Alumina1

Al2O3

[1344-28-1]  · Al2O3  · Alumina  · (MW 101.96)

(a mildly acidic, basic, or neutral support for chromatographic separations; a reagent for catalyzing dehydration, elimination, addition, condensation, epoxide opening, oxidation, and reduction reactions)

Alternate Name: g-alumina.

Physical Data: mp 2015 °C; bp 2980 °C; d 3.97 g cm-3.

Solubility: slightly sol acid and alkaline solution.

Form Supplied in: fine white powder, widely available in varying particle size (50-200 mm; 70-290 mesh), in acidic (pH 4), basic (pH 10), and neutral (pH 7) forms. Drying: the activity of alumina has been classified by the Brockmann scale into five grades. The most active form, grade I, is obtained by heating alumina to 200 °C while passing an inert gas through the system, or heating to ~400 °C in an open vessel, followed by cooling in a dessicator. Addition of 3-4% (w/w) water and mixing for several hours converts grade I alumina to grade II. Other grades are similarly obtained (grade III, 5-7%; grade IV, 9-11%; grade V, 15-19% water).2,3

Handling, Storage, and Precautions: inhalation of fine mesh alumina can cause respiratory difficulties. Alumina is best handled under a fume hood and stored under dry, inert conditions.

Introduction.

Alumina is one of the most widely used packing materials for adsorption chromatography and is available in acidic, basic, and neutral forms. Use of the correct type is important to avoid unwanted reactions of the substrate being purified.1,3 Possessing both Lewis acidic and basic sites, alumina has been found to catalyze a wide range of reactions, generally under conditions that are milder and more selective than comparable homogeneous reactions.1

Dehydration and Eliminations.

One of the earliest uses of alumina as a catalyst was for the dehydration of alcohols.4,5 These reactions generally require high temperature and yield primarily non-Saytzeff products. Complex terpenes have been dehydrated with Pyridine or Quinoline doped alumina (eq 1).6b Numerous other groups can be eliminated in the presence of alumina, including OR, OAc, O3SR, O2SR, and halides.1,7 Some of these eliminations proceed under mild conditions,1 often during chromatographic purification (eq 2).7d Sulfonates can be eliminated in the presence of acid and base sensitive groups, without skeletal rearrangements. However, a large excess of properly activated alumina is required, and poor stereo- and regiocontrol are observed.7e Dehydrohalogenations, particularly dehydrofluorinations, occur readily over alumina (eq 3).8 Stereoselective syntheses of vinyl halides have been developed that take advantage of desilicohalogenation9 or deborohalogenation10 of vinylsilane or vinylboronic acid derived dihalides. Benzol[c]thiophene has been synthesized by dehydration of a sulfoxide precursor.11 The oxidation of selenides to selenoxides and their elimination to alkenes can be accomplished in one step using basic alumina and t-Butyl Hydroperoxide in THF.12

Alumina has been used for various dehydration reactions, including those leading to piperidines,13 pyrroles (eq 4) and pyrazoles,14 and other heterocycles.15 It is also an effective catalyst for the selective protection of aldehydes in the presence of ketones.16

Addition and Condensation Reactions.

Alumina promotes the addition of various heteroatom species, whether by electrophilic or nucleophilic processes. In contrast to the elimination reactions described earlier, alumina also promotes the intramolecular addition of OH and OR groups to isolated (eq 5)6c and carbonyl-activated alkenes.17 It is also reported to catalyze the conjugate addition of other nucleophiles, such as amines.18 In the presence of alumina, Iodine can be used to iodinate aromatics, hydroiodinate alkenes, and diiodinate alkynes (eq 6).19 Hydrochlorinations and hydrobrominations of alkenes and alkynes give the Markovnikov products, with good stereoselectivity.20

