Dissertations / Theses on the topic 'Flow Synthesis'
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1
Simon, Mark David. "Fast flow biopolymer synthesis." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/117929.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 125-129).
This thesis describes the development and application of fast flow solid phase synthesis for the preparation of peptides and phosphorodiamidate morpholino oligomers (PMOs), as well as the application of fast, reliable peptide synthesis to study non-natural protein folding and function. In the first chapter, solid supported peptide synthesis was accelerated using flow by continuously delivering preheated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentrations, quickly exchanging reagents, and eliminating the need to heat reagents after they were added to the vessel. In the second chapter, these chemical principles were expanded upon and mechanical challenges particular to accelerated solid phase synthesis were overcome to build a fully automated fast flow peptide synthesizer than incorporates amino acids in as little as 40 seconds each. First, mechanical systems were developed to rapidly switch between the many reagents needed for peptide synthesis while maintaining the proper stoichiometry of all reaction components at all times. Second, conditions under which reagents did not appreciably degrade during storage or synthesis were found. Finally, synthetic outcomes were substantially improved by increasing temperature without degrading the protected, resin bound peptide. The third chapter describes the expansion of fast flow synthesis to PMOs. A 10-fold acceleration of PMO synthesis was realized using mechanical systems adapted from chapter 1, increasing the reaction temperature to 90°C, and introducing a Lewis acid catalyst. The acidity of the deprotection reagent was reduced to prevent cleavage of the backbone during 3' detritylation. In the final chapter, a "D-scan" of two small proteins, the disulfide-rich Ecballium elaterium trypsin inhibitor II (EETI-II) and a minimized Z domain of protein A (Z33), is reported. For each protein, the chirality of one amino acid at a time was inverted to generate a series of diastereomers, and study the critical stereocenters of EETI-I and Z33. Twelve out of 30 EETI-II analogs folded and were high-affinity trypsin inhibitors, but most active analogs were less stable to reduction than EETI-II. Similarly, twelve Z33 analogs retained high binding affinity to IgG, but most were substantially less stable than WT-Z33.
by Mark David Simon.
Ph. D.
2
Mijalis, Alexander James. "Automated flow peptide synthesis." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/118272.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2018.Cataloged from PDF version of thesis.
Includes bibliographical references.
Though reported by Merrifield nearly sixty years ago, batch solid phase peptide synthesis remains slow at minutes to hours per residue. Here we report a fully automated, flow based approach to solid phase polypeptide synthesis with amide bond formation in seven seconds and total synthesis times of forty seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to standard batch solid phase peptide synthesis. Process monitoring with absorbance spectroscopy allows for the immediate detection and rapid optimization of difficult-to-synthesize peptides. This instrument is flexible and allows for synthesis of peptide nucleic acids, glycopeptides, removal of orthogonal amine protecting groups, and click chemistry on the solid phase. At full capacity, this approach to peptide synthesis can yield tens of thousands of individual 30-mer peptides per year.
by Alexander James Mijalis.
Ph. D.
3
Hayes, Simon Jonathan. "Flow system for heterocyclic synthesis." Thesis, Cardiff University, 2007. http://orca.cf.ac.uk/54663/.
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The potential of the silver-catalysed cyclisation has been illustrated by the synthesis of furans, pyrroles and pyrazole-N-oxides. With yields predominantly being >95%, and ubiquitous high purity, the results herein show the compatibility of many substituents including alkyl, aryl and silyl, to name but a few. Extended investigations have improved our understanding of reaction rates, the effect of stereochemistry and the use of protection strategies as well as identifying a handful of limitations. With the above results in hand, and a desire to recognise the practical advantages of a metal-catalysed procedure, we have further described two continuous flow systems for heterocyclic synthesis. The first, a trickle-bed reactor, produces heterocycles in excellent yields (>95% except where volatile products were produced) and has been shown to exhibit < 1 ppm silver leaching. Our understanding of the optimal flow rates, catalyst loading and practical attributes associated with such a reactor is then described. The second, a supercritical carbon dioxide : ionic liquid system, has been shown to produce furans in excellent yields (>95%), when used in batch mode, and in slightly lower yield (>70%) when used in a continuous fashion. Once again silver leaching was seen to be <1 ppm. The success of these two systems, and the speed in which their success was achieved, clearly demonstrates the ease of working with silver-catalysed cyclisations. In a further brief foray, the use of heat and microwave irradiation is discussed in view of potential applications to other continuous systems. Finally, several specific applications of the silver-catalysed cyclisation have been shown. It is seen that this procedure is suitable for the synthesis of scented furans and has uses in the preparation of heterocyclic substrates, which can be used for bigger and better things. One such example, which is described in Chapter 6, is the formation of oxepan-4-ones, oxepin-4-ones and oxocins-5-ones from their corresponding furyl alcohols.
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Phillips, Thomas William. "Flow synthesis of silver nanowires." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/64907.
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This thesis reports the development of a droplet-based flow synthesis of silver nanowires. Using traditional batch methods of production it can be difficult to achieve the consistent reaction conditions needed to obtain nanocrystals with the desired properties. Microfluidic reactors offer superior control over reaction conditions and enable the scalable and continuous production of consistent and monodisperse nanoparticles. Silver nanowires are typically synthesised using the polyol reaction, where silver nitrate is reduced in hot ethylene glycol. Previous reports describing the synthesis of silver nanowires have come to contradictory conclusions about the conditions needed for growth. In this thesis a hot-injection polyol synthesis was adapted to a straightforward heat-up procedure for the production of silver nanowires. The success of the reaction was found to be dependent on the batch of ethylene glycol used. The modified synthesis enabled the development of a flow process using a polytetrafluoroethylene tubing-based droplet-based flow reactor. The reactor produced consistent silver nanowires over an eight hour period with no sign of reactor fouling. The reactor was used to investigate the effect of varying the reaction temperature, residence time, and concentration of iron nitrate and sodium chloride additives on the length of the silver nanowires produced. This thesis finishes with the development of an inline liquid-liquid separator based on the selective wetting and permeation of a porous capillary by one of the liquids. Efficient separation of aqueous-organic, aqueous-fluorous, and organic-fluorous flows was achieved over a wide range of flow rates. The separator was successfully applied to the inline aqueous-organic extraction of the pH indicator 2,6-dichloroindophenol. The organic extract and aqueous raffinate were separated using a porous capillary. UV-visible absorption spectroscopy showed the concentration of indicator in the aqueous raffinate to be less than one percent of its original value, confirming the efficacy of the extraction and separation process.
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Roper, Kimberley Ann. "New flow chemistry methods for organic synthesis." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607846.
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Kelly, Liam P. (Liam Porter). "Development of a continuous-flow synthesis of neostigmine methylsulfate and studies toward a continuous-flow synthesis of lisinopril." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122853.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019Cataloged from PDF version of thesis.
Includes bibliographical references.
[color illustration] Herein, we describe the development of a continuous flow synthesis of neostigmine methyl sulfate, an acetylcholinesterase inhibitor on the WHO list of essential medicines, and the transfer of the synthesis into a next-generation reconfigurable frame developed by our collaborators. Starting from 3-dimethylaminophenol, the synthesis provides a throughput of approximately 46.8 g/day (or 93,600 doses/day) of crude neostigmine methyl sulfate. The synthesis also showcases a prototype in-line evaporation unit that operates without any added carrier gas. Dr. Christina Dai performed early screening of lithium bases. Dr. Yuqing Cui and Dr. Naomi Briggs developed the downstream purification sequence. Dr. Nopphon Weeranoppanant developed the in-line evaporator and, along with Dr. Dale Thomas, assisted with performing the synthesis within their developed frame. Liam P. Kelly developed the continuous synthesis of neostigmine methyl sulfate. [color illustration] Lisinopril is a member of a large family of ACE inhibitors generally known as N-carboxyethyl dipeptides. Of this family, lisinopril is the most commonly prescribed. All known routes to lisinopril require isolation of several synthetic intermediates and protecting group manipulations, thus, development of an efficient continuous synthesis would provide great benefit. Herein we describe our investigation of several routes to generate intermediates of lisinopril with the end goal of a fully continuous synthesis, high material throughput, and minimal protecting group manipulations. Liam P. Kelly performed all work described within this chapter.
by Liam P. Kelly.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemistry
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Lau, Shing Hing. "Organic synthesis : taming chemistry using enabling technologies." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273347.
