The following application notes show the range of synthesis that are possible with the Vapourtec system.
Application notes
Application Note 73: Use of CSTR for biphasic reaction scale up

Vapourtec has teamed up with UK based reactor manufacturer Stoli Chem to demonstrate a new range of continuous stirred tank reactors for continuous flow applications.
In this application note we demonstrate how a biphasic reaction can be scaled up to kilos/day under very mild conditions using the SABRe reactor. The mixing provided by this reactor enabled a throughout of ~8 mol/day, equating to 1.4 kg/day.
Read moreApplication Note 72: Cleaving peptides in flow

In this application note, we demonstrate how safe, fast, and reliably a peptide is cleaved from a resin in continuous flow. Different cleavage conditions were evaluated using Glucagon-like peptide-1 (GLP-1) as an example peptide. By using the Variable Bed Flow Reactor (VBFR), the packing density of the resin was controlled throughout the reaction, minimising dilution and eliminating the channelling of reagents. Temperature, residence time, and cleavage cocktail were evaluated. The optimised protocol yielded GLP-1 with a crude purity of 82 % in only 30 minutes, compared to a traditional batch reaction taking between 2 to 4 hours.
Read moreApplication Note 71: Photochemistry – Process development and scale up to kilos / day

This application note demonstrates a 385 % increase in throughput in the ene-like reaction of singlet oxygen with citronellol, by increasing the photon molar output. By using Vapourtec’s UV-150 photochemical reactor equipped with a 420 nm High Power LED, a throughput of 59 g/h (1.4 kg/day or over half a tonne a year) can be achieved.
Read moreApplication Note 70: Fast Stern Volmer analysis in flow

This application note illustrates how a Vapourtec E-Series can be configured with a spectrophotometer for Stern-Volmer fluorescence quenching studies.
This set up was developed for undergraduate teaching laboratory sessions. The results obtained in both batch and flow highlight the benefits of the flow system over manual data collection for determining Stern-Volmer quenching rates.
Produced for Vapourtec by Christopher G. Thomson, Arno Kraft and Filipe Vilela, Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
Read moreApplication Note 69: Automated CF SPPS and evaluation of GLP-1 peptide

This application note illustrates the capabilities of a Vapourtec RS-400 system, equipped with a novel flow reactor, the Variable Bed Flow Reactor, for continuous flow Solid-Phase Peptide Synthesis. Glucagon like peptide (GLP-1), a 30-mer peptide used to treat diabetes, was chosen to show the advantages of the Variable Bed Flow Reactor for solid-phase peptide synthesis regardless of the resin core used. By keeping the solid media continuously packed, the contact surface between the resin’s active sites and the reagents pumped through is optimised. The use of the Variable Bed Flow Reactor not only reduces the amount of solvent required, but it also ensures a more efficient synthesis.
The packing density and overall protocol allows a final crude purity of the 30-mer peptide, GLP-1 up to 82 % in under 5 hours.
Application Note 69 – Automated CF SPPS and evaluation of GLP-1 peptide
Read moreApplication Note 68: Photocatalytic Synthesis of γ-Lactams and α-Tertiary Amine Derivatives in Continuous Flow

We report a simple and direct solution to the synthesis of γ-lactams 4 (incl. azaspirocycles) and α-tertiary amine derivatives 5. Using a cheap organic photocatalyst (4CzIPN) in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, the α-C–H alkylation of aliphatic primary amines 1 with acrylate Michael acceptors 2 can be affected (Scheme 1).1
Read moreApplication Note 67: Generation of Grignard reagents on demand

This application note illustrates the capabilities of Vapourtec’s new packed bed reactor for a fast, consistent generation of Grignard reagents in flow. Under continuous flow conditions, an organic bromide reacts with magnesium packed inside the Variable Bed Flow Reactor, adjusting its volume to keep a constant packing density. In a second inline reactor, an aldehyde is added to the Grignard reagent to form a secondary alcohol.
Read moreApplication Note 66: 230% increase in throughput of a photocycloaddition demonstrated by Vapourtec High Power LED.

