Bench-scale processes

Bench-scale processes have an optimized catalyst performance and have been carried out a few times on a small scale, but are for some reason not yet ready for production purposes. 

Various Pilot- and Bench-Scale Processes for a-Amino Acid Derivatives... 

Earlier examples of pilot- and bench-scale processes are summarized in [14]. Several cases with high ee-values and medium activity using Rh-bpm ligands were reported by Hoechst (now Sanofi Aventis) [46] Ru-binap and Ru-biphep... 

The hydrogenation of a number of aromatic ketones is shown in Figure 37.30. Noyori s very effective Ru-diphosphine-diamine technology was developed by several companies. It is not clear on which scale the processes developed by Takasago (dm-binap = 3,5-xylyl-binap) [16] and Dow/Chirotech [109-111] for the reduction of substituted acetophenones are actually applied commercially. Using the Xyl-PhanePhos-dpen catalyst, a highly efficient bench-scale process was developed for the hydrogenation of p-fluoroacetophenone (ee 98%, TON 100000, TOF 50000 IT1 at r.t., 8 bar) [109]. Ru-P-Phos (licensed to Johnson Matthey [112]) achieved ee-values >99.9% and TON up to 100000 for sev-... 

Chemi Proprietary diphosphine ligands, process R D, custom manufacturing. Some pilot and bench scale processes. 

Although the process requires the treated gas to have a certain minimum carbon dioxide partial pressure for removal of sulfurous compounds with liquid carbon dioxide, promising new SNG processes under development produce medium to high carbon dioxide content crude gases ideally suited for acid gas removal via the CNG process (12,13). The novel features of the CNG process have been demonstrated with bench-scale process development units second generation process development units are in various stages of... 

In an attempt to replace the organohalides as starting materials, diazonium salts have been investigated as starting material. They, too, can react in an oxidative addition with the Pd° to form the first intermediate of the catalytic cycle. In a recent bench scale process for a herbicide in development (CGA 308956) a diazonium salt proved to be suitable. The product of the oxidative addition will... 

In this chapter we will describe some of our initial evaluation work on Paraho shale oil. This initial evaluation was not performed in depth rather, this first step consisted of chemical characterizations and high-spot, bench-scale processing of oil shale and several other syncrudes for direct comparisons of chemical feedstocks potential. Conventional analytical and petroleum processing techniques were used in the expectation that these would provide reference data on which to base specifically adapted techniques for evaluations of individual syncrudes. The results represent only our first attempts and except for occasional comparisons, are only for Paraho shale oil. 

Product recovety is some combination of rote methods of using processing tools and inspired application of new and conventional separation tools. For example, if aldehydes make distillation infeasible because of polymerization products and/or vacuum distillation costs, then one can consider utilizing the Cannizzaro reaction to make organic acid salts and ketones from the aldehydes before proceeding. Many bench-scale processing techniques such as thin-film evaporation have been scaled up to handle larger quantities of temperature sensitive materials. Assistance in utilization of these techniques can usually be obtained from the equipment vendors. 

Production processes are operated on a regular basis. Pilot processes are technically on a similar level but are not (yet) applied on a regular basis. Bench-scale processes have an optimized catalyst system and have been carried out on a kilogram scale. 

Cost of the Bench-scale Process. The cost of materials for the treatment of 1 liter of partially purified rSLPI, containing approximately 1 gram of the protein of interest was 20.65. At a refold yield of 50%, this represented a cost of refolding of 41.29 per active gram of rSLPI produced. Note that this cost calculation does not include the upstream cost of preparing the partially purified rSLPI. 

Two bench-scale processes were developed for the enantioselechve hydrogenahon of p-chlorophenylglyoxylic acid derivatives using both homogeneous and heterogeneous catalysts (Scheme 12.11) [29]. For the production of kilogram amounts of ( S)-p-chloro mandelic acid a Ru/MeO-biphep catalyst achieved 90-93% ee... 

Process qualification strategy using bench-scale process... 

In categories II and III, the most important processes with volumes of up to 2000 t/y are carried out with biocatalysts, whereas only small scale or pilot processes were reported with homogeneous metal complexes. In addition, there were further reports on four bench-scale processes by Takasago (3) and HoechstMarion-Roussel/Aventis (1) [1],... 

Because most examples in category IV described in this monograph use biocatalysts, it could be inferred that chemical catalysis is not suitable for the synthesis of NCEs. Just to show that this is not correct but rather due to the choice of our authors, Tab. 7 shows an extensive list of examples illustrating this point. In addition to these production and pilot processes, there were further reports on 19 bench-scale processes using homogeneous catalysts by Roche (7), HoechstMarion-Roussel/Aventis (5), SmithKline Beecham (2), Sepracor (2), Pharmacia/Upjohn (1), Eli Lilly (1) and Merck (1) [1],... 

Develop and demonstrate a bench scale process to remove the identified contaminants from a 5-kg sample of the soil. Develop a conceptual design of the process applicable to the field-scale project. 

Abstract This review describes the application of chiral organometallic catalysts for the enantioselective (transfer) hydrogenation of C=C, C=0 and C=N bonds in the fine chemicals industry. Covered are processes that have been and/or are presently used for the commercial manufacture of chiral compounds as well as selected pilot and bench-scale processes not (yet) used in production. The review is organized according to the metal precursor actually employed in the hydrogenation reactions. Described are large scale applications of Rh, Ru, and Ir complexes with chiral P P, P N and N N ligands, either used as preformed, isolated complexes or as in situ-prepared catalyst precursors. 

Bench-scale processes (see Fig. 6) were described by Hochst [53] for the synthesis of a thiophene-containing a-amino acid derivative for a hradykinin... 

A number of bench-scale processes are shown in Fig. 11. Merck described the hydrogenation of an a,()-unsaturated aryloxy acid [77, 78] and of a (3-ketoester [79] as intermediate for the DPP-IV inhibitor sitagliptin MK-0431. Monsanto [80] also developed a process for naproxen (compare results in Figs. 9 and 10) and Roche [64] achieved the reduction of an a-ketoester for the Ro 40-2148 with remarkable ton of 2,000. 

A number of bench-scale processes with Ru/P P/N N catalysts are summarized in Fig. 13. Dow/Chirotech [91] used Ru/Xyl-PhanePhos/dpen for the hydrogenation of p-fluoro acetophenone. Kanto Chemicals developed a very effective Ru/bdpp/N N catalyst (the only case where the diphosphine is not a biaryl type) and applied it to the large scale hydrogenation of acetophenone [92] and of a quinuclidine [93] for a muscarinic receptor antagonist. Nycomed/JMC [94] scaled up the hydrogenation of rather complex ketone intermediate for the synthesis of a potassium competitive acid blocker. 

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