Charlotte Wiles

• University of Hull

A safe and scalable continuous flow strategy for Wolff-Kishner reductions that employs methanol as solvent has been developed. The use of low-cost hydrazine as reducing agent in combination with a caustic base provides an atom efficient, environmentally friendly method for the deoxygenation of aldehydes and ketones to alkanes. Due to the required h...

The invention is directed to a method for the preparation of an acyl or alkyl halide, comprising, respectively, reacting a carboxylic acid or an alcohol with a halogenation agent in the presence of a base, wherein the reaction is at least partially carried out in a continuous-flow reactor.

The invention is directed to a method for the preparation of an acyl or alkyl halide, comprising, respectively, reacting a carboxylic acid or an alcohol with a halogenation agent in the presence of a base, wherein the reaction is at least partially carried out in a continuous-flow reactor.

Microreactor systems are now used more and more for the continuous production of metal nanoparticles and metal oxide nanoparticles owing to the controllability of the particle size, an important property in many applications. Here, for the first time, we used microreactors to prepare metal oxide nanoparticles with controlled and varying metal stoic...

Whilst continuous processing is a mainstream technique in the petrochemical and food industries as a tool for accessing highly productive and low cost production processes, until recently the pharmaceutical, fine chemical and specialty chemical industries were still dominated by batch processes and segmented unit operations. Through multi-disciplin...

A facile and benign route to N-heterocycles, including triazoles and triazolopyrimidines, has been developed. Using continuous-flow microreactor technology, organic azides are prepared in situ and reacted with cyanoacetamide in a [3 + 2] cycloaddition to produce a variety of substituted 1,2,3-triazoles, which can be elaborated into useful building...

Reviewing the open literature, the authors give their perspective on if continuous process technology has a role to play in sustainable production within the chemical industry.

Microreactor technology is an emerging technique that enables those working in research and development to screen reactions rapidly using continuous flow, leading to the identification of reaction conditions that are suitable for use at a production level. Furthermore, in addition to using conventional reaction methodology, the inherent safety asso...

Continuous-flow methodologies have been applied to the synthesis of a number of fluorinated alkynyl arenes and heteroarenes. Through a series of optimizations reagent stoichiometry and reaction time were improved and substrate specificity was interrogated. Using optimized conditions under copper-free Sonogashira type couplings readily available are...

A multichannel microreactor was fabricated to perform metal-catalyzed reactions and its efficiency was evaluated by comparing the yields and rates obtained within the micro-environment with batch processes. The microreactor was realized in glass so as to be compatible with a wide range of solvents and designed with a geometry suitable to increase t...

Nucleophilic Substitution at Saturated Carbon Nucleophilic Substitution at Carbonyl Carbon Conclusion References

The preparation of magnetic iron oxide nanoparticles within microreactors is reported. The proportion of γ-Fe2O3 and Fe 3O4 in the sample was determined, an important parameter for reproducibility in applications.

With the chemical industry acknowledging its pivotal role in the development and application of sustainable processes, the emergence of micro reaction technology, and more broadly flow chemistry, has captured the attention of chemists in all disciplines, ranging from those involved in research and development to those concerned with large-scale pro...

Dr Paul Watts is a reader in organic chemistry at The University of Hull and since graduating from the University of Bristol, where he completed a PhD in bio-organic natural product synthesis, he has led the Micro Reactor Group at Hull. In this role, he has published 90 papers, and he regularly contributes to the field by way of invited book chapte...

In light of the growing interest in the use of rare earth metal triflates as water-tolerant Lewis acid catalysts, we embarked upon the development of a solid-supported gallium triflate (PS-Ga(OTf)(2) ) derivative as a means of increasing the cleanliness and cost effectiveness of using these increasingly expensive catalytic materials in synthetic pr...

With aspects of continuous processing featuring heavily in efforts towards increasing the ‘green’ prospects of pharmaceutical and fine chemical manufacturing, this article focuses on the developments made into the application of continuous flow reactors for sustainable chemical research and production.

Whilst microwave heating has been widely demonstrated as a synthetically useful tool for rapid reaction screening, a microwave-absorbing solvent is often required in order to achieve efficient reactant heating. In comparison, microreactors can be readily heated and pressurised in order to "super-heat" the reaction mixture, meaning that microwave-tr...

