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A versatile continuous flow reactor system
This article explains the functionality and gives examples of the FlowCAT - versatile continuous flow reactor system focusing on reactions under elevated pressure and/or involving heterogeneous catalysis. The utility of a versatile, research scale flow reactor has been demonstrated with numerous reactions. In addition, the FlowCAT is extremely simple to and opens up the possibility of doing pressure reactions, including hydrogenations, in normal laboratories by chemists who are not specialists in pressure equipment. The flowCAT allows all manner of chemistries to be studied interchangeably with virtually no change in set up being necessary. Feeds of all liquid, all gas and mixtures of gas and liquid are possible and the same is true for products.
The FlowCAT represents a freely-configurable platform on which to build versatile, automated systems for Flow Chemistry. In this example we take a look at a configuration which optimises conversion through liquid recycle.
Application Note-Adapting Catalytic Platforms For Greener Chemistry
Among the other potential benefits of moving to fixed bed flow reactors, is the ease with which benefits of supercritical CO2 (scCO2) can be investigated. HEL has been looking at the hydrogenation of phenol, both on stirred batch platforms (such as HP ChemSCAN) and FlowCAT. Starting with a process documented in the literature, we were able to replicate and extend this easily and quickly using the 8-reactor, 200bar parallel stirred reactor system.
Application Note: Effect of mechanical nail penetration on battery thermal stability
Two separate experiments were performed in the Adiabatic Calorimeter Phi-TEC BTC to determine the thermal stability of a 3-battery, Li-ion battery pack. The objective was to compare the stability of the battery when it is complete and undamaged with the result when the batteries were penetrated with a nail.
Application Note: Battery life-time testing with BTC
The useful life of a battery can be determined by connecting to a power supply that can do the charging and then connected to an external load, to discharge it. Using charging and load units that are computer controlled, this was done to a Li-ion battery situated inside an adiabatic reaction calorimeter.
Application Note: Battery Safety Data
BATTERY SAFETY DATA DIRECT FROM MANUFACTURER: Safety of batteries under different temperature conditions needs to be verified experimentally and "adiabatic" calorimetry is the widely accepted method. Data collected recently by MGL in China from one of their prototypes shows how under adiabatic conditions, the temperature at which a battery starts to undergo self-heating is detected and this provides the maximum safe temperature under which it can ideally be used. In addition, the calorimeter allows the battery to continue thermal runaway and hence provides direct information about the extent of the hazard.
Application Note: Battery Specific Heat Determination
Batteries are complex objects and the Cp is rarely known. Fortunately, this can be measured in an adiabatic calorimeter again using equation Q = m cp ΔT. Demonstrated in this application note.
Application Note: Data for safe scale-up of a heterogeneous liquid phase reaction
The calorimetry (heat output) information provides a convenient means of monitoring the progress of the reaction. Combined with a simple visual observation of mixing it has enabled the process problem to be quickly identified and a solution to be tested.
Application Note: Evaluation of increase in throughput using a catalyst
A test of the effectiveness of an acid catalyst in reducing the batch time of an esterification reaction and whether the cooling system on a full scale reactor would be able to cope with the increased power output.
Application Note: FlowCAT for tuning stereoselective hydrogenations of API's
Hydrogenation of organic substrates to achieved desired product slates can be difficult and expensive using conventional stirred reaction. The HEL flowCAT overcomes many difficulties with inherent flexibility, an accessible interface and features for easy use by specialist and non-specialist chemists alike.
Application Note: Improvement in nitration process economics
Process optimistaion resulted in a significant increase in yield as well as simplified product work-up procedure, thus reducing the batch time in the process of nitration of an aromatic substrate.
Application Note: Investigation of plant crytallisation problem using an automated lab reactor
Looking at an existing process which invloved the crystallisation of an active pharmaceutical for an organic medium, precise control and recording of reactor and oil jacket temperature, plus stirrer speed enabled the study of the following: - Solubility curve, for different solvent purities - Systematic (factorial) study of several process variables and their influence on crystal shape and form.
Application Note: Method development for a crystallisation step
The use of computer control rapidly produced substantial improvements in the commercial viability of a process. This greatly improved the crystallisation step in the case of a product that previously took nearly a week to filter, wash and dry, thus dominating the production cycle.
Application Note: Protection of dryer in the event of product composition
Adiabatic calorimetry in the Phi-TEC II shows that the product that needs drying before transportation will begin to decompose signficantly at around 100 degrees C (around 85 degrees C lower than quoted in the literature).
Application Note: Runway Li-ion battery explosion during charging / discharging
The rate at which batteries are charged and discharged is limited by many factors including safety. If excessive rates of charging and discharging are used, the battery can overheat and potentially lead to a runaway explosion. A battery connected to a computer controlled cycler was used to investigate this potential with the battery placed in a Battery Testing Calorimeter (BTC) that operates adiabatically.
