (9). Hydrolysis with amyl alcoholic alkali gave methyl mercaptan and the phenol XV which, upon permanganate oxidation, furnished /3-carboline-l-carboxylic acid. The phenol did not form a quinoxaline with o-phenylenediamine, and its acetate in moist ethereal diazomethane... 

Oxidation of quinoxaline with nitric acid yields 6-nitroquinoxaline-2,3(lW,4//)-dione. Treatment of 6,7-dialkoxyquinoxaline-2,3(l/7,4//)-diones with fuming nitric acid in acetic acid results in acetoxylation, giving 5-acetoxy-6,7-dialkoxyquinoxaline-2,3(l//,47/)-diones in moderate yields (48-52%). A mechanism involving attack of nitronium ion as the first step has been proposed. " ... 

Quinoxaline 1,4-dioxide is convened on prolonged heating with acetic anhydride to 1-acet-oxyquinoxalin-2(l//)-one (2), l-hydroxyquinoxalin-2(l//)-one (3), and quinoxaline-2,3(l//,-4i/)-dione (4), respectively. ... 

Reduction of quinoxaline with lithium aluminum hydride in ether yields 43% of 1,2,3,4-tetrahydroquinoxaline (81), also obtained in 20% yield by reduction with sodium in refluxing alcohol. Both sodium borohydride in acetic acid, and hydrogen and platinum, have been used to reduce 6-substituted quinoxalines to the 1,2,3,4-tetrahydro compounds. Quinoxaline and its 2-methyl derivative undergo reductive formylation when treated with formic acid in formamide 1,4-diformyl-... 

A complete first-order analysis of the quinoxaline tetra-acetate confirms the acyclic structure. Coupling constants (7i 2 3-0, 72 3 8 5, /4 a, 4b 12-0, 73, 4a 3-0, Js 4b 5 5 c./sec.) for the acyclic chain, were obtained that were indicative of a high degree of conformational purity and which were in agreement with an extended planar zig-zag arrangement as the favoured conformation. 

A careful study of the phenylation of quinoxaline with benzoyl peroxide, various benzenediazonium salts, and N-nitrosoacetanilide showed that position 2 is the most reactive and that position 5 is more reactive than position 6. With benzoyl peroxide in glacial acetic acid at 118°, the product formed contains 77% 2-phenylquinoxaline and 23% 5- and... 

Quinoxaline 1-oxide (32) can be reduced to the parent base by hydrogenation in the presence of a Raney nickel catalyst or by treatment with phosphorus tribromide. Reaction of the N-oxide with acetic anhydride gives initially a mixture of quinoxaline (33) and quinoxalin-2-one (34) but on more prolonged reaction a third product, l-(2-quinoxalinyl)-quinoxalin-2-one (35), is formed. ... 

An earlier report stated that quinoxaline N-oxide is unchanged when heated with acetic anhydride. 

Many quinoxaline-2,3-dithiones have been prepared from the corresponding 2,3-dichloroquinoxalines by heating under reflux with excess of aqueous potassium hydrogen sulfide solution. The alkali-soluble product on acidification with acetic acid yields the quinoxaline-2,3-dithione. When 2,3-dichloroquinoxaline is treated with two molecular proportions of thiourea in ethanolic solution, S-2-(3-mercaptoquinoxalinyl)-isothiouronium chloride is formed in almost quantitative yield. This on treatment with boiling aqueous sodium hydroxide solution yields quinoxaline-2,3-dithione (15). Substituted quinoxaline-2,3-dithiones have also been prepared by this method. Quinoxaline-2,3-dithione has also been prepared from quinoxaline-2,3-dione by treatment with phosphorus pentasulfide in pyridine, thus avoiding the necessity of first forming the dichloroquinoxaline from the dione. ... 

Alkylquinoxalines have also been prepared by homolytic substitution. Thus reaction of quinoxaline with a mixture of the appropriate carboxylic acid and its sodium salt in the presence of aqueous ammonium perox-idisulfate gives the 2-alkylated quinoxaline. Alkylation can also be achieved by the use of the acid and salt in the presence of trifluoroacetic acid and lead(IV) acetate in benzene (Scheme 2-... 

N-H stretching. The H NMR spectrum, in deuterated acetone, shows a methylene singlet at 5 4.44 and a broad band at 5 5.3 due to N-H absorption, which disappears on addition of D2O. 3-Aryl-l,2-dihydro-quinoxalines give monoacetyl derivatives on treatment with acetic anhydride and are oxidized to the corresponding quinoxalines with ben-zoquinone, ferric chloride, or m-nitrobenzoic acid. Other 1,2-dihydroquinoxalines have been prepared from o-phenylenediamine as illustrated in Scheme 2. 