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This thesis describes the application of flow chemistry to discovery and development of medicinal compound synthesis and new chemical methodologies respectively. It is divided into three distinct sections. The first section addresses a brief introduction to flow chemistry, highlighting the advantages and challenges that have been faced in the past and present and also the outlook to the future. The second section reports the integration of machine-assisted methods with batch processes to produce two medicinal compounds, a precursor to the sacubitril and OZ439 respectively. In the respect to the precursor to sacubritil, a flow-batch integrated synthesis is developed to provide the desired product in 54% yield over 7 steps from commercially available 4-iodophenyl. In particular, a tube-in-tube gas flow reactor was employed in three gas-liquid reactions without the need for installing a costly highpressure autoclave. These gas-lquid reactions were an ethylene Heck coupling reaction, an anti-Markovnikov Wacker oxidation and a rhodium-catalysed stereoselective hydrogenation respectively. In addition, a diastereoselective Reformatsky-type carbethoxyallylation using zinc metal was also highlighted in this synthesis to install an important stereocentre. A new antimalarial agent, OZ439 containing a trioxolane unit as the main structural feature, has the unique property of providing a single-dose cure for malaria in humans and has recently completed phase IIb trials. A machine-enabled process for the preparation of OZ439 was developed in 33% overall yield over 5 steps without the need of column chromatography purification. This preparation features a selective continuous hydrogrenation, Griesbaum ozonlysis and a Zn-catalysed amide reduction in the present of triethoxylsilane. The third section contains the development of two new methodologies of diazo compounds with organoboron compounds. The first methodology involves an in situ generation of transient allylic boronic species by reacting TMSCHN2 and E-vinyl boronic acids in flow, followed by subsequent trapping with a range of aldehydes (15 examples, 55-97% yield) and on a large scale (10 mmol) to provide homoallylic alcohols with high diastereoselectivity (>20:1 dr confirmed by 1H NMR). This multicomponent metal-free reaction could also be applied under batch conditions (20 further examples, 60-82% yield). The second methodology involves the preparation of an organodimetallic compound, α-trimethylsilyl benzylboronic acid pinacol esters, by reacting TMSCHN2 and phenylboronic anhydrides (21 examples, 60-91% yield), and the development of their applications as bifunctional building blocks to complex structures.
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Prinzi, Roberta. "Synthesis of functional polymers by flow processes." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/15804/.
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Questo lavoro di tesi vuole essere un valido contributo per lo sviluppo di nuove tecnologie nell'ambito della green chemistry soprattutto nell'ambito dei processi a flusso continuo, catalisi e l'utilizzo di polimeri funzionalizzati. Innanzitutto si è portata a termine la sintesi del poli(acrilammide-omocisteina tiolattone), (PAHT) tramite polimerizzazione RAFT. Successivamente il PAHT è stato modificato tramite un sistema a flusso continuo e tecnica "oil-oil" per ottenere un polimero funzionalizzato con gruppi funzionali amminici e tiolici sotto forma di "beads". Il prodotto ottenuto è stato caratterizzato e la struttura è stata quindi confermata; in seguito si è testata l'attività catalitica come catalizzatore eterogeneo per la reazione di Knoevenagel dimostrando risultati positivi. La presenza di diversi gruppi funzionali del polimero capaci di essere facilmente modificati ha reso possibile la post-modificazione delle "beads" di polimero per inserire nuove funzionalità e proprietà quali gruppi solfonici, gruppi metil-metacrilici e nanoparticelle di oro. In conclusione è possibile affermare che tutti gli obiettivi prefissati sono stati ottenuti.
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Onder, Aylin. "Synthesis Of Zeolite Membranes In Flow System." Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614815/index.pdf.
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Zeolite membranes are formed as a thin zeolitic layer on the supports. They are usually synthesized by hydrothermal methods in batch systems. In this study, MFI and SAPO-34 type zeolite membranes were produced on macroporous tubular alumina supports in a recirculating flow system at elevated temperatures for the first time in the literature. During the synthesis, the synthesis mixture is flown between the reservoir and the membrane module which includes the support material.
The synthesis temperatures were 180°C and 220°
C, and the corresponding system pressures were approximately 20 and 30 bars for MFI and SAPO-34, respectively. The CH4 and n-C4H10 single gas permeances were measured through MFI membranes and the performance of membranes was investigated in the separation of equimolar CH4/n-C4H10 mixtures. The best MFI membrane had a CH4 single gas permeance of 1.45x10-6 mol/m2-s-Pa and CH4/n-C4H10 ideal selectivity of 35 at 25oC. The membranes preferentially permeated n-C4H10 in the separation of mixtures. The n-C4H10/CH4 separation selectivity was 43.6 with a total permeance of approximately 0.8x10-6 mol/m2-s-Pa at 25oC. The ideal selectivities of CO2/CH4 of SAPO-34 membrane synthesized in stagnant medium were 227, and >
1000 at 220 and 200oC, respectively. Formation of amorphous structure and the additional secondary phases (impurities) were observed on SAPO-34 membranes synthesized in recirculating flow system. The results showed that it is possible to produce SAPO-34 and high quality MFI membranes by a recirculating flow system operating at elevated temperature.
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Nagy, Kevin David. "Catalyst immobilization techniques for continuous flow synthesis." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/70405.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2012.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 181-199).
Catalytic processes are ubiquitous in both research and industrial settings. As continuous flow processes continue to gain traction in research labs and fine and pharmaceutical chemical processes, new opportunities exist for implementing previously difficult catalytic transformations. The major goal of this thesis is to expand and evaluate techniques for immobilized catalyst systems relevant to continuous flow. Fundamental studies in characterizing mixing, dispersion, and residence time distributions in small scale continuous flow systems are also presented. Given the numerous benefits associated with studying chemical processes at small length scales, microfluidic devices are the tool of choice for most studies in this thesis. Thermomorphic solvents offer the potential for homogeneous catalytic processes with biphasic catalyst recovery and recycle. A major limitation of these processes is the number of synthetically useful thermomorphic solvent combinations demonstrated in literature. A screening program using the modified UNIFAC (Dortmund) activity coefficient model to evaluate phase splitting behavior has been developed to predict thermomorphic behavior. Calculation of 861 binary solvent combinations results in 43 potential thermomorphic and 44 biphasic solvent combinations. Extension of the program to ternary solvents resulted in a new class of ternary solvents that display thermomorphic behavior with tunable critical solution temperatures. Evaluation of thermomorphic processes as a general method is presented. Traditional catalyst immobilization techniques rely on covalent grafting and are well suited to continuous flow processing due to the strong interactions of the catalyst to the support. Fluorous physisorption, which relies on interactions between a fluorous support and a fluorous-tagged catalyst, is characterized and presented as an immobilization technique for flow chemistry. The use of a fluorous-tagged Co(III)-salen catalyst to effect the ring opening of epoxyhexane with water is presented. Application of the platform to the ring closing metathesis of N,Ndiallyltosylamide using a fluorous-tagged Hoveyda-Grubbs metathesis catalyst results in significantly accelerated loss of activity over time compared to the salen catalyst. Use of continuous flow selective adsorption reactors to enhance catalytic processes is presented. Continuous feeds of a homogeneous catalyst into a sorbent where the catalyst displays an affinity for the sorbent results in accumulation of the catalyst in the packed bed. The net effect is an enhancement in turnover frequency and turnover number relative to homogeneous flow. Application of this platform to a Lewis acid catalyzed Diels-Alder reaction results in an order of magnitude improvement in turnover frequency compared to batch and homogeneous flow.
by Kevin David Nagy.
Ph.D.
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Kralj, Jason G. "Continuous flow separation techniques for microchemical synthesis." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/34164.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2006.Includes bibliographical references (leaves 146-153).
