Ind. Eng. Chem. Res. 1994,33,
2887-2899
2887
Catalysis for Environmentally Benign Processing? Christopher B. Dartt and Mark E. Davis' Chemical Engineering, California Institute of Technology, Pasadena, California 91125
A short overview of the types of catalytic processes that have shown progress in creating clean technology and are likely through continued material improvements to lead to new environmentally benign processing is presented. Chemistries involving solid acidhase catalysis, clean oxidation catalysis, catalysis in water, and asymmetric catalysis are discussed. Suggested reactions and catalytic materials for future clean processing are enumerated and unifying concepts for implementing catalysis for environmentally benign technologies are outlined.
Introduction Environmentally benign processing has been and will continue t o be a primary goal for all industries that produce chemicals whether they be commodity or specialty, e.g., styrene or ibuprofen, respectively. According to statistics compiled by the Chemical Manufacturers Association the industry as a whole decreased emissions to air, water, and land by 41% between 1987 and 1991 while production levels increased by more than 10% (Amato, 1993). However, not all of these reductions were voluntary or due to economic factors. In addition to the economic incentives for creating clean processing, environmental legislation, e.g., HF regulation in California is now in many cases the primary motivating factor for new technologies (Cusumano, 1992). Catalysis in principle is environmentally benign in that the ultimate goal is to convert a given set of molecules into another with near 100% selectivity. If this is done in the absence of a solvent and the catalyst never deactivates, then catalysis would always provide benign processing. However, the real world is not so perfect and even in the rare case of high selectivity, solvents are typically needed and deactivation does occur. Thus, one can only attempt to design and develop catalytic processes that minimize wastes and energy consumption. A good example of how catalytic processing can minimize the formation of byproducts is illustrated in Figure l. The new, completely catalytic Hoechst route to ibuprofen significantly decreases the number of reaction steps and byproduct formation. Although chemical manufacturers are doing well in reducing emissions of all forms, the data in Table 1 illustrate that all segments of the petrochemical industries should be capable of decreasing the amount of byproducts formed. Of the inorganic and organic wastes produced, the primary byproducts formed in terms of tonnages are inorganic salts. For example, the processes illustrated in Figure 2 demonstrate the reduction of inorganic byproducts in the production of hydroquinone through catalytic technology. Additionally, as we look to the future, the problem of COa release will most likely come to the forefront of discussions on environmentally benign processing. In this paper we provide a short overview of the types of catalytic processes that have shown some progress in creating clean technology and are likely through continued material improvements to lead to new environmentally benign processing. Our goal is to discuss Paper presented at the Symposium on Catalytic Reaction Engineering for Environmentally Benign Processes, San Diego ACS Meeting, March 13-18, 1994. * To whom correspondence should be addressed.
0888-5885/94/2633-2887$04.50/0
I
CHCH=NOH
Ibuprofen
Figure 1. Two routes to ibuprofen. Notice that the Hoechst route only involves catalytic steps. Adapted from Sheldon, 1992.
Table 1. Wastes Produced by Various Industrial Sectors' industry segment oil refinery bulk chemicals fine chemicals pharmaceuticals
A, kg of byprodud kg of product -0.1 1-5 5-50 25 100
-
B, product (tons) 106-108
104-106
102-104 10-103
s u m of AandB
105-107 104-106 io2 105 102 105
--
Adapted from Sheldon, 1992.
catalysis as technology for primary prevention, i.e., does not pollute, rather than secondary prevention, i.e., cleanup. We will cover chemistries involving solid acid base catalysis, clean oxidation catalysis, catalysis in water, and asymmetric catalysis. The first three subjects will concentrate on systems that yield reductions in byproducts whether they be unwanted side products of the main reaction, spent catalysts, or used solvents. The final topic will deal with minimizing what we will call biological pollutants, i.e., enantiomers that do not show the desired biological response. Our hope is that through these illustrations, we can highlight the classes of problems currently being encountered and give specific examples of how success has occurred. We will 0 1994 American Chemical Society
2888 Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 CATALYTIC
n I
F&CI
Figure 2. Two routes to hydroquinone. Adapted from Sheldon, 1990.
close by suggesting reactions and new types of catalytic materials that would have a large impact on environmentally benign processing if they could be accomplished or prepared, respectively, and by outlining unifying concepts in the implementation of catalysts for environmentally benign processing.
Catalysis by Solid Acids and Bases Numerous processes involve the use of acids and bases as catalysts. However, there are a variety of environmental problems associated with using liquid acidshases. Typical liquid acids include H2S04, H3P04, and HF. Additionally, nonregenerable Lewis acids, e.g., BF3, AlCl3, are used in the liquid phase. Although high reaction activities and selectivities are commonplace, the use of organic solvents and dealing with used acidcontaining solutions are two major problems with liquid acid catalysts. The same issues are relevant with liquid base catalysts. A good example of the problems associated with liquid acidhase catalysts is the production of gasoline alkylates from isobutane and butenes. A typical alkylation plant of 10 000 barreldday capacity requires 400000 lbs. of anhydrous HF (Cusumano, 1992). Although the HF can be recycled, it is highly toxic and extremely corrosive. Because of the toxicity problem, California is phasing out HF alkylation. Cusumano suggests that many foresee the complete phaseout of HF within the next decade (Cusumano, 1992). Alternatively, H2S04 can be used to produce gasoline alkylate. However, large amounts of spent acid must be continuously removed. It is speculated that if a safe catalyst, e.g., a solid acid, could be used to perform the alkylation, then the current worldwide capacity of approximately 1.5 million barrelslday (Cusumano, 1992) could be significantly increased. This is because Clean Air Act amendments are directed toward decreasing aromatics and olefins. The loss of octane number by the removal of aromatics and olefins could be compensated for by the addition of alkylate, but manufacturers
are not willing to do so until an environmentally acceptable process is available to replace HF/HzS04. Acids. The desire to replace mineral acids and/or nonregenerable Lewis acids, i.e., metal halides, by solid acids has motivated an enormous amount of research. Solids such as mounted mineral and metal halide acids, metal oxides, zeolites, supported heteropolyacids,cation exchange resins, etc., have been investigated for many years (Tanabe, 1970; Chen et al., 1989; Tanabe et al., 1989; Jacobs and Martens, 1991; Maxwell and Stork, 1991; Holderich and van Bekkum, 1991; Holderich, 1993). Progress has been achieved in the use of solid acids as commercial catalysts and many of the newer applications have been nicely reviewed by Holderich (1993). Here, we discuss only the use of zeolites as solid acid catalysts since they have a proven record in creating reaction chemistries that improve environmental processing issues and the future for their increased usage appears high. Zeolites have long been known as solid acid catalysts. A short review of zeolites and molecular sieves is available (Davis, 1991) and numerous other references can be found in the review. Zeolites are ideally suited to create environmentally benign processes because (i) they can perform shape-selectivecatalysis to yield ultrahigh reaction selectivities, (ii)they have a high number density of active sites giving high reaction rates, (iii) they can be regenerated, and (iv) their disposal is not an environmental issue since they are natural materials as well as synthetic. A good example of how zeolite catalysis has already had an impact on primary prevention of pollutants is the synthesis of ethylbenzene from benzene and ethylene. Ethylbenzene