Introduction: Catalysis in the Chemical Industry

PHILIP HOWARD, GEORGE MORRIS AND GLENN SUNLEY

1.1 Catalysis in the Chemical Industry

1.1.1 The Importance of Catalysis

In 1985 the National Academy of Sciences of the United States published a landmark study "Opportunities in Chemistry" which mapped out some of the important discoveries in the field over the preceding 20 years. The very first point made in the Pimentel Report (named after the chairman of the study group) was that the successful competitiveness of the chemical industry depends critically on the constant improvements of existing processes and the introduction of new ones. Thus advances in chemical catalysis and synthesis hold the key to a successful chemical industry. Indeed they estimated that a large proportion (ca.20%) of the entire US Gross National Product is generated through the use of catalytic processes.

More than 20 years have elapsed since the Pimentel Report and all mankind has benefitted enormously from the improvements to our lives that catalysis has brought. We now have access to cheaper and more effective fuels, to new drugs and medications, new polymers and other materials with useful properties, and new routes to a whole host of commodity and fine chemicals. Especially significant are the new, energy-saving, and environmentally more friendly ("greener") methodologies that chemists have devised to make the chemicals. These changes have largely been brought about by better catalysts. And metal catalysts, developed jointly by industrial and academic chemists, form one of the main classes of present-day industrial catalysts. We now understand how many catalysts work and are beginning to tune them to high degrees of selectivity and activity; in some cases such catalysts now begin to rival enzymes, the catalysts of Nature.

This book is primarily a textbook that aims to help students see chemistry from the perspective of the industrial or academic scientist who wants to find new processes for making compounds. To do this it examines and classifies the transformations that organic compounds undergo when catalyzed by metals. Many new and profitable processes based on metal catalyses have been developed by industry. The intellectual stimulus that the study of catalytic reactions has given to chemistry is also reflected in the award of Nobel Prizes to the many who have made significant contributions to the science of catalysis and the role of metal catalysts, for example, Ostwald (1909), Haber (1918), Bergius and Bosch (1931), Natta and Ziegler (1963), Fischer and Wilkinson (1973), Knowles, Noyori, and Sharpless (2001) and, most recently, Chauvin, Grubbs and Schrock (2005). Their contributions range from the development of basic kinetic principles, to high pressure processes, and to new catalysts for hydrogenation, stereospecific polymerization, enantioselective reactions and olefin metathesis.

Ostwald recognized that catalysis was about the interplay of reaction rates, i.e. the fundamental role played by a catalyst to accelerate one kinetic pathway against several other different thermodynamically feasible pathways. Since the catalyst does not appear in the reaction product, catalysis has been to some extent the Cinderella of chemistry: vital, hard-working, but unrecognized. Although in a few cases consumers buy a product that contains a catalyst: the enzymes in detergents, the cerium oxide coating on the walls of ovens, the car exhaust catalyst, or the yeast to make bread, wine or beer – even there the consumers are not buying a catalyst – they are buying cleaner clothes, washed with less electricity, a self-cleaning oven, a car that pollutes less, and the means to make food and drink. Generally, the value of catalysis lies not in the catalyst itself but in the products or effects they produce.

Catalysts and catalysis are fundamental to being able to produce the fuels, polymers, medicines, plant growth regulators and herbicides, paints, lubricants, fibres, adhesives and a vast array of other consumer products. As well as catalysis contributing some 20% to the Gross Domestic Product of the USA, it is also estimated that 80% of all chemicals processes, with a total value of more than US$1800 billion, involve a catalyst at some point.

In 2001 it was estimated that the world merchant market for catalysts was worth ca. US$25 billion, divided roughly equally between refining, petrochemicals, polymers, environmental (20–25% each) and with about 11% being used in fine chemicals. Refining is about the production of fuels (Chapter 3, Box 2), petrochemicals cover many of the basic commodity chemicals and the monomers required for the polymer industries; fine chemicals include pharmaceuticals and agrochemicals, as well as flavours and fragrances; and environmental is about exhaust gas and waste product clean-up. Vehicle catalytic converters use catalysts, as does the production of the main tonnage polymers: polyethylene, polypropylene, polystyrene, polyvinyl chloride and polyethylene terephthalate.

But these catalyst sales figures do not reflect the number of tonnes or the value added by the catalysts in each sector. For example even though the use of catalysts (by volume) are similar for refining and polymers, the annual world production of gasoline in 2004 was about 1 billion tonnes, that of polyethylene was around 50 million tonnes.

Catalysts add value in many ways, ranging from reducing the cost of manufacture to increasing the quality of a chemical product, to the production of novel chemical compounds and to the reduction in environmental emissions. To take one example, the catalytic cracking of crude oil was started by Houdry in 1936 using simple silica/alumina catalysts in a fixed bed; further development of refining technology has not only enabled huge increases in volumes of gasoline fuel obtained from a barrel of oil (now about 50%), but has also led to dramatic quality improvements by increasing the octane rating, while reducing sulfur and aromatics. Processes used to bring this about include fluid catalytic cracking (FCC), isomerization, catalytic reforming, hydrotreating, and hydro-cracking (see Section 3.2).

