There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous-flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.

Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

The increasing amount of papers published on ionic liquids generates an extensive quantity of data. The thermal stability data of divergent ionic liquids are collected in this paper with attention to the experimental set-up. The influence and importance of the latter parameters are broadly addressed. Both ramped temperature and isothermal thermogravimetric analysis are discussed, along with state-of-the-art methods, such as TGA-MS and pyrolysis-GC. The strengths and weaknesses of the different methodologies known to date demonstrate that analysis methods should be in line with the application. The combination of data from advanced analysis methods allows us to obtain in-depth information on the degradation processes. Aided with computational methods, the kinetics and thermodynamics of thermal degradation are revealed piece by piece. The better understanding of the behaviour of ionic liquids at high temperature allows selective and application driven design, as well as mathematical prediction for engineering purposes.

Ionic liquid thermal stabilities: decomposition mechanisms and analysis tools

Over the last two decades, flow technologies have become increasingly popular in the field of organic chemistry, offering solutions for engineering and/or chemical problems. Flow reactors enhance the mass and heat transfer, resulting in rapid reaction mixing, and enable a precise control over the reaction parameters, increasing the overall process selectivity, efficiency and safety. These features allow chemists to tackle unexploited challenges in their work, with the ultimate objective making chemistry more accessible for laboratory and industrial applications, avoiding the need to store and handle toxic, reactive and explosive reagents. This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.

Taming hazardous chemistry by continuous flow technology

Crystalline porous materials are important in the development of catalytic systems with high scientific and industrial impact. Zeolites, ordered mesoporous silica, and metal-organic frameworks (MOFs) are three types of porous materials that can be used as heterogeneous catalysts. This review focuses on a comparison of the catalytic activities of zeolites, mesoporous silica, and MOFs. In the first part of the review, the distinctive properties of these porous materials relevant to catalysis are discussed, and the corresponding catalytic reactions are highlighted. In the second part, the catalytic behaviors of zeolites, mesoporous silica, and MOFs in four types of general organic reactions (acid, base, oxidation, and hydrogenation) are compared. The advantages and disadvantages of each porous material for catalytic reactions are summarized. Conclusions and prospects for future development of these porous materials in this field are provided in the last section. This review aims to highlight recent research advancements in zeolites, ordered mesoporous silica, and MOFs for heterogeneous catalysis, and inspire further studies in this rapidly developing field.

Heterogeneous Catalysis in Zeolites, Mesoporous Silica, and Metal-Organic Frameworks.

Over the past few years, isoindoles have found wide application in materials science. Isoindole containing BODIPY dyes are highly fluorescent materials and have been extensively used in various fields of science. Phthalocyanines, metal containing cyclic tetramers of isoindole, form coordination complexes with most elements of the periodic table. These complexes are intensely coloured and are used as pigments and dyes. However, isoindoles are relatively unstable 10π-heteroaromatic systems and few synthetic methods provide these compounds in good yields. This tutorial review will give an overview of the reported synthetic methods towards isoindoles and related heteroaromatic systems over a time span of approximately 10 years (2000 to current), including the applications where they have been reported. The importance of the field will be illustrated and factors influencing product stability will be discussed.

Synthesis of isoindoles and related iso-condensed heteroaromatic pyrroles

Transglucosylation potential of six sucrose phosphorylases toward different classes of acceptors

This review covers the formation of N- and S-containing heterocycles, initiated by gold-catalyzed nucleophilic attack of N- or S-nucleophiles onto alkynes. These types of nucleophiles have been somewhat overlooked as compared to their C- or O-counterparts in other reviews. In this particular work, their intramolecular gold-mediated attack onto alkynes is reviewed in depth. It is structured in such a fashion that the reader will get a clear view of which substrates react in which cyclization mode.

Homogeneous Gold-Catalyzed Cyclization Reactions of Alkynes with N- and S-Nucleophiles

2.6. Radical Reactions 5932 2.6.1. Radical Halogenation 5932 2.6.2. Ring-Opening and Expansion 5932 2.6.3. Miscellaneous 5934 2.7. Ring-Opening and Ring Expansion 5934 2.7.1. Cyclic Acetals 5934 2.7.2. Epoxides 5934 2.7.3. Cycloalkanes 5935 2.7.4. Ozonides 5937 2.7.5. Ring Expansion 5938 2.8. Ring Closure and Contraction 5939 2.8.1. Ring Closure 5939 2.8.2. Ring Contraction 5943 2.8.3. Ring Rearrangements 5943 2.9. Oxidation 5943 2.9.1. Oxidation of Halogenated Alcohols 5943 2.9.2. Oxidation of Olefins 5945 2.10. Pericyclic Reactions 5945 2.10.1. Cycloadditions 5945 2.10.2. Sigmatropic Rearrangements 5945 3. Synthesis of γ-Halo Ketones and Aldehydes 5946 3.1. Nucleophilic Substitution 5946 3.1.1. Enolate Alkylation 5946 3.1.2. Conversion of an Alcohol or Ether into an Alkyl Halide 5947

Bart Roman

Papers

Synthesis of isoindoles and related iso-condensed heteroaromatic pyrroles

Transglucosylation potential of six sucrose phosphorylases toward different classes of acceptors

Homogeneous Gold-Catalyzed Cyclization Reactions of Alkynes with N- and S-Nucleophiles

Synthesis of β-, γ-, δ-, ..., ω-halogenated ketones and aldehydes.

Plant based Pickering stabilization of emulsions using soluble flaxseed protein and mucilage nano-assemblies