A mild and efficient synthesis of chloroesters by the cleavage of cyclic and acyclic ethers using Bi(NO3)3·5H2O as a catalyst under solvent-free conditions

Article abstract of DOI:10.1139/V07-126

A facile, efficient synthesis of chloroesters is described. The reaction of cyclic and acyclic ethers with acid chlorides in the presence of catalytic amounts of Bi(NO₃)₂·5H₂O under solvent-free conditions yielded the corresponding chloroesters. Also, the catalyst can be recovered conveniently and reused efficiently for at least six times.

Full text of DOI:10.1139/V07-126

1037
A mild and efficient synthesis of chloroesters by
the cleavage of cyclic and acyclic ethers using
Bi(NO3)3·5H2O as a catalyst under solvent-free
conditions
V. Suresh, N. Suryakiran, and Y. Venkateswarlu
Abstract: A facile, efficient synthesis of chloroesters is described. The reaction of cyclic and acyclic ethers with acid
chlorides in the presence of catalytic amounts of Bi(NO3)3·5H2O under solvent-free conditions yielded the correspond-
ing chloroesters. Also, the catalyst can be recovered conveniently and reused efficiently for at least six times.
Key words: Bismuth(III) nitrate pentahydrate, cyclic and acyclic ethers, chloroesters.
Résumé : On décrit une méthode simple et efficace de synthèse des chloroesters. La réaction d’éthers cycliques et
acycliques avec des chlorures d’acides, en présence de quantités catalytiques de Bi(NO3)2·5H2O et dans des conditions
sans solvant, fournit les chloroesters correspondants. De plus, il est possible de récupérer facilement le catalyseur et
de le réutiliser d’une façon efficace au moins six fois.
Mots-clés: pentahydrate du nitrate de bismuth(III), éthers cycliques et acycliques, chloroesters.
[Traduit par la Rédaction] V. Suresh et al. 1040
Introduction
Scheme 1.
The cleavage of cyclic and acyclic ethers with acid chlorides,
leading to the synthesis of the corresponding chloroesters, is
a versatile organic transformation, as they are important and
key constituents in organic synthesis, particularly in the syn-
thesis of natural products (1). Transformation of cyclic
ethers into haloesters is a direct and straightforward method
for producing bifunctional synthetic intermediates and also
an important method for the removal of ethereal protecting
groups (2). In organic synthesis, hydroxyl groups are pro-
tected as aliphatic, benzylic, and allylic ethers (3), which can
subsequently be cleaved for further transformations (4–7).
The cleavage of ethers with acyl chlorides has been reported
using Lewis acids, such as SmI2 (8), ZnCl2 (9), FeCl3 (10),
I2 (11), MoCl5 (12), PdCl2(PPh3)2 (13), CoCl2 (3), and very
recently InBr3 (14). However, using strongly acidic condi-
tions frequently leads to the formation of undesirable side
products, which in turn decrease the purity and yields of the
desired products. Most of the reported methods have one or
other limitations, such as long reaction time, unavailability
of the catalyst, difficulties in handling, and tedious workup
procedures with unsatisfactory yields. Thus, a mild, efficient
catalyst for the cleavage of cyclic and acyclic ethers with
acid chlorides is highly desirable. In view of the merits in
catalytic processes, we are interested in the development of
.
Bi(NO3)3 5H2O
O
[ ]
n
H3C
O
[ ]
+
n
Cl
H3C
Cl
RT, 5–75 min
O
O
solvent-free conditions
1
2
3
inexpensive, mild, and non-polluting reagent for the acid-
chloride-directed cleavage of cyclic and acyclic ethers.
Organic reactions using mild and water-tolerant catalysts
received much attention in recent years, as they can be han-
dled conveniently, and the products can be easily recovered
from the reaction mixture, thus making the experimental
procedure simple and eco-friendly. Among Lewis acid cata-
lysts, the bismuth(III) nitrate pentahydrate is relatively non-
toxic, inexpensive, stable in atmospheric conditions, and
used in various organic transformations (15). Also, to the
best of our knowledge, there is no report on the use of
Bi(NO3)3·5H2O for the cleavage of cyclic and acyclic ethers
with acid chlorides. Recently, we reported Bi(NO3)3·5H2O
as a mild and efficient Lewis acid catalyst for N-tert-butoxy-
carbonylation of amines (16). In continuation of our work on
catalytic application of metal nitrate salts in the multi-step
synthesis of natural products in our laboratory, we have ob-
served that Bi(NO3)3·5H2O can be utilized efficiently for the
cleavage of cyclic and acyclic ethers with different acid
chlorides into the corresponding chloroesters under solvent-
free conditions.
Received 31 May 2007. Accepted 20 October 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 9 November 2007.
V. Suresh, N. Suryakiran, and Y. Venkateswarlu.1 Organic
Chemistry Division I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India.
Results and discussion
In this report (Scheme 1), we describe an efficient and
facile method for the synthesis of chloroesters. This method
1Corresponding author (e-mail address: luchem@iict.res.in).
Can. J. Chem. 85: 1037–1040 (2007)
doi:10.1139/V07-126
© 2007 NRC Canada

