3- benzo quinoxaline oxidation

The pyrazine ring is relatively stable to oxidation, and many pyrazine-carboxylic acids have been prepared from quinoxalines, phenazines, and other fused pyrazines by oxidation with potassium permanganate. This reaction has been most used for the oxidation of quinoxalines, for example, 77 -> 78. The oxidations are usually carried out with potassium permanganate in alkali (397), but may also be effected without added base (398). Crippa and Perroncito (399) have also used chromic oxide in acetic acid-acetic anhydride to oxidize benzo(/]quinoxalines (79). Pyrazines prepared by this method are summarized in Table 11.9 (397-419). 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzo-furazan oxide (171) with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Earlier developments to 1981 were surveyed by Porter <84CHEC-I(3)157>, and later progress has been reviewed by Haddadin and Issidorides <93H(35)1503> who first demonstrated this reaction. Dienamines and azadienes (172) also react with benzofurazan oxide to yield... 

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... 

Several transformations of 2- and 3-D-arabotetrahydroxybutyl benzo[/]quinoxalines have been reported. Thus oxidation of the 2-tetrahydroxybutyl derivative with hydrogen peroxide in dilute sodium hydroxide gives the 2-carboxylic acid, m.p. 185°, and oxidation with potassium periodate in dilute acetic acid gives the 2-aldehyde,... 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

The pyrazine ring is stable toward permanganate oxidation, and this explains a variety of pyrazinecarboxylic acids that have been prepared from quinoxalines or benzo-fused quinoxalines. In contrast, alkyl side chains on pyrazines are effectively oxidized by permanganate, selenious acid, selenium dioxide, or dichromate to afford the corresponding carboxylic acids (Section 8.03.7.1). Oxidation of pyrazines with hydrogen peroxide or percarboxylic acids gives pyrazine A -oxides and/or A, A -dioxides (Section 8.03.5.2). 

Biologically interesting benzo[ ]furyl quinoxalines were prepared by sequential oxidation and condensation (Scheme 83) <2004T6063>. 

Benzofuroxan reacts with benzo[6]furan-3(2//)-oncs to give a product at an oxidation level lower than the expected di-lV-oxide in a process where benzo[A]furan-3(2//)-one plays the dual role of substrate as well as reductant during the reaction, and redox processes determine the structure of the products,This is a general, one-step synthesis of 2-(2-hydroxyaryl)-quinoxaline 4-oxidcs, c.g. formation of 3. ... 

Both the C and N chemical shifts of a number of quinoxalines substituted at position 2 with the n-electron excess 2 -benzo[ ]furanyl substituent, which has at position 3 a hydroxy or amino group, could be satisfactorily calculated by the GIAO method on the basis of HF and DFT ab initio structures. Quantum mechanical calculations using the 3-21 G(d) basis-set were performed on some p-substituted diaryl tellurides and aryl Me tellurides, and the corresponding cationic radicals of these compounds. Calculated relative radical stabilization energies were shown to correlate with experimental data, and the peak oxidation potentials and Te chemical shifts were... 

The reaction of benzene-1,2-diamines with 3,4,6-trichloropyridazine leads to 3-chloro-5,10-di-hydropyridazino[3,4- >]quinoxalines (6,7-benzo-annulated pyiazino[2,3-c]pyridazines) which can be oxidized to the fully conjugated system using potassium dichromate.74... 

The pyrazine ring is stable to permanganate oxidation, and this accounts for a variety of pyrazinecarboxylic acids that have been prepared from quinoxalines, benzo-fused quinoxalines including phenazines, and pyrido-fused pyrazines . In other fused systems, particularly pter-idines, the pyrimidine ring is easily hydrolyzed under either acidic or basic conditions to give numerous 3-aminopyrazinecarboxylic acid derivatives. 

Relatively few reactions of quinoxaline derivatives occur with change of ring size. Isolated examples are noted in the following text. For example, ring contraction to benzimidazole derivatives occurs when 2,3-diphenylquinoxaline (Chapter XV) or 2-halogenoquinoxalines (Chapter X) are treated with potassium amide in liquid ammonia and quinoxalin-2-one is treated with hydrazine (Chapter VX It is also found that oxidation of l-aminoquinoxalin-2-ones with lead tetraacetate give benzo-1,2,4-triazines (Scheme 6) (Chapter V). 

Peracetic acid oxidation of benzo[g]quinoxaline does not give an N-oxide/ and oxidation of the 5,10-dione with chromium trioxide in glacial acetic acid, or 40% sulfuric acid, yields the 2,3-dioxo derivative 15. The latter compound gives 2,3,5,10-tetrachlorobenzo[g]quinoxaline (16) on treatment with phosphorus pentachloride. ... 

To a solution of 0.2 g 4-butyl-l-[(benzo[l,2-c]l,2,5-oxadiazol-5(6)-yl-A/ i-oxide) methylidene]semicarbazide (0.72 mmol) and 0.07 mL Et2NH in 0.5 mL DMF, was added 0.13 mL vinyl acetate (1.44 mmol) over 10 min at 0" C. The reaction mixture was then stirred at 40°C for 24 h. An additional 1.3 mL vinyl acetate (14.4 mmol) and 1.0 mL Et2NH were added, and the stirring was continued at 40°C for 48 h. After that, the solvent was removed in vacuo and the oily residue was co-evaporated with toluene (3 x 10 mL). The residue was purified by silica gel column chromatography using CH2CI2 as the eluent to afford 7% 4-butyl-l-[(quinoxalin-6-yl-Ai,A4-dioxide)methylidene] semicarbazide as colorless oil. 

The condensation of 2,3-diaminobenzo-15-crown-5 2a with s-trans-chloroethanedial dioxime proceeds with the formation of the (15-crown-5)eno[g]quinoxaline-2(lfJ)-one oxime 11a, which when heated in absolute ethanol at 60 °C in the presence of C0CI2 for 4h results in 2,2 -azobis[(15-crown-5-eno[g]quinoxaline)] 12 (1986CB3870).The use of cyanogen-di-AT-oxide and (E,fr)-dichloroglyoxime instead of the s-twns-chloroethanedial dioxime in the reaction with 2,3-diamino-benzo-15-crown-5 2a and 12,13-diamino-4,7-bis(ferrocenylmethyl)-2,3,4,5,6,7,8,9-octahydrobenzo[k]-4,7-di-aza-l,10-dithiacyclo do decine (2b) makes it possible to synthesize the macrocyclic dioximes 11b,c (1986JCR(S)90, 2007JCOC2509). 

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