It is the intention of this review to provide the reader with a survey of the current literature pertaining to the use of micro reactors in synthetic chemistry; recent advances are briefly discussed, with references provided to assist with further reading on this rapidly growing research topic.

A novel method has been devised to derive kinetic information about reactions in microfluidic systems. Advantages have been demonstrated over conventional procedures for a Knoevenagel condensation reaction in terms of the time required to obtain the data (fivefold reduction) and the efficient use of reagents (tenfold reduction). The procedure is ba...

With an average lead time of 10–12 years for a compound to progress from initial identification through clinical trials and finally into a medicine, the pharmaceutical industry are interested in the development of techniques which have the potential to reduce the time taken to generate prospective lead compounds and translate the protocols into pro...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Whilst it is widely acknowledged that micro reactors can be used to generate products in higher yield, purity and selectivity when compared to batch reactors, a perceived disadvantage of the technology is the fact that only small quantities of product can be prepared. In this article, recent literature demonstrating industrial uptake of the technol...

Through the preparation of a novel controlled pore glass-poly(pyrrole) material we have developed a conducting support that is not only suitable for the co-immobilisation of enzymes and co-factors, but also enables the facile electrochemical regeneration of the co-factor during a reaction. Employing the selective reduction of (rac)-2-phenylpropiona...

Micro-reactors containing a monolith-immobilised thermophilic l-aminoacylase, from Thermococcus litoralis, have been developed for use in biotransformation reactions and a study has been carried out to investigate the stereospecificity and stability of the immobilised enzyme. The potential to use the developed micro-reactors as a tool for rapid scr...

Medicinal chemists are under increasing pressure, not only to identify lead compounds and optimize them into clinical candidates, but also to produce materials in sufficient quantities for subsequent investigation. With this in mind, continuous-flow methodology presents an opportunity to reduce the time taken to, first, identify the compound and, s...

Using lipase catalysed, enzymatic esterification as a model reaction, we successfully demonstrate the use of miniaturized technology for biocatalytic reactions. Benchmarked against batch reactions, nine alkyl esters have been synthesized effectively, using Novozyme 435 in a pressure driven, packed-bed, miniaturized, continuous flow reactor. In some...

Focussing its' research on illustrating the potential of continuous flow reactors to enhance chemical synthesis, the micro reactor group at The University of Hull has spent the past nine years developing continuous processes for an array of common synthetic reactions, enabling advantages such as reduced reaction times, enhanced reaction selectivity...

A (+)-gamma-lactamase was precipitated, cross-linked and the resulting solid crushed prior to immobilisation within a capillary column microreactor. The microreactor was subsequently used to study enzyme stability, activity, kinetics and substrate specificity. The thermophilic (+)-gamma-lactamase retained 100% of its initial activity at the assay t...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

In addition to their high affinity for inorganic cations, crown ethers have been shown to efficiently sequester ammonium ions, forming a stable adduct via hydrogen bonding. Using this principle, several authors have reported the use of crown ethers as protecting groups for amines however to date, their widespread use has been somewhat precluded by...

We report the use of an immobilised form of Candida antarctica lipase B, Novozym((R)) 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes). Initial inv...

Synthesis involving isotopes is an important aspect of pharmaceutical development as the in-vivo evaluation of isotopically labelled lead compounds allows the biological fate of metabolites to be determined. Common synthetic problems associated with isotope labelling such as the cost of reagents and lack of automation may be overcome by the effecti...

Building on our experience of micro-reaction technology, we present herein the evaluation of an integrated borosilicate glass micro reactor in which 51 α-aminonitriles were synthesized via a series of continuous solution-phase and heterogeneously catalyzed reaction steps, affording analytically pure products in yields > 99.6 %. As an extension to t...

Initial steps have been taken to develop an integrated microreactor, capable of performing multicomponent reactions consisting of both solution phase and heterogeneously catalyzed steps. Using the multicomponent Strecker reaction as a model, five α-aminonitriles were synthesized in excellent yields (>99.5%) and analytical purity, under continuous f...

The rupture of N-N bonds in three specific N-nitrosoarylamines (N,N'-dimethyl-N,N-dinitroso-para-phenylenediamine, Cupferron, and N-nitrosodiphenylamine) upon electrochemical oxidation in acetonitrile solution is investigated. In two cases, viz., Cupferron and N-nitrosodiphenylamine, self-inhibition via partial blocking of the electrode due to adso...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Building on an array of synthetic transformations reported within micro fabricated systems, we present an evaluation of a borosilicate glass micro reactor, suitable for conducting multi-component reactions. Introduction: With interest in the preparation of non-proteinogenic -amino acids growing, there are increasing demands for novel and efficient...