Performing multistep microchemical synthesis requires many techniques from combining micromixers in series to the development of continuous microfluidic separation tools. Safety, high heat and mass transfer rates, and cost savings all continue to motivate microreactor development as a research tool, but many reactions generate a variety of (by)products including solid particles, immiscible fluids (gas and liquid), and miscible components requiring purification. We have endeavored to develop microfluidic systems which compliment existing microreactor technology, using forces that grow stronger with decreasing length scales such as electric fields and interfacial phenomena, and to use straightforward microfluidic mixers for kinetic studies of energetic material synthesis. Dielectrophoresis was used to study the continuous separation of polystyrene particles based on size. Essentially, a microfluidic particle "ratchet" was created using a soft-lithography microchannel and slanted interdigitated electrodes which provide a transverse force component on the particles. Experimental behavior agreed well with the model predictions, and 4 & 6 micron particles were continuously separated. Liquid-liquid extraction is another useful tool for microchemical synthesis and well-suited to small length scales because high mass transfer rates can be attained.
(cont.) However, emulsion formation and phase separation can provide significant challenges to continuous processing. To address breaking emulsions, a microfluidic tool was developed that uses AC E-fields to enhance coalescence of emulsified phases even where high surfactant concentrations are present, transforming the flow regime from disperse to slug. Phase separation of immiscible fluids is achieved by interfacial tension using porous membrane films which selectively wet only one fluid phase. An integrated mixer-contactor-separator was fabricated and used to separate fluids with low interfacial tensions due to miscible components. Solvent extraction and solvent switching were demonstrated using the device, which help enable continuous multistep microchemical synthesis. Kinetic studies and optimization of energetic material synthesis were performed with a relatively simple micromixers-in-series setup for diazotization and nucleophilic substitution reactions. Typical batch operation is performed in sub-ambient conditions with copper salts to precipitate the product and avoid degradation, resulting in a slow, hazardous, laborious synthesis. High heat and mass transfer enabled studying reaction temperatures at 300C to obtain kinetic parameters for both reaction steps.
(cont.) In addition, an optimum pH range for the substitution reaction was found, which will lead to a streamlined, faster process. Though still early in their development, these new tools will hopefully open the door to a range of new chemical syntheses and applications under conditions unachievable on the macroscale. Full integration of these technologies will enable multistep chemistry in microfluidic systems, which in turn will allow screening of new compounds, synthesis optimization, and reduction in chemical waste in a safe, efficient platform usable by chemists and biologists.
by Jason G. Kralj.
Ph.D.
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Koecher, Matthew R. "Hardware Synthesis of Synchronous Data Flow Models." BYU ScholarsArchive, 2004. https://scholarsarchive.byu.edu/etd/20.
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Synchronous Dataflow (SDF) graphs are a convenient way to represent many signal processing and dataflow operations. Nodes within SDF graphs represent computation while arcs represent dependencies between nodes. Using a graph representation, SDF graphs formally specify a dataflow algorithm without any assumptions on the final implementation. This allows an SDF model to be synthesized into a variety of implementation techniques including both software and hardware. This thesis presents a technique for generating an abstract hardware representation from SDF models. The techniques presented here operate on SDF models defined structurally within the Ptolemy modeling environment. The behavior of the nodes within Ptolemy SDF models is specified in software and can be simple, such as a single arithmetic operation, or arbitrarily complex. This thesis presents a technique for extracting the behavior of a limited class of SDF nodes defined in software and generating a structural description of the SDF model based on primitive arithmetic and logical operations. This synthesized graph can be used for subsequent hardware synthesis transformations.
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Boldrin, Paul. "Synthesis and characterisation of nanomaterial catalysts made using continuous hydrothermal flow synthesis." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497781.
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Carter, Catherine Frances. "The application of flow chemistry to natural product synthesis." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610524.
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Wang, Zhenhong. "Power flow analysis of engineering structure using substructure techniques." Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270373.
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Takahashi, Yusuke. "Flow Microreactor Synthesis Using Short-Lived Organolithium Intermediates." 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215961.
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Chiu, Chuang-Wei. "Biodiesel synthesis and impact of cold flow additives /." free to MU campus, to others for purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p1421124.
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Lee, Peter D. "Organometallic synthesis in supercritical fluids." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336862.
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Sagandira, Cloudius Ray. "Exploring acyl azides chemistry in continuous flow systems." Thesis, Nelson Mandela Metropolitan University, 2017. http://hdl.handle.net/10948/12065.
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Organic azides are important in the synthesis of many target molecules of great use in fine chemical and pharmaceutical production. The use of this class of compounds is however limited due to their hazardous nature and many safety concerns, as they are highly exothermic. Micro reactors can handle exotherms extremely well, due to the inherent high surface area to volume ratio, unlike the conventional batch process. This dissertation therefore aims to investigate the safe application of micro reactors in acyl azide chemistry.With this in mind, Chapter 1 provides a comprehensive background on organic azides, reaction calorimetric studies, flow chemistry technology (micro reactors) and their theoretical advantages. This chapter also discusses the preparation of organic azides in continuous flow systems and scaling up in continuous flow systems. Chapter 2 illustrates and discusses multivariate optimisation of benzoyl azide synthesis as a model reaction, synthesis of other acyl azides using the model reaction optimised conditions and multistep synthesis of carbamates, amides and amines in continuous flow systems via the Curtius rearrangement of benzoyl azide formed in situ from benzoyl chloride and sodium azide. The chapter also discusses process hazards analysis and evaluation of benzoyl azide synthesis and decomposition using calorimetric studies. It also investigates and discusses the effects of different mixing regimes and channel sizes on scale up. Chapter 3 has comprehensive experimental details for the whole dissertation with Chapter 4 providing the concluding remarks and future work recommendations.
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Baker, Alastair. "Flow reactors for the continuous synthesis of garlic metabolites." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/86704/.
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Garlic secondary metabolites are organosulfur compounds that possess prophylactic properties. The chemical composition of garlic oil extracts consists of a combination of these compounds. The instability of a major component, allicin 5, limits the commercial viability of garlic oil extracts. The synthesis of garlics organosulfur compounds has been performed in batch reactors. In this thesis, flow reactors were utilised to improve the throughput, reduce the operating conditions. The thermolysis of allicin 5 is the solitary approach to produce the garlic metabolite, ajoene 14. Ajoene 14 has greater stability compared to allicin 5 that possesses interesting biological activity. The primary three-step synthesis investigated consisted of dialkyl polysulfide synthesis, subsequent oxidation and finally the terminal thermolysis. In addition, other garlic metabolites have also been produced. The synthesis of unsymmetrical monosulfides and their subsequent oxidation was investigated using novel heterogeneous packed-bed flow reactors. The stable amino acid, alliin 15, is the precursor of allicin 5. Alliin 15 was also synthesised in homogeneous flow mode. The telescoped synthesis of alliin 15 was successfully completed using a semi-batch reactor. Development of novel approaches to synthesise garlics organosulfur compounds is reported in this thesis. Finally, the flow reactor systems, experimental details and characterisation of the compounds are described.
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Smith, Laura Katherine. "Synthesis of value-added intermediates by continuous flow technology." Thesis, Durham University, 2018. http://etheses.dur.ac.uk/12526/.
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We present three projects linked by our use of continuous flow chemistry in the synthesis of organic intermediates. The first is the synthesis of 1,1'-spirobiindane-7,7'-diol (SPINOL) in 6 steps and 32% overall yield. The synthesis has been improved over the previous literature protocols as it is safer, scalable, and higher-yielding, with better robustness and reproducibility. We introduce two attempts towards the enantioselective synthesis of SPINOL. In the second project, we have developed a flow process based on the Vapourtec reactor to synthesise coumalic acid and methyl coumalate from malic acid in concetrated sulfuric acid. A new heated rotating flow reactor is also presented for the intensified synthesis of coumalic acid, a valuable intermediate in organic synthesis derived from biorenewable sources of malic acid. Methyl coumalate has been used in two Diels-Alder reactions where the products have applications in molecular electronics and organic light-emitting diodes. Finally, the Darzens reaction for the synthesis of epoxides is presented here for the first time in flow, providing access to a range of benzaldehyde-derived products, including precursors to the pharmaceutical compound ibuprofen.
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Bourne, Samuel. "Development of novel gas-flow methodologies for pharmaceutical synthesis." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708895.
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Qian, Zizheng. "Synthesis of pharmaceutical molecules using flow based chemical processing." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610172.
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Smith, Christopher David. "The application of continuous flow technology for organic synthesis." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611296.
