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Application of Thiol-Modified Dual-Pore Silica Beads as Practical Scavenger of Leached Palladium Catalyst in C–C Coupling Reaction Tsuyoshi Yamada, Tomohiro Matsuo, Aya Ogawa, Tomohiro Ichikawa, Yutaka Kobayashi, Hayato Masuda, Riichi Miyamoto, Hongzhi Bai, Kanji Meguro, Yoshinari Sawama, Yasunari Monguchi, and Hironao Sajiki Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.8b00291 • Publication Date (Web): 20 Nov 2018 Downloaded from http://pubs.acs.org on November 25, 2018
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Organic Process Research & Development
Application of Thiol-Modified Dual-Pore Silica Beads as Practical Scavenger of Leached Palladium Catalyst in C–C Coupling Reaction Tsuyoshi Yamada a, Tomohiro Matsuo a, Aya Ogawa a, Tomohiro Ichikawa a, Yutaka Kobayashi a
, Hayato Masuda a, Riichi Miyamoto b, Hongzhi Bai b, Kanji Meguro b, Yoshinari Sawama a,
Yasunari Monguchi c and Hironao Sajiki a* a
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu
501-1196, Japan b
c
DPS Inc., 1-39-2215, Goryo-Ohara, Nishikyo-ku, Kyoto 615-8245, Japan Laboratory of Organic Chemistry, Daiichi University of Pharmacy, 22-1 Tamagawa-cho,
Minami-ku, Fukuoka 815-8511, Japan
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Organic Process Research & Development
KEYWORDS Palladium scavenger; Thiol-modified silica; Dual-pore; Perfusion effect; Sonogashira coupling; Palladium on carbon ABSTRACT
A practical and efficient method for scavenging leached palladium to the reaction mixture using thiol-modified dual-pore silica beads has been developed. Reducing the level of metal contamination, especially palladium, in pharmaceutical and bioactive compounds, and fine chemicals to below the regulatory value is quite important for the quality assurance of industrial products. We have evaluated the performance of dual-pore silica beads as a palladium scavenger by investigating their ability to eliminate the divalent palladium ions in dilute palladium (II) acetate in methanol (5 and 50 ppm) and ethyl acetate (5 ppm) solutions. The ability of the dualpore silica beads to eliminate the palladium species leached from a 10% palladium on carbon (Pd/C) catalyst during the ligand- and copper-free 10% Pd/C-catalyzed Sonogashira-type coupling reaction was also investigated. The thiol-modified dual-pore silica beads exhibit a more rapid and effective elimination ability toward leached palladium species in the reaction mixture in comparison with commercially available conventional thiol-modified silica scavengers because of the effects of diffusion and perfusion effect due to the dual-pore skeleton of the silica beads. When methanol is used as a diluting and an eluent solution for the filtered reaction mixture, the leached palladium species were removed almost entirely (
