Scale-up to pilot plant

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

As a reason for not using h.v.t. it is often stated that its use leads to experimental results that cannot be reproduced on an industrial scale. This is untrue. A closed system, such as an all-glass vacuum line, has more in common with an industrial plant than the typical apparatus used at the laboratory bench. Furthermore, because of the considerably more favourable surface to volume ratios in a large plant, the typical concentrations of those impurities which originate from surfaces are more accurately reproduced by h.v.t. experiments than by the typical bench experiment. This is often reflected in the problems encountered during development work when bench experiments are being scaled up to pilot plant and beyond. 

The process has been successfully scaled-up to pilot plant level and the product characteristics are yield > 98%, purity 95-99% and particle size 40-60 pm. At the same time, this process reduces the environmental impact of TATB production as compared with the traditional TCB Route [52]. 

Other work has been mainly concerned with the scale-up to pilot plant or full-scale installations. For example, Beltran et al. [225] studied the scale-up of the ozonation of industrial wastewaters from alcohol distilleries and tomato-processing plants. They used kinetic data obtained in small laboratory bubble columns to predict the COD reduction that could be reached during ozonation in a geometrically similar pilot bubble column. In the kinetic model, assumptions were made about the flow characteristics of the gas phase through the column. From the solution of mass balance equations of the main species in the process (ozone in gas and water and pollution characterized by COD) calculated results of COD and ozone concentrations were determined and compared to the corresponding experimental values. 

All scales of operation are dominated by the effects of supersamration, although the outcome is usually more critical on scale-up to pilot plant and plant operations. The local and global supersamration ratios that are experienced over the course of a crystallization operation are critical because they determine the balance between nucleation and growth, not only at the onset of crystallization, but throughout the course of a batch or semibatch operation. This balance, in mrn, determines the resulting physical properties and, in many cases, the distribution of chemical impurities between the crystals and the liquors. 

Abstract A synthesis of an aryl boronic acid and the subsequent Suzuki coupling to an aryl indole has been developed and successfully scaled up to pilot plant scale. The Suzuki coupling was optimized by design of experiments and run with a catalyst loading of 0.1 mol%. The article describes the strategic approach for the optimization of the reaction and the most critical issues, such as the cryogenic synthesis of the boronic acid, the catalyst optimization, and the palladium removal, are discussed in detail. 

Reactions that are best for scale-up to pilot plant and industrial scale would ideally possess the following traits " ... 

Nutritional studies of polyene-producing Streptomyces have been carried out with batch cultures, usually in shake flasks, with occasional scale-up to pilot-plant or large-scale fermenters of those polyenes that are produced industrially. In most studies, several nutri-... 

The determination of kinetic parameters is an essential step in developing a catalytic process. Parameters determined in laboratory-scale steady-state reactors are necessary to formulate models for scale-up to pilot plant and process-scale reactors. Kinetic parameters also provide insight into the fundamental processes that occur during a catalytic reaction and form the basis for creating microkinetic models that describe the individual steps (e.g., adsorption, surface reaction, and desorption) of a complex reaction. 

Logic dictates that when corrosion occurs in a calciner, one should lower the temperature to determine if a satisfactory product can be obtained. This was done and corrosion became much worse. It was soon learned that the bed was much less corrosive to steel at higher temperatures where melt crystallized to crystals more quickly. When optimum temperatures and feed rates were determined, high-quality crystals could be made without causing harm to the calciner. This process was scaled up to pilot plant size and will be discussed in more detail in Chapter 7. 

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