One-step reaction of friedel-crafts acylation and demethylation of aryl-methyl ethers catalyzed by ytterbium(III) triflate

Article abstract of DOI:10.1081/SCC-200036628

Catalytic amount of ytterbium(III) inflate [Yb(OTf)₃] has been used to catalyze Friedel-Crafts acylation and demethylation of aryl-methyl ethers in one-step reaction to produce hydroxyacylphenones with moderate yields under mild conditions.

Full text of DOI:10.1081/SCC-200036628

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One‐Step Reaction of
Friedel–Crafts Acylation
and Demethylation of
Aryl‐Methyl Ethers Catalyzed
by Ytterbium(III) Triflate
Weike Su a & Can Jin a
a College of Pharmaceutical Sciences, Zhejiang
University of Technology, Hangzhou, 310014, P.R.
China
Version of record first published: 10 Jan 2011.
To cite this article: Weike Su & Can Jin (2004): One‐Step Reaction of Friedel–Crafts
Acylation and Demethylation of Aryl‐Methyl Ethers Catalyzed by Ytterbium(III)
Triflate, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:22, 4199-4205
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 22, pp. 4199–4205, 2004
One-Step Reaction of Friedel–Crafts
Acylation and Demethylation of
Aryl-Methyl Ethers Catalyzed by
Ytterbium(III) Triflate
*
Weike Su and Can Jin
College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou, P.R. China
ABSTRACT
Catalytic amount of ytterbium(III) triflate [Yb(OTf)3] has been used to
catalyze Friedel–Crafts acylation and demethylation of aryl-methyl
ethers in one-step reaction to produce hydroxyacylphenones with moder-
ate yields under mild conditions.
Key Words: Demethylation; Ethers; Friedel–Crafts acylation;
Ytterbium(III) triflate.
*
Correspondence: Weike Su, College of Pharmaceutical Sciences, Zhejiang University
of Technology, Hangzhou 310014, P.R. China; Fax: (0086)57188320752; E-mail:
suweike@zjut.edu.cn.
4199
DOI: 10.1081/SCC-200036628
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Su and Jin
Lanthanide trifluoromethanesulfonate [lanthanide triflates; Ln(OTf)3],
especially ytterbium triflate [Yb(OTf)3], as a new versatile Lewis acid has
been used in Friedel–Crafts reactions with a catalytic amount of catalyst,[1]
which can be reused easily.[2] For example, Friedel–Crafts reactions of
aromatic compounds with ethyl a-chloro-a-(ethylthio)acetate promoted by
ytterbium triflate can proceed smoothly.[3] Methylation is a very important
method to protect hydroxy group in organic chemistry, which can be regenerated
via demethylation. Deprotecting of methoxy group can proceed with nucleo-
philic reagents under acidic or basic condition. There are several methods[4]
that have been used in deprotection of alkoxyl group. Recently, Lisa et al.[5]
reported demethylation of aryl-methyl ethers using no-odorous thiolate. How-
ever, some methods need drastic conditions, which usually bring about the struc-
tural and stereochemical changes or have low yields because aryl-methyl ether is
difficult to be demethylated under mild conditions.[6] As a very strong Lewis
acid, Yb(OTf)3 can catalyze Friedel–Crafts acylation as well as demethylation.
Herein, we report demethylation of aryl-methyl ethers using acyl chloride
as acylation and demethylation reagents by one-step reaction to obtain hydro-
xyacylphenones catalyzed by Yb(OTf)3 (Scheme 1) and the results are shown
in Table 1.
From Table 1, it was found that the aryl-methyl ethers can be deprotected
by acyl chloride in the presence of catalytic amount of Yb(OTf)3 with moder-
ate yields except that when the substrate is o-nitroanisole (entry 2). When,
o-nitroanisole reacts with acylation reagents for longer time, unfortunately,
none of the desired product was detected (entry 2). Furthermore, the highly
chemselective products was obtained in our experiment and 0.2 equivalents
of Yb(OTf)3 is enough to complete the reaction. It is of interest that the
main product 3e was obtained when 2 equivalents of acetyl chloride was
used to react with m-methyl-anisole for 10 hr in the presence of Yb(OTf)3.
On the other hand, the amounts of acyl chloride was studied in our experi-
ment, and it was found that when 2 equivalents of acylation reagent are used, a
by-product is obtained from esterification of phenol (Scheme 2). However, there
are no by-products under the condition that 1 or 1.5 equivalents of acyl chloride
are used. In addition, when aroyl chloride is used, the reaction needs longer
time, and the yield is not so high as using alkyl acyl chloride (entries 6 and 7).
Scheme 1.

