Catalytic Friedel-Crafts acylation of alkoxybenzenes mediated by aluminum hydrogensulfate in solution and solvent-free conditions

Article abstract of DOI:10.1246/bcsj.76.1863

Friedel-Crafts acylation of alkoxybenzenes was achieved efficiently by a reaction with aliphatic acid anhydrides in the presence of catalytic amounts of aluminum hydrogensulfate, Al(HSO₄)₃, in nitromethane and under solvent-free conditions. Alkylbenzenes and aryl halides, as well as aromatic anhydrides, remained intact under these conditions.

Full text of DOI:10.1246/bcsj.76.1863

Short Articles
Bull. Chem. Soc. Jpn., 76, 1863–1864 (2003) 1863
Catalytic Friedel–Crafts Acylation
of Alkoxybenzenes Mediated by
Aluminum Hydrogensulfate in Solu-
tion and Solvent-Free Conditions
Scheme 1.
Aluminum hydrogensulfate is a very stable and non-hygro-
scopic solid material that is insoluble in most organic solvents.
To the best of our knowledge, there is not any report on its ap-
plication in organic synthetic methodology. In continuation of
our studies on the application of metallic hydrogensulfate salts
in organic synthesis,3 we wish to report on a selective method
for the acylation of alkoxybenzenes with aliphatic acid anhy-
drides in the presence of 0.15 molar amount of Al(HSO4)3
in nitromethane and also under solvent-free conditions
(Scheme 1).
ꢀ
ꢀ;y
Peyman Salehi, Mohammad Mehdi Khodaei,
Mohammad Ali Zolfigol,yy and Sara Sirouszadehy
Department of Phytochemistry, Medicinal Plants
Research Institute, Shahid Beheshti University,
Evin, Tehran 1983963113, Iran
yDepartment of Chemistry, Faculty of Science,
Razi University, Kermanshah, Iran
As shown in the Table 1, the catalytic acylation of alkoxy-
benzenes was proceeded well in solution with a high position
selectivity for the formation of para-acylated products in good
yields. Among the common organic solvents that have been
used for Friedel–Crafts acylation, we found that nitromethane
is the solvent of choice for these reactions.
yyDepartment of Chemistry, Faculty of Science,
Bu-Ali Sina University, Hamadan, Iran
Received February 1, 2003; E-mail: p-salehi@cc.sbu.ac.ir
We also conducted similar reactions in the absence of a sol-
vent, and observed that at the same temperature omitting the
solvent had a little effect in shortening the reaction times,
but the product yields did not change significantly (Table 1).
We also observed that aromatic acid anhydrides reacted
sluggishly under the same conditions. Therefore, a competi-
tive reaction between acetic anhydride and benzoic anhydride
with anisole was studied and under both conditions; a high de-
gree of chemoselectivity was observed (Scheme 2).
Friedel–Crafts acylation of alkoxybenzenes was
achieved efficiently by a reaction with aliphatic acid anhy-
drides in the presence of catalytic amounts of aluminum hy-
drogensulfate, Al(HSO4)3, in nitromethane and under sol-
vent-free conditions. Alkylbenzenes and aryl halides, as well
as aromatic anhydrides, remained intact under these condi-
tions.
Friedel–Crafts acylation is one of the most important proto-
cols for bringing about the formation of carbon–carbon bonds
between aromatic rings and aliphatic moieties.1 The tradition-
al methods generally involve the use of stoichiometric
amounts of aluminum chloride or sulfuric acid.2 Many of
the classic catalysts, such as metallic halides and Brꢀnsted
acids, are corrosive and some of them suffer from unavailabil-
ity, instability or hygroscopicity.
This method also permits us to conduct the selective acyla-
tion of alkoxybenzenes in the presence of the less reactive ar-
omatic compounds, such as arenes and aryl halides.
In conclusion, aluminum hydrogensulfate is a stable, non-
hygroscopic and heterogeneous catalyst for the selective acyla-
tion of alkoxybenzenes. Although aluminum chloride is also
used for this purpose, its hygroscopic nature limits its applica-
tions in the laboratory. Moreover, AlCl3 should be used in
quantitative amounts. The catalytic nature of Al(HSO4)3 can
be attributed to the presence of hydrogensulfate anion, which
acts as a source of proton. The method also enjoys the chem-
Thus, the development of heterogeneous solid acid catalysts
to replace the use of strongly acidic, homogeneous and corro-
sive reagents can be considered extensively.
Table 1. Friedel–Crafts Acylation of Alkoxybenzenes with Acid Anhydrides Mediated by Al(HSO4)3
Reaction in CH3NO2
Solvent-free conditions
Entry
R
R0
Time
/h
Molar amount
of the catalyst
Yield
/%
Time
/h
Molar amount
of the catalyst
Yield
/%
1
2
3
4
5
6
7
8
9
10
–CH3
–CH2CH3
–CH2(CH2)2CH3
–CH2CH(CH3)2
–CH2(CH2)4CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH3
–CH2CH3
–CH2CH3
–CH2CH3
–CH2CH3
–CH2CH3
2
3
4
5.8
5
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
78
77
75
72
77
80
75
75
80
83
1.3
2.1
3.3
5
4.5
1.5
2
4
4
3.5
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
77
79
75
78
82
78
75
79
82
83
2
–CH2CH3
2.5
4.9
5
–CH2(CH2)2CH3
–CH2CH(CH3)2
–CH2(CH2)4CH3
4
Published on the web September 15, 2003; DOI 10.1246/bcsj.76.1863