Aldol-type condensations between aldehydes and various active methylene compounds,21 Michael reactions (eq 7),22 as well as Wittig-type reactions23 can be carried out on alumina under mild conditions, often without a solvent. An interesting nitroaldol reaction-cyclization sequence gives 2-isoxazoline 2-oxides with good diastereoselectivity (eq 8).24

Orbital symmetry controlled reactions that have been promoted by alumina include the Diels-Alder,25 the ene,26 and the Carroll rearrangement.27 These reactions proceeded under milder conditions and with greater stereoselectivity. In a spectacular example, chromatographic purification promoted a diastereoselective intramolecular Diels-Alder that produced the verrucarol skeleton (eq 9).25b

Alkylation reactions that have been induced by alumina include per-C-methylation of phenol,28 intramolecular alkylation to yield a spiro-fused cyclopropane,29 and S-30 and O-alkylations (eq 10).31 The activation of Diazomethane by alumina has provided methods for the conversion of ketones to epoxides32 and for the selective monomethylation of dicarboxylic acids.33 Basic alumina has been used for the generation and trapping of dichlorocarbene.34

Epoxides.

Epoxides can be opened under mild, selective conditions using alumina impregnated with a variety of nucleophiles, such as alcohols, thiols, selenols, amines, carboxylic acids (eq 11),35 and peroxides.36 Use is made of this process in a route to (Z)-enamines (eq 12).37 Formation of C-C bonds by intramolecular opening of epoxides has been reported (eq 13),38 as have alumina catalyzed epoxide formations23,39 and rearrangements.40

Oxidations and Reductions.

Posner has shown that Oppenauer oxidations, with Cl3CCHO or PhCHO as the hydrogen acceptors, are greatly accelerated in the presence of activated alumina.41 Secondary alcohols are oxidized selectively over primary alcohols (eq 14) and groups susceptible to other oxidants (sulfides, selenides, and alkenes) are unaffected. Even cyclobutanol, which is prone to fragmentation with one-electron oxidants, can be oxidized to cyclobutanone in 92% yield.

The complementary reduction reaction (Meerwein-Ponndorf-Verley), using isopropanol as the hydride donor, is also facilitated by alumina and allows the selective reduction of aldehydes over ketones.42 Functional groups that survive these conditions include alkene, nitro, ester, amide, nitrile, primary and secondary iodides, and benzylic bromide.

Air oxidation of a fluoren-9-ol to the fluoren-9-one and thiols to disulfides are accelerated on the alumina surface.43 Alumina has also been used as a solid support for a variety of inorganic reagents,44 and for immobilizing chiral catalysts.45

Miscellaneous Reactions.

Many rearrangements are catalyzed by alumina.1 The Beckmann rearrangement46 of the O-sulfonyloxime shown gives the expected amide with activated alumina, and the corresponding oxazoline with basic alumina (eq 15).46d Alumina has long been used for isomerization of b,g-unsaturated ketones to the conjugated ketones.47 Isomerizations of alkynes to allenes,48 and allenes to conjugated dienoates49 have also been reported (eq 16).

Alumina promotes the hydrolysis of acetates of primary alcohols,50 the deacylation of imides,51 the hydrolysis of sulfonylimines,52 and the decarbalkoxylation of b-keto esters and carbamates.53 It can also be used for acylations and esterifications, with high selectivity for primary alcohols over secondary alcohols.54


