ALUMINUM CHLORIDE

1

Aluminum Chloride

1

AlCl

3

[7446-70-0]

AlCl

3

(MW 133.34)

InChI = 1/Al.3ClH/h;3*1H/q+3;;;/p-3/fAl.3Cl/h;3*1h/

qm;3*-1

InChIKey = VSCWAEJMTAWNJL-GZMOREBICG

(Lewis acid catalyst for Friedel–Crafts, Diels–Alder, [2 + 2] cy-
cloadditions, ene reactions, rearrangements, and other reactions)

Physical Data:

mp 190

◦

C (193–194

◦

C sealed tube); sublimes

at 180

◦

C; d 2.44 g cm

−3

.

Solubility:

sol many organic solvents, e.g. benzene, nitroben-

zene, carbon tetrachloride, chloroform, methylene chloride,
nitromethane, and 1,2-dichloroethane; insol carbon disulfide.

Form Supplied in:

colorless solid when pure, typically a gray

or yellow-green solid; also available as a 1.0 M nitrobenzene
solution.

Handling, Storage, and Precautions:

fumes in air with a strong

odor of HCl. AlCl

3

reacts violently with H

2

O. All containers

should be kept tightly closed and protected from moisture.

1c

Use in a fume hood.

Friedel–Crafts Chemistry.

1

,

2

AlCl

3

has traditionally been

used in stoichiometric or catalytic

3

amounts to mediate Friedel–

Crafts alkylations and acylations of aromatic systems (eq 1).

RCOCl

RCl

AlCl

3

AlCl

3

R

R

O

(1)

This is a result of the Lewis acidity of AlCl

3

which complexes

strongly with carbonyl groups.

4

Adaptations of these basic reac-

tions have been reported.

5

In chiral systems, inter- and intramolec-

ular acylations have been achieved without the loss of optical
activity (eq 2).

6

Cl

NHCO

2

Me

O

AlC

3

Cl

NHCO

2

Me

O

AlC

3

MeO

2

CHN

O

O

NHCO

2

Me

(2)

benzene
50–60%

55–75%

>98% ee

Friedel–Crafts chemistry at an asymmetric center generally pro-

ceeds with racemization, but the use of mesylates or chlorosul-
fonates as leaving groups has resulted in alkylations with excellent
control of stereochemistry.

7

The reactions proceed with inversion

of configuration (eq 3). Cyclopropane derivatives have been used
as three-carbon units in acylation reactions (eq 4).

8

In conjunc-

tion with triethylsilane, a net alkylation is possible under acylation

conditions (eq 5).

9

These conditions are compatible with halogen

atoms present elsewhere in the molecule. Acylation reactions of
phenolic compounds with heteroaromatic systems have also been
accomplished (eq 6).

10

CO

2

Me

X

AlCl

3

PhH

50–80%

>97%

CO

2

Me

Ph

(3)

X = OSO

2

Me, OSO

2

Cl

(S)

(S)

CO

2

Et

AlCl

3

PhH

93%

O

(4)

(5)

RCOCl, AlCl

3

Et

3

SiH

43–94%

R

R

R

OH

OH

N

N

Cl

Cl

Cl

AlCl

3

63%

N

N

Cl

OH

Cl

HO

(6)

+

Treatment of aryl azides with AlCl

3

has been reported to give

polycyclic aromatic compounds (eq 7),

11

or aziridines when the

reactions are run in the presence of alkenes (eq 8).

12

N

3

AlCl

3

89%

N
H

(7)

AlCl

3

63–93%

N

3

R

N

Ar

(8)

+

n

n

n

= 1, 2

The scope of Friedel–Crafts chemistry has been expanded

beyond aromatic systems to nonaromatic systems, such as alkenes
and alkynes and the mechanistic details have been investigated.

13

The Friedel–Crafts alkylation

14

and acylation

15

of alkenes pro-

vide access to a variety of organic systems (eq 9). The acylation of
alkynes provides access to cyclopentenone derivatives (eq 10).