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Anwar, A. "Continuous plastic flow synthesis and characterization of nanoscale bioceramics." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1458257/.
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The development and use of nanoscale biomaterials offer tremendous potential for future medical diagnosis and analysis. Various types of ceramic biomaterials (bioceramics) have been studied intensively for their potential in numerous biomedical applications. Among others, advances in the synthesis and characterisation of calcium phosphate (CaP) bioceramics have contributed much to this field. The growing demand for CaP bioceramics has stimulated research and production of materials suitable for biomedical applications such as implants. Among all the materials presented by the recent technology, only a very small fraction overcome biological and mechanical limitations rendering them suitable for use as a biomaterial. There is, therefore, a need to develop a clean synthesis methodology which could work under mild conditions to allow the synthesis of high purity, nanoscale bioceramic materials with a fine particle size and controlled surface area. The work in this thesis involves the use of a continuous plastic flow synthesis (CPFS) technology to synthesise various nano-scale bioceramics. Novel CPFS is a single step, continuous synthesis method for a stable, high purity phase-pure nanosized hydroxyapatite and other calcium phosphates at near ambient conditions (20°C to 80°C). The phase-pure HA nanoparticles obtained from this method possess a substantially superior high-temperature stability (1200°C), with remarkably high surface area (up to 264 m2/g) and the smallest particle size (20 nm) ever reported. These high surface area nanoparticles have a great range of applications for use in replacement of living hard tissues such as bone and teeth, as bone graft substitutes, injectable, coatings on metallic implants, as fillers or additives in commercial products, such as toothpastes; materials for the controlled release of drugs, or other controlled release therapies; reinforcements in biomedical composites, and in bone and dental cements. Other calcium phosphate phases (Brushite, β-TCP, CDHA and biphasic HA / β-TCP) were also obtained by changing the Ca:P ratio and pH of the precursor solutions. A variety of ion substituted calcium phosphates (Mg, Sr, Ba, Zn, Fe, Mn, Si, CO32-), nanocomposite materials (Fe3O4-HA, TiO2-HA) and surface modified organopolymer nano-dental composites have also been developed successfully by using CPFS. Furthermore, the process has the potential to offer high purity calcium phosphates because the reactor components are made of plastic and therefore will not cause contamination of the product with metals. The in vitro biocompatibility analysis indicate that these high surface area nano-sized bioceramics have better performance than commercial products and may have the potential to be used for biomedical applications where bone regeneration / replacement is required.
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Wu, O. Y. "Continuous hydrothermal flow synthesis of lithium ion battery materials." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1455944/.
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There are a number of ways to improve the capacity of rechargeable batteries as suggested in the literature; carbon coating and reducing the particle size of the active material appear to be the most effective. In this work, the synthesis of pure phase LiFePO₄ nanoparticles was carried out directly in one step using the continuous hydrothermal flow synthesis (CHFS) system. Conventional synthesis methods require many steps and longer duration to obtain this cathode material. Microscopic data confirmed that the particles were successfully covered with an even carbon coating in situ where fructose was used. Through the use of the CHFS pilot plant, larger batches of the samples were made to allow thorough characterisation and electrochemical analysis. Coin cells were assembled from electrode sheets with the samples synthesised as the active material. The data collected from carbon coated LiFePO₄ cells showed good performance in terms of high C rate cycling and the specific capacity the cells provided. The results were comparable to those seen in the literature and amongst the highest of LiFePO₄ produced from a CHFS method. The doping of LiFePO₄ with manganese was successful as confirmed by various analysis techniques but it did not appear to have improved the electrochemical operation of LiFePO₄. However, upon certain doping levels the energy density of the material was approaching the theoretical value. The CHFS system was also used in an attempt to synthesise cathode materials optimised for electrochemical performance. For example, reaction conditions were tailored to produce samples with reduced particle sizes and samples intimately mixed with conductive carbon in situ. Further work will be to optimise the material ratio for electrodes and increase the amount of active material to be used. Also, to investigate fully how the morphology and thickness of an electrode can affect the performance of the cell.
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Starkey, Christopher L. "Continuous-flow hydrothermal and solvothermal synthesis of inorganic nanomaterials." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/37016/.
Full textAbstract:
Nanomaterials and nanotechnology are presently receiving high levels of interest which is aiding significant advancements to industrial and technological applications. New strategies towards nanoparticle synthesis are needed to produce high quality nanomaterials at industrially viable levels. This thesis presents the continuous flow hydrothermal and solvothermal synthesis (CFHSS) of a range of inorganic nanomaterials produced using a continuous-flow reactor designed at the University of Nottingham. The materials presented herein are currently industrially applicable or projected future trend materials. The aim is to widen the library of materials accessible via this relatively new synthetic strategy. It is mostly concerned with the development of the synthetic protocol towards specific materials and classes of materials, via both chemical and reactor configuration innovations, but additionally yields information about the chemical processes occurring within the reactor and how these can be controlled and exploited. This provides insight into not only the reactor but the field of CFHSS as a whole. Selected materials are subject to application based testing. With a fully industrial scale facility under construction, promising materials are trialled at pilot scale to assess the viability of the transfer of chemistry from laboratory to pilot scale with industrial scale production in mind. Chapter 1 provides an introduction to nanotechnology and nanomaterials in general, giving background to their unique properties and application. Traditional routes of synthesis are discussed, with particular focus then given to hydrothermal methods and continuous flow reactor design and nanoparticle production. Chapter 2 presents the characterisation techniques used in this thesis in terms of their theory and application. Application specific testing of the materials is explained in the relevant chapters. Chapter 3 reports the production of two different metal oxide materials, namely titania and doped titania photocatalyts, and barium strontium titanate nanopowders. Photocatalysis results are reported for the titania nanocrystals, and the barium strontium titanate nanopowders are produced in the first fully hydrothermal continuous flow synthesis at both laboratory and pilot scales to assess their viability for industrial scale production. Chapter 4 presents the development of the first continuous flow hydrothermal production of metal sulphide nanomaterials, via a general route using thiourea as the sulphur source. Full synthetic details and characterisation are discussed, together with information yielded about the materials and reactor and the implications this may have on future materials synthesis using CFHS and the Nottingham reactor. Chapter 5 details firstly batch hydrothermal and solvothermal synthesis of lithium iron phosphate materials to investigate the effect of a range of conditions on the reaction pathway and resulting products, followed by a translation of the knowledge learned into continuous flow hydrothermal and solvothermal reactions using the counter-current reactor. Scale up of the synthesis is achieved, together with electrochemical testing of selected products. Finally, chapter 6 provides general conclusions, summaries and outlooks for future work.
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Channa, Sikandar Ali. "Synthesis of Ti-based nanoparticles in continuous flow microreactors." Thesis, Nantes, 2017. http://www.theses.fr/2017NANT4067/document.
