ALUMINA 1
oxidation of selenides to selenoxides and their elimination to
Alumina1
alkenes can be accomplished in one step using basic alumina and
tert-Butyl Hydroperoxide in THF.12
Al2O3
alumina
pyridine
220 230 °C
[1344-28-1] Al2O3 (MW 101.96)
(1)
HO
InChI = 1/2Al.3O/rAl2O3/c3-1-5-2-4 44%
H H
O O
InChIKey = TWNQGVIAIRXVLR-XYRCZMGDAJ
O O
(a mildly acidic, basic, or neutral support for chromatographic
Ph Ph
alumina
separations; a reagent for catalyzing dehydration, elimination, ad- O O
Ph Ph
activity I
dition, condensation, epoxide opening, oxidation, and reduction
(2)
65 80%
reactions)
EtO
Alternate Name: Å‚-alumina.
F O
ć% ć% F F
Physical Data: mp 2015 C; bp 2980 C; d 3.97 g cm-3.
alumina
Solubility: slightly sol acid and alkaline solution.
CCl4, 25 °C
+ (3)
Form Supplied in: fine white powder, widely available in varying
24 h
particle size (50 200 m; 70 290 mesh), in acidic (pH 4), basic
60% <4%
(pH 10), and neutral (pH 7) forms.
Drying: the activity of alumina has been classified by the Brock-
Alumina has been used for various dehydration reactions,
mann scale into five grades. The most active form, grade I, is
including those leading to piperidines,13 pyrroles (eq 4) and
ć%
obtained by heating alumina to 200 C while passing an inert
pyrazoles,14 and other heterocycles.15 It is also an effective cat-
ć%
gas through the system, or heating to <"400 C in an open vessel,
alyst for the selective protection of aldehydes in the presence of
followed by cooling in a dessicator. Addition of 3 4% (w/w)
ketones.16
water and mixing for several hours converts grade I alumina to
EtNH2, alumina
grade II. Other grades are similarly obtained (grade III, 5 7%;
0 to 20 °C
grade IV, 9 11%; grade V, 15 19% water).2,3 (4)
N
96%
O O
Handling, Storage, and Precautions: inhalation of fine mesh alu-
Et
mina can cause respiratory difficulties. Alumina is best handled
under a fume hood and stored under dry, inert conditions.
Addition and Condensation Reactions. Alumina pro-
motes the addition of various heteroatom species, whether by
Introduction. Alumina is one of the most widely used packing
electrophilic or nucleophilic processes. In contrast to the elimi-
materials for adsorption chromatography and is available in acidic,
nation reactions described earlier, alumina also promotes the in-
basic, and neutral forms. Use of the correct type is important to
tramolecular addition of OH and OR groups to isolated (eq 5)6c
avoid unwanted reactions of the substrate being purified.1,3 Pos-
and carbonyl-activated alkenes.17 It is also reported to catalyze
sessing both Lewis acidic and basic sites, alumina has been found
the conjugate addition of other nucleophiles, such as amines.18 In
to catalyze a wide range of reactions, generally under conditions
the presence of alumina, Iodine can be used to iodinate aromat-
that are milder and more selective than comparable homogeneous
ics, hydroiodinate alkenes, and diiodinate alkynes (eq 6).19 Hy-
reactions.1
drochlorinations and hydrobrominations of alkenes and alkynes
give the Markovnikov products, with good stereoselectivity.20
Dehydration and Eliminations. One of the earliest uses of
acidic
alumina as a catalyst was for the dehydration of alcohols.4,5 These
alumina
basic
O
reactions generally require high temperature and yield primarily alumina PhH, 75 °C
O
non-Saytzeff products. Complex terpenes have been dehydrated O
84% 72%
with Pyridine or Quinoline doped alumina (eq 1).6b Numerous
OH
