ALUMINUM CHLORIDE 1
conditions (eq 5).9 These conditions are compatible with halogen
Aluminum Chloride1
atoms present elsewhere in the molecule. Acylation reactions of
phenolic compounds with heteroaromatic systems have also been
AlCl3
accomplished (eq 6).10
CO2Me CO2Me
[7446-70-0] AlCl3 (MW 133.34) AlCl3 PhH
(3)
InChI = 1/Al.3ClH/h;3*1H/q+3;;;/p-3/fAl.3Cl/h;3*1h/
50 80%
X Ph
>97%
qm;3*-1
(S)(S)
InChIKey = VSCWAEJMTAWNJL-GZMOREBICG
X = OSO2Me, OSO2Cl
(Lewis acid catalyst for Friedel Crafts, Diels Alder, [2 + 2] cy-
cloadditions, ene reactions, rearrangements, and other reactions)
O
ć% ć%
AlCl3 PhH
Physical Data: mp 190 C (193 194 C sealed tube); sublimes
(4)
CO2Et
ć%
at 180 C; d 2.44 g cm-3.
93%
Solubility: sol many organic solvents, e.g. benzene, nitroben-
zene, carbon tetrachloride, chloroform, methylene chloride,
nitromethane, and 1,2-dichloroethane; insol carbon disulfide.
R
RCOCl, AlCl3
Form Supplied in: colorless solid when pure, typically a gray
(5)
Et3SiH
or yellow-green solid; also available as a 1.0 M nitrobenzene
RR
43 94%
solution.
Handling, Storage, and Precautions: fumes in air with a strong
odor of HCl. AlCl3 reacts violently with H2O. All containers OH Cl
HO OH
should be kept tightly closed and protected from moisture.1c
Cl Cl
AlCl3
N
+
Use in a fume hood.
(6)
N 63% N
OH
N
Cl
Cl
Friedel Crafts Chemistry.1,2 AlCl3 has traditionally been
used in stoichiometric or catalytic3 amounts to mediate Friedel
Treatment of aryl azides with AlCl3 has been reported to give
Crafts alkylations and acylations of aromatic systems (eq 1).
polycyclic aromatic compounds (eq 7),11 or aziridines when the
reactions are run in the presence of alkenes (eq 8).12
O
R
RCOCl R
RCl
AlCl3
(1)
(7)
AlCl3
AlCl3
89%
N3 N
H
This is a result of the Lewis acidity of AlCl3 which complexes
strongly with carbonyl groups.4 Adaptations of these basic reac-
N3
tions have been reported.5 In chiral systems, inter- and intramolec-
AlCl3
ular acylations have been achieved without the loss of optical
+
(8)
activity (eq 2).6 N
63 93%
nn
Ar
R
O
n = 1, 2
O
AlC3
Cl (2)
benzene
The scope of Friedel Crafts chemistry has been expanded
NHCO2Me
50 60%
MeO2CHN
beyond aromatic systems to nonaromatic systems, such as alkenes
O
and alkynes and the mechanistic details have been investigated.13
O
AlC3
The Friedel Crafts alkylation14 and acylation15 of alkenes pro-
Cl NHCO2Me
vide access to a variety of organic systems (eq 9). The acylation of
55 75%
>98% ee
NHCO2Me
alkynes provides access to cyclopentenone derivatives (eq 10).16
In addition, one can use this chemistry to access indenyl systems17
and vinyl chlorides.18 Allylic sulfones can undergo allylation
Friedel Crafts chemistry at an asymmetric center generally pro-
chemistry (eq 11).19
ceeds with racemization, but the use of mesylates or chlorosul-
fonates as leaving groups has resulted in alkylations with excellent
Ac
H
AcCl
control of stereochemistry.7 The reactions proceed with inversion
AlCl3
(9)
of configuration (eq 3). Cyclopropane derivatives have been used
