Song, GuoQ; Qin, F; Huang, XF; Lv, XB; Yang, Bei
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 HPLC analysis. 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.