有機合成反応の自動化を指向したフローマイクロ電解合成技術の創製

• Project Area: Digitalization-driven Transformative Organic Synthesis (Digi-TOS)
• Project/Area Number: 21H05215
• Research Category: Grant-in-Aid for Transformative Research Areas (A)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (II)
• Research Institution: Yokohama National University
• Principal Investigator: 跡部 真人 横浜国立大学, 大学院工学研究院, 教授 (90291351)
• Project Period (FY): 2021-09-10 – 2026-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥39,130,000 (Direct Cost: ¥30,100,000、Indirect Cost: ¥9,030,000); Fiscal Year 2025: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2024: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2023: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2022: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2021: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: フローマイクロ電解 / 有機電解合成 / 自動最適化技術 / フロー電解

Outline of Research at the Start

有機電解合成をフローマイクロ技術と融合することが出来れば、環境にやさしい多彩な合成反応モジュールを一挙に提供可能になる。創製されたフローマイクロ電解合成技術において、電解反応特有のパラメータとフローマイクロ特有のパラメータ操作により、再現性に優れ、研究者個々の技術に依存しない実験が行えることから、機械学習を利用した反応条件の自動最適化システムを組み込めば、理想的な自動合成装置の開発に繋がる。
そこで本研究課題では、フローマイクロ電解合成の自動化促進を目的とし、フロー電解合成デバイスおよびインラインフロー分析を組み込んだ反応条件の自動最適化技術の開発を行う。

Outline of Annual Research Achievements

本研究項目で開発されるフロー電解合成デバイスは革新的な基礎反応開発を支援するために主としてA01班に提供することをも想定している。そのため、フロー電解はもとより電解反応を初めて実施する共同研究者にも使いやすいものにする必要があり、組み立て容易なシンプルな構造から成るデバイスを設計することが肝要となる。一方、各種有機電解反応に適用できる汎用性に富んだ仕様にする必要もあることから、様々な電極材料を反応に応じて選択出来たり、あるいは対極での反応阻害を抑制するために、必要に応じて隔膜を介在させたり出来るなどの柔軟性に富んだものが求められる。
一昨年度は、このような要求を満たすためのフロー電解合成デバイスを設計し、これに基づいて試作されたデバイス特性を電気化学測定やモデル電解実験などから検証し、その仕様を固め、また昨年度は、このデバイスにインラインフローNMR分析を組み込んだフロー電解合成システムを構築した。今年度は環状カルバメート類の電解メトキシ化をモデル反応とした電解反応結果のデータベース化に注力し、本電解反応システムが電解結果の迅速なデータ提供において極めて有効であることが検証された。さらに電解メトキシ化の収率および生産速度の最適化を図った。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

2023年度に予定されていた研究項目「環状カルバメート類の電解メトキシ化反応のデータベース化」を滞りなく進めることができ、データベースの収集における本電解反応システム有用性が検証され、電解メトキシ化の収率および生産速度の最適化が図られた。

Strategy for Future Research Activity

今年度は一級アルコールの電解酸化によるアルデヒドへの高効率・高選択的変換を実現するための信頼度・精度が高いデータを本電解システムにより大量に収集し、データベースに提供する。

