Quinoxaline-2,3-dione reactions

Keywords o-phenylenediamine, oxalic acid dihydrate, cyclization, quinoxaline-dione, 2,3-dichloroquinoxaline, cascade reaction, solid-solid reaction, melt reaction, bis-benzimidazolyl, fluoflavin... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

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

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-... 

Quinoxaline A-oxides undergo rearrangement under a variety of conditions. Thus on treatment of 2-ethoxy- and 2-methoxy-quinoxa-line 4-oxide with hydrochloric acid, rearrangement and hydrolysis occurs to give quinoxaline-2,3-dione. A possible intramolecular mechanism of rearrangement is shown in Scheme 7. Reaction of 2,3-... 

Hie basic reaction is the condensation of a bisorthodiamine with a bisethane-dione (Fig. 5.38). The first papers described the unsubstituted quinoxalines,161 but die phenylquinoxalines described later162 are more stable against oxydative... 

Depending on the reaction temperature and reaction time, tetrahydroisoquinoline 357 afforded different mixtures of 1,2,3,4,11,11 a-hcxahydro-6//-pyrazino[ 1,2-3]isoquinolines 358-361 and tetracyclic compound 362 (Scheme 30) <2005JA16796>. Each of the individual diastereoisomers 358-361 could be transformed into the compound 362. z7r-3//,4a//-3-Phcnylpcrhydropyra/ino[ 1,2-7]isoquinoline-l,4-dione was prepared via automated parallel solid-phase synthesis on Kaiser oxime resin <1998BML2369>. l,2,3,5,6,7-Hexahydropyrido[l,2,3-r/f ]quinoxaline-2,5-dionc was obtained by catalytic hydrogenation of ethyl 3-(2-oxo-l,2,3,4-tetrahydro-5-quinoxalinyl)acrylate in the presence of TsOH over 5% Pd/C catalyst under 40 psi of hydrogen <1996JME4654>. 

The Stille reaction featuring bromoquinoxaline 84 and vinylstannane delivered vinylquinoxaline 85. In addition, 85 was further manipulated to a 5-aminomethylquinoxaline-2,3-dione 86 as an AMPA receptor antagonist [47]. Pd-catalyzed nucleophilic substitution on the benzene ring has also been described [48]. Thus, transformation of 5,8-diiodoquinoxalines to quinoxaline-5,8-dimalononitriles with sodium malononitrile was promoted by PdCl2,(Ph3P)2. 

Attempts to directly iodinate quinoxaline failed, and the synthesis of 2,3-diphenyl-5,8-dibromoquinoxaline is somewhat more involved (Scheme 9) [61]. Starting from ort/zo-phenylenediamine, reaction with SOCI2 gives benzothia-diazole in high yield. Bromination in HBr furnishes 4,7-dibromobenzothiadi-azole, which can be alkynylated or directly reduced [62]. Reduction of the dibromide with sodium borohydride leaves the halide substituents unmolested but opens the ring to furnish l,4-dibromo-2,3-diaminobenzene. Reaction of this intermediate with a 1,2-dione furnishes a 2,3-disubstituted 5,8-dibromo-quinoxaline. Pd-catalyzed alkynylation finishes the sequence off and removal of the TMS groups yields the desired 5,8-diethynylquinoxaline monomers (Table 9, entries 13,14). 

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... 

Bis(bromomethyl)quinoxaline (126) is better prepared by the condensation of o-phenylenediamine and l,4-dibromobutane-2,3-dione than by side-chain bromination of 2,3-dimethylquinoxaline. It reacts with secondary amines, forming quinoxalino[2,3-c]pyrrolidine salts, e.g. (127).134 Reaction with thiols yields 2,3-bis(thiomethyl)quinoxalines,135... 

Benzils, like other 1,2-diones, react with 1,2-benzenediamines to form diaza-arenes known as quinoxalines. This kind of reaction is an important general procedure for the synthesis of aromatic ring systems containing nitrogen ... 

Cyclocondensation of pipecolinic acid and malic acid anhydride in pyridine afforded 3-hydroxy-2,3-dimethylperhydropyrido[l,2-a]pyrazine-l, 4-dione (74CB2804). Cyclocondensation of bis(2,4,6-trichlorophenyl) mal-onates with 2-methyl-, 2-benzyl- and 2-ethoxycarbonylmethylquinoxalines and -3-ones at 250°C afforded 8-hydroxy-10//-pyrido[l,2-a]quinoxalin-10-ones and their 5,6-dihydro-6,10-dione derivatives (77M103). Under Horner-Wittig reaction conditions, the reactions of 2-formylquinoxaline and dialkyl phosphonosuccinates (314) also involved cyclization to give alkyl 10-oxo-10//-pyrido[l,2-a]quinoxahne-8-carboxylate (80LA542). 

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