SELECTBIO Conferences Flow Chemistry Asia 2019

アジェンダ



同時併催される学会のアジェンダ

Microfluidics & Organ-on-a-Chip Asia 2019 | Flow Chemistry Asia 2019 | 


2019年11月14日 (木)

08:00

参加登録、資料配布、コーヒー


セッションのタイトル:学会開会セッションと学会議長 Timothy Noel (アイントホーフェン工科大学准教授) の紹介

09:00

Timothy Noel学会議長

電気化学的な手法の開発とフロー技術の融合−2つの世界の最良の要素
Timothy Noel, Associate Professor, Eindhoven University of Technology, Editor-in-Chief, The Journal of Flow Chemistry, Netherlands

Electrochemistry constitutes a mild, green and versatile activation method of organic molecules. Despite these innate advantages, its widespread use in organic chemistry has been hampered due to technical limitations, such as mass and heat transfer limitations which restraints the scalability of electrochemical methods. Most of the limitations associated with organic electrochemistry can be overcome by performing electrochemical reactions in continuous-flow microreactors. Specifically, the confined dimensions of micro-flow reactors (up to 1 mm internal diameter) allows to reduce the Ohmic drop, to minimize the total amount of supporting electrolytes, and to increase mass transfer from the bulk solution to the electrode surface.

In this lecture, we will describe the development of an electrochemical flow reactor which allows not only to accelerate electrochemical transformations but also to scale the chemistry without the need for reoptimization of the reaction conditions. Furthermore, we will exemplify the versatility of this reactor for a variety of different electrochemical methods developed in our group, including selective oxidation of thioethers and the synthesis of sulfonamides and sulfonyl fluorides.

09:45

Shu Kobayashi基調講演

タイトルは未定です。
Shu Kobayashi, Professor, The University of Tokyo, Japan

10:30

フローケミストリーとプラズマケミストリー−テーマに基づく手法を用いて破壊的な技術による業界の変化を促す試み
Volker Hessel, Professor, School of Chemical Engineering, The University of Adelaide, Australia

At our Faculty at the University of Adelaide, we have developed a unique Theme-based approach which truly leads to an interdisciplinary research outcome (as opposed to multidisciplinary), and this is run as cross-faculty and cross-discipline action. Core is a selection and targeting of industrial windows of opportunity to be translated to an industrial showcases, which is followed by technology development and stakeholder engagement. Outcome is an aim for transformative change of industry by disruptive technologies, breaking with existing approaches, and pharmaceutical industry was changed that way. This offers release of large sustainability gain and leads to entirely new business models.
One feature and benefit of themes is to allow to cluster own research. First attempt was in 2007 with a cluster on Novel Process Windows (NPW). Those regimes systematically utilise unusual and typically harsh process conditions for enhanced activation of chemistries in continuous-flow and connection of multi-step chemistries [Hessel, ChemSusChem 2013]. In this talk, three recent thematic research clusters will be presented, to show how above methodology guides and promotes holistic, transformative research.

Solvent Factory (2017 onward) The FET-Open project ONE-FLOW translates the ‘vertical hierarchy’ of chemical multistep synthesis with its complex machinery into self-organising ‘horizontal hierarchy’ of a compartmentalized flow reactor system (www.one-flow.org). The new concept of a ‘Solvent Factory’ uses multi-phase liquids as integrated reactor-separator; ideally without need of any post-processing and -purification steps. This switch from hardware- to soft matter processing tools is especially beneficial, when approaching multi-step reactions with its many reactors and separators, and replacing them by one.
Fertilizing with Wind (2014 onward) Plasma-enabled chemical nitrogen fixation using air (N2) allows to manufacture NO/NO2 which can be further converted to yield nitric acid by absorption in aqueous solution. In a similar way, nitrogen and hydrogen can be reacted by plasma catalysis to give ammonia. In this way, fertilisers can be made “out of air” and using wind as green energy source. It will be discussed how this can lead to a transformation of agriculture to a precision horticulture. This is currently implemented in Uganda, as much growing AgTech nation, and e-agriculture, based on ICT using mobile phones, is a cross-discipline enabler. With U Warwick, the ERC Synergy research offers a large opportunity for fundamental revisit of plasma catalysis and its symbiosis.