16

In addition, one can use this chemistry to access indenyl systems

17

and vinyl chlorides.

18

Allylic sulfones can undergo allylation

chemistry (eq 11).

19

AcCl

AlCl

3

48%

H

H

Ac

Cl

(9)

Avoid Skin Contact with All Reagents

2

ALUMINUM CHLORIDE

(10)

1. AlCl

3

,

45–70%

CH

HC

2. Zn

R

1

R

2

Cl

O

O

R

1

R

2

O

SO

2

Ph

AlCl

3

O

O

AlCl

3

(11)

78%

90%

The use of silyl derivatives in Friedel–Crafts chemistry has

not only improved the regioselectivity but extended the scope
of these reactions. Substitution at the ipso position occurs with
aryl silanes (eq 12).

20

The ability of silyl groups to stablize

β

-carbenium ions (β-effect) affords acylated products with

complete control of regiochemistry (eq 13).

21

TMS

Cl

O

TMS

TMS

AlCl

3

TMS

O

TMS

(12)

75%

+

TMS

AcCl

AlCl

3

O

(13)

77%

The use of silylacetylenes gives ynones (eq 14),

22

cyclopen-

tenone derivatives (eq 15),

23

and α-amino acid derivatives

(eq 16).

24

R

Cl

O

TMS

TMS

AlCl

3

R

O

TMS

(14)

85–94%

+

Cl

O

TMS

AlCl

3

O

Cl

TMS

(15)

63%

+

EtO

2

CNH

CO

2

Me

Cl

H

TMS

TMS

AlCl

3

EtO

2

CNH

CO

2

Me

H

TMS

(16)

65%

+

Propargylic silanes undergo acylation to generate allenyl

ketones (eq 17),

25

while alkylsilanes afford cycloalkanones

(eq 18).

26

TMS

R

AcCl

AlCl

3

R

O

•

(17)

COCl

TMS

R

AlCl

3

O

R

(18)

60–87%

Several name reactions are promoted by AlCl

3

. For exam-

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-

matic systems is known as the Fries rearrangement (eq 20).

28

Aryl aldehydes are produced by the Gatterman aldehyde synthe-
sis (eq 21).

29

The initial step of the Haworth phenanthrene syn-

thesis makes use of a Friedel–Crafts acylation.

30

The acylation

of phenolic compounds is called the Houben–Hoesch reaction
(eq 22).

31

The Leuckart amide synthesis generates aryl amides

from isocyanates (eq 23).

32

O

O

S

(19)

87%

S

AlCl

3

O

OAc

OAc

AlCl

3

O

OH

OH

O

(20)

85%

AlCl

3

OR

OR

CHO

(21)

HCl
HCN

AlCl

3

RCN

OH

OH

OH

OH

R

O

(22)

HCl

AlCl

3

NHR

O

(23)

RNCO

Amides can also be obtained by AlCl

3

catalyzed ester amine

exchange which proceeds primarily without racemization of chi-
ral centers (eq 24).

33

The reaction of phenols with β-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

derivatives are prepared in the Stolle synthesis (eq 28).

37

In the

Zincke-Suhl reaction, phenols are converted to dienones (eq 29).

38

AlCl

3

Et

2

NH

77%

CO

2

Me

Cl

CONEt

2

Cl

(24)

(S) 98%

S

:R = 82:18

AlCl

3

40–55%

OH

CO

2

Me

O

O

O

(25)

+

AlCl

3

NH

3

O

N

(26)

+

+

AlCl

3

68%

O

O

(27)

AlCl

3

(28)

N

O

Cl

R

2

R

1

R

N

O

R

2

R

1

R

AlCl

3

CCl

4

37–42%

OH

O

CCl

3

(29)

Diels–Alder Reactions. There is some evidence that AlCl

3

catalysis of Diels–Alder reactions changes the transition state
from a synchronous to an asynchronous one.

39

This also enhances

asymmetric induction by increasing steric interactions at one end
of the dieneophile. There are many examples of AlCl

3

promoted

Diels–Alder reactions (eq 30).

