Process synthesis illustrative example

Chemical synthesis in microreactors can be conducted in both continuous-flow and batch modes, with the first being typically utilized for synthesis of one product and the second for parallel processing. Some illustrative examples are given in Refs. 57-59. 

An illustrative example of an alternative strategy (cf Fig. 11c) involving the use of a novel traceless linker is found in the multistep synthesis of 6-epi-dysidiolide (363) and several dysidiolide-derived phosphatase inhibitors by Waldmann and coworkers [153], outlined in Scheme 70. During the synthesis, the growing skeleton of 363 remained attached to a robust dienic linker. After completion of intermediate 362, the terminal olefin in 363 was liberated from the solid support by the final metathesis process with concomitant formation of a polymer-bound cyclopentene 364. Notably, during the synthesis it turned out that polymer-bound intermediate 365a, in contrast to soluble benzoate 365b, produced diene 367 only in low yield. After introduction of an additional linker (cf intermediate 366), diene 367 was released in distinctly improved yield by RCM. 

Two illustrative examples are presented. The first deals with the scheduling of a small batch process operating in zero effluent mode and the second deals with the synthesis of a small batch operation. 

The zero effluent synthesis formulation was applied to a second illustrative example. In the example the number of processing units and the size of the central storage vessel were not known. The resulting plant required only 3 processing units and no storage vessel. The resulting schedule produced 68% less effluent than the same operation without wastewater reuse. 

The synthesis of phthalimidines by dicobalt octacarbonyl-catalyzed carbonylation of Schiff bases was first described by Pritchard78 and the scope of the reaction was evaluated by Murahashi et a/.79 Later Rosenthal et al.80-83 subjected a variety of related compounds to carbonylation, and also achieved a phthalimidine synthesis directly from benzonitrile under the conditions of the oxo process.84 An example illustrating the formation of a phthalimidine is shown in Scheme 49 a comprehensive review of the scope and mechanism of reactions of this type is available.85... 

Inter- and intramolecular (cyclometallation) reactions of this type have been ob-.served, for instance, with titanium [408,505,683-685], hafnium [411], tantalum [426,686,687], tungsten [418,542], and ruthenium complexes [688], Not only carbene complexes but also imido complexes L M=NR of, e.g., zirconium [689,690], vanadium [691], tantalum [692], or tungsten [693] undergo C-H insertion with unactivated alkanes and arenes. Some illustrative examples are sketched in Figure 3.37. No applications in organic synthesis have yet been found for these mechanistically interesting processes. 

In contrast, amino acid dehydrogenases comprise a well-known class of enzymes with industrial apphcations. An illustrative example is the Evonik (formerly Degussa) process for the synthesis of (S)-tert-leucine by reductive amination of trimethyl pyruvic acid (Scheme 6.12) [27]. The NADH cofactor is regenerated by coupling the reductive amination with FDH-catalyzed reduction of formate, which is added as the ammonium salt. 

An illustrative example of the use of this process in the preparation of nitrogen heterocycles is presented in (1.1.) Stahl and co-workers reported12 the synthesis of a series of pirrolidine derivatives exploiting the fact that 5-ethynyl-amides undergo ring closure in the presence of a palladium(II) catalyst, base and oxidant. 

Part 3 of this book presents a number of major developments and applications of MINLP approaches in the area of Process Synthesis. The illustrative examples for MINLP applications, presented next in this section, will focus on different aspects than those described in Part 3. In particular, we will consider the binary distillation design of a single column, the retrofit design of multiproduct batch plants, and the multicommodity facility location/allocation problem. 

The existence of chirality in nature is of particular importance in numerous recognition processes, often illustrated by examples detectable by non-spectroscopic methods such as the different orange and lemon odors of R-(+)- and S-(-)-limonene, respectively (Fig. 3) [8]. As such, chiral discrimination is also of considerable consequence in the medical sciences, as often one enantiomer is pharmaceutically active whereas the other may show adverse side effects. A historic example is the anti-emetic activity of one of the enantiomers of thalidomide, while the other can cause fetal damage [9,10]. These considerations highlight the importance of chiral discrimination in the production of biologically active materials, whereas on the other hand, the design of routes to asymmetric synthesis presents an active challenge to synthetic chemists worldwide. 

These early examples of macromonomer synthesis illustrate some of the chief principles that have subsequently led to a great variety of methods. Ionic polymerization is often preferred because of the long lifetime of the active sites. Transfer reactions in free-radical processes are also used quite often, yielding both acceptable molecular weights and an adequate proportion of terminal functions. 

Figure 1.2 A few illustrative examples of chemicals and classes of chemicals that are manufactured by homogeneous catalytic processes. In 1.6 low-pressure methanol synthesis by a heterogeneous catalyst is one of the steps. In 1.9 it is ethylene that is converted to acetaldehyde. In 1.7 all the available building blocks may be used.

Polypeptides would have played only a limited role early in the evolution of life because their structures are not suited to self-replication in the way that nucleic acid structures are. However, polypeptides could have been included in evolutionary processes indirectly. For example, if the properties of a particular polypeptide favored the survival and replication of a class of RNA molecules, then these RNA molecules could have evolved ribozyme activities that promoted the synthesis of that polypeptide. This method of producing polypeptides with specific amino acid sequences has several limitations. First, it seems likely that only relatively short specific polypeptides could have been produced in this manner. Second, it would have been difficult to accurately link the particular amino acids in the polypeptide in a reproducible manner. Finally, a different ribozyme would have been required for each polypeptide. A critical point in evolution was reached when an apparatus for polypeptide synthesis developed that allowed the sequence of bases in an RNA molecule to directly dictate the sequence of amino acids in a polypeptide. A code evolved that established a relation between a specific sequence of three bases in RNA and an amino acid. We now call this set of three-base combinations, each encoding an amino acid, the genetic code. A decoding, or translation, system exists today as the ribosome and associated factors that are responsible for essentially all polypeptide synthesis from RNA templates in modem organisms. The essence of this mode of polypeptide synthesis is illustrated in Figure 2.8. 

In this section, we reconsider the van de Vusse process to illustrate our synthesis approach. This example also shows the application of the unified reaction-separation-energy integration model. Comparisons are made between sequential and simultaneous modes of synthesis, and the applicability of the simplified model is verified. 

The use of simulation software to analyze this type of process is illustrated in Example 5, which considers a simplified ternary system for illustration. The simulation of an actual aromatics extraction process is more complex and can exhibit considerable difficulty converging on a solution however. Example 5 illustrates the basic considerations involved in carrying out the calculations. For more detailed discussion of process simulation and optimization methods, see Sei-der, Seader, and Lewin, Product and Process Design Principles Synthesis, Analysis, and Evaluation, 2d ed. (Wiley, 2004) and Turton et al.. Analysis, Synthesis, and Design of Chemical Processes, 2d ed. (Prentice-Hall, 2002). 

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