other groups can be eliminated in the presence of alumina, in-
cluding OR, OAc, O3SR, O2SR, and halides.1,7 Some of these
O
eliminations proceed under mild conditions,1 often during chro-
(5)
matographic purification (eq 2).7d Sulfonates can be eliminated
O
in the presence of acid and base sensitive groups, without skele-
tal rearrangements. However, a large excess of properly acti-
vated alumina is required, and poor stereo- and regiocontrol are
cyclohexene 1-hexyne
observed.7e Dehydrohalogenations, particularly dehydrofluorina-
pet ether
I
I
I2 pet ether
tions, occur readily over alumina (eq 3).8 Stereoselective syn-
35 °C, 2 h rt, 4 h
Bu
activated (6)
theses of vinyl halides have been developed that take advantage
85% 92%
alumina
I
of desilicohalogenation9 or deborohalogenation10 of vinylsilane
or vinylboronic acid derived dihalides. Benzol[c]thiophene has
Aldol-type condensations between aldehydes and various ac-
been synthesized by dehydration of a sulfoxide precursor.11 The
tive methylene compounds,21 Michael reactions (eq 7),22 as well
Avoid Skin Contact with All Reagents
2 ALUMINA
4% RXH
as Wittig-type reactions23 can be carried out on alumina under
OH
neutral alumina
mild conditions, often without a solvent. An interesting nitroaldol
O (11)
Et2O, 25 °C, 1 h
reaction cyclization sequence gives 2-isoxazoline 2-oxides with
XR
good diastereoselectivity (eq 8).24
RX = MeO, 66%; PhS, 70%, PhSe, 95%; n-BuNH, 73%
NO2
basic alumina
O O
O O N
+
H
O
HO SiMe3
NO2 O rt, 5 8 h
neutral alumina KH
88%
O
SiMe3 85 °C, 4 d n-Hex N THF, rt
n-Hex
(7)
63%
O
O
n-Hex N (12)
NO2 Al2O3 O N+
Ph
H + (8)
CO2Et
24 h Ph
CO2Et
Br
62%
OH
1. basic
alumina (I)
OAc
trans:cis = 9:1
O
hexanes
rt, 24 h
(13)
Orbital symmetry controlled reactions that have been promoted
2. Ac2O, py
O
O
by alumina include the Diels Alder,25 the ene,26 and the Carroll
90 100%
rearrangement.27 These reactions proceeded under milder condi-
tions and with greater stereoselectivity. In a spectacular exam-
ple, chromatographic purification promoted a diastereoselective
Oxidations and Reductions. Posner has shown that Oppe-
intramolecular Diels Alder that produced the verrucarol skeleton
nauer oxidations, with Cl3CCHO or PhCHO as the hydrogen
(eq 9).25b
acceptors, are greatly accelerated in the presence of activated
alumina.41 Secondary alcohols are oxidized selectively over pri-
mary alcohols (eq 14) and groups susceptible to other oxidants
H
(sulfides, selenides, and alkenes) are unaffected. Even cyclobu-
neutral alumina (I)
O
column, rt
tanol, which is prone to fragmentation with one-electron oxidants,
O
(9)
can be oxidized to cyclobutanone in 92% yield.
O
83%
O
O
O
H
H
2 equiv PhCHO
OH O
alumina
(14)
OH OH
Alkylation reactions that have been induced by alumina in-
8 8
25 °C, 24 h
clude per-C-methylation of phenol,28 intramolecular alkylation 65%
to yield a spiro-fused cyclopropane,29 and S-30 and O-alkylations
The complementary reduction reaction (Meerwein
(eq 10).31 The activation of Diazomethane by alumina has pro-
Ponndorf Verley), using isopropanol as the hydride donor,
vided methods for the conversion of ketones to epoxides32 and
is also facilitated by alumina and allows the selective reduction
for the selective monomethylation of dicarboxylic acids.33 Basic
of aldehydes over ketones.42 Functional groups that survive these
alumina has been used for the generation and trapping of
conditions include alkene, nitro, ester, amide, nitrile, primary and
dichlorocarbene.34
secondary iodides, and benzylic bromide.
