As discussed in Chapter 2, catalytic reagents (as selective as possible) are superior to stoichiometric reagents. You will no doubt recall from general chemistry that catalysts are substances that increase the rate of a reaction without being used up in the process. You will also recall that before a particular chemical reaction can take place, energy, calledactivation energy, is required to break and form bonds. It represents the thermodynamic energetic barrier that must be surpassed for a reaction to proceed. There are several ways in which a catalyst can lower the activation energy:
. By forming bonds with one or more of the reactants and so reducing the energy needed by the reactant molecules to complete the reaction
. By bringing the reactants together and holding them in a way that makes reaction more likely
Catalysts cannot make energetically unfavorable reactions possible because they have no effect on the chemical equilibrium of a reaction, as the rate of the forward and reverse reactions are affected equally. The net free energy change of a reaction is the same whether or not a catalyst is used; the catalyst just makes it easier to activate, as shown in Figure 6.11.
From the green chemistry/green engineering prospective, catalysts have a series of advantages related to the enhanced efficiency and use of resources, as shown in Table 6.6.
For example, the BHC Company (now BASF) developed a synthetic process to manufacture ibuprofen, a well-known nonsteroidal anti-inflammatory painkiller mar- keted under brand names such as Advil and Motrin. The new technology commercial- ized since 1992, involves only three catalytic steps with approximately 80% atom utilization, replacing technology with six stoichiometric steps and less than 40% atom utilization.
This process provides a great example of an elegant catalytic solution to eliminate large quantities of solvents and waste associated with the traditional stoichiometric use of auxiliary chemicals. Large volumes of aqueous waste (salts) normally associated with such
manufacturing are virtually eliminated. The anhydrous hydrogen fluoride catalyst/solvent is recovered and recycled with greater than 99.9% efficiency, and no other solvent is needed in the process, simplifying product recovery. For its innovation, BHC was the recipient of the Kirkpatrick Achievement Award for “outstanding advances in chemical engineering technology” in 1993 and the EPA’s Green Chemistry Challenge Award for Greener Synthetic Pathways in 1997.25,26
TABLE 6.6 Potential Advantages and Disadvantages of Catalysts from a Green Standpoint
Potential Advantages Potential Disadvantages
Productivity Productivity
Increased yield Reduced cycle time Increased reactor
volume efficiency Increased selectivity
If the turnover number or turnover frequency is too low, the productivity will decrease
Reduced variability
Environment Environment
Elimination or reduction of solvent Reduced by-products
Increased resource efficiency
Catalysts containing heavy metals have a significant impact on the environment if released and not recycled
Safety
Control of exotherms
Can reduce the use of hazardous materials
Reactants
Products Heat of Reaction Activation Energy Uncatalyzed
Reaction
Catalyzed Reaction
Time
FIGURE 6.11 Catalyst effect on activation energy of a reaction. Note that the enthalpy of reaction (energy of products minus energy or reactants) remains unchanged.
Ibuprofen stoichiometric synthesis: Ibuprofen catalytic synthesis:
CH3
H3C
H
CH3
H3C
CH3 O
CH3
H3C Raney nickel
CH3 O
CH3
H3C
CH3 O CH3
H3C
O H3C
CO2C2H5
H5O+
NH2OH CH3
H
Cl COOC2H5 NaOC2H5 AlCl3
H3C
CH3
O
10 9 13
12
11
Step 5 Step 6
Step 4 Step 3 Step 2 Step 1
Step 1
Step 2
Step 3
8 6
5 4
3 2
7 6 5
3 2 1
CH3
H3C
H
HF
H2
1
4
CH3
H3C
CH3
N OH CH3
H3C
COOH Ibuprofen
CH3
CH3
H3C
C CH3
N H
O H H
O H
H3C O H3C
O
O
H3C O H3C
O
O
H
CO Pd
13 CH3
H3C
COOH Ibuprofen
CH3
6.2.1 Selecting Catalyst–Catalyst Efficiency
When selecting catalysts it is important to compare how well the catalyst will perform for the desired reaction relative to the existing chemistry and associated process. The more efficient a catalyst is, the less waste that will be generated in the reaction and the more efficient the use of resources will be. There are several ways to measure catalytic efficiency that are commonly used to compare and select catalysts. In this section we cover several of them.
