Synlett 2020; 31(19): 1937-1941
DOI: 10.1055/s-0040-1707307
Integrated Synthesis Using Continuous-Flow Technologies

Accelerating Heat-Initiated Radical Reactions of Organic Halides with Tin Hydride Using Flow Microreactor Technologies

Yiyuan Jiang
Yosuke Ashikari
Kaiteng Guan
Aiichiro Nagaki
Kyoto University: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyotodaigaku-katsura Nishikyo-ku, Kyoto, 615-8150, Japan   Email:
› Author Affiliations

This work was partially supported by the Japan Society for the Promotion of Science [JSPS KAKENHI, Grant Numbers JP15H05849 (Grant-in-Aid for Scientific Research on Innovative Areas 2707 middle molecular strategy), JP26288049 (Grant-in-Aid for Scientific Research (B)), JP26220804 (Grant-in-Aid for Scientific Research (S)), JP25220913 (Grant-in-Aid for Scientific Research (S)), JP17865428 (Grant-in-Aid for Scientific Research (C)), and JP20K15276 (Grant-in-Aid for Early-Career Scientists)]. This work was also partially supported by the Japan Agency for Medical Research and Development (AMED, Grant Number JP19ak0101090), the Core Research for Evolutional Science and Technology (CREST), and the Japan Science and Technology Agency’s (JST) A-step program (Adaptable and Seamless Technology Transfer Program through Target-Driven R and D, Grant Number 18067420).


We herein report that flow microreactors can promote an efficiency of radical chain reactions. The chain reactions with a fast propagation step can be accelerated by virtue of an efficient heat-transfer character of the microreactors, whereas the yield of those reactions with a slow propagation step was increased by flow microreactors. Moreover, the yield was further increased by a sequential addition of the initiators, which was allowed by a flow-sequential-addition system.

Supporting Information

Publication History

Received: 04 August 2020

Accepted after revision: 02 September 2020

Article published online:
09 October 2020

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  • 11 For the sequential-addition flow reactions with system, a flow microreactor system consisting of two T-shaped micromixers (M1 (φ = 250 μm) and M2 (φ = 500 μm)) and four microtube reactors (R1, R2, R3, and R4) was used. R2 and R3 were dipped in an oil bath (120 °C), and R4 was cooled in an ice bath (0 °C). A xylene solution containing 1-chloroadamantane (0.20 M, 4), tri-n-butyltin chloride (0.24 M), and internal standard (n-tetradecane) was introduced into M1 (0.5 mL/min). Also, a xylene solution of AIBN (0.04 M) was introduced into M1 (F1 mL/min). The mixed solution was passed through R1 (length L = 100 cm, φ = 1000 μm) and R2 (L = L1 cm, φ = 1000 μm, residence time = t 1 s) where the reaction proceeds. Another AIBN solution (in xylene, 0.04 M) was introduced into M2 (F2 mL/min) and mixed with the reaction solution. The resultant mixture was passed through R3 (L = L2 cm, φ = 1000 μm, residence time = t 2 s), and R4 (L = 100 cm, φ = 500 μm) where the reaction was stopped. The sum of F1 and F2 is 0.5 (mL/min), and the total reaction time (t 1 + t 2) was set as 1885 s by varying L 1 and L 2. After a steady state was reached, an aliquot of the solution was collected and analyzed by gas chromatography.