Nafion-catalyzed preparation of benzhydryl ethers

Article abstract of DOI:10.1016/S0040-4039(02)01755-0

Nafion-H is found to be an efficient and recyclable catalyst for the preparation of diphenylmethyl ethers of alcohols.

Full text of DOI:10.1016/S0040-4039(02)01755-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7307–7309
Nafion-catalyzed preparation of benzhydryl ethers
Marina A. Stanescu and Rajender S. Varma*
Clean Processes Branch, National Management Research Laboratory, US Environmental Protection Agency, MS 443,
26 W. Martin Luther King Drive, Cincinnati, OH 45268, USA
Received 31 July 2002; revised 13 August 2002; accepted 21 August 2002
Abstract—Nafion-H is found to be an efficient and recyclable catalyst for the preparation of diphenylmethyl ethers of alcohols.
Published by Elsevier Science Ltd.
The selective protection of alcohols as diphenylmethyl
(DPM) ethers is commonly used in organic synthesis.1
DPM ethers are relatively inexpensive to prepare, stable
towards a variety of reagents and are also found as an
integral part of several pharmacologically active com-
pounds.2 Several reagents are available for the prepara-
tion of DPM ethers such as diphenylmethyl
diazomethane or diphenylmethyl phosphate-tri-
fluoroacetic acid,3 diphenylmethyl chloride or bromide
in the presence of a base,4 diphenylmethanol in the
presence of concentrated sulfuric5or p-toluenesulfonic
acid,6 xenon difluoride,7 ytterbium triflate-ferric
chloride8 and iron salts.9 These methods require a high
catalyst to substrate ratio, longer reaction times, and
larger amounts of solid supports which results in gener-
ation of waste. Thus there is a need for an efficient
metal- or support-free catalyst for the preparation of
DPM ethers, preferably using a solid acid. Nafion-H, a
perfluorinated sulfonic acid resin, represents such a
useful solid acid catalyst for a variety of organic trans-
formations.10 The high catalytic activity of Nafion-H,
its selectivity and ease of separation from the reaction
mixture as well as its regeneration renders it a very
attractive candidate.10 As part of an ongoing research
program to develop greener chemical transformations,11
herein, we report an efficient Nafion-catalyzed prepara-
tion of DPM ethers of alcohols at moderate
temperature.
otherwise indicated, to afford the corresponding DPM
ether. After completion of the reaction, the organic
solvent containing the crude product was simply
decanted off and the solvent evaporated. The crude
product was purified by column chromatography using
hexane/ethyl acetate as eluent. The formation of DPM
ethers starting from benzhydrol and benzyl alcohol was
examined under a variety of reaction conditions. Ini-
tially, the identification of appropriate solvent and the
reaction temperature were optimized. The reaction
delivered highest yield in acetonitrile compared to ethyl
acetate and methylene chloride. The reaction was
almost complete in 3 h at 80°C affording DPM ether
(93%), while the reaction at room temperature was
slower, providing ꢀ60% in 3 h and 95% overnight.
Next, the catalyst to substrate ratio was optimized. The
reaction worked well at a catalyst to substrate ratio of
50 mg/1 mmol. At lower ratios, such as 50 mg/10
mmol, the reaction slowed down considerably and
equal amounts of self-condensed ether of benzhydrol
was formed overnight along with unreacted benzhydrol.
Having established acetonitrile as the reaction solvent,
80°C as the reaction temperature and 50 mg/1 mmol
catalyst to substrate ratio, the method was extended to
a variety of hydroxyl compounds and the results are
summarized in Table 1. For these rapid reactions, the
reactivity trend for different alcohols was found to be
primary>secondary>tertiary. This chemoselective fea-
ture of the method became apparent when DPM ethers
of benzylic alcohols and primary alcohols were formed
in high yields with only trace amount of dibenzhydryl
ether (<5%). The reactions involving secondary (entries
4 and 5) and tertiary alcohols (entry 6), however,
proceeded relatively slow and the amount of dibenz-
hydryl ether was also increased in these cases.
In the present method, a mixture of alcohol and
diphenylmethanol was warmed in the presence of a
catalytic amount of Nafion-H in acetonitrile, unless
Keywords: alcohols; diphenylmethyl ethers; Nafion-H.
* Corresponding author. Fax (513)-569-7677; e-mail: varma.rajender
@epa.gov
0040-4039/02/$ - see front matter. Published by Elsevier Science Ltd.
PII: S0040-4039(02)01755-0

7308
M. A. Stanescu, R. S. Varma / Tetrahedron Letters 43 (2002) 7307–7309
Table 1. Nafion-catalyzed preparation of DPM ethers
from alcohols
In conclusion, the present preparative method is an
efficient and practical alternative to the preparation of
DPM ethers of alcohols. The operational simplicity, the
absence of solid supports and of inorganic salts, and
the catalyst recyclability makes this high yield method-
ology an attractive alternative to the existing methods.
Disclaimer—This article was authored by US Govern-
ment employees as part of their official duties. In view
of Section 105 of the Copyright Act (17 USC Section
105) the work is not subject to US copyright protection.
The views expressed in this article are those of the
individual authors and do not necessarily reflect the
views and policies of the US Environmental Protection
Agency. The use of trade names does not imply
endorsement by the US Government.
Entry
Alcohol
Time (h)
Yield% (isolated)
1
2
3
4
5
6
7
8
1-Hexanol
1-Hexanol
1-Pentanol
2-Pentanol
2
3
2
4
4
3
2
2
1
2
1
78
91
76
42
35
B5
51
75
85
92
89
3-Pentanol
Acknowledgements
2-Methyl-2-propanol
Cyclohexanol
Cyclohexylmethanol
Benzyl alcohol
Benzyl alcohol
4-Fluorobenzyl
alcohol
2-Fluorobenzyl
alcohol
2-Bromobenzyl
alcohol
2-Chlorobenzyl
alcohol
3-Chlorobenzyl
alcohol
4-Chlorobenzyl
alcohol
Allylic alcohol
9
10
11
M.A.S. is a postgraduate research participant at the
National Risk Management Research Laboratory
administered by the Oak Ridge Institute for Science
and Education through an interagency agreement
between the US Department of Energy and the US
Environmental Protection Agency. We thank Dr.
Vasudevan V. Namboodiri for his assistance.
12
13
14
15
16
17
1
1
1
1
1
2
83
90
81
87
89
67
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