Guanidines are interesting molecules containing carbon surrounded by three nitrogen atoms, with unique structural characteristics that contribute to their remarkable physico-chemical properties. In particular, their high basicity (superbasicity) and ability to form hydrogen bonds set them apart from other organic compounds.(1) Their physicochemical properties make guanidines valuable in various applications, including their use as neutral, organic catalysts or components of receptor functionalities in anionic sensors.(2) Various guanidine derivatives are found in nature, and they have also been explored synthetically. Numerous synthetic routes and reagents have been employed for guanidine synthesis. Mechanochemistry has been recognised as a sustainable, solvent-free alternative to conventional organic solution-based synthesis. This solid-state synthetic approach offers several benefits, such as eliminating solvents, reducing the usage of chemicals, simplifying experimental procedures, and shortening reaction times. (3,4) Consequently, mechanosynthesis often provides higher reaction yields in more environmentally friendly conditions than solution synthesis. Solution and mechanochemical methods for the synthesis of thioureas and guanidines will be presented, and their efficiencies will be compared. Synthetic routes starting from aromatic amines, the preparation of isothiocyanates, followed by aromatic thioureas, and finally substituted guanidines will be discussed.

Dr. Davor Margetić is a senior research scientist and head of the Laboratory for Physical‑Organic Chemistry at the Ruđer Bošković Institute in Zagreb, Croatia. He holds a Ph.D. in Chemistry from the University of Zagreb and completed postdoctoral research in Australia. His work focuses on physical‑organic chemistry, particularly mechanochemistry, high‑pressure and microwave‑assisted synthesis, and green synthetic methods. Dr. Margetić has published over 130 scientific papers and authored several books, including Mechanochemical Organic Synthesis (2016) and High-Pressure Organic Synthesis (2019). He is an expert in reaction mechanisms, supramolecular chemistry, and the development of environmentally friendly technologies in organic synthesis. Dr. Margetić also serves as president of the Croatian Chemical Society and frequently collaborates on international research projects.