Polycyclic heterocycles with acidic N-H groups IX 1 . The unexpected decomposition route of 2-(3-oxo-3,4-dihydroquinoxalin-2-yl)benzenediazosulfonates

The diazosulfonates obtained by diazocoupling of 2-(3-oxo-3,4-dihydroquinoxalin-2-yl)benzene-diazonium chloride and its 6,7-dimethyl-derivative 2a,b with sodium sulfite decompose by an unique route in aqueous solution to afford 1-(1 H -indazol-3-yl)-1 H -benzimidazol-2(3 H )-one 4a , and its 5,6-dimethyl-derivative 4b , respectively. The structure of 4a was confirmed by single crystal X-ray analysis.

The aim of the present work was to arrive at a spatial depiction of this molecule by single crystal X-ray analysis and to propose a probable mechanism for this anomalous reaction.Furthermore, in accordance with the latest knowledge, we also revise the structure of the product formed from 3-(2-aminophenyl)-6,7-dimethylquinoxalin-2(1H)-one 1b by the reaction described in our previous communication 2 on the basis of analogy.

Results and Discussion
Primarily we were interested in whether the unusual transformation of diazonium salts 2a and 2b, as described in reference 2 , occurs after the preceding coupling reaction with sodium sulfite forming the corresponding diazosulfonates 3a, 3b, or whether other factors are involved in the transformation.Therefore, the reaction of diazonium salts 2a and 2b with sodium sulfite was not carried out according to the previously published standard method for preparation of arylhydrazines, which we used in the previous paper 2 .As expected, we were successful in isolation of the diazosulfonates 3a and 3b by the reaction of diazonium salts with sodium sulfite without acidification of the reaction mixture.Diazosulfonates 3a and 3b are bright yellow crystalline substances which are quite stable in the solid state at room temperature.In aqueous solution they transform slowly into 1-(1H-indazol-3-yl)-1H-benzo[d]imidazol-2(3H)-one 4a resp.its 5,6-dimethylderivative 4b even at low temperature.We were concerned with whether the tendency of these compounds 3a and 3b to undergo the described reaction would restrain their coupling ability, or not.
As reaction component we chose 1,3-diaminobenzene, which is a well-tested component for azocoupling reactions.We found that, in this regard, diazosulfonates 3a and 3b behaved identically to all known arenediazosulfonates 4 and it was possible to prepare the corresponding substituted chrysoidines 5a or 5b.The reaction rate of the described coupling reactions was substantially lower than that of the coupling reactions of diazonium salts 2a or 2b with the same compound.This corresponds to the known reactivity of diazosulfonates 4 .Interestingly, high antiprione activity 13 was discovered at the unsubstituted chrysoidine.From this point of view, substituted chrysoidines 5a and 5b may also possibly be of interest.
As mentioned earlier, in aqueous solution the diazosulfonates 3a and 3b undergo a remarkable transformation yielding 1-(1H-indazol-3-yl)-1H-benzo[d]imidazol-2(3H)-one 4a or its 5,6-dimethyl-derivative 4b.The transformation proceeds rather rapidly and quantitatively as the diazosulfonates 3a or 3b are warmed in a highly acidic aqueous medium.This implies that diazosulfonates 3a or 3b are the key intermediates in the described 2,3 transformation of 3-(2aminophenyl)quinoxalin-2(1H)-one 1a and its 6,7-dimethyl derivative 1b into compounds 4a or 4b.It is noteworthy that the described transformation of diazosulfonates 3 takes place even when mineral acids are absent.In this case the reaction is slower, but follows the same stoichiometry.Also the quantity of hydrogen sulfate anion eliminated during the reaction precisely corresponds to the equations shown above.This was confirmed by adding BaCl2 solution to the filtrate after the isolation of the compound 4. The amount of precipitated BaSO4 was precisely the stoichiometric amount.The product formed by the mentioned cleavage reaction of diazosulfonate 3a, 1-(1H-indazol-3-yl)-1H-benzo[d]imidazol-2(3H)-one 4a, has already been characterized in paper 2 , however with an incorrect structure.It forms bright yellow crystals almost insoluble in water, and only slightly soluble in nonpolar solutions.During its formation from diazosulfonate 3a and also during its crystallization from solvents containing water it crystallizes as the monohydrate 4a×H2O, which has been used for single crystal X-ray analysis.The molecular structure of 4a×H2O is shown in Figure 1 while selected bond lengths and angles are given in Table 1.The molecule of 4a contains two different N-containing heterocyclic rings: indazole (A) and benzimidazole (B).Each of the rings is essentially planar with the maximum deviation from the least-squares planes being 0.0114(33) Å for C11 (ring A), and 0.0120(29) Å for C6 (ring B).The dihedral angle between rings (A) and (B) is 47.663(54).Both the oxygen atoms O1 and O2 lie nearly in the least-square plane B, with the deviations being 0.0329(20) Å (for O1) and 0.0225(20) Å (for O2).Surprisingly, no X-ray structure of the compounds involving the skeleton forming indazole and benzimidazole rings, and connected by a mode as in 4a×H2O, has been deposited in the Cambridge Structural Database (CSD, Version 5.29). 12However, the bond lengths and angles are quite normal, thus supporting the presence of a high degree of aromaticity in 4a.The secondary structure is further stabilized by intermolecular hydrogen bonds of the O-H…O, N-H…O and O-H…N type (Table 2, Figure 2).The key step of the mentioned unusual transformation of diazosulfonates 3a and 3b into indazolylbenzimidazoles 4a resp.4b is the contraction of the quinoxaline cycle to the benzimidazole ring.A possible mechanism could be initiated by a nucleophilic addition of the N atom of the diazosulfonate group to a C=N quinoxaline cycle bond resulting in the spirocycle 8.After hydrolytic cleavage of hydrogen sulfate the spirocycle 9 rearranges into benzimidazole derivative 4.This step, in which C-C bond splitting of the quinoxaline cycle occurs, differs this transformation from similar previously known reactions 5,14 in which the quinoxaline ring also contracts.