Catalytic converters (containing precious metal catalysts dispersed on ceramic honeycomb structures that oxidize carbon monoxide and unburnt hydrocarbons to carbon dioxide and water, and reduce nitrogen oxides to nitrogen) are now fitted on more than 85% of new cars, and achieve emission reductions of over 90%.

Catalysis has also resulted in the creation of novel chemical structures, especially in the area of polymers, which give rise to new products and applications, as is discussed in Chapter 7. In 1933 the first polyethylene (PE), a highly branched flexible and soft polymer known as Low Density Polyethylene (LDPE), was made by the free radical polymerization of ethylene in a very high pressure (2000 bar) process. This was followed in the 1950s by catalytic routes to new higher density polyethylene (HDPE), and polypropylene (PP), Sections 7.3.1 and 7.3.2. One of the first contributions to society of the new HDPE was in providing a stiff, light and easy to mould material ideal for the 1958 Hula Hoops craze. Today we may complain about plastic bags littering the streets and plastic waste but the advantages of these light, strong, low cost, easy to manufacture, chemically resistant polymers are numerous – from HDPE pipes which do not rot or corrode underground for our water and gas pipes, to sterile, disposable medical equipment and to lightweight packaging keeping our food fresh whilst reducing freight costs.

Another example of how catalysis plays a key role in enabling our lives is in the synthesis of pharmaceuticals. Knowles's development, at Monsanto in the early 1970s, of the enantioselective hydrogenation of the enamide precursor to L-DOPA (used to treat Parkinson's disease), using a Rh-chiral phosphine catalyst (Section 3.5), led to a share in the Nobel prize. His co-laureates, Noyori and Sharpless, have done much to inspire new methods in chiral synthesis based on metal catalysis. Indeed, the dramatic rise in the demand for chiral pharmaceutical products also fuelled an intense interest in alternative methodologies, which led to a new one-pot, enzymatic route to L-DOPA, using a tyrosine phenol lyase, that has been commercialized by Ajinomoto.

1.1.2 Chemical Processes

Whether the end product is a pharmaceutical or a plastic bag, each industry is part of a value chain. The pharmaceutical company that markets the drug depends on fine chemicals or speciality producers to make the active pharmaceutical or its precursors. In turn, the commodity chemical companies supply the building blocks for the basic fine chemicals, whilst the refiners produce the feedstock for the commodity chemical companies.

If we consider a simplified, four-fold chain involving, 1) refining, 2) commodity (including petrochemicals and polymers), 3) fine (or speciality) chemicals, and 4) pharmaceuticals, the progression from refining to pharmaceuticals, is one of scale and product value – the latter being a consequence of the former. Refining and commodity chemicals are about very large plants, dedicated to one process. They are said to be process intensive: a lot of material is processed in one particular unit and so benefits from economies of scale. As the size of a reactor, for example, increases, the cost of manufacture increases roughly with its surface area. However, its throughput increases with its volume, hence the cost of the reactor per unit of feed is proportional to area/volume i.e. the capital cost only increases to the power of 2/3. In fact the actual value used is to the power 0.6 since manpower and other services do not increase with size. So as the process scale increases, so the product becomes cheaper. A single refinery unit, such as an FCC, can process up to 8 Mt/a. The units are run within narrow limits of feedstock quality and operating conditions. The crude oil feedstock comes literally straight out of the ground with little pre-treatment other than a simple distillation. As a consequence refining processes have huge economies of scale enabling profits to be made on what are sometimes very narrow margins. In addition carbon efficiencies are high, while manpower needs are relatively low, with continuous 24-hour operations. Since the products are rarely pure compounds, but often complex mixtures of hydrocarbons characterized by their boiling point and some simple chemical and physical properties, product separation is usually straightforward.

Commodity chemicals share the same benefits of economies of scale. Typical process units are 1-2 orders of magnitude smaller than refinery units, although large methanol synthesis plants can produce up to several Mt/a (Section 4.7.1). Since a chemically pure material is being produced, often in a stoichiometric reaction, the catalyst system now becomes more specialized, the reactor may require special metallurgy, and product purification starts to be an issue.