48%
as three-carbon units in acylation reactions (eq 4).8 In conjunc-
H
Cl
tion with triethylsilane, a net alkylation is possible under acylation
Avoid Skin Contact with All Reagents
2 ALUMINUM CHLORIDE
O O
Propargylic silanes undergo acylation to generate allenyl
R1
1. AlCl3, HC CH
R1
ketones (eq 17),25 while alkylsilanes afford cycloalkanones
2. Zn
Cl
(10)
(eq 18).26
45 70%
R2
R2
"
AcCl
R R
TMS
(17)
AlCl3
SO2Ph
O
O O
O
AlCl3 AlCl3
R COCl R
AlCl3
78% 90%
(18)
60 87%
TMS
O
Several name reactions are promoted by AlCl3. For exam-
(11)
ple, the Darzens Nenitzescu reaction is simply the acylation
of alkenes. The Ferrario reaction generates phenoxathiins from
diphenyl ethers (eq 19).27 The rearrangement of acyloxy aro-
The use of silyl derivatives in Friedel Crafts chemistry has
matic systems is known as the Fries rearrangement (eq 20).28
not only improved the regioselectivity but extended the scope
Aryl aldehydes are produced by the Gatterman aldehyde synthe-
of these reactions. Substitution at the ipso position occurs with
sis (eq 21).29 The initial step of the Haworth phenanthrene syn-
aryl silanes (eq 12).20 The ability of silyl groups to stablize
thesis makes use of a Friedel Crafts acylation.30 The acylation
²-carbenium ions (²-effect) affords acylated products with
of phenolic compounds is called the Houben Hoesch reaction
complete control of regiochemistry (eq 13).21
(eq 22).31 The Leuckart amide synthesis generates aryl amides
from isocyanates (eq 23).32
TMS
O O
S
TMS TMS S
AlCl3
AlCl3
Cl
+
(19)
75%
87%
O
TMS
O
TMS
(12)
O
AlCl3
O
(20)
85%
AcCl O
TMS
OAc
O
OH
AlCl3
OAc
(13)
OH
77%
OR OR
The use of silylacetylenes gives ynones (eq 14),22 cyclopen-
AlCl3
tenone derivatives (eq 15),23 and Ä…-amino acid derivatives
(21)
HCl
(eq 16).24
HCN
CHO
O
O
AlCl3
+ TMS TMS
(14)
85 94%
R
R Cl
OH OH
AlCl3
TMS
RCN
(22)
HCl
OH OH
O
Cl
O R
AlCl3
Cl O
+ (15)
TMS
63%
O
TMS
AlCl3
NHR
(23)
RNCO
TMS
TMS
Cl H
AlCl3
+ Amides can also be obtained by AlCl3 catalyzed ester amine
H
(16)
EtO2CNH CO2Me
65%
exchange which proceeds primarily without racemization of chi-
EtO2CNH CO2Me
TMS
ral centers (eq 24).33 The reaction of phenols with ²-keto esters is
A list of General Abbreviations appears on the front Endpapers
ALUMINUM CHLORIDE 3
known as the Pechmann condensation (eq 25).34 Aryl amines are
used in the Riehm quinoline synthesis (eq 26).35 Aromatic sys-
tems may be coupled via the Scholl reaction (eq 27)36 and indole
AlCl3
O CN
derivatives are prepared in the Stolle synthesis (eq 28).37 In the +
(31)
70%
Zincke-Suhl reaction, phenols are converted to dienones (eq 29).38
O
Cl
Cl
Ph
AlCl3
H
(24)
CONEt2
CO2Me
N
Ph
Et2NH AlCl3
Ph
+
(32)
77%
NPh
60%
S:R = 82:18
(S) 98%
OTMS
OTMS
AlCl3 can also be used to catalyze [2 + 2] cycloaddition reac-
OH
AlCl3
O
tions (eq 33)43 and ene reactions (eq 34).44
(25)
+
40 55%
CO2Me
O O
H
Et
AlCl3
(33)
+
16%
NH3
O
O
AlCl3
O
(26)
+
O
O
N
AlCl3
OO
(34)
MVK
80 90%
AlCl3
O O
(27)
O
68%
Rearrangements. AlCl3 catalyzed rearrangement of hydro-
carbon derivatives to adamantanes has been well documented