Application Note: The Development of Solubility and Metastability Design Spaces
UCD Crystallization Research Group found that the HEL polyblock turbidity screening device, when combined with polythermal methods, enhances process understanding and enhances quality by design (QbD). By gaining a understanding of the limitations and benefits of a solubility and metastability design space a suitable crystallization technique can be designed.
Application Note: The use of statistical experimental design in process optimization
This application note describes a case study completed by HEL to demonstrate how a straightforward experimental design approach and a miniature computer controlled multiple reactor system can be used to reduce the manufacturing costs of a commercial chemical process. The process investigated was the pilot plant scale manufacture of 1,3,5-triphenylbenzene.
Application Note: Video battery Testing
The performance demands on modern batteries subject them to considerable physical stresses. HEL supply a range of battery testing systems and now include Remote Video Monitoring to record deformation, smoking and degradation in real-time...
Automated Measurement of Metastable Zones for Pharmaceutical Compounds
The automated laboratory reactor combined with turbidity meter method was used successfully to measure the metastable zone for a pharmaceutical intermediate, thus providing useful information to aid the development of the crystallization process for that compound.
Breakthroughs in on-line process particle sizing
Recent designs of laser reflection probes can be described as " process microscopes " because they now can report the true size of particles on-line and do this over a wide range of sizes, fully integrated into process equipment.
Call for Papers: 12th HEL Conference
Catalytic reactions, hydrogenation in particular, have seen a remarkable surge in interest over the last 10 years, most strikingly in the pharmaceutical and fine chemical industries. More recently, flow chemistry has begun to attract a similar level of interest for a wide range of chemistries, but especially involving heterogeneous catalysis. Join the 12th HEL Conference on September 27th 2011, Cambridge, UK, to speak and hear about recent developments in these areas.
Crystallisation Tools for the Research Chemist
It is clear that crystallisation studies in parallel can be performed at sample sizes as low as 1ml or as large as several hundred millilitres. The data scales up reliably and thus provides an excellent early insight into the key variables. This article expands the functionality and applications of CrystalSCAN and Crystal Eyes from HEL.
Design & characterisation of a miniature stirred bioreactor for parallel microbial fermentation
The establishment of a high productivity microbial fermentation process requires the experimental investigation of many interacting variables. In order to speed up this procedure a novel miniature stirred bioreactor system is described which enables parallel operation of 4 - 16 independently controlled fermentations.
Development of hydrogenation reaction using parallel processing
Heterogeneous hydrogenation reactions can be performed in parallel and quantitative data can be generated in real time as the reaction proceeds. This is an important component of parallel processes development as it allows rapid evaluation of the results. Equally important, it has been shown that with well designed and fully instrumented reactors, performance at different scales varying by two orders of magnitude can be directly compared. This shows that for the three systems studied (HP Chemscan, HP auto-MATE and SIMULAR) the data is perfectly consistent.
Enantio- and Diastereoselective Hydrogenation of Pharmaceutical Intermediates
A presentation from Dr Joel M. Hawkins, Chemical Research and Development at Pfizer PharmaTherapeutics, at the Stereochemistry Gordon Conference, Newport, Rhode Island, August 4, 2010.
Exothermicity Characteristics of Wolf Lake Heavy Oil, Athabasca Tar Sand and Medium Heavy Clair Oil
High pressure accelerating rate calorimetry (ARC) tests - using HEL's Phi-TEC II adiabatic calorimeter - have been performed on three different crude oils, at their respective reservoirs pressures. The experiments on medium heavy Clair oil and heavy Wolf Lake oil used clean silica sand, incorporating 3% kaolinite, to represent the reservoir matrix, whereas Athabasca Tar Sand was used in its preserved, virgin state.
FlowCAT - continuous flow reactor system for hydrogenation screening and small scale production
A presentation given by Dr Jasbir Singh at the Chemistry Today 2nd Symposium on Continuous Flow Reactor Technology for Industrial Applications, about the developments of the FlowCAT system, including performance data and examples of the use of DOE with hydrogenation reactions, carried out on a continuous flow reactor. Have a look at the presentation that includes data recently presented by Dr Joel Hawkins of Pfizer.
Laboratory Product Focus: Crystallisation Tools for the Research Chemist
The need to study crystallisation is extremely widespread in the chemical industry due to the importance of solids as the final form of many products. The most basic information required is the solubility of crystals - proceeding without this basic information is like trying to locate a house without knowing the address - it can be done but will take a long time.
Minimisation of Scale-up Difficulties
This article discusses what chemists and engineers can do in advance, both in the laboratory and kilo laboratory, to prevent or at least minimise scaleup issues. Scale-up of chemical processes, particularly those involving batch or semi-batch manufacture is well-known to be a problematic area of chemistry and chemical engineering, and can be costly when it goes wrong. By correctly choosing and designing the synthetic route to a fine chemical or drug substance, as well as controlling the reaction and work up/product isolation parameters, many of the difficulties in scale up can be avoided. The more complex a process is in terms of chemistry and unit operations, the more there is to go wrong.
