PhD Scientific Days 2026

Poster Session 1.F - Pharmaceutical Sciences and Health Technologies

Continuous-Flow CuAAC with Copper Granules

Name of the presenter

Mándoki, András

Institute/workplace of the presenter

Institute of Organic Chemistry

Authors

Dr. András Mándoki PhD¹
1: Institute of Organic Chemistry

Text of the abstract

Introduction: The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a highly reliable and regioselective click reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles. Its implementation in continuous-flow systems offers important practical advantages, including enhanced heat and mass transfer, improved safety, simplified catalyst handling, and increased process scalability.

Aims: To develop and evaluate a continuous-flow click-chemistry platform based on a packed-bed column filled with metallic copper granules for the azide–alkyne cycloaddition of 6-monodeoxy-6-monoazido-beta-cyclodextrin and Boc-propargyl-Gly-OH.

Method: The CuAAC reaction was performed under continuous-flow conditions through a fixed-bed reactor packed with copper granules, using 6-monodeoxy-6-monoazido-beta-cyclodextrin as the azide component and Boc-propargyl-Gly-OH as the terminal alkyne partner. The heterogeneous copper bed served as the catalytic medium, enabling continuous substrate conversion and triazole bond formation within the reactor column. The reaction was conducted at elevated temperature and under pressure to support efficient flow operation and to promote catalytic turnover within the packed-bed system.

Results: The packed-bed flow configuration enabled efficient azide–alkyne coupling and afforded the corresponding triazole-linked product with the expected CuAAC regioselectivity. The use of metallic copper granules provided a simple heterogeneous catalytic platform, reducing reliance on soluble copper reagents and facilitating product isolation. The flow format also supported operational robustness and offered a convenient basis for further optimization and scale-up.

Conclusion: Continuous-flow CuAAC using a copper granule-packed column represents a practical and scalable approach for the synthesis of triazole-linked cyclodextrin conjugates. This strategy combines the intrinsic selectivity of click chemistry with the process advantages of flow chemistry, making it a promising platform for the preparation of functionalized bioconjugates.

Funding: This work was supported by the Hungarian Research Foundation (OTKA ANN 139484).