6-bromo-2,1,3-benzoxadiazole 1-oxide synthesis

Yield:-

Reaction Conditions:

Stage #1: 4-Bromo-2-nitroanilinewith potassium hydroxide in ethanol at 47 - 65; for 2 h;
Stage #2: with sodium hypochlorite in ethanol;water at 5; for 1.5 h;

Steps:

6-bromobenzo[c][1,2,5]oxadiazole 1-oxide (9)

A stirred solution of potassium hydroxide (1.6 mmol) in ethanol (0.95 mL) at 47°C was treated portion-wise with 4-bromo-2-nitroaniline (1 mmol), ensuring the maintenance of a constant temperature; then, the solution was heated at 65°C for 2 hours. The reaction mixture was cooled to 2°C, treated with aqueous sodium hypochlorite (15%, 2.1 mL), and stirred for 90 minutes, keeping the temperature below 5°C. Then, the reaction was gradually warmed to room temperature and stirred for an additional 18 hours. After completion, the precipitate was filtered off, washed with water and dried in vacuo, to afford the desired product as a red solid. The product was used without further purification [4].

References:

Chiarelli, Laurent R.;Mori, Matteo;Barlocco, Daniela;Beretta, Giangiacomo;Gelain, Arianna;Pini, Elena;Porcino, Marianna;Mori, Giorgia;Stelitano, Giovanni;Costantino, Luca;Lapillo, Margherita;Bonanni, Davide;Poli, Giulio;Tuccinardi, Tiziano;Villa, Stefania;Meneghetti, Fiorella [European Journal of Medicinal Chemistry,2018,vol. 155,p. 754 - 763] Location in patent:supporting information