is generally manufactured by the alkylation of benzene with ethylene using either Lewis acids, e.g., MC13(Friedel-CraRs chemistry) in the liquid phase or with mounted Hap04 or BF3 in a gas-phase process. With Friedel-Crafts catalysts, approximately 1ton of AlC4 is required for the production of 100 tons of ethylbenzene (Weissermel and Arpe, 1978). Likewise, the former Shell process that employed the UOP BFd A1203 catalyst produced 500 tons/year of solid waste and 800 tons/year liquid waste (water saturated with benzene) per 390 000 tons/year of ethylbenzene (vanBekkum, 1993). However, the new Mobil-Badger process that uses H-ZSM-5 as the catalyst produces 35 tons/ year solid and 264 tons/year of liquid wastes for the same amount of ethylbenzene synthesized (van Bekkum, 1993). In addition to the dramatic reduction in wastes for the ZSM-5 based process, this high temperature (-370 "C)vapor-phase synthesis allows for efficient energy recovery (AH= -27 kcal/mol). Thus, the zeolitebased, Mobil-Badger process is a proven step in the commercial movement to implement more environmentally benign processing. Like the ethylbenzene synthesis, new alkylation technology is necessary for other segments of the benzene derivative market in order for it to become more environmentally friendly. A recent discovery by workers at Dow is one of the next major steps in new alkylation technology (Meina et al., 1992). Cumene is an important benzene derivative that is used in the production of phenol and acetone and its worldwide production is quite large. Cumene is currently synthesized by either liquid-phase processes, e.g., using H2S04, MCl3 or HF, or gas-phase processing, e.g., using H3POdSi02. As pointed out by Meina et al. (19921, the extreme corrosiveness of hc13 streams and their dis-
Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 2889 posal can present environmental problems while the HsPOdjSiO2 catalyst is prone t o leaching of H3P04 and also presents a catalyst disposal problem. Thus, these workers have developed a new mordenite-based catalyst for the vapor-phase synthesis of cumene. Like the ZSM-5-catalyzed process for ethylbenzene synthesis, the mordenite-based conversions produces a technology for cumene synthesis that is significantly more environmentally benign than the current liquid- or vapor-phase processing. Although zeolite-based solid acid catalysts show great promise for creating numerous environmentally acceptable processes, we believe that their use as solid superacid catalysts is not one of them. A superacid is an acid that exhibits an acid strength greater than 100% HzS04 (Hammett acidity function Ho < -12). Although zeolites can show acid strengths that qualify them as superacids, the number density of superacid sites is generally quite low. Additionally, the fact that these sites are contained within micropores will limit their access to large molecules and will also most likely cause high deactivation rates due to hydrocarbon deposition. Thus, zeolites are not likely to replace liquid HF and/ or H&04 for gasoline alkylation processing (vide supra). The need for a solid superacid catalyst that can be regenerated and is of reasonable cost continues to increase. Solid superacids to replace HF, H2S04, and SbF5 based catalysts are highly desired for environmental as well as safety issues. Currently, sulfated oxides and heteropolyacids show promise as solid superacids. Misono and Okuhara (1993) recently reviewed the progress on heteropolyacids and have reported that these catalysts can act as solid superacids (Ho -13, -14). To date, sulfated zirconia is the strongest solid superacid with HO = -16. Although sulfated oxides such as ZrOz/S042- and Fe~03/S04~are low cost, easily prepared materials, their low stability and reactivity to water have proven to be somewhat detrimental to commercial application. However, workers at Sun Oil Co. have recently reported the preparation of the most active, nonhalide, superacid catalyst (Hsu et al., 1992). Hsu and co-workers synthesized sulfated ZrO2 that is promoted with iron and manganese. This catalysis is able t o isomerize n-butane to isobutane at room temperature and do so with an activity that is approximately 3 orders of magnitude greater than sulfated zirconia. Additionally, the catalyst can be regenerated by calcination in air. We investigated these remarkable claims and have been able t o show that they are indeed true (Jatia et al., 1994). Thus, we believe that the materials first produced by Hsu et al. will stimulate much further work in the area of sulfated oxides as catalysts for liquid superacid replacement. Bases. Many of the same problems that are discussed above for liquid acid catalysts hold true for liquid base catalysts as well. For example, NaOH and/or KOH catalyst solutions have to be neutralized prior to release. Thus, large amounts of salts are formed. As with acid catalysis, a reasonable number of solid base catalysts have been investigated and include alkali metal oxides, alkaline earth metal oxides, anionic exchange resins, zeolites, transition metal oxides and solid superbases such as Na/NaOWAl203 (Tanabe et al., 1989; Holderich, 1993). In general, much less research has been carried out on solid base catalysts than with solid acid catalysts, and thus, there are many opportunities for exploration in the use of solid base catalysis.
-
CH3, CHj'
NH+CaO
-
Ca2'
0'. CH2 = CH - CH = CH2
Figure 3. Base-catalyzed reaction of an amine with butadiene.
As is well-known, base-catalyzed reactions produce reaction selectivities quite different from acid-catalyzed pathways. For example, the acid-catalyzed alkylation of toluene with methanol gives xylenes while the base catalyzed products are styrene and ethylbenzene. A particularly interesting example of base catalysis is illustrated in Figure 3. Primary and secondary amines can be reacted with conjugated olefins over CaO to give secondary and tertiary amines (Holderich, 1993; Hattori, 1993). Obviously, this reaction could not proceed in the presence of an acid because of the strong interaction with the basic amine. At present there are several solid base catalyzed processes that are commercialized (Holderich, 1993). In the area of solid superbase catalysis, Sumitomo Chemical Co. appears t o be the leader (Holderich, 1993). These superbases are typically of the form M/MOW A 1 2 0 3 where M = Li, Na, K, Rb, or Cs, and they are quite sensitive to moisture and COS. Additionally, if any leaching occurs, then the contaminated solutions are highly corrosive. Thus, there is room for continued efforts to synthesize new, solid, superbase catalysts. As in the section on acid catalysis, we discuss only one class of new solid base catalysts that appear to show great promise for creating environmentally benign processes. Zeolites are inherently acid catalysts since their anionic framework can charge balance H+ ions. However, if alkali metal cations such as K+, Rb+,or Cs+ are exchanged into zeolites, they reveal base catalysis. Although the ion exchanged zeolites can serve as solid base catalysts, their activities are in general not very high. Hathaway and Davis (1989a,b,c,) synthesized zeolite-supported cesium oxide clusters and showed that these robust catalysts had activities equal to or in excess of other well-known base catalysts, e.g., MgO. These zeolite-supported clusters have many of the desired features for an environmentally benign solid base catalyst, e.g., shape-selectivity, regenerability, nonbiohazard upon disposal with no required neutralization. Subsequent work by Kim et al. (1994) revealed that these materials are solid superbases. In fact, Hattori and co-workers have shown that the catalysts first prepared by Hathaway and Davis are capable of isomerizing 1-butene at 0 "C while no other alkali metal oxides or hydroxides are capable of doing so (Tsuji et al., 1991; Tsuji et al., 1993). Hattori and co-workers and Brownscombe and co-workers (1990,1991) have extended the concepts of Hathaway and Davis t o include intrazeolite alkaline-earth clusters. Additionally, Brunel and coworkers (Laspbras et al., 1993; Rodriguez et al., 1993) have used results from C02 temperature-programmed desorption to suggest that the intrazeolitic cesium oxide is in fact isolated Cs20 species. Rodriguez et al. (1993) showed that these catalysts are capable of performing the Knoevenagel reaction of benzaldehyde and ethyl cyanoacetate. Thus, the potential for using zeolite-
2890 Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994
CI2 + CH3COCH)
csz
2NH3
t
-
NHZCSS"4 Srcp 2.
