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Vapor Phase Carbonylation of Methanol with Supported Nickel Metal Catalysts Kaoru Fujlmoto, Tsutomu Shlkada, KoujI Omata, and Hlro-o Tomlnaga Depariment of Synthetic Chemistry, Facum of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan
Vapor phase carbonylation of methanol on supported nickel and other iron group metals was studied under pressurized condiins in the presence of methyl halide promoters. A nickel metal catalyst supported on an activated carbon exhibited an excellent activity to convert most of the methanol to carbonylated Rroducts (acetic acid and methyl acetate) selectively. The typical reaction conditions utilized were 300 "C and 11 bar. However, nickel on a yalumina or a silica gel exhibited quite low activity. Iron and cobalt on activated carbon gave small amounts of carbonylated products with a large amount of dimethyl ether. Methyl iodide exhibited an excellent promoting effect while methyl bromide showed a fairly good effect. With increasing methyl iodide concentration, both conversions of methanol and carbon monoxide increased accompanied by the marked changes in the product selectivity of increasing acetic acid and decreasing methyl acetate. The yields of carbonylated products were markedly increased with a rise in the operating pressure. The role of activated carboq as the carrier and that of methyl halide as the promoter are discussed.
Introduction Carbonylation of methanol has been performed industrially in the liquid phase under extremely high pressure (ca. 400 atm) using iodide or carbonyls of cobalt as a catalyst and organic or inorganic iodide such as methyl iodide, hydrogen iodide, or potassium iodide as a promoter. Recently, it has been reported in a few patents that nickel carbonyl or nickel compounds are effective catalysts for carbonylation of methanol in the presence of iodide at pressure as low as 30 bar, when some organic amines or phosphines are incorporated in the liquid reaction media (Rizkalla and Naglieri, 1978; Isshiki et al., 1979). Roth et al. (1971) and Paulik and Roth (1968) have found that carbonyl complexes of rhodium are exceedingly active for methanol carbonylation in the presence of iodide promoters. They are sufficiently active at atmospheric pressure and give methyl acetate and acetic acid, very selectively. Extensive work on the catalysis of rhodium has clarified the mechanism which is comprised of oxidative addition of methyl iodide to rhodium, insertion of CO, and reductive decomposition of acyl complex with methanol or water (Forster, 1976; Hjortkjaer and Jensen, 1976). Rhodium is also an effective catalyst for the vapor phase carbopylation of methanol when it is supported on activated carbon or metal oxides by impregnation method (Schultz and Montgomery, 1969; Robinson et al., 1972; Krzywicki and Marczewski, 1979) or on zeolite with the ion-exchange method (Yashima et al., 1979; Andersson and Scurrell, 1979; Scurrell and Howe, 1980). One of the authors has studied the catalytic features of rhodium Chloride supported on various carriers for the reaction apd pointed out that rhodium on activated carbon maintains its catalytic activity even if it is reduced to the metallic state, whereas rhodium on other carriers loses its activity when it is reduced by reactants such as methanol or carbon monoxide (Fujimoto et al., 1977). Fujimoto et al. (1981) have reported that nickel on activated carbon exhibits an excellent catalytic activity for the carbonylations of methanol and dimethyl ether at moderately pressurized conditions in the presence of methyl iodide. In the present work, vapor phase carbonylation of methanol on supported iron group metals under 0196-4321/82/1221-0429$01.25/0
moderate pressures was studied. Several catalytic features of nickel, cobalt, and iron on an activated carbon and other supports are also discussed.
