Catalyst-free [3+2] cycloaddition of azodicarbonyls and o-hydroxyaryl azomethine ylides on water

Abstract

An environment-friendly methodology for the synthesis of 1,2,4-triazoline derivatives on water is described. This method provides an environmental and useful strategy for catalyst-free synthesis of 1,2,4-triazolines derivatives. The gram scale reaction and one-pot reaction are also performed to ensure the scalability and high efficiency of the reaction.

Introduction

Water, as the most important core role in nature, participates almost all physiological activities, such as photosynthesis, cell respiration, metabolism, regulation of body temperature etc. [1] Among them, when water participates in the chemical changes in nature, the most indispensable role is the solvent, for example, water can dissolve many substances in organisms, thereby ensuring the normal transportation of nutrients and metabolites [2]. Yet, in the early chemical and industrial fields, scientists often shunned water, it may be because the presence of water is an unfavorable factor for the reaction, such as the poor solubility of the substances or may induce some hydrolysis reactions etc. [3] Even so, exploring the role of water in chemical reactions is still the focus of research [4].

Well known, due to the diversity of existing dipoles and dipolarophiles, 1, 3-dipolar cycloaddition have been widely used in the construction of complex molecular structures [5]. In 1977, the Grigg's research group reported that arylimine ylide reacted with azodicarboxylate in boiling benzene or toluene to obtain triazole. However, benzene and toluene have almost derailed from our current green chemistry concept [6]. It is worth noting that among the dipole building blocks involved in the 1,3-dipolar cycloaddition reaction, o-hydroxyimine ylide is a special type of dipole discovered in recent years. At first, Zhou's group used o-hydroxy azomethines as the starting material for the initial reaction, and many interesting heterocyclic compounds have been synthesized by using its subtle hydroxyl group (Fig. 1). [7] Then, Zhou’ group further discovered that the intramolecular hydrogen bonds of o-hydroxyimine ylide might have a good effect on the “reaction in water” (Fig. 1). [8] The hydrogen bond in the o-hydroxyimine leaf may reduce the energy of the front orbit by reducing the electron density and the repulsive force between the orbitals. The presence of water may promote this effect [9].

On the other hand, 1,2,4-triazolines have been widely concerned due to their outstanding biological activity [10]. Thus, the synthesis of 1,2,4-triazolines has always been a focus in the field of organic synthesis. Although there are more mature methods for the synthesis of 1,2,4-triazolines [11], few methods that follow the concept of green chemistry have been reported.

Here, we described a [3 + 2] cycloaddition reaction of o-hydroxy azomethines with Dialkyl Azodicarboxylates on water to affording unsaturated 1,2,4-triazolines. The highlight of our work is that no catalyst was used while the water used as the solvent.