Air oxidation of a fluoren-9-ol to the fluoren-9-one and thiols
LDA
to disulfides are accelerated on the alumina surface.43 Alumina
glyme
Ph SO2Ph
90%
has also been used as a solid support for a variety of inorganic
Br
O
reagents,44 and for immobilizing chiral catalysts.45
(10)
Ph SO2Ph
Miscellaneous Reactions. Many rearrangements are cat-
O
neutral alumina
alyzed by alumina.1 The Beckmann rearrangement46 of the O-
toluene O
Ph
rt sulfonyloxime shown gives the expected amide with activated
95%
alumina, and the corresponding oxazoline with basic alumina
SO2Ph
(eq 15).46d Alumina has long been used for isomerization of ²,Å‚-
unsaturated ketones to the conjugated ketones.47 Isomerizations
of alkynes to allenes,48 and allenes to conjugated dienoates49 have
Epoxides. Epoxides can be opened under mild, selective
also been reported (eq 16).
conditions using alumina impregnated with a variety of nucle-
ophiles, such as alcohols, thiols, selenols, amines, carboxylic acids
O
(eq 11),35 and peroxides.36 Use is made of this process in a route to
activated alumina
(15)
(Z)-enamines (eq 12).37 Formation of C C bonds by intramolec-
N
80%
H H
H
ular opening of epoxides has been reported (eq 13),38 as have
OH N OH
OSO2Ar
alumina catalyzed epoxide formations23,39 and rearrangements.40
A list of General Abbreviations appears on the front Endpapers
ALUMINA 3
alumina
CO2Me 20. Kropp, P. J.; Daus, K. A.; Tubergen, M. W.; Kepler, K. D.; Wilson,
Et "
(16)
Et
CO2Me PhH, reflux, 5 h
V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G. W., J. Am. Chem. Soc.
82%
1993, 115, 3071, and references cited therein.Addition of HN3:Breton,
G. W.; Daus, K. A.; Kropp, P. J., J. Org. Chem. 1992, 57, 6646.
21. (a) Rosan, A.; Rosenblum, M., J. Org. Chem. 1975, 40, 3621. (b) Texier-
Alumina promotes the hydrolysis of acetates of primary
Boullet, F.; Foucaud, A., Tetrahedron 1982, 23, 4927. (c) Rosini, G.;
alcohols,50 the deacylation of imides,51 the hydrolysis of
Ballini, R.; Sorrenti, P., Synthesis 1983, 1014. (d) Varma, R. S.; Kabalka,
sulfonylimines,52 and the decarbalkoxylation of ²-keto esters and
G. W.; Evans, L. T.; Pagni, R. M., Synth. Commun. 1985, 15, 279. (e)
carbamates.53 It can also be used for acylations and esterifica-
Nesi, R.; Stefano, C.; Piero, S.-F., Heterocycles 1985, 23, 1465. (f)
tions, with high selectivity for primary alcohols over secondary
Rosini, G.; Ballini, R.; Petrini, M.; Sorrenti, P., Synthesis 1985, 515.
alcohols.54
(g) Foucaud, A.; Bakouetila, M., Synthesis 1987, 854. (h) Moison, H.;
Texier-Boullet, F.; Foucaud, A., Tetrahedron 1987, 43, 537.
22. (a) Rosini, G.; Marotta, E.; Ballini, R.; Petrini, M., Synthesis 1986, 237.
(b) Ballini, R.; Petrini, M.; Marcantoni, E.; Rosini, G., Synthesis 1988,
1. Posner, G. H. , Angew. Chem., Int. Ed. Engl. 1978, 17, 487.
231.
2. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals;
23. Texier-Boullet, F.; Villemin, D.; Ricard, M.; Moison, H.; Foucaud, A.,
Pergamon: New York, 1988; pp 20, 310.
Tetrahedron 1985, 41, 1259.
3. (a) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R.
24. Isoxazoline:Rosini, G.; Galarini, R.; Marotta, E.; Righi, P., J. Org. Chem.
Vogel s Textbook of Practical Organic Chemistry; Longman-Wiley:New
1990, 55, 781.Rosini, G.; Marotta, E.; Righi, E.; Seerden, J. P., J. Org.
York, 1989; p 212. (b) Fieser & Fieser 1967, 1, 19.
Chem. 1991, 56, 6258.