Experimental Section Catalysts were prepared by impregnating a commercially available granular activated carbon (Takeda Shirasagi C, charcoal base, activated with steam, specific surface area 1200 m2/g, particle size 20-40 mesh) with nickel nitrate aqueous solution, followed by drying in an air oven at 120 "C for 24 h and then reducing in flowing hydrogen at 400 "C for 3 h. The nickel content in the catalyst was 2.5 wt % as metal. The reference catalysts were prepared by the same procedure but using y-alumina (Tokaikonetsu TKS 99651), silica gel (Davison ID), graphite (Yoneyama Chem. Ind. Ltd.), or carbon black (Yoneyama Chem. Ind. Ltd.) as the carriers. A continuous flow type reaction apparatus with a fixed catalyst bed was employed at both atmospheric and pressurized conditions. The reactor was made of stainless steel with an inner diameter of 14 mm. The weight of the loaded catalyst was 2.3 g and the bed length was about 4.2 cm. The catalyst was placed in the reactor, heated up to 400 "C in an inert atmosphere and reduced in a stream of hydrogen under atmospheric pressure and at 400 "C for 3 h. After the catalyst was cooled down to the reaction temperature in an inert atmosphere, carbon monoxide was fed up to the desired pressure and then a mixture of methanol and methyl halide promoter (methyl iodide or methyl bromide) was introduced with a microfeeder to start the reaction. Reaction conditions were as follows: 5 or 10 g of cat. reaction temperature, 200-320 "C; W/F, h/mol; CO/MeOH/methyl halide, 20/ 1&19.8/0.2-2 molar ratio; reaction pressure, 1-15 atm. A quantitative analysis of the products was carried out with gas chromatographs. A column of PEG-1500 on Uniport R for methane, dimethyl ether, methyl iodide, methyl bromide, methyl acetate, and methanol and a column of FFAP on Cbromosorb W for acetic acid were used. The analysis of the gaseous products such as carbon monoxide, methane, and carbon dioxide was performed by use of a Porapak Q column. 0 1982 American Chemical Society
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Ind. Eng. Chem. Prod. Res. Dev., Vol. 21, No. 3, 1982
Table I. Effect of Support Materials on Conversion and Product Selectivity in the Carbonylation of Methanola product yield, % CO,/CH,, cat. temp, "C CH, Me,O AcOMe AcOH molar ratio 300 293 290 257 254 256
Ni/A.C. Ni/r-A1,0, Ni/SiO, Ni/A.C.b Ni/C .B.d Ni/G.e
3.0 0.7 0.4 1.7 0 0.1
2.1 96.2 0.4 14.9
21.6 2.2 1.1 58.2 3.3 1.2
1.3 4.8
69.1 0 0 8.0 0 0
0.30 0.29 0 0.42 0
0
Reaction conditions: CO/MeOH/CH,I, 2 0 / 1 9 / 1 molar ratio; W / F , 1 0 g of cat. h/mol; pressure, 11 atm. activated carbon. Ni content, 10 w t %. 2.5 w t % Ni/carbon black. e 2.5 w t % Ni/graphite.
2.5 wt % Nil
Table 11. Catalytic Activities of Iron Group Metals in the Presence of Methyl Halidea cat. elementb Ni Ni Fe Fe CO
co
a
product yield, % ' promoter
temp, "C
CH,
Me,O
AcOMe
AcOH
CO,/CH,, molar ratio
CH,I CH,Br CH,I CH ,Br CH,I CH,Br
300 300 29 3 29 2 292 293
3.0 4.2 3.0 2.7 3.1 1.2
2.1 23.6 47.6 83.5 77.7 91.6
21.6 24.2 4.2 2.1 10.8 1.1
69.1 4.1 0.1 0 0.4 0
0.30 0.31 0.03 0.19 0.23 0.17
Reaction conditions: see footnote a, Table I.
Catalyst: 2.5 w t % metal/activated carbon.
The product yield and selectivities were calculated by the following equations. product yield = ([(product, mol/h) X (no. of methyl groups in a molecule)]/(methanol fed, mol/h)/ X 100 (1)
-bl
selectivity = ([(product, mol/h) X (no. of methyl groups in a molecule)]/(methanol reacted, mol/h)) X 100 (2)
20
t'
0 1
1
This implies that all methyl groups in the molecules of acetic acid, methyl acetate, dimethyl ether, and methane are derived from methanol.
