Johnson-Claisen Rearrangement ジョンソン-クライゼン転位反応

Outline

Org. Process. Res. Dev., 2018, 22, 1029-1033.
DOI: 10.1021/acs.oprd.8b00185

“Scalable Microwave-Assisted Johnson-Claisen Rearrangement with a Continuous Flow Microwave System”

Hiromichi Egami¹, Souma Tamaoki¹, Masato Abe¹, Noriyuki Ohneda, Takeo Yoshimura, Tadashi Okamoto, Hiromichi Odajima, Nobuyuki Mase², Kazuhiro Takeda², and Yoshitaka Hamashima¹

¹School of Pharmaceutical Sciences, University of Shizuoka
²Applied Chemistry and Biochemical Engineering Course, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University

Abstract
  We demonstrated the rapid Johnson-Claisen rearrangement of allyl alcohol and triethyl orthoacetate with a continuous flow apparatus combined with a microwave reactor. The reaction could be carried out without solvent, and only a catalytic amount of acetic acid was sufficient to promote the reaction under microwave irradiation conditions. To confirm the optimal reaction conditions found experimentally, we performed Design of Experiments (DoE) by the Nelder-Mead method and a least-squares method regarding the amount of acetic acid and the flow rate. Consequently, the highest yield of the desired γ,δ-unsaturated ester was obtained, and the productivity at the reaction step of the continuous process was 89.5 g/h under the optimal conditions, suggesting that 2.1 kg of the product would be theoretically obtained in 1 day. We also investigated the Johnson-Claisen rearrangement using other allylic alcohols, and the corresponding products were obtained in good to high yields per unit of time.

Equipment information Reactor size: 100 mm, Maximum power: 100 W (SAIDA FDS INC.)

概要

実験結果提供：　静岡県立大学　濱島義隆先生、江上寛通先生、
静岡大学　間瀬暢之先生、武田和宏先生
装置情報：100 mmキャビティ、100W