Catalyst Activity Catalytic activityis a measure of the catalyzed reaction rate per unit mass of catalyst. The SI-derived unit for measuring catalytic activity is thekatal, which is the amount of catalyst that converts 1 mol of reactant or substrate per second under specified conditions (e.g., the reaction rate).27,28For example, trypsin is a natural enzyme found in the digestive system that helps to break down proteins (a serine protease). In recent times it has also been used in numerous biotechnological processes. One katal of trypsin is that amount of trypsin that breaks down 1 mol of peptide (protein) bonds per second under specified conditions. By mode of action, catalysts can be classified as chemical or enzymatic. A biochemical equivalent is theenzyme unit(U), defined as that amount of the enzyme that catalyzes the conversion of 1mmol of substrate per minute at a given temperature, pH, and substrate concentration. Although the General Conference on Weights and Measures has recommended that the katal replace the enzyme unit (U),
biochemistry. Since 1 katal is the amount of enzyme that converts 1 mol of substrate per second, 1 Uẳ1/60mkatalẳ16.67 katal.
Turnover Number and Frequency The degree of activity of a catalyst can also be described by the turn over number (TON) and the catalytic efficiency by the turnover frequency (TOF).TONis defined as the number of synthesized molecules per number of catalyst molecules used (or catalytic sites when talking about enzymes). A different common use of the term in chemically catalyzed reactions is to express the maximum number of times a catalyst may be used for a specific reaction before there is a decay in its activity. In this context, the turnover number for industrial applications is between 106and 107.29
TOFis a mass-independent unit that accounts for the time of conversion, defined as the number of molecules converted by each catalytic site in a unit of time:
TOFẳ ns
tncat
wherensare the moles of converted starting material,ncatare the moles of active sites, andtis the time of conversion (s).30For example, carbonic anhydrase has a turnover frequency of 400,000 s1, which means that each carbonic anhydrase molecule can produce up to 400,000 molecules of product (CO2) per second.
When using TON or TOF to compare catalysts, it is important to provide the specifics of the reaction. For most industrial applications, the TOF is in the range 102to 102, and for enzymatic processes it is from 103to 107. Although biological catalysts generally have higher TOF values than those of chemical catalysts, there is still a need to account for the differences in molecular masses and stability of the catalyst. For example, the Mn–Salen epoxidation and sulfidation catalyst has a TOF of 3 h1, while the chloroperoxidase (enzymatic counterpart) has a TOF of 4500 h1. However, the molecular masses are 635 and 42,000 g/mol respectively.30
Catalyst Selectivity Another important measure of catalyst efficiency is selectivity, defined as the number of molecules synthesized per number of molecules converted:
selectivityẳsẳnpnp0
ns0ns ns
np
wherenprepresents the moles of product at the end of the reaction,np0the moles of product at the beginning of the reaction,nsthe moles of starting material at the end of the reaction,ns0 the moles of starting material at the beginning of the reaction, and np and ns are the stoichiometric factors for the product and starting material, respectively. For a catalyzed reaction, the reaction yield would be the product between selectivity and conversion. In other words, selectivity is an indication of the accuracy of conversion to the product desired, and it therefore needs to be as close to unity as possible, to avoid waste. For example, a selectivity of 99.99% means that the catalyst renders one undesired product in 10,000 conversions. This is the performance achieved by enzymes in living systems, although most enzymes do better than this. Few synthetic industrial catalysts achieve this degree of control over the chemistry they catalyze. For example, Table 6.7 shows the selectivities of several zeolite catalysts for the isopropylation of naphthalene.31
Catalyst Stability Chemical, stability, temperature, and in the case of a heterogeneous catalyst, mechanical stability are important factors in the selection of a catalyst. A way to express the chemical stability of a catalyst is via the deactivation rate and half-life. The deactivation ratemeasures the loss of a catalyst activity per unit of time (s1), and the half- life is the time (s) in which the catalyst activity is halved.
Example 6.4 For the production of methyl propanoate via the methoxycarbonylation of ethene:32
CH3OH + CO + CH2 CH2 H (CH2CH2C)n O
OCH3
Recently there have been several reports of results using palladium-complexed catalysts.