This application note demonstrates a 230 % increase in throughput on the direct [2+2] cycloaddition of maleic anhydride with ethene to form a cyclobutane motif by using the new Vapourtec’s 365 nm High Power LED.
Read moreApplication Note 65: Lithiation-substitution of alkyl-1,3,4- oxadiazoles

1,3,4‐Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. This application note illustrates the use of Vapourtec E-series flow reactor for a fast, convenient, high yielding and general α‐substitution of 1,3,4‐oxadiazoles via a lithiation-substitution approach. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in-flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur. This is the first reported example of the formation of otherwise unstable intermediate via organolithium reagents followed by trapping at room temperature in flow.
Read moreApplication Note 64: Direct electrochemical oxidation of 4- tert-butyltoluene

This application note demonstrates the use of the Vapourtec Ion electrochemical reactor for the direct oxidation of 4-tert-butyltoluene into 4-tert-butyl benzaldehyde dimethyl acetal. After optimization of this key reaction, the desired product was afforded in a yield of 88%.
Read moreApplication Note 63: Electrochemical pathway for cross coupling of organic halides – Csp2-Csp3 bonding

We now present a new application note prepared from work undertaken by New Path Molecular Research Ltd. This research project uses the Vapourtec Ion electrochemical reactor for the reductive cross-electrophile coupling of organic halides, constructing a Csp2-Csp3 bond. After optimization of this key reaction, the desired product was afforded in a yield of 81%.
In 2017, Pfizer revealed a reductive cross coupling reaction to construct Csp2-Csp3 bonds from organic halides in a batch electrochemical system (Perkins, Pedro, & Hansen, 2017). An electrochemical protocol was used to reduce a nickel catalyst (NiII to Ni0 or NiIII to NiII according to literature). In the application note presented by Vapourtec this same reaction is optimised under continuous flow conditions using the Vapourtec Ion electrochemical reactor.
Read moreApplication Note 62: Synthesis of pharmaceutical intermediate by cross-coupling with non-stabilised diazo compounds

After the Ley group, of the University of Cambridge, published a fascinating method of generating nonstabilised diazo compounds using a photochemical method,1,2 the team at New Path Molecular Research have applied the method to increase the product throughput of the synthesis of a pharmaceutical intermediate, using a newly developed high-power low-pressure mercury lamp.
This application note describes:
- The use of a 28 W low-pressure mercury
lamp at 310 nm - The effective, 3-fold increase in product
throughput of a pharmaceutical
intermediate
Application Note 61: Photochemical bromination with elemental bromine in continuous flow

In this application note, we demonstrate how to safely use solutions of bromine under a wide range of reaction conditions. This is achieved with the versatility of the Vapourtec E-series, V-3 pumps and our UV-150 photochemical reactor.
This application describes:
- Safe and easy pumping of an elemental bromine solution
- Effective and repeatable photobromination in a UV-150 photochemical reactor
- Rapid scale-up to over 10 g/hr
Safer Handling of Bromine
Elemental bromine is an efficient reagent for incorporating bromine into a range of benzyl, allylic and heterocyclic bromomethyl compounds but can present a hazard for handling in the laboratory. The resultant bromomethyl benzenes are often toxic and lachrymatory, and careful handling to avoid exposure is needed. Using the E-Series and UV-150 photochemical reactor it has been possible to carry out a range of photochemical brominations without needing to handle bromine, beyond making a stock solution.
Improved reaction rates
In the chemical literature, we found an example that required a significantly longer reaction time than any other example in the paper. Using the E-Series and UV-150 photochemical reactor, we have been able to reduce the reaction time from 7.5 minutes to 1 minute, with improved reaction yields (from 69% to 89%).
Read moreApplication Note 60: Photochemical hydration and scale-up of an anti-cancer candidate

