Studies in the heterocyclic series. XIX. Synthesis of 1,4‐diazaphenothiazine and its benzo derivatives

Abstract

1,4‐Diazaphenothiazine, the parent compound of this heterocyclic ring has now been prepared from 2,3‐dichloropyrazine and 2‐aminothiophenol. Replacement of 2,3‐dichloropyrazine with 2,3‐dichloroquinoxaline and 2,3,6‐trichloroquinoxaline led to the corresponding 1,4‐diazabenzo[b]phenothiazine in good yields. Structural assignments were made by spectroscopic studies and by certain chemical transformations.

Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors

“…Standard protocol 1 with 601 mg (2.99 mmol) of 10 H -benzo­[ b ]­pyrazino­[2,3- e ]­[1,4]­thiazine ( 2k ; synthesized according to Okafor) in 2.0 mL of anhydrous DMF, 5.95 mL (5.95 mmol, 2.0 equiv) of LiHMDS (1 M), and 1.15 g (5.02 mmol, 1.7 equiv) of methyl 4-(bromomethyl)­benzoate ( 3 ) in 1.0 mL of anhydrous DMF was used. The reaction mixture was stirred for 3 h and was extracted with CH 2 Cl 2 (3 × 50 mL).…”

10H-Pyrazino[2,3-b][1,4]benzotellurazine, a Novel Tellurium-Containing Heterocyclic System

“…[15,16] e current work offers a novel approach to such compounds, starting with readily accessible bis(2-aminophenyl) ditelluride. Conceptually, the synthesis of 2 and 4, based on that of 10H-pyrazino[2,3-b] [1,4]benzothiazine [10], was straightforward. In practice, however, this reaction was difficult to implement.…”

“…Several solvents were tested without success (ethanol, acetonitrile, dimethylformamide, and p-dioxane), but DMSO, under carefully controlled conditions, was suitable for ring closure. Much more drastic conditions were required than had been reported for the preparation of sulfur congeners [10,17]. Below 160°C, ring closure remained incomplete, while at the boiling point of DMSO (189°C), decomposition was rapid.…”

“…Our attempts to prepare 10H-pyrazino [2,3-b] [1,4]benzotellurazine were based on the synthesis of 10H-pyrazino [2,3-b] [1,4]benzothiazine, which was rst reported in 1974 in the patent literature [8,9] and noted for its strongly antibacterial e ects. Further works extended the synthesis used to prepare the parent compound to several derivatives [10]. Only one reference exists for the preparation of a selenium analog [11].…”

2,3-Dichloro-1-alkylpyrazinium tetrafluoroborates: the synthesis and reactions with nucleophiles

“…In particular, nucleophilic substitution for chlorine atoms in 2,3-dichloropyrazine leading to fused pyrazines is well documented. 5,6 The ortho-cyclisation based on the diaddition of bifunctional nucleophiles at C-2 and C-3 (C-5 and C-6) carbon atoms in N-alkylpyrazinium salts also seems to be a promising synthetic approach to fused pyrazines. 7,8 By the reactions of 2,3-dichloropyrazine with the Meerwein reagents R 3 O + BF 4 -(R = Me or Et) in CH 2 Cl 2 at 20 °C, we first prepared 1-alkyl-2,3-dichloropyrazinium tetrafluoroborates 1a,b (Schemes 1 and 2).…”