Results Effect of Support Materials. Table I shows the catalytic activities of nickel supported on activated carbon, y-alumina, or silica gel for the carbonylation of methanol in the presence of methyl iodide promoter. With the activated carbon-supported catalyst, methanol fed was easily converted to give acetic acid and methyl acetate in high selectivities. The yields of methane, dimethyl ether, and carbon dioxide formed were small. On the other hand, the activity and the selectivity for carbonylated products over the nickel catalysts supported on other carriers were markedly different from those over the attivated carbonsupported one. They gave methane or dimethyl ether as the major product but a small amount. of carbonylated products. Carbonaceous material such as graphite or carbon black seems to be a poor support for nickel. It is apparent that the reduced nickel exhibits excellent carbonylation activity only when it is supported on activated carbon. Activities of Iron Group Metal Catalysts aad Effect of Methyl Halide Promoters. Table I1 compares catalytic features of nickel, iron, and cobalt metals supported on an activated carbon for the methanol carbonylation in the presence of methyl iodide or methyl bromide. In the case of methyl iodide promoter, nickel on activated carbon catalyst (Ni/A.C.) gave acetic acid and methyl acetate with high yield as mentioned above, and cobalt on activated carbon (Co/A.C.) and iron on activated carbon (Fe/A.C.) catalysts exhibited poor carbonylation activities. When methyl bromide was used as a promoter, only Ni/A.C. catalyst showed modest catalytic activity while Co/A.C.
2
60
2 40 rl
m 20
n 0
0.4
0.2
0.6
PARTIAL PRESSURE OF C H I I ( a t n )
Figure 1. Conversion and product selectivity as a function of partial pressure of methyl iodide. Catalyst: 2.5 w t % Ni/activated carbon. Reaction conditions: Co/(MeOH CHJ) = 1molar ratio; W/F= 5 g of cat. h/mol; pressure = 11 atm; temp = 320 O C .
+
and Fe/A.C. gave dimethyl ether as the major product together with some carbonylation products as minor ones. Thus, it is concluded that Ni/A.C. plus methyl iodide is the most preferable catalyst system for carbonylation of those studied. The reason why methyl iodide is superior to methyl bromide as the promoter for the methanol carbonylation will be discussed later. Effects of Methyl Iodide Concentration and Operating Pressure. Figure 1shows how the concentration of methyl iodide affects the catalytic features of the Ni/ A.C. catalyst. The conversions of methanol and carbon monoxide increased with an increase in the concentration of methyl iodide in methanol. The products consisted mainly of methyl acetate when the concentration of methyl iodide was kept low, but the selectivity of methyl acetate decreased and that of acetic acid increased with increasing promoter concentration. Both methane and dimethyl ether were independent of the methyl iodide concentration in their selectivities.
Ind. Eng. Chem. Prod. Res. Dev., Vol. 21, No. 3, 1982 431
80
Role of Promoters and Activated Carbon. As is shown in Figure 1, the yield of carbonylated product increases with increasing concentration of CH31. In the absence of CH31, decomposition of methanol and methanation of CO take place rapidly whereas carbonylation proceeds very slowly. Obviously the presence of a promoter is essential, and the role of promoter is assumed to be the same as that proposed for reactions catalyzed by cobalt or rhodium complex. In this connection, it should be noticed that methyl bromide, which has been shown to be inactive with rhodium catalysts, shows some activity with nickel. This suggests that the dissociative addition of methyl bromide to metal catalyst, which is not easy with rhodium, occurs rather easily with nickel possibly because of the lower softness of nickel ion. Since rhodium ion is a soft acid and bromide ion is a fairly hard base, the oxidative addition of methyl bromide to rhodium (eq 6) is difficult.
-
CH3Br + Rh(+)
4
I
5
0
10
PRESSURE
15
(atm)
Figure 2. Conversion and product selectivity as a function of reaction pressure. Catalyst: 2.5 wt % Ni/activated carbon. Reaction conditions: CO/MeOH/CH31 = 20/19/1 molar ratio; W/F= 5 g of cat. h/mol; temp = 320 "C.
