Combination of air/moisture/ambient temperature compatible organolithium chemistry with sustainable solvents: selective and efficient synthesis of guanidines and amidines

Abstract

Highly-efficient and selective fast addition of in situ generated lithium amides [LiN(H)R] (obtained via an acid–base reaction between n-BuLi and the desired primary amine) into carbodiimides (R–NCN–R) or nitriles (R–CN) has been studied, for the first time, in 2-MeTHF or CPME as ethereal green solvents, at room temperature and in the absence of a protecting atmosphere (i.e., under air/moisture), reaction conditions that are generally forbidden in the field of highly-reactive main group polar compounds, such as lithium amides. The correct selection of: (i) the employed synthetic methodology (one-pot/two-step protocols are preferred); (ii) the unsaturated organic electrophile (carbodiimides or nitriles were assayed); and (iii) the sustainable ethereal solvent (2-MeTHF or CPME) allows the straightforward and successful synthesis of either guanidines or amidines under air/moisture at room temperature without the need for isolation or purification of any halfway reaction intermediate. Finally, we were able to scale up the reaction, thus proving that our new and environmentally-friendly protocol is amenable for a possible applied synthesis of highly-substituted iminic-type fine chemical products (guanidines/amidines) under bench-type reaction conditions.