The products are not necessarily single compounds. Polymers for example are a range of compounds of varying molecular weights but which are chemically identical. For commodity chemicals the expense of feed purification, a more exotic catalyst, the corrosion resistant metallurgy and the need for a product purification train, start to add cost. But like refinery processes these are dedicated to one product, run 24 hours a day and are part of an integrated complex benefiting from heat and waste recovery. As the cost to build these refinery and petrochemical complexes is many billions of dollars, time is needed to pay back the investment. Once built, both commodity chemical and refinery processes will operate for more than 25 years producing the same product since either the product is well developed serving a large entrenched market, such as gasoline, or because the product has a multitude of uses, such as acetic acid, so that demand is not overly sensitive to the vicissitudes of any particular application. European production capacities of some major chemicals are estimated at, ethylene (24 Mt/a); propylene (17 Mt/a); ethylene dichloride (11 Mt/a); polypropylene, benzene (both 10 Mt/a); HDPE, ethylbenzene, and vinyl chloride monomer (all ca. 7 Mt/a); styrene, urea, and LDPE (all ca. 6 Mt/a); p-terephthalic acid and ester, methanol, and LLDPE (ca. 4 Mt/a). Other production capacities are given in the appropriate chapters; a useful rule of thumb is that world capacity of many chemicals is often around 3 times the European tonnage. Many important commodity chemicals (eg., adipic acid, caprolactam, glycols, acrylates, vinyl acetate) are produced by routes involving oxidation: the impacts of economics on these processes are also discussed in Chapter 2, Sections 2.2, 2.4, and 2.8-2.15.

The fine and speciality chemicals industries span a wide range from the manufacture of well defined, characterizable chemical compounds such as are used in pharmaceuticals, to making compounds which have a critical performance in a defined end-use application for a specific customer, such as inks for ink-jet printers where the design of the printer is closely matched to the performance of the ink. Indeed the manufacture of a catalyst is an example of a speciality chemical in itself.

The scale of production of a fine chemical can range from a few t/a up to tens of kt/a. Two of the final intermediates in the synthesis of the world's top selling drug, the anticholesterol Lipitor®, or atorvastin, are only produced on a scale of 500 t/a each. The consequence of the smaller scale and more specialist nature of these industries, is that the processes are far more likely to be batch or discontinuous. Thus process units will be flexible to produce more than one product and the product's lifetime in the market may be comparatively short, either for economic or performance reasons. However, product added value is high.

The final sector is the pharmaceutical (which can also extend to crop protection and agrochemicals) sector that produces a formulated product, the drug, which contains the Active Pharmaceutical Ingredient, API. Increasingly pharmaceutical companies are contracting out the synthesis of the API to the fine chemicals sector whilst focussing themselves on the drug discovery phase, the drug formulation and clinical trials. The drug formulation takes place using general-purpose equipment of low capital cost, where the emphasis is on quality control, product purity and avoidance of cross-contamination. The cost of production is much smaller compared to the price than in the fine chemicals sector. For the Pfizer drug Lipitor® one estimate puts the price of the drug at 20 times the cost of production of the API. But the R&D and clinical trial costs for the pharmaceutical industry are high and its R&D investment can be compared to the capital investments required in refining and commodity chemicals.

So how do the different characteristics of the various industrial sectors affect what they look for in developing and understanding catalysts, catalysis and catalytic processes, and how do they look for it? The most obvious difference is that as you go from refining to pharmaceuticals you need to spend a lot more money on R&D – both in absolute and relative terms. On average an oil and gas company spends about 1% of its sales on R&D, a purely commodity chemical company about 2.5–5%, a fine chemicals producer around 5–77% whilst the average for the pharmaceutical sector is about 15%. In 2004 among the world's top 700 companies, pharmaceutical/bio-industry companies spent $67 billion on R&D, the commodity chemical companies around $19 billion and the oil and gas industry about $5 billion. Pfizer alone spent $7 billion on R&D, being the second highest of all US industries, only behind Ford.

The reason for these large differences lies in the nature of the sectors. In refining and commodity chemicals more focus goes into improving existing processes. Since they are large scale and often replicated around the world, small improvements in selectivity, yield, heat recovery, catalyst cost or other process efficiencies, reap big rewards. There is relatively little emphasis on products since these are well defined and industry accepted. Due to the high cost of the feedstock as a percentage of the overall cost of production, new lower cost feedstocks are often a source for "step-out" processes. But small increases in process efficiencies can still result from detailed understanding of the kinetics, by-product formation or the catalytic cycles. The long life cycle of the product means that time can be invested to obtain this understanding, and one will get the full lifetime of a patent to protect from the competition. There is more emphasis on purely process improvements in refining, and more on the catalyst and mechanisms in commodity chemicals. This reflects the maturity of the refining processes where sufficient mechanistic understanding has been obtained and catalyst developments are still possible but ever harder to justify.

In the fine chemicals and pharmaceuticals sectors the emphasis is on the product, and getting new products to market as quickly as possible. Once a product is launched, depending on its projected life cycle, there may be little point in optimizing a process which is a smaller fraction of the product value and which may even become redundant within the time needed for further R&D. Fundamental understanding is more applied to new processes to give new products, to reduce the cost of a product to make a competitor's process uneconomic, or to the development of new applications for the product – both to increase its demand and prolong its product life. In the case of pharmaceuticals where quality control is very important, it may be that once a drug is approved, this approval is not only against a chemical structure but also against the process for its manufacture. Thus, any changes in process could require the lengthy and costly process of re-approval.