Catalytic Friedel-Crafts acylation of alkoxy benzenes by ferric hydrogensulfate

Article abstract of DOI:10.1081/SCC-120018697

Friedel-Crafts acylation of alkoxy benzenes is achieved efficiently by reaction with aliphatic acid anhydrides in the presence of catalytic amounts of ferric hydrogensulfate, Fe(HSO₄)₃, in nitromethane. Alkyl benzenes and aryl halides, as well as aromatic anhydrides, remain intact under these conditions.

Full text of DOI:10.1081/SCC-120018697

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Catalytic Friedel–Crafts Acylation of Alkoxy Benzenes
by Ferric Hydrogensulfate
Peyman Salehi a , Mohammad Mahdi Khodaei b , Mohammad Ali Zolfigol c & Shahpour
Zeinoldini b
a Department of Phytochemistry , Medicinal Plants Research Institute , Shahid Beheshti
University , Evin, Tehran, Iran
b Department of Chemistry , Faculty of Science , Razi University , Kermanshah, Iran
c Department of Chemistry , Faculty of Science , Bu-Ali Sina University , Hamadan, Iran
Published online: 15 Aug 2006.
To cite this article: Peyman Salehi , Mohammad Mahdi Khodaei , Mohammad Ali Zolfigol & Shahpour Zeinoldini (2003)
Catalytic Friedel–Crafts Acylation of Alkoxy Benzenes by Ferric Hydrogensulfate, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:8, 1367-1373, DOI: 10.1081/SCC-120018697
To link to this article: http://dx.doi.org/10.1081/SCC-120018697
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 8, pp. 1367–1373, 2003
Catalytic Friedel–Crafts Acylation of Alkoxy
Benzenes by Ferric Hydrogensulfate
2
Peyman Salehi,1, Mohammad Mahdi Khodaei,
*
Mohammad Ali Zolfigol,3 and Shahpour Zeinoldini2
1Department of Phytochemistry, Medicinal Plants
Research Institute, Shahid Beheshti University,
Evin, Tehran, Iran
2Department of Chemistry, Faculty of Science,
Razi University, Kermanshah, Iran
3Department of Chemistry, Faculty of Science,
Bu-Ali Sina University, Hamadan, Iran
ABSTRACT
Friedel–Crafts acylation of alkoxy benzenes is achieved efficiently by
reaction with aliphatic acid anhydrides in the presence of catalytic
amounts of ferric hydrogensulfate, Fe(HSO4)3, in nitromethane.
*Correspondence: Peyman Salehi, Department of Phytochemistry, Medicinal
Plants Research Institute, Shahid Beheshti University, Evin, Tehran, Iran;
Fax: 98(21)2418679; E-mail: p-salehi@cc.sbu.ac.ir.
1367
DOI: 10.1081/SCC-120018697
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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1368
Salehi et al.
Alkyl benzenes and aryl halides, as well as aromatic anhydrides,
remain intact under these conditions.
Key Words: Friedel-Crafts; Acylation; Ferric hydrogensulfate;
Catalysis; Alkoxy benzenes.
Friedel–Crafts acylation is one of the most important protocols for
bringing about the formation of carbon–carbon bonds between aromatic
rings and aliphatic moieties.[1] The traditional methods generally involve
the use of stoichiometric amounts of aluminum chloride or sulfuric acid.[2]
Various other Lewis acids have been used intensively.[3] Many of the classic
catalysts such as metallic halides and Bronsted acids cause serious
environmental problems and are corrosive.[4–9] Some of them suffer from
unavailability, instability or hygroscopicity. Among the new reported
reagents for Friedel–Crafts acylation are graphite,[10] zeolites,[11] activated
zinc,[12] zirconium sulfate,[13] bismuth trifluoromethansulfonate,[14] and
titanium chloride.[15] Recently the acylation reaction was also carried
out in the absence of both solvent and catalyst.[16,17]
So, the development of heterogeneous solid acid catalysts to replace
the use of strongly acidic, homogeneous, corrosive, and polluting
reagents can be considered extensively.
We have already reported the application of iron(III) salts in the
formation of carbon–nitrogen and carbon–oxygen bonds in organic
compounds.[18–22] Herein we report a selective method for acylation of
alkoxy benzenes with aliphatic acid anhydrides in the presence of 20 mol%
of ferric ion as Fe(HSO4)3 in nitromethane (Sch. 1).
As shown in the Table 1, the catalytic acylation of alkoxy benzenes
proceeded well with 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 nitro-
methane is the solvent of choice for our reactions.
We also observed that the aromatic acid anhydrides react sluggishly
under the same conditions. Therefore the competitive reaction between
acetic anhydride and benzoic anhydride with anisole was studied and a
high degree of chemoselectivity was observed (Sch. 2).
Scheme 1.

