Scale-Up of a Batch Reactor

Consider the scale-up of a batch reactor from a pilot plant reactor to a full-scale reactor. Rewriting Equation 13-82 to the full-scale reactor yields ... 

ASPECT RATIO (R) IN JACKET ZONING AND SCALE-UP OF A BATCH REACTOR ... 

Aspect ratio R2 (L/D)2 for zoning scale-up of a batch reactor using Equation 13-119... 

The following reviews scale-up of chemical reactors, considers the dimensionless parameters, mathematical modeling in scale-up, and scale-up of a batch system. 

Hydrothermal Synthesis Systems. Of the unit operations depicted in Figure 1, the pressurized sections from reactor inlet to pressure letdown ate key to hydrothermal process design. In consideration of scale-up of a hydrothermal process for high performance materials, several criteria must be considered. First, the mode of operation, which can be either continuous, semicontinuous, or batch, must be determined. Factors to consider ate the operating conditions, the manufacturing demand, the composition of the product mix (single or multiple products), the amount of waste that can be tolerated, and the materials of constmction requirements. Criteria for the selection of hydrothermal reactor design maybe summarized as... 

In Scheme 4 it can be seen that cyclisation of the ketoester with hydrazine-hydrate was part of a reaction sequence given to the kilo lab and is described in literature with a yield of approximately 60% (Schenker and Salzmann 1979). Under conventional conditions (refluxing in ethanol for 4 h), we obtained the product in 53% yield. Performing the same reaction in the Synthos 3000 microwave reactor at 140°C for 20 min, we improved the yield to 64% on a 20-g scale. Further scale-up to a batch size of 130 g of product was performed under the same conditions (140°C/20 min) with no significant problems. 

Figure 4-1 shows two nozzles at the top of a batch reactor where charging of the reactants occurs. Batch reactors are used extensively in a final scale-up of an industrial plant. The choice of a batch reaction over a continuous system is often a result of special considerations. The size of batch reactors range from 5 gal (19 1) in small industrial pilot plants to 10,000-20,000 gal (38,000-76,000 1) in large plants. 

The effect of coalescence and break-up of droplets on the yield of chemical reactions was studied by Villermaux (33). Micromixing effects may occur even in batch reactors if there is a drop size distribution and mass-transfer control. Although practical rules for the design and scale-up of liquid-liquid reactors are available as Oldshue showed in the case of alkylation (152), many problems remain unsolved (.5) mass transfer effects, high hold-up fractions (> 20 %), large density differences, high viscosities, influence of surfactants. 

Batch processes present challenging control problems due to the time-varying nature of operation. Chylla and Haase [4] present a detailed example of a batch reactor problem in the polymer products industry. This reactor has an overall heat transfer coefficient that decreases from batch to batch due to fouling of the heat transfer surface inside the reactor. Bonvin [5] discusses a number of important topics in batch processing, including safety, product quality, and scale-up. He notes that the frequent repetition of batch runs enables the results from previous runs to be used to optimize the operation of subsequent ones. 

Doran outlines several of the key parameters involved in the scale-up of a biological process from laboratory-scale shake flasks to production-scale bioreactors. In the first stage of studies a bench-top bioreactor, typically 1-2 L, is used to determine the oxygen requirements of the cells, their shear sensitivity, foaming characteristics, and any limitations that the reactor imposes on the organism. The results of these early studies enable decisions regarding operation in the batch, fed-batch, or continuous mode. A pilot-scale... 

As it is hoped that the issue of polymorphism is resolved during prenomination and early development, it can remain a concern when the synthesis of the drug is scaled up into a larger reactor or transferred to another production site. It is not unlikely that a metastable form identified in prenomination may not be reproduced in later batch products because of some unrecorded conditions in the early phases of development. Related substances, whether identified or not, can significantly alter the predominance of a specific polymorph. To develop a reliable commercial recrystallization process, the following scheme should be followed in the production of candidate drugs ... 

An adsorption isotherm is useful for scaling up small-scale batch processes usually carried out in a laboratory. Once the laboratory data are fitted to an isotherm, one can predict the amount of adsorbent required to reach a specific effluent solute concentration (in terms of a batch reactor) or the breakthrough time (for a plug-flow column). 

By means of an ETHOS MR oven, Nuchter et al. [33] accomplished scaling-up of a microwave-assisted Fischer glycosylation to the kilogram scale with improved economic efficiency. In batch reactions, carbohydrates (o-glucose, o-mannose, d-galactose, butyl o-galactose, starch) were converted on the 50-g scale (95-100% yield, from 95 5 to 100%) with 3-30-fold molar excesses of an alcohol (methanol, ethanol, butanol, octanol) in the presence of a catalytic amount of acetyl chloride under pressure (microwave flow reactor, 120-140 °C, 12-16 bar, 5-12 min) or without applying pressure (120-140 °C or reflux temperature, 20-60 min). Furano-sides are not stable under these reaction conditions. 

As far as industrial applications are concerned, the easy scale-up of two-phase catalysis can be illustrated by the first oxo aqeous biphasic commercial unit with an initial annual capacity of 100,000 tons extrapolated by a factor of 1 24,000 (batch-wise laboratory development production reactor) after a development period of 2 years [4]. 

Establishing the process sensitivity with respect to the above-mentioned factors is crucial for further scale-up considerations. If the sensitivity is low, a direct volume scale-up is allowed and the use of standard batch reactor configurations is permitted. However, many reactions are characterized by a large thermal effect and many molecules are very sensitive to process conditions on molecular scale (pH, temperature, concentrations, etc.). Such processes are much more difficult to scale up. Mixing can then become a very important factor influencing reactor performance for reactions where mixing times and reaction times are comparable, micromixing also becomes important. 

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