In our application note 59 we found an unexpected photohydration taking place, instead of a cycloaddition during a photochemical library synthesis of [2+2] cycloadducts. Investigating further, we learned that it has not been reported in continuous flow in the literature before. We decided to explore this reaction further in this application note, which describes:
– Efficient and clean functionalisation of a candidate for an anti-cancer pharmaceutical
– New reaction for continuous flow
– Rapid investigation of reaction conditions, enabling double the throughput
– Optimisation of a photochemical reaction
– Throughput of 0.67 g/hr from a photochemical reaction
– Isolated yield of 80% with 99% purity
Read moreApplication Note 59 – Automated photochemical library synthesis

A synthesis of a library of compounds enables the chemist to rapidly screen possible chemistries and produce small quantities to be used for other screening processes. This application note describes:
- Rapid synthesis of a library of 12 [2+2] photo-cycloadducts in 50 mg quantities
- Rapid screening of a range of photosensitisers
- Optimisation and scale-up of two products to several grams scale
Application Note 58 – Visible light singlet oxygen

In this application, the conversion of α-terpinene to ascaridole was used to indirectly detect the formation of singlet oxygen in continuous flow. The production of singlet oxygen in continuous flow was optimised using the two methods, and the heterogeneous photocatalyst stability was investigated. Once optimised, the singlet oxygen was used for the aerobic oxidation of boronic acids to phenols, and to degrade two environmental pollutants: bis-phenol A and cimetidine.
This application note describes:
- Production of singlet oxygen in continuous flow
- The use of the UV-150 photochemical reactor for heterogeneous dispersions
- Use of heterogeneous photocatalysts as slurries and packed beds in continuous flow
- Easy handling of a complex flow stream of solid, liquid and gas
Application Note 57 – Automated library synthesis

Equipping a Vapourtec R-Series with a liquid handler creates a powerful, automated synthesis platform that has been used to carry out reaction screening of nucleophilic aromatic substitution partners, including volatile amines.
This application note describes:
– Automated reaction screening using automated reagent loading and collection
– Safe out-of-hours operation permitted by Flow Commander™
– The use of highly volatile amines and ammonia at 160 °C through the use of high pressures difficult to achieve in batch
Application Note 56 – Photodecarboxylative addition of phenylacetic acid to N-methyl phthalimide

This application note illustrates the use of the Vapourtec UV-150 photochemical reactor for the photodecarboxylative benzylation of N-methyl phthalimide. The transformation has been systematically optimized in terms of reagent concentration and residence time. The optimized procedure was subsequently performed on large-scale, achieving a productivity of 1.34 g (88%) of product per hour (or 32.16 g per day). The reactor enabled continuous photochemistry in an easy-to-use, safe and efficient manner.
Read moreApplication Note 55 – Selective hydrogenation with Stoli Catalysts reactor

Vapourtec have teamed up with Innovate UK award winning catalyst manufacturer Stoli Catalysts Ltd to demonstrate a new range of catalyst-coated tube reactors for continuous flow selective hydrogenation.
Read moreApplication Note 54 – Selective hydrogenation of O-benzyl vanillin using hydrogen gas and a palladium on charcoal slurry

As part of our ongoing work with slurries, the powerful combination of the Vapourtec E-series and SF-10 has made it possible to quickly achieve the selective hydrogenation.
Read moreApplication Note 53 – Sodium Hydride as a Slurry in Continuous Flow

As part of our ongoing series of application notes on pumping slurries of reagents we have turned our attention to sodium hydride, one of the most versatile heterogeneous strong bases.
Read moreApplication Note 52 – Rapid Mixing Reactor for Amide Formation under Biphasic Flow Reaction Conditions

In this application, Dr Claudio Battilocchio of the Ley group, University of Cambridge, has used Vapourtec’s 20 ml Rapid Mixing Reactors to perform an amide synthesis under biphasic flow reaction conditions.
Read moreApplication Note 51 – Palladium on Charcoal Slurries in Continuous Flow Hydrogenation