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Acylation of Alkoxy Benzenes
1369
Table 1. Friedel–Crafts acylation of alkoxy benzenes by aliphatic anhydrides in
the presence of Fe(HSO4)3.
Time
(h)
Fe(HSO4)3/sub.
(mole ratio)
Yield
(%)
Entry
R
R0
1
2
–CH3
–CH2CH3
–CH3
–CH3
1.5
2.5
3.5
5
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
71
74
73
69
70
70
72
74
75
73
3
–CH2(CH2)2CH3
–CH2CH(CH3)2
–CH2(CH2)4CH3
–CH3
–CH3
–CH3
–CH3
4
5
4
6
–CH2CH3
–CH2CH3
–CH2CH3
–CH2CH3
–CH2CH3
1.5
2.5
3
7
–CH2CH3
8
–CH2(CH2)2CH3
–CH2CH(CH3)2
–CH2(CH2)4CH3
9
10
4.5
3.5
Scheme 2.
This method also permits us to conduct the selective acylation of
alkoxy benzenes in the presence of the less reactive aromatic compounds
such as arenes and aryl halides. For example ethylbenzene remained
untouched in the competitive reaction with anisole in the presence of
acetic anhydride and 20 mol% of the catalyst (Sch. 3).
In conclusion, ferric hydrogensulfate is an inexpensive, non-toxic,
stable, efficient, and heterogeneous catalyst for the selective acylation of
alkoxy benzenes. Although ferric chloride can also be used for this purpose,
its hygroscopic nature limits its applications in the laboratory.[23]
Fe(HSO4)3 is proposed as a very good successor for FeCl3 in other organic
reactions such as alcoholysis and hydrolysis of epoxides,[18] Beckmann
rearrangement,[19] etherification, and transetherification reactions,[20,22]
Biginelli reaction,[24] etc.

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1370
Salehi et al.
Scheme 3.
EXPERIMENTAL
Products are known compounds and were characterized by compar-
ison of their spectral data (1H NMR, IR) and physical properties with
1
those reported in the literature. H NMR spectra were run on a Bruker
Avance 200 MHz spectrometer. IR spectra were obtained by a Shimadzu
470 spectrophotometer. Progresses of the reactions were followed by
TLC using silica gel Polygrams SIL G/UV 254 Sheets. Melting points
were determined in open capillaries with a Gallen-Kamp melting point
apparatus and are corrected. All yields refer to isolated products.
General Procedure for the Acylation of Alkoxy Benzenes
Ferric hydrogensulfate (0.21 g, 0.6 mmol) was added to a solution of
alkoxy benzene (3 mmol) and acid anhydride (6 mmol) in nitromethane
(7 mL). The mixture was stirred magnetically at 75–80ꢀC for the appro-
priate period of time (Table 1). The progress of the reaction was monitored
by TLC (eluent: n-hexane/diethyl ether: 2/1). Then nitromethane was
evaporated under reduced pressure andasolution ofNaHCO3 (5%, 20 mL)
was added. The aqueous mixture was extracted with diethyl ether
(3 Â 20 mL). The organic layer was dried (Na2SO4) and concentrated.
Final purification on a short silica gel column afforded the desired
products in 69–75% yield.

