Multistep Continuous Flow Synthesis of Fine Chemicals with Heterogeneous Catalysts

Author: Yuki Saito

Publisher: Springer Nature Singapore

Book Series : Springer Theses

Part of: Springer Professional "Wirtschaft+Technik" , Springer Professional "Technik"

Table of Contents

About this book

This book describes the development of two kinds of continuous-flow transformation using heterogeneous catalysts, and explains how they can be applied in the multistep synthesis of active pharmaceutical ingredients. It demonstrates and proves that fine chemicals can be synthesized under continuous-flow conditions using heterogeneous catalysis alone. Importantly, the book also proposes a general concept and strategy for achieving multistep flow synthesis and developing heterogeneous catalysts, and shows that commercially available anion exchange resin can be used as a water-tolerant strong base catalyst for various types of continuous-flow aldol-type reaction. Reviewing the state of the art in heterogeneous catalysis in flow chemistry – a “hot topic” and rapidly developing area of organic synthesis – the book will provide readers with a deeper understanding of fine chemical flow synthesis and its future prospects.

Frontmatter

Chapter 1. Introduction and Strategy

Abstract

We, synthetic chemists, deeply rely on flasks as reaction environments. They have been used since the era of alchemy and most of the modern organic syntheses are still performed using conventional glassware. Such a manufacturing method is called batch synthesis, where reagents, reactants, catalysts, and solvent are charged in a reaction vessel at once to perform target organic transformations. Because it is reliable and is a well-established method from a laboratory to industry, almost all fine chemicals such as active pharmaceutical ingredients (APIs), agrochemicals, and functional organic materials are synthesized by repeating this method. However, this method has several drawbacks, especially for mass production.

Yuki Saito

Chapter 2. Synthesis of Nitro-Containing Compounds Through Multistep Continuous Flow with Heterogeneous Catalysts

Yuki Saito

Chapter 3. Polysilane-Supported Pd Catalysts for Continuous-Flow Hydrogenations

Abstract

Continuous-flow hydrogenation is an important technology component to achieve multistep flow synthesis. Especially, hydrogenation of functional groups with high oxidation states such as nitrile, nitro, and carbonyl compounds are essential chemical transformations in my aldol-hydrogenation strategy (Scheme 3.1). To establish this method, I first focused on the hydrogenation of nitriles to primary amines as a target reaction.

Yuki Saito

Chapter 4. Anion Exchange Resins as Catalysts for Direct Aldol-Type Reactions of Ketones, Esters, and Nitriles Under Continuous-Flow Conditions

Abstract

Continuous-flow aldol-type reactions are the other essential part of the aldol-hydrogenation strategy (Scheme 4.1). In Chap. 2, flow aldol condensation between nitromethane and aldehyde using amine-functionalized SiO₂ catalyst was described. To expand the scope of nucleophiles and to access both aldol compounds and dehydrated compounds selectively, I decided to investigate different types of heterogeneous catalysts.

Yuki Saito

Chapter 5. Multistep Continuous-Flow Synthesis of APIs Based on Aldol-Hydrogenation Strategy

Abstract

Venlafaxine hydrochloride is a commonly used antidepressant agent. It inhibits the reuptake of serotonin and norepinephrine [Harvey et al. in Arch Gen Psychiatry 57:503, 2000]. It was first developed by Wyeth, a pharmaceutical company in the U.S., in 1993 and is now marketed by Pfizer. It was the sixth most used antidepressant in the U.S. in 2007 with >17 million prescriptions.

Yuki Saito

Backmatter

Title: Multistep Continuous Flow Synthesis of Fine Chemicals with Heterogeneous Catalysts
Author: Yuki Saito
Publisher: Springer Nature Singapore
Electronic ISBN: 978-981-19-7258-4
Print ISBN: 978-981-19-7257-7
DOI: https://doi.org/10.1007/978-981-19-7258-4