40

Hetero-Diels–Alder reactions

can be used to generate oxygen (eq 31)

41

and nitrogen (eq 32)

42

containing heterocycles.

OMe

O

H

AlCl

3

62%

OMe

O

H

H

CO

3

Et

(30)

+

CO

2

Et

O

AlCl

3

70%

O

CN

(31)

+

OTMS

Ph

NPh

AlCl

3

60%

N

Ph

Ph

H

OTMS

(32)

+

AlCl

3

can also be used to catalyze [2 + 2] cycloaddition reac-

tions (eq 33)

43

and ene reactions (eq 34).

44

AlCl

3

16%

O

H

Et

O

(33)

O

O

AlCl

3

(34)

O

MVK

80–90%

O

O

Rearrangements. AlCl

3

catalyzed rearrangement of hydro-

carbon derivatives to adamantanes has been well documented
(eq 35).

45

Other rearrangements have been used in triquinane syn-

thesis (eq 36).

46

AlCl

3

(35)

60%

AlCl

3

(36)

93%

H

O

H

O

Miscellaneous Reactions. AlCl

3

has been used to catalyze the

addition of allylsilanes to aldehydes and acid chlorides (eq 37).

47

Cyclic ethers (pyrans and oxepins) have been prepared with hy-
droxyalkenes (eq 38).

48

The course of reactions between aldehy-

des and allylic Grignard reagents can be completely diverted to
α

-allylation by AlCl

3

(eq 39).

49

The normal course of the reaction

gives γ-allylation products.

R

′

TMS

RCHO

R

OTMS

R

′

(37)

AlCl

3

40–45%

Avoid Skin Contact with All Reagents

4

ALUMINUM CHLORIDE

Ph

OH

MeCHO

O

Cl

Ph

(38)

AlCl

3

57%

MgBr

RCHO

R

OH

(39)

AlCl

3

AlCl

3

can be used to remove t-butyl groups from aromatic

rings (eq 40),

50

thereby using this group as a protecting ele-

ment for a ring position. AlCl

3

has also been used to remove

p

-nitrobenzyl (PNB) and benzhydryl protecting groups (eq 41).

51

The combination of AlCl

3

and Ethanethiol has formed the ba-

sis of a push–pull mechanism for the cleavage of many types of
bonds including C–X,

52

C–NO

2

,

53

C=C,

54

and C–O.

55

Further-

more, AlCl

3

has been used to catalyze chlorination of aromatic

rings,

56

open epoxides,

57

and mediate addition of dichlorophos-

phoryl groups to alkanes.

58

OH

t

-Bu

t

-Bu

t

-Bu

AlCl

3

OH

(40)

80%

N

R

O

S

CO

2

PNB

NHCO

2

PNB

AlCl

3

N

R

O

S

CO

2

H

NH

2

(41)

24–82%

1.

(a) Thomas, C. A. Anhydrous Aluminum Chloride in Organic
Chemistry

; ACS Monograph Series; Reinholdt: New York, 1941.

(b) Shine, H. J. Aromatic Rearrangements; Elsevier: Amsterdam, 1967.
(c) Fieser & Fieser 1967, 1, 24. (d) Olah, G. A. Friedel–Crafts Chemistry;
Wiley: New York, 1973. (e) Roberts, R. M.; Khalaf, A. A. Friedel–Crafts
Alkylation Chemistry

; Marcel Dekker: New York, 1984.

2.

Gore, P. H., C. R. Hebd. Seances Acad. Sci. 1955, 55, 229.

3.

Pearson, D. E.; Buehler, C. A., Synthesis 1972, 533.

4.

(a) Tan, L. K.; Brownstein, S., J. Org. Chem. 1982, 47, 4737. (b) Tan, L.
K.; Brownstein, S., J. Org. Chem. 1983, 48, 3389.

5.

Drago, R. S.; Getty, E. E., J. Am. Chem. Soc. 1988, 110, 3311.