NH#X~CHZOSQH+ 2 NnOH
-
CH2
- CH2+ Na2S04 + 2 H20
'HN'
HS
(3 +
NaOH
/ +
Oz
+
H - 0
t
1
-o--
MI-
HzO
N.S
0 : baseskc
(4-Mn
Figure 4. (A) Industrial route to 4-MT. (B)New Merck route to 4-MT. From Gortsema et al., 1992b.
supported oxide clusters in environmentally benign, solid base catalysts appears rather high. A very recent important example of a new environmentally sound process that involves a solid base catalyst has been reported by workers at Merck and Co. (Gortsema et al., 1992a,b). The compound 4-methylthiazole (4-MT) is an intermediate in the synthesis of thiabendazole, which is used as a systemic fungicide (Gortsema et al., 1992b). The current industrial route to 4-MT is shown in Figure 4 and involves numerous steps that use hazardous chemicals. Gortsema et al. report a new environmentally sound method for preparing 4-MT (see Figure 4) that involves the use of a zeolite catalyst to perform a base-catalyzed reaction. Cesiumloaded ZSM-5 gives excellent activity, selectivity and lifetime for the synthesis of 4-MT from the imine and SO2. Also, the catalyst has been prepared as extrudates and has been investigated through full scale pilot plant studies (Gortsema et al., 1992b). There are three important features of this work: (i) a zeolite catalyst is used for the production of a pharmaceutical, (ii) the zeolite performs base catalysis, and (iii)the new process is environmentally sound. Acid-Base Bifunctionality. To reduce processing steps, bifunctional catalysts can sometimes be prepared. It is common to combine an acid function with a hydrogenation function (metal) but it is rare to be able to create bifunctional acid-base catalysts. However, this is another area for which there is great opportunity for new materials preparation. We will describe only one example of where a solid acid-base bifunctional catalyst has been synthesized and shown to make a significant environmental impact since the number of examples is extremely low. Ethylenimine is mainly converted to polyethylenimine which is used in the paper industry; however, it is also useful as an intermediate for other syntheses including pharmaceutical intermediates (Holderich, 1993). Ethylenimine is toxic, so storage and transportation is not
Figure 6. (A) Old industrial route to ethylenimine. (B)New Nippon Shokubai route to ethylenimine. From Hattori, 1993.
desirable. Thus, it should be synthesized immediately prior to its further conversion. Typically, ethylenimine is synthesized as illustrated in Figure 5 (Weissermel and Arpe, 1978). In this process, HzS04 and NaOH are used, and about 4 tons of NazSOdton of ethylenimine are produced (Holderich, 1993). Additionally, a Dow process for producing ethylenimine involves reacting 1,2-dichloroethane with NH3 in the presence of CaO to give ethylenimine, water, and CaClz (Weissermel and Arpe, 1978). Again, large amounts of unwanted salt, CaC12, are produced. Recently, Nippon Shokubai has developed a new, solid, acid-base bifunctional catalyst for the synthesis of ethylenimine and a commercial facility has been in operation (2000 tons/year) since 1990 (Ueshima, 1993 and Holderich, 1993 and references therein). The catalyst is a Si/Cs/P mixed oxide. Since ethanolamine has two strong functional groups, two weak sites on the catalyst surface are necessary in order to inhibit undesirable byproducts. Figure 5 illustrates a proposed reaction cycle (Hattori, 1993 and references therein). Using this solid, weak acid-weak base bifunctional catalyst, salt wastes are eliminated.
Catalytic Oxidations Catalytic oxidation is important to both the bulk and fine chemical industries. For example, governmental regulations now require the addition of oxygenated compounds to gasoline in certain urban areas in order to reduce emissions. Also, smaller volume, higher value products such as pharmaceutical intermediates often require the stereoselective addition of oxygen to form alcohol and ketone functional groups. Traditionally, oxidation chemistries have been environmentally detrimental. Even though oxygenated products are often produced in much smaller volumes than most bulk petrochemical products, the ratio of the volume of byproducts to the volume of desired products is generally large for traditional oxygenations. The byproducts
Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 2891 Table 2. Oxygen Donors" (Bu= Butyl, Ph = Phenyl) molecule MN02 PhIO HzOz t-BuOOH NaOCl KzCrz07 KMn04
w t % active oxygen
byproduct MnO PhI H2O t-BuOH NaCl Crz03 MnO2
18.4 7.3 47.0 17.8 21.6 21.8 20.2
Adapted from Sheldon, 1993.
Scheme 2. Wacker Oxidation of Ethylene to Acetaldehyde CzH4
+
PdC12
+
H20
+
Pdo ZCUCI~ CuzC12 + 2HCI + '/zOz C2H4
+
'/&
-
-CHsCHO
+ Pdo + 2HCI
PdC12 + C U ~ C I ~ PCUCI2 + H20
(i) (2) (3)
CH3CHO
(4)
Scheme 3. Catalytic Oxygen Transfer; M = Metal, L = Ligand (Adapted from Sheldon, 1993)
Scheme 1. Autoxidation Mechanism
+ M"+ R02H + M("+')+ R02H R02*
+
R*+
02
RH
-
M("+')+ Mn+
+
+
R02*
ROO
R* + RO2H ROz*
+
+ H+ HO-
(11 (2)
(3) (4)
result primarily from the oxidant and poor selectivity to the desired product. These two points are discussed in detail below. The choice of oxidant is an extremely important issue. Until recently, cost has been the main criterion used in the choice of the oxidant. Molecular oxygen is the obvious winner due to its low cost and simplicity. It is also the cleanest of all oxidants from an environmental standpoint. Table 2 lists several other oxygen donors. Classical stoichiometric oxidants such as dichromate, permanganate, and manganese dioxide have been favorites with synthetic organic chemists for over 100 years. These oxidants are used without a catalyst and are converted to their corresponding salts after reacting. Environmental legislation is now making the disposal of large amounts of hazardous salts difficult and costly. Alkyl hydroperoxides have been used extensively for catalytic oxidations over the past 40 years. The byproducts from these oxygen donors are alcohols. If these alcohols can not be used in other downstream processing, they must be disposed of, thus creating their own environmental waste problem. The most promising oxidant (other than dioxygen) is hydrogen peroxide (H202). The byproduct from H202 is water. If H202 can be used as an aqueous solution, it does not pose the handling problems associated with concentrated peroxides. These two facts alone give H202 (as) great advantages in terms of environmental costs. Classes of Catalytic Oxidation. There are three basic types of catalytic oxidations. The first involves only the use of molecular oxygen while the remaining two typically use a peroxide or hydroperoxide as oxidant. The reaction mechanisms that occur with stoichiometric oxidants will not be discussed here; many excellent references exist on the use of these oxidants (Lee, 1980; Rinehart, 1973). Free-radical autoxidation initiates by the formation of radicals through the cleavage of a peroxide or hydroperoxide and proceeds by using dioxygen as the oxidant. As is implied in Scheme 1,the oxidation is not directed to occur at any specific carbon atom. This type of process does indeed demonstrate poor selectivity and is typically used with simple substrates containing one reactive site (Sheldon, 1991). Molecular oxygen is certainly the oxidant of choice as has been mentioned previously. However, it is not without its difficulties (Sheldon, 1990). First, dioxygen has a triplet ground state, so that its reaction with most organic molecules is a spin-forbidden process. Therefore, although these reactions are thermodynamically favored, they normally reveal high activation barriers