Using a Vapourtec E-Series with V-3 peristaltic pumps it has been possible to handle solids in flow, to perform a continuous flow hydrogenation of 4-(2-fluoro-4-nitrophenyl)morpholine to the Linezolid intermediate 3-fluoro-4-(4-morpholinyl)aniline, using ammonium formate, and a heterogeneous palladium on charcoal slurry.
Read moreApplication Note 50 – Rapid Mixing Reactor for Biphasic Reaction Scale-up

In this application note the Vapourtec High Flow pump module and an R-series equipped with a Vapourtec large diameter Reactor for Rapid Mixing has been used to perform a scale-up of biphasic Stevens oxidation. The Reactor for Rapid Mixing enabled yields of greater than 99% to be reached with a 58 second residence time at just 50 °C, achieving a throughput of 4.5 kg/day.
Read moreApplication Note 49 – Suzuki Coupling with SiliaCat DPP-Pd Heterogeneous Catalyst

In this application, a Vapourtec R-Series has been used to achieve rapid reaction times and high conversion of a Suzuki coupling, using a commercially available supported palladium catalyst. With a reaction time of just 1 min 15 seconds, it was possible to achieve yields of over 80%, at greater than 95% purity following a simple chromatographic separation. This application demonstrates how the Vapourtec R-Series can be used as a tool for the synthetic flow chemist, or for a development chemist beginning the scale up process.
Read moreApplication Note 48 – Photochemical synthesis of Cubanes

This application note demonstrates the preparation of cage compound 2 from an advanced diene precursor 1, which can be prepared from cyclopentanone. After optimization, this key photochemical [2+2] photocycloaddition was successfully scaled up to multigram scale, and the cycloadduct was transformed to 1,4-cubane dicarboxylate 3.
Read moreApplication Note 47 – [2+2] Photocycloaddition with wavelength specific low pressure mercury lamps

This application note uses the photochemical reaction explored in application note 36, the photocycloaddition of maleimide and 1-hexyne, to explore the performance of Vapourtec’s new low pressure mercury lamps. For this reaction the low pressure lamps are used in place of the
medium pressure lamp with filters. Three low pressure mercury lamps are tested, each with a specific and very narrow wavelength emission band.
Application Note 46 – Photochemical hydrogenation with TiO2 packed column

This application note expands on the work described in application notes 41 and 42 describing a
photochemical hydrogenation using an immobilized photo catalyst. Using an immobilized catalyst
allows the reactants to be free of a titanium dioxide slurry/suspension. Instead the TiO2 is packed
into a column type reactor. The versatility the of Vapourtec’s systems is demonstrated and a new
UV illumination system for column reactors is presented.
Application Note 45 – Selective oxidation using 50% aqueous hydrogen peroxide

This new application note demonstrates the oxidation of thioanisole using hydrogen peroxide in continuous flow. It highlights the use of 50 wt% aqueous hydrogen peroxide which can be pumped neat with Vapourtec systems. Both cooled and heated conditions are explored for this exothermic reaction. The reaction temperature was controlled using a Vapourtec cooling module for the sub-ambient conditions. To explore the highest possible throughput, mildly heated conditions were also explored.
Read moreApplication Note 44 – Direct, [2+2] photocycloaddition using LED light

This application note demonstrates the potential throughput capabilities of the UV-150, using an uncatalysed, intramolecular photochemical [2+2] cycloaddition. Further, it showcases the efficiency of the Vapourtec LED gen 2 light source, showing that a single, relatively small reactor together with low power LED can achieve a noteworthy throughput.
Read moreApplication Note 43 – Singlet oxygen reaction in continuous flow, an example of an ene reaction.

