Solvent-Free, Mechanochemically Scalable Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Using Brønsted Acid Catalyst

Abstract

Although the synthesis of novel N-heterocyclic molecules is extremely demanding as well as challenging, the involvement of toxic solvents often triggers environmental safety concerns, resulting in process-engineering challenges. Herein, we have demonstrated a rapid, environmentally benign and energy efficient scalable method for the synthesis of 2,3-dihydroquinazolin-4­(1H)-one by grinding in a mortar pestle as well as mechanochemically via ball milling using p-TSA catalyst. The ability to accomplish the reaction in the absence of solvent via grinding or milling with p-TSA catalyst, with an immediate reduction in the cost and operational procedures, features the significant advantages of this protocol. The scalability and significance of the operational parameters during mechanochemical milling in the tubular ball mill were also demonstrated. Excellent yield in short duration, large substrate scope, product scalability, and easy recoverability are the prime features of this mechanochemical solvent-free protocol for the synthesis of 2,3-dihydroquinazolin-4­(1H)-one. The study also demonstrated the significant role of ball diameter to improve the efficiency of the milling operation in this mechanochemical synthesis.

Synthesis and Evaluation of Anticancer Activity of Pyrazolone Appended Triarylmethanes (TRAMs)

“…[38][39][40] Analysis and review of small molecules based on TRAM with potent anticancer activities has prompted us to design a pyrazolone ring containing triarylmethanes which aligns with our ongoing research project on designing and developing bioactive molecules as well as molecules for applications in biology. [41][42][43][44][45][46][47][48][49] It was interesting to note that several compounds are known in the literature, that possess a triphenylmethyl motif, appear to be potent anticancer agents. We, therefore, created a series of pyrazolone-appended hetero triarylmethane scaffolds.…”

“…Analysis and review of small molecules based on TRAM with potent anticancer activities has prompted us to design a pyrazolone ring containing triarylmethanes which aligns with our ongoing research project on designing and developing bioactive molecules as well as molecules for applications in biology [41–49] …”

Mechanochemical Organocatalysis: Do High Enantioselectivities Contradict What We Might Expect?

“…This type of reactor technology is very effective at homogenizing reactions mixtures (mixing) and inputting energy in the form of heat and pressure to reaction centres. All of this can be largely achieved in the absence of solvent, and thus the reactor environment of a ball mill is receiving increasing interest in recent times [32–60] …”

Mechanochemical Synthesis and Thermal Dehydrogenation of Novel Calcium-Containing Bimetallic Amidoboranes

“…In comparison with conventional wet synthesis of MABs in dry tetrahydrofuran (THF), mechanochemical procedures are generally completely solventless, thus providing a very attractive means of preparation from these sensitive reactants. , Even more important, they result exclusively in targeted amidoborane and hydrogen as a byproduct. This was applied to prepare the entire diversity of MABs as they are known today.…”