Palladium(II) chloride catalyzed selective acetylation of alcohols with vinyl acetate

Article abstract of DOI:10.1039/b401218f

PdCl₂ can catalyze the acetylation of primary and secondary alcohols with vinyl acetate. The reaction is selective and mild with high yields. Tertiary alcohols, phenols and amines are unaffected under these reaction conditions.

Full text of DOI:10.1039/b401218f

Palladium(II) chloride catalyzed selective acetylation of alcohols with
vinyl acetate†
J. W. J. Bosco and Anil K. Saikia*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, India.
E-mail: asaikia@iitg.ernet.in; Fax: +91 361 2690762
Received (in Corvallis, OR, USA) 26th January 2004, Accepted 8th March 2004
First published as an Advance Article on the web 5th April 2004
PdCl2 can catalyze the acetylation of primary and secondary
alcohols with vinyl acetate. The reaction is selective and mild
with high yields. Tertiary alcohols, phenols and amines are
unaffected under these reaction conditions.
In conclusion, an efficient catalytic acetylation method using
vinyl acetate as the acetylating agent under mild conditions has
been developed. A variety of primary and secondary alcohols were
acetylated in good yields under mild conditions. Groups such as
methoxy, benzyloxy, thioether, thiol, chloro, and phenolic hydroxyl
are unaffected under these reaction conditions. As the catalyst is
heterogeneous, the work up process is very simple. The catalyst can
be recovered by filtering the reaction mixture. The only byproduct
acetaldehyde can be removed by evaporation along with the
solvent. This catalytic acetylation of alcohols offers an additional
The acetylation of alcohols is an important and frequently used
transformation in organic synthesis.1 Acetyl chloride2 and acetic
anhydride3 are generally used as the acetylating agents in the
presence of tributylphosphine4 or pyridine derivatives.5 Lewis acid
catalysts such as Sc(OTf)3,6 TMSOTf,7 Cu(OTf)2,8 TaCl4,9
In(OTf)3,10 CoCl2,11 yttria–zirconia based Lewis acids12 have been
reported to be efficient catalysts for acetylation of alcohols. Ishii
and co-workers13 have reported that Sm(II) complexes catalyze the
acylation of alcohols with vinyl acetate.
Table 1 Palladium catalyzed acetylation of alcohols with vinyl acaetate
%
Palladium chloride has long been used as a useful reagent for
various organic reactions such as oxidation of olefins,14 Cope
rearrangement,15 cyclization reaction,16 deprotection of allyl
No.
1
Substrate (a)
t/h
Product (b)
Yielda
3.5
96
ethers,17 etc. Here we describe, for the first time, the palladium(II
)
chloride catalyzed acetylation of alcohols with vinyl acetate. It was
reported that vinyl acetate reacts with lower aliphatic alcohols in
the presence of palladium(II) catalyst to give vinyl ethers.18 To our
surprise, when a mixture of vinyl acetate, alcohol and catalytic
amounts of PdCl2 and CuCl2 was allowed to stir in dry toluene at
room temperature, acetate was obtained in high yields (Scheme 1).
The reaction was generalized as shown by entries 1–16 of Table
1.‡
2
3
3
4
93
94
4
5
PhCH2O(CH2)4OH
CH3(CH2)8CH2OH
6
5.5
PhCH2O(CH2)4OAc
CH3(CH2)8CH2OAc
82
84
6
5
85b
It was observed from Table 1 that reaction proceeds more rapidly
with primary alcohols than secondary. Sterically hindered secon-
dary alcohols like menthol need 2 mol% of the catalyst. Tertiary
alcohols, phenols, thiols, aliphatic and aromatic amines are
unaffected under these reaction conditions. With amines a palla-
dium complex is formed. When acetic anhydride was used instead
of vinyl acetate only a trace amount of the substrate 2 was converted
to acetate after 3 hours. On the other hand, there were no reactions
of ethyl acetate and acetic acid with 2 under the same reaction
conditions. It was observed that PdCl2 alone is not a good catalyst
and the reaction is accelerated by the addition of CuCl2. When
CuCl2 was used as a catalyst only a trace amount of acetate was
formed after 12 h. This type of catalytic transesterification seems to
be of interest, since acetylation of alcohols with acetyl chloride or
acetic anhydride in the presence of base resulted in side products.11
It is important to note that even 0.3 mol% palladium catalyst is
enough for this transformation.
7
3.5
89
8
9
9.5
4
92
96
10
11
C6H13S(CH2)2OH
HSCH2CH2OH
5
3
C6H13S(CH2)2OAc
HSCH2CH2OAc
58
95
12
13
9
4
0
86
14
15
16
9
9
9
0
0
0
Scheme 1
† Electronic supplementary information (ESI) available: 1H, 13C NMR and
IR spectral data of 4b, 1H NMR, elemental analysis and IR spectral data of
5b; 1H and IR spectral data of 1b, 2b, 3b, 6b, 7b, 8b, 9b, 11b and 13b. See
http://www.rsc.org/suppdata/cc/b4/b401218f/
a Yield refers to isolated yield. The compounds are characterized by 1H
NMR, elemental analysis and IR spectroscopy and comparison with the
literature. b 2 mol% PdCl2 was used.
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C h e m . C o m m u n . , 2 0 0 4 , 1 1 1 6 – 1 1 1 7
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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chloride, as acetylating agent under mild conditions.
The authors are grateful to the Council of Scientific and
Industrial Research, New Delhi for financial assistance and CDRI,
Lucknow for providing 1H NMR.
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‡ Typical experimental procedures: A mixture of the substrate 2 (300 mg,
2.17 mmol), vinyl acetate (373 mg, 4.35 mmol), PdCl2 (1.1 mg, 0.0065
mmol) and CuCl2 (23 mg, 0.17 mmol) in dry toluene (1.0 mL) was stirred
at room temperature for 3 h. The reaction was monitored by TLC using ethyl
acetate and hexane as eluent. After completion of the reaction the catalyst
was removed by fitration and the filtrate evaporated to dryness. Finally the
product was purified by column chromatography to give 364 mg (93%) of
the pure product. The compound was characterized by spectroscopic
methods.
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Sakaguchi, J. Org. Chem., 1996, 61, 3088.
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C h e m . C o m m u n . , 2 0 0 4 , 1 1 1 6 – 1 1 1 7
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