Full textAbstract:
Des nanoparticules à basede titane dispersées dans des sols ou des gels avec une distribution de taille étroite permettent l’exacerbation des propriétés photochimiques de films photosensibles. Utilisés comme absorbeurs solaires dans les photobatteries, ils permettraient la conversion et le stockage de l'énergie solaire sous forme électrochimique. Dans ce travail, ces matériaux nanostructurés ont été produits par l'hydrolyse de TiOCl2,1.4HCl,7H2O dans du N, N-diméthylformamide (DMF),à l'intérieur d'un microréacteur afin d’assurer un meilleur contrôle en température et de confiner les fluides. En fonction du temps de vieillissement ou par étuvage, cette hydrolyse conduit à l’obtention de sols et de gels constitués de nanoparticules dispersées dans le solvant. La signature thermique de l’hydrolyse du TiOCl2en microréacteur observée par caméra infrarouge montre des instabilités de l'écoulement préjudiciables au contrôle de la taille des nanoparticules. Ceproblème a été finalement résolu par la pré-dilution de TiOCl2 avec du DMF. Par ailleurs, l'usage d'un procédé actif de mélange(champ électrique) a permis d'accélérer la réaction d’hydrolysedu TiOCl2pré-dilué ou pur pour certaines valeurs des conditions opératoires par ex. 7 VAC, 1MHz et ceci sans constater d’effets parasites (électrolyse de l’eau et formation d’ions Ti3+). Finalement,les nanoparticules produites ont été analysées en utilisant la technique de diffusion dynamique de la lumière. Une taille moyenne de nanoparticules s'étendant de 5 à 50 nma été obtenueavec du TiOCl2 pré-dilué, celle-ci dépendant de la vitesse d'écoulement, de l’âge des échantillons etde laprésence ou non de champ électriqueTi-based nanoparticles dispersed in solutions or gels with narrow size distribution may constitute innovative materials as absorbers in new devices such as photobatteries, allowing conversion and electrochemical storage of solar energy. In our work, these nanostructured materials were produced inside a microreactor by hydrolysis of TiOCl2 stabilized in aqueous HCl solution reacting with N,N-dimethylformamide (DMF). The use of a microreactor aims at providing a better temperature control and also a confinement of the reactive fluids. The thermal signature of the hydrolysis of TiOCl2 recorded by an infrared camera shows flow instabilities detrimental to the control of nanoparticle sizes. This problem was solved by the pre-dilution of TiOCl2 with DMF in the following proportion 0.52 DMF/Ti (16.7% vol. DMF).Otherwise, the use of an active mixing process based on an electric field implemented inside the microreactor has clearly shown the acceleration of the hydrolysis of TiOCl2without generating parasitic effects(water splitting,formation of Ti3+ions), if operating conditions are adequately chosen (for ex. 7 V AC and 1 MHz). Finally, using Dynamic Light Scattering, an average size of nanoparticles ranging from 5 to 50 nm for pre-diluted TiOCl2 with 16.7% vol. DMFwas obtained depending on flow rates, ageing of samples and implementation or not of an AC electric field
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Bannock, James Henry. "Controlled synthesis of semiconducting polymers in droplet flow microreactors." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/45405.
Full textAbstract:
This thesis reports the development of droplet flow reactors for the preparation of semiconducting polymers, focussing specifically on poly(3-hexylthiophene) (P3HT) pre- pared by Grignard metathesis polymerisation, and random copolymers of P3HT with poly(3-hexylselenophene) (P3HS). In contrast to conventional continuous flow reactors (where the flow consists of a single solvent phase), droplet reactors incorporate an immiscible ’carrier fluid’ that divides the solvent phase into a stream of near-identical microlitre-sized droplets which then pass through the reactor sequentially. In this way, the solvent phase is confined to a well-defined volume that no longer makes contact with the surrounding reactor architecture, and thereby overcomes blockage problems associated with preparation of polymers in continuous flow reactors. To overcome the limited solubility of the Ni(dppp)Cl2 catalyst widely used in Grignard metathesis polymerisation, a more soluble derivative, Ni(dppp)Br2, has been prepared. This catalyst allows P3HT to be synthesised with accurate control over a wide range of molecular weights, even at high throughput (up to 1 kg/day). A scalable ’tube-in-shell’ reactor was developed to provide improved thermal uniformity along the flow reac- tor, enabling the preparation of high molecular weight P3HT with Mw up to 190 kg/mol (PDI 1.5) and lower weight polymers with narrow polydispersity (PDI 1.1). To facilitate multistep chemistries in droplets, a new three-phase methodology is presented that enables the controlled addition of reagents downstream of the original droplet gener- ation. With a view to applying P3HT in electronic devices, an investigation into the influ- ence of polymer purity on the efficiency of P3HT:fullerene bulk heterojunction devices is reported. Polymer purity is shown to have a strong influence over polymer solubility and final device efficiency. With the purest polymers, efficiencies of up to 5.0 % and 7.0 % were obtained with PC60BM and IC60BA, respectively (PC60BM: phenyl-C61-butyric acid methyl ester, IC60BA: indene-C60 bis-adduct). The thesis finishes with the development of a new style of liquid-liquid separator, a key tool for post-processing droplet flows and enabling sequential operations.
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Russell, Mary Grace. "Invention and implementation of technologies for continuous flow synthesis." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/127715.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, May, 2019Cataloged from the PDF of thesis.
Includes bibliographical references.
In this thesis, I have optimized a synthesis of rufinamide an important epilepsy medication. This convergent synthesis generates two reactive intermediates in situ (aryl azide and propiolamide) and then combines them in a regioselective click reaction utilizing copper tubing as the catalyst. Next, I have optimized a synthesis of nicardipine which is prescribed to treat high blood pressure. The nature of the project required that the final product be relatively pure (>90 %) so that the final product could be crystallized from the reaction mixture. Nicardipine was synthesized in three steps, but in two flow reactors where one of the reactors induced two steps. The reaction mixture was then purified using two in-line aqueous extrations. First, the reaction stream was washed with HCl to produce the salt of nicardipine and wash away polar compounds. Then, the product is extracted into the aqueous layer by using a 1:1 water DMSO mixture.
Finally, the synthesis's scale was increased and run in the system that was created in collaboration with the Jensen lab and Myerson lab. Next, a fully continuous synthesis of linezolid was optimized and run. The synthesis targeted the challenging intermediate amide epoxide that rapidly cyclizes into unwanted oxazolines. We were able to circumvent this side reactivity by masking the nucleophilic amide N-H by quenching the resulting nitrillium after Ritter type reaction with 2-propanol to produce the imidate. After accessing the masked amide epoxide, linezolid was produced by nucleophilic addition to the epoxide with the aniline made from a nucleophilic aromatic substitution (SNAr) reduction sequence. Finally, late stage oxazolidinone formation produces linezolid in a 73% yield in 27 minutes longest linear sequence. Next, I contributed to a system that automatically optimized and analyzed organic reactions in continuous flow.
This system in collaboration with the Jensen lab fully integrated software, hardware that controlled the continuous platform, and in-line analytics. This system, after the chemist had provided the desired chemical space, could optimize a reaction without any manual intervention. Finally, I developed a monolithic cellular solid made of functionalized silica for catalyst support. This system could solve some of the problems associated with packed bed reactors including catalyst deactivation due to channeling or clogging of the reactor. This type of catalyst support could be applicable to a large number of catalysts by attaching the catalyst to silane side chains with appended functionality. Portions of this thesis have been published in the following articles co-written by the author and have been reprinted and/or adapted with permission from their respective publishers.Zhang, P.; Russell, M.G.; Jamison, T.F. "Continuous Flow Total Synthesis of Rufinamide" Org. Proc. Res. Dev.
2014, 15671570. © 2014 American Chemical Society. MGR ran the optimization of the synthesis as well as isolation and characterization of the final product. PZ wrote the manuscript and validated the results under TFJ's guidance. Zhang, P.; Weeranoppanant, N.; Thomas, D. A.; Tahara, K.; Stelzer, T.; Russell, M. G.; OMahony, M.; Myerson, A. S.; Lin, H.; Kelly, L. P.; Jensen, K. F.; Jamison, T. F.; Dai, C.; Cui, Y.; Briggs, N.; Beingessner, R. L.; Adamo, A. Advaced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing, Chem. Eur. J. 2018, 24, 2776-2784. DOI: 10.1002/chem.201706004. © 2018 John Wiley & Sons, Inc. MGR optimized the synthesis of nicardipine as well as ran the synthesis in the synthesis frame. PZ, HL, LPK, CD, RLB all woked to develop chemistry for the syntheses of the different drug targets. NW, DAT, and AA worked to develop the up-steam synthesis unit as well as necessary undeveloped components.
KT, TS, MM, YC, and NB woked to deleop the continuous recrystalization unit and purified the drug targets. TFJ, KFJ, and ASM provided instrumental guidance to the teams. Russell, M. G.; Jamison, T. F. "Seven-Step Continuous Flow Synthesis of Linezolid Without Intermediate Purification," Angew. Chem Int. Ed. 2019, 58, 7678-7681. DOI: 10.1002/anie.201901814. © 2019 John Wiley & Sons, Inc. All synthetic work was carried out by MGR under TFJ's guidance. B6dard, A.-C.; Adamo, A.; Aroh, K. C.; Russell, M. G.; Bedermann, A. A.; Torosian, J.; Yue, B.; Jensen, K. F.; Jamison, T. F. Reconfigurable System for Automated Optimization of Diverse Chemical Reactions, Science 2018, 361, 1220-1225. © 2018 American Association for the Advancement of Sciences. Reprinted with permission from AAAS. MGR and ACB worked together to run the various optimizations as well as substrate scopes. AAB developed initial conditions for several of the reactions. AA developed the system with JT and BJ's assistance.
