Synthesis of ethyl arylacetates by means of Friedel-Crafts reactions of aromatic compounds with ethyl α-chloro-α-(ethylthio)acetate catalysed by ytterbium triflate

Article abstract of DOI:10.1016/S0040-4039(00)01626-9

An efficient Friedel-Crafts alkylation of aromatic compounds with ethyl α-chloro-α-(ethylthio)acetate catalysed by ytterbium triflate, followed by desulfurisation of the product provides a convenient methodology for the synthesis of ethyl arylacetates of aromatic and heteroaromatic compounds. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01626-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9109–9112
Synthesis of ethyl arylacetates by means of Friedel–Crafts
reactions of aromatic compounds with ethyl
a-chloro-a-(ethylthio)acetate catalysed by ytterbium triflate
Surajit Sinha, Bhubaneswar Mandal and Srinivasan Chandrasekaran*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 18 July 2000; revised 15 September 2000; accepted 20 September 2000
Abstract
An efficient Friedel–Crafts alkylation of aromatic compounds with ethyl a-chloro-a-(ethylthio)acetate
catalysed by ytterbium triflate, followed by desulfurisation of the product provides a convenient
methodology for the synthesis of ethyl arylacetates of aromatic and heteroaromatic compounds. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: catalysis; Friedel–Crafts reaction; lanthanides; substitution.
The Friedel–Crafts reaction is generally achieved using a Lewis acid as the catalyst. A
common problem, particularly in industrial processes, is that the Friedel–Crafts reaction
requires stoichiometric amounts of the Lewis acid which cannot be reused because of its
instability in the usual aqueous work up.
Lanthanide trifluoromethanesulfonates1 [lanthanide triflates; Ln(OTf)3] work efficiently as
versatile Lewis acids and have been employed in a number of reactions both in organic and
aqueous media in catalytic quantities. Since the first utilisation of Yb(OTf)3 by Forsberg et al.,2
it has found wide utility in organic synthesis and recently Kobayashi et al.1a have used Yb(OTf)3
as the catalyst in Friedel–Crafts acylation reactions. It was demonstrated in these reactions that
the catalysts were easily recovered after the reactions were completed and could be reused.
As one of many synthetic applications of a-chlorosulfides, Tamura3 has accomplished the
preparation of arylacetates by the Friedel–Crafts reaction of ethyl a-chloro-a-
(methylthio)acetate in the presence of stoichiometric quantities of a Lewis acid such as SnCl4 or
TiCl4. Subsequently, this methodology has been extended by Arai4 for the synthesis of naproxen.
Herein, we describe an excellent preparative method for the synthesis of ethyl aryl-acetates by
Friedel–Crafts reactions of aromatic compounds with ethyl a-chloro-a-(ethylthio)acetate 1 using
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01626-9

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Yb(OTf)3 as the right catalyst, followed by desulfurisation of the resulting ethyl-a-
(ethylthio)arylacetates (Eq. (1)). The results in this regard are presented in Table 1.
(1)
Initially, the reaction of anisole 2 with ethyl a-chloro-a-(ethylthio)acetate 1 (1.1 equiv.) in the
presence of Yb(OTf)3 (5 mol%) was carried out in CH3NO2 at room temperature to give the
product 3 in 92% yield (para:ortho 2.5:1). In the case of phenol 4, the reaction also proceeded
smoothly at room temperature and afforded the product 5 in excellent yield. This method has
also been applied to aryl alkyl ethers such as 6 and 8 and the products 7 and 9, respectively,
were isolated in excellent yields. It is worth mentioning that the allyl group in 9 survived the
reaction conditions. Compound 9 after desulfurisation and saponification afforded the anti-
inflammatory agent, alclofenac 273 in 97% yield.
This reaction has been extended to substituted benzenes such as toluene 10 and xylene 12 (50°,
12–14 h) and the corresponding products 11 and 13 were obtained in almost quantitative yields.
Next, we examined the reaction of naphthalene, 14 with 1 and isolated the a-substituted product
15 in 85% yield. In the case of substituted naphthalenes such as 16 and 18, the corresponding
products 17 and 19, respectively, were obtained in moderate yields as a mixture of 1 and
6-substituted products. The reactivity of substrate 22 containing the acetamido group was much
slower under the reaction conditions and gave the product 23 with poor conversion. The
reaction of methyl 3,5-dimethoxybenzoate 20 with 1 was very sluggish at room temperature but
at 50°C the ortho product 21 was obtained in good yield, the methyl ester surviving the reaction
conditions.
Heteroaromatic compounds such as furan, 14, which is sensitive to acidic conditions, were
also found to react with 1 affording the ortho substituted furan 25 in excellent yield, whereas
both mono and disubstituted products were obtained when this reaction was carried out in the
presence of ZnCl2.3 The direct insertion of ethyl acetate was not possible using a-bromo ethyl
acetate in the presence of Yb(OTf)3.
In conclusion, Yb(OTf)3 is an excellent catalyst for the insertion of ethyl acetate to aromatic
and heteroaromatic nuclei under mild conditions. Generally, a variety of functional groups are
tolerated and this method has distinct advantages over the classical Friedel–Crafts alkylation
reaction. Thus, we believe this method will find useful application in organic synthesis.
Typical experimental procedure: A mixture of Yb(OTf)3 (28 mg, 0.046 mmol), ortho allyloxy-
chlorobenzene 8 (155 mg, 0.92 mmol) and ethyl a-chloro-a-(ethylthio)acetate (184 mg, 1 mmol)
in distilled nitromethane (1 mL) was stirred at room temperature for 5 h and the reaction
mixture was filtered through a pad of Celite and directly loaded for chromatographic separation
onto silica gel. The product was eluted with 2% EtOAc in petroleum ether (60–80°C) to give 93
1
as a colourless oil (246 mg, 85%). H NMR (CDCl3) l: 1.22 (two triplets, J=7.2 Hz, 6H); 2.50
(q, J=7.4 Hz, 2H); 4.20 (q, J=7.0 Hz, 2H); 4.48 (s, 1H); 4.60 (dt, J1=5.1, J2=1.5 Hz, 2H); 5.30

9111
Table 1

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(dd, J1=11, J2=1.5 Hz, 1H); 5.44 (dd, J1=17, J2=1.5 Hz, 1H); 6.05 (m, 1H); 6.85 (d, J=8.0
Hz, 1H); 7.30 (dd, J1=8.7, J2=2.1 Hz, 1H); 7.49 (d, J=2.4 Hz, 1H).
Acknowledgements
We are grateful to the Department of Science and Technology, New Delhi, for financial
support.
References
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1995, 28, 77; (c) Kobayashi, S. Synlett 1994, 689.
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J. J.; Brown, P. S.; Miller, J. L. J. Org. Chem. 1987, 52, 1017.
3. Tamura, Y.; Choi, H. D.; Shindo, H.; Ishibashi, H. Chem. Pharm. Bull. 1982, 30, 915.
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