The competitive nature of the chemical industry means that researchers involved in product development and lead compound generation are under continued pressure to identify, and develop, promising programmes of research in order to secure vital intellectual property. The potential of a compound, however, depends not only on structural complexity, b...

Sol-gel nanoprobes, also known as Photonic Explorer for Bioanalysis with Biologically Localised Embedding (PEBBLE), capable of performing in-vitro intracellular monitoring of reactive oxygen species have been developed using a modified form of 5(6)-carboxyfluorescein diacetate. A sol-gel matrix was selected for the design of the probes as it is pho...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

We present herein a micro reactor set-up that enables parallel syntheses to be performed under electroosmotic flow conditions.

Owing to the competitive nature of the pharmaceutical industry, researchers involved in lead compound generation are under continued pressure to identify and develop promising programmes of research in order to secure intellectual property. The potential of a compound for therapeutic development depends not only on structural complexity, but also o...

By optimizing a reagent’s residence time within a packed-bed reactor, it is possible to overcome selectivity issues frequently encountered in stirred reaction vessels. This important feature is demonstrated for the chemoselective protection of 4-acetylbenzaldehyde whereby 1-[4-1,3-dithian-2-yl-phenyl]ethanone is obtained in excellent yield and puri...

To date, the synthesis of L-anserine has relied on the use of naturally occurring 1-methyl-L-histidine as a precursor, however its high cost prevents its use in the large-scale synthesis of L-anserine. With this in mind, we report herein a concise and efficient synthetic strategy, employing the 160-fold less expensive, L-histidine methyl ester dihy...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

This review focuses on the use of micro reactors as tools in synthetic organic chemistry, aiming to highlight the many advantages associated with their use, in particular their ability to synthesise products in high yield, purity and, where relevant, selectivity.

By employing a series of reactions we demonstrate the use of electroosmotic flow as a continuous pumping mechanism suitable for semi-preparative scale synthesis, affording an array of small organic compounds, of analytical purity, with yields ranging from 0.57-1.71 g h(-1).

Flow reactor technology typically generates compounds in higher yield, purity and selectivity, however purification is generally conducted using standard batch procedures which negate some of the advantages of performing reactions in flow reactors. This paper describes the results of conducting a variety of reactions in flow reactors incorporating...

Micro reaction technology offers a safe, controllable and information rich technique suitable for the long-term production of pharmaceutical agents and fine chemicals. To date however, few of the syntheses performed using this technology have addressed the problems associated with product purification. With this in mind, we report herein the incorp...

Coumarin C343 (C(16)H(15)NO(4)), a dye used to enhance the weak chemiluminescence associated with lipid peroxidation, was conjugated to silica nanoparticles and entrapped in a sol-gel matrix to produce a nanosensor capable of enhancing low-level chemiluminescence by approximately 100%.

Although in its infancy, the field of micro reaction technology is growing rapidly, with many research groups investigating the practical advantages associated with reaction miniaturisation. With this in mind, the following Feature Article aims to provide an overview of the progress made in the past decade, paying particular attention to the field...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

By exploiting the high surface to volume ratio obtained within continuous flow reactors, we are able to oxidise selectively an array of primary alcohols to either the aldehyde or carboxylic acid, depending on the flow rates employed, demonstrating a degree of reaction control unattainable in traditional stirred reactors.

This review focuses on the use of continuous flow reactors as tools in synthetic organic chemistry and aims to highlight their many advantages, including their ability to synthesise products in high yield, purity and, where relevant, selectivity.

Meeting Programme Dr Nigel Botting [University of St Andrews, UK] – Isotopic Labelling of Lignan Phytoestrogens . Prof. Frédéric Dollé [CEA PET Centre, Orsay, France] – Fluorine‐18 Chemistry: A Selection of Recent Advances . Prof. Peter Scott [University of Warwick, UK] – Creating Chiral Metal Centres . Mr Laurent Brichard [WBIC, University of Camb...

The unique operational characteristics of microreactors are described in this article, with particular reference to their use as tools for chemical synthesis. With reference to the future automation, an example is presented to illustrate how microreactors can be readily integrated into current HPLC systems, to enable fully integrated chemical synth...