KCA integrated the system with the software as well as modeled the optimization protocols. KFJ and TFJ provided instrumental guidance to the teams. Leibfarth, F. A.; Russell, M. G.; Langley, D. M.; Seo, H.; Kelly, L. P.; Carney, D. W.; Sello, J. K.; Jamison, T. F. Continuous-Flow Chemistry in Undergraduate Education: Sustainable Conversion of Reclaimed Vegetable Oil into Biodiesel, J. Chem. Ed. 2018, 95, 1371-1375. DOI: 10.1021/acs.jchemed.7b00719. © 2018 American Chemical Society. MGR and DML developed and optimized the chemistry. FAL wrote the manuscript and the laboratory experiment. MGR, HS, and LPK, taught the experiment. DWC provided assistance. JKS and TFJ provided guidance.
by Mary Grace Russell.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemistry
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Burns, Bradley Justin. "Method and applications of fiber synthesis using Laminar Flow." Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/475545639/viewonline.
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Newby, James. "Synthesis and reactions of isocyanides using a flow reactor." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/4127/.
Full textAbstract:
The work described in this thesis is divided into eight chapters: Chapters one and two contain an overview of the literature surrounding the project, focussing on flow chemistry and the chemistry of the isocyanide functional group. Chapter three explains project aims and objectives, and contains information relevant to the flow machine used in this project. Chapter four describes efforts towards developing a method for the synthesis of isocyanides from primary amines using the flow reactor. A procedure for synthesising N-formamides from primary amines using either a solution-phase or solid-phase catalyst was developed, with the solid-phase catalyst giving N-formamides in quantitative yields with no requirement for purification. Alongside this methodology, a procedure for synthesising several isocyanides from N-formamides using the flow reactor was also developed. Furthermore, investigations into a one-step synthesis of isocyanides from primary amines are described. In chapter five a group of medicinally-valuable heterocyclic compounds were synthesised via a 3-component Ugi reaction using the flow machine. The results of the investigation were compared to literature examples of similar reactions performed using either batch or microwave irradiation techniques. In chapter six a 4-component Ugi reaction was used to synthesise a 40-compound library of cyclic amides in order to showcase the benefit of using a flow reactor to perform multiple similar reactions in sequence. The method developed was also applied to the synthesis of a natural product methyl-glutamic acid. Chapter seven discusses possible future projects that build upon the methodology developed, and chapter eight contains data of all experimental procedures featured in this thesis.
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Wang, Yantao. "Synthesis and conversion of furfural-batch versus continuous flow." Thesis, Compiègne, 2019. http://www.theses.fr/2019COMP2474/document.
Full textAbstract:
Le furfural, identifié comme l'un des 30 principaux produits chimiques biologiques, est une molécule importante en terme de chimie verte et développement durable. L'objectif de ce travail de doctorat est de réaliser la synthèse et la conversion du furfural en flux continu et par lots. Ici, nous avons développé des méthodes plus éco-efficiente pour la synthèse du furfural, et valorisé le furfural en produits à haute valeur ajoutée, tels que le 2-furonitrile, l'alcool furfurylique, etc... Plusieurs questions clés ont été identifiées afin de concevoir des processus plus écologiques que les processus actuels. En détail, des expériences de synthèse du furfural ont été réalisées dans l'eau pure ou dans un mélange eau-solvants organiques lorsque des co-solvants (verts ou écologiques) sont nécessaires. L'irradiation par micro-ondes a été choisie comme méthode de chauffage pour accélérer le processus de déshydratation, et un réacteur à flux continu à micro-ondes a également été utilisé pour améliorer la productivité du furfural. En partant du furfural pour produire des produits chimiques à haute valeur ajoutée, des réacteurs à flux efficace, tels que Pheonix, H-cube Pro ainsi que des micro-ondes à flux continu avec micro-réacteur, ont également été identifiés comme des alternatives intéressantes pour améliorer la productivité des composés cibles. En conséquence, certains résultats prometteurs ont été obtenus du point de vue de l'industrieFurfural, which has been identified as one of top 30 bio-based chemicals, is an important green platform molecule, The aim of this PhD work is to realize the synthesis and conversion of furfural in batch and continuous flow. Here, we developed sorne greener methods for furfural synthesis, and valorized furfural into high value-added products, such as 2-furonitrile, furfuryl alcohol etc. Several keys issues were identified in order to design processes greener than the current ones. ln detail, experiments for furfural synthesis were performed in water or in water and organic solvent when co-solvents (green or eco-friendly) are necessary. Microwave irradiation has been chosen as the heating method to accelerate the dehydration process, and microwave continuous flow reactor was also applied to improve furfural productivity. When starting from furfural to produce high value-added chemicals, efficient flow reactors, suc as Pheonix, H-cube Pro as well as microwave continuous flow With micro-reactor, were also identified as interesting alternatives to improve the productivities of target compounds. As a result, some promising results were obtained in the viewpoint of industry
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Jong, Thing Soon. "Continuous flow synthesis of chemical building blocks for biological application." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17938.
Full textAbstract:
A collection of twenty three selectively mono-protected di- and triamines, masked with the Boc, Fmoc or Ddiv protecting groups, were synthesised via continuous flow synthesis in a self-assembled meso-scale PTFE flow reactor. The continuous flow strategy offered direct access to the mono-protected compounds in good yields, especially in the case of the Fmoc carbamates which circumvented the use of another sacrificial protecting group. Two of the mono-Boc-protected carbamates were used as starting materials to generate N-alkylglycine monomers; synthesised via tandem mono-alkylation and Fmoc carbamation, linked by an in-line scavenging protocol using a silica-based trisamine scavenger resin. The final step of the monomer synthesis employed catalytic transfer hydrogenolysis using 20% Pd(OH)2/C and 1,4- cyclohexadiene. The three-step flow procedure gave access to two monomers, with one of them being a novel N-alkylglycine unit bearing a triethylene glycol bridge. The monomers were used as building blocks to assemble new oligo-N-alkylglycines (peptoids) via microwave-assisted solid phase synthesis. Three different types of peptoids were synthesised: (i) oligo-N-(6-aminohexyl)glycines (“standard” peptoids), (ii) oligo-N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}glycines (“triethylene glycol” [TEG] peptoids) and (iii) hetero-oligomers of alternating “standard” and “TEG” monomers (“hybrid” peptoids). The peptoids were evaluated for their cellular permeability and cytotoxicity with HeLa, HEK-293 and CHO cells. All the peptoids were shown to be non-cytotoxic at 10 μM based on cell proliferation assays. In general, it was found that the cellular uptake of the hybrid peptoids outperformed their standard and TEG analogues. Flow cytometry and confocal microscopy results revealed that the hybrid nonamer had the highest cellular uptake efficiency of all the peptoids synthesised. At a concentration of 1 μM, it outperformed the second best molecular transporter (standard nonamer) by a factor of seven.
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Azeez, Qaisar A. "Synthesis of ultrafine aluminum nitride powders in a flow reactor." Ohio : Ohio University, 1988. http://www.ohiolink.edu/etd/view.cgi?ohiou1182779122.
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Zante, Remi C. "A mechatronic design synthesis for very low flow control valves." Thesis, University of Strathclyde, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501848.
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Hsueh, Nathanael. "Synthesis and reactions of aziridines via batch and flow processes." Thesis, University of Warwick, 2017. http://wrap.warwick.ac.uk/90783/.