The electronic effects of various substituents in the 6-position are pronounced enough to allow selective monoacylation. Thus 1,2,3,4-tetrahydro-6-nitroquinoxaline is exclusively monoacylated with acetic anhydride or trifluoracetic anhydride at the 4-position. The corresponding 1,4-diacylated derivatives are conveniently prepared by nitration of 1,4-diacetyl- and l,4-bistrifluoroacetyl-l,2,3,4-tetrahydro-quinoxaline, respectively." ... 

Routes via o-aminophenylpyrroles present the most convenient syntheses of a wide variety of pyrrolo[l,2-a]quinoxalines. Thus reaction of the amino compound 6 with acetic anhydride in acetic acid gave the acetamido derivative which was cyclized with phosphoryl chloride to give the 4-methyl compound 7 (R = Me) in 56% yield. The 4-phenyl compound 7 (R = Ph) has been prepared similarly. An even more convenient synthesis of 4-aryl compounds is achieved by reaction of compound 6 with aromatic aldehydes to give the 4,5-dihydro derivatives These are readily oxidized to 4-arylpyrrolo[l,2-a]quinoxalines 9 with manganese dioxide. This approach may be carried out in one step by reaction of compound 6 with aromatic aldehydes (e.g., benzaldehyde) in the presence of cupric acetate. Reaction of the aminophenylpyrrole 6 with 90% formic acid gave pyrrolo[l,2-a]quinoxaline (7, R = H) directly in 98% yield. Pyrrolo[l,2-a]quinoxalines substituted in the l-position and the 7-position have also been prepared from appropriately substituted... 

There is little systematic knowledge of the chemistry of this ring system. Oxidation of 3-phenylbenzo[/]quinoxaline with chromic anhydride in boiling acetic acid gives 3-phenylbenzo[/]quinoxaline-5,6-quinone (28). The quinone reacts with aromatic aldehydes to form addition products 29 on exposure to light. Reduction of 28 with phenylhydrazine gives the corresponding hydroquinone, which is characterized as a diace-... 

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... 

Both D-threo-2,5-hexodiulose (7) and kojic acid (10) afford the pyrido[l,2-a]quinoxaline 11 on treatment with o-phenylenediamine. The pathway via 8 and 9 explains the formation of the tricyclic compound from the hexodiulose. The product 11 forms the N-benzenesulfonate 12 on reaction with benzenesulfonyl chloride. Treatment with acetic anhydride in pyridine gives the diacetyl derivative 13. Quinoxaline-2-carboxylic acid is produced when 11 is oxidized with potassium permanganate. The condensation of o-phenylenediamine with the pyrylium salt 14 affords the pyridoquinoxalinium salt 16 by way of the intermediate N-phenylpyridinium salt 15. ... 

Reduction of quinoxaline with potassium borohydride in acetic acid gives an excellent yield of l,4-diethyl-l,2,3,4-tetrahydroquinoxaline phthalazine reacts similarly, and other carboxylic acids can be used. ... 

The quinoxalines 24 with P-dicarbonyl, p-dinitrile, and p-nitrilecarbonyl fragments, produced in the reaction of 3-(a-chlorobenzyl)quinoxalin-2-one 23 with the anions of p-dicarbonyl compounds, dicyanomethane, and cyanoacetic ester, form the pyrroloquinoxalines 25 when treated with acetic acid (Scheme 3.9) (Mamedov et al. 2004). This cyclization could lead to one and/or two compounds differing in the position of the substituents and R, but only the tricyclic compounds 25a-f are formed as a result of the reaction. 

Similarly, condensed derivatives of pyrrolo[ 1,2-a]quinoxalines 157-160 were obtained from 5-(pyrrol-l-yl)-quinoIines 161 (Scheme 3.46) (Lancelot et al. 1983a), 3-(pyrrol-l-yl)dibenzofurans 162 (Scheme 3.47) (Rault et al. 1979), and 3-(pyrrol-l-yl)carbazole 163 (Scheme 3.48) (Lancelot et al. 1984) containing at positions 6, 2, and 4, respectively, the functional group RC(X)NH, which was introduced by condensation of the corresponding amines with acetic anhydride, phenyl isocyanate, phenyl isothiocyanate, and aliphatic isothiocyanates. 

---