4. Knözingery, H., Angew. Chem., Int. Ed. Engl. 1968, 7, 791.
25. (a) Parlar, H.; Baumann, R., Angew. Chem., Int. Ed. Engl. 1981, 20, 1014
5. (a) Hershberg, E. B.; Ruhoff, J. R., Org. Synth. 1937, 17, 25. (b) Newton,
(b) Koreeda, M.; Ricca, D. J.; Luengo, J. I., J. Org. Chem. 1988, 53,
L. W.; Coburn, E. R., Org. Synth., Coll. Vol. 1955, 3, 312. (c) Sawyer,
5586.
R. L.; Andrus, D. W., Org. Synth., Coll. Vol. 1955, 3, 276.
26. (a) Tietze, L. F.; Beifuss, U.; Ruther, M., J. Org. Chem. 1989, 54, 3120.
6. (a) von Rudloff, E., Can. J. Chem. 1961, 39, 1860. (b) Corey, E. J.;
(b) Tietze, L. F.; Beifuss, U., Synthesis 1988, 359.
Hortmann, A. G., J. Am. Chem. Soc. 1965, 87, 5736. (c) Barrett, H. C.;
27. Pogrebnoi, S. I.; Kalyan, Y. B.; Krimer, M. Z.; Smit, W. A., Tetrahedron
Büchi, G., J. Am. Chem. Soc. 1967, 89, 5665.
1987, 28, 4893.
7. (a) Kobayashi, S.; Shinya, M.; Taniguchi, H. , Tetrahedron 1971, 71.
28. Cullinane, N. M.; Chard, S. J.; Dawkins, C. W. C., Org. Synth., Coll. Vol
(b) Ishii, H.; Tozyo, T.; Nakamura, M.; Funke, E., Chem. Pharm. Bull.
1963, 4, 520.
1972, 20, 203. (c) Gotthardt, H.; Hammond, G. S., Chem. Ber. 1974,
29. Baird, R.; Winstein, S., J. Am. Chem. Soc. 1963, 85, 567.
107, 3922. (d) Mayr, H.; Huisgen, R., Angew. Chem., Int. Ed. Engl.
30. Villemin, D., J. Chem. Soc., Chem. Commun. 1985, 870.
1975, 14, 499. (e) Posner, G. H.; Gurria, G. M.; Babiak, K. A., J. Org.
Chem. 1977, 42, 3173. (f) Vidal, J.; Huet, F., Tetrahedron 1986, 27, 31. (a) Ogawa, H.; Chihara, T.; Teratani, S.; Taya, K., Bull. Chem. Soc.
3733. Jpn. 1986, 59, 2481. (b) Cooke, F.; Magnus, P., J. Chem. Soc., Chem.
Commun. 1976, 519.
8. (a) Strobach, D. R.; Boswell, G. A., Jr., J. Org. Chem. 1971, 36, 818. (b)
Boswell, G. A., Jr., J. Org. Chem. 1966, 31, 991. 32. Hart, P. A.; Sandmann, R. A., Tetrahedron 1969, 305.
9. (a) Miller, R. B.; McGarvey, G., J. Org. Chem. 1978, 43, 4424. (b) Miller, 33. Ogawa, H.; Chihara, T.; Taya, K., J. Am. Chem. Soc. 1985, 107, 1365.
R. B.; McGarvey, G., Synth. Commun. 1977, 7, 475.
34. Sarratosa, F., J. Chem. Educ. 1964, 41, 564.
10. Sponholtz, W. R., III; Pagni, R. M.; Kabalka, G. W.; Green, J. F.; Tan,
35. (a) Posner, G. H.; Rogers, D. Z., J. Am. Chem. Soc. 1977, 99, 8208.
L. C., J. Org. Chem. 1991, 56, 5700.
(b) Posner, G. H.; Rogers, D. Z., J. Am. Chem. Soc. 1977, 99, 8214. (c)
Evans, D. A.; Golob, A. M.; Mandel, N. S.; Mandel, G. S., J. Am. Chem.
