Background: A new method for the removal of Cbz protective group was established. It is
accomplished by using methanol, ethanol or t-butanol as a deprotective reagent, and the scope and
limitations of this method were also preliminarily investigated. These results broaden utility of N-Cbz
protective group in synthetic chemistry, especially in synthesis or use of imidazole, benzimidazole,
pyrazole or their derivatives.
Methods: Using N-Cbz-imidazole as a model compound, the feasibility of the deprotection method
was investigated. We studied various reaction conditions including solvent, reaction temperature and catalyst on the influence
of the deprotection reaction. Typical experimental procedure, N-Cbz-imidazole (0.40 g, 2.0 mmol) was added to a
solution of methanol (30 mL), and the reaction mixture was stirred at room temperature. Hourly tracking and detection by
Results: These results indicate that the deprotection method effectiveness is closely related with the substrate structure. In
the explored scope, it is valid for some heterocyclic compounds, such as N-Cbz-protected imidazole, pyrazole compound,
benzimidazole and benzimidazole derivatives, but possibly not for other amino chemicals. Further application of the
method to other types of heterocyclic amine compounds is in progress in our labs. The novel deprotection approach can
widen use of N-Cbz protective group in synthetic chemistry. There currently are many active pharmaceutical ingredients
containing azole structures, for example: omeprazole, esomeprazole, lansoprazole, dexlansoprazole and pantoprazole etc.
It has potential to be utilized in pharmaceutical industries and fine chemicals.
Conclusion: In summary, this new method of removal of Cbz protective group using low-carbon alcohols of methanol,
ethanol or tert-butanol as deprotective reagents is feasible and effective in the kind of heterocyclic amino compounds of
imidazoles, pyrazoles and their derivatives. This new approach is simple and mild. Furthermore, removal of Cbz protective
group does not affect other functional groups on the molecule, i.e., the structure remains unchanged.