Vibrational Spectroscopic Analysis of Minoxidil (2,4-Diamino-6-Piperidinopyrimidine-3-Oxide) and Related Analogs

Abstract

Tentative vibrational assignments for 2,4-diamino-6-piperidinopyrimidine-3-oxide (minoxidil) between 4000 and 600 cm⁻¹ have been made. Complementary infrared and Raman studies indicate that the two amino groups of minoxidil are not equivalent in the solid state. One of them is a free amino group, while the other is hydrogen bonded to the N-oxide. Vibrational spectroscopic analyses of minoxidil in different molecular environments, such as in polar solvents, aprotic solvents, and deuterium oxide, as well as in the pH = 1.5–12.5 range, have been performed to probe the structural variations generated by these conditions. Spectral comparison of minoxidil and its derivatives reveals that most spectral changes involve the amino and N-oxide functional groups. For instance, the N-oxide stretching vibration occurs at 1210 cm⁻¹ in the solid state, but it shifts to 1193 cm⁻¹ in polar solvents.

The amino hydrogens of minoxidil and desoxyminoxidil (2,4-diamino-6-piperidinopyrimidine) are readily exchanged with deuterium, as reflected in the ND₂ stretching region (2600–2300 cm⁻¹) in the infrared spectra of deuterated crystalline minoxidil and desoxyminoxidil. The similarity of band contours in the NH₂ stretching region suggests that there are no structural alterations on deuteration for either minoxidil or desoxyminoxidil.