Scale reaction, mixing sensitive

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. 

Similarly, when moving from the pilot plant to manufacturing, a process engineer will either choose an existing vessel or specify the design criteria for a new reactor. A necessary condition for operation with a specified reactor temperature profile is that the required jacket temperature is feasible. We have therefore chosen to focus on heat transfer-related issues in scale-up. Clearly there are other scale-up issues, such as mixing sensitive reactions. See Paul [1] for several examples of mixing scale-up in the pharmaceutical industry. 

Guidelines to minimize yield loss in mixing-sensitive reactions on scale-up from bench-scale to industrial reactors. 

The rates of a reaction are determined by rate constants, concentrations of reactants, and temperature. At a given temperature, the rate of a second-order reaction depends on the product of the rate constant and the concentrations of the reactants. The concentration at which the chemical reaction becomes faster than the mixing is the critical concentration at which conversion and yield will be affected by mixing. It must be emphasized that the relative reaction rate at a point in the reactor is proportional to the product of the rate constant and the local concentration. It is recommended that bench and pilot data for mixing-sensitive reactions can be obtained at the same concentrations as they are to be used in the commercial plant. This eliminates concentration as a concern in scale-up. 

The importance of feed rate on yield for a mixing-sensitive reaction was demonstrated in Ref. ". The addition time in a semibatch reaction is often increased on scale-up because of heat transfer limitations. In the case of a mixing-sensitive reaction, the time of addition is increased on scale-up to compensate for the increase in blend time and to maintain the expected molar ratio at the feed point. The minimum feed time to achieve the expected yield is, therefore, scale dependent. Feed times that are too short will result in mesomixing conditions and reduced yield. 

Simple Guidelines for Scale-Up of Mixing-Sensitive Homogenous Reactions... 

If experiments show a possibility of mixing-sensitive reactions and the rate of addition is important, consider multiple point injections. The feed time will have to be increased in large-scale equipment. 

The complex interaction between mass transfer and reaction kinetics requires determination of mixing sensitivity for virtually all heterogeneous reactions for which competitive and/or consecutive reactions are possible to be sure of successful scale-up. This requirement is prompted by issues of both 1) overall reaction completion time and 2) undesired reactions in the films around the discontinuous phase(s). The following set of guidelines may be useful in evaluating mixing sensitivity and for scale-up. 

Create a similar environment to that of the large scale. This means using the same concentrations and purity of reactants as on the industrial scale. In some reaction systems, it may be possible to reduce mixing sensitivity by changing temperature. 

Stirred tank case, it has been difflcnlt to find experimental evidence of segregation for single-phase reactions. Real CSTRs approximate perfect mixing when observed on the time and distance scales appropriate to indnstrial reactions provided that the feed is premixed. Even with unmixed feed, the experimental observation of segregation requires very fast reactions. The standard assumption of perfect mixing in a CSTR is usually justified. Worry when a highly reactive component is separately fed and when the reaction is sensitive to mixing time. See Section 4.6. 

These results continue to indicate mixing sensitivity, indicating that extreme caution must be taken on scale-up to manufacturing. The effect of addition time is not as expected for a classic consecutive-competitive reaction system, suggesting that the reaction pathway contains a step that requires maintaining short addition time on scale-up. 

As in Example 13-3, time was not available to measure individual rate constants. However, the laboratory and initial poor pilot plant results showing the effect of scale-up on product distribution were sufficient to illustrate the mixing sensitivity of the reaction. The key to solving the problem was not to try to improve mixing but to eliminate the mass transfer and local effects of a dissolving powder by changing the process to use a solution addition. An improvement was realized at both the laboratory and pilot plant scales. 

Generally, it is recommended that bench and pilot data for mixing sensitive reactions be obtained at the same concentrations as are to be used in the commercial plant. That eliminates concentration as a concern in scale-up. 

Summarizing, the output of the reactor is an integral over time and over the entire reaction space with all interconnections between different zones of the reactor. Mixing and heat- and mass-transfer conditions are usually different in various zones and the pattern of these differences as well as proportions between size of zones vary with scale. Obviously, the histories of concentrations and temperatures in the zones differ. Whether the integral outputs of laboratory and full-scale reactors differ from each other, depends on the sensitivity of the process to mixing and heat- and mass-transfer conditions. If the sensitivity is low only minor... 

In most applications, the first reaction in each set is an acid-base reaction so that k is very large. For Eq. (59), B and C are premixed and added to A under conditions such that B is in stoichiometric excess to A. Likewise, for Eq. (58), B is reacted in stoichiometric excess with A to produce the desired product R. Under these conditions, the first reaction in each set is favored. However, if mixing occurs with the same time scale as the second reaction, the undesired byproduct (S in Eq. (58) and P2 in Eq. (59)) will be produced. Thus, the amount of by-product produced is a sensitive measure of the quality of mixing in the chemical reactor. 

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