Bi(OTf)3-catalyzed acylation of p-quinones: A facile synthesis of acylated hydroquinones

Article abstract of DOI:10.1016/j.tetlet.2004.06.032

p-Quinones undergo smooth acylation with acetic anhydride in the presence of 2mol% of bismuth triflate under mild conditions to afford the corresponding 1,4-diacylated-2-acetoxylated hydroquinones in excellent yields with high selectivity.

Full text of DOI:10.1016/j.tetlet.2004.06.032

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6037–6039
Bi(OTf) -catalyzed acylation of p-quinones:
3
a facile synthesis of acylated hydroquinones
*
J. S. Yadav, B. V. Subba Reddy, T. Swamy and K. Raghavender Rao
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 29 January 2004; revised 28 May 2004; accepted 4 June 2004
Available online 26 June 2004
Abstract—p-Quinones undergo smooth acylation with acetic anhydride in the presence of 2 mol % of bismuth triflate under mild
conditions to afford the corresponding 1,4-diacylated-2-acetoxylated hydroquinones in excellent yields with high selectivity.
ꢀ
2004 Elsevier Ltd. All rights reserved.
1
0
Hydroxyhydroquinones are widely distributed in nature
and are known to possess a broad spectrum of biological
alternatives to conventional Lewis acids. However,
lanthanide triflates are rather expensive and their use in
large-scale synthesis is limited. Therefore, cheaper and
more efficient catalysts are desirable. Bismuth triflate
has evolved as a remarkable Lewis acid catalyst for
1
activities. Many functionalized hydroxyquinones are
extensively used as anti-oxidants, in the photo-industry
2;3
and as polymeric materials. In addition, many qui-
nones derived from aromatic compounds are used as
11
effecting various organic transformations. Compared
to lanthanide triflates, bismuth triflate is cheap and is
easy to prepare even on a multi-gram scale, from com-
4
dienophiles in the Diels–Alder reaction. Thus the syn-
thesis of hydroxyquinones is of some importance. The
Thiele–Winter acetoxylation is one of the most simple
and straightforward approaches for the synthesis of the
1
2
mercially available bismuth oxide and triflic acid.
5a
triacetoxyaromatic precursors of hydroxyquinones.
The method involves the reaction of quinones with
acetic anhydride and is generally catalyzed by sulfuric
We wish to report a procedure for the synthesis of 1,4-
diacylated-2-acetoxylated hydroquinones using a cata-
lytic amount of Bi(OTf)
treatment of p-benzoquinone 1 (R ¼ R ¼ H) with acetic
3
under mild conditions. Thus,
0
5b
acid. The use of sulfuric acid results in the formation
of tars in some cases, due to its strong acidity and oxi-
dizing character. Zinc chloride has been reported as a
anhydride 2 in the presence of 2 mol % of Bi(OTf)
resulted in the formation of 1,2,4-triacetoxybenzene 3a
3
5c
0
milder catalyst but generally chloroquinones are
formed as by-products. Subsequently, boron trifluo-
ride, perchloric acid and triflic acid have been found to
(R ¼ R ¼ H) in 91% yield (Scheme 1).
5a
The reaction was complete in a short time (45 min).
Substituted benzoquinones, such as 2-methyl-, 2-ethoxy-,
2-methoxy-, 2,3-dimethyl-, 2,5-dimethyl-, 2,6-dimethyl-,
and 2,5-dichloro-derivatives also reacted rapidly with
acetic anhydride to afford the corresponding tri-acet-
oxybenzenes (Table 1, entries b–h) in moderate to
excellent yields. With mono-substituted quinones such
6–8
give higher yields than sulfuric acid. However, qui-
nones bearing electron-donating groups failed to give
the desired triacetates with boron trifluoride or sulfuric
7c
acid as the catalyst.
Lanthanide triflates are unique Lewis acids that are
9
currently of interest. The high catalytic activity, low
toxicity, moisture and air tolerance, and their recycla-
bility, make the use of lanthanide triflates attractive
O
OAc
R
2 mol% Bi(OTf)3
R
OAc
R1
Ac O
+
2
R1
CH CN, r.t.
3
O
1
Keywords: p-Quinones; Acid anhydride; Thiele–Winter reaction; Bis-
muth triflate.
OAc
3
2
*
Corresponding author. Tel.: +91-40-27193434; fax: +91-40-2716
512; e-mail: yadav@iict.res.in
0
Scheme 1.
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.032

