Aromatic C-nitrosation of a bioactive molecule. Nitrosation of minoxidil

作者：Gonzalez Jimenez Mario; Arenas Valganon Jorge; Calle Emilio; Casado Julio^*

来源：Organic and Biomolecular Chemistry, 2011, 9(22): 7680-7684.

DOI：10.1039/c1ob05686g

Minoxidil (2,4-diamino-6-(piperidin-1'-yl) pyrimidine N(3)-oxide; CASRN 38304-91-5) is a bioactive molecule with several nitrosatable groups widely used as an antihypertensive and antialopecia agent. Here the nitrosation of minoxidil was investigated. The conclusions drawn are as follows: (i) In the pH = 2.3-5.0 range, the minoxidil molecule undergoes aromatic C-nitrosation by nitrite. The dominant reaction was C-5 nitrosation through a mechanism that appears to consist of an electrophilic attack on the nitrosatable substrate by H2NO2+/NO+, followed by a slow proton transfer; (ii) the reactivity of minoxidil as a C-nitrosatable substrate proved to be 7-fold greater than that of phenol, this being attributed to the preferred para-and ortho-orientations of the two -NH2 groups at positions 2 and 4 of the minoxidil molecule, which activate electrophilic substitution in the C-5 position through their mesomeric effect. The N-nitrosominoxidil resulting from the nitrosation could be potentially harmful to the minoxidil users.

• 出版日期2011