Space manufacturing (2018 onward) Space manufacturing is off-earth manufacturing - the advanced technologies are for dual use: also on earth, in deep sea, in dry lands, and other disruptive scenarios. Space medicine is already now a business case and the next cancer drug might be developed in space. A think tank analysis has been made how to make medicines and nanoformulations stable to cosmic rays. Space mining is at the edge to become a business case. Flow-based extraction of artificial asteroid ores is investigated with coiled micro-flow inverters, posing adjacent metal separation tasks, not known on earth. A topic of similar importance is the continuous-flow based soil-solvent extraction of phosphorus (with and without rare earths); the remote mine might be in Morocco’s Western Sahara or in Moon’s Procellarum KREEP Terrane. Space farming is a mid-term development issue, and plasma based N-fixation can play a key role. Space chemistry research on flow-made quantum dots will be presented, hosted on a satellite, will be reported, to sever as satellite decoy for counterstrike measure. This demands fluid flow without pumps. A stop-flow for three reaction steps comprises solid-liquid mixing under zero gravity, heating and reaction, and ejection of a nanodust cloud in the space.

11:00

午前のネットワーキングブレイク

11:30

自動化に向けた動き:原薬の連続フロー合成
Wu Jie, Assistant Professor, Chemistry Department, National University of Singapore, Singapore

Compared to stepwise batch synthesis, multistep continuous flow synthesis enables the combination of multiple synthetic steps into a single and uninterrupted reactor network, thereby circumventing the need to isolate intermediates, and enabling automated synthesis. However, despite many advantages and much progress in end-to-end API continuous-flow synthesis, several hurdles still need to be overcome. For instance, solvent and reagent incompatibility between individual steps, build-up pressure of reactors, substrate dispersion, and requirement of regeneration of reagent and scavenger columns. I this talk, I will present our recent progresses in this research field, which enables a novel automated API synthesis platform.

12:00

CreaflowHANUリアクター:拡張可能な連続フローフォトリアクターの開発
Hannes Gemoets, R&D Engineer, Creaflow

In the last decade, continuous-flow photochemistry has received much attention from researchers in academia as well as industry. With the groundwork now in place, the focus has been shifted to the realization of scalable photochemistry, and in this context, the HANU-reactor was developed. This pulsating-flow plate reactor contains static mixing elements that induce a split-and-recombine flow path, and is equipped with a large window lid for maximum light exposure. The synergetic use of the reactor geometry with a pulsating flow regime, results in plug flow behavior combined with intense mixing, regardless of its net flow rate. The innovative design allows the user to operate the reactor at both short and very long light exposure times, without compromising the mixing efficiency or the need for flow recirculation. To demonstrate its potential, an intramolecular [2+2]-cycloaddition was performed, producing an impressive 2.3 kg of Cookson’s diketone per day, utilizing a single 15 mL lab-scale HANU-reactor. Thanks to the innovative design, the HANU-reactor can be linearly scaled. Preparative photochemistry is now readily accessible by simply widening its process channel without the need to change any process parameters.[4] In addition, the pulsatile flow expands the window to heterogeneous reaction processing (e.g. heterogeneous photocatalyst). Furthermore, the window lid allows visual inspection as well as application of non-invasive, through-window inline spectroscopic PAT.

12:30

ネットワーキングランチ、展示会とポスター発表の見学


セッションのタイトル:フローケミストリーの分野における新たなテーマと技術

14:00

フローケミストリーの産業化を促す大容量マイクロチャネルリアクター (SMCR®)
Akira Matsuoka, Researcher, Technical Development Group, Kobe Steel Ltd., Japan

  • Concept of a large capacity micro channel reactor (SMCR®) with simple numbering up method by multi-channel plate stacking
  • Several practical applications of SMCR®

14:30

マイクロリアクターの粒子合成戦略
Simon Kuhn, Professor, Department of Chemical Engineering, KU Leuven, Belgium

This talk will present approaches for the controlled and continuous formation of particles, either as organic crystals or as inorganic precipitates. Control of the particle size distribution is achieved by either implementing a two-phase flow strategy or using high-frequency ultrasound. Both presented reactor concepts serve as important stepping stones to efficiently handle solids in microreactors.