Full textAbstract:
This thesis describes the synthesis and ring opening reactions of aziridines performed under batch as well as continuous flow conditions. Chapter 1 gives a brief introduction to the synthesis and ring opening reactions of aziridines. Chapter 2 gives a brief introduction to flow chemistry, and describes the synthesis of aziridines from 1,2-amino alcohols, as well as their subsequent ring opening reactions. Using continuous flow methodology, various aziridines were successfully synthesized in moderate to good yields. Ring opening of these aziridines with different nucleophiles was also possible in flow. These two processes could be combined in a telescoped sequence, enabling the continuous flow synthesis of functionalized products directly from the 1,2-amino alcohols, without having to isolate the aziridine intermediates. Chapter 3 describes the aziridination of alkenes using soluble aryliminoiodanes under continuous flow. The aziridination of alkenes could be combined with further ring opening reactions via a telescoped, continuous flow process. This enabled the direct synthesis of ring opened products directly from the alkene, via in situ formed aziridines, in moderate to good yields. This second approach had broader scope than the method described in Chapter 2. Chapter 4 reports the stereocontrolled aziridinations of alkenes with different N-tosyl aryliminoiodanes. Under some conditions, the asymmetric aziridination of styrene gave different enantioselectivities when the aryl group of ArI=NTs was changed. The diastereoselective aziridination of a chromene was also briefly investigated. Chapter 5 gives a summary of the key findings, as well as possible future work. In Chapter 6, detailed experimental procedures for the work carried out in Chapters 2 – 4 are provided.
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Atluri, Lava Kumar. "Design Automation Flow using Library Adaptation for Variation Aware Logic Synthesis." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397466797.
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Chigondo, Fidelis. "Continuous flow synthesis of silicon compounds as feedstock for solar-grade silicon production." Thesis, Nelson Mandela Metropolitan University, 2016. http://hdl.handle.net/10948/4529.
Full textAbstract:
This thesis describes the key steps in the production of high purity (solar-grade) silicon from metallurgical-grade silicon for use in the production of photovoltaic cells as alternative renewable, environmentally benign and cheap energy source. The initial part of the project involves the development and optimization of a small chemical production platform system capable of producing alkoxysilanes from metallurgical-grade silicon as green precursors to solar-grade silicon production. Specifically, the main aim of the study was to synthesize trialkoxysilanes in continuous flow mode, although the synthesis on monosilane was also done in batch mode. The alkoxylation reaction was carried out in a traditional slurry phase batch reactor, packed bed flow tubular reactor and also attempted in a continuous flow falling film tubular reactor. The effect of key parameters which affect the silicon conversion and selectivity for the desired trialkoxysilane were investigated and optimized using ethanol as a reagent model. The synthesis was then extended to the other alcohols namely methanol, n-propanol and n-butanol. Copper catalysts which were tested in the alkoxylation reaction included: CuCl, Cu(OH)2, CuO and CuSO4. CuCl and Cu(OH)2 showed comparable activity in the batch mode but the former was more efficient in the packed bed flow tubular reactor. Cu(OH)2 could be used as a non-halide catalyst but its activity is limited to short reaction cycles (<10 h). The uncatalysed reaction resulted in negligible reaction rates in both types of reactors. High temperature catalyst pre-heating (>500 oC) resulted in a lower rate of reaction and selectivity than when slightly lower temperatures are used (<350 oC) in both reactors, although much difference was noticed in the packed bed flow tubular reactor. Synthesis in the batch reactor needed longer silicon-catalyst activation time, higher pre-heating temperature and higher catalyst amounts as compare to the packed bed flow tubular reactor. Reaction temperature and alcohol flow rate influenced the reaction in both methods. The optimum reaction temperature range and alcohol flow rate was comparable in both reactors (230 to 240 oC) and 0.1mL/min respectively. The effect of alcohol R-group (C1 to C4) on the reaction revealed that conversion and selectivity generally decrease with an increase in carbon chain length in both methods. Ethanol showed highest selectivity (>95% in batch and >97% in flow) and conversion (about 88% in batch and about 64% in flow) as compared to all other alcohols studied showing that it could be the most efficient alkoxylation alcohol for this reaction. Overally, the packed bed flow tubular reactor resulted in higher selectivity to trialkoxysilanes than the batch system. Performing the reaction under pressure resulted in increased conversion but selectivity to the desire trialkoxysilane diminished. Synthesis in a continuous flow falling film tubular reactor was not successful as it resulted in very poor conversion and selectivity. Monosilane was successfully synthesized from the disproportionation of triethoxysilane using homogeneous and heterogeneous catalysts in batch mode. The results obtained from homogeneous catalysis showed that the reaction can be conducted at room temperature. The heterogeneous catalysis method resulted in slow conversion at room temperature but mild heating up to 55 oC greatly improved the reaction. Conducting the reaction under neat conditions produced comparable results to reactions which were carried out using solvents. The disproportionation reaction was best described by the first order kinetic model. The results obtained in this research indicate that the packed bed flow tubular reactor can be utilized with future modifications for continuous flow synthesis of alkoxysilanes as feedstock for the solar-grade silicon production.
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Akbay, Sezin. "Synthesis Of Low Silica/alumina Zeolite Membranes In A Flow System." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12608697/index.pdf.
Full textAbstract:
Zeolite A-type membranes are usually synthesized from hydrogels and rarely
synthesized from clear solutions mostly in batch systems. Few studies were carried
out using semi-continuous systems for zeolite A membrane synthesis. Zeolite A
membranes are mainly used in pervaporation processes for separation of water from
water/organic mixtures because of their hydrophilic property.
In this study, zeolite A membranes were synthesized on -alumina supports from a
clear solution with a molar composition of 49Na2O: 1Al2O: 5SiO2: 980H2O.
Synthesis was done both in a batch system and in a flow system in which solution
was circulated through the support under atmospheric pressure. Effects of synthesis
temperature, time, flow rate and seeding on membrane formation were investigated.
The membranes were characterized by X-ray diffraction (XRD), scanning electron
microscopy (SEM), single gas permeation measurements and pervaporation tests.
In batch system, pure zeolite A membranes having cubic form of zeolite A was
obtained for the syntheses carried out at 60°C for 24 h and 80°
C for 8 h. Thicknesses of the membranes synthesized at 80°
C and 60°
C were about 2 µ
m and 4 µ
m, respectively. N2 permeances were 2*10-8 mol/m2sPa and 8*10-8 mol/m2sPa for of the membranes synthesized in the batch system at 60°
C and 80°
C, respectively. When synthesis was carried out in flow system pure and continuous zeolite A membranes were obtained for all conditions. Membranes synthesized at 60°
C and 80°
C had thicknesses of about 1.5 and 2 µ
m, respectively. Lower N2 permeations were obtained for the membranes synthesized in flow system. It was observed that flow rate and seeding did not significantly affect the thickness of the membrane layer. The membranes synthesized in this study are significantly thinner than the membranes reported in the literature. Single gas permeation tests at 25°
C for the membranes showed that comparable membranes with the ones in literature were obtained in this study. For a double layer membrane synthesized in flow system at 80°
C for 8h separation factor about 3700 was obtained for the separation of 92:8 (wt.%) ethanol/water mixture at 45°
C.
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Kim, HeeJin. "Flow Microreactor Synthesis via Unstable Organolithium Intermediates Bearing Electrophilic Functional Groups." 京都大学 (Kyoto University), 2011. http://hdl.handle.net/2433/151992.
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Torbey, Elie. "Control/data flow graph synthesis using evolutionary computation and behavioral estimation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ37080.pdf.
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Mehmood, Khalid. "Studies on sewer flow synthesis with special attention to storm overflows." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245819.
Full textAbstract:
A model is developed, using a unit hydrograph approach for sewer flow synthesis and a simple mixing model to calculate the pollution load from combined sewer overflows, to simulate the long-term behaviour of storm overflows in combined sewerage systems. It is shown that this procedure synthesizes overflow operation characteristics to acceptable engineering accuracy, measured relative to the adopted standard for UK practice, namely predictions from the WALLRUS suite of engineer's software. This is achieved at only a small fraction of the computer runtime and so makes practicable a wide range of overflow performance and river impact studies using local rainfall records of unlimited extent. The model is applied successfully to three drainage networks. Results show that the model, COSSOM, achieves predictions with respect to runoff volume and overflow characteristics well within : 00 % of full. WALLRUS applications. Sensitivity studies demonstrate that performance of the model improves when catchment unit hydrographs are obtained, by preliminary application of WALLRUS using a rainfall intensity close to the maximum in the observed data and for rain duration close to the time of concentration of each sub-catchment under study. It is also shown that with little loss in accuracy relative to application of the WALLRUS approach for unit hydrograph development, COSSOM can be operated with other rainfall/runoff/pipeflow models.
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Heckman, Laurel Millikan. "Enabling the use of unstable, hazardous reagents with continuous flow synthesis." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/118267.