Figure 2 shows the conversions of methanol and carbon monoxide and the product selectivities as a function of the operating pressure. The conversions of methanol and carbon monoxide increased with an increase in operating pressure. The selectivity of methyl acetate decreased gradually and that of acetic acid increased slightly with increasing operating pressure. Discussion Reaction Path. Mechanistic studies of methanol carbonylation have suggested that acetic acid and methyl acetate are formed in parallel according to the stoichiometric reactions (Roth et al., 1971) CH3OH + CO CH3COOH (3) 2CH3OH + CO CH3COOCH3 + HzO (4)
-
It is apparent from the results shown in Figures 1 and 2 that the major products in the early stage of the reaction are dimethyl ether and methyl acetate, while acetic acid, methane, and carbon dioxide increase as the reaction proceeds. These observations show that the former two are the primary products and that the latter three products are formed successivelyfrom them. They also suggest that methyl acetate is not formed from acetic acid and methanol. There are two possible routes of acetic acid formation. The first one is hydrolysis of methyl acetate and the second one is the formation of acetic anhydride and its subsequent hydrolysis. Figures 1and 2 point out that the conditions which accelerate carbonylation (high pressure and high concentration of CH31) favor the high selectivity of acetic acid suggesting that the second route is more probable. On the other hand, it has been proven by the authors that dimethyl ether is easily carbonylated to methyl acetate and acetic acid, especially in the presence of water (Shikada, 1981). As a whole, the overall reaction path of methanol carbonylation on this catalyst appears to be described as in eq 5. CH30CH3 CH30H
Y
loCHJCOOH
CHsCOOCH3
-
CH3(-)-Rh(s+)-Br(-)
(6)
,
CH4, COZ
(5)
On the other hand, oxidative addition of methyl bromide to nickel (eq 7 ) is assumed to be easier because both nickel CH3Br + Ni(O) CH3(-)-Ni(2+)-Br(-) (7) 4
ion and bromide ion are half soft and half hard acid and base, respectively (Pearson et al., 1967). It is apparent from the data shown in Figure 1 that activated carbon is the best nickel catalyst carrier for methanol carbonylation. One of the authors has reported that palladium salts supported on activated carbon are excellent catalysts for the oxidation of aliphatic olefins in the presence of steam, indicating that activated carbon is the effective catalyst for the oxidation of zero valent palladium (Fujimoto et al., 1972). Also he has reported that palladium metal on an activated carbon can be a catalyst for the oxychlorination of propylene to allyl chloride and that palladium on activated carbon is partly oxidized during reaction (Fujimoto et al., 1976). These facts suggest that palladium with zero valence is easily oxidized when it is loaded on activated carbon. The same mechanism might be operating for nickel on activated carbon. In the oxidation addition step of methyl iodide to nickel it becomes electron deficient (eq 7 ) and it is reduced when acyl complex on nickel is reductively decomposed (eq 8).
-
CH3CO-Ni2+-I + CH30H CH3COOCH3+ HI
+ Nia
(8)
If nickel is supported on activated carbon, reaction 7 might proceed easily because of the donation of an electron from carbon to nickel. Conclusions (1)It is found that supported nickel metals on activated carbon can be effective catalysts for methanol carbonylation which give acetic acid or methyl acetate with high selectivity. (2) While methyl iodide is the best promoter, methyl bromide is also found to be effective to some extent. (3) Electron transfer between activated carbon and nickel is assumed to be essential for the catalysis of nickel. Literature Cited Andersson, S. L. T.; Scurrell, M. S. J . Catel. 1979, 5 9 , 340. Forster, D. J . Am. Chem. SOC. 1978, 98, 846. Fujimoto, K.; Takahashi, T.; Kunugi, T. I n d . Eflg. Chem. Prod. Res. D e v . 1972, 1 1 , 303. Fujimoto, K.; Takashima, H.;Kunugi, T. J . Catal. 1978, 43, 234. Fujimoto, K.; Tanemura. S.; Kunugi, T. Nippon Kagaku Kalshl 1977, 167. Fujimoto, K.; Shikada. T.; Omata, K.; Tominaga, H. Preprints 2V26-27, 48th Annual Meeting, Catalysis Society of Japan, Okayama, Oct 1981.
Ind. Eng. Chem. Prod, Res. Dev. 1902, 21, 432-437
432
HJorIkjaer, J.; Jensen, V. W. Ind. Eng. Chem. Prod. Res. Dev. 1976, 15, 46. Isshkl, T.; Kijima, Y.; Mlyauchi, Y. (to Mitsubishi Gas Chemical Co.) Japan Kokai 79-59211, July 26, 1979. Krzywkki. A.; Marczewsi, M. J . Mol. Catal. 1979, 6 , 431. Pauiik, F. E.; Roth, J. F. Chem. Commun. 1968, 1578. Pearson, R. G.; Mawby, R. J. “Halogen Chemistry”; Gutmann, V., Ed.; Vol. 3, Academic Press: New York, 1967; p 55. Rlzkalla, N.; Naglieri, A. N. (to Hakon) Ger. Offen. 2749955, May 11, 1978. Robinson, K. K.; Hershman, A.; Craddock, J. H.; Roth, J. F. J . Catal. 1972, 27, 380.