One of these complexes was reported as being capable of converting ethene, CO, and MeOH to methyl propanoate at a rate of 50,000 mol of product per mole of catalyst per hour with a selectivity of 99.98% under relatively mild conditions (80C and 10 atm combined pressure of ethene and CO). Another catalyst has now also been operated under steady-state conditions for extended periods, giving total turnover numbers for palladium in excess of 100,000, with similar selectivity.
Additional Points to Ponder The same source reports TOF data for a second catalyst as being on the order of 12,000 mol of product per mole of catalyst per hour when operated in a batch mode. Why does the continuous process appear significantly more efficient than the batch process?
6.2.2 Selection by Types of Catalysts
Catalysts can be classified by several criteria, including their state of aggregation, their structure, their area of application, and their composition. A simplified general classification is given in Figure 6.12.
Heterogeneous and Homogeneous Catalysts When classifying catalysts by their state of aggregation, they fall into two classes, known as heterogeneous or homogeneous.
Homogeneous catalysts are part of reacting systems in which reactant and catalyst are in the same state, most commonly liquid. Examples of homogeneous catalysts include liquid-phase acid or basic catalysts and transition metal complexes in solution. The most TABLE 6.7 Selectivities of Natural Zeolite Catalysts for the Isopropylation of
Naphthalene
Product Distribution of Diisopropyl Naphthalene (%)
Catalyst 1,3- 1,4- 1,5- 1,6- 1,7- 2,6- 2,7-
HY 23.7 0.6 0.2 6.8 4.9 32.6 31.2
HL 39.9 7.9 6.7 15.3 16.3 6.7 7.2
HM 5.3 3.8 1.9 7.1 6.1 50.8 24.9
important industrial application of homogeneous catalysts is for the oxidation of hydrocarbons with oxygen or peroxides. Industrial processes using homogeneous catalysts include hydroformylation (with reported annual capacities of 2000 to 3000 tons), hydrocyanation (DuPont), acetic acid (Eastman Kodak), acetic acid anhydride (Eastman Kodak), Indenoxide (Merck, at an annual scale of about 600 kg), and the oxo synthesis, among others.
Heterogenous catalysts are generally solids (or supported on a solid framework or backbone), and the reactants are in either the liquid or gas phase. Examples of heteroge- neous catalysts include metal oxides, transition metal catalysts, zeolites, or acid catalysts supported on a solid. Heterogeneous catalysts are by far the most important class of catalysts on the market. The market share of homogeneous catalysts is estimated to be only about 10 to 15%.
Example 6.5 Scientists Vladimir Dioumaev and Morris Bullock of Brookhaven National Laboratory in New York have developed a tungsten-based catalyst that facilitates a reaction and then easily separates out from the product and can be reused.33 This homogeneous catalyst is initially dissolved in the ingredients and then begins to form oily clumps as the reaction progresses, to precipitate finally as a solid. They have focused on reactions that create alkoxysilanes-a common ingredient in ceramics and in organic compounds used in agriculture and pharmaceuticals:
R′ R C
O O
catalyst C + HSiEt3
SiEt3 R′ RH
In this reaction system they exploited the fact that a charged, or polar, catalyst would be soluble in the initial polar solvent but not in the nonpolar product. They created a catalyst that remained soluble and kept working until the very end of the reaction, when all of the ingredients had been used up. They used compounds that tend to form an oily mass in a nonpolar solution before separating out.
CATALYSTS
Homogeneous
Heterogeneous Bulk
Supported Chemical
Enzymatic
By state of aggregation By mode of action
Biocatalysts (enzymes)
FIGURE 6.12 General classification of catalysts.
Additional Points to Ponder Why is this discovery important from a green chemistry/
green engineering perspective?
Chemical Catalysts There are many varieties of chemical catalysts, and they are used for a vast range of industrial applications. Some of the types of elements and chemicals commonly used in catalysts are given in Table 6.8.
Industrial processes that are run with catalysts include selective oxidations, alkane activation, stereo and regioselective synthesis, alkylation reactions, olefin polymerization, and others.