R1
R1
R2 (eq 35).45 Other rearrangements have been used in triquinane syn-
Cl R2
thesis (eq 36).46
AlCl3
O (28)
N
N O
R
R
AlCl3
(35)
60%
CCl3
AlCl3
(29)
CCl4 O
37 42%
H
OH O
AlCl3
(36)
93%
O
H
Diels Alder Reactions. There is some evidence that AlCl3
catalysis of Diels Alder reactions changes the transition state
from a synchronous to an asynchronous one.39 This also enhances
Miscellaneous Reactions. AlCl3 has been used to catalyze the
asymmetric induction by increasing steric interactions at one end
addition of allylsilanes to aldehydes and acid chlorides (eq 37).47
of the dieneophile. There are many examples of AlCl3 promoted
Cyclic ethers (pyrans and oxepins) have been prepared with hy-
Diels Alder reactions (eq 30).40 Hetero-Diels Alder reactions
can be used to generate oxygen (eq 31)41 and nitrogen (eq 32)42 droxyalkenes (eq 38).48 The course of reactions between aldehy-
des and allylic Grignard reagents can be completely diverted to
containing heterocycles.
Ä…-allylation by AlCl3 (eq 39).49 The normal course of the reaction
gives Å‚-allylation products.
OMe OMe
AlCl3
OTMS
+
H
62%
CO3Et
RCHO
(37)
O O R
R2 TMS
H H
AlCl3
CO2Et
R2
(30)
40 45%
Avoid Skin Contact with All Reagents
4 ALUMINUM CHLORIDE
Cl
13. (a) Puck, R.; Mayr, H.; Rubow, M.; Wilhelm, E., J. Am. Chem. Soc. 1986,
OH
108, 7767. (b) Brownstein, S.; Morrison, A.; Tan, L. K., J. Org. Chem.
MeCHO
1985, 50, 2796.
(38)
Ph
AlCl3
14. Mayr, H.; Striepe, W., J. Org. Chem. 1983, 48, 1159.
Ph O
57%
15. (a) Ansell, M. F.; Ducker, J. W., J. Chem. Soc. 1960, 5219. (b) Cantrell,
T. S., J. Org. Chem. 1967, 32, 1669. (c) Groves, J. K., Chem. Soc. Rev.
RCHO
R
(39) 1972, 1, 73. (d) House, H. O. Modern Synthetic Reactions; Benjamin-
MgBr
AlCl3
Cummings: Menlo Park, CA, 1972; p 786.
OH
16. (a) Martin, G. J.; Rabiller, C.; Mabon, G., Tetrahedron Lett. 1970, 3131.
(b) Rizzo, C. J.; Dunlap, N. A.; Smith, A. B., J. Org. Chem. 1987, 52,
AlCl3 can be used to remove t-butyl groups from aromatic
5280.
rings (eq 40),50 thereby using this group as a protecting ele-
17. Maroni, R.; Melloni, G.; Modena, G., J. Chem. Soc., Perkin Trans. 1
ment for a ring position. AlCl3 has also been used to remove
1974, 353.
p-nitrobenzyl (PNB) and benzhydryl protecting groups (eq 41).51
18. Maroni, R.; Melloni, G.; Modena, G., J. Chem. Soc., Perkin Trans. 1
The combination of AlCl3 and Ethanethiol has formed the ba-
1973, 2491.
sis of a push pull mechanism for the cleavage of many types of
19. Trost, B. M.; Ghadiri, M. R., J. Am. Chem. Soc. 1984, 106, 7260.
bonds including C X,52 C NO2,53 C=C,54 and C O.55 Further-
20. (a) Eaborn, C., J. Chem. Soc 1956, 4858. (b) Habich, D.; Effenberger,
more, AlCl3 has been used to catalyze chlorination of aromatic
F., Synthesis 1979, 841.
rings,56 open epoxides,57 and mediate addition of dichlorophos-
21. (a) Fleming, I.; Pearce, A., J. Chem. Soc., Chem. Commun. 1975, 633.
phoryl groups to alkanes.58
(b) Fristad, W. E.; Dime, D. S.; Bailey, T. R.; Paquette, L. A., Tetrahedron
Lett. 1979, 1999.