and once underway go to the thermodynamically most favored products, i.e., carbon dioxide and water. Second, the primary oxidation products, e.g., alcohols, epoxides, aldehydes, are generally more easily oxidized than the parent hydrocarbon. Third, dioxygen is usually indiscriminate, i.e., shows little chemo- or regioselectivity. The exception to these comments is the enzymatic oxidations of hydrocarbons with dioxygen which can be chemo-, regio-, and enantioselective. The other two families of oxidation reactions can be illustrated through examples involving olefin oxidation. One of these is the oxidation of a substrate that has coordinated to a catalytically active metal ion. The classic example of this pathway is the Wacker Process. Since 1894 it had been known that acetaldehyde could be produced from ethylene and oxygen using stoichiometric amounts of palladium chloride (reaction 1, Scheme 2) (Parshall and Ittel, 1992). It took another 60 years t o realize that the addition of small amounts of CuC12 could reoxidize the PdO to Pd2+(reactions 2 and 3, Scheme 2). The reoxidation of the palladium allows the expensive metal salt to now operate catalytically as is shown in reaction 4, Scheme 2. While the catalytic process has obvious benefits over a stoichiometric one, it is not entirely environmentally benign. Chlorinated organic waste byproducts are formed, and their disposal or incineration is of environmental concern. Catalytica has tested a Pd-heteropoly acid catalyst which has all but eliminated the need for chloride (Cusumano, 1992). The activity has been increased to the point where 100 times less palladium is required to match the performance of a typical Wacker catalyst. Very little chlorinated byproduct is formed in the Catalytica technology. The last of the major catalytic oxidation types involves an oxometal or peroxometal center as the active species. A good example of this family of reactions is the homogeneous epoxidation of propylene with tert-butyl hydroperoxide (TBHP). While many catalysts are active for this reaction, the typical one consists of a molybdenum complex, such as Mo(CO)~.In this reaction sequence, the oxygen is transferred from the alkyl peroxometal ligand to the olefin (Scheme 3). While 0 2 autoxidation typically limits reactions to simple substrates with little functionality, oxygen transfer through peroxometal and oxometal complexes is extremely versatile. Reactant molecules in the specialty chemicals industries are usually complex, multifunctional species with limited thermal stability. Oxidations of these compounds often have strict chemo-, regio-, and enantioselectivity requirements. Due to these constraints, the use of peroxometal oxygen transfer is the
2892 Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994
method of choice because it can be accomplished in a stereoselective fashion. Oxidation and the Environment. One area of oxidation chemistry where catalysis using hydroperoxides has triumphed over an environmentally undesirable process is in the manufacture of epoxides. The outmoded process consists of two steps. The first step produces a chlorohydrin by reacting the olefin with hypochlorous acid. In the second step, the chlorohydrin is reacted with calcium hydroxide to yield the epoxide. In addition to the desired epoxide, large amounts of calcium chloride are formed. In fact, 2 tons of salt/ton of epoxide are produced in the case of propylene oxide (Holderich, 1993). Between the disposal of the salt and the handling of concentrated calcium hydroxide, this technology is not environmentally friendly. It should be stressed that propylene oxide is of major commercial interest. In 1992,2.7 billion pounds of propylene oxide were synthesized in the U.S., making it the 39th largest volume chemical (Reisch, 1993). Propylene oxide is used in the manufacture of polymers and glycols. Epoxides, in general, are extremely valuable compounds because they are easily opened to produce 1,2 functionality in a stereospecific manner. Additionally, asymmetric epoxidation is commercially viable (Harrington, 1990) and ring opening of the chiral epoxide can produce two contiguous chiral centers, a real bonus in the production of fine chemicals. In the mid-1960s a breakthrough in epoxidation catalysis quickly led to Oxirane's commercial process (a joint venture between ARC0 and Halcon) for propylene oxide production (Kollar, 1960). Molybdenum compounds such as Mo(CO)~were found to convert into catalytically active species under reaction conditions. Other homogeneous metal complexes, e.g., W(CO)s,Ti(OBuk, were found t o be active as well. Most alkyl hydroperoxides are suitable oxidants for this reaction and two popular choices are TBHP, and l-phenylethyl hydroperoxide. The coproduct of the former can be converted to methyl tert-butyl ether, a high-octane component for gasoline, while the coproduct of the latter can be dehydrated to styrene. H202 cannot be used because it is not soluble in nonpolar solvents. If a polar solvent is used, e.g., alcohol or HzO, the solvent molecules strongly coordinate t o the catalytic centers and render them inactive (Sheldon and Van Doorn, 1973). This is a common problem among oxometal and peroxometal catalysts. However, this process is certainly more environmentally friendly than the salt-producing chlorohydrin route. A heterogeneous catalyst capable of performing the epoxidation reaction was discovered in the early 1970s by researchers at Shell (Wulff, 1975). The catalyst consists of titanium supported on amorphous silica. The exact nature of the titanium site is not fully understood, however, it is believed that titanium(IV) centers are responsible for the activity. The same alkyl hydroperoxides that are used with the homogeneous molybdenum catalyst can be used with the heterogeneous titanium catalyst. However, the Ti(IV)/SiOz material affords the advantages that go along with all heterogeneous catalysts: ease of regeneration, high thermal stability, ease of separation, and ease of handling. Like the Mo catalyst, the Ti catalyst is very sensitive to water and care must be taken to exclude H20 from the reaction mixture. The two preceding epoxidation examples demonstrate how catalytic processing has replaced stoichiometric
OH
OH
6
ArH
s
HoNo
Figure 6. Oxidation reactions catalyzed by TS-1.