The most widely used catalysts are for acid-catalyzed reactions and are based largely on inexpensive Brứnsted and Lewis acids, such as sulfuric acid, hydrogen fluoride, and aluminum chloride. These can be used for very diverse types of chemistries. A statistical survey looking at industrial applications of solid acid–base catalysts was completed in 1999 and found 127 industrial processes using either solid acid, solid base, or solid acid–base catalysts (Figure 6.13), with 81% of these processes using solid acid catalysts, 8% solid base catalysts, and 11% bifunctional solid acid-base catalysts. The survey also found that 180 TABLE 6.8 Examples of Types of Chemicals Used in Catalysis
Catalyst Types of Reactions Examples
Metals Hydrogenation Fe, Ni, Pt, Ag, Ru, Rh, Os
Dehydrogenation
Metal oxides Oxidation NiO, ZnO, Al2O3, SiO2, MgO
Dehydration
Acids Polymerisation H3PO4, H2SO4, SiO2/Al2O3, zeolites Isomerisation
Cracking Alkylation
20 15
10 5
0 MTBEi-C04 Disproportionation
Esterification Hydrocracking Hydrogenation MTG/MTO processes Oligomerization and polymerization Aromatization Hydration Cracking Amination Etherification Alkylation Isomerization Others Dehydration and condensation
FIGURE 6.13 Industrial processes using acid–base catalysts.
different types of catalysts were being used at an industrial level, with zeolites being the most used catalysts in industry, followed by oxides, ion-exchange resins and phosphates (Figure 6.14).34
Example 6.6 Cumene is produced from propylene and benzene. The total worldwide production capacity of cumene is about 6 million tons/year. The conventional processes use solid phosphoric acid (SPA) or aluminum trichloride as catalysts. SPA production is still heavily predominant.
+ CH
2 H2C
CH2 H2C catalyst
Several companies have been involved in the development of new zeolite-based processes. The Mobil/Badger cumene process uses a novel zeolite catalyst developed by Mobil that offers higher yield and product purity than the traditional processes while eliminating problems with corrosion, catalyst handling, and disposal, such as significant amounts of acid waste. The pilot plant results show a 100% propylene conversion and nearly 100% selectivity in the alkylation reactor over a period of 5000 h of operation. Dow has also commercialized its process using a novel dealuminated mordenite with a pseudo-three- dimensional structure.34
Additional Points to Ponder Even after the process improvements with the catalytic process, are there any concerns with regard to the cumene route? Would it be possible to produce cumene from another source besides benzene?
0 10 20 30 40 50 60 70
Oxides, Zeolites
complex oxides
Ion-exchange resins
Solid acids Phosphates
(not specified)
Immobilized Clays
enzymes Sulfate, carbonate
Sulfonated polysiloxanes
FIGURE 6.14 Type of catalysts used in industrial processes.
Example 6.7 Ethyleneimines are important chemicals commercially for the production of pharmaceuticals, coatings, and textiles. Ethyleneimine has been produced by the dehydration of monoethanolamine (MEA) in the liquid phase using sulfuric acid and sodium hydroxide (the Wenker process).
The Wenker process has very low mass productivity, however, and produces large amounts of sodium sulfate waste (4 kg/kg ethyleneimine). The vapor-phase process using solid acid–base catalysts is more efficient than the Wenker process, provided that the formation of undesirable by-products (e.g., acetaldehyde, piperidine, acetonitrile) is mini- mized. A new catalyst has been developed by Nippon Shokubai35with 86% conversion of monoethanolamine and 81% selectivity for aziridine. A plant with a capacity of 2000 tones/
yr has been onstream since 1990.
MEA (liquidphase)
solidcatalyst (vaporphase)
El OH H2SO4
H2N
OSO3H H2N
N H H2SO4
Additional Points to Ponder How could the formation of by-products in the vapor-phase process be minimized or eliminated? What are the implications of the equipment and plant layout in the vapor-phase process?