6.

McClure, D. E.; Arison, B. H.; Jones, J. H.; Baldwin, J. J., J. Org. Chem.
1981, 46, 2431.

7.

Piccolo, O.; Spreafico, F.; Visentin, G.; Valoti, E., J. Org. Chem. 1985,
50

, 3945.

8.

Pinnick, H. W.; Brown, S. P.; McLean, E. A.; Zoller, L. W., J. Org. Chem.
1981, 46, 3758.

9.

Jaxa-Chamiel, A.; Shah, V. P.; Kruse, L. I., J. Chem. Soc., Perkin Trans.
1 1989

, 1705.

10.

(a) Pollak, A.; Stanovnik, B.; Tisler, M., J. Org. Chem. 1966, 31, 4297.
(b) Coates, W. J.; McKillop, A., J. Org. Chem. 1990, 55, 5418.

11.

Takeuchi, H.; Maeda, M.; Mitani, M.; Koyama, K., J. Chem. Soc., Chem.
Commun. 1985

, 287.

12.

Takeuchi, H.; Shiobara, Y.; Kawamoto, H.; Koyama, K., J. Chem. Soc.,
Perkin Trans. 1 1990

, 321.

13.

(a) Puck, R.; Mayr, H.; Rubow, M.; Wilhelm, E., J. Am. Chem. Soc. 1986,
108

, 7767. (b) Brownstein, S.; Morrison, A.; Tan, L. K., J. Org. Chem.

1985, 50, 2796.

14.

Mayr, H.; Striepe, W., J. Org. Chem. 1983, 48, 1159.

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.
1972, 1, 73. (d) House, H. O. Modern Synthetic Reactions; Benjamin-
Cummings: Menlo Park, CA, 1972; p 786.

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,
5280.

17.

Maroni, R.; Melloni, G.; Modena, G., J. Chem. Soc., Perkin Trans. 1
1974, 353.

18.

Maroni, R.; Melloni, G.; Modena, G., J. Chem. Soc., Perkin Trans. 1
1973, 2491.

19.

Trost, B. M.; Ghadiri, M. R., J. Am. Chem. Soc. 1984, 106, 7260.

20.

(a) Eaborn, C., J. Chem. Soc 1956, 4858. (b) Habich, D.; Effenberger,
F., Synthesis 1979, 841.

21.

(a) Fleming, I.; Pearce, A., J. Chem. Soc., Chem. Commun. 1975, 633.
(b) Fristad, W. E.; Dime, D. S.; Bailey, T. R.; Paquette, L. A., Tetrahedron
Lett. 1979

, 1999.

22.

(a) Walton, D. R. M.; Waugh, F., J. Organomet. Chem. 1972, 37, 45. (b)
Newman, H., J. Org. Chem. 1973, 38, 2254.

23.

Karpf, M., Tetrahedron Lett. 1982, 23, 4923.

24.

Casara, P.; Metcalf, B. W., Tetrahedron Lett. 1978, 1581.

25.

Flood, T.; Peterson, P. E., J. Org. Chem. 1980, 45, 5006.

26.

Urabe, H.; Kuwajima, I., J. Org. Chem. 1984, 49, 1140.

27.

Ferrario, E., Bull. Soc. Chem. Fr. 1911, 9, 536.

28.

(a) Blatt, A. H., Org. React. 1942, 1, 342. (b) Gammill, R. B., Tetrahedron
Lett. 1985

, 26, 1385.

29.

Truce, W. E., Org. React. 1957, 9, 37.

30.

Berliner, E., Org. React. 1949, 5, 229.

31.

Spoerri, P. E.; Dubois, A. S., Org. React. 1949, 5, 387.

32.

Effenberger, F.; Gleiter, R., Chem. Ber. 1964, 97, 472.

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.

37.

Sumpter, W. C., C. R. Hebd. Seances Acad. Sci. 1944, 34, 393.

38.

Newman, M. S.; Wood, L. L., J. Am. Chem. Soc. 1959, 81, 6450.