OH OH
22. (a) Walton, D. R. M.; Waugh, F., J. Organomet. Chem. 1972, 37, 45. (b)
t-Bu t-Bu
AlCl3
Newman, H., J. Org. Chem. 1973, 38, 2254.
(40)
80%
23. Karpf, M., Tetrahedron Lett. 1982, 23, 4923.
24. Casara, P.; Metcalf, B. W., Tetrahedron Lett. 1978, 1581.
t-Bu
25. Flood, T.; Peterson, P. E., J. Org. Chem. 1980, 45, 5006.
26. Urabe, H.; Kuwajima, I., J. Org. Chem. 1984, 49, 1140.
NHCO2PNB
R
27. Ferrario, E., Bull. Soc. Chem. Fr. 1911, 9, 536.
AlCl3
S
28. (a) Blatt, A. H., Org. React. 1942, 1, 342. (b) Gammill, R. B., Tetrahedron
N
Lett. 1985, 26, 1385.
24 82%
O
CO2PNB
NH2 29. Truce, W. E., Org. React. 1957, 9, 37.
R
30. Berliner, E., Org. React. 1949, 5, 229.
S
31. Spoerri, P. E.; Dubois, A. S., Org. React. 1949, 5, 387.
(41)
N
32. Effenberger, F.; Gleiter, R., Chem. Ber. 1964, 97, 472.
O
CO2H
33. Gless, R. D., Synth. Commun. 1986, 16, 633.
34. Sethna, S.; Phadke, R., Org. React. 1953, 7, 1.
35. Elderfield, R. C.; McCarthy, J. R., J. Am. Chem. Soc. 1951, 73, 975.
36. Clowes, G. A., J. Chem. Soc., Perkin Trans. 1 1968, 2519.
1. (a) Thomas, C. A. Anhydrous Aluminum Chloride in Organic
Chemistry; ACS Monograph Series; Reinholdt: New York, 1941.
37. Sumpter, W. C., C. R. Hebd. Seances Acad. Sci. 1944, 34, 393.
(b) Shine, H. J. Aromatic Rearrangements; Elsevier: Amsterdam, 1967.
38. Newman, M. S.; Wood, L. L., J. Am. Chem. Soc. 1959, 81, 6450.
(c) Fieser & Fieser 1967, 1, 24. (d) Olah, G. A. Friedel Crafts Chemistry;
39. Tolbert, L. M.; Ali, M. B., J. Am. Chem. Soc. 1984, 106, 3806.
Wiley: New York, 1973. (e) Roberts, R. M.; Khalaf, A. A. Friedel Crafts
40. (a) Cohen, N.; Banner, B. L.; Eichel, W. F., Synth. Commun. 1978, 8, 427.
Alkylation Chemistry; Marcel Dekker: New York, 1984.
(b) Fringuelli, F.; Pizzo, F.; Taticchi, A.; Wenkert, E., Synth. Commun.
2. Gore, P. H., C. R. Hebd. Seances Acad. Sci. 1955, 55, 229.
1979, 9, 391. (c) Ismail, Z. M.; Hoffmann, H. M. R., J. Org. Chem. 1981,
3. Pearson, D. E.; Buehler, C. A., Synthesis 1972, 533.
46, 3549. (d) Vidari, G.; Ferrino, S.; Grieco, P. A., J. Am. Chem. Soc.
4. (a) Tan, L. K.; Brownstein, S., J. Org. Chem. 1982, 47, 4737. (b) Tan, L.
1984, 106, 3539. (e) Angell, E. C.; Fringuelli, F.; Guo, M.; Minuti, L.;
K.; Brownstein, S., J. Org. Chem. 1983, 48, 3389.
Taticchi, A.; Wenkert, E., J. Org. Chem. 1988, 53, 4325.