This application note demonstrates the use of singlet oxygen in flow. A range of parameters are investigated that determine the conversion and throughput. The ene like reaction of singlet oxygen with citronellol is used as a model. The versatility of the V-3 pump is showcased by the simultaneously pumping of both the reagent solution and gaseous oxygen. The bi-phasic gas / liquid mixture enters the reactor in Taylor flow. On exiting the UV-150 photochemical reactor the bi-phasic flow is no longer seen as the majority of the gas is consumed in the reactor. Further, by using a variable backpressure regulator, reaction parameters are controlled individually and optimized. Significant advantage is shown over traditional batch singlet oxygen reactions in which some reaction parameters are difficult to control.
Read moreApplication Note 42 – Photochemical hydrogenation of a range of Nitro compounds

This application note builds upon the previous application note 41’s exploration into green photochemical reductions. The range of aromatic nitro compounds is extended, including the hydrogenation of a Linezolid intermediate (Pfizer brand name Zyvox), and demonstrating excellent adaptability for the varying chemical properties. Vapourtec’s efficient and precise generation 2 LED (Gen-2) is the sole light source used, allowing accurate and uniform 365 nm irradiation while providing impressive throughput. The optimized condition for each reduction is quickly achieved; residence time, concentration and reaction temperature are modified to maximize throughput while concurrently achieving close to 100% conversion to desired product. The aim of this work was to showcase the capability of the Vapourtec’s E-Series when used in combination with the UV-150 photochemical
Read moreApplication Note 41 – Photochemical hydrogenation of 3-nitroacetophenone

*See Mahdavi et. al. for suggested reaction mechanisms
This application note demonstrates a green photochemical route to the reduction of Nitro compounds. The powerful combination of Vapourtec’s V-3 pump and the UV-150 Photochemical reactor is utilised to deliver the photo catalyst as a slurry and provide precise control over the continuous flow photochemical reaction, even with the short reaction times of less than 1 minute. The TiO2 photo catalyst is safe, cheap and simply removed by filtration. There is also a fascinating comparison of the performance of three different 365 nm light sources; filtered mercury lamp, LED Gen-1 and LED Gen-2. The Gen-2 LED achieves comparable throughput of the mercury lamp while consuming <50% of the power.
Read moreApplication Note 40 – Preparation of Silver Nanoparticles under Continuous Flow Conditions

This application note illustrates the use of the Vapourtec E-Series to synthesise nanoparticles under continuous flow conditions. Two classes of silver nanoparticles are reported. The properties of metal nanoparticles are highly dependent on size and morphology, so ensuring consistency is paramount. Flow chemistry brings the advantages of precise control over experimental conditions (temperature, pressure, and residence time) and essentially limitless scale. As such, it is often the method of choice for production of nanoparticles.
Read moreApplication Note 39 – Synthesis of Artemisinin using E-Series and UV-150 reactor

This application note demonstrates the use of the UV-150 photochemical reactor and E-Series system in the continuous synthesis of Artemisinin via the photooxidation of dihydroartemisinic acid. This application note shows how the easy-Photochem system can deliver not only the substrate but also oxygen in a safe, efficient continuous manner with the UV-150 effectively generating the singlet oxygen required for the reaction. This self-contained unit, coupled to an additional room temperature reactor is shown to synthesise the anti-malarial medicine artemisinin in comparable yields to previously published methods.
Read moreApplication Note 38 – α-Photodecarboxylation of Phthaloyl Glycine

This application note illustrates the use of the Vapourtec UV-150 photochemical reactor for the conversion of phthaloyl glycine to N-methylphthalimide. The transformation has been systematically optimized in terms of reagent concentration and residence time. The optimized procedure was subsequently performed on large-scale, achieving a productivity of 1.15 g of product per hour (or 27.6 g per day). The reactor enabled continuous photochemistry in an easy-to-use, safe and efficient manner.
Read moreApplication Note 37 – Photochemical Transformation of Methyl Coumalate

This application note illustrates the advantages of the UV-150 in performing continuous photochemistry against a published batch photochemical method demonstrating precise irradiation time, temperature control and wavelength selectivity . The 4π electrocyclisation of methyl coumalate shows an eight fold decrease in reaction times, an eight fold decrease in the amount of solvent used, a thirty fold decrease in the energy consumed by the lamp and switches to a greener solvent using acetonitrile compared to dichloromethane.
Application Note 36: [2+2] Photocycloaddition of Maleimide and 1-Hexyne