1038
Can. J. Chem. Vol. 85, 2007
Scheme 2. Plausible mechanism.
Bi(III)
Bi(III)
O
O
R
O
Cl
-
R
R
major
O
+
+
O
R
R
O
O
+
..
R
Cl
Cl
..
Cl
R
O
minor
R
Bi(III)
Table 1. Comparison of various catalysts on the reaction of
tetrahydrofuran with acetyl chloride at room temperature under
solvent-free conditions.
ethers in the same substrate, formation of products
(chloroesters) was observed only with acyclic part of the
substrate (Table 2, entries 17 and 18).
Further, we have studied the reusability of the catalyst
without any modification of the reaction conditions. After
completion of the reaction, ethyl acetate (10 mL) was added;
the catalyst was recovered by filtration and reused without
loss of its activity for six runs (Table 3). The organic layer
was concentrated under reduced pressure to get the crude
product. From the foregoing results, it is evident that
Bi(NO3)3·5H2O is an efficient and reusable catalyst for the
synthesis of chloroesters under solvent-free conditions.
Entry
Catalyst [mol%]
Time (min)
Yield (%)
1
2
3
Bi(NO3)3·5H2O [50]
Bi(NO3)3·5H2O [10]
Bi(NO3)3·5H2O [5]
10
10
10
96
95
95
4
5
CAN [5]
Zr(NO3)2·xH2O [5]
90
40
85
80
6
7
La(NO3)3·6H2O [5]
Bi(OTf)3 [5]
BiCl3 [5]
30
90
90
90
95
91
60
8
120
60
Conclusion
9
ZnCl2 [5]
10
I2 [5]
120
In conclusion, we described an efficient and facile synthe-
sis of chloroesters in the presence of catalytic amount of
Bi(NO3)3·5H2O under solvent-free conditions. The advan-
tages of the method are reduced reaction time, inexpensive
catalyst, and simple experimental and work up procedure
with high yields of products. This makes it a useful addition
to the existing methodologies.
11
12
13
Zn [5]
Graphite [5]
InBr3 [5]
180
360
180
87
90
89
14
HNO3
60
50
does not need expensive reagents or special care to exclude
the moisture from the reaction medium. All the reactions
proceeded efficiently and smoothly at room temperature, and
the products were obtained in excellent yields (Table 1).
Furthermore, the reaction conditions are very mild. Bis-
muth(III) nitrate pentahydrate is highly oxophilic and forms
labile bond with carbonyl oxygen to initiate the formation of
C–O bond with cyclic and acyclic ethers (Scheme 2). We
first examined the reaction of tetrahydrofuran 1 with acetyl
chloride 2 under solvent-free conditions to give the corre-
sponding chloroesters 3 in 95% yield (Table 2, entry 2). To
compare the catalytic activity of the bismuth(III) nitrate
pentahydrate, we carried out the reaction in different Lewis
acid catalysts, such as Bi(OTf)3, BiCl3, La(NO3)3·6H2O,
CAN, ZrO(NO3)2·xH2O, and other reported catalysts. How-
ever, bismuth(III) nitrate pentahydrate was found to be the
most effective in terms of reaction time as well as yields of
the product (Table 1). This success of the reaction encour-
aged us to carry out the reaction on various cyclic and acy-
clic ethers with different acid chlorides in the presence of
5mol% of Bi(NO3)3·5H2O. The ring cleavage of tetra-
hydropyran is considerably slower than that of tetrahydro-
furan at room temperature with low yields (55%). Using
slightly elevated temperature (50 °C), the reaction is com-
pleted in 1 h with 90% yield (Table 2, entries 7–9). In the
case of asymmetrical ethers, the cleavage took place selec-
tively at the unsubstituted side of ether (Table 2, entries 10
and 13). However, in the presence of cyclic and acyclic
Experimental
Typical experimental procedure for preparation of
chloroesters
To a mixture of cyclic/acyclic ether (10 mmol) and acid
chloride (10 mmol), was added Bi(NO3)3·5H2O (5 mol%) at
0–5 °C followed by stirring at room temperature for an ap-
propriate time (Table 2). After completion of the reaction as
monitored by TLC, ethyl acetate (10 mL) was added, and
the catalyst was recovered by filtration. The solvent ethyl ac-
etate was washed with water, brine, dried over anhyd. so-
dium sulphate, and removed under reduced pressure to give
a crude product, which was purified on a silica-gel column
to yield the pure products. The products were characterized
by spectral and analytical data or by comparison with au-
thentic samples.
Table 2. Entry 4
1H NMR (CDCl3, 300 MHz) δ: 1.99 (m, 4H), 3.6 (m, 2H),
4.4 (m, 2H), 7.28 (dd, J = 7.4 and 1.5Hz, 1H), 7.5 (d, J =
1.5 Hz, 1H), 7.8 (d, J = 7.4 Hz, 1H). EI-MS: 281 (M+).
Anal. calcd. for C11H11Cl3O2: C, 47.14; H, 3.92; Cl, 38.03.
Found: C, 46.92; H, 3.94; Cl, 37.77.
Entry 5
1H NMR (CDCl3, 200 MHz) δ: 1.97 (m, 4H), 3.60 (m,
2H), 4.40 (m, 2H), 7.31 (m, 1H), 8.13 (dd, J = 8.1 and
© 2007 NRC Canada