Experimental Section
Melting points were determined on a Boetius stage apparatus.NMR spectra of solutions in DMSO-d6 were measured on a Bruker Avance 300 spectrometer (300 MHz).Elemental analyses were obtained with an EA 1108 Elemental Analyzer (Fison Instrument).Mass spectrometric experiments were performed using an LCQ ion trap mass spectrometer (Finnigan MAT, San Jose, CA, USA).X-ray diffraction data for the compound 4a×H2O were collected on a four-circle ĸ-axis Xcalibur2 diffractometer (Oxford Diffraction, Ltd.) equipped with a CCD detector using monochromated (monochromator Enhance, Oxford Diffraction, Ltd.) Mo K radiation ( = 0.71073 Å) at 110(2) K. Data collection, cell parameter refinements and data reduction were performed with the CrysAlis program package (Oxford Diffraction, Ltd.). 9The structure was solved by direct methods using SHELXS-97 and all non-hydrogen atoms were refined anisotropically on all F 2 data using a full-matrix least-squares procedure (SHELXL-97) with weight: w = 1/[ 2 (Fo) 2 + (0.07P) 2 + 0.80P], where P = (Fo 2 + 2Fc 2 )/3. 10 All atoms were localized in differential maps of electron densities and their parameters were refined with a riding model, with C-H distances of 0.95 Å and N-H distances of 0.88 Å, and with Uiso(H) values of 1.2Ueq(C,N), while parameters of the crystal water molecule were refined with the O-H distances restrained to 0.94(2) Å.Additional calculations were performed using the DIAMOND program. 11The crystal data and the structure refinement of compound 4a×H2O are given in Table 3.