Friedel–Crafts Acylation and Demethylation of Aryl-Methyl Ethers
4201

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Su and Jin
Scheme 2.
The mechanism of this reaction has not been clarified yet, according to
literature 4f and considering Friedel–Crafts acylation, a possible mechanism
is postulated in Scheme 3 (when R1 is para-NO2 and R2 is CH3). In Scheme 3
we suppose that the presence of catalyst is propitious to not only Friedel–
Crafts acylation but also demethylation.
In conclusion, with moderate yields, simple operation and mild conditions,
the work described gives a useful method for deprotecting of aryl-methyl ethers
to obtain hydroxyacylphenones by one-step reaction. Further studies to the
strong catalytic reactivity of ytterbium triflate are now in progress.
EXPERIMENTAL
1
All reagents used are commercially available. H NMR spectra were
recorded on a Varian-400 MHz instrument using CDCl3 as the solvent with
TMS as an internal standard. IR spectra were recorded on a AVATAR-370
Scheme 3.

Friedel–Crafts Acylation and Demethylation of Aryl-Methyl Ethers
4203
Infrared Spectrophotometer. Mass spectra were tested by a Thermo Finnagan
LCQ Advantage instrument. Microanalysis was carried out on a Carlo-Erba
1106 instrument. Melting points were determined on a Digital Melting
Point Apparatus WRS-1B and uncorrected. Yb(OTf)3 was prepared from
Ytterbium oxide and trifluoromethanesulfonic acid in water according to the
literature.[7]
General Experimental Procedure
Acyl chloride (3 mmol) was added to a solution of substrate (2 mmol) in
carbon bisulfide (10 mL) in a 25-mL dry flask. The mixture was refluxed for
5 min, cooled to room temperature, and Yb(OTf)3 (0.4 mmol, 0.248 g) was
added. The solution was refluxed for the given time (see Table 1) after
being cooled to room temperature, and then quenched by 5 mL ice water.
The organic layer was washed by 5% sodium bicarbonate (10 mL) and
extracted by chloroform, and then the combined organic layer was dried
over anhydrous Na2SO4. After concentrated in vacuo, the residue was purified
by TLC to yield corresponding products.
Compound 4a
Mp 1078C (Lit[8] 106–1078C). IR ymax/cm21: 3288, 1644; NMR dH:
8.71 (1H, s, ArOH), 7.95 (2H, d, J ¼ 8.4 Hz, ArH), 6.99 (2H, d, J ¼ 8.4 Hz,
ArH), 2.54 (3H, s, CH3).
Compound 3c
Mp 102.5–103.08C (Lit[9] 102–1038C). IR ymax/cm21: 3364, 1668;
NMRdH: 7.71 (1H, s, ArOH), 7.75 (1H, s, ArH), 7.73 (1H, d, J ¼ 8.0 Hz,
ArH), 6.84 (1H, d, J ¼ 8.0 Hz, ArH), 2.56 (3H, s, CH3).
Compound 4d
Mp 114–1158C (Lit[10] 1158C). IR ymax/cm21: 3328, 1648; NMR dH:
10.12 (1H, s, ArOH), 7.58–7.48 (2H, m, ArH), 6.99–6.81 (1H, s, ArH),
3.93 (3H, s, CH3), 2.54 (3H, s, CH3); (ESI) MS (m/z): 165.2 (M-H)2.
Compound 3e
Mp 102–1048C. IR ymax/cm21: 3314, 1678, 1665; NMR dH: 12.53
(1H, s, ArOH), 8.16 (1H, s, ArH), 6.81 (1H, s, ArH), 2.66 (3H, s, CH3),

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Su and Jin
2.59 (3H, s, CH3), 2.57 (3H, s, CH3); (ESI) MS (m/z): 191.1 (M-H)2; Anal.
calcd. for C11H12O3: C, 68.74; H, 6.29. Found: C, 68.77; H, 6.33.
Compound 4f
Mp 133.8–134.38C (Lit[11] 133.8–133.98C). IR ymax/cm21: 3221, 1637;
NMR dH: 12.25 (1H, s, ArOH), 7.79–7.74 (3H, m, ArH), 7.62–7.56 (2H, m,
ArH), 7.48 (2H, d, J ¼ 8.2 Hz, ArH), 6.95 (2H, d, J ¼ 8.2 Hz, ArH).
Compound 3g
Mp 122–1248C (Lit[12] 122–1248C). IR ymax/cm21: 3228, 1641; NMR
dH: 8.14–8.11 (3H, m, ArH), 7.64–7.60 (2H, m, ArH), 7.50–7.47 (3H, m,
ArH), 4.85 (1H, s, ArOH).
Compound 3h
Mp 163–1648C. IR ymax/cm21: 3418, 3302, 1668, 1647; NMR dH: 12.08
(1H, s, ArOH), 8.18 (1H, s, NH), 8.08 (1H, s, ArH) 7.42 (1H, m, ArH), 6.97
(1H, m, ArH), 2.62 (3H, s, CH3), 2.17 (3H, s, CH3). (ESI) MS (m/z): 194.1
(M þ H)þ; 192.2 (M-H)2; Anal. calcd. for C10H11NO3: C, 62.17; H, 5.74;
N, 7.25. Found: C, 62.19; H, 5.78; N, 7.26.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
[20276072] for financial support.
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Received in UK December 15, 2003