15:00

午後のネットワーキングブレイク

16:00

原薬の連続製造に対応するマイクロ充填床リアクター
Jisong Zhang, Assistant Professor, Tsinghua University , China

The engineering principles of micropacked bed reactors and applications of this reactor on the continuous API manufacturing will be discussed.

16:30

エンジニアリング機能材料のための微量反応技術
Guangsheng Luo, Professor, Tsinghua University, China

Microchemical process technologies have high promising prospects for the development of green and low-carbon chemical industries. The new technologies are also expected to make some great changes in the preparation of engineering and functional polymer materials. The microreaction processes with high viscosity polymer solutions as reactants are very hard to control for the poor mixing, high pressure drop, and complex phase change performances. In our recent work, controllable preparation of polymer materials in microreactors have been carried out. For the preparation of bromobutyl rubber (BIIR), we have developed a PTFE-lined microreactor platform and obtained high quality BIIR based on excellent mixing ability. We developed a highly efficient method for the synthesis of polyvinyl butyral (PVB) in a microchemical system. In this presentation, we will present the details of the development.

17:00

フロー法での反応工学と粒子光学:拡張可能な強化された化学反応からデザイナードラッグへ
Saif Khan, Associate Professor, Chemical and Biomolecular Engineering, National University of Singapore, Singapore

In this talk, I will provide an overview of our research on engineering micro- and milli-fluidic systems to develop advanced manufacturing processes that bridge both primary (drug substance) and secondary (drug product) pharmaceutical manufacturing.

17:30

フロー法での大環状化プロセス
Shawn Collins, Full Professor, Universite de Montreal, Canada

Traditional macrocyclization reactions often use batch reactors and/or apparatus for slow addition protocols. However, an emerging alternative exists in performing macrocyclizations in continuous flow. Continuous processing can offer several advantages, including higher yields and shorter reaction times due to improved mass and energy transfer. Continuous flow macrocyclizations involving the olefin metathesis reaction, the Glaser-Hay coupling, CuAAC as well as new photochemical macrocyclizations will be discussed.

18:00

レセプション

19:00

学会1日目終了

2019年11月15日 (金)

08:00

朝のネットワーキングブレイク


ブレックファストチュートリアル:学会議長Timothy Noel氏によるフローケミストリーについての短期講座

08:30

合成有機化学分野におけるフローケミストリーの基本原理
Timothy Noel, Associate Professor, Eindhoven University of Technology, Editor-in-Chief, The Journal of Flow Chemistry, Netherlands

Flow chemistry is typically used to enable challenging reactions which are difficult to carry out in conventional batch equipment. Consequently, the use of continuous-flow reactors for applications in organometallic and organic chemistry has witnessed a spectacular increase in interest from the chemistry community in the last decade. However, flow chemistry is more than just pumping reagents through a capillary and the engineering behind the observed phenomena can help to exploit the technology’s full potential. Here, we aim to give a concise overview of the most important engineering aspects associated with flow chemistry, such as mixing, heat transfer, multistep reaction sequences, etc. In addition, we will give suitable chemistry examples where appropriate to demonstrate the impact of flow processing on synthetic organic chemistry.


セッションのタイトル:フローリアクター技術の進歩

09:30

不均一系触媒に対応する3D印刷されたリアクターインサート−化学薬品製造の新たなソリューション
Christian Hornung, Director of FloWorks, CSIRO, Australia

With a design guided by CFD, 3D-printed from base metals such as stainless steel, and coated with a catalyst using either cold spraying, electroplating or wash coating, catalytic static mixers are used to replace fixed bed columns in continuous flow heterogeneous catalysis. The deposition methods have been optimized in order to minimize catalyst leaching levels, resulting in only ppb levels of catalyst contamination in the product. We have demonstrated the versatility of this technology for gas-liquid hydrogenations in the pharmaceutical, fine chemical and related industries.

