A. G. Posternak et al. / Tetrahedron Letters 50 (2009) 446–447
447
Lit.
Table 1
Entry
X
Ratio 3/2
2
T (°C)
Acid (mol %)
Time
4
Isolated yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
F
F
F
F
F
F
F
F
F
3:1
3:1
3:1
3:1
3:1
4:1
3:1
3:1
3:1
3:1
3:1
12:1
4:1
3:1
2:1
3:1
12:1
3:1
12:1
3:1
3:1
3:1
12:1
3:1
2i
2i
2f
2b
2a
2a
2i
130
130
130
130
132
135
80
80
80
80
80
100
90
85
—
85
100
85
100
85
85
85
1 (1%)
1 (2%)
1 (1%)
1 (1%)
TfOH (1%)
Fe2(SO4)3 (1–5%)
1 (1%)
1 (1%)
1 (1%)
TfOH (1%)
TfOH (1%)
TfOH (50%)
Fe2(SO4)3 (5%)
1 (1%)
AlCl3 (117%)
1 (1%)
TfOH (50%)
1 (1%)
TfOH (50%)
1 (5%)
1 (1%)
1 (1%)
TfOH (50%)
1 (1%)
24
16
16
17
5
24
22
3
4a
4a
4b
4c
4d
4d
4e
4e
4f
4g
4h
4i
4i
4j
69 (o:p = 1:8)
96 (para)
94 (para)
58
13 (o:p = 1:3)
17
8
34–55a
76
2i
41b
88
2d
2h
2a
2a
2a
2i
16
4
82
17
17
19
8
8.5
144
43
19
—
17
144
18
144
15
20
21
144
18
14
79c
61a
76
2i
4j
53
76
76
82
85
40
87
95
3
2d
2d
2b
2b
2b
2h
2c
2c
2e
4k
4k
4l
4l
4l
4m
4n
4n
4o
19
19
F
F
F
F
100
85
98
99
19
a
Yield includes a small amount of unreacted aroyl chloride 2.
Yield calculated from the 19F NMR spectrum.
b
c
Yield calculated from the 1H NMR spectrum.
catalyst,19 the yields of the corresponding benzophenones 4 are
comparable. However, the amount of TfOH required is 0.5 M equiv
(i.e., 50 times greater than acid 1) and the reactions take a long
time.
If activated aromatic nucleophiles (p-xylene, toluene) or a
strong electrophile such as 2h is used in the reaction, the acylation
proceeds well when 1 mol % of TfOH is used as the catalyst;17 how-
ever, the yield of 4-chlorobenzophenone was very small (entry 5).
It should be stressed that acylation of chlorobenzene in the
presence of acid 1 occurs in moderate to excellent yields and pref-
erably at the para-position (entries 1–4). This atypical effect is
most likely due to steric issues in the transition complex (aroyl
chloride:acid 1) hindering reaction at the ortho-position of
chlorobenzene.
Tetrahedron Lett. 1996, 37, 3015–3018; (d) Fujisawa, T.; Ito, T.; Fujimoto, K.;
Shimizu, M.; Winberg, H.; Staring, E. G. J. Tetrahedron Lett. 1997, 38, 1593–1596.
6. Paul, S.; Nanda, P.; Gupta, R.; Loupy, A. Synthesis 2003, 2877–2881.
7. (a) Dermer, O. C.; Billmeier, R. A. J. Am. Chem. Soc. 1942, 64, 464; (b) Murakami,
Y.; Tani, M.; Aryuasu, T.; Nischiyama, C.; Watanabe, T.; Yokoyama, Y.
Heterocycles 1988, 27, 1855; (c) Tolkunov, S. V.; Voshchula, V. N.; Zemskaya,
E. A.; Dulenko, V. I. Khim. Geterotsikl. Soedin. 1990, 1569; (d) Mukaiyama, T.;
Nagaoka, H.; Ohshima, M.; Murakami, M. Chem. Lett. 1986, 165 and references
cited therein.
8. Morley, J. O. Synthesis 1977, 54–55.
9. Krespan, C. G.; Petrov, V. A. Chem. Rev. 1996, 96, 3269.
10. (a) Henne, A. L.; Newman, M. S. J. Am. Chem. Soc. 1938, 60, 1697–1698; (b)
Yagupolskii, L. M.; Kondratenko, N. V. Zh. Obsch. Khem. 1967, 37, 1770–1775.
11. Marx, A.; Yamamoto, H. Angew. Chem., Int. Ed. 2000, 39, 178.
12. Kawada, A.; Mitamura, S.; Kobayashi, S. J. Chem. Soc., Chem. Commun. 1993,
1157.
