Fine chemistry

In 1993, shortly after the FDA announced their first policy statement on enantiopure drugs, separations of pharmaceutical compounds were performed using SMB technology [25, 26]. Other applications now include fine chemistry, cosmetics, and perfume industry [27]. 

Goyau B. Fine Chemistry and Acrolein Chim. Oggi 1999 17 22-27... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Firstly, there are technical reasons concerning catalyst and reactor requirements. In the chemical industry, catalyst performance is critical. Compared to conventional catalysts, they are relatively expensive and catalyst production and standardization lag behind. In practice, a robust, proven catalyst is needed. For a specific application, an extended catalyst and washcoat development program is unavoidable, and in particular, for the fine chemistry in-house development is a burden. For coated systems, catalyst loading is low, making them unsuited for reactions occurring in the kinetic regime, which is particularly important for bulk chemistry and refineries. In that case, incorporated monolithic catalysts are the logical choice. Catalyst stability is crucial. It determines the amount of catalyst required for a batch process, the number of times the catalyst can be reused, and for a continuous process, the run time. 

Alkylcatechols are important as chemicals and chemical intermediates in the fine chemistry industry for the synthesis of flavouring agents, agricultural chemicals and pharmaceuticals [1]. 3-methyl catechol has a special value from the industrial point of view. Previously y-alumina was found to be an effective catalyst for the gas-phase methylation of catechol with methanol [2]. The process can be schematically presented as ... 

Kleine Reaktoren mit grower Zukunji, Chemische Rundschau, April 2002 PAMIR study large commercial potential large industrial interest market volume standardization strategic cooperations time horizon potential for pharmaceuticals and fine chemistry Clariant pilot with caterpillar mixer [211],... 

Gezdhmte Chemie im Mikroreaktor, VDI Nachrichten, June 2000 Micro-reactor enterprises shape and material variety of micro reactors selectivity gains and new project regimes direct fluorination faster process development BASF investigations safety increase speed-up of catalyst development production for fine chemistry and pharmacy numbering-up first industrial examples for micro-reactor production [215]. 

Metal Vapor-Derived Nanostructured Catalysts in Fine Chemistry The Role Played by Particle Size in the Catalytic Activity and Selectivity... 

These metal vapor-derived nanostructured systems are valuable catalytic precursors for a wide range of reactions of great interest in fine chemistry. 

Fine chemicals are often manufactured in multistep conventional syntheses, which results in a high consumption of raw materials and, consequently, large amounts of by-products and wastes. On average, the consumption of raw materials in the bulk chemicals business is about 1 kg/kg of product. This figure in fine chemistry is much greater, and can reach up to 100 kg/kg for pharmaceuticals (Sheldon, 1994 Section 2.1). The high raw materials-to-product ratio in fine chemistry justifies extensive search for selective catalysts. Use of effective catalysts would result in a decrease of reactant consumption and waste production, and the simultaneous reduction of the number of steps in the synthesis. 

For complex reaction systems the establishment of a reliable kinetic network and accompanying parameters is often difficult or even impossible. Paul (1988, 1990) has categorized complex systems of fine chemistry reactions in the following way ... 

This chapter focuses on heterogeneous catalysis, which is most important in fine chemicals production. Table 3.1 presents a number of examples of catalysis in fine chemistry. These examples are divided in heterogeneously catalysed processes and homogeneously catalysed processes. A detailed treatment of heterogeneously catalysed processes for the production of fine chemicals is also given in the book edited by Sheldon and van Bekkum (2001). 

Example.s of gas-liquid catalytic reactions in fine chemistry, based on information compiled... 

The most important example of this category is Raney nickel, which is extensively used in hydrogenation reactions in fine chemistry. The catalyst has been named after Murray Raney who invented this catalyst in 1924. It is prepared by the reaction of a powdered nickel-aluminium alloy with aqueous sodium hydroxide to selectively remove a large fraction of the aluminium component (.see Figure 3.12). The product consists of porous nickel with a high... 