1864 Bull. Chem. Soc. Jpn., 76, No. 9 (2003)
Ó 2003 The Chemical Society of Japan
solution of NaHCO3 (5%, 20 mL) was added. The aqueous mix-
ture was extracted with diethyl ether (3 ꢃ 20 mL). The organic
layer was dried (Na2SO4) and concentrated. Final purification
on a silica gel column afforded the desired products in 75–83%
yields.
Spectral and Physical Data of the Products. Entry 1: Mp
6
35 C (lit. 37 C), mp of semicarbazone derivative 195–197 C
ꢂ
ꢂ
ꢂ
6
(lit. 197–198 C).
ꢂ
Entry 2: Mp 34 ꢂC (lit.6 36–37 ꢂC), mp of semicarbazone de-
Scheme 2.
6
rivative 178–180 C (lit. 179–180 C).
ꢂ
ꢂ
ical and environmental advantages of solvent-free reactions.4
Al(HSO4)3 is proposed as a very good successor for AlCl3
in other organic reactions.
Entry 3: Mp 23 ꢂC (lit.7 22 ꢂC), mp of oxime derivative 83 ꢂC
7
(lit. 86 C).
ꢂ
8
Entry 4: Mp of oxime derivative 105–106 C (lit. 107 C).
ꢂ
ꢂ
8
Entry 5: Mp of oxime derivative 77 C (lit. 78 C).
ꢂ
ꢂ
Experimental
Entry 6: Mp 25–27 ꢂC (lit.6 26–27 ꢂC), mp of semicarbazone
6
derivative 170–172 C (lit. 171–172 C).
ꢂ
ꢂ
The products were characterized by comparison of their spec-
tral data (1H NMR, IR) and physical properties with those reported
in the literature. 1H NMR spectra were run on a Bruker Avance
200 MHz spectrometer. IR spectra were obtained by a Shimadzu
470 spectrophotometer. The progress of the reactions was fol-
lowed by TLC using silica gel Polygrams SIL G/UV 254
Sheets. All yields refer to isolated products.
Entry 7: Mp 28–30 ꢂC (lit.6 29–30 ꢂC), mp of semicarbazone
6
derivative 182 C (lit. 181–183 C).
ꢂ
ꢂ
9
Entry 8: Mp 27–29 C (lit. 28 C), mp of oxime derivative
ꢂ
ꢂ
9
ꢂ
ꢂ
77 C (lit. 79 C).
Entry 9: IR (KBr), ꢀ (cmꢁ1): 3050(w), 2950(s), 2910(s),
1673(s), 1600(s), 1472(m), 1255(s), 1230(s), 1020(s), 795(s);
1H NMR (CDCl3), ꢁ 7.9 (2H, d, J ¼ 8:8 Hz), 6.9 (2H, d,
J ¼ 8:8 Hz), 3.8 (2H, d, J ¼ 6:5 Hz), 3.0 (2H, q, J ¼ 7:3 Hz),
2.1 (1H, m, J ¼ 6:8 Hz), 0.8–1.5 (9H, m); mp 44 ꢂC, mp of
Preparation of Aluminum Hydrogensulfate. A 500 mL suc-
tion flask was equipped with a constant-pressure dropping funnel.
The gas outlet was connected to a vacuum system through an ad-
sorbing solution (water) and an alkali trap. Anhydrous aluminum
chloride (33.4 g, 0.25 mol) was charged in the flask and concen-
trated sulfuric acid (98%, 73.5 g, 0.75 mol) was added dropwise
over a period of 30 min at room temperature. HCl evolved
immediately. After completion of the addition, the mixture was
shaken for 30 min, while the residual HCl was eliminated by
suction. Finally, a pale-brown solid material was obtained in 77
g. Al(HSO4)3 was characterized by the determination of its Hþ
content by titration with NaOH (Calcd 0.95%, Found 0.96%)
ꢂ
2,4-dinitrophenylhydrazone derivative 155–157 C.
Entry 10: IR (neat), ꢀ (cmꢁ1): 3050(w), 2930(s), 1675(s),
1600(s), 1460(m), 1250(s), 1220(s), 795(m); 1H NMR (CDCl3),