10:00

John Naber基調講演

MSDにおけるフローケミストリーの新たな手段と最新の応用分野
John Naber, Director, Flow Chemistry and Lab Automation, Process Research & Development, Merck & Co, United States of America

The manufacturers of active pharmaceutical ingredients (APIs) and their intermediates have recently rediscovered flow chemistry and continuous processing.  This renewed interest in these technologies has arisen from the anticipated benefit in supply chain economics and regulatory pressure in addition to the obvious opportunity for improved control including heat and mass transfer, process safety, access to high pressure and high temperature conditions, and use of supported catalysts and biocatalysts.

To take advantage of these benefits it is often necessary to develop new tools and platforms, including methods for characterizing fast mixing reactions or new reactors for scaling up photochemical reactions.  This talk will describe the development of some of these tools and the subsequent application of these tools to pharmaceutical manufacturing processes.

10:45

午前のネットワーキングブレイク

11:15

マイクロリアクターシステムでのアゾ染料の連続フロー合成
Jianhong Xu, Professor, Department of Chemical Engineering, Tsinghua University, China

Azo dyes are a kind of synthetic dyes containing azo group (Ar-N=N-Ar), which accounts for more than 70% of all dye structure categories. In industry they are prepared by batch reactor under ice bath,which brings about the difference in color strength and color shade. And the yield is not high. In this talk, a new method for the continuous synthesis of azo dyes is developed by using microreaction system. The continuous-flow synthesis of azo dyes in a microreactor system has great potential in industrial applications.

11:45

マイクロフロー技術をベースにした効率的なアミド結合の形成
Shinichiro Fuse, Associate Professor, Tokyo Institute of Technology, Japan

Efficient amide bond formations were developed based on rapid mixing and precise control of temperature using micro-flow reactors. The developed synthetic methodology was used for low cost, less wasteful, and high yielding synthesis of peptides and amino acid N-carboxy anhydrides.

12:15

Dong Pyo Kim基調講演

医薬品製造のためマイクロリアクターシステムをスケールアップする技術の進歩
Dong Pyo Kim, Yonsan Chaired Professor, Pohang University of Science And Technology (POSTECH), Korea South

Continuous-flow technology is emerging for efficient, sustainable and safe synthesis of drug and the precursors. Scale-up production approach is generally achieved by numbering-up microreactors in parallel as well as increasing channel size-up. At here, we present various economic numbering-up microreactor systems with robustness for scale-up production of several drug compounds. The stacked stainless steel metal microreactors and portable polymer pad are developed to demonstrate a drug via azide-alkyne reaction, fast synthesis of organophosphates in a cost-effective and single-step manner. Moreover, an upscaling photocatalysis in flow is also performed in an multi-capillary assembly system for synthesis of indazoles with improved productivity.

13:00

ネットワーキングランチ

13:30

医薬品製造にとってのフローケミストリーの高い重要性
Andrew Rutter, Senior Director, GlaxoSmithKline, United Kingdom

Flow chemistry’s importance to medicines manufacture goes far beyond enabling different (better) chemistry - it is about providing agility (and compliance) in how we design and build medicines supply chains. I will explore how flow chemistry builds to Continuous Manufacturing processes and how this approach supports agility in the supply of medicines. I will link this approach to advances in modularization and a digital twin of the process. This philosophy is equally applicable in Small and Large Molecule manufacture.

14:00

連続フロー法での自動化された精密ポリマー合成からナノ粒子形態制御までの工程の概要
Tanja Junkers, Professor, School of Chemistry, Polymer Reaction Design group, Monash University, Australia

An overview is given on the continuous flow multistep synthesis of complex macromolecules, the employment of machine learning to achieve unprecedented polymer synthesis accuracy and inline purification of polymers. Further, it will be demonstrated how continuous flow can improve nanoparticle synthesis in polymerization-induced self-assembly, and how kinetic morphology control over size and shape of nanoobjects can be achieved by flow mixing of block copolymers.