chemistries that produce large quantities of byproducts. The use of alkyl hydroperoxides as oxidants with the right catalysts lead to efficient low-temperature, liquidphase reactions. If the large volume of coproducts from the hydroperoxide can be utilized in a profitable manner with some type of solvent recycling, then these processes are quite environmentally sound. Because of the cost, safety, and environmental concerns associated with alkyl hydroperoxides, there remains a continuing search for new chemistries that alleviate a t least some of these hazards. Hydrogen peroxide certainly has some distinct environmental advantages over alkyl hydroperoxides. First and foremost, the byproduct is water. Also, H202 has a high weight percentage of active oxygen and is soluble in both aqueous and polar organic media. Because concentrated solutions are expensive and dangerous to handle, hydrogen peroxide is often sold as an aqueous solution, e.g., 30 wt %. At this concentration, the peroxide is stable if care is taken to remove contaminants such as organics and alkali-metal ions (Schumb et al., 1955). When handled correctly, H202 will lose less than 1wt %/year of its oxygen content (Dear, 1993). HzOz-based technology is well suited to compete with other oxidants, except 0 2 , and offers a greater environmental acceptability. One of the biggest breakthroughs in catalytic partial oxidation with H202 was the synthesis of titanium silicalite-1 (denoted TS-1) by Taramasso et al. in 1983. TS-1 is a zeolite-based catalyst capable of activating a broad spectrum of hydrocarbons with aqueous hydrogen peroxide (see Figure 6). The shape selectivity, ease of separation and recovery, and the regenerability of the zeolite make this type of catalyst more attractive than traditional homogeneous ones. A comparison between TS-1 and the Shell catalyst (titanium deposited on amorphous silica) is presented below. Although the active site in TS-1 is still not fully understood, it has been postulated that the same type of titanium site is present in both materials (Notari, 1988). The zeolite structure is relatively hydrophobic and this may result in screening out bulk water from the internal voids of TS-1 (Khouw et al., 1994). This may be the reason why TS-1 is not affected by water in contrast to the Shell catalyst. Hence, aqueous H202 can be employed as oxidant with TS-1. Because the titanium resides in the zeolite lattice, all the Ti atoms are accessible and exposed t o the same reaction environment; this is difficult to achieve by depositing metal complexes on an amorphous support. As a result, TS-1 is extremely active and selective (Huybrechts et al., 1992). For example, the reaction of propylene and Hz02 results in a propylene oxide selectivity of 97% at 97% peroxide conversion (Clerici et al., 1991) in methanol a t 50 "C. These results compare favorably to those obtained from the Shell catalyst using alkyl hydroper-
Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 2893 Table 3. Phenol Hydroxylation Using Hydrogen Peroxide4 Rhone-Poulenc Brinchima Enichem
(HC104,HgP04) (Fe2+,Co2+) phenol conv, 96 Ha& conv, % diol eelectivity, 96 ratio catecholhydroquinone a
5 70
10 50
90 1.4
80
TS-1 26
70 90
2.3
1
Adapted from Notari, 1988.
Scheme 4. Conventional Synthesis Route to +Caprolactam (“30H)2s04
2
c)=.-
+ (“&SO,
+
ZH202
oxides. Presently, the cost of the HzO2 is preventing the TS-1 process from having an economic advantage for epoxidation. Changes in the value of the coproduct from the alkyl hydroperoxide (or the cost of disposal) and the development of a new, cheaper catalytic route to aqueous HzOz by DuPont (Glosser, 1988) may swing the balance in favor of TS-1 in the future. Shape-selective oxidation can be observed with TS-1. For the epoxidation of C4 olefins, conversion rates followed the order: cis-2-butene > 1-butene > isobutene > trans-2-butene (Clerici and Ingallina, 1993). It has also been shown that 2-hexene can be selectively epoxidized when mixtures of 2-hexene/cyclohexene are used (Tatsumi et al., 1991). Within a short time after its synthesis, TS-1 was employed as a commercial catalyst for the production of catechol and hydroquinone from phenol and aqueous HzOz (Romano et al., 1990). The TS-1 catalyzed process now operates at 10 tondyear. The classical route to hydroquinone is shown in Figure 2. For every kilogram of hydroquinone produced in the conventional process, more than 10 kg of salt is formed. The yields from the TS-1 catalyzed reaction compare favorably to other HzOdphenol reactions such as the acid-catalyzed scheme, as well as the process employing Fenton’s reagent: an iron salt and HzOz (see Table 3). TS-1 produces the lowest ratio of catechol to hydroquinone. Since hydroquinone is the desired product, there is less byproduct from the reaction and the reaction is environmentally friendlier. The amount of tars produced with TS-1 is nearly equal to the liquid-acid catalyzed process and half that of the Fenton chemistry (Notari, 1988). An important example of where TS-1 may be used to develop new chemistry to replace an environmentally undesirable process is in the manufacture of Nylon 6. This is the second most widely used polyamide (to Nylon 6-6) in the United States (Parshall and Ittel, 1992). It is produced from the ring-opening polymerization of 6-caprolactam. The classical route to 6-caprolactam is shown in Scheme 4. Because of the low yield and rapid catalyst deactivation in the ammoxidation step, other processes were developed by which the ketone was reacted with ammonia and H2Oz in the liquid phase using an acid catalyst (phosphotungstic acid). This process also suffers from low yields and catalyst deactivation (Roffia et al., 1990). TS-1 overcomes these problems and gives excellent yields a t moderate temperatures. At a reaction temperature of 60 “C, cyclohexanone conversions above 90% and selectivities above 99% for the oxime have been reported (Thangaraj et al.,
1991). Very little hydrogen peroxide decomposition to dioxygen is observed in contrast to the liquid-acidcatalyzed reaction. While many routes to the oxime exist, all commercial caprolactam production makes use of a Beckmann rearrangement to transform the oxime to the desired product. Traditional methods employ oleum, a very strong acid consisting of HzSO4 and SOs, to facilitate the rearrangement. To recover the product, the mixture must be neutralized with ammonium hydroxide. This produces approximately 5 tons of ammonium sulfate/ ton of lactam (Immel, 1984). Mobil has patented a gasphase process using a medium-pore zeolite, ZSM-5, with low-to-moderate acidity (Bell and Haag, 1990). Very high conversions (>95%) and selectivities (>go%) t o oxime were reported at 300 “C. Union Carbide has already tested the molecular sieves SAPO-11and SAPO41 as catalysts for the rearrangement at pilot plant scale (Cusumano, 1992). At 350 “C the oxime is converted to +caprolactam with 95% selectivity at 98% conversion (Holderich, 1989). By using a heterogeneous catalyst, all of the environmental disadvantages have been eliminated. The comment has been made that “oxidation continues to be the most promising of the major process reactions used industrially for the conversion of hydrocarbons to useful organic products” (Marek, 1954). This statement was made in 1954 and is still true today. As environmental regulations (and consumer concerns) mandate the removal of stoichiometric oxidants due to massive amounts of byproducts, new catalytic technologies must fill the void to produce this important class of chemicals. The use of homogeneous, transition-metal catalysts with alkyl hydroperoxides as oxidants has already started to do just that. However, the use of hydroperoxides carries with it economic and environmental concerns. Hydrogen peroxide has been labeled “Mr. Clean” (Sheldon, 1993) and appears well suited to become the oxidant of choice as the chemical industry turns toward “green” processes. It is important to remember that the ultimate goal is the use of molecular oxygen at moderate temperatures in the liquid phase where overoxidation to carbon dioxide and water is eliminated. This will bring commercial catalytic oxidation toward the sophistication observed from enzymes.
