Industrial examples

Two examples are highlighted below where precious metal catalysts are used to produce fine chemicals on an industrial scale via carbon-carbon bond forming reactions. The first (a) is rhodium-catalysed hydroformylation in the oxo-process , which is a well established industrial process. The second (b) highlights a new process developed by Lucite involving a palladium-catalysed methoxy-carbonyla-tion. Many of the points mentioned above in this article are illustrated in the examples, with efficient recycle of catalyst (precious metal) and the extra cost of ligands being justified by the costs savings of the novel chemistry. 

METAL CATALYSED CARBON-CARBON BOND-FORMING REACTIONS 

The Rh Oxo process comprises two main steps, hydroformylation followed by hydrogenation. The hydroformylation is carried out in the liquid/gas phase with a homogeneous rhodium catalyst. This is the carbon-carbon bond forming step. 

This is followed by a hydrogenation reaction, which is carried out in the vapour or liquid phase over heterogeneous catalyst 

In general, a rhodium catalyst is used as it efficiently converts olefin to alcohol  

1 Process selectivity. The objective in many process development exercises is to increase the selectivity of chemical reactions thereby eliminating undesirable byproduct formation. The use of raw materials and energy is thereby optimised. 

As the product came off patent, there was enormous pressure from generic competition and process economics became fundamental for the original patent holders, Boots, to maintain market share. Boots, in association with Hoechst Celanese in USA developed a process using hydrogen fluoride in place of aluminium trichloride to catalyse the acetylation step [17]. Liquid hydrogen fluoride requires sophisticated technology and relatively expensive plant for safe handling. It is also important to remove 

Other catalysts for clean Friedel-Craft reactions, the so-called Enviro-cats, have been developed for industrial use and are described in detail elsewhere. These supported reagents can easily be removed from the reaction mixture and recycled. It is claimed that their use, when compared with aluminium trichloride, reduces volumes of waste to be treated by 30% and waste disposal costs by 50%. They cost 10 times the price of aluminium trichloride but, in a cost/benefit calculation, show sound economic sense and sound environmental practice. 

2 Glyphosate - a bulk active herbicide. One of the world s leading herbicides is glyphosate (Roundup) (21) produced by Monsanto. They key intermediate is disodium iminodiacetate (DSIDA) (20). 

13 Cilastatin - a bulk active pharmaceutical. Merck Co produce an antibiotic Primaxin (cilastatin (22) + imipenem (6)). To produce cilastatin, a process using methylene chloride was used. Methylene chloride features on the US Toxic Release Inventory (TRI) and elimination of emissions from chemical processes has become a priority. Merck have developed a novel process avoiding the use of methylene chloride altogether [13]. The new process, which cost some US 34 million to implement, required a further expenditure of some US 5 million on a fume stripper and US 500 000 on a waste water stripper. However, they claim to have cut their total TRI air emissions by more than 160 tonnes, of which 150 tonnes would have been methylene chloride. Merck also claim that the economics of the new process saved some US 7.2 million during the second half of 1992 alone. 

Ib/year. It has developed a process that leads to total replacement of chlorofluorocarbons (CFCs) and volatile organic compounds (VOCs) by CO2 as blotving agent in the manufacture of these foams. By implementing this process, Dovr has removed3.5 million pounds of CFCs from the atmosphere every year. 

FIGURE 9.1. Green product manufacturing and usage methodology (cradle-to-grave or life-cycle analysis). 

Analgesics are a group of drugs that include aspirin, acetaminophen (commercial name Tylenol), and ibuprofen (commercial 

The old Boots process uses aluminum trichloride in a stoichiometric amount, which is then converted into aluminum trichloride hydrate waste. In the BHC process, hydrogen fluoride, Raney nickel, and palladium are used as catalysts, which are recovered and reused. The batch cycle times and capital expenditure in the BHC process are much less when compared to the Boots process. This results in significant economic benefits to the company. The process won the Presidential Green Chemistry Challenge Award in 1997 and the Kirpatrick Chemical Engineering Achievement Award in 1993. 

The BHC Company is a joint venture of the Hoechst Celanese Corporation and the Boots Company. BASF purchased the Boots Company and Celanese sold its interest in the BHC Company to BASF. Celanese operates the new ibuprofen manufacturing facility in Bishop, Texas, for BASF. Ibuprofen manufactured via the BHC process is marketed under the brand names Advil and Motrin. The industrial-scale facility created in Bishop, Texas, in 1992 is the world s largest ibuprofen manufacturing plant, is operated by the Celanese Corporation for BASF, and currently produces approximately 20-25 % (more than 7 million pounds) of the world s yearly supply of ibuprofen. 