1. Posner, G. H. AG(E) 1978, 17, 487.
2. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals; Pergamon: New York, 1988; pp 20, 310.
3. (a) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel's Textbook of Practical Organic Chemistry; Longman-Wiley: New York, 1989; p 212. (b) FF 1967, 1, 19.
4. Knözinger, H. AG(E) 1968, 7, 791.
5. (a) Hershberg, E. B.; Ruhoff, J. R. OS 1937, 17, 25. (b) Newton, L. W.; Coburn, E. R. OSC 1955, 3, 312. (c) Sawyer, R. L.; Andrus, D. W. OSC 1955, 3, 276.
6. (a) von Rudloff, E. CJC 1961, 39, 1860. (b) Corey, E. J.; Hortmann, A. G. JACS 1965, 87, 5736. (c) Barrett, H. C.; Büchi, G. JACS 1967, 89, 5665.
7. (a) Kobayashi, S.; Shinya, M.; Taniguchi, H. TL 1971, 71. (b) Ishii, H.; Tozyo, T.; Nakamura, M.; Funke, E. CPB 1972, 20, 203. (c) Gotthardt, H.; Hammond, G. S. CB 1974, 107, 3922. (d) Mayr, H.; Huisgen, R. AG(E) 1975, 14, 499. (e) Posner. G. H.; Gurria, G. M.; Babiak, K. A. JOC 1977, 42, 3173. (f) Vidal, J.; Huet, F. TL 1986, 27, 3733.
8. (a) Strobach, D. R.; Boswell, G. A., Jr. JOC 1971, 36, 818. (b) Boswell, G. A., Jr. JOC 1966, 31, 991.
9. (a) Miller, R. B.; McGarvey, G. JOC 1978, 43, 4424. (b) Miller, R. B.; McGarvey, G. SC 1977, 7, 475.
10. Sponholtz, W. R., III; Pagni, R. M.; Kabalka, G. W.; Green, J. F.; Tan, L. C. JOC 1991, 56, 5700.
11. Cava, M. P.; Pollack, N. M.; Mamer, O. A.; Mitchell, M. J. JOC 1971, 36, 3932.
12. Labar, D.; Hevesi, L.; Dumont, W.; Krief, A. TL 1978, 1141.
13. (a) Bourns, A. N.; Embleton, H. W.; Hansuld, M. K. OSC, 1963, 4, 795. (b) Glacet, C.; Adrian, G. CR(C) 1969, 269, 1322.
14. (a) Texier,-Boullet, F.; Klein, B.; Hamelin, J. S 1986, 409. (b) Tolstikov, G. A.; Galin, F. Z.; Makaev, F. Z. ZOR 1989, 25, 875.
15. (a) LeBlanc, R. J.; Vaughan, K. CJC 1972, 50, 2544. (b) Higashino, T.; Suzuki, K.; Hayashi, E. CPB 1978, 26, 3485. (c) Bladé-Font, A. TL 1980, 21, 2443. (d) Hooper, D. L.; Manning, H. W.; LaFrance, R. J.; Vaughan, K. CJC 1986, 65, 250. (e) Hull, J. W., Jr.; Otterson, K.; Rhubright, D. JOC 1993, 58, 520.
16. Kamitori, Y.; Hojo, M.; Masuda, R.; Yoshida, T. TL 1985, 26, 4767.
17. McPhail, A. T.; Onan, K. D. TL 1973, 4641.
18. (a) Pelletier, S. W.; Venkov, A. P.; Finer-Moore, J.; Mody, N. V. TL 1980, 21, 809. (b) Pelletier, S. W.; Gebeyehu, G.; Mody, N. V. H 1982, 19, 235. (c) Dzurilla, M.; Kutschy, P.; Kristian, P. S 1985, 933.
19. Pagni, R.; Kabalka, G. W.; Boothe, R.; Gaetano, K.; Stewart, L. J.; Conaway, R.; Dial, C.; Gray, D.; Larson, S.; Luidhardt, T. JOC 1988, 53, 4477.