This application note illustrates the use of the Vapourtec UV-150 photochemical reactor which allows
access to continuous photochemistry in an easy-to-use, safe and efficient manner.
Application Note 35 – Reaction of Grignard Reagents using the E-Series

This application note illustrates the use of the Vapourtec E-Series system to run reactions such as Grignard reactions under continuous flow conditions for extended periods with no pump issues.
Read moreApplication Note 34 – Reaction of Organolithium Reagents using the E-Series

This application note illustrates the use of the Vapourtec E-Series system to run organometallic reagents such as n-Butyl lithium under continuous flow conditions.
Read moreApplication Note 33 : Chromium Arene Synthesis

This application note demonstrates the preparation of arene chromium tricarbonyl complexes using continuous-flow processing: (η6C6H5CH3)Cr(CO)3 as an example.
Read moreApplication Note 32: High Pressure and Temperature Process Scale S N Ar Reaction under Solvent Free Conditions using Liquefied Dimethylamine.

This application note illustrates the use of the Vapourtec R-Series system to run reactions under solvent free (neat) conditions and it’s ability to pump liquefied gases at high temperatures and pressures. This expands on work carried out in Application note 29 (where a game changing throughput of material from a bench top system was demonstrated).
Read moreApplication Note 31: Process Scale Uncatalysed Amination of 2-Chloropyridine (SNAr) under Solvent Free (Neat, 10.6M) Conditions

This application note illustrates the use of the Vapourtec R-Series system to run reactions under solvent free (neat) conditions. It expands the work previously highlighted in Application note 29 in which a novel stratagem for throughput of material was demonstrated using a bench top system. By harnessing the higher temperatures and pressures available on the Vapourtec R-Series and again running the reaction solvent free it is possible to perform direct uncatalyzed amination of 2-chloropyridine on potentially larger scales than previously thoughti.
Read moreApplication Note 30: Oxidation using a Gas/Liquid Membrane Reactor

This application note illustrates the use of the Vapourtec R-Series system with gas-liquid “tube-in-tube” reactor to perform in flow an oxidation previously shown in batch in the publication
“Transition-Metal free approach to efficient aerobic oxidation of alcohols to aldehydes and ketones under mild conditions”
Application Note 29: Process Scale SNAr Reaction under Solvent Free (Neat) Conditions

This application note illustrates the use of the Vapourtec R-Series system to run reactions under solvent free (neat) conditions. This expands on work previously carried out in Application note 4 where it was shown that by using the the Vapourtec R-series facility of placing four reactors in series the mass transfer of the reaction could be dramatically increased. By taking this a step further and demonstrating the ability of running reactions of this type solvent free, this application note shows a game changing increase in the amount of material that can be generated.
Read moreApplication Note 28: Continuous O-Methylation of Carboxylic Acids with Trimethylsilyldiazomethane

This application note illustrates the use of the Vapourtec R-Series system to pump highly reactive, hazardous reagents in a safe and stable continuous reaction. Here we describe the continuous O-methylation of a carboxylic group with trimethylsilyldiazomethane (TMSCHN 2 ) pumping directly through the R-series acid resistant pump heads.
Read moreApplication Note 27 : Decarboxylative Cross-Couplings with a Soluble Catalyst System

This Application Note illustrates how the R-Series flow chemistry system can be used to develop a transfer of novel decarboxylative cross-coupling reactions from batch to flow.
Read moreApplication Note 26: Continuous Fluorination Reaction with Diethyl Amino Sulfur Trifluoride (DAST)

This application note illustrates the use of the Vapourtec R-Series system to pump highly reactive, moisture sensitive reagents in a safe and stable continuous reaction. Here we describe the continuous fluorination of a carbonyl group with diethylaminosulfurtrifloride (DAST) pumping directly through the R-Series acid resistant pump heads.
Read moreApplication Note 24: Solvent Free Synthesis of an Imidazolium based Ionic Liquid under Continuous Flow Conditions

