Automated laboratory reactors

CHEMICAL PROCESS SCALE-UP TOOLS MIXING CALCULATIONS, STATISTICAL DESIGN OF EXPERIMENTS, AND AUTOMATED LABORATORY REACTORS... 

When performing such DoEs, the use of automated laboratory reactors is highly recommended. In addition to having recipe capabilities and agitation and temperature controls, they also have data acquisition and analysis modules. Eor example, the Mettler Toledo RCI (reactor calorimeter) is an automated laboratory reactor capable of measuring heats of reaction. Such measuranents are important in mechanistic investigations and safety evaluations. We also believe that after the development chemist, reaction calorimetry is the development engineer s best Mend. 

In conclusion, in this case study we showed how the use of mixing and scale-up calculations with VisiMix, combined with experimentation in automated laboratory reactors such as the reactor calorimeter RCl, assisted us in scaling up the Bourne III system, a typical reactive chemical system. 

Mettler Toledo Autochem (wwwjnt.com) and Argonaut Technologies (www.argotech.com) are two well-known manufacturers of automated laboratory reactors. 

Chemical engineering plays a central and pivotal role in scale-up operations. Dr. Andrei Zlota discusses chemical process scale-up tools, mixing calculations, statistical design of experiments, and automated laboratory reactors. 

Bosch and co-workers devised laboratory reactors to operate at high pressure and temperature in a recycle mode. These test reactors had the essential characteristics of potential industrial reactors and were used by Mittasch and co-workers to screen some 20,000 samples as candidate catalysts. The results led to the identification of an iron-containing mineral that is similar to today s industrial catalysts. The researchers recognized the need for porous catalytic materials and materials with more than one component, today identified as the support, the catalyticaHy active component, and the promoter. Today s technology for catalyst testing has become more efficient because much of the test equipment is automated, and the analysis of products and catalysts is much faster and more accurate. 

The RC1 is an automated laboratory batch/semi-batch reactor for calorimetric studies which has proven precision. The calorimetric principle used and the physical design of the system are sound. The application of the RC1 extends from process safety assessments including calorimetric measurements, to chemical research, to process development, and to optimization. The ability of the RC1 to generate accurate and reproducible data under simulated plant scale operating conditions may result in considerably reduced testing time and fewer small scale pilot plant runs. 

Many speciahzed laboratory reactors and operating conditions have been used. Sinfelt has alternately passed reactants and inert materials through a tubular-flow reactor. This mode of operation is advantageous when the activity of the fixed bed of catalyst pellets changes with time. A system in which the reactants flow through a porous semiconductor catalyst, heated inductively, has been proposed for studying the kinetics of high-temperature (500 to 2000°C) reactions. An automated microreactor... 

Vapour-phase catalytic oxidation of isobutene was carried out at atmospheric pressure in a completely automated laboratory setup, including a fixed bed reactor (700 mm length, 10 mm inner diameter) with corundum as wall material. In order to ensure isothermicity, the heated section (200 mm in length) was divided into five independently heated zones and the catalyst bed was diluted with inert pellets (a-Al203). Inert pellets were placed above and below the catalyst bed to ensure a well-mixed feed stream, and to preheat the gas to the reaction temperature. Bi203 catalyst (Merck) was pressed into thin wafers and broken into small particles. Granules with a diameter of 0.8 -1.2 mm were used. 

All zeolite samples were synthesized by the hydrothermal method described in detail in [6]. The experiments were performed in a completely automated laboratory setup including an integrally operated plug flow tubular reactor. Reaction components were analyzed by on-line gas chromatography with FID and TCD [5-7]. Table 1 summarizes the reaction conditions for the benzene hydroxylation on the H-Ga-ZSM5 catalyst. Nitrogen was used as balance. 

This samphng technique can be easily automated to increase the frequency of samphng [67, and Reuss et al., unpublished results]. However, as far as the very fast and initial response of intracellular metabolites in the millisecond range is concerned - and this is the time span of interest for the dynamic situation in the bioreactor - this method shows an inherent limitation. The time span for the first sample after disturbance is determined by the mixing time of the glucose pushed into the bioreactor. Even in small laboratory reactors, mixing times are in the order of 2-3 s. 

The application of solid catalysts in microreactors has been studied for different processes. Automated laboratory systems were applied for catalyst screenings [53,54]. Ag/Al and Ag/Al203 were applied in microflow-through reactors for the partial oxidation of ethylene [55]. For catalytic applications, a microflow-through arrangement with a static micromixer was used to prepare Au/Ag nanoparticles [56]. Microfluid segments are also of interest for catalytic reactions in microreactors [57]. 

Apparatus. Since all the polymer modification reactions presented in this paper involved gas consumption, an automated gas consumption measuring system was designed, fabricated and used to keep constant pressure and record continuously the consumption of gas in a batch type laboratory scale reactor. Process control, data acquisition, and analysis was carried out using a personal computer (IBM) and an interface device (Lab-master, Tecmar Inc.). 

Figure 3.1 shows a typical laboratory flow reactor for the study of catalytic kinetics. A gas chromatograph (GC, lower shelf) and a flow meter allow the complete analysis of samples of product gas (analysis time is typically several minutes), and the determination of the molar flow rate of various species out of the reactor (R) contained in a furnace. A mass spectrometer (MS, upper shelf) allows real-time analysis of the product gas sampled just below the catalyst charge and can follow rapid changes in rate. Automated versions of such reactor assemblies are commercially available. 

Automated testing of heterogeneous catalysts by means of parallel reactors still requires laboratory-made systems at the academic scale, due to the prohibitive costs of existing commercial systems. In contrast, for liquid phase reactions, a domain closer to mature pharmaceutical research, reasonably cheap systems are available. 

The CMR and MBRs provided the basis for modern commercial microwave reactors, including robotically operated automated systems that are now widely employed in synthetic research and pilot-scale laboratories in academia and industry [13]. Since 2000, commercial microwave reactors have become available. Batch systems, produced by three major companies in Italy and Germany, Sweden and the United States, typically operate on a scale from 0.5 mL up to 2 L. Other companies based in Austria, Poland and Japan have also recently entered the market. Systems possessing either multimodal or monomodal cavities are produced with one recent addition being a single unit capable of performing in either mode as required. Microwave reactors are employed extensively in chemical discovery where successive reactions can be performed rapidly in parallel or sequentially. One manufacturer recently estimated that about 10000 reactions per week were performed in its systems alone. This indicates the extent to which microwave chemistry in closed vessels has dramatically influenced approaches to synthesis. 

This issue highlights the characterization difference between parallel synthesis and combinatorial synthesis. Parallel synthesis is automated traditional organic chemistry. Each compound is made in a separate reactor, purified and characterized. There is no excuse for not fully characterizing compounds made by parallel synthesis. Jonathan Ellman s laboratory at UC Berkeley has been a pioneering academic center for solid-phase chemistry development. His philosophy is to synthesize libraries of discrete compounds in a spatially separate fashion, rather than libraries of compound mixtures, to allow for rigorous analytical characterization [48,49],... 

The fuUy automated, sequential flow-through synthesis of a 44-member array of thioethers via a resin capture-and-release reactor column was performed in our laboratory. Each of the acidic heterocycles (49-52) containing thiourea moieties were deprotonated by the use of a strong polymer-supported base, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene polystyrene (PS-TBD) to generate an immobilised ionic complex on the column (Figure 12). 

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