Abstract

Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) was primarily recognized as a drug for reducing vascular resistance to blood flow. It was later introduced as a more important medicine for topical stimulation of hair growth and baldness reverting as well as treatment of androgenic alopecia through increasing prostaglandin endoperoxide synthesis. In this study, magnetic nanoparticles (MNPs) of spinel ferrites (MFe$_{2}$O$_{4}$, M = Co, Ni, Fe, Cu, and Zn) via solid-state grinding procedure were prepared and then characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometer, and Fourier transform infrared techniques. The prepared nanoferrites were utilized as efficient and green heterogeneous catalysts for $N$-oxidation of 2,6-diamino-4-chloro-pyrimidine with H$_{2}$O$_{2\, }$in refluxing ethanol giving 2,6-diamino-4-chloro-pyrimidine $N$-oxide as a starting material for the synthesis of 2,4-diamino-6-piperidinopyrimidine 3-oxide (minoxidil). Among the examined nanoferrites, CoFe$_{2}$O$_{4}$ MNPs exhibited prominent catalytic activity giving the product in 95% yield within 60 min. Moreover, the reusability of nano-CoFe$_{2}$O$_{4\, }$was examined for 6 consecutive cycles without significant loss of catalytic activity and magnetic property.

Highlights

  • Minoxidil was primarily recognized as an effective antihypertensive and peripheral vasodilator drug for reducing vascular resistance to blood flow [1,2]

  • Synthesis of 2,6-diamino-4-chloro-pyrimidine N -oxide In a two-neck round-bottom flask equipped with magnetic stirrer and condenser, a mixture of 2,6-diamino-4chloro-pyrimidine (1 mmol, 0.14 g) and CoFe 2 O 4 magnetic nanoparticles (MNPs) (0.01 g, 0.05 mmol, 5 mol%) in EtOH (5 mL) was placed

  • After the completion of reaction, the mixture was cooled to room temperature and MNPs of CoFe 2 O 4 were separated from the reaction mixture using an external magnetic field

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Summary

Introduction

Minoxidil was primarily recognized as an effective antihypertensive and peripheral vasodilator drug for reducing vascular resistance to blood flow [1,2]. As a part of our research program on the synthesis of nanomagnetic materials and their application in functional group transformations [20,21,22], we wish to introduce nanospinel ferrites as efficient and reusable heterogeneous catalysts for N -oxidation of 6-chloro-2,4-diaminopyrimidine to 2,6-diamino-4-chloropyrimidine N -oxide by H 2 O 2 in ethanol under reflux conditions. Through the nucleophilic reaction of piperidine with 2,6-diamino-4-chloro-pyrimidine N -oxide, minoxidil (2,4-diamino-6-piperidino-pyrimidine 3oxide) was produced in high yield and purity (Figure 1).

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