6038
J. S. Yadav et al. / Tetrahedron Letters 45 (2004) 6037–6039
Table 1. Bismuth(III) triflate catalyzed acylation of p-quinones with acetic anhydride
a
b
Entry
a
Quinone 1
Product 3
Reaction time (min)
Yield (%)
O
OAc
OAc
45
91
O
OAc
O
OAc
EtO
EtO
b
50
65
OAc
O
OAc
OAc
O
Me
Me
Me
Me
Me
Me
c
55
60
86
82
OAc
O
OAc
OAc
O
Me
OAc
Me
d
O
OAc
O
OAc
Me
Me
Me
OAc
e
55
85
Me
O
OAc
O
OAc
OAc
MeO
MeO
Cl
f
70
60
70
45
50
68
70
79
84
75
OAc
O
O
OAc
Cl
OAc
Cl
g
h
i
Cl
O
OAc
O
OAc
Me
Me
OAc
O
O
OAc
OAc
OAc
O
O
OAc
OAc
Me
Me
j
OAc
O
OAc
a
1
All products were characterized by H NMR, IR, and mass spectroscopy.
Isolated and unoptimized yields.
b
5
a
as 2-methyl-1,4-benzoquinone, 2-ethoxy- or 2-methoxy-
,4-benzoquinone, the addition occurred selectively at
catalyst). The triacetate derived from menadione is a
precursor of phthiocol, an antibiotic isolated from
1
13
the 5-position (Table 1, entries b, f, h) to give 1,2,4-tri-
acetoxy derivatives. 1,4-Naphthoquinone and 2-methyl-
naphthoquinone (menadione) also afforded triacetoxy
derivatives under these conditions (Table 1, entries i and
j), even though, 2-methylnaphthoquinone fails to pro-
duce a triacetate under the literature conditions (even in
the presence of sulfuric acid or boron trifluoride as the
Mycobacterium tuberculosis. In all cases, the reactions
proceeded rapidly at room temperature with high effi-
ciency. As a solvent, acetonitrile appeared to give the
1
best results. The products were characterized by
NMR, IR, and mass spectroscopic data and also by
H
5a
comparison with authentic samples. This method is
clean and free from the chlorinated side products which