1-(1H-Indazol-3-yl)-1H-benzo[d]imidazol-2(3H)-one (4a)
(a) Decomposition of diazosulfonate (3a) in neutral medium.A mixture of diazosulfonate monohydrate 3a (37.0 mg, 0.10 mmol) and water (10 ml) was stirred at room temperature until a solution was formed.This was placed in a water bath and after ca. 15 min.the crystalline precipitate began to deposit.The reaction mixture was heated in the water bath for 90 min.with constant stirring and cooled afterwards.Next day, the bright yellow crystalline precipitate was collected by suction, washed several times with water and dried in air.The yield of monohydrate was 25.4 mg (95%).This substance is in every attribute (m.p., ms, IR, NMR spectra, anal.C,H,N) identical with the one prepared previously 2,3 .(b) Decomposition of diazosulfonate (3a) in acidic medium.To the solution of monohydrate diazosulfonate 3a (37.0 mg, 0.10 mmol) in water (9.0 ml), 35% HCl (1.0 ml) was added and reactive mixture was put into the boiling water bath.Just after less than half a minute the precipitate began to separate.After 15 min. of heating and cooling of reaction mixture it was collected by suction, washed with water and dried.The yield was 24.1 mg (90%).This substance is identical with the substance prepared previously.A solution of BaCl2 (5 ml, 0.1 M) was added into the filtrate.The amount of separated BaSO4 precipitate (23.2 mg), obtained by filtration, washing with water and drying, precisely corresponds with 0.1 mmol of sulfate anions.
(c) Decomposition of diazosulfonate in the mother liquor after isolation (3a).To the collected filtrates after the isolation of the diazosulfonate 3a (see procedure for preparation of 3a) 35% HCl (12.0 ml) was added and the reaction mixture was left for three days at room temperature.The separated crystalline precipitate was later collected by suction, washed with water and dried.The yield was 75.3 mg (14% -related to the initial amino derivative 1a).After the recrystallization from the acetic acid-aqua mixture the substance was identical with the substance as prepared previously.

3-(2´,4´-Diaminoazobenzene-2-yl)quinoxalin-2(1H)-one (5a) (a) From diazonium salt (2a).
To the mixture of aminoderivate 1a (119.0 mg, 0.50 mmol), water (20 ml) and 35% HCl (1.1 ml) cooled in an ice-bath to 0-5 °C, a solution of NaNO2 (36.5 mg, 0.53 mmol) in ice water (6 ml) was added portionwise.The reaction mixture was stirred in the ice bath until the solution was formed (approximately for 1h).Diazonium salt solution was added over 8 min.under stirring to the solution of 1,3-diaminobenzene (200.0 mg, 1.85 mmol) and CH3COONa (1.2 g, 14.6 mmol) dissolved in water (20 ml), which had been already cooled to 0-5 °C.The reaction mixture was stirred for 30 min mostly in the cooling bath and then was left in the fridge at 0-5 °C.The red precipitate was the next day collected by suction, thoroughly washed with water and dried at the room temperature.The yield of dihydrate was 184.(b) From diazosulfonate (3a).A solution of monohydrate 3a (37.0 mg, 0.10 mmol) and 1,3diaminobenzene (108.0 mg, 1.00 mmol) was left in a closed flask for 14 days at 5-10 °C with occasional stirring.The separated crystalline precipitate was then collected by suction, washed with water and dried.The yield was 12.1 mg.After the following 19 days another portion of the same compound (11.0 mg) was separated from the filtrate.Therefore, the total yield was 23.1 mg (60%).After recrystallization from ethanol-water mixture, the substance is identical with the azo dye, which was prepared by the preceding method.

Figure 1 .
Figure 1.The molecular structure of compound 4a×H2O, showing the atom numbering scheme.Non-hydrogen atoms are drawn as thermal ellipsoids at the 50% probability level.

Table 3 .
Crystal data and structure refinement for 4a×H2O min and the resulting reaction mixture was stirred (ca. 1 hour) until a solution was obtained.During vigorous stirring a solution of Na2SO3 (12.0 g, 74.0 mmol) in ice water (55 ml) was quickly added to this solution.The bright yellow solution formed was stirred at the temperature between 0-5 °C until deposition of the crystalline precipitate started (after ca.30-40 min).The solution was kept at of 0-5 °C for 48h.The bright yellow crystalline precipitate was later collected by suction, washed several times with a small amount of ice water and dried in the air at room temperature to constant weight.The yield of monohydrate was 586.