Direct scale-up

Direct Scale-Up of Laboratory Distillation Ljficiency Measurements It has been found by Fair, Null, and Bolles [Ind. Eng. Chem. Process Des. Dev., 22, 53 (1983)] that efficiency measurements in 25- and 50-mm (1- and 2-in-) diameter laboratory Oldersbaw columns closely approach tbe point efficiencies [Eq. (14-129)] measured in large sieve-plate columns. A representative comparison of scales of operation is shown in Fig. 14-37. Note that in order to achieve agreement between efficiencies it is necessaiy to ensure that (1) tbe systems being distilled are tbe same, (2) comparison is made at tbe same relative approach to tbe flood point, (3) operation is at total reflux, and (4) a standard Oldersbaw device (a small perforated-plate column with downcomers) is used in tbe laboratoiy experimentation. Fair et al. made careful comparisons for several systems, utibzing as large-scale information tbe published efficiency studies of Fractionation Research, Inc. 

A second Scheibel tower design [Am. Jn.st. Chem. Eng. J., 2, 74 (1956) U.S. Patent 2,850,362, 1958] reduced HETS and permitted more direct scale-up. The impellers are surrounded by stationaiy... 

In process design, it is frequently discovered that many of the basic data needed to rmderstand a process are lacking. Because most crrrrent mathematical models are not sufficiently accrrrate to permit direct scale-up of the process from laboratory data to full plant size, a pilot plant must be constracted. As models are improved, it may become possible to evaluate design decisions with more confidence, and bypass the pilot plant stage. 

Reactors Often yes Direct scale-up from the laboratory to the full scale often possible for homogeneous systems. 

Direct scale-up from laboratory to commercial size often possible. 

Cassettes Cassette is a term used to describe two different cross-flow membrane devices. The less-common design is a usually large stack of membrane separated by a spacer, with flow moving in parallel across the membrane sheets. This variant is sometimes referred to as a flat spiral, since there is some similarity in the way feed and permeate are handled. The more common cassette has long been popular in the pharmaceutical and biotechnical field. It too is a stack of flat-sheet membranes, but the membrane is usually connected so that the feed flows across the membrane elements in series to achieve higher conversion per pass. Their popularity stems from easy direct scale-up from laboratory to plant-scale equipment. Their limitation is that fluid management is inherently very limited and inefficient. Both types of cassette are very compact and capable of automated manufacture. 

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. 

Abstract. The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands. 

Without the experience and the equipment to perform solid-phase supported syntheses on a larger scale, chemists explore alternative routes utilising solution-phase chemistry. To compare the direct scale-up on solid support and to evaluate the advantages and disadvantages of both approaches, pyrimidine 1 was prepared in solution phase as well. For this relatively small and simple molecule, similar chemistry was applied (see Scheme 3) with some interesting results arising. 

The transfer hydrogenation methods described above are sufficient to carry out laboratory-scale studies, but it is unlikely that a direct scale-up of these processes would result in identical yields and selectivities. This is because the reaction mixtures are biphasic liquid, gas. The gas which is distilled off is acetone from the IPA system, and carbon dioxide from the TEAF system. The rate of gas disengagement is related to the superficial surface area. As the process is scaled-up, or the height of the liquid increases, the ratio of surface area to volume decreases. In order to improve de-gassing, parameters such as stirring rates, reactor design and temperature are important, and these will be discussed along with other factors found important in process scale-up. 

The Reactive System Screening Tool (RSST) was described in Section 33.2.7. This apparatus is a relatively recent development. Therefore, only limited literature data are available regarding the application of results from this equipment for direct scale-up of reactor systems. The Vent Size Package (VSP) is discussed further in Section 3.3.2.6. 

When data are available in the form of the flow rate-pressure gradient relationship obtained in a small diameter tube, direct scale-up for flow in larger pipes can be done. It is not necessary to determine the r-y curve with the true value of y calculated from the Rabinowitsch-Mooney equation (equation 3.20). 

Direct scale-up may be used to obtain a relief system size that is less conservative than the DIERS equation. Direct scale-up and its many conditions of applicability are detailed in A5.12. A direct scale-up test is only applicable if the test reactor empties totally by two-phase relief161, and the applicability of the method can therefore only be assessed after the scale-up test has been performed. Direct scale-up may not be feasible if the reacting system contains solids with a particle size similar to or larger than the diameter of the small-scale relief system. 

As for gassy systems, detailed computer simulation or direct scale-up (if applicable) can be used as alternative relief sizing methods for untempered hybrids. These methods are further discussed in section 7.4. 

Direct scale-up from a small-scale experiment can be a valid method of obtaining a relief system size However, it is imperative that the small-scale experiment is conducted in such a way that scale-up is valid. The following listI16,17] of requirements for valid scale-up should be achieved as far. as possible. If any of the list are not satisfied, the designer needs to,carefully consider the effects and be convinced that the result will be to overestimate the required relief size. t... 

In some cases, direct scale-up may be impracticable, for example because of blockage of the small-scale relief line. The requirement for complete emptying of the small-scale reactor by two-phase relief may also not be met in practice. If this occurs for a tempered system, the problem could be overcome by using a small-scale relief system from the bottom of the test reactor to simulate one at the top of the large-scale reactor. This procedure would not be safe for untempered reactions. 

Direct scale-up requires the, use of a series of different small-scale tests with different relief sizes in order to find the minimum safe size. This can be costly, so that the use of calorimetry to obtain data to be used in appropriate relief sizing equations may be a better option. 

Solid-phase syntheses of pyrimidines continue to appear at a rapid pace. A solid-phase synthesis of 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide was directly scaled up in excellent yields and high purity <03OPRD553>. The synthesis of imidazo[l,2-a]pyrimidines 59 via condensation of a solid-supported a-bromoketone and 2-aminopyridines was reported <03TL6265>. Pyrimido[4,5-t/]pyrimidine-2,4(l//,3W) diones have been accessed via a versatile solid-phase synthetic route <03S1739>. A microwave-assisted solid support synthesis of 5-methyl-6-ethylcarboxyIate-2-thioxothieno[3,2-iflpyrimidine-4(l//)-ones from 2-amino-3,5-diethyl carboxylate-4-methylthiophene and monosubstituted thioureas was reported <03BKC1038>. 

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