Pyrrolo quinoxalin-2-ones

Thermolysis of 3-alkyloxy- and 3-aroyloxy-5-phenyl-l,2,4-pyrrolo[l,2- ]quinoxaline-l,2,4-triones afforded 5-phenyl-9-(4-phenyl-3-oxo-3,4-dihydro-2-quinoxalinyl)-6,8,10-trioxo-5,6,9,10-tetrahydro-87/-pyrido[l,2-tf ]quinoxaline-7,9-dicarboxylates <2000CHE615, 2004CHE1295> and 7-aroyl-8-aroyloxy-5-phenyl-9-(4-phenyl-3-oxo-3,4-dihydro-2-quinoxalinyl)-5,6-dihydro-1077-pyrido[l,2- ]quinoxaline-6,10-diones <2002CHE498>, respectively. Thermolysis of 3-aryl-2-(5-aryl-2,3-dioxo-2,3-dioxo-4-furanyl)quinoxalines gave 7-aroyl-8-aroyloxy-6-aryl-9-(3-aryl-2-quinoxalyl)-10/7-pyrido[l,2- ]quinoxalin-10-ones <2001CHE1314, 2002RCB850>. 

Inspired by the bioorganometallic approach, two series of ferrocenyl pyrrolo[ 1,2-a] quinoxalines were designed and prepared (Fig. 17). The derivatives were tested in vitro against three different strains of P. falciparum F32, FcBl, and PFB [107]. The best results (IC50 between 30 and 70 nM in comparison to CQ IC5o = 225 nM) were observed in the first series with a bis(3-aminopropyl)piperazine as a linker. These compounds were tested for then ability to inhibit p-hematin formation. For all but one case, the derivatives did not interfere with hemozoin formation... 

Treatment of 4-substituted benzene-l,2-diamines with 6-hydroxy-6-(2,3,5-tri-C -benzoyl-)3-D-ri-bofuranosyl)-6/f-pyran-3(2//)-one leads to 6- and 7-substituted 2-()8-D-ribofuranosyl)quinox-alines and 7- and 8-substituted l-()8-D-ribofuranosyl)pyrrolo[l,2-a]quinoxalines the synthesis of a quinoxaline acyclo-C-nueleoside from benzene-1,2-diamine and a furanone glycoside... 

Pyrrolol3,4-6 quinoxaline 4-oxide, 1164 Pyrrolol 12.3-de Iquinoxalin-S-one, 1242 Pyrrolo 2.l-61thiazole, 840,912 Pynolol3,4- thiazole-4,6-dione. 1067 P rrolo[2,l-6]thiazoi-5-one, 913... 

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... 

Catalytic hydrogenation of l-chloropyrrolo[l,2-a]quinoxalines results in removal of the halogen atom. Apparently the dechlorinated products are themselves reducible, and care must be taken in dechlorinations to allow the absorption of only one mole of hydrogen. A recent paper describes reduction of the 4,5 bond in pyrrolo[l,2-a]quinoxalines. 1,5-Dihydro-1-0X0 compounds are resistant to hydrogenation at atmospheric pressure. Reduction of the 1-oxo compound 117 over palladium on charcoal at 2000 psi gave an unidentified tetrahydro derivative. " The dioxo compounds 118 have been reduced with lithium aluminum hydride to give the hexahydro products 119. Heating 4,5-dihydro-4-thioxo derivatives with Raney nickel results in formation of the aromatic, desulfurized compound. Stannous chloride has been used to reduce... 

Scheme 2.73 One-pot synthesis of the pyrrolo[l, 2-a]quinoxalines 406 and a plausible mechanism for their formation...

One of the most widespread and most widely used among methods for the synthesis of pyrrolo[ 1,2-a]quinoxaUnes is the method involving the intramolecular cycliza-tion of derivatives of quinoxaline with substituents at position 2 and containing at least three carbon atoms with reaction centers capable of nucleophilic attack. Quinoxalines 1, containing a ycarbonylalkyl substituent at position 2 (ketones, carboxylic acids, esters) undergo intramolecular cyclization under the influence of acids with the formation of pyrroloquinoxalines 2-4 (Scheme 3.1) (Kumashiro 1961 Taylor and Hand 1962, 1963 Cheeseman and Roy 1969). 

However, the reaction of 2,3-dimethylquinoxaline 51a with maleic anhydride 46a under standard conditions (Taylor and Hand 1963) takes place with the formation of a compound with the empirical formula C14H12N2O3, the IR spectrum of which does not contain bands for the stretching vibrations of the anhydride groups but there are bands for the stretching vibrations characteristic of NH, the OH of the carboxyl function, the double bond, and an amide vinylog (Scheme 3.16). The NMR spectra and the chemical properties of the adduct show that pyrrolo[l,2-a]quinoxaline 52a is formed as a result of the reaction, and this can be represented by the Scheme 3.16 (Taylor and Hand 1962, 1963). Accordingly, the condensation of maleic anhydride with 2-methylquinoxaline and 2-methyl-3-phenylquinoxaline gives 2-carboxymethyl- 52b and 2-carboxymethyl-4-phenylpyrrolo[l,2-a] quinoxalin-l(5H)-ones 52c (Taylor and Hand 1963 Taylor and Cheeseman 1964). 

The formation of the pyrrolo[l,2-a]quinoxaline stmcture in this reaction can be represented in one of two ways (Scheme 3.38) (a) isomerization of the 2-hydroxy-1,5-diketone 118 to the 5-hydroxy-l,4-diketone 121 with the subsequent formation of the o-aminophenylpyrrole 122 and closure of the dihydroquinoxaline structure 123 (b) reaction of the a-hydroxyketone fragment with 1,2-DAB with the formation of the hydroquinoxaline derivative 125 and subsequent closure of the dihydropyrrole ring and isomerization of the 3,3a-dihydropyrrolo[l,2-a]quinoxaline structure 124 to the more stable 4,5-dihydropyrrolo[l,2-a]quinoxaline structure 123. 

Thus, a rare one-pot reaction for assembling pyrrolo[l,2-fl]quinoxalines from 1-(2-nitrophenyl)pyrroles and various alcohols. The nitro reduction, alcohol oxidation, heterocycle formation, and heterocycle oxidation were realized in a cascade. A wide range of these fused heterocycles bearing different alkyl and aryl groups in position 4 have been elaborated from suitable substrates thereby 3-nitro-2-pyrrolopyridine was also compatible with this process, giving the corresponding fused tricyclic compounds. 

Alizadeh A, Ghanbaripour R, Zhu L-G (2014) Pipaidine-Todine a dual system catalyst for synthesis of coumarin bearing pyrrolo[l,2-a]quinoxaline dtaivatives via a one-pot three-component reaction. Tetrahedron 70 2048-2053. doi 10.1016. tet2014.01.038... 

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