Microwave-induced Bismuth Salts-mediated Synthesis of Molecules of Medicinal Interests

Background: Bismuth salts-mediated reactions have become a powerful tool for the synthesis of diverse medicinally-significant compounds because of their low-toxicity (non-toxic) and Lewis acidic capacity. In fact, LD50 of bismuth nitrate is lower than table salt. On the other hand, microwave-induced chemical synthesis is considered as a major greener route in modern chemistry. Methods: A total of 139 publications (including a few authentic web links) have been reviewed mainly to discuss bismuth salts-induced electrophilic aromatic substitution, protection-deprotection chemistry of carbonyl compounds, enamination, oxidation, carbohydrate chemistry, hydrolysis, addition-elimination route, Paal-Knorr reaction, Clauson-kaas synthesis, Michael addition, aza-Michael addition, Hantzsch reaction, Biginelli reaction, Ferrier rearrangement, Pechmann condensation, Diels-Alder and aza-Diels- Alder reactions, as well as effects of microwave irradiation in a wide range of chemical transformations. Results: Bismuth salts-mediated reactions are developed for the synthesis of diverse organic molecules of medicinal significance. Reactions conducted with bismuth salts are environmentally benign, economical, rapid and high yielding. Microwave irradiation has accelerated these reactions significantly. It is believed that bismuth salts released corresponding acids in the media during the reaction. However, a coordination of bismuth salt to the electronegative atom is also observed in the NMR study. Bismuth has much less control (less attractive forces) over anions (for example, halides, nitrate, sulfate and triflates) compared to alkali metals. Therefore, it forms weak bond with electronegative atoms more readily and facilitates the reactions significantly. Many products obtained via bismuth salts-mediated reactions are medicinally active or intermediate for the synthesis of biologically active molecules including antifungal, anti-parasitic, anticancer and antibacterial agents, as well as agents to prevent Leishmaniosis and Chagas' diseases. Conclusion: Bismuth salts are able to (i) generate mineral acids in the reaction media and (ii) coordinate with electronegative atoms to facilitate the reaction. When the reagents and the catalyst (bismuth salt) are subjected to microwave irradiation, microwave passes through the (glass) walls of the reaction vessel and heat only the reactants avoiding local overheating at the wall of the vessel. Accordingly, the possibility of side reaction and subsequent by-product formation are reduced abruptly which in turn increases the yield of the desired product. The extreme rapidity with excellent yield of the product can be rationalized as a synergistic effect of the bismuth salts and microwave irradiation.