1,2,3-Benzotriazine Synthesis by Heterocyclization of p-Tosylmethyl Isocyanide Derivatives
Francisco Maqueda-Zelaya, José Luis Aceña*, Estíbaliz Merino, Juan J. Vaquero and David Sucunza*
*Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, IRYCIS, 28805, Alcalá deHenares, Madrid, Spain, Email:
jose.acena
uah.es, david.sucunzauah.es
F. Maqueda-Zelaya, J. L. Aceña, E. Merino, J. J. Vaquero, D. Sucunza, J. Org. Chem., 2023, 88, 14131-14139.
DOI: 10.1021/acs.joc.3c01675
Abstract
An efficient intramolecular heterocyclization of 1-azido-2-[isocyano(p-tosyl)methyl]benzenes with alcohols and phenols under basic conditions provides 4-alkoxy- and 4-aryloxybenzo[d][1,2,3]triazines in very good yields with a broad scope.
see article for more examples
proposed mechanism based on DFT calculations
General Procedure for the Formation of Benzo[d][1,2,3]triazines
NaH (3.0 equiv) was dissolved in THF (0.2 M) and stirred for about 5 min under Ar. The corresponding alcohol or phenol (3.0 equiv) was added at rt. After 2 min, the mixture was cooled to 0 °C and a solution of the corresponding isocyanide (1 equiv) in THF (0.04 M) was added. The reaction mixture was stirred at 0 °C for 1 h. After this time, the reaction mixture was warmed to room temperature and diluted with ethyl acetate and water. The aqueous layer was extracted 2 times with ethyl acetate, and the collected organic phases were then washed one more time with brine. After evaporation of the solvent, the crude material was purified by flash chromatography using mixtures of hexane/EtOAc as eluents to obtain the corresponding triazine.
Key Words
1,2,3-Benzotriazines, benzo-fused N-heterocycles
ID: J42-Y2023
