Three fundamental mechanisms of base-catalysed reactions of isocyanates with hydrogen-acidic compounds

Abstract

The base-catalysed addition of H-acidic compounds HX, such as alcohols, phenols and amines, to isocyanates giving carbamates and ureas may proceed by three fundamental mechanisms depending on the acidity and nucleophilicity of the particular HX and the basicity of the catalyst B. Acidic, less nucleophilic HX, such as phenols and acidic alcohols, are transformed by the base catalyst into the anionic X^– which is then added to the isocyanate (mechanism I). HX of moderate acidity, like the common alcohols, may react in a concerted single-step reaction, in which proton transfer to the base and nucleophilic addition to isocyanate occur simultaneously (mechanism II). With strong bases as catalysts, a changeover of mechanism II into I can occur. Less acidic, stronger nucleophilic HX, such as aromatic amines, are added directly to the isocyanate followed by base-catalysed proton transfer in the resulting adduct (mechanism III).

The three mechanisms leads to different rate laws and structure–reactivity relationships. The concerted and the stepwise mechanisms II and III are susceptible to steric hindrance of HX and the catalyst B, whereas the anionic mechanism I is not influenced by steric effects of B. The relative reactivity of HX towards isocyanate rises with the basicity (decreasing acidity) of HX in mechanism III (amines: Brønsted β_nuc > 0), but is independent of it in mechanism II (common alcohols: β_nuc= 0). In mechanism I with strong acidic HX, the reactivity of HX increases with decreasing acidity (strong acidic phenols: β_nuc > 0), but decreases with the less acidic HX (less acidic phenols and acidic alcohols: β_nuc < 0).