5. Drago, R. S.; Getty, E. E., J. Am. Chem. Soc. 1988, 110, 3311.
41. Ismail, Z. M.; Hoffmann, H. M. R., Angew. Chem., Int. Ed. Engl. 1982,
21, 859.
6. McClure, D. E.; Arison, B. H.; Jones, J. H.; Baldwin, J. J., J. Org. Chem.
1981, 46, 2431.
42. LeCoz, L.; Wartski, L.; Seyden-Penne, J.; Chardin, P.; Nierlich, M.,
Tetrahedron Lett. 1989, 30, 2795.
7. Piccolo, O.; Spreafico, F.; Visentin, G.; Valoti, E., J. Org. Chem. 1985,
50, 3945.
43. Jung, M. E.; Haleweg, K. M., Tetrahedron Lett. 1981, 22, 2735.
8. Pinnick, H. W.; Brown, S. P.; McLean, E. A.; Zoller, L. W., J. Org. Chem.
44. (a) Snider, B. B.; Rodini, D. J.; Conn, R. S. E.; Sealfon, S., J. Am. Chem.
1981, 46, 3758.
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9. Jaxa-Chamiel, A.; Shah, V. P.; Kruse, L. I., J. Chem. Soc., Perkin Trans. 1979, 2625. (c) Snider, B. B., Acc. Chem. Res. 1980, 13, 426.
1 1989, 1705.
45. (a) Bingham, R. C.; Schleyer, P. R., Top. Curr. Chem. 1971, 18, 1. (b)
10. (a) Pollak, A.; Stanovnik, B.; Tisler, M., J. Org. Chem. 1966, 31, 4297. McKervey, M. A., Chem. Soc. Rev. 1974, 3, 479. (c) McKervey, M. A.,
(b) Coates, W. J.; McKillop, A., J. Org. Chem. 1990, 55, 5418. Tetrahedron 1980, 36, 971.
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Commun. 1985, 287. Odaira, Y.; Yasuda, M.; Shima, K., J. Am. Chem. Soc. 1989, 111, 3707.
12. Takeuchi, H.; Shiobara, Y.; Kawamoto, H.; Koyama, K., J. Chem. Soc., 47. (a) Deleris, G.; Donogues, J.; Calas, R., Tetrahedron Lett. 1976, 2449.
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A list of General Abbreviations appears on the front Endpapers
ALUMINUM CHLORIDE 5
48. Coppi, L.; Ricci, A.; Taddai, M., J. Org. Chem. 1988, 53, 911. 55. Node, M.; Nishide, K.; Ochiai, M.; Fuji, K.; Fujita, E., J. Org. Chem.
1981, 46, 5163.
49. Yamamoto, Y.; Maruyama, K., J. Org. Chem. 1983, 48, 1564.
56. Watson, W. D., J. Org. Chem. 1985, 50, 2145.
50. Lewis, N.; Morgan, I., Synth. Commun. 1988, 18, 1783.
57. Eisch, J. J.; Liu, Z.-R.; Ma, X.; Zheng, G.-X., J. Org. Chem. 1992, 57,
51. Ohtani, M.; Watanabe, F.; Narisada, M., J. Org. Chem. 1984, 49, 5271.
5140.
52. Node, M.; Kawabata, T.; Ohta, K.; Fujimoto, M.; Fujita, E.; Fuji, K., J.
58. Olah, G. A.; Farooq, O.; Wang, Q.; Wu, A.-H., J. Org. Chem. 1990, 55,
Org. Chem. 1984, 49, 3641.
1224.
53. Node, M.; Kawabata, T.; Ueda, M.; Fujimoto, M.; Fuji, K.; Fujita, E.,
Tetrahedron Lett. 1982, 23, 4047.
Paul Galatsis
54. Fuji, K.; Kawabata, T.; Node, M.; Fujita, E., J. Org. Chem. 1984, 49,
University of Guelph, Guelph, Ontario, Canada
3214.
Avoid Skin Contact with All Reagents