We report a simple and efficient technique for the covalent immobilisation of a tris(2,2'-bipyridyl)ruthenium(II) derivative suitable for both chemiluminescence and electrochemiluminescence detection.

Over the past 5 years, interest in the miniaturisation of chemical synthesis has grown rapidly, however in order to facilitate transfer of the technology from its current position as a research tool to industrial applications, a core understanding of the challenges associated with transferring reactions from the macro to the micro domain is require...

Through incorporating a series of polymer-supported acid catalysts into a miniaturised EOF-based flow reactor, we demonstrate a clean and efficient technique for the protection of aldehydes as their respective dimethyl acetal. In addition, we also report the acid catalysed deacetalisation of 11 dimethyl acetals to their respective aldehyde. In all...

As a result of increasing environmental pressure, the chemical industry as a whole are exploring many routes in order to improve both the cleanliness and efficiency of many synthetic processes. One such approach is the application of micro reaction technology, which enables reactions to be performed more rapidly, efficiently and selectively than tr...

Using a series of silica-supported bases, we demonstrate the synthesis of eight condensation products within an EOF-based flow reactor; in all cases, high yields (>99%) and product purity are obtained.

A simple technique for the diastereoselective alkylation of a metal stabilised enolate is demonstrated within a pressure-driven micro reactor whereby enhanced diastereoselectivities were obtained compared to batch.

A range of techniques are demonstrated for the solution phase synthesis of esters within an EOF-based borosilicate glass micro reactor, including the use of mixed anhydrides and the in situ preparation of acyl halides.

We demonstrate the successful synthesis of an array of 1,2-azoles within a borosilicate glass microreactor whereby conversions in the range of 98−100% were obtained. In terms of large-scale production, this corresponds to 0.339 g day-1 per microreactor when employing reagent concentrations of 1.0 M.

We demonstrate that peptides derived from alpha-amino acids may be prepared in a micro reactor. The peptides were prepared in 20 min with quantitative conversion, compared to batch reactions which require prolonged reaction times. We illustrate that by using dilute reagent concentrations and short reaction times, less racemisation is observed in mi...

The synthesis of β-peptides has been successfully performed using a borosilicate glass micro reactor, in which a network of channels has been produced using a photolithographic and wet etching method. The reagents were mobilised by electroosmotic flow (EOF). The micro reactor was initially evaluated using a carbodiimide coupling reaction to form a...

We demonstrate a simple method for the regioselective preparation of 1,3-diketones within a micro reactor from silyl enol ethers where the products are free from both competing O-acylation and diacylation products.

We demonstrate the formation of a series of diketone enolates and their subsequent reaction with alpha,beta-unsaturated carbonyl compounds in order to prepare a variety of Michael adducts. In all cases, the conversions observed within a micro reactor were greater than those obtained in batch.

The regioselectivity of the acylation of Li enolates and silyl enol ethers is reported using acyl halides and acyl cyanides. We illustrate a simple method for the preparation of 1,3-diketones via the silyl enol ether in excellent yields, free from competing O-acylation and diacylation products.

We have demonstrated the use of silyl enol ethers in the aldol reaction within a micro reactor. Quantitative conversion of the silyl enol ether to a beta-hydroxyketone was observed in a 20 min period compared to traditional batch systems, where quantitative yields were only obtained when extended reaction times of 24 h were employed.

The synthesis of peptides has been successfully performed using a borosilicate glass micro reactor, in which a network of channels has been produced using a photolithographic and wet etching method. The reagents were mobilised by electroosmotic flow (EOF) and electrophoretic mobility. In addition, microporous silica frits were used in the micro rea...

As a resource recovery alternative, the use of refuse-derived fuel (dRDF) is being investigated as a substitute for coal in industrial spreader stoker boilers. Experiences are summarized from the combustion testing of 1/2-inch-diameter pellets using a modified animal pellet mill. Storage and handling experiences are also discussed. Approximately 18...

We report a novel method for conducting "green" singlet oxygen-mediated oxidations within a microfluidic device by immobilising a photosensitiser (prophyrin) on the channel walls. A strategy for immobilising molecules with an isothiocyanate group onto the amine group of a silanised glass surface was optimised using rhodamine B isothiocyanate (RBITC...