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An important industrial example of W/O emulsions arises in water-in-crude-oil emulsions that form during production. These emulsions must be broken to aid transportation and refining [43]. These suspensions have been extensively studied by Sjoblom and co-workers [10, 13, 14] and Wasan and co-workers [44]. Stabilization arises from combinations of surface-active components, asphaltenes, polymers, and particles the composition depends on the source of the crude oil. Certain copolymers can mimic the emulsion stabilizing fractions of crude oil and have been studied in terms of their pressure-area behavior [45]. 

In 1973 the Semiconductor Equipment and Materials Institute (SEMI) held its first standards meeting. SEMI standards are voluntary consensus specifications developed by the producers, users, and general interest groups in the semiconductor (qv) industry. Examples of electronic chemicals are glacial acetic acid [64-19-7] acetone [67-64-17, ammonium fluoride [12125-01 -8] and ammonium hydroxide [1336-21 -6] (see Ammonium compounds), dichloromethane [75-09-2] (see Cm.OROCARBONSANDcm.OROHYDROCARBONs), hydrofluoric acid [7664-39-3] (see Eluorine compounds, inorganic), 30% hydrogen peroxide (qv) [7722-84-1] methanol (qv) [67-56-1] nitric acid (qv) [7697-37-2] 2-propanoI [67-63-0] (see Propyl alcohols), sulfuric acid [7664-93-9] tetrachloroethane [127-18-4] toluene (qv) [108-88-3] and xylenes (qv) (see also Electronic materials). 

Industrial examples of phase-transfer catalysis are numerous and growing rapidly they include polymerisa tion, substitution, condensation, and oxidation reactions. The processing advantages, besides the acceleration of the reaction, include mild reaction conditions, relatively simple process flow diagrams, and flexibiHty in the choice of solvents. 

Oxychlorination of methane can yield significant amounts of methylene chloride. A number of patents were obtained by Lummus in the mid-1970s on a high temperature, molten salt oxychlorination process (22,23). Catalyst development work has continued and generally consists of mixtures of Cu, Ni, Cr, or Fe promoted with an alkah metal (24—27). There are no industrial examples of this process at the present time. 

Hydrogenation of Carbon Tetrachloride. Carbon tetrachloride can be hydrogenated, ie, hydrodechlorinated, to chloroform over a catalyst (25,26) or thermally (27). Although there are no industrial examples of this process at this time, it will receive more attention as more carbon tetrachloride becomes available as the CFC-11 and -12 markets decline (see, Chlorocarbons and chlorohydrocarbons, carbon tetrachloride). Chloroform can be further hydrodechlorinated to methylene chloride (28,29). 

An industrial example of acidolysis is the reaction of poly(vinyl acetate) with butyric acid to form poly(vinyl butyrate). Often a butyric acid—methanol... 

Transesterification has a number of important commercial uses. Methyl esters of fatty acids are produced from fats and oils. Transesterification is also the basis of recycling technology to break up poly(ethylene terephthalate) [25038-59-9] to monomer for reuse (29) (see Recycling, plastics). Because vinyl alcohol does not exist, poly(vinyl alcohol) [9002-89-5] is produced commercially by base-cataly2ed alcoholysis of poly(vinyl acetate) [9003-20-7] (see Vinyl polymers). An industrial example of acidolysis is the reaction of poly(vinyl acetate) with butyric acid to form poly(vinyl butyrate) [24991-31-9]. 

Dente and Ranzi (in Albright et al., eds.. Pyrolysis Theory and Industrial Practice, Academic Press, 1983, pp. 133-175) Mathematical modehng of hydrocarbon pyrolysis reactions Shah and Sharma (in Carberry and Varma, eds.. Chemical Reaction and Reaction Engineering Handbook, Dekker, 1987, pp. 713-721) Hydroxylamine phosphate manufacture in a slurry reactor Some aspects of a kinetic model of methanol synthesis are described in the first example, which is followed by a second example that describes coping with the multiphcity of reactants and reactions of some petroleum conversion processes. Then two somewhat simph-fied industrial examples are worked out in detail mild thermal cracking and production of styrene. Even these calculations are impractical without a computer. The basic data and mathematics and some of the results are presented. 

Few mechanisms of liquid/liquid reactions have been established, although some related work such as on droplet sizes and power input has been done. Small contents of surface-ac tive and other impurities in reactants of commercial quality can distort a reac tor s predicted performance. Diffusivities in liquids are comparatively low, a factor of 10 less than in gases, so it is probable in most industrial examples that they are diffusion controllech One consequence is that L/L reactions may not be as temperature sensitive as ordinary chemical reactions, although the effec t of temperature rise on viscosity and droplet size can result in substantial rate increases. L/L reac tions will exhibit behavior of homogeneous reactions only when they are very slow, nonionic reactions being the most likely ones. On the whole, in the present state of the art, the design of L/L reactors must depend on scale-up from laboratoiy or pilot plant work. 