Catalysis in Water When catalytic chemistries are conducted in the liquid-phase, hydrocarbon-based solvents, e.g., chlorofluorocarbons, benzene, carbon tetrachloride, are typically employed. The solvents themselves can be environmental problems if they are released to air, land or water. The movement to environmentally benign solvents, e.g., water, is already occurring. For example, Louis Hegedus of W. R. Grace states, “Our manufacturing operations are all involved in programs to replace hydrocarbon solvents with aqueous ones” (Amato, 1993). However, the replacement of hydrocarbon-based solvents by water is not straightforward. The solvent does not usually act as an inert diluent but rather plays an active role in the catalysis. Gilbert and Mercier (1993) have recently reviewed numerous issues concerning solvent effects in heterogeneous catalysis. Additionally, water is a very good coordinating ligand for many catalytically active materials. Thus, the replacement of organic-based by aqueous-based solvents will require a significant amount of effort. In this section we describe a commercial process that successfully made
2894 Ind. Eng. Chem. Res.,Vol. 33, No. 12,1994
Scheme 5. Rhodium Hydroformylation Catalyst Precursors
a. ~rganiC.~~Iuble
b. watOI.MIuIe
Table 4. Hydroformylation of a k1:1 Mixture of I-Hexene, I-Octene, and 1-Decene with Aqueous and Organic Soluble Rhodium Complexes and a SAP Catalyst (Adapted from Horvath, 1990) T O P W') heptanals nonanals undecanals
biphasic6
organic!
SAPCd
0.0047 0.0014
0.46 0.50 0.50
0.12 0.12 0.11
0.0003
TOF turnover frequency estimated fmm conversionsspecified at various reaction times. Values are only estimates since the levels ofconvenion in some cases were very high. HRh(CO)[P(rnCsH4SOsNahb in water. T = 125 "C, P = 825 psig. HRh(C0)[P(CsHshb in hexane. T = 100 "C, P = 725 psig. SAP catalyst containing HRh(CO)[P(rn-CsHIS03Na)3L. Hexane solvent. T = 100 "C, P = 725 psig.
the transition from organic to aqueous solvent and then outline some of the current progress of catalysis in water. Hydroformylation is the addition of CO and Hz into an olefin to yield an aldehyde. A typical propene hydroformylation process involves the use of [HRh(CO)(PRd31where R = CsHs (Scheme 5a) in organic solvent. Propene, CO and Hz enter the reactor and n- and i-butyraldehyde are the products formed. The desired isomer is the linear aldehyde. The catalysis is homogeneous, and the products are distilled off of the reaction solution. Thus, this process is not able to accommodate heavier olefins due to the low volatility of the product aldehydes. RuhrchemielRhone-Podenc have developed a propene hydroformylation process that uses water as the solvent (Kuntz, 1987). Two plants now produce 300 000 tons of butyrddehyddyear (Henman and Kohlpainter, 1993). The key to the success of this process is the ligand triphenylphosphone trisulfonate, TPFTS. This ligand has a solubility of 1100 g/L in water (Kuntz, 1987). Thus, [HR~(CO)(TPF'TS)BI (Scheme 5h) is extremely water soluble and is not soluble in most organics. Propene is slightly soluble in water. Therefore, the hydroformylation can take place homogeneously in water and as the reaction proceeds a second, waterimmiscible, butyraldehyde phase forms. The product phase is easily separated from the aqueous-phase without significant catalyst loss (Kuntz, 1987). With the aqueous-based process, the problem of hydroformylating large olefins is no longer the removal of the product but the solubility of the substrate. For example, the data given in Table 4 show that the water solubility of the olefin clearly affects the rate of hydroformylation in the aqueous (biphasic) system. The number of organic reactions that can proceed in aqueous media is continuing to increase (Henmann and
Figure 7. Schematic diagram of supported aqueous-phase catalysis. MLG represents a generic water-soluble organometallic complex.
Kohlpainter, 1993). Li (1993) has recently provided a review of carbon-carbon bond formation reactions in water and illustrates that reactions such as Diels-Alder reactions, carhonylations, alkylations, and polymerizations can all successfully proceed in aqueous media. For example, Novak and Grubbs (1988) reported the synthesis of polynorbornene in aqueous solution and an atmosphere of air. Continued work in this area has concentrated on improvements to the water-soluble ruthenium catalyst, and more robust and active catalysts are available (Nguyen and Gruhbs, 1994). Now, even asymmetric hydrogenations of olefins can he conducted in pure water without a loss in enantioselection (Wan and Davis, 1993). A n interesting new report of catalysis in water involves the reaction of COz to formic acid. Gassner and Leitner (1993) show that water-soluble rhodium catalysts, e.g., Rh(TPFTS)&l, are capable ofhydrogenating COz to HCOzH. This result is quite interesting since the solvent is water and the reactant is COZ;the process involves two environmentally friendly features-no organic solvent and removal of a greenhouse gas. Additionally, Jessop et al. (1994) have also concentrated on this reaction and have been able to increase the reaction rate above that reported by Gassner and Leitner. As discussed above, one of the problems with converting from organic to aqueous solvents is the change in solubility. Like biological systems that function in water, e.g., vitamin BIZ(Co), chlorophyll (Mg), hemoglobin (Fe),the organometallic catalysts contain ligands that ensure hydrophilic properties while the local environment at the metal remains hydrophobic in character (Arhancet et al., 1989). However, similar manipulations on the reactants to increase their water solubility are not desired. Thus, one solution to this problem is to support the aqueous media (Davis, 1992). A supported aqueous-phase (SAP) catalyst consists of a thin film that resides on a high-surface-area hydrophilic support, such as controlled-pore glasses or silica, and is composed of water-soluble organometallic complexes and water (Figure 7). Reactions of liquid-phase, water-insoluble organic reactants take place a t the film-organic interface. This point is critical since it eliminates the need for water-soluble reactants. Clearly, the data in Table 4 demonstrate that the water solubility of the olefins does not limit the performance of the SAP catalyst since the TOFs are essentially independent of olefin carbon number. SAP catalysis has been demonstrated for hydroformylation, hydrogenation, and Wacker chemistries (Davis, 1992). Also, SAP enzyme catalysis has appeared (Davis, 1992; Panda et al., 1992). Although none of the published examples were con-
Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 2895 Table 5. Relationships between Absolute Configuration e n d Biological Effect of Chiral Compound@ ComDound
eonfirmration
Ishloropropane-2.3-diol
R S R S R
propanolol
S R
asparagine carvone
S optidly Fure
,26.5%
chloramphenicol
R, R
ethambutol
R, R
s, s
s,s
hiolodcal effect sweet taste bitter taste spearmint flavor caraway flavor toxic antifertilitv activitv contraceptive antihypertensive, antiarrhythmic antibacterial inactive causes blindness tuberculostatic
Adapted h m Federsel, 1993 and references therein.
Figum 8. Optical character of 25 topselling, synthetically produced drugs (A, 1982; B, 1991). From Layman, 1993.
ducted in neat reactant, i.e., no organic solvent, SAP catalysis should be possible in the absence of an organic solvent. Finally, it is important to point out that unlike organometallic species that are immobilized onto solids by covalent bonds, the activity of a SAP catalyst is quite high when compared to the analogous chemistry in organic solvents (see data in Table 4 as a typical example).
