First synthesis of 6,7-diaminoindole and 1,2,5-selenadiazolo[3,4 -g ]indole

5-Methyl-4-nitro-2,1,3-benzoselenadiazole ( 1 ) was converted into 1,2,5-selenadiazolo[3,4-g ]indole ( 3 ) by the Batcho-Leimgruber indole synthesis. Subsequent deselenation afforded 6,7-diaminoindole ( 4 ) which on treatment with biacetyl afforded 2,3-dimethylpyrrolo[2,3-f ]quinoxaline ( 5 ) in 80% yield from 3 .


Introduction
Aromatic amines represent an important class of compounds for a wide variety of pharmaceuticals, pesticides, additives and dyes.In recent years, mutagenic aminoimidazoquinoxalines, -quinolines and -naphthyridines have been prepared 1 for analytical purposes and for structure-biological activity studies related to food carcinogens. 2Retrosynthetic analysis of some needed bioisosteric pyrroloquinoxalines led to 6,7-diaminoindole (4).Surprisingly, although derivatives of 4 are known, 3 the unsubstituted indole 4 has not been reported.Moreover, neither has the possible precursor 6,7-dinitroindole nor any suitable aminonitro(so)indole. On the other hand, deselenation of 2,1,3-benzoselenadiazoles (bsd) has previously afforded ortho-benzenediamines which have then been conveniently converted into, eg, less accessible 4-nitrobenzimidazoles 4 and elusive 5-nitroquinoxalines. 5 Thus, we thought that the unsubstituted indole 4 might be obtained from the readily available 1 6 via the novel 1,2,5-selenadiazolo [3,4-g]

indole (3).
This paper communicates the first preparation of selenadiazoloindole 3 and diaminoindole 4, together with an illustration of their synthetic use en route to nitrogen heterocycles.
Batcho-Leimgruber indole synthesis 7 on bsd 1, using N,N-dimethylformamide dimethyl acetal (DMFDMA) in acetonitrile or DMF gave the trans isomer (J = 13.1 Hz) of enamine 2 in 84% isolated yield.The reductive cyclization is usually done with hydrogen over a palladium catalyst or with Raney nickel and hydrazine. 7Attempts to transform 2 into 3 by hydrogenation over 10% Pd-C in THF, at ambient conditions and up to 50 psi, gave only intact 2. Further, no traces of 3 were detected in the dark reaction mixtures produced when hydrogen and Raney nickel in THF and/or alcohols were employed at various temperatures.Heating 2 with hydrazine hydrate and Raney nickel in THF and/or alcohols gave the desired 3 in less than 10% yield.However, more efficient ring closure to 3 was eventually achieved by heating 2 with iron powder in acetic acid and ethanol, conditions known to convert 4-nitro-bsd into the amino compound without substantial deselenation.Deselenation of bsd is usually accomplished by, eg, hydrogen iodide in hydrochloric acid, 4,5 stannous chloride and hydrochloric acid, 9 zinc and hydrochloric acid 10 or by ammonium sulfide.1a,4,5a Because of the potential oligomerization of the 2-unsubstituted indole 3 in acid, 11 we first attempted deselenation by ammonium sulfide in ethanol.In contrast to previous efficient deselenations with this reagent, 1a,4,5a only a small amount of 3 was deselenated even in higher boiling alcohols.However, the desired diaminoindole 4 12 could be obtained in high yield by heating 3 with hydrazine hydrate and Raney nickel.Treating crude 4 with selenium dioxide gave selenadiazoloindole 3, quantitatively and spontaneously as indicated by TLC.Furthermore, crude 4 was treated with diacetyl to provide the apparently unknown pyrroloquinoxaline 5 in 80% isolated yield from 3. Other pyrrolo[2,3-f]quinoxalines have been prepared and tested for biological activity. 13Derivatives of the sulfur analogue of 3 have been obtained via Fisher indole synthesis on 4-amino-benzothiadiazole. 3,14n conclusion, the Batcho-Leimgruber indole synthesis has been successfully applied to 1 for the synthesis of unsubstituted 6,7-diaminoindole.Since the indole unit occurs widely in nature, and its chemistry is one of the most active areas of heterocyclic chemistry, we believe that access to ortho-diaminoindoles will find many applications.ortho-Diamines are easily transformed into, eg, benzimidazoles, quinoxalines and benzodiazepines which are often found in numerous pharmaceuticals.Work is in progress on the preparation of the isomeric 5,6-and 4,5diaminoindoles.

Experimental Section
General Procedures.Yields are not optimized.Evaporations were performed under reduced pressure at 40 o C. All reactions and purifications were monitored by thin layer chromatography (UV detection and Van Urk's reagent 15 ) on aluminium sheets coated with silica gel 60 F 254 plates (Merck).'Flash' and 'dry flash' column chromatography was performed on silica gel 60 (35-70 µ, Grace).Melting points (uncorrected) were determined on a Büchi Melting Point B-545.The 1 H and 13 C NMR spectra were recorded on a Bruker DPX 300 spectrometer at 25 o C, and referenced to the solvent (Me 2 SO δ H 2.50 and δ C 39.5 or CHCl 3 δ H 7.26 and δ C 77.0).Gradient HMBC experiments were used for the assignments.Coupling constants J are given in Hz and without sign.The infrared spectra were recorded on a Perkin-Elmer FT-IR 1600 instrument.The electrospray mass spectra were taken on a Perkin-Elmer API 150Ex spectrometer and the EI (70 eV, direct insertion) mass spectrum of 1 was taken on a Micromass Platform spectrometer.Ions containing isotopes other than 80 Se are not listed.

Materials.
Unless otherwise stated, these were commercial samples.All organic solvents were either freshly distilled or of pa quality.Solvent mixtures are defined by volume ratios (v/v).Petrol refers to petroleum ether, bp 60-70 o C.