J. S. Yadav et al. / Tetrahedron Letters 45 (2004) 6037–6039
6039
5
c
are normally observed under zinc chloride catalysis.
W.; Saleh, S. A. J. Chem. Soc., Perkin Trans. 1 1974, 384;
(
. (a) Imamoto, T. Lanthanides in Organic Synthesis; Aca-
demic Press: London, 1994; (b) Molander, G. A. Chem.
Rev. 1992, 92, 29.
0. (a) Kobayashi, S. Synlett 1994, 689; (b) Kobayashi, S. J.
Synth. Org. Chem. Jpn. 1995, 53, 370; (c) Kobayashi, S.
Eur. J. Org. Chem. 1999, 15.
1. Leonard, M. N.; Wieland, L. C.; Mohan, R. S. Tetrahe-
dron 2002, 58, 8373.
12. Repichet, S.; Zwick, A.; Vendier, L.; Le Roux, C.; Dubac,
c) Hirama, M.; Ito, S. Chem. Lett. 1977, 627.
The method works well with both electron-donating as
well as electron-deficient benzoquinones to give the
corresponding triacetates. However, most other meth-
ods which fail to produce a triacetate with 2-methyl-
naphthoquinone are also reported to give lower
conversions with methoxy- or ethoxy-substituted qui-
nines as found here. Among the metal triflates such as
Cu(OTf) , Yb(OTf) , In(OTf) , and Ce(OTf) studied
9
1
1
2
3
3
3
for this transformation, bismuth(III) triflate was found
to be the more effective in terms of conversion and
reaction rates. However, similar results were also
J. Tetrahedron Lett. 2002, 43, 993.
1
3. General procedure: A mixture of p-quinone 1 (2 mmol),
Bi(OTf)3 (0.05 mmol) and acetic anhydride (8 mmol) in
acetonitrile (10 mL) was stirred at room temperature for
the specified time (see Table 1). After completion of the
reaction as indicated by TLC, the reaction mixture was
quenched with saturated aqueous sodium bicarbonate
solution and extracted with ethyl acetate (2 · 10 mL).
Evaporation of the solvent followed by purification on
silica gel (Merck, 100–200 mesh, ethyl acetate–hexane, 0.5/
13
obtained using 5 mol % of scandium(III) triflate.
In conclusion, we describe a simple and highly efficient
protocol for the preparation of 1,2,4-triacetylated
hydroquinones via Thiele–Winter reaction using bis-
muth(III) triflate as a novel catalyst.
9.5) afforded pure product. Spectral data for selected
products: 3d: 2,5-Dimethyl-3,4-di-acetoxyphenyl acetate
(
see Table 1): solid, mp 96–98 ꢁC. IR (KBr): m 2929,
Acknowledgements
ꢀ1
1
1
NMR (200 MHz, CDCl
(s, 9H), 6.80 (s, 1H). C NMR (75 MHz, proton decou-
pled): d 168.6, 167.7, 167.5, 146.7, 141.8, 139.1, 129.4,
763, 1439, 1377, 1194, 1079, 1015, 923, 823 cm
): d 1.95 (s, 3H), 2.20 (s, 3H), 2.30
. H
3
3
1
B.V. S. and T.S. thank CSIR, New Delhi, for the award
of fellowships.
1
(
22.4, 121.3, 20.6, 20.1, 20.1, 15.9, 10.0. FAB MS: m=z
%): 280 M (30), 260 (25), 238 (35), 196 (60), 154 (100),
þ
1
2
21 (20), 107 (10), 75 (40). HRMS calcd for C14
80.0946. Found: 280.0909. 3f: 2-Methoxy-4,5-di-acetoxy-
16 6
H O :
References and notes
phenyl acetate (see Table 1): solid, mp 128–130 ꢁC. IR
KBr): m 2940, 1771, 1618, 1505, 1371, 1198, 1159, 1014,
(
ꢀ
3
919 cm . H NMR (200 MHz, CDCl ): d 2.25–2.35 (m,
13
1
1
1
2
. Spyroudis, S. Molecules 2000, 5, 1291.
. Yamamura, T.; Nishiwaki, K.; Tanigaki, Y.; Terauchi, S.;
Tomiyama, S.; Nishiyama, T. Bull. Chem. Soc. Jpn. 1995,
9H), 3.90 (s, 3H), 6.80 (s, 1H), 6.92 (s, 1H). C NMR
(75 MHz, proton decoupled): d 166.6, 166.4, 166.3, 147.6,
138.5, 135.4, 133.3, 116.3, 106.3, 54.9, 19.3, 18.8, 18.5.
6
8, 2955.
þ
3
. (a) Ozaki, Y.; Hosoya, A.; Okamura, K.; Kim, S.-W.
Synlett 1997, 365; (b) Brugging, W.; Kampschulte, U.;
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R., Ed.; Wiley: New York, 1949; Vol. 5, p 136.
. (a) McOmie, J. F. W.; Blatchly, J. M. Org. React. 1972, 19,
199; (b) Thiele, J. Ber. 1898, 31, 1247; (c) Thiele, J.;
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997, 38, 4777.
. (a) Goodwin, S.; Witkop, B. J. Am. Chem. Soc. 1957, 79,
79; (b) Metlesics, W.; Wessely, F.; Budzikiewicz, H.
EIMS: m=z (%): 282 M (10), 241 (30), 199 (45), 156 (100),
142 (25), 43 (65). HRMS calcd for C13
14 7
H O : 282.0739.
Found: 282.0783. 3h: 2-Methyl-4,5-di-acetoxyphenyl ace-
tate: solid, mp 102–104 ꢁC. IR (KBr): m 2930, 1769, 1509,
4
5
ꢀ
1 1
1371, 1219, 772 cm . H NMR (200 MHz, CDCl ): d 2.10
13
3
(s, 3H), 2.15–2.20 (m, 9H), 6.90 (s, 1H), 7.0 (s, 1H).
C
NMR (50 MHz, proton decoupled): d 168.6, 167.9, 167.7,
147.7, 142.6, 138.5, 128.4, 120.8, 117.1, 20.8, 20.5, 20.4,
þ
6
15.7. FAB MS: m=z (%): 266 M (15), 224 (50), 182 (40),
140 (100), 43 (60). HRMS calcd for C H O : 266.0790.
1
3
14
6
Found: 266.0756. 3i: 1,4-Di(methylcarbonyloxy)-2-naph-
thyl acetate: solid, mp 91–92 ꢁC. IR (KBr): m 2924, 1775,
1
ꢀ1 1
7
1618, 1375, 1097, 915, 801 cm
CDCl ): d 2.30 (s, 9H), 7.05–7.25 (m, 5H). C NMR
H NMR (200 MHz,
1
3
1
3
Tetrahedron 1959, 6, 345; (c) Fieser, L. F.; Fieser, M.
Advanced Organic Chemistry; Reinhold: New York, 1961;
p 855.
. (a) Blatchly, J. M.; Green, R. J. S.; McOmie, J. F. W. J.
Chem. Soc., Perkin Trans. 1 1972, 2286; (b) McOmie, J. F.
(75 MHz, proton decoupled): d 170.3, 169.5, 169.3, 146.1,
140.2, 136.5, 129.7, 129.2, 128.2, 127.2, 123.4, 123.2, 116.2,
22.5, 22.3, 21.9. EIMS: m=z (%): 302 M (10), 210 (15), 168
(30), 126 (85), 110 (40), 43 (100). HRMS calcd for
þ
8
16 14 6
C H O : 302.0791. Found: 302.0762.