Research Products

• [Journal Article] Organic Electrosynthetic Processes Using Solid Polymer Electrolyte Reactor (2024)
  • Author(s): Mahito Atobe, Naoki Shida
  • Journal Title: Current Opinion in Electrochemistry Volume: 44 Pages: 101440-101440
  • DOI: 10.1016/j.coelec.2024.101440
  • Peer Reviewed
• [Journal Article] Voltammetric Studies on the Reduction Potentials of Perfluoroalkyl Halides and Their Analogous Compounds (2023)
  • Author(s): Airi Yamaguchi, Naoki Shida, Mahito Atobe, Tomoko Yajima
  • Journal Title: Electrochemistry Volume: 91 Issue: 11 Pages: 112016-112016
  • DOI: 10.5796/electrochemistry.23-67111
  • ISSN: 1344-3542, 2186-2451
  • Year and Date: 2023-11-30
  • Peer Reviewed / Open Access
• [Journal Article] C–C Bond Cleavage at the <i>N</i>-α Position Enabled by the Low-potential Electrochemical Oxidation of the 2,7-Dimethoxynaphthyl Electroauxiliary (2023)
  • Author(s): OKAMOTO Kazuhiro、IMADA Yasushi、SHIDA Naoki、KITANO Yoshikazu、ATOBE Mahito、CHIBA Kazuhiro
  • Journal Title: Electrochemistry Volume: 91 Issue: 11 Pages: 112006-112006
  • DOI: 10.5796/electrochemistry.23-67076
  • ISSN: 1344-3542, 2186-2451
  • Year and Date: 2023-11-28
  • Peer Reviewed / Open Access
• [Journal Article] β-Scission by Direct Electrochemical Oxidation: Proton-coupled Electron Transfer Mechanism Dictated by Synthetic Study and Computations (2023)
  • Author(s): IZUMIYA Rumi、ATOBE Mahito、SHIDA Naoki
  • Journal Title: Electrochemistry Volume: 91 Issue: 11 Pages: 112003-112003
  • DOI: 10.5796/electrochemistry.23-67010
  • ISSN: 1344-3542, 2186-2451
  • Year and Date: 2023-11-28
  • Peer Reviewed / Open Access
• [Journal Article] Susceptibility of Polycyclic Aromatic Hydrocarbons in Oxidative Voltammetry: Unveiling the Effect of Electrolyte-coordination (2023)
  • Author(s): YOSHINAGA Shohei、ATOBE Mahito、SHIDA Naoki
  • Journal Title: Electrochemistry Volume: 91 Issue: 11 Pages: 112002-112002
  • DOI: 10.5796/electrochemistry.23-67013
  • ISSN: 1344-3542, 2186-2451
  • Year and Date: 2023-11-28
  • Peer Reviewed / Open Access
• [Journal Article] Electrochemical [3+2] Cycloaddition Proceeding at Low Electrolyte Concentration in Laminar‐Flow Microreactor (2023)
  • Author(s): Okamoto Kazuhiro、Shida Naoki、Atobe Mahito
  • Journal Title: ChemElectroChem Volume: 10 Issue: 23
  • DOI: 10.1002/celc.202300386
  • Peer Reviewed / Open Access
• [Journal Article] Electrochemically Triggered Hole-Catalytic Benzylic Substitution Reaction at a Polymer Chain Containing β-O-4 Linkage (2023)
  • Author(s): Izumiya Rumi、Atobe Mahito、Shida Naoki
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 96 Issue: 4 Pages: 353-358
  • DOI: 10.1246/bcsj.20230019
  • Peer Reviewed
• [Journal Article] Diastereoselective Electrocatalytic Hydrogenation of Cyclic Ketones Using a Proton-Exchange Membrane Reactor: A Step toward the Electrification of Fine-Chemical Production (2023)
  • Author(s): Yugo Shimizu, Juri Harada, Atsushi Fukazawa, Tomohiro Suzuki, Junko Kondo, Naoki Shida, Mahito Atobeobe Mahito
  • Journal Title: ACS Energy Letters Volume: 8 Issue: 2 Pages: 1010-1017
  • DOI: 10.1021/acsenergylett.2c02573
