Interconversions of isatin-containing condensed tetracyclic systems

Abstract

A new pathway has been proposed for the synthesis of dioxodihydro-1H-benzo [b]thiophenoindoles from the corresponding isomeric "amino acids" with amino groups at C (2) and C (3) . This method yields these tetracyclic systems not only as a single isomer but also permits their interconversion. Linear isomers may be obtained from angular tetracyclic systems and, vice versa, the isomer with angular fusion of the pyrrole ring may be obtained from the linear isomer. The classical Sandmeyer reaction was used as a model for such conversions.Syntheses have been reported for benzo [b]thiopheno-1H-indoles, which are tetracyclic systems [1,2]. In light of the strong antibacterial activity of methisazone (β-thiosemicarbazone of N-methylisatin, Marboran), which belongs to the 1-methylisatin system containing a thiosemicarbazide fragment [3-6], we developed methods for the synthesis of tetracyclic condensed systems, containing "amino acid" elements as well as benzothiophene structures with linear and angular fusion of the pyrrole and benzene rings. We found that it is relatively facile to convert the angular structures into linear structures and vice versa.The starting "amino acids" 5-8 were obtained according to our previous procedure [1, 2]. The physicochemical and spectral characteristics of these compounds are given in Tables 1-3. EXPERIMENTALThe reaction course and purity of the products were monitored by thin-layer chromatography on Silufol UV-254 silica gel plates. The UV spectra of the samples in ethanol were taken on a Specord UV-vis spectrophotometer and the IR spectra of the samples in vaseline mull were taken on a UR-20 spectrometer using NaCl and LiF prisms. The 1 H NMR spectra were taken on a Bruker WP-200 SY spectrometer at 200 MHz with TMS as the internal standard.2-Isonitrosoacetamidodibenzothiophene (3). Na 2 SO 4 ·10H 2 O (25.7 g, 0.8 mol), 2-aminodibenzothiophene 1 (19.9 g, 0.1 mol) dissolved in water (3 l) acidified with conc. HCl (20 ml), and hydroxylamine hydrochloride (22.0 g, 0.32 mol) dissolved in water (100 ml) was added consecutively to a solution of chloral hydrate (16.5 g, 0.1 mol) in water (150 ml). The mixture was heated at reflux for 2 h. The crystalline precipitate was filtered, thoroughly washed with water, dried, and recrystallized from ethyl acetate.