During water storage slow oxidation takes place. In particular the most active Raney catalysts show. severe deactivation (they should not be stored more than a few weeks). Other types of catalysts though less active are much more stable. In fine chemistry activity is often not the most important catalytic property. This certainly holds for Raney nickel. On a nickel... 

Figure 5.2-1 illustrates the iterative and interactive nature of process development for fine chemicals. As shown, a process is evaluated at any stage to decide whether to continue or to stop process development and abandon it. In the development of fine chemistry processes, the sequence of steps is often laboratory-miniplant-commercial production. It must be emphasized that in process development for fine chemicals efforts in various sectors, including process design, are often made in parallel and not necessarily in sequence. 

In spite of decades of experience gained with scale-up of chemical processes, there still appear unexpected, sometimes mysterious scale-up effects. In terms of chemical reaction characteristics, these effects are mainly lower yields (selectivities) and products less pure than on the laboratory scale. Chemists involved in fine chemistry usually do not study the nature of scale-up effects. They expect these effects to appear if engineers do not take appropriate... 

In the vast majority of gas-solid reactions, gaseous or evaporated compounds react at the surface of a solid catalyst. These catalytic processes are very frequently used in the manufacture of bulk chemicals. They are much less popular in processing of the large molecules typical of fine chemistry. These molecules are usually thermally sensitive and as such they will at least partially decompose upon evaporation. Only thermally stable compounds can be dealt with in gas-solid catalytic processes. Examples in fine chemicals manufacture are gas-phase catalytic aminations of volatile aldehydes, alcohols, and ketones with ammonia, with hydrogen as... 

Column reactors are the second most popular reactors in the fine chemistry sector. They are mainly dedicated reactors adjusted for a particular process although in many cases column reactors can easily be adapted for another process. Cocurrently operated bubble (possibly packed) columns with upflow of both phases and trickle-bed reactors with downflow are widely used. The diameter of column reactors varies from tens of centimetres to metres, while their height ranges from two metres up to twenty metres. Larger column reactors also have been designed and operated in bulk chemicals plants. The typical catalyst particle size ranges from 1.5 mm (in trickle-bed reactors) to 10 mm (in countercurrent columns) depending on the particular application. The temperature and pressure are limited only by the material of construction and corrosivity of the reaction mixture. 

Equilibrium for a single reaction in the liquid-phase. A significant proportion of fine chemistry processes occur in the liquid phase. The equilibrium constant is expressed by Eqn. (5.4-8), which can be rewritten as ... 

The most widely used reactors for gas-solid reactions in fine chemistry are fixed-bed tubular... 

Essentially, there are no general guidelines for preliminary model selection for complex reactions. Mechanistic studies are the best basis for model formulation. Literature data and indications clear to experienced organic chemists will certainly be the most helpful. Studies on individual reactions are always recommended, but for the complex reactions involved in fine chemistry such an opportunity is rather a rare case. 

Empirical grey models based on non-isothermal experiments and tendency modelling will be discussed in more detail below. Identification of gross kinetics from non-isothermal data started in the 1940-ties and was mainly applied to fast gas-phase catalytic reactions with large heat effects. Reactor models for such reactions are mathematically isomorphical with those for batch reactors commonly used in fine chemicals manufacture. Hopefully, this technique can be successfully applied for fine chemistry processes. Tendency modelling is a modern technique developed at the end of 1980-ties. It has been designed for processing the data from (semi)batch reactors, also those run under non-isothermal conditions. 

In fine chemistry, mathematical models are scarce yet. However, even gross kinetics provides a lot of information on the influence of the mode of operation on seleetivity. In general, semi-quantitative criteria are used in preliminary reactor selection. They are mainly based mainly on operational characteristics, experience, and a rough economic estimation. Factors affecting the choice of the reactor and mode of operation are listed in Table 5.4-42. 

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