This example illustrates the use of the Vapourtec R-series to safely control the highly exothermic synthesis of the first generation ionic liquid [bmim]Br as well as handling the highly viscous product.
Read moreApplication Note 23 – SNAr with dimethylamine

This example illustrates the use of the Vapourtec R-Series system to react dissolved gases under pressure without the use of scale limiting pressure reactors (e.g. Parr ‘bombs’). The SnAr displacement of an aryl fluoride with dimethylamine is described.
Read moreApplication Note 22- Continuous Reduction of N-Boc Protected Amines to N-Me Amines

This example illustrates the use of the Vapourtec R-Series system to carry out reactions with moisture sensitive, highly reactive reagents under flow conditions. It demonstrates how the proper drying procedure allows the Vapourtec R2 pump to handle this highly water sensitive reagent.
Read moreApplication Note 21- Michael Addition with Nitromethane

This example illustrates the use of the Vapourtec R-Series flow chemistry platform to safely process an extremely energetic, reactive intermediate.
Read moreApplication Note 20 – Ethoxycarbonylation of Unprotected Iodoindole with CO Gas

This example illustrates the use of the new Vapourtec tube in tube gas reactor combined with the Vapourtec R-Series system to react reagent gases under pressure without the use of scale limiting pressure reactors (e.g. Parr ‘bombs’). Here we describe the catalytic ethoxycarbonylation of unprotected iodoindole with CO gas.
Read moreApplication Note 19 – Ethoxycarbonylation of Iodotoluene with CO Gas

This example illustrates the use of the new Vapourtec tube in tube gas reactor combined with the Vapourtec R-Series system to react reagent gases under pressure without the use of scale limiting pressure reactors (e.g. Parr ‘bombs’). Here we describe the catalytic ethoxycarbonylation of iodotoluene with CO gas.
Read moreApplication Note 18 – Aromatic Nitration with fuming nitric acid

This Application Note illustrates how a Vapourtec acid resistant R Series flow chemistry system (with acid resistant pumps, sensors, connectors, tubing and back pressure regulator) was used to pump highly corrosive, fuming nitric acid and determine optimal flow-through conditions suitable for a scale-up nitration of an aromatic starting material, all in a period of 3 days.
Read moreApplication Note 17 – Simplified Aromatic Nitro Reduction with Iron Granules

This study demonstrates a flow based approach to reduction of an aromatic nitro compounds using a column of iron granules as the catalyst.
Read moreApplication Note 16 : Bromination of Alkenes with NBS under continuous flow

This application note illustrates ease of scale-up and ease of control of a reaction that in batch would require careful incremental addition of reagents.
Read moreApplication Note 15 – Bromination of Ketones

α-Bromination of ketones is an important reaction in organic synthesis as the resulting α-Bromo-ketones are widely used in organic synthesis as valuable reaction intermediates used in the synthesis of variety of biologically active compounds. Various bromination procedures for carbonyl compounds have been developed, in which the most commonly used protocol involved the use of molecular bromine.
Read moreApplication Note 14: Phase Transfer Catalysis Alkylation of 2-Oxo-cyclopentanecarboxylic acid ethyl ester under biphasic conditions using phase transfer catalysis

This example illustrates how a continuous flow tubing reactor can be used to carry out biphasic reactions.
It demonstrates Phase Transfer Catalyzed (PTC) alkylation of β-Keto ester under segmented flow conditions using the Vapourtec flow system along with the flow Commander software enabling fast screening of reaction conditions.
Application Note 13: Suzuki Coupling with a Heterogeneous Pd Catalyst

This example illustrates use of a heterogeneous catalyst to perform a Suzuki coupling with high conversion and short residence times.
Read moreApplication Note 12 : Trimethylaluminium mediated (Weinreb) amide bond formation

This application note illustrates how a reaction which would be subject to thermal runaways and possible explosions in batch mode can be carried out safely using a continuous flow approach.
Read moreApplication Note 11: Array Synthesis using Loop Injection and a Tubing Reactor Combined with a Scavenger Column

