Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Ureido-functionalized compounds play an indispensable role in important biochemical processes, as well chemical synthesis and production. Isocyanates, KOCN particular, are the preferred reagents for ureido functionalization of amine-bearing compounds. In this study, we evaluate potential urea a reagent to graft groups onto amines at relatively low temperatures (<100 °C) aqueous media. Urea is inexpensive, non-toxic biocompatible alternative functionalization. From early 1864, was go-to polyurea polycondensation, before falling into disuse after advent isocyanate chemistry. We systematically re-investigate advantages disadvantages amine transamidation. High ureido-functionalization conversion obtained wide range substrates, including primary secondary amino acids. Reaction times nearly independent substrate pH, but excess required practically feasible reaction rates. Near full can be achieved within 10 h 90 °C 24 80 °C, much slower rates were determined lower temperatures. The importance urea/amine ratio temperature dependence indicate that decomposition isocyanic acid or carbamate intermediate rate-limiting step. presence water leads modest increase rates, also possible absence neat alcohol, consistent with mechanism mediated by (where assists proton transfer). Hence, avoids use toxic situ generation reactive intermediate, requirement separate from product remains major disadvantage.