Roth, J. F.; Graddock, J. H.; Hershman, A.; Pauiik. F. E. CHEMECH 1971,
600. Schukz, R. G.; Montgomery, P. D. J . Catal. 1969, 13, 105. Scurreii, M. S.; Howe, R. F. J . Mol. Catal. 1960, 7 , 535. Shikada, T.; Miyauchi, M.; Fujimoto, K.; Tominaga, H. University of Tokyo, unpublished data, 1981. Yashima, T.; Orikasa, Y.; Takahashi, N.; Hara, N. J . Catal. 1979, 59, 53.
Received f o r review December 7, 1981 Accepted April 28, 1982
GENERAL ARTICLES Drug Interactions, Modeling, and Simulations Walter D. WosilaR’ and Rlchard H. Luecke Department of Pharmacology and Department of Chemical Engineering, University of Missouri, Columbia, Missouri 652 12
Drug interactionscan be dangerous, especially when multiple combinations of drugs are used. The anticoagulant warfarin is noted for its involvement in drug interactions in humans. Similar interactions are being studied in experimental animals, such as the rat, to obtain kinetic data as well as tissue concentrations which cannot be done safely in man. A model has been developed for the elimination of warfarin from the plasma and its excretion in the bile. The model includes organ masses and blood flow for plasma, liver, kidney, muscle, skin, gut, and bile; differential equations have been formulated for each organ. A computer program has been developed for the model to simulate drug interactions affecting the elimination of warfarin from the rat. The model has successfully simulated acute interactions such as the inhibitory effect of bromosulphophthalein and chronic interactions such as induction by phenobarbital, as well as damaged liver produced by CCI,.
Introduction Drugs are potentially dangerous, and multiple combinations of drugs used in therapy are potentially even more dangerous than the administration of a single drug (May et al., 1977; Hull et al., 1978). The anticoagulants and the antihypertensives are the classes of drugs reported to be most often involved in drug interactions. Drug interactions result when drugs used for different therapeutic purposes interfere with the action of one of the drugs, and the likelihood of such interactions increases dramatically as the number of drugs used in a patient increases. The anticoagulant warfarin which we have been studying will be used as an example to illustrate the principles involved. Warfarin has a wide variety of medical uses. The most common therapeutic goal is to prevent either the formation of a blood clot at a location in the body which may be harmful or to prevent the extension of an existing clot at such a location. Warfarin acts by inhibiting a key enzyme in the liver which is involved in the final stage of synthesis of clotting factors, and the desired degree of inhibition of the enzyme occurs over a rather narrow range of concentrations of warfarin. If the treatment is inadequate, the risk of coagulation still exists and the treatment is not beneficial. On the other hand, if the drug treatment is excessive, there is the risk of hemorrhage. The use of other drugs for a different therapeutic purpose such as antibiotics, analgesics, or sedatives can alter either the distribution or the rate of elimination of the anticoagulant, or both. Table I shows only a few selected examples of the different types of drug interactions which 0 196-4321 /82/ 1221-0432$01.25/0
Table I. Selected Interactions between Anticoagulants and Other Drugsa interacting drug clofibrate
a
adverse effect increased anticoagulation
barbiturates
decreased anticoagulation
thyroid hormone
increased anticoagulation
phenytoin
increased phenytoin toxicity
probable mechanism displacement from binding sites on serum albumin induction of microsomal enzymes in liver increased catabolism of clotting factors inhibition of microsomal enzymes
Medical Letter, March 6 , 1981.
are of medical importance in order to illustrate the diversity of the drug interactions which have been encountered in humans ( M e d i c a l L e t t e r , 1981). Pharmacological Properties of Warfarin There are a number of pharmacological properties of warfarin which must be considered in the formulation of a model for drug interactions. For example, most of the warfarin in plasma is reversibly bound (more than 99% of the drug) by serum albumin. Many other drugs are also bound reversibly at multiple binding sites on the protein as are various endogenous substances such as bilirubin and free fatty acids. Substances which may be bound at the 0 1982 American Chemical Society