This Application Note illustrates how the R-2+ pump/injector and R-4 flow reactor modules can be used in combination with a tubing reactor and a PACT scavenger column to perform sequential array synthesis employing simultaneous loop injection. Excess starting material 2{n} is used to drive the SNAr reaction with the aryl fluoride 1 to completion by incubation in the tubing reactor. The remaining amine is then scavenged prior to collection of the product 3{n}.
Read moreApplication Note 10: Heterocycle Formation in Flow: 4,5-Disubstituted Oxazoles

This Application Note illustrates how the R-2 pump/injector and R-4 flow reactor modules can be used to prepare oxazoles utilising a combination of a tubing reactor and polymer-assisted continuous flow-through (PACT) reactors1. Reagents are introduced into the flow stream via sample
loops attached to the injection valves.
Application Note 9: Amide Formation using ‘Catch and Release’

This Application Note illustrates how the R-2 pump/injector and R-4 flow reactor modules can be used to prepare amides uilising polymer-assisted continuous flow-through (PACT) chemistry1.
Read moreApplication Note 7: Flow-Through Ester Hydrolysis under Superheated Conditions

This Application Note illustrates how the R-2 pump/injector and R-4 flow reactor modules can be readily used to perform flow-through chemistry under superheated conditions.
Read moreApplication Note 6: Transfer Hydrogenation using a Monolithic Nanoparticular Pd[0] PACT Reactor Cartridge

This Application Note illustrates how the R-2 pump/injector and R-4 flow reactor modules can be used in combination with a reactor column to perform Polymer Assisted Continuous flow-Through (PACT) chemistry.
Read moreApplication Note 5: Heck C-C Coupling using a Monolithic Nanoparticular Pd[0] PACT Reactor Cartridge

This Application Note illustrates how the R-2 pump/injector and R-4 flow reactor modules can be used in combination with reactor columns to perform Polymer Assisted Continuous flow-Through (PACT) chemistry.
Read moreApplication Note 4: Example: Scale-up SNAr using 4 Reactor Channels in Series

The flow reactor was configured using a combination of the R-2 Pump Module and R-4 Reactor Module as shown in Scheme 1. Four Tubing Reactors (10 mL each) were installed and connected together in series. A 40 psi BPR was fitted in-line between the reactor outflow and the collection Valve.
Read moreApplication Note 3: Example: Scale-up SNAr using Single 12 mL Tubing Reactor

The flow reactor was configured using a R4 Flow Reactor Module and 2 Knauer A120 high pressure pumps as shown in Figure 1. The pumps were connected to a 12 mL tubing reactor via a T-piece. Each pump was connected to the T-piece through a 100psi BPR. A ‘T’ pressure release safety valve fitted with a 250 psi BPR was fitted between the T-piece and the tubing
reactor. The outflow from the tubing reactor was directed into either a 100 mL Duran waste collection bottle or into a 5L Duran product collection bottle filled with 4L of water, which was placed on a magnetic stirrer and stirred at approximately 600 rpm. A manual 2-position 3-way valve from used to direct the outflow to either ‘waste’ or collect. A 40psi BPR was connected in-line between the tubing reactor outflow and the selection valve.
Application Note 2 – Optimisation of Step 1 in the Synthesis of Linezolid using a ‘Dual-Core™’ Tubing Reactor

This Application Note illustrates how the smaller volume tubing reactor (810 mL) within a Dual-CoreTM element was used to determine optimal flow-through conditions suitable for the scale-up synthesis of the intermediate 3 required for the preparation of UpJohn’s oxazolidinone antibiotic linezolid (Zyvox®).
Read moreApplication Note 1: Example: Reaction Profiling using a ‘Dual-Core™’ Tubing Reactor

This Application Note illustrates, using an SNAr reaction as a simple example, how a continuous flow tubing reactor containing a dual core can be used for reaction profiling, using the smaller capacity reactor to minimise sample wastage, to obtain optimal reaction conditions that may be directly scaled-up in the larger reactor.
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