20. Kropp, P. J.; Daus, K. A.; Tubergen, M. W.; Kepler, K. D.; Wilson, V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G. W. JACS 1993, 115, 3071, and references cited therein. Addition of HN3: Breton, G. W.; Daus, K. A.; Kropp, P. J. JOC 1992, 57, 6646.
21. (a) Rosan, A.; Rosenblum, M. JOC 1975, 40, 3621. (b) Texier-Boullet, F.; Foucaud, A. TL 1982, 23, 4927. (c) Rosini, G.; Ballini, R.; Sorrenti, P. S 1983, 1014. (d) Varma, R. S.; Kabalka, G. W.; Evans, L. T.; Pagni, R. M. SC 1985, 15, 279. (e) Nesi, R.; Stefano, C.; Piero, S.-F. H 1985, 23, 1465. (f) Rosini, G.; Ballini, R.; Petrini, M.; Sorrenti, P. S 1985, 515. (g) Foucaud, A.; Bakouetila, M. S 1987, 854. (h) Moison, H.; Texier-Boullet, F.; Foucaud, A. T 1987, 43, 537.
22. (a) Rosini, G.; Marotta, E.; Ballini, R.; Petrini, M. S 1986, 237. (b) Ballini, R.; Petrini, M.; Marcantoni, E.; Rosini, G. S 1988, 231.
23. Texier-Boullet, F.; Villemin, D.; Ricard, M.; Moison, H.; Foucaud, A. T 1985, 41, 1259.
24. Isoxazoline: Rosini, G.; Galarini, R.; Marotta, E.; Righi, P. JOC 1990, 55, 781. Rosini, G.; Marotta, E.; Righi, E.; Seerden, J. P. JOC 1991, 56, 6258.
25. (a) Parlar, H.; Baumann, R. AG(E) 1981, 20, 1014 (b) Koreeda, M.; Ricca, D. J.; Luengo, J. I. JOC 1988, 53, 5586.
26. (a) Tietze, L. F.; Beifuss, U.; Ruther, M. JOC 1989, 54, 3120. (b) Tietze, L. F.; Beifuss, U. S 1988, 359.
27. Pogrebnoi, S. I.; Kalyan, Y. B.; Krimer, M. Z.; Smit, W. A. TL 1987, 28, 4893.
28. Cullinane, N. M.; Chard, S. J.; Dawkins, C. W. C. OSC 1963, 4, 520.
29. Baird, R.; Winstein, S. JACS 1963, 85, 567.
30. Villemin, D. CC 1985, 870.
31. (a) Ogawa, H.; Chihara, T.; Teratani, S.; Taya, K. BCJ 1986, 59, 2481. (b) Cooke, F.; Magnus, P. CC 1976, 519.
32. Hart, P. A.; Sandmann, R. A. TL 1969, 305.
33. Ogawa, H.; Chihara, T.; Taya, K. JACS 1985, 107, 1365.
34. Sarratosa, F. J. Chem. Educ. 1964, 41, 564.
35. (a) Posner, G. H.; Rogers, D. Z. JACS 1977, 99, 8208. (b) Posner, G. H.; Rogers, D. Z. JACS 1977, 99, 8214. (c) Evans, D. A.; Golob, A. M.; Mandel, N. S.; Mandel, G. S. JACS 1978, 100, 8170.
36. Kropf, H.; Amirabadi, H. M.; Mosebach, M.; Torkler, A.; von Wallis, H. S 1983, 587.
37. Hudrlik, P. F.; Hudrlik, A. M.; Kulkarni, A. K. TL 1985, 26, 139.
38. (a) Boeckman, R. K., Jr.; Bruza, K. J.; Heinrich, G. R. JACS 1978, 100, 7101. (b) Niwa, M.; Iguchi, M.; Yamamura, S. TL 1979, 4291.
39. (a) Dhillon, R. S.; Chhabra, B. R.; Wadia, M. S.; Kalsi, P. S. TL 1974, 401. (b) Antonioletti, R.; D'Auria, M.; De Mico, A.; Piancatelli, G.; Scettri, A. T 1983, 39, 1765.
