A Novel Protocol for the Synthesis of Substituted Benzo-Amidine (or Imidate) Derivatives from C-C Cross-Coupling Reactions of Various ArylHalides, Isocyanides, and Amines (or Alcohols)

Abstract: In this new study, a simple and efficient method for the synthesis of novel functionalized benzo-amidine (or imidate) derivatives in 40 min is reported, using ultrasonic waves to improve the reaction rate and efficiency. In this experiment, a three-component, one-pot, copper-catalyzed reaction was carried out via the C-C cross-coupling method, involving isocyanides, aryl halides, and amines (or alcohols) with different electron-donating and electron-withdrawing groups. Some of the advantages of the proposed protocol include: performing the reaction under simple and facile conditions at ambient temperature, without the addition of expensive ligands; using readily available starting materials and a cheap and suitable copper iodide catalyst; employing an ultrasonic device to achieve optimal conditions for speed and efficiency; purification without the use of column chromatography; and the successful synthesis of fourteen new heterocyclic compounds in acceptable yields. Efforts have also been made to adhere to the principles of green chemistry, sustainable development, and cost reduction in the design and synthesis. results: To identify the most effective catalytic conditions, a comprehensive screening of different catalysts, bases, and solvents was conducted, employing aryl halides, amines (or alcohols), and isocyanides as representative model substrates. As presented in Table 1, a series of copper salts CuI, CuBr, and CuCl (each at 10 mol%) were evaluated, among which CuI emerged as the most efficient catalyst. Additionally, MeCN was identified as the optimal solvent for the reaction after thorough screening. Various bases, including Cs2CO3, KOH, and NaOH, were also examined, with KOH delivering the superior outcome. Consequently, the reaction was carried out in MeCN utilizing 10 mol% CuI as the catalyst, 1.0 mmol KOH as the base, 1.5 mmol isocyanides, and equimolar amounts (1.0 mmol) of assorted aryl halides and amines (or alcohols) under ultrasonic conditions for 40 min. Furthermore, to gain deeper insight into the catalytic function of copper salts, the reaction was conducted both in the presence of elemental copper and in the absence of any catalyst under identical conditions. The results indicate that the desired product was not produced.