11. Cava, M. P.; Pollack, N. M.; Mamer, O. A.; Mitchell, M. J., J. Org. Chem.
1971, 36, 3932. Soc. 1978, 100, 8170.
36. Kropf, H.; Amirabadi, H. M.; Mosebach, M.; Torkler, A.; von Wallis,
12. Labar, D.; Hevesi, L.; Dumont, W.; Krief, A., Tetrahedron 1978, 1141.
H., Synthesis 1983, 587.
13. (a) Bourns, A. N.; Embleton, H. W.; Hansuld, M. K., Org. Synth., Coll.
37. Hudrlik, P. F.; Hudrlik, A. M.; Kulkarni, A. K., Tetrahedron 1985, 26,
Vol. 1963, 4, 795. (b) Glacet, C.; Adrian, G., C.R. Hebd. Seances Acad.
139.
Sci., Ser. C 1969, 269, 1322.
38. (a) Boeckman, R. K., Jr.; Bruza, K. J.; Heinrich, G. R., J. Am. Chem. Soc.
14. (a) Texier-Boullet, F.; Klein, B.; Hamelin, J., Synthesis 1986, 409.
1978, 100, 7101. (b) Niwa, M.; Iguchi, M.; Yamamura, S., Tetrahedron
(b) Tolstikov, G. A.; Galin, F. Z.; Makaev, F. Z., Zh. Org. Khim. 1989,
1979, 4291.
25, 875.
39. (a) Dhillon, R. S.; Chhabra, B. R.; Wadia, M. S.; Kalsi, P. S., Tetrahedron
15. (a) LeBlanc, R. J.; Vaughan, K., Can. J. Chem. 1972, 50, 2544.
1974, 401. (b) Antonioletti, R.; D Auria, M.; De Mico, A.; Piancatelli,
(b) Higashino, T.; Suzuki, K.; Hayashi, E., Chem. Pharm. Bull. 1978,
G.; Scettri, A., Tetrahedron 1983, 39, 1765.
26, 3485. (c) Bladé-Font, A., Tetrahedron 1980, 21, 2443. (d) Hooper,
D. L.; Manning, H. W.; LaFrance, R. J.; Vaughan, K., Can. J. Chem.
40. (a) Tsuboi, S.; Furutani, H.; Takeda, A., Synthesis 1987, 292. (b)
1986, 65, 250. (e) Hull, J. W., Jr.; Otterson, K.; Rhubright, D., J. Org.
Harigaya, Y.; Yotsumoto, K.; Takamatsu, S.; Yamaguchi, H.; Onda, M.,
Chem. 1993, 58, 520.
Chem. Pharm. Bull. 1981, 29, 2557.
16. Kamitori, Y.; Hojo, M.; Masuda, R.; Yoshida, T., Tetrahedron 1985, 26, 41. (a) Posner, G. H.; Perfetti, R. B.; Runquist, A. W., Tetrahedron 1976,
4767. 3499. (b) Posner, G. H.; Chapdelaine, M. J., Synthesis 1977, 555. (c)
Posner, G. H.; Chapdelaine, M. J., Tetrahedron 1977, 3227.
17. McPhail, A. T.; Onan, K. D., Tetrahedron 1973, 4641.
42. Posner, G. H.; Runquist, A. W.; Chapdelaine, M. J., J. Org. Chem.
18. (a) Pelletier, S. W.; Venkov, A. P.; Finer-Moore, J.; Mody, N. V.,
1977, 42, 1202.Also see:Suginome, H.; Kato, K., Tetrahedron 1973,
Tetrahedron 1980, 21, 809. (b) Pelletier, S. W.; Gebeyehu, G.; Mody, N.
4143.
V., Heterocycles 1982, 19, 235. (c) Dzurilla, M.; Kutschy, P.; Kristian,
P., Synthesis 1985, 933. 43. (a) Pan, H.-L.; Cole, C.-A.; Fletcher, T. L., Synthesis 1975, 716. (b) Liu,
K.-T.; Tong, Y.-C., Synthesis 1978, 669.