14:30

フロー法での時間と分子構造で分解された反応のモニタリング:イオン移動度分析法と質量分析法の可能性
Maarten Honing, Professor, Maastricht University, M4I Institute Maastricht MultiModal Molecular Imaging, Netherlands

In this presentation, recent results on the application of novel ionization technologies, and Ion Mobility Spectrometry combined with MS or MS/MS methodologies will be presented. Its potentials will be discussed using different “stereo-selective” chemical conversions in flow, and attention will be given to the detection of low abundant “synthesis byproducts” lacking chromophores hampering spectroscopic detection.

15:00

マイクロリアクターでの複合流体の輸送現象と応用分野
Yuanhai Su, Associate Professor, Shanghai Jiao Tong University, China

Chemical industry often involves fluids that change its phase states or physical properties significantly during reaction processes. The phase states variation can be easily observed when solid particles or gas bubbles are produced during liquid phase reaction processes, while physical properties such as viscosity are changed greatly and even the reaction mixture can be easily varied from Newtonian fluid to non-Newtonian fluid during polymerization processes. Although the hydrodynamics, transport phenomena and reaction performance of Newtonian fluid systems in microchannels or microreactors have been widely investigated, complex fluids and its applications in microreactors have not attracted much attention up to now. In this talk, we will focus on liquid phase reaction processes involving complex fluids, and its characteristics of transport phenomena and reaction performance in microreactors will be clearly shown. In particular, several application examples such as free radical polymerization, ionic liquid synthesis and nanocatalysis in microreactors will be thoroughly discussed, and the remaining challenges will be revealed.

15:30

ガスによる液滴フローリアクターを用い、TBD触媒でポリマー化されたd-Valerolactoneの動態研究
Kai Wang, Associate Professor, Department of Chemical Engineering, Tsinghua University, China

The kinetic model and reaction mechanism of ring opening polymerization of d-valerolactone catalyzed by TBD were established by gas-driven droplet flow technology.

16:00

発熱を伴う有機合成のスケールアップおよび製造強化のための戦略
Chaoqun Yao, Associate Professor, Dalian Institute of Chemical Physics, China

In this talk, exothermic synthesis processes with micro-reaction systems will be  introduced, including neutralization reaction,sulfonation and nitration. These reactions behave differently in that the reactions either only release heat, or produce solids, or are temperature-sensitive in side reactions. Regarding this, we will present our studies on specific products and show different strategies to intensify and scale-up the processes.

16:30

Multigram-Scale Flow Synthesis of the Chiral Key Intermediate of (-)-Paroxetine Enabled by Solvent-Free Heterogeneous Organocatalysis
Sandor B. Otvos, Researcher, Institute of Chemistry, University of Graz, Austria

(-)-Paroxetine is a selective serotonin reuptake inhibitor which is broadly used for the treatment of depression, anxiety and panic disorder. It is currently manufactured by batch processes of 10?15 reaction steps which typically apply classical resolution methods, chiral auxiliaries, enzymatic asymmetrizations or naturally occurring homochiral starting materials as sources for asymmetry. Catalytic enantioselective transformations have also been harnessed for the synthesis of (-)-paroxetine. These methods require less synthetic steps and provide more direct access to the target API, but their applicability for manufacturing is limited by the low productivity of the catalytic asymmetric key step. Motivated by these limitations, we developed a flow process for the synthesis of the chiral phenylpiperidine key intermediate of (-)-paroxetine. The critical step to introduce asymmetry was a solvent-free enantioselective conjugate addition in the presence of a highly robust heterogeneous organocatalyst. The chiral adduct was processed further via a telescoped reductive amination?lactamization?amide/ester reduction sequence which took advantage of a heterogeneous catalytic hydrogenation approach and the application of neat BH3dimethylsulfide complex as an efficient reducing agent unprecedented in earlier flow syntheses. The solvent-free or highly concentrated conditions in combination with the remarkably robust catalysts enabled multigram per hour scale production of the chiral target. In addition, the process generated minimal amounts of waste as demonstrated by a cumulative E-factor of 6.

17:00

学会閉幕

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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