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Acylation of Alkoxy Benzenes
Spectral and Physical Data of the Products
1371
Entry 1. IR (KBr), ꢀ (cmÀ1): 3060 (w), 3000 (w), 2960 (m), 1665 (s),
1600 (s), 1470 (m), 1250 (s), 1020 (s), 830 (s); 1H NMR (CDCl3), ꢁ (ppm):
7.9 (2H, d), 6.9 (2H, d), 3.8 (3H, s), 2.6 (3H, s); m.p. ¼ 35ꢀC (lit.[25] ¼ 37ꢀC),
m.p. of semicarbazone derivative ¼ 195–197ꢀC (lit.[25] ¼ 197–198ꢀC).
Entry 2. IR (KBr), ꢀ (cmÀ1): 3050 (w), 2980 (m), 2910 (w), 1665 (s),
1600 (s), 1475 (m), 1250 (s), 1030 (m), 845 (m); 1H NMR (CDCl3),
ꢁ (ppm): 7.9 (2H, d), 6.9 (2H, d), 4.0 (2H, q), 2.6 (3H, s), 1.3 (3H, t);
m.p. ¼ 34ꢀC (lit.[25] ¼ 36–37ꢀC), m.p. of semicarbazone derivative
178–180ꢀC (lit.[25] ¼ 179–180ꢀC).
Entry 3. IR (neat), ꢀ (cmÀ1): 3060 (w), 2950 (s), 1675 (s), 1600 (s),
1470 (m), 1250(s), 1020 (m), 830 (s);1H NMR(CDCl3), ꢁ(ppm):7.9 (2H, d),
6.8 (2H, d), 4.0 (2H, t), 2.6 (3H, s), 0.9–1.5 (7H, m); m.p. ¼ 23ꢀC
(lit.[26] ¼ 22ꢀC), m.p. of oxime derivative ¼ 83ꢀC (lit.[26] ¼ 86ꢀC).
Entry 4. IR (neat), ꢀ (cmÀ1): 3050 (w), 2950 (s), 1678 (s), 1600 (s),
1
1470 (m), 1250 (s), 1020 (m), 830 (m); H NMR (CDCl3), ꢁ (ppm): 7.8
(2H, d), 6.8 (2H, d), 3.7 (2H, d), 2.6 (3H, s), 2.0 (1H, m), 1.2 (6H, d); m.p.
of oxime derivative ¼ 105–106ꢀC (lit.[27] ¼ 107ꢀC).
Entry 5. IR (neat), ꢀ (cmÀ1): 3050 (w), 2940 (s), 1678 (s), 1600 (s),
1470 (m), 1250 (s), 1030 (m); 1H NMR (CDCl3), ꢁ (ppm): 7.8 (2H, d), 6.8
(2H, d), 4.0 (2H, t), 2.5 (3H, s), 0.8–1.7 (11H, m); m.p. of oxime
derivative ¼ 77ꢀC (lit.[27] ¼ 78ꢀC).
Entry 6. IR (neat), ꢀ (cmÀ1): 3050 (w), 2950 (s), 1675 (s), 1600 (s),
1470 (m), 1255 (s), 1220 (s), 1025 (s), 950 (m), 700 (s); 1H NMR (CDCl3),
ꢁ (ppm): 7.9 (2H, d), 6.9 (2H, d), 3.8 (3H, s), 2.9 (2H, q), 1.2 (3H, t);
m.p. 25–27ꢀC (lit.[25] ¼ 26–27ꢀC), m.p. of semicarbazone derivative ¼
170–172ꢀC (lit.[25] ¼ 171–172ꢀC).
Entry 7. IR (neat), ꢀ (cmÀ1): 3050 (w), 2980 (s), 2910 (s), 1678 (s),
1600 (s), 1475 (w), 1250 (s), 1220 (s), 800 (m); 1H NMR (CDCl3),
ꢁ (ppm): 7.8 (2H, d), 6.9 (2H, d), 4.0 (2H, q), 3.0 (2H, q), 0.9–1.7 (6H, m);
m.p. ¼ 28–30ꢀC (lit.[25] ¼ 29–30ꢀC), m.p. of semicarbazone derivative ¼
182ꢀC (lit.[25] ¼ 181–183ꢀC).
Entry 8. IR (neat), ꢀ (cmÀ1): 3050 (w), 2950 (s), 2910 (s), 1680 (s), 1600 (s),
1
1460 (s), 1250 (s), 1220 (s), 950 (m), 795 (m); H NMR (CDCl3), ꢁ (ppm):
7.8 (2H, d), 6.8 (2H, d), 4.0 (2H, t), 3.0 (2H, q), 0.9–1.8 (10H, m); m.p. ¼
27–29ꢀC (lit.[28] ¼ 28ꢀC), m.p. of oxime derivative ¼ 77ꢀC (lit.[28] ¼ 79ꢀC).
Entry 9. IR (KBr), ꢀ (cmÀ1): 3050 (w), 2950 (s), 2910 (s), 1673 (s),
1600 (s), 1472 (m), 1255 (s), 1230 (s), 1020 (s), 795 (s); 1H NMR (CDCl3),
ꢁ (ppm): 7.9 (2H, d), 6.9 (2H, d), 3.8 (2H, d), 3.0 (2H, q), 2.1 (1H, m),
0.8–1.5 (9H, m); m.p. ¼ 44ꢀC, m.p. of 2,4-dinitrophenylhydrazone
derivative ¼ 155–157ꢀC.

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1372
Salehi et al.
Entry 10. IR (neat), ꢀ (cmÀ1): 3050 (w), 2930 (s), 1675 (s), 1600 (s),
1
1460 (m), 1250 (s), 1220 (s), 795 (m); H NMR (CDCl3), ꢁ (ppm): 7.8
(2H, d), 6.8 (2H, d), 3.9 (2H, t), 2.9 (2H, q), 0.7–1.6 (14H, m); m.p. of
2,4-dinitrophenylhydrazone derivative ¼ 161–163ꢀC.
ACKNOWLEDGMENT
We are grateful to Razi University Research Council for financial
supportof ht is work.
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Acylation of Alkoxy Benzenes
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Received in the USA June 15, 2002

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