Quinoxaline-5,8-diones synthesis

At least two derivatives of pyran have been used for the primary synthesis of quinoxalines. Thus o-phenylenediamine (390) and 6-(p-methoxyphenyl)-6-methyl-5,6-dihydro-2//-pyran-2,5-dione (391) in methylene chloride at 20°C open to the air for 48 h gave 3-[2-hydroxy-2-(p-methoxyphenyl)propionyl]methyl-3,4-dihydro-... 

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>. 

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). 

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 ... 

Synthesis of 14C- and 3H-labelled 6-nitro-7-sulphamoylbenzo[F]quinoxalin-2,3-dione (173)... 

Oxidations of quinoxalines without ring opening include 7V-oxide formation (see Section 6.3.2.1.4.1.) and synthesis of quinoxalinones (see Section 6.3.2.1.4.4 ). 5- or 5,8-Dihy-droxyquinoxalines are oxidized to quinoxaline-5,8-diones i/ s7.4.s8... 

Hui X, Desrivot J, Bories C, Loiseau PM, Franck X, Hocquemiller R, Figadtae B (2006) Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines. Bioorg Med Chem Lett 16(4) 815-820. doi 10.1016/j.bmcl.2005.11.025 Hulme C, Tang S-Y, Bums CJ, Morize 1, Labaudiniere R (1998) Iminoved procedure for the solution phase preparation of l,4-benzodiazepine-2,5-dione libraries via Armstrong s convertible isonitrile and the Ugi reaction. J Org Chem 63(22) 8021—8023. doi 10.1021/jo980622r Humplett WJ, Lamon RW (1964a) 4-Thiazoline-2-thiones. 1. The Stmcture of intermediate... 

Scheme 3.25 4-[(Ttrimethylsilyl)methyl]quinoxaline-2,3(lff,4//)-diones in the synthesis of pyirolo[ 1,2- ]quinoxalines...

When an analogous strategy was used for the synthesis of pyrrolo[l,2-fl] quinoxaline from 3,6-dimethoxy-2-nitroaniline, 6,9-dimethoxypyrrolo[l,2-a] quinoxaline 191c, interesting in view of the presence of the methoxy groups, was obtained under the right conditions, it was converted into 6,9-dihydroxypyrrolo [ 1,2-a]quinoxaline and pyrrolo[l,2-a]quinoxaline-6,9-dione 192 (Scheme 3.57). 

A method of synthesis of imidazoquinoxalin-4-ones that affords these heterocyclic systems with different substiments in the 3-, 5-, 6- and 7-positions has been well developed (Waetjen 1987 Wae en and Hansen 1988, 1990, 1991 Hansen and Wae en 1989b, c Jacobsen et al. 1996a TenBrink et al. 1993). The method is based on the reaction of quinoxaline-2,3-dione derivatives 53 with diethyl chlorophosphite leading to diethyl quinoxaUnyl phosphates 54. The latter, without isolation, are introduced into the reaction with substimted methyl isocyanides in the presence of a base leading to products 55 (Scheme 4.27). 

Scheme 4.46 l-(o-Methylaminophenyl)imidazole-2,5-dione as precursor for the synthesis of imidazo[ 1,5-a]quinoxalines... 

Scheme 4.61 Synthesis and cyclization of l,4-bis(aioylmethyl)quinoxalin-2,3.diones...

The procedure for the synthesis of macrocycles 224a, b, i.e., the precursores of 218a, b is given in Scheme 5.51. The synthesis is based on the 3-chloroquinoxalin-2-ones. In this process, a 7-methoxy derivative has been obtained from 7-methoxyquinoxalin-2,3-dione 69b by the treatment with thionyl chloride in DMF. 3-Chloroquinoxaline-2-ones are transformed into quinoxaline... 

Ferfra S, Ahabchane NH, Essassi EM, Bellan J, Pierrot M (2005) Synthesis and complexation of new macrocycles derived from quinoxaline-2,3-dione. J Mar Chim Heterocycl 4 49-58 Forster HI, Niclas HI, Lukyanenko NG (1985) Umsetzungen von benzofuroxan-kronenethem darstellung kronenetheranellierter heterocyclischer /V-oxide. Zeit Chem 25(3) 102-103. doi 10. 1002/zfch. 19850250315... 

Synthesis of 3-(l-phenylhydrazono-L-threo-2,3,4-trihydroxybutyl)-lH-quinoxalin-2-one 34 was achieved in 86% yield by MW irradiation for 2.5 min of L-ascorbic acid 30 with o-phenylenediamine and phenylhydrazine in the presence of acetic acid (Scheme 34). Another method of synthesis of a fused heterocyclic tetracycle could be obtained from MW irradiation of 2-(N,N-dimethylamino)methylene-5,5-dimethylcyclohexane-l,3-dione and 2-benzimid-azoleacetonitrile (Scheme 35). The reaction proceeds in isopropanol using a catalytic amount of piperidine leading to the formation of tetrahydrobenzimidazo[l,2-fl]quinoline derivative 38 [57]. 

Cheap and easily recyclable graphite has also been used as a green, heterogeneous catalyst for the synthesis of qui-noxaline derivatives [121] starting from diketones (substituted benzils, phenanthrene-9,10-dione) and/or benzoins and aromatic diamines in 71-93% yields at room temperature in ethanol (Scheme 87). Iodine (10mol%) has also been used as an efficient catalyst for a similar synthesis of quinoxalines at room temperature (Scheme 87) [122,123]. The reaction is carried out in DMSO/MeCN at room temperature to yield 85-95% product. 

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