Particular reactions can occur in either or both phases or near the interface. Nitration of aromatics with HNO3-H2SO4 occurs in the aqueous phase (Albright and Hanson, eds.. Industrial and Laboratoiy Nitration.s, ACS Symposium Series 22 [1975]). An industrial example of reaction in both phases is the oximation of cyclohexanone, a step in the manufacture of caprolactam for nylon (Rod, Proc. 4th Interna-tional/6th European Symposium on Chemical Reactions, Heidelberg, Pergamon, 1976, p. 275). The reaction between butene and isobutane... 

An industrial example of the reduction of stable oxides to form a metallic element as a vapour, is the Pidgeon process for the production of magnesium. 

Many applications of novolacs are found in the electronics industry. Examples include microchip module packaging, circuit board adhesives, and photoresists for microchip etching. These applications are very sensitive to trace metal contamination. Therefore the applicable novolacs have stringent metal-content specifications, often in the low ppb range. Low level restrictions may also be applied to free phenol, acid, moisture, and other monomers. There is often a strong interaction between the monomers and catalysts chosen and attainment of low metals levels. These requirements, in combination with the high temperature requirements mentioned above, often dictate special materials be used for reactor vessel construction. Whereas many resoles can be processed in mild steel reactors, novolacs require special alloys (e.g. Inconel ), titanium, or glass for contact surfaces. These materials are very expensive and most have associated maintenance problems as well. 

Ribbon blenders are essentially self-contained mixers. They are employed in a variety of solid-liquid, solid-solid, and liquid-liquid blending applications in the chemical process industries. Examples include plastics, pigments, pharmaceuticals, specialty chemicals, confectionary. 

An industrial example of series reactions is the substitution process involving methane and chlorine ... 

An industrial example of a eonseeutive reversible reaetion is the eatalytie isomerization reaetions of n-hexane to 2-methyl pentane and 3-methyl pentane and is represented as ... 

The dotted lines in the diagram indicate the various feedback paths that exist to enable the individual to identify if a particular stage of the processing chain was executed correctly. Thus, if the operating team had planned a strategy to handle a complex plant problem, they would eventually obtain feedback with regard to whether or not the plan was successful. Similar feedback loops exist at the rule and skill-based levels, and indicate opportunities for error correction. The application of the stepladder model to a process industry example is given in Appendix 2A at the end of this chapter. 

Numbering-up can be performed in two ways (Figure 1.4). External numhering-up is referred to as the connection of many devices in a parallel fashion [8] (a similar, but less elaborate, definition was already provided in [9, 10] see also [11] for a realized industrial example). A device in the sense as it is used here is defined as a functional element, e.g. a micro-mixing flow configuration such as an interdigital... 

There is common agreement that with the aid of micro reactors, process development can be speeded up considerably [5]. First industrial examples on the implementation of micro-reaction technology for pilot-scale and production seem to con-... 

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]. 

Downstream Processing Microfiltration plays a significant role in downstream processing of fermentation products in the pharmaceutical and bioprocessing industry. Examples are clarification of fermentation broths, sterile filtration, cell recycle in continuous fermentation, harvesting mammahan cells, cell washing, mycelia recovery, lysate recovery, enzyme purification, vaccines, and so forth. 

The use of copolymers is essentially a new concept free from low-MW additives. However, a random copolymer, which includes additive functions in the chain, usually results in a relatively costly solution yet industrial examples have been reported (Borealis, Union Carbide). Locking a flame-retardant function into the polymer backbone prevents migration. Organophosphorous functionalities have been incorporated in polyamide backbones to modify thermal behaviour [56]. The materials have potential for use as fire-retardant materials and as high-MW fire-retardant additives for commercially available polymers. The current drive for incorporation of FR functionality within a given polymer, either by blending or copolymerisation, reduces the risk of evolution of toxic species within the smoke of burning materials [57]. Also, a UVA moiety has been introduced in the polymer backbone as one of the co-monomers (e.g. 2,4-dihydroxybenzophenone-formaldehyde resin, DHBF). 

Adhesion or printability of polymeric surfaces, including films, is often promoted by plasma or glow discharge treatment. In particular for apolar (low surface energy) surfaces such as polyolefins this is a commonly applied procedure. As a practical industrial example, the adhesion behaviour of polypropylenes after... 

Research is also strongly influenced by the admittedly legitimate interests of the pharmaceutical industry examples of this include contract clauses reserving copyright, the initial selection of researchers and topics, and the recent consolidation of the position of companies specializing in clinical trials (to the detriment of academic centres). Frequently there is a conflict of interests between social welfare and private welfare that does not necessarily amount to fraud or malpractice, but which should be made public - through... 

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