Easy Removal of N-carboxybenzyl (Cbz) Protective Group by Low- Carbon Alcohol

Author(s): Guo-Qiang Song, Feng Qin, Xian-Feng Huang, Xiao-Bing Lv, Bei Yang

Journal Name: Letters in Organic Chemistry

Volume 13 , Issue 3 , 2016


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Abstract:

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.

Keywords: Carboxybenzyl (Cbz), deprotection, imidazoles, low-carbon alcohol, pyrazoles.

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2016
Published on: 10 February, 2016
Page: [177 - 180]
Pages: 4
DOI: 10.2174/1570178613666151230211110
Price: $65

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