Continuous, Solvent-Free, and Mechanochemical Synthesis of N-Acylhydrazone Derivatives by Spiral Gas–Solid Two-Phase Flow

Abstract

In this work, we report a novel spiral gas−solid two-phase flow (S-GSF) technique for the continuous mechanochemical synthesis of N-acylhydrazone derivatives. The synthesis of (E)-N′-(4-nitrobenzylidene)benzoylhydrazide (compound 1) was used as a model reaction to demonstrate the feasibility of this approach. The prepared products were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, ultraviolet−visible (UV−vis) spectroscopy, and scanning electron microscopy (SEM). Results showed that the product prepared by this method was analytically pure and had a high yield. No solvent was used in the reaction, and the byproduct water was in the form of water of crystallization. Moreover, SEM images showed that the method can directly obtain ultrafine powder products that are attractive to the pharmaceutical industry. Subsequently, kinetic analysis was performed by detecting the UV−vis spectra of the products under different optimized reaction conditions. The green chemistry metrics of the method showed that it is more environmentally friendly than the conventional solution method. In addition, the method was used in preparing a variety of N-acylhydrazone derivatives by using aldehydes with different substituents.