3- -quinoxalinone reaction

When activating substituents are present in the benzenoid ring, substitution usually becomes more facile and occurs in accordance with predictions based on simple valence bond theory. When activating substituents are present in the heterocyclic ring the situation varies depending upon reaction conditions thus, nitration of 2(177)-quinoxalinone in acetic acid yields 7-nitro-2(177)-quinoxalinone (21) whereas nitration with mixed acid yields the 6-nitro derivative (22). The difference in products probably reflects a difference in the species being nitrated neutral 2(177)-quinoxalinone in acetic acid and the diprotonated species (23) in mixed acids. 

In contrast, the reaction of dimethyl acetylenedicarboxylate with the benzodiazepinone 4-oxide 21 gives the quinoxalinone 24 by way of the isolable intermediates 22 and 23.249... 

The important conversion of tautomeric quinoxalinones into halogenoqui-noxalines has been discussed in Section 3.1.1. Other reactions are covered in the subsections that follow. 

Note There appear to be no recent examples of this reaction with simple alkoxy substrates (perhaps because normal aliphatic ethers need quite vigorous treatment, such as boiling hydriodic acid), but so-called isopropylidenedioxy derivatives (that undergo facile hydrolysis) have been used in this way. l-[2,3-(Isopropylidenedioxy)propyl]-3-methyl-2(17/)-quinoxalinone (165) gave l-(2,3-dihydroxypropyl)-3-methyl-2(l//)-quinoxahnone (70% AcOH, reflux, 2 h 35% homologs likewise). ... 

These ethers, both nuclear and extranuclear, undergo a few useful reactions, including hydrolysis to corresponding quinoxalinones or hydroxyquinoxalines, which has been covered in Sections 4.1.1 and 4.3.1, respectively. The other reactions are illustrated in the following classified examples. 

The few recently reported reactions of fixed quinoxalinones are illustrated in the following examples. 

Hydrazinocarbonylmethyl-2(l//)-quinoxalinone (112) gave 3-azidoformyl-methyl-2(l//)-quinoxalinone (113) (crude material uncharacterized) and thence 3-oxo-3,4-dihydro-2-quinoxalinecarbonitrile (114) [NaN02, H2O, 5°C solid azide, which redissolved on prolonged stirring then 95°C, 2 h product (114) (27% after separation from a major tricyclic product) a mechanism for this one-pot reaction is suggested]... 

In a less straightforward way, D-glucose (393) underwent a Maillard-type reaction with an excess of glycine (394) under microwave irradiation to afford 5-hydroxy-l,3-dimethyl-2(lZ/)-quinoxalinone (395) as a major product,926 Repetition with labeled reactants suggested that the product contained six carbon atoms from the sugar and four from the amino acid on this evidence, a detailed mechanism has been postulated.926... 

This category is represented in the facile reaction of o-phenylenediamine (408) with 4-benzoyl-5-phenyl-2,3-dihydro-2,3-thiophenedione (409) (in toluene at 20°C for 30 min) to afford 3-(a-benzoyl-p-mercaptostyryl)-2(l//)-quinoxalinone (410) in 98% yield 744 also in the complicated reaction of 3-methyl-2,2,4-trinitro-2,5-dihydrothiophene 1,1-dioxide (411) with 2 equiv of ethyl 4-aminobenzoate (412) (in acetonitrile but no further details) to give ethyl 2-(p-ethoxycarbonylphenyl)-3-(l-methyl-2-nitrovinyl)-6-quinoxalinecarboxylate (413) in 51% yield.831 Several... 

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

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