40. (a) Tsuboi, S.; Furutani, H.; Takeda, A. S 1987, 292. (b) Harigaya, Y.; Yotsumoto, K.; Takamatsu, S.; Yamaguchi, H.; Onda, M. CPB 1981, 29, 2557.
41. (a) Posner, G. H.; Perfetti, R. B.; Runquist, A. W. TL 1976, 3499. (b) Posner, G. H.; Chapdelaine, M. J. S 1977, 555. (c) Posner, G. H.; Chapdelaine, M. J. TL 1977, 3227.
42. Posner, G. H.; Runquist, A. W.; Chapdelaine, M. J. JOC 1977, 42, 1202. Also see: Suginome, H.; Kato, K. TL 1973, 4143.
43. (a) Pan, H.-L.; Cole, C.-A.; Fletcher, T. L. S 1975, 716. (b) Liu, K.-T.; Tong, Y.-C. S 1978, 669.
44. Review: Laszlo, P. COS 1991, 7, 839. Recent examples: (a) Singh, S.; Dev, S. T 1993, 49, 10959. (b) Lee, D. G.; Chen, T.; Wang, Z. JOC 1993, 58, 2918. (c) Morimoto, T.; Hirano, M.; Iwasaki, K.; Ishikawa, T. CL 1994, 53. (d) Santaniello, E.; Ponti, F.; Manzocchi, A. S 1978, 891.
45. Soai, K.; Watanabe, M.; Yamamoto, A. JOC 1990, 55, 4832.
46. (a) Craig, J. C.; Naik, A. R. JACS 1962, 84, 3410. (b) Gonzalez, A.; Galvez, C. S 1982, 946. (c) Luh, T.-Y.; Chow, H.-F.; Leung, W. Y.; Tam, S. W. T 1985, 41, 519. (d) Nagano, H.; Masunaga, Y.; Matsuo, Y.; Shiota, M. BCJ 1987, 60, 707. See also: (e) Métayer, A.; Barbier, M. BSF 1972, 3625.
47. (a) Marshall, J. A.; Roebke, H. JOC 1966, 31, 3109. (b) Hudlicky, T.; Srnak, T. TL 1981, 22, 3351. (c) Reetz, M. T.; Wenderoth, B.; Urz, R. CB 1985, 118, 348. (d) Hatzigrigoriou, E.; Roux-Schmitt, M.-C.; Wartski, L. T 1988, 44, 4457. Also see: (e) Scettri, A.; Piancatelli, G.; D'Auria, M.; David, G. T 1979, 35, 135.
48. (a) Larock, R. C.; Chow, M.-S.; Smith, S. J. JOC 1986, 51, 2623. (b) Manning, D. T.; Coleman, H. A. J. JOC 1969, 34, 3248.
49. Tsuboi, S.; Matsuda, T.; Mimura, S.; Takeda, A. OSC 1993, 8, 251.
50. Johns, W. F.; Jerina, D. M. JOC 1963, 28, 2922.
51. Boar, R. B.; McGhie, J. F.; Robinson, M.; Barton, D. H. R.; Horwell, D. C.; Stick, R. V. JCS(P1) 1975, 1237.
52. Coutts, I. G. C.; Culbert, N. J.; Edward, M.; Hadfield, J. A.; Musto, D. R.; Pavlidis, V. H.; Richards, D. J. JCS(P1) 1985, 1829.
53. (a) Greene, A. E.; Cruz, A.; Crabbé, P. TL 1976, 2707. (b) van Leusen, A. M.; Strating, J. OSC 1988, 6, 981.
54. (a) Posner, G. H.; Oda, M. TL 1981, 22, 5003. (b) Rana, S. S.; Barlow, J. J.; Matta, K. L. TL 1981, 22, 5007. (c) Posner, G. A.; Okada, S. S.; Babiak, K. A.; Miura, K.; Rose, R. K. S 1981, 789. (d) Nagasawa, K.; Yoshitake, S.; Amiya, T.; Ito, K. SC 1990, 20, 2033.

Viresh H. Rawal, Seiji Iwasa, Alan S. Florjancic, & Agnes&thsp;Fabre

The Ohio State University, Columbus, OH, USA



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