V. Suresh et al.
1039
Table 2. Bi(NO3)3·5H2O-catalyzed cleavage of cyclic and acyclic
ethers by acid chlorides under solvent-free conditions.
Table 3. Synthesis of chloroesters using Bi(NO3)3·5H2O as an
efficient and reusable catalyst.
Entry
Ether
Acid
Producta
Temp.,
Time (min)
Yield
(%)b
Entry
1
Substrates
Time (min)
10
Yield (%)
96
chloride
O
O
O
1
2
RT, 10
RT, 10
96
96
O
Cl
O
O
H3C
Cl
H3C
+
O
H3C
Cl
O
O
O
Cl
Cl
Cl
2
3
4
5
6
2nd run
3rd run
4th run
5th run
6th run
10
10
10
10
10
95
96
96
95
95
O
O
O
Cl
3
4
5
6
RT, 15
RT, 15
RT, 15
RT, 10
90
87
92
98
Cl
O
O
Cl
O
O
O
Cl
Cl
Cl
Cl
Cl
Cl
O
O
O
Cl
Cl
O
O
Cl
N
Cl
O
N
O
O
H3C
H3C
O
O
Cl
Cl
O
O
O
7
8
50 oC, 60
50 oC, 75
90
90
1.5 Hz, 1H,), 8.51 (dd, J = 8.1 and 1.5 Hz, 1H). EI-MS: 248
(M+). Anal. calcd. for C10H11Cl2NO2: C, 48.38; H, 4.43; Cl,
28.62; N, 5.64. Found: C, 48.41; H, 4.47; Cl, 28.58; N, 5.65.
O
O
H3C
Cl
H3C
Cl
O
O
O
O
O
O
O
Cl
Cl
Cl
Cl
Entry 6
9
50 oC, 60
RT, 10
90
85
1H NMR (CDCl3, 200 MHz) δ: 1.39 (t, J = 6.90 Hz, 3H),
1.90 (m, 4H), 3.58 (m, 2H), 4.31 (m, 4H). EI-MS: 208 (M+).
Anal. calcd. for C8H13ClO4: C, 46.15; H, 6.49; Cl, 17.06.
Found: C, 46.05; H, 6.28; Cl, 16.99.
O
Cl
O
Cl
O
Cl
Cl
10
OAc
O
O
Cl
O
Cl
OAc
Cl
+
Entry 10a
O
OAc
1H NMR (CDCl3, 200 MHz) δ: 1.66 (m, 2H), 1.79 (m,
2H), 2.00 (s, 3H), 3.41 (m, 2H), 4.29 (d, 2H, J = 3.5 Hz),
4.79 (m, 1H), 7.47 (m, 2H), 7.73 (m, 1H), 7.6 (m, 1H). EI-
MS: 275 (M+). Anal. calcd. for C13H16Cl2O2: C, 56.72; H,
5.81; Cl, 25.81. Found: C, 56.74; H, 5.86; Cl, 25.77.
O
Cl
(9:1)
O
H3C
O
11
12
13
RT, 15
RT, 5
RT, 5
70
90
85
Cl
OAc
H
3C
Cl
O
O
OAc
O
+
Cl
O
CH3
