Scale-up Protocols

The concepts embodied in the mixing Damkoehler number (Dum) are extremely useful for initial evaluation of reaction conditions in which mixing effects must 

These concepts can be further utilized in a developmental program for a new chemical reaction as summarized in the following brief outline of an experimental protocol for a homogeneous reaction. Similar protocols for heterogeneous reactions are ontlined in Sections 13-4.3.2, 13-4.3.3, and 13-4.3.4. 

1 Scale-up Protocol for Homogeneous Reactions. Chemists report a yield of R of 68% for a reaction in which they added reagent B to A in the ratio 1.05 A/B in a round-bottomed flask with paddle impeller over a 1 h period with cooling to control the temperature at 50°C. A and B are both dissolved in solvents that are miscible in all proportions. B is consumed completely. The amounts of unreacted A and by-product S in the final reaction mixture were determined analytically to be 19% and 14%, respectively. Evaluation of the effectiveness of mixing in the round-bottomed flask can be useful but is difficult to characterize, as the types of impellers often used provide good circulation but low shear. The small scales involved may mask mixing effects. 

The development and scale-up of this reaction is now taken on by the chemical engineering group, who need to answer the following questions  

Is this the maximum yield that can be obtained in this reaction  

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Note The reaction can also be performed at multigram scale. Owing to the CO released in this reaction, a bubbler should be connected to the condenser in the scaled-up protocol rather than an argon-filled balloon.)... 

Go through a linear scale up protocol by increasing the column geometry to deliver the required amount and purity of material while maintaining load and separation conditions. 

Scale-up Protocol for Solid-Liquid Reactions. Refer to Section 13-4.3.1 and change reagent B from being dissolved in a miscible solvent to being added as a fine powder, all other factors remaining unchanged. 

The earher the information on resource efficiency is used in synthesis design, the more efficient process development wiU be. Therefore, appropriate metrics are initially applied to a choice of literature protocols and prehminary experimental data. As knowledge about the process increases, for example, during scale up, it is successively fed into the mass balance. In addition, environmental impacts associated with the mass balance can be evaluated. 

Mass balances of four case studies were evaluated. Additionally, an LCA is considered for the last case study. Case study 1 and Case study 2 are academic and include a comparison between alternative synthesis protocols. In the industrial Case study 3 and Case study 4, a comparison of the steps of a scale up was possible. 

In contrast to the quantity of solvent 1 used during the reaction, the quantity of extraction solvent 2 (work up) increases during scale up (Laboratory 100% Operation 103%), especially when it is related to substrate 2 (Laboratory 100% Operation 169%). Compared to the yield obtained from the literature protocol in which an extraction procedure is missing, an efficient extraction seems to be important in order to achieve sufficient product accumulation. However, as the mass index and the environmental factor demonstrate with respect to the possibility for reducing the volume of water used (see above), solvent 2 demand should be able to be reduced as well, since less water use means less solvent is required for extraction. StiU, at least the recycle rate of solvent 2 is as high as 72.8% (from 169% to 46%, Table 5.1), regarding the current data of the technical operation scale. 

The intention of this chapter is to provide a general survey on the preparative methodologies for the size- and shape-selective synthesis of metallic nanoparticles that have emerged from the benches of chemical basic research during the last few decades and become established as practical standard protocols. Industrial scale-up, however, has only just started to test the economic viability of these procedures and to determine whether they can meet the challenges of a number of very specific applications. The commercial manufacture of such thermodynamically extremely unstable nanoparticles in defined sizes and shapes on the kilo-scale is still confronted by a number of major problems and it remains to be seen how these can be solved. 

A general flowchart is presented in Fig. 13.5B that we followed for identifying and sorting inhibitors of translation. Shown below is an in vitro translation protocol tailored for ten 96-well assay plates (800 compounds), which can be scaled up or down as required. Negative and positive controls are present in wells A1 to D1 and El to HI, respectively. Compounds are added to wells A2 to Hll. Column 12 is left blank and could be used for additional controls, if desired. 

Prepare diazotized p-aminobenzoyl biocytin by using the protocol outlined in Chapter 11, Section 5, but instead of starting with 2mg the biotinylation reagent dissolved in 40 il of IN HC1, use 9mg in 180pi of IN HC1. Proportionally scale up the other reactant quantities used in the protocol. After the reaction is complete, immediately adjust the pH of the final solution to 9. 

The Anton Paar Synthos 3000 (Fig. 3.16 and Table 3.5) is the most recent multi-mode instrument to come onto the market. It is a microwave reactor dedicated for scaled-up synthesis in quantities of up to approximately 250 g per run and designed for chemistry under high-pressure and high-temperature conditions. The instrument enables direct scaling-up of already elaborated and optimized reaction protocols from single-mode cavities without changing the reaction parameters. 

Figure 4.9 Scale-up of proposed biopharmaceutical production process to generate clinical trial material, and eventually commercial product. No substantive changes should be introduced to the production protocol during scale-up...

In summary, we demonstrated the possibility of the fast scale-up of solid-phase supported synthesis. In one case (pyrimidine derivate), the research protocols could be used directly with only minor modifica-... 

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