19. Pagni, R.; Kabalka, G. W.; Boothe, R.; Gaetano, K.; Stewart, L. J.;
Conaway, R.; Dial, C.; Gray, D.; Larson, S.; Luidhardt, T., J. Org. Chem. 44. Review:Laszlo, P., Comprehensive Organic Synthesis 1991, 7, 839.
1988, 53, 4477. Recent examples: (a) Singh, S.; Dev, S., Tetrahedron 1993, 49, 10959.
Avoid Skin Contact with All Reagents
4 ALUMINA
(b) Lee, D. G.; Chen, T.; Wang, Z., J. Org. Chem. 1993, 58, 2918. 49. Tsuboi, S.; Matsuda, T.; Mimura, S.; Takeda, A., Org. Synth., Coll. Vol
(c) Morimoto, T.; Hirano, M.; Iwasaki, K.; Ishikawa, T., Chem. Lett. 1993, 8, 251.
1994, 53. (d) Santaniello, E.; Ponti, F.; Manzocchi, A., Synthesis 1978,
50. Johns, W. F.; Jerina, D. M., J. Org. Chem. 1963, 28, 2922.
891.
51. Boar, R. B.; McGhie, J. F.; Robinson, M.; Barton, D. H. R.; Horwell,
45. Soai, K.; Watanabe, M.; Yamamoto, A., J. Org. Chem. 1990, 55, 4832.
D. C.; Stick, R. V., J. Chem. Soc., Perkin Trans. 1 1975, 1237.
46. (a) Craig, J. C.; Naik, A. R., J. Am. Chem. Soc. 1962, 84, 3410. (b)
52. Coutts, I. G. C.; Culbert, N. J.; Edward, M.; Hadfield, J. A.; Musto,
Gonzalez, A.; Galvez, C., Synthesis 1982, 946. (c) Luh, T.-Y.; Chow,
D. R.; Pavlidis, V. H.; Richards, D. J., J. Chem. Soc., Perkin Trans. 1
H.-F.; Leung, W. Y.; Tam, S. W., Tetrahedron 1985, 41, 519. (d) Nagano,
1985, 1829.
H.; Masunaga, Y.; Matsuo, Y.; Shiota, M., Bull. Chem. Soc. Jpn. 1987,
53. (a) Greene, A. E.; Cruz, A.; Crabbé, P. , Tetrahedron 1976, 2707.
60, 707.See also: (e) Métayer, A.; Barbier, M., Bull. Soc. Chem. Fr. 1972,
(b) van Leusen, A. M.; Strating, J., Org. Synth., Coll. Vol 1988, 6,
3625.
981.
47. (a) Marshall, J. A.; Roebke, H., J. Org. Chem. 1966, 31, 3109. (b)
54. (a) Posner, G. H.; Oda, M., Tetrahedron 1981, 22, 5003. (b) Rana,
Hudlicky, T.; Srnak, T., Tetrahedron 1981, 22, 3351. (c) Reetz, M. T.;
S. S.; Barlow, J. J.; Matta, K. L., Tetrahedron 1981, 22, 5007. (c) Posner,
Wenderoth, B.; Urz, R., Chem. Ber. 1985, 118, 348. (d) Hatzigrigoriou,
G. A.; Okada, S. S.; Babiak, K. A.; Miura, K.; Rose, R. K., Synthesis
E.; Schmitt, M.-C.; Wartski, L., Tetrahedron 1988, 44, 4457. Also see: (e)
1981, 789. (d) Nagasawa, K.; Yoshitake, S.; Amiya, T.; Ito, K., Synth.
Scettri, A.; Piancatelli, G.; D Auria, M.; David, G., Tetrahedron 1979,
Commun. 1990, 20, 2033.
35, 135.
48. (a) Larock, R. C.; Chow, M.-S.; Smith, S. J., J. Org. Chem. 1986, 51,
Viresh H. Rawal, Seiji Iwasa, Alan S. Florjancic, & Agnes Fabre
2623. (b) Manning, D. T.; Coleman, H. A. J., J. Org. Chem. 1969, 34,
The Ohio State University, Columbus, OH, USA
3248.
A list of General Abbreviations appears on the front Endpapers