39.

Tolbert, L. M.; Ali, M. B., J. Am. Chem. Soc. 1984, 106, 3806.

40.

(a) Cohen, N.; Banner, B. L.; Eichel, W. F., Synth. Commun. 1978, 8, 427.
(b) Fringuelli, F.; Pizzo, F.; Taticchi, A.; Wenkert, E., Synth. Commun.
1979, 9, 391. (c) Ismail, Z. M.; Hoffmann, H. M. R., J. Org. Chem. 1981,
46

, 3549. (d) Vidari, G.; Ferrino, S.; Grieco, P. A., J. Am. Chem. Soc.

1984, 106, 3539. (e) Angell, E. C.; Fringuelli, F.; Guo, M.; Minuti, L.;
Taticchi, A.; Wenkert, E., J. Org. Chem. 1988, 53, 4325.

41.

Ismail, Z. M.; Hoffmann, H. M. R., Angew. Chem., Int. Ed. Engl. 1982,
21

, 859.

42.

LeCoz, L.; Wartski, L.; Seyden-Penne, J.; Chardin, P.; Nierlich, M.,
Tetrahedron Lett. 1989

, 30, 2795.

43.

Jung, M. E.; Haleweg, K. M., Tetrahedron Lett. 1981, 22, 2735.

44.

(a) Snider, B. B.; Rodini, D. J.; Conn, R. S. E.; Sealfon, S., J. Am. Chem.
Soc. 1979

, 101, 5283. (b) Mehta, G.; Reddy, A. V., Tetrahedron Lett.

1979, 2625. (c) Snider, B. B., Acc. Chem. Res. 1980, 13, 426.

45.

(a) Bingham, R. C.; Schleyer, P. R., Top. Curr. Chem. 1971, 18, 1. (b)
McKervey, M. A., Chem. Soc. Rev. 1974, 3, 479. (c) McKervey, M. A.,
Tetrahedron 1980

, 36, 971.

46.

Kakiuchi, K.; Ue, M.; Tsukahara, H.; Shimizu, T.; Miyao, T.; Tobe, Y.;
Odaira, Y.; Yasuda, M.; Shima, K., J. Am. Chem. Soc. 1989, 111, 3707.

47.

(a) Deleris, G.; Donogues, J.; Calas, R., Tetrahedron Lett. 1976, 2449.
(b) Pillot, J.-P.; Donogues, J.; Calas, R., Tetrahedron Lett. 1976, 1871.

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.

49.

Yamamoto, Y.; Maruyama, K., J. Org. Chem. 1983, 48, 1564.

50.

Lewis, N.; Morgan, I., Synth. Commun. 1988, 18, 1783.

51.

Ohtani, M.; Watanabe, F.; Narisada, M., J. Org. Chem. 1984, 49, 5271.

52.

Node, M.; Kawabata, T.; Ohta, K.; Fujimoto, M.; Fujita, E.; Fuji, K., J.
Org. Chem. 1984

, 49, 3641.

53.

Node, M.; Kawabata, T.; Ueda, M.; Fujimoto, M.; Fuji, K.; Fujita, E.,
Tetrahedron Lett. 1982

, 23, 4047.

54.

Fuji, K.; Kawabata, T.; Node, M.; Fujita, E., J. Org. Chem. 1984, 49,
3214.

55.

Node, M.; Nishide, K.; Ochiai, M.; Fuji, K.; Fujita, E., J. Org. Chem.
1981, 46, 5163.

56.

Watson, W. D., J. Org. Chem. 1985, 50, 2145.

57.

Eisch, J. J.; Liu, Z.-R.; Ma, X.; Zheng, G.-X., J. Org. Chem. 1992, 57,
5140.

58.

Olah, G. A.; Farooq, O.; Wang, Q.; Wu, A.-H., J. Org. Chem. 1990, 55,
1224.

Paul Galatsis

University of Guelph, Guelph, Ontario, Canada

Avoid Skin Contact with All Reagents