  • Peer Reviewed
• [Journal Article] 固体高分子電解質電解技術を活用した有機電解プロセス ～有機合成プロセスの「電化」に向けたキーテクノロジー～ (2023)
  • Author(s): 跡部真人
  • Journal Title: ファルマシア Volume: 59 Pages: 810-814
• [Journal Article] Comparative Investigation of Electrocatalytic Oxidation of Cyclohexene by Proton-Exchange Membrane and Anion-Exchange Membrane Electrolyzers (2022)
  • Author(s): Shida Naoki、Atobe Mahito、Ido Yuto、Shimizu Yugo
  • Journal Title: Synthesis Volume: 55 Issue: 18 Pages: 2979-2984
  • DOI: 10.1055/a-2000-8231
  • Peer Reviewed
• [Journal Article] Pd?H Species on Electrode Stabilized by Solvent Co-Adsorption: Observation by Operando IR Spectroscopy (2022)
  • Author(s): Kondo Junko N.、Ge Shuo、Suzuki Tomohiro、Osuga Ryota、Matsumoto Takeshi、Yokoi Toshiyuki、Shimizu Yugo、Fukazawa Atsushi、Shida Naoki、Atobe Mahito
  • Journal Title: The Journal of Physical Chemistry C Volume: 126 Issue: 45 Pages: 19376-19385
  • DOI: 10.1021/acs.jpcc.2c05127
  • Peer Reviewed
• [Journal Article] Designing Modular Assembly of Electrochemical Flow Microreactor as an Enabling Technology of Electrosynthesis in Laminar Flow (2022)
  • Author(s): Yata Ayano、Nakamura Yuto、Okamoto Kazuhiro、Shida Naoki、Atobe Mahito
  • Journal Title: European Journal of Organic Chemistry Volume: 2022 Issue: 45
  • DOI: 10.1002/ejoc.202200980
  • Peer Reviewed
• [Journal Article] Mechanistic Insights into the Electrocatalytic Hydrogenation of Alkynes on Pt?Pd Electrocatalysts in a Proton-Exchange Membrane Reactor (2022)
  • Author(s): Nogami Shuji、Shida Naoki、Iguchi Shoji、Nagasawa Kensaku、Inoue Hideo、Yamanaka Ichiro、Mitsushima Shigenori、Atobe Mahito
  • Journal Title: ACS Catalysis Volume: 12 Issue: 9 Pages: 5430-5440
  • DOI: 10.1021/acscatal.2c01594
  • Peer Reviewed
• [Journal Article] カーボンニュートラル実現に向けたキーテクノロジー ―固体高分子電解質電解技術を活用する有機電解プロセス― (2022)
  • Author(s): 跡部真人
  • Journal Title: 化学 Volume: 77 (10) Pages: 66-67
• [Journal Article] Integrated Flow Emulsion Electrosynthetic System by In Situ Generation of Emulsions, Subsequent Emulsion Electrolysis, and Final Phase Separation (2022)
  • Author(s): Mikami Rio、Shida Naoki、Atobe Mahito
  • Journal Title: Organic Process Research &amp; Development Volume: 21 Issue: 4 Pages: 1268-1278
  • DOI: 10.1021/acs.oprd.2c00004
  • Peer Reviewed
• [Journal Article] Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor (2022)
  • Author(s): Naito Yuki、Shida Naoki、Atobe Mahito
  • Journal Title: Beilstein Journal of Organic Chemistry Volume: 18 Pages: 350-359
  • DOI: 10.3762/bjoc.18.39
  • Peer Reviewed / Open Access
• [Journal Article] Bayesian optimization with constraint on passed charge for multiparameter screening of electrochemical reductive carboxylation in a flow microreactor (2022)
  • Author(s): Naito Yuki、Kondo Masaru、Nakamura Yuto、Shida Naoki、Ishikawa Kazunori、Washio Takashi、Takizawa Shinobu、Atobe Mahito
  • Journal Title: Chemical Communications Volume: 58 Issue: 24 Pages: 3893-3896
  • DOI: 10.1039/d2cc00124a
  • Peer Reviewed
• [Journal Article] Investigation of Parameter Control for Electrocatalytic Semihydrogenation in a Proton-Exchange Membrane Reactor Utilizing Bayesian Optimization (2022)
