The Four 6-Halo-7-nitroquinoxalines

The study of relative nucleofugicities of nitro and halogen in quinoxalines required the synthesis of the four 6-halo-7-nitroquinoxalines 2a-d.The fluoro-, chloro-and bromo-derivatives were made from the commercially available or readily accessible 1.2-diamino-4-halobenzenes, using the nitration of the corresponding p-toluenesulfonamides.T h ~s scheme failed in the case of the iodo compound because of extensive nitrodeiodination.The synthesis of 6-iodo-7-nitroquinoxaline was finally achieved from m-fluoroiodobenzene by taking advantage of the high reactivity of fluorine, compared to iodine, in 2,4-dinitrohalobenzenes. 1 The relative nucleofugicities of nitro and halogen in quinoxalines towards various nucleophiles are presently being examined in our ; in a planned extension of this study involving a comparison between the halogens, we needed the title compounds, 6-fluoro-, 6-chloro-, 6-bromo-and 6-iodo-7-nitroquinoxaline (2-d) respectively.2,3-Disubstituted 6-chloro-7-nitroquinoxalines were previously reported by 4 BOyer et al. who condensed "impure" 1,2-diamino-4-chloro-5-nitrobenzene with 2.3butanedione or 9,lO-phenanthrenequinone.Our first attempts in this field were 5 based on the finding of Bailey and Wood who observed a facile displacement of a nitro group by a chlorine atom in a quinoline derivative using HC1.Treating 6.7dinitroquinoxaline 1 with dry hydrogen chloride in DMF at 85'C (Scheme 1) gave, besides unreacted starting material, a mixture of 6-chloro-7-nitroquinoxaline 3 and 6,7-dichloroquinoxaline 2 .When it was attempted to force the conditions in order to transform all of the starting material, 2 was the sole product, isolated with a 75% yield.Similar results were obtained with 6,7-dinitro-2.3-diphenylquinoxaline.Z 1, R= H, C H 6 5 2 -3 -Scheme 1. Reagents; HC1, DMF, 85'CThis method suffers several disadvantages.the major one being the need for large scale chromatographic separations.Moreover, this route is precluded for the corresponding methyl derivatives : when 2,3-dimethyl-6,7-dinitr0quin0xa1ine was