Asymmetric Catalysis It should be noted that the large (and rapidly growing) pharmaceutical industry produces the largest amount of byproducts per kilogram of desired product. This is due to many reasons that include (1) the complexity of the final products (2) the high number of reaction steps (3) the low yields a t some steps (4) very high purity required of the final products (5) difficult separation of byproducts, products, and catalyst ( 6 )the limited thermal stability of intermediates and final products Additionally, byproducts may chemically resemble the desired drug and could thus have devastating health effects on living organisms if released to the environment. This may be true even for small concentrations. In 1982, synthetically produced compounds made up 72%of the 25 topselling drugs. The percentage rose to 83% in 1991 (Layman, 1993). In the same time period, an even larger jump was observed in the fraction of these synthetic drugs sold in their optically pure form (see Figure 8). Chiral organic compounds often elicit strong biological activity because receptor sites in living organisms are chiral. Thus, it is not surprising that enantiomers can stimulate different biological responses. The most infamous and tragic example of this is the case of thalidomide. Thalidomide was first dispensed in its racemic form; both isomers were present in equal amounts. It was later discovered that only the R isomer is a n effective sedative. The S isomer, first assumed inactive, produced fetal deformities (Parshall and Nugent, 1988a). Thus, the nontherapeutic enan-
tiomer can be considered a "biological pollutant". Many other common drugs including ibuprofen, Prozac, and Seldane are still sold in their racemic form with only one enantiomer being active (Ariens, 1993); the assumption is that the inactive enantiomer has no toxic effect. Table 5 lists other pairs of enantiomers with their biological effect (Federsel, 1993). Two strategies are available for the production of a single enantiomer. The first,and more elegant strategy, involves the direct manufacture of the pure enantiomer through asymmetric catalysis. The second is to produce a racemic mixture through traditional routes. The desired product must then be separated from the racemic mixture using techniques that include crystallization, chromatography, and kinetic resolution. These methods are often labor intensive and expensive. Despite this, these procedures are used regularly because the desired enantiomer is so valuable. The undesired enantiomer must be recycled, discarded, or destroyed. The large amounts of byproducts and the high volumes of solvents used in the purification make these systems targets for environmentally benign replacements. The combination of environmental, cost, and health concerns are causing governmental regulatory boards to look seriously into the "biological pollutantn problem. The Food and Drug Administration recently published a new policy statement for development of drugs comprised of stereoisomers (FDA, 1992). It states that adverse reactions could be attributed to one enantiomer and recommends the study of individual isomers if toxic effects are found for the racemate. It also states that the racemic mixture is not expected to be the optimal ratio of isomers for therapeutic value. Health officials in Japan have put forth the same type of recommendations (Smith and Caldwell, 1988). The US. Patent Office is encouraging the development of single enantiomer drugs. A company can patent the single-enantiomeric form of a drug, even if the racemic form is already claimed (Amato, 1992). For example, Sepracor Inc. has recently acquired the patent for the active isomer of Prozac, a leading antidepressant. Such incentives will help convince pharmaceutical companies that single-enantiomeric drugs are profitable. Thus, there are two distinct opportunities in increasing the environmental benignancy of drug production: (i) minimizing byproducts and (ii) eliminating unwanted enantiomers. Homogeneous Catalysis. One would like to limit the number of processing steps needed to reach the desired enantiomer. Numerous problems arise due to the need for high enantiomeric purity. The obvious, but difficult, solution is to produce only the desired enantiomer in a catalytic step that introduces the chirality.
2896 Ind. Eng. Chem. Res., Vol. 33,No. 12, 1994
CH3
chirnlcalalyst HZ CH30
a 3 0
&
S-Naproxsn
Figure 9. Monsanto naproxen process. From Chan, 1993.
This has been shown to be feasible for many classes of reactions using homogeneous catalysts. The uniformity of the active metal centers and the high activity1 selectivity characteristics of soluble chiral organometallic species gives homogeneous, asymmetric catalysis numerous advantages over heterogeneous catalysis. Until recently, only two families of heterogeneous, asymmetric catalytic systems existed: (i) a Raney-Ni catalyst modified with tartrate/NaBr and (ii)Pt (or Pd) catalysts modified with cinchona alkaloids. These two systems show low enantiomeric excesses (88’s) relative to homogeneous systems and work on only small classes of chemical compounds (Blaser and Muller, 1991). Homogeneous, asymmetric catalysts have been developed over the past 25 years that are able to perform syntheses that result in near-optically-pure products. Homogeneous, asymmetric catalysis was employed for the first time commercially in 1971 for the production of l-dopa, a drug used for treatment of Parkinson’s disease. This process sparked extensive research on new asymmetric catalysts and uses. Monsanto’s enantioselective synthesis of l-dopa involves the hydrogenation of a prochiral olefin using a rhodium catalyst containing a chiral biphosphine ligand. Another of the most well-known systems is the Sharpless-epoxidation catalyst (Sharpless, 1985). This catalyst can be prepared from simple, relatively inexpensive sources and results in ee’s well above 90%. Its main disadvantage is that it can only perform the chiral oxidation of allylic alcohols. Despite this, it is used commercially to produce (+I-dispalure, a sex pheromone of the gypsy moth (Parshall and Nugent, 198813). The Sharpless chemistry is also used by ARC0 to manufacture both enantiomers of glycidol (Armor, 1991). Greater than 10 tons of optically-pure glycidols are produced every year, making it one of the largest chiral syntheses. Unfortunately, the catalyst is sensitive to water, so alkyl hydroperoxides must be used as the oxidant. Naproxen, a widely prescribed antiinflammatoryagent, has been the object of intense research because it has recently been approved for over-the-counter sales. The conventional route to naproxen produces a racemic mixture that is then purified by resolution. The resolution requires the recycling of large amounts of resolving agents because the per-cycle yield is quite low (Chan, 1993). The recycling steps and the production of 50% unwanted enantiomer make this process both inefficient and environmentally undesirable. Monsanto has disclosed a process that leads directly to the S enantiomer. This scheme consists of two key steps: electrocarboxylation and asymmetric hydrogenation (Figure 9). The electrochemical step leads to a prochiral olefin. Unfortunately, the asymmetric rhodium catalyst used for the synthesis of l-dopa gives ee’s below 70% for naproxen. Commercially viable asymmetric syntheses typically require ee’s greater than 95%. The breakthrough came in 1987 when Noyori et al. (Ohta et al., 1987) reported
the use of a ruthenium catalyst containing a BINAP ligand t o yield S-naproxen (the desired enantiomer) at a 97% ee. Subsequent work by the Monsanto group (Chan, 1993) led to ee’s greater than 98% at commercially reasonable conditions (0 “C, 500 psi). However, water and oxygen must be rigorously excluded for good yields and long catalyst lifetimes. Chemistry analogous to that described for the naproxen synthesis has been proposed as a route t o S ibuprofen, another important 2-arylpropionic acid. Ibuprofen is currently sold as a racemic mixture, even though studies show only the S enantiomer has significant therapeutic effect (Chan, 1993). The conventional route and the environmentally preferable catalytic route are shown in Figure 1. The proposed Monsanto route would start with an electrochemical reaction on the ketone. This eventually leads to the prochiral olefin required for the chiral hydrogenation step. High ee’s (’96%) are possible with the Ru-BINAP catalyst. While this route also involves the use of liquid acid catalyst, it doubles the possible yield of biologically active product. This in turn halves the starting material required and, as Ariens (1988) points out, halves the amount of material that must be transported and applied. Incidently, Ariens also refers to the “inactive” enantiomers as “environmental pollutants”. Modification of Existing Catalysts. There is no doubt that new homogeneous catalysts will play a major role in expanding the scope of asymmetric synthesis. However, the development of such catalysts is often determined by serendipity. Through modification of processes utilizing existing catalysts, many environmental gains may be realized. A good example of this is in work to immobilize homogeneous catalysts. Corma et al. (1991) have anchored chiral rhodium complexes t o modified zeolites and shown that the ee’s increase from the purely homogeneous analogue. Fast reaction rates were observed, and no induction period was detected in contrast to the homogeneous system. The higher rates and ee’s are thought to arise from enhanced substrate concentration in the zeolite and/or electrostatic interactions between zeolite and substrate. No rhodium losses from the support were observed, although minimum detection levels were not reported. The same procedure has been shown to work with other catalysts including chiral Ru(II), Co(II), and Ni(I1) complexes (Corma et al., 1992). By immobilizing the catalyst, separation becomes trivial and loss of the expensive, possibly toxic catalyst is negligible. The limitations of this new, hetero eneous, asymmetric catalyst is the small pore size (-8 ) of the zeolite. This size range severely restricts the types of substrates that can be reacted. Another manner by which traditional homogeneous catalysis can be made more environmentally sound is through changes in reaction media, i.e., solvents. Typically, these reactions are conducted in organic solvents, e.g., benzene, THF, methanol. Because of the large volumes of solvent used, the environmental choice would certainly be water. The water solubilization of organometallic catalysts is performed by adding highly polar groups, such as sulfonate groups, t o phosphine ligands. This has been done for a number of Rh(1) catalysts but the drop in ee from the parent system is usually quite dramatic aRer sulfonation. This decreases further when water is used as the solvent. Wan and Davis (1993a) have reported the first example of asymmetric catalysis in neat water where
x
Ind. Eng. Chem. Res., Vol. 33, No. 12, 1994 2897
CI0;
Figure 10. Water-soluble rhodiudsulfonated BINAP complex.