Phase-Transfer Catalysts In a heterogeneous system phase-transfer catalysts (PTCs) facilitate the migration of an insoluble reactant from one phase into another phase by making the reactant soluble in both phases. These type of catalysts are often quaternary ammonium salts. The importance of PTCs to green chemistry and engineering is that these types of catalysts have the potential to dramatically increase reaction rates and thereby reduce the overall process energy requirements and energy-related emissions. They can also increase the specificity of a reaction system, reducing waste in general. PTCs are generally nontoxic, and they enable the use of less toxic solvents as substitutes for dipolar aprotic solvents such as dimethylformamide or facilitate the use of liquid reactants as solvents. In general, all these factors contribute to process efficiency and improve process design in terms of equipment size and process simplification. Some of the reactions and applications of PTCs are shown in Table 6.9.
There are many examples of PTC applications that have been commercialized. Following are a few examples of PTC applications.
Example 6.8 The synthesis of 2,6-diisopropylphenyl [(2,4,6-triisopropylphenyl)acetyl]- sulfamate, a pharmaceutical agent investigated in the treatment of high cholesterol and arteroesclerosis, initially required the production of 2,4,6-triisopropylbenzyl cyanide as an intermediate for the synthesis. The original synthesis included the use of dimethyl sulfoxide:36
Cl
LiAlH4, Et2O 98%
O
OH
CN Cl
NaCN, DMSO 80–85%
SOCl2,
toluene 95–98%
As part of the development work, phase-transfer catalysis chemistry was used for the cyanation step, with tetra-n-butylammonium bromide (1.5% by weight) in a solution of toluene and water. Water had the added benefit of being a safer medium for both the handling and disposal of cyanide:
Cl CN
NaCN, H2O,toluene Bu4NBr
The reaction was essentially quantitative, generating only trace amounts of new impurities. The reaction proceeded quickly and exhothermically, but the exotherm was controlled through the rate of mixing instead of by stepwise cyanide addition. The reaction can now be run with high throughput and a reduction of sodium cyanide from 1.7 to 1.05 equivalents, decreasing the need to treat and handle cyanide-containing waste. The final product was sufficiently pure that the separate isolation, drying, and purification steps used were no longer necessary, enabling the toluene solution to be used directly in the hydrolysis step.
Additional Points to Ponder Why is the reduction of sodium cyanide important? What are the implications of not having to perform the isolation steps required in the original reaction?
Biocatalysts Enzymes or biocatalysts have increased in importance in recent years because they have extremely high selectivities and activities. In addition, they function under mild conditions: normally at room temperature, in aqueous media, and with a pH close to 7. Biocatalysts are generally more efficient than their chemical counterparts; for example, enzymes exhibit turnover numbers on the order of 100,000 s1in comparison to values of
about 1 s1for chemical catalysts. This increased efficiency has direct green chemistry/
green technology implications given:
. The potential for using materials from renewable sources in the production of commodity and fine chemicals
. The potential reduction of waste and increased mass efficiency due to their unsur- passed enantio- and regioselectivity
. The elimination or reduction in the use of hazardous materials and reagents
. The possibility of running the reactions under mild conditions of temperature, pressure, and pH
TABLE 6.9 Applications of Phase-Transfer Catalysts Commercial
Applications of Phase-Transfer
Catalysts Reactions Benefits
Polymers O-Alkylation (Etherification) Improved mass and heat transfer Agricultural chemicals N-Alkylation
Pharmaceuticals C-Alkylation and chiral alkylation
Improved control of residence time and temperature distribution
Monomers S-Alkylation
Reduced solvent use
Additives Dehydrohalogenation
Reduced work-ups Flavors and fragances Esterification
Possibility of higher selectivity, yield, and quality
Dyes Displacement with cyanide
hydroxide, hydrolysis
Linear scale-up (larger-scale vortex mixers will yield the same results given that the residence time and flow velocities used at lab level are matched)
Explosive Fluoride thiocyanate,
cyanate
Faster development of new processes or substances
Surfactants Iodide sulfide, sulfite Continuous operation of traditional batch processes
Petrochemicals Azide nitrite, nitrate Commodity, specialty
and fine chemicals
Other nucleophilic, aliphatic and aromatic substitution Oxidation
Epoxidation and chiral epoxidation Michael addition Aldol condensation Wittig
Darzen’s condensation Carbene reactions Thiophosphorylation Reduction
Carbonylation HCl/HBr reactions Transition metal cocatalysis