Full textAbstract:
Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018.Cataloged from PDF version of thesis. Page 300 blank.
Includes bibliographical references.
[chemical formula] Highly functionalized 2-arylindoles were synthesized from 2-alkenylarylisocyanides and arylboronic acids using a simple, inexpensive copper catalyst. The reaction exhibits excellent functional group tolerance for both the arylisocyanide and boronic acid coupling partners. To avoid the direct handling of the pungent arylisocyanide starting materials, continuous flow chemistry is further demonstrated to provide safe and effective access to 2-arylindoles through in situ dehydration and cyclization of easy-to-handle 2-alkenyl-N-formylanilines. Laurel M. Heckman and Dr. Zhi He contributed equally to initial reaction investigation. Z.H. carried out the arylboronic acid scope. L. M. H. carried out reaction optimization, isocyanide scope and reactions in continuous flow. [chemical formula] Despite its utility, monochloramine (NH₂Cl) has not achieved widespread use as a nitrogen transfer reagent due to its unstable and hazardous nature. We developed a continuous flow platform for the safe, reliable, and inexpensive on-demand synthesis of NH₂Cl. Additionally we demonstrate the synthetic utility of NH2Cl by converting it to valuable NH aziridne and nitrile products in good to excellent yield in exceedingly short reaction times. Dr. Evan Styduhar developed continuous flow synthesis of NH₂Cl. E.S. also developed the reaction of NH2 Cl to form aziridines and nitriles in batch and continuous flow. Laurel M. Heckman helped optimize the continuous flow setup, performed the reaction scope in continuous flow, and explored additional substrates in batch. [chemical formula] A rapid, operationally simple synthesis of 6-TAMRA, an important probe for labeling biomolecules, from 2-carboxycarbonylterephthalic acid and 3-dimethylaminophenol is described herein. The intermediate ketoacid was synthesized in a single step from commercially available dimethylacetophenone. Additionally, progress was made towards a facile scalable synthesis in continuous flow. Dr. Justin A. M. Lummiss carried out the oxidation batch synthesis. Laurel M. Heckman carried out reaction screening and optimization of step 2 of the batch synthesis. L.M.H and J.A.M.L contributed equally to the experiments in continuous flow. Dale Thomas (graduate student, Jensen Research Group, MIT Department of Chemical Engineering) developed the fully automated platform. Bruce Adams (Staff, DCIF of MIT Department of Chemistry) helped with low temperature and 2-D NMR experiments. Peter MUller (Director, Diffraction Facility of MIT Department of Chemistry) carried out the single-crystal X-ray diffraction experiments.
by Laurel Millikan Heckman.
Ph. D. in Organic Chemistry
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Chakkaravarthy, Manoj. "BDD Based Synthesis Flow for Design of DPA Resistant Cryptographic Circuits." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330025314.
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Torbey, Elie Carleton University Dissertation Engineering Electronics. "Control/data flow graph synthesis using evolutionary computation and behavioral estimation." Ottawa, 1999.
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Vicens, Jim. "Continuous Zeolite Crystallization in Micro-Batch Segmented Flow." Digital WPI, 2018. https://digitalcommons.wpi.edu/etd-theses/1307.
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Zeolites are porous aluminosilicates that occur both naturally and synthetically, having numerous applications in catalysis, adsorption and separations. Despite over a half century of characterization and synthetic optimization of hundreds of frameworks, the exact mechanism of synthesis remains highly contested, with crystallization typically occurring under transport-limited regimes. In this work, a microcrystallization reactor working under segmented oscillatory flow has been designed to produce a semi-continuous flow of zeolite A. The fast injection of the reactants in a mixing section forms droplets of aqueous precursors in a stream of paraffin, dispersing microdroplets and avoiding any clog from occurring in the system. The crystallization occurred in the system at atmospheric pressure and isothermal conditions (65ºC). This allowed for a rather slow crystallization kinetics which was important to study and highlight the different crystallization mechanisms between flow and batch synthesis. The morphology, size distributions, crystallinity, and porosity were examined by ex-situ characterization of the samples by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and N2 Physisorption to support the conclusions drawn. The size distribution of the particles achieved in the flow reactor was conclusively narrower than the distribution achieved in the batch reactor. The average size of the crystals for both synthesis methods is reported as 400 nm and the crystallinity achieved was comparable between the two. However, the morphology was quite different between the two systems, the flow products having a much higher mesoporosity due to the presence of crystal aggregates at high crystallinity when compared to the batch crystals. Finally, extended crystallization times leads to a decline of the crystallinity of the product, which might be explained by the metastable state of zeolites in solution.
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Skrotzki, Eric. "Taming Highly Reactive Species for Use in Organic Synthesis." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42739.
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Chemical processes and reactions are never perfect; there are always some problems in scope, scalability, applicability or safety. Sometimes, if these limitations pose a seemingly insurmountable barrier to the chemistry’s overall usefulness, decades can go by without a single new development even in fields that were initially very promising or popular in their infancy. By looking back on these forgotten topics through the lens of modern technology, new cutting-edge materials and methods can be applied to solve the problems that posed too great a challenge in previous decades. In this thesis, two such examples of reactions initially discovered and developed around the late 1960’s and remained largely untouched ever since will be explored.
Chapter 1 will describe the use of ozone as an oxidant to transform amines into the corresponding alkyl nitro species. Ozone is a very powerful oxidant but tends to overreact with most organic substrates, which significantly reduces its potential as a commonplace synthetic tool. These limitations in applicability stem from an inherent lack of control over the reaction, which is the issue that we sought out to address. By applying modern principles of flow chemistry, the functional group tolerance of this oxidation reaction has been drastically increased from its initial state of simple small hydrocarbons.
Chapter 2 will follow a similar narrative involving the use of ‘super-bases’ to activate benzylic C-H bonds and generate a variety of benzyllithium species. Organolithiums have also had historic issues with tolerance in transition metal-catalyzed cross coupling reactions. With a surge of new publications addressing this issue by using principles of flow chemistry, there remains a lack of easy methods to generate organolithium nucleophiles as coupling partners. Generation of benzyllithiums from toluene derivatives has historically been limited to require solvent quantities of substrate, along with unreasonably long reaction times at cryogenic temperatures. By utilizing modern tools and synthetic strategies, an easy and streamlined path from toluene derivatives to organolithiums for direct use in cross coupling has been developed.
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Deadman, Benjamin Jade. "New tools for flow chemistry and the machine assisted synthesis of pharmaceuticals." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648306.
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Cancogni, D. "MICROFLUIDIC REACTOR TECHNOLOGY IN OLIGOSACCHARIDE SYNTHESIS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229555.
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Although carbohydrates offer new therapeutic opportunities in biomedical field, the industrial implementation of carbohydrate-based drugs is yet greatly thwarted by the difficulties and challenges inherent in oligosaccharide synthesis, especially for large scale preparation. Any tool or new technology enabling a cost-effective improvement of the lead generation process is therefore highly desirable in order to reduce the manufacturing costs of carbohydrate drugs. During last years, continuous-flow synthesis in microreactors has gained a great deal of attention featuring practical advantages such as high reproducibility, easy scalability and fast reaction optimization using small amounts of reagents or synthetic intermediates. This technique may therefore offer an effective support to make carbohydrates more attractive targets for drug discovery processes. In addition, also basic research in academia can benefit from microreactor technology as a tool to improve the organic synthesis of oligosaccharides. Here I report a systematic exploration of the glycosylation reaction, the most important and difficult transformation in oligosaccharide synthesis, carried out in microreactors under continuous-flow conditions. Various trichloroacetimidates and thioglycosides have been investigated as glycosyl donors in this study, using both primary and secondary glycosyl acceptors. Each microfluidic glycosylation has been compared with the same reaction performed under traditional conditions, in order to highlight advantages and drawbacks of microreactors technology. As a significant example of multistep continuous-flow synthesis, we also describe the preparation of a trisaccharide by means of two consecutive glycosylations performed in two interconnected microreactors. Furthermore I report preliminary study on the synthesis of glycosyl phosphodiester under microfluidic conditions for the preparation of short oligomers of Neisseria Meningitidis type X capsular polysaccharide fragments.