Stopped-flow reactor

For the Michael addition of 2,4-pentanedione enolate to ethyl propiolate, improvements in conversion were determined. This example serves also to demonstrate that proper process conditions are mandatory to have success with micro-reactor processing. A conversion of only 56% was achieved when using electroosmotically driven flow with a two-fold injection, the first for forming the enolate and the second for its addition to the triple bond (batch synthesis 89%) [151]. Using instead a stopped-flow technique to enhance mixing, a conversion of 95% was determined. 

The conversions observed followed the sequence of reactivity known from batch experiments carried out in advance. For example, only 15% conversion was found for the less reactive reagent benzoylacetone in the micro reactor experiment, while 56% was determined when using the more reactive 2,4-pentanedione (batch syntheses 78% and 89%, respectively) [8]. Using the stopped-flow technique (2.5 s with field applied 5.0 s with field turned off) to enhance mixing, the conversions for both syntheses were increased to 34 and 95%, respectively. Using a further improved stopped-flow technique (5.0 s with field applied 10.0 s with field turned off), the conversion could be further enhanced to 100% for the benzoylacetone case. For the other two substrates, diethyl malonate and methyl vinyl ketone, similar trends were observed. 

Figure 3.7 — (A) Cross-sectional view of the McPherson stopped-flow mixer unit. The outer aluminum housing (a) and quartz windows b) are press-fitted with three bolts. Mixing occurs at e, where the streams meet at 90° to each other one stream is in the figure plane and the other normal to it. The immobilized enzyme reactor is placed inside d. With the reactor in place, the observation cell is 1.75 cm in length. The dashed arrow represents the lightpath inside the cell. (B) Flow-cell used to accommodate enzymes on CPG. (Reproduced from [48] and [49] with permission of Elsevier Science Publishers).

The apparatus used are mostly stirred-tank-, tubular-, and differential recycle reactors. Also, optical cells are used for spectroscopic measurements, and differential thermal-analysis apparatus and stopped flow devices are applied at high pressures. 

The stopped-flow method uses syringe-type pumps, (a), to feed the components, A and B, through a mixing cell, (c), into the reaction cell, (d), which can be an optical cell (Fig. 3.3-5). The pumps, mixing cell, and reactor are well thermostatted. The flow is stopped when the syringe, (e), is loaded and operates a switch, (f), to start the monitoring device. The change in concentration is detected either by spectroscopy or conductivity measurement. 

A chip-based integrated precolumn microreactor with 1 nl reaction volume has been explored by Jacobson et al. [67]. The reactor is operated in a continuous manner by electrokinetically mixing of sample (amino acids) and reagent (o-phthaldialdehyde) streams. The reaction time is adjusted via the respective flow velocities. By switching of potentials, small plugs of the reaction product were injected into a 15.4 mm separation channel in a gated injection scheme (< 1.8% RSD in peak area). The separation efficiency achieved was relatively poor, however, electrokinetic control of reaction time (and yield) permitted to monitor the kinetics of the derivatization under pseudo first-order conditions. A similar integrated precolumn reactor operated in a stopped flow mode has been described by Harrison et al. [68]. 

BR = batch reactor SBBC = semibatch bubble column SBBPR = semibatch bubble photoreactor CBPR = continuous bubble photoreactor system SBPR = semibatch photoreactor BPR = batch photoreactor SBBT = semibatch bubble tank CFPR = continuous flow photoreactor CFCB = continuous flow bubble column CST = continuous flow stirred tank SBR = semibatch stirred reactor SFC = stopped flow cell. 

Measurements of kinetic parameters of liquid-phase reactions can be performed in apparata without phase transition (rapid-mixing method [66], stopped-flow method [67], etc.) or in apparata with phase transition of the gaseous components (laminar jet absorber [68], stirred cell reactor [69], etc.). In experiments without phase transition, the studied gas is dissolved physically in a liquid and subsequently mixed with the liquid absorbent to be examined, in a way that ensures a perfect mixing. Afterwards, the reaction conversion is determined via the temperature evolution in the reactor (rapid mixing) or with an indicator (stopped flow). The reaction kinetics can then be deduced from the conversion. In experiments with phase transition, additionally, the phase equilibrium and mass transport must be taken into account as the gaseous component must penetrate into the liquid phase before it reacts. In the laminar jet absorber, a liquid jet of a very small diameter passes continuously through a chamber filled with the gas to be examined. In order to determine the reaction rate constant at a certain temperature, the jet length and diameter as well as the amount of gas absorbed per time unit must be known. 

More popular for reactions in the millisecond range is the "stopped-flow" technique [4], which consumes less fluid and for which commercial equipment is available (e.g., see Figure 3.7). Over an extremely short time span, liquids are injected into and mixed in a small reaction chamber, and the composition of the mixture is then monitored continuously or analyzed after short, preset reaction times. In contrast to the Hartridge-Roughton reactor, a stopped-flow reactor functions essentially as a micro-batch reactor. 

Goldfinger et have studied the reaction between CI2 and HBr to form HCl and BrCl in the gas phase. Using a stopped-flow reactor and absorption spectroscopy they conclude, but not convincingly, that the mechanism is bimo-lecular, four-centered and molecular. 

Enzyme reactor systems may be of the continuous flow or the stopped-flow variety. Continuous flow systems are further categorized as open or closed systems. The open system, shown in Figure 4.9, continuously pumps fresh buffer through the injector, reactor and detector, ultimately into a waste reservoir for discarding. This arrangement is preferred for the testing of enzyme reactors, since unreacted substrate, cofactors and the products of the enzymatic reactions will not be reexposed to the column. 

These systems are designed for the endpoint determination of substrate concentrations, and do not provide a straightforward means for making kinetic measurements. Stopped-flow enzyme reactor systems have been designed for automated kinetic assays. A diagram of a stopped-flow reactor that uses a postcolumn chemical indicator reaction is shown in Figure 4.12.31 In this system, the flow rate of the... 

Figure 4.12. Stopped-flow enzyme reactor with absorbance detection.

The gradual decay with time in the polymerization rate characteristic of Cr/aluminophosphate is different from that of Cr/silica. It has sometimes been attributed to mass transport limitations caused by polymer buildup around the active sites. To test this hypothesis, a stopped-flow experiment was conducted, as represented in Figure 170. In this run, the polymerization rate with Cr/AIPO4 was allowed to build up to its highest value, which occurred in 10 min. Then the ethylene flow was stopped, and the reactor was depressurized to remove residual ethylene. After about 75 min, the ethylene was readmitted and polymerization continued. However, it continued not at the rate at which it had left off,... 

FIGURE 2.1 Didactic representation of a stopped-flow analyser. S — sample R — reagent Rc = reactor (often a transmission line) ... 

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