OAc
Entry 10b
(9:1)
O
O
1H NMR (CDCl3, 200 MHz) δ: 1.72 (m, 4H), 2.02, (s,
3H), 2.15 (m, 2H), 4.00 (m, 2H), 6.67 (m, 1H), 7.50 (m,
2H), 7.61 (m, 1H), 7.87 (m, 1H). EI-MS: 275 (M+). Anal.
calcd. for C13H16Cl2O2: C, 56.72; H, 5.81; Cl, 25.81. Found:
C, 56.75; H, 5.84; Cl, 25.75.
Cl
Cl
Cl
Cl
OCOPh
+
Cl
OCOPh
Cl
(7:3)
O
O
O
CH3
Cl
Cl
H
3C
Cl
O
Entry 17
Cl
+
O
1H NMR (CDCl3, 300 MHz) δ: 3.03 (t, J = 6.79 Hz, 2H),
4.49 (t, J = 7.5 Hz, 2H), 7.23 (m, 8H), 7.7 (d, 1H, J =
1.5 Hz). EI-MS: 260 (M+). Anal. calcd. for C15H13ClO2: C,
69.23; H, 4.99; Cl, 13.65. Found: C, 69.10; H, 5.03; Cl,
13.60.
Cl
O
CH3
Cl
(9:1)
H3C
O
CH3
O
O
O
Cl
14
15
16
RT, 30
RT, 10
RT, 10
85
90
91
Cl
CH3
Cl
Cl
O
O
Ph
O
O
Ph
Entry 18
O
+
Ph
1H NMR (CDCl3, 300 MHz) δ: 1.97 (m, 1H), 2.64 (m,
2H), 4.41 (t, J = 6.79 Hz, 2H,), 7.3 (m, 1H), 7.47 (s, 1H),
7.81 (d, 2H, J = 7.5 Hz). EI-MS: 243 (M+). Anal. calcd. for
C11H8Cl2O2: C, 54.32; H, 3.29; Cl, 29.21. Found: C, 54.35;
H, 3.32; Cl, 29.17.
Cl
Ph
O
Ph
Ph
O
Ph
Ph
Cl
O
+
Ph
Cl
O
O
17
18
RT, 25
RT, 30
85
80
Ph
Cl
O
O
O
Cl
Cl
O
Acknowledgements
O
Cl
O
O
O
Cl
Cl
Cl
Cl
The authors are thankful to CSIR, UGC, and MoES, New
Delhi for financial assistance and to Dr J.S. Yadav, Director,
IICT for his constant encouragement.
a The structures of the products were established from their spectral data (IR, 1H NMR, EI-MS).
b Isolated yields obtained after column chromatography.
© 2007 NRC Canada

1040
Can. J. Chem. Vol. 85, 2007
12. Q. Guo, T. Miyaji, G. Gao, R. Hara, and T. Takahashi. Chem.
Commun. 1018 (2001).
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