  • Author(s): Ashikari Yosuke、Tamaki Takashi、Takahashi Yusuke、Yao Yiyue、Atobe Mahito、Nagaki Aiichiro
  • Journal Title: Frontiers in Chemical Engineering Volume: 3 Pages: 819752-819752
  • DOI: 10.3389/fceng.2021.819752
  • Peer Reviewed / Open Access
• [Journal Article] Electrochemical Trimerization of Catechol to 2,3,6,7,10,11-Hexahydroxytriphenylene Using a Flow Microreactor (2021)
  • Author(s): NAKAMURA Yuto、SATO Yasushi、SHIDA Naoki、ATOBE Mahito
  • Journal Title: Electrochemistry Volume: 89 Issue: 4 Pages: 395-399
  • DOI: 10.5796/electrochemistry.21-00053
  • NAID: 130008062334
  • ISSN: 1344-3542, 2186-2451
  • Year and Date: 2021-07-05
  • Peer Reviewed / Open Access
• [Journal Article] Triple‐phase Boundary in Anion‐Exchange Membrane Reactor Enables Selective Electrosynthesis of Aldehyde from Primary Alcohol (2021)
  • Author(s): Ido Yuto、Fukazawa Atsushi、Furutani Yuka、Sato Yasushi、Shida Naoki、Atobe Mahito
  • Journal Title: ChemSusChem Volume: 14 Issue: 24 Pages: 5405-5409
  • DOI: 10.1002/cssc.202102076
  • Peer Reviewed
• [Journal Article] Anodic substitution reaction of carbamates in a flow microreactor using a stable emulsion solution (2021)
  • Author(s): Mikami Rio、Nakamura Yuto、Shida Naoki、Atobe Mahito
  • Journal Title: Reaction Chemistry and Engineering Volume: 6 Issue: 11 Pages: 2024-2028
  • DOI: 10.1039/d1re00403d
  • Peer Reviewed
• [Journal Article] Electrocatalytic hydrogenation of benzoic acids in a proton-exchange membrane reactor (2021)
  • Author(s): Fukazawa Atsushi、Shimizu Yugo、Shida Naoki、Atobe Mahito
  • Journal Title: Organic and Biomolecular Chemistry Volume: 19 Issue: 34 Pages: 7363-7368
  • DOI: 10.1039/d1ob01197a
  • Peer Reviewed
• [Journal Article] Integrated Flow Synthesis of α-Amino Acids by <i>In Situ</i> Generation of Aldimines and Subsequent Electrochemical Carboxylation (2021)
  • Author(s): Naito Yuki、Nakamura Yuto、Shida Naoki、Senboku Hisanori、Tanaka Kenta、Atobe Mahito
  • Journal Title: The Journal of Organic Chemistry Volume: 86 Issue: 22 Pages: 15953-15960
  • DOI: 10.1021/acs.joc.1c00821
  • Peer Reviewed
• [Journal Article] Electrolytic oxidation of 1H-1,2,4-triazole, 3-amino-1,2,4-triazole, and 4-amino-1,2,4-triazole for energetic material synthesis (2021)
  • Author(s): Mori Kanae、Kumasaki Mieko、Atobe Mahito
  • Journal Title: Science and Technology of Energetic Materials Volume: 82 Issue: 2 Pages: 44-49
  • DOI: 10.34571/stem.82.2_44
  • NAID: 130008037386
  • ISSN: 0368-5977, 1347-9466, 2434-6322
  • Peer Reviewed
• [Presentation] Electrocatalytic Hydrogenation Reactions Using a Solid Polymer Electrolyte (SPE) Reactor (2023)
  • Author(s): Mahito Atobe
  • Organizer: International Joint Symposium on Synthetic Organic Chemistry 2023
  • Int'l Joint Research / Invited
• [Presentation] 固体高分子電解質電解技術が革新する新たな有機電解プロセス (2023)
  • Author(s): 跡部真人
  • Organizer: 第13回CSJ化学フェスタ
  • Invited
• [Presentation] フローリアクターが革新する新たな有機電解プロセス (2023)
  • Author(s): 跡部真人
  • Organizer: 第７回FlowSTシンポジウム
  • Invited
• [Presentation] フローリアクターが革新する新たな有機電解合成プロセス (2022)
  • Author(s): 跡部真人
  • Organizer: 2022 年度有機合成化学講習会
  • Invited