the optical yield obtained is as high as that observed in nonaqueous solvents. Using a Rh(1) catalyst with a tetrasulfonated BINAP ligand (see Figure lo), an ee of 70.4% was observed for the hydrogenation of 2-acetamidoacrylic acid in neat water; the unsulfonated catalyst in ethanol resulted in an ee of 67%. This study proves that homogeneous, asymmetric catalysis is indeed possible in an environmentally benign solvent. While the BINAP ligand has proven useful for a wide scope of asymmetric reactions (Noyori, 1988),the variety of Rh(1)-catalyzedreactions is rather limited. Ruthenium complexes often shown hydrogenation activity for a broader range of substrates. In an attempt to combine the utility of sulfonated BINAP with the reaction’ chemistry of ruthenium, Wan and Davis (1993b) prepared a Ru analogue to their successful Rh catalyst. It indeed revealed superior enantioselectivity and stability to the corresponding Rh complex. For certain substrates, the ee’s are lower in neat water than in organic media. However, others have equal or even higher ee’s in H20 than in nonaqueous solvents. The thermal stability of the ruthenium catalyst allows it to be used in water well above room temperature; the rhodium catalyst is not stable above room temperature. The water-soluble, asymmetric, hydrogenation catalyst represents a significant step toward viable asymmetric processes in environmentally benign solvents. However, as with all homogeneous processes it still suffers from the catalyst separation problem. Wan and Davis (1994)have developed a supported aqueous phase catalyst (SAPC) using the water-soluble Ru-BINAP complex. The SAPC is only seven times less active than its homogeneous analogue, but 50 times more active than an ethyl acetate/water two-phase reaction mixture in the hydrogenation of the naproxen precursor. This is due to the much larger interfacial area resulting from the controlled-pore-glasssupport. It was found that the upper limit in ee (75%) is fxed by the intrinsic enantioselectivity limit for the homogeneous catalyst in water. Elemental analysis (detection limit 1ppm) and catalytic testing of the filtrate suggest that no soluble Ru species leach into the organic phase. Upon replacement of the water-phase by ethylene glycol, Wan and Davis have now prepared a heterogeneous catalyst capable of synthesizing naproxen at 96% ee (Wan and Davis, 1994). This type of asymmetric heterogeneous catalysis is a good example of how new technologies can be created by modifying existing catalysts.
Future The aforementioned examples illustrate the types of issues currently being addressed in implementing new catalytic technologies with a view toward more environmental regulation. From these data we are able to outline several unifylng concepts that we believe will be useful in designing future catalytic technologies. First, and somewhat obvious, the disposal of the catalyst system (catalyst, solvent) must be seriously considered
when evaluating the environmental impact of a new catalytic technology, and this should begin in the early stages of catalyst development. Thus, the disposability of the catalyst system needs t o be considered in the effective design of new catalyst systems. Certainly there is a movement from liquid catalysts to solids and from organic-based to aqueous-based solvents. Additionally, there is an increasing amount of work on supercritical solvents, e.g., HzO, COz, and the complete removal of solvents. Second, since the demands on the new catalytic technology will be much higher due to stricter environmental regulation, the complexity of the catalyst is most likely to increase. It goes without saying that as the catalyst becomes more sophisticated, its cost will rise. This increasing cost does not appear to be that detrimental in light of the following argument. If environmental regulation forces particular emissions standards then there are two options: (i) develop new catalytic technologies (primary prevention) or (ii) addon further cleanup processing (secondary prevention). Thus, pay for the catalyst or pay for the cleanup. In view of this tradeoff, we feel that increased catalyst cost will win in a large number of situations. Given the issues outlined above, we now suggest several reactions and new catalytic materials that successful implementation thereof would have a high impact on environmentally benign processing. First and foremost, the stereoselective oxidation of organic species by dioxygen at low temperature would have an enormous environmental impact. This is because one could eliminate production of CO,, salt byproducts, and the need for expensive oxidants. Typical examples would be the conversions: alkanes t o alcohols, benzene to phenol, and propylene to propylene oxide. Second, the anti-Markovnikov addition of H2O and NH3 to terminal olefins to give terminal alcohols and amines, respectively, would also have a very large environmental impact by reducing the number of reaction steps required to obtain organic species with terminal functionality. Third, the synthesis of an inexpensive solid superacid capable of substituting for HF, HzS04, and SbFb would certainly be quickly implemented in numerous technologies throughout the world. Fourth, continued emphasis on zeolite-based catalysts is necessary as these systems penetrate into chemical and pharmaceutical usages. Stress should be placed on the synthesis of large- and extra-large-pore materials with welldefined positioning of catalytically active sites within the crystalline structures. The expansion in the types of chemistries accomplished by zeolite-based catalysts is illustrated in this review and demands further attention. Finally, we believe that the synthesis of zeolite membranes could be one of the most important materials problems leading to environmentally benign processing since this type of catalyst system could provide low energy consumption, high reaction selectivity operation. No doubt there are many other important reactions and materials that will play significant roles in providing “cleaner” technologies. Our hope is that through this illustration of our biasedly chosen examples and suggestions we will stimulate further thoughts and suggestions on the important issue of keeping our planet clean.
Acknowledgment C.B.D. is supported by a fellowship from Dr. Ralph Landau.
2898 Ind. Eng. Chem. Res., Vol. 33, No. 12,1994
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Abstract published in Advance ACS Abstracts, November 1, 1994. @