Monitoring & feedback control of supersaturation using ATR-FTIR to produce an API
Automation, in-situ monitoring and process analytical technology control tools are implemented to understand and control the crystallization of an active pharmaceutical ingredient in development.
Multi-scale segmentation image analysis for the in-process monitoring of particle shape
On-line imaging represents a potentially powerful technique for real-time monitoring of the morphological forms during crystal growth, but a major challenge is the availability of methods for image analysis that need to be tolerant to the quality of on-line images, accurate, fast and robust. This paper describes a multi-scale segmentation methodology for analysis of images obtained for batch cooling crystallisation of (L)-glutamic acid using an on-line high-speed imaging system developed by the pharmaceutical manufacturer GlaxoSmithKline. The method proves to be able to analyse effectively the on-line images of different crystal morphological forms, and of varied qualities.
Obtaining Better Information From Simple Ramped Temperature Screening Tests
Thermal screening of materials is a vital part of hazard assessment in the chemical industry. There is the need to identify the worst potential hazards and to further investigate these scenarios. Several screening methods are presented, and the subject of ramped temperature screening tests is studied in detail.
Power consumption & Oxygen Transfer in Miniature Bioreactor for Predictive Fermentation Scaleup
Miniature parallel bioreactors are becoming increasingly important as tools to facilitate rapid bioprocess design.. This article considers some important practical consideration in selection of scale-up basis, with respect to HEL parallel bioreactor platforms.
Presentation: Battery Safety Testing - Nov 2010, Beijing
A presentation made by Dr J Singh at the 5th International Forum on Li-ion Battery Technology, Beijing, China, Nov 2010, about HEL's advanced Battery Testing Calorimeter (BTC) as a unique solution for both small scale testing of battery components as well as direct simulation of larger scale battery incidents, including the "abuse" testing methods specified by various codes.
Rapid Process Development and Scale-Up Using A Multiple Reactor System
This article presents case studies that show how computer control involving parallel synthesis in specially designed reactors, particularly on the 25-100 mL scale, can provide significant benefits to the development cycle of new synthetic compounds of commercial interest. By employing a combination of calorimetry data and other analytical measurements, it has been demonstrated that small-scale experimentation can produce data that is both representative and scaleable.
Runaway reaction hazard and venting of cyanide reaction
The runaway reaction hazard of a cyanide reaction initiated by an amine and caustic has been studied extensively and a venting strategy formulated from the data. The relief size necessary to safely relieve such a reaction has been calculated using thermal runaway data for a number of different situations, allowing for two-phase flow.
Scale Up Of Hazardous Chemistry- With Thermal Runaway Potential
This paper describes (with examples) how with a range of experimental methods and with the correct equipment, it is possible to simulate a thermal runaway. The data produced (with samples less than 100ml) can help prevent potential hazards. (As published in Chemistry Today)
The Design of Safe Chemical Processes
A typical process in the pharmaceutical and related industries consists of a number of sequential steps where a range of carefully selected compounds are allowed to react in order to produce the required product or intermediate. In many cases, the reactions involved are exothermic, and therefore require cooling and careful process control in order to ensure safe operation. In addition, some of the raw materials or products may be unstable and have a tendency to thermally explode under certain operating conditions.
Thermal profiling for parallel on-line monitoring of biomass growth in miniature stirred bioreactors
The combination of a parallel miniature bioreactor system with a noninvasive on-line technique for estimation of culture kinetic parameters provides a valuable approach for the rapid optimisation of microbial fermentation processes. Here we report on the use of thermal profiling techniques for parallel online monitoring of cell growth in these bioreactors based on the natural heat generated by microbial culture.
Thermal Runaway in Li-ion- getting the missing data
Most modern high energy batteries, not only Li-ion, contain highly reactive and potenitally explosive chemicals as exemplified by the recent Boeing incident.
Transferring batch to continuous flow and including use of scCO2 as solvent
Development of heterogeneous catalytic processes. Transferring batch to continuous flow and including use of scCO2 as solvent
The limitations of DSC as a tool for thermal screening are discussed and the Thermal Screening Unit (TSU) is described. Ramped temperature experimental data for families of experiments on di tertiary butyl peroxide in toluene and azobis cyano valeric acid in dimethyl formamide are presented and used to illustrate the absolute necessity of recording pressure as well as temperature during any thermal screening tests.
TSU: A Tool for Reactive Chemical Engineering
The thermal screening unit is an instrument specifically designed for the fast and efficient hazard screening of liquids, solids and heterogeneous systems. The unit provides an alternative device to DSC and DTA for use in hazard assessment and provides information regarding reaction “onset temperatures”, rates of temperature rise as well as crucial information regarding the rates and magnitudes of pressure rise in chemical systems.