ꢁ 7.8 (2H, d, J ¼ 8:7 Hz), 6.8 (2H, d, J ¼ 8:7 Hz), 3.9 (2H, t, J ¼
6:7 Hz), 2.9 (2H, q, J ¼ 7:3 Hz), 0.7–1.6 (14H, m); mp of 2,4-di-
ꢂ
nitrophenylhydrazone derivative 161–163 C.
We are grateful to Razi University Research Council for fi-
nancial support of this work.
2ꢁ
and SO4
by precipitation with Ba2þ (Calcd 90.57%, Found
90.48%). Al3þ was determined by two methods; conversion to
Al2O3 (Calcd 8.48%, Found 8.31%) and spectrophotometric de-
termination by complex formation with aluminon (Calcd 8.48%,
Found 8.38%).5
References
1
G. A. Olah, ‘‘Friedel–Crafts and Related Reactions,’’
Vol. 1, John Wiley & Sons, New York (1963).
General Procedure for the Acylation of Alkoxybenzenes in
Nitromethane. Aluminum hydrogensulfate (0.45 mmol) was
added to a solution of alkoxybenzene (3 mmol) and acid anhy-
dride (6 mmol) in nitromethane (10 mL). The mixture was stirred
magnetically at 65–70 ꢂC for an appropriate period of time
(Table 1). The progress of the reaction was monitored by TLC
(eluent: hexane/diethyl ether: 2/1). Then, nitromethane was
evaporated under reduced pressure and a solution of NaHCO3
(5%, 20 mL) was added. The aqueous mixture was extracted with
diethyl ether (3 ꢃ 20 mL). The organic layer was dried (Na2SO4)
and concentrated. Final purification on a silica gel column afford-
ed the desired products in 72–83% yields.
2
(1984).
3
J. A. Hyat and P. W. Raynolds, J. Org. Chem., 49, 384
a) P. Salehi, M. M. Khodaei, M. A. Zolfigol, and A.
Keyvan, Synth. Commun., 31, 1947 (2001). b) P. Salehi, M. M.
Khodaei, M. A. Zolfigol, and A. Keyvan, Monatsh. Chem., 133,
1291 (2002), and references cited therein.
4
5
K. Tanaka and F. Toda, Chem. Rev., 100, 1025 (2000).
A. I. Vogel, ‘‘Quantitative Inorganic Analysis,’’ Longman,
London (1972), pp. 462, 472, 792.
X. A. Dominguez, B. Gomez, J. Slim, D. Giesecke, and E.
Ureta, J. Am. Chem. Soc., 76, 5150 (1954).
R. E. Lutz, R. K. Allison, G. Ashburn, P. S. Bailey, M. T.
6
7
General Procedure for Acylation Reactions under Solvent-
Free Conditions.
Clark, J. F. Codington, A. J. Deinet, J. A. Freek, R. H. Jordan, N.
H. Leake, T. A. Martin, K. C. Nicodemus, R. J. Towlett, N. H.
Shearer, J. D. Smith, and J. W. Wilson, J. Org. Chem., 12, 617
(1947).
Alkoxybenzene (3 mmol), acid anhydride
(3.6 mmol) and aluminum hydrogensulfate (0.45 mmol) were
placed in a mortar and mixed. The mixture was heated at 65–
70 ꢂC in an oven for an appropriate period of time (Table 1).
Progress of the reaction was followed by dissolving a sample in
dichloromethane and monitoring by TLC (eluent: hexane/diethyl
ether: 2/1). The mixture was cooled to room temperature and a
8
E. Eckhart and J. Varga, Mag. Kem. Foly., 67, 509 (1961);
Chem. Abstr., 56, 15557e (1962).
E. Hanning and G. Leuschner, Pharm. Zentralhalle, 96,
570 (1957); Chem. Abstr., 52, 14078d (1958).
9