13. Mikami, K.; Kotera, O.; Motoyama, Yu.; Sakaguchi, H.; Maruta, M. Synlett 1996,
171–172.
14. Cho, H.; Matsuki, S.; Mizuno, A.; Annoura, H.; Tatsuoka, T. J. Heterocycl. Chem.
1997, 34, 87.
15. (a) Mizuno, A.; Miya, M.; Kamei, T.; Shibata, M.; Tatsuoka, T.; Nakanishi, K.;
Takiguchi, C.; Hadaka, T.; Yamaki, A.; Inomata, N. Chem. Pharm. Bull. 2000, 48,
1129; (b) Eaton, P. E.; Yeusaf, T. I. J. Org. Chem. 1973, 38, 4071–4073.
16. Yamoto, T.; Hideshama, C.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 1991, 36,
3955.
Thus, the selectivity and small amounts of acid 1 required are
advantages over other catalysts for Friedel–Crafts acylation. Acid
1 is very soluble in various organic solvents including methylene
chloride. It can be recycled from large-scale synthesis and its cata-
lytic activity in other organic reactions is currently under study.
17. Effenberger, F.; Eppel, G. Angew. Chem. 1972, 84, 295–296.
18. Anderson, K. W.; Tepe, J. J. Tetrahedron 2002, 58, 8475–8481.
19. Akiko, O.; Katsuya, M.; Hideaki, O.; Noriyuki, Y. Synth. Commun. 2007, 37,
2701–2715.
Supplementary data
20. (a) Yoneda, N.; Fukuhara, T.; Takahashi, Y.; Suzuki, A. Chem. Lett. 1979, 1003;
(b) Olah, G. A.; White, A. M.; O’Brien, D. H. Chem. Rev. 1970, 70, 561; (c)
Repinskaya, I. B.; Barkhutova, D. D.; Makarova, Z. S.; Alekseeva, A. V.; Koptyug,
V. A. J. Org. Chem. USSR (Engl. Transl.) 1985, 21, 759.
Supplementary data associated with this article can be found,
21. Garlyauskayte, R. Yu.; Chernega, A. N.; Michot, Ch.; Armand, M.; Yagupolskii,
Yu. L.; Yagupolskii, L. M. Org. Biomol. Chem. 2005, 3, 2239–2243.
22. Burk, P.; Koppel, I. A.; Koppel, I.; Yagupolskii, L. M.; Taft, R. W. J. Comput. Chem.
1996, 17, 30–41 and references cited therein.
23. Prakash, G. K. S.; Yan, P.; Torok, B.; Olah, G. A. Synlett 2003, 527–531 and
references cited therein.
24. Typical procedure for the synthesis of benzophenones 4: Benzoyl chloride 2
(1 mmol) was dissolved in aromatic substrate 3 (3 mmol), and acid 1 as 20%
solution in CH2Cl2 (0.01 mmol) was added at room temperature under a dry
Ar-current. The reaction mixture was refluxed with stirring and protection
from moisture. On completion, the mixture was diluted with CH2Cl2 (10 ml)
and carefully neutralized with saturated aqueous NaHCO3 solution, the organic
layer was washed with water and dried over anhydrous MgSO4. The solvent
and excess of 3 were removed in vacuo. The residue was distilled in vacuo or
recrystallized from hexane.
References and notes
1. Olah, G. A. Friedel–Crafts and Related Reactions; Wiley-Interscience: New York,
1963.
2. (a) Kranzlein, G. Aluminium Chloride in der Organischen Chemie, 3rd ed.; Verlag
Chemie: Berlin, 1939; (b) Thomas, C. A. Anhydrous Aluminium Chloride in
Organic Chemistry; Rainhold: New York, 1961.
3. Bradlow, L. H.; VanderWerf, C. A. J. Am. Chem. Soc. 1947, 69, 662–663.
4. (a) Hyatt, J. A.; Raynolds, P. W. J. Org. Chem. 1984, 49, 384; (b) Fodor, G.; Kiss, J.;
Szekerke, M. J. Org. Chem. 1950, 15, 227; (c) Kindler, K.; Oelschlager, H. Chem. Ber.
1954, 87, 194; (d) Schiemenz, G. P.; Schmidt, U. Liebigs Ann. Chem. 1976, 1514; (e)
Walker, H. G.; Sanderson, J. J.; Hauser, C. R. J. Am. Chem. Soc. 1953, 75, 4109.
5. (a) Bensari, A.; Zaveri, N. T. Synthesis 2003, 267–271; (b) Chiba, K.; Arakawa, T.;
Tada, M. Chem. Commun. 1996, 1763–1764; (c) Lin, G.-Q.; Zhong, M.