• [Presentation] Organic Electrosyntheses Using a Proton Exchange Membrane (PEM) Reactor (2022)
  • Author(s): Mahito Atobe
  • Organizer: International Symposium on Innovative Reactions through Controlling Electrons (ISIRCE)
  • Int'l Joint Research / Invited
• [Presentation] Integrated Flow Emulsion Electrosynthetic System for Oxidation of Hydrophobic Amines (2022)
  • Author(s): Mahito Atobe, Rio Mikami, Naoki Shida
  • Organizer: The 15th International Symposium on Organic Reactions (ISOR-15)
  • Int'l Joint Research / Invited
• [Presentation] Electrochemical C-N Coupling Reaction Mediated by π-Extended Iodoarene Catalyst (2022)
  • Author(s): Naoki Shida, Shohei Yoshinaga, Mahito Atobe
  • Organizer: 9th German-Japanese Symposium on Electrosynthesis
  • Int'l Joint Research
• [Presentation] Bayesian Optimization for Multiparameter Screening of Electrosynthetic Processes in a Flow Microreactor (2022)
  • Author(s): Yuto Nakamura, Yuki Naito, Kazuhiro Okamoto, Naoki Shida, Mahito Atobe
  • Organizer: 9th German-Japanese Symposium on Electrosynthesis
  • Int'l Joint Research
• [Presentation] Development of Integrated Flow Emulsion Electrosynthetic System for Oxidation of Hydrophobic Amines (2022)
  • Author(s): Mahito Atobe, Rio Mikami, Naoki Shida
  • Organizer: 9th German-Japanese Symposium on Electrosynthesis
  • Int'l Joint Research
• [Presentation] Development of Integrated Flow Emulsion Electrosynthetic System (2022)
  • Author(s): Mahito Atobe, Rio Mikami, Naoki Shida
  • Organizer: 17th Meeting of the European Society of Sonochemistry
  • Int'l Joint Research / Invited
• [Presentation] 固体高分子電解質（SPE）電解技術が革新する有機電解合成プロセス (2022)
  • Author(s): 跡部真人
  • Organizer: 第30回グリーンケミストリーフォーラム
  • Invited
• [Presentation] Anodic Substitution Reaction of Carbamates in a Flow Microreactor Using a Tandem Acoustic Emulsified Solution (2021)
  • Author(s): Rio Mikami, Yuto Nakamura, Naoki Shida, Mahito Atobe
  • Organizer: ESS-JSS-AOSS 1st Joint Sonochemistry Conference
  • Int'l Joint Research
• [Presentation] Organic Electrosynthetic Reactions Using a Proton-Exchange Membrane (PEM) Reactor (2021)
  • Author(s): Mahito Atobe, Atsushi Fukazawa, Naoki Shida
  • Organizer: 72nd ISE Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Electrocatalytic Nuclear Hydrogenation of Benzoic Acids in a Proton Exchange Membrane Reactor (2021)
  • Author(s): Mahito Atobe, Atsushi Fukazawa, Naoki Shida
  • Organizer: 239th ECS Meeting
  • Int'l Joint Research
• [Book] 有機電解合成の新潮流 (2021)
  • Author(s): 淵上寿雄、跡部真人、稲木信介
  • Total Pages: 340
  • Publisher: シーエムシー出版
  • ISBN: 9784781316260
• [Remarks] 跡部研究室ホームページ
  • URL: http://www.atobe-lab.ynu.ac.jp
• [Patent(Industrial Property Rights)] 環状アミンの製造装置及び環状アミンの製造方法 (2023)
  • Inventor(s): 跡部真人、信田尚毅、清水勇吾
  • Industrial Property Rights Holder: 跡部真人、信田尚毅、清水勇吾
  • Industrial Property Rights Type: 特許
  • Filing Date: 2023
  • Overseas
• [Patent(Industrial Property Rights)] 環状アミンの製造装置及び環状アミンの製造方法 (2022)
  • Inventor(s): 跡部真人、信田尚毅、清水勇吾
  • Industrial Property Rights Holder: 跡部真人、信田尚毅、清水勇吾
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-134327
  • Filing Date: 2022