Synthesis of chloroesters by the cleavage of cyclic and acyclic ethers using La(NO3)3·6H2O as a mild and efficient catalyst under solvent-free conditions

Article abstract of DOI:10.1080/00397910701649403

A mild and an efficient synthesis of chloroesters is described by the reaction of cyclic and acyclic ethers with acid chlorides in the presence of a catalytic amount of La(NO3)3·6H2O under solvent-free conditions, affording the corresponding chloroesters in excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701649403

Synthetic Communicationsw, 38: 92–99, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701649403
Synthesis of Chloroesters by the Cleavage
of Cyclic and Acyclic Ethers using
.
La(NO3)3 6H2O as a Mild and Efficient
Catalyst under Solvent-Free Conditions
V. Suresh, N. Suryakiran, K. Rajesh, J. Jon Paul Selvam,
M. Srinivasulu, and Y. Venkateswarlu
Natural Products Laboratory, Organic Chemistry Division I, Indian
Institute of Chemical Technology, Hyderabad, India
Abstract: A mild and an efficient synthesis of chloroesters is described by the reaction
of cyclic and acyclic ethers with acid chlorides in the presence of a catalytic amount of
.
La(NO3)3 6H2O under solvent-free conditions, affording the corresponding chloroe-
sters in excellent yields.
Keywords: acid chlorides, chloroesters, cyclic and acyclic ethers, lanthanum(III)
nitrate hexahydrate
INTRODUCTION
The synthesis of chloroesters via cleavage of cyclic and acyclic ethers with acid
chlorides is great interest because they are important key constituents in
organic synthesis, particularly in the synthesis of natural products.[1] Trans-
formation 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, frequently hydroxyls are protected as aliphatic, benzylic, and
Received May 15, 2007
Address correspondence to Y. Venkateswarlu, Natural Products Laboratory,
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad
500 007, India. E-mail: luchem@iict.res.in
92

Synthesis of Chloroesters
93
allylic ethers,[3] which can subsequently be cleaved for further transform-
ations.[4] The cleavage of ethers with acyl chlorides have been reported
using Lewis acids, such as SmI2,[5] ZnCl2,[6] FeCl3,[7] I2,[8] MoCl5,[9]
PdCl2(PPh3)2,[10] CoCl2,[3] NaI,[11] Zn,[12] and graphite.[13] However, the use
of strongly acidic conditions frequently leads to the formation of undesirable
side products. Thus, a mild and efficient catalyst for the cleavage of cyclic and
acyclic ethers with acid chlorides is highly advantageous.
In recent years, organic reactions using mild and water-tolerant catalysts
received much attention. They can be conveniently handled and removed from
the reaction mixture, making the experimental procedure simple and
ecofriendly.
Recently, we reported that lanthanum(III) nitrate hexahydrate is relatively
nontoxic, inexpensive, insensitive to air, and used in various organic trans-
formations, such as chemoselective tetrahydropyranylation of primary
alcohols,[14] chemoselective deprotection of acetonides,[15] synthesis of quina-
zolinones,[16] mild and efficient acetylation of phenols and amines,[17]
synthesis of a-amino nitriles,[18] synthesis of benzodiazepines,[19] and
N-tert-butoxycarbonylation and N-benzyloxycarbonylation of amines.[20,21]
In the course of study in these transformations, it has been observed
that the substrates containing other acid labile functional groups, such as
tert-butyldimethylsilane (TBDMS) ethers, some isopropylidene-protected
diols, and N-tert-Boc-protected amines, were intact in the presence of
.
.
La(NO3)3 6H2O. In continued efforts toward the utility of La(NO3)3 6H2O,
we found that it is an efficient and mild Lewis acid catalyst for the cleavage
of cyclic and acyclic ethers with acid chlorides in the presence of a catalytic
.
amount of La(NO3)3 6H2O under solvent-free conditions.
RESULTS AND DISCUSSION
In this report, we describe an efficient and facile method for the synthesis of
chloroesters. This method does not need expensive reagents or special care
to exclude the moisture from the reaction medium. Lanthanum(III) nitrate
pentahydrate is highly oxophilic, forms a labile bond with carbonyl oxygen,
and initiates the formation of C-O bond with cyclic and acyclic ethers
(Scheme 1). We first examined the reaction of tetrahydrofuran with acetyl
chloride under solvent-free conditions to give the corresponding chloroesters
in 96% yield (Table 1, entry 1). This success of the reaction encouraged us to
Scheme 1.

.
Table 1. La(NO3)3 6H2O-catalyzed cleavage of cyclic and acyclic ethers by acid chlorides under solvent-free conditions
Temp.,
time (min)
Yield (%),b
[Ref.]
Entry
1
Ether
Acid chloride
Producta
rt, 15
96[8]
2
3
rt, 15
rt, 15
96[8]
92[8]
4
5
rt, 15
rt, 15
90
95
6
7
rt, 10
96
608C, 70
94[3]

8
9
608C, 90
95
90
rt, 10
10
rt, 40
94[11]
11
rt, 30
92[8]
(continued)

Table 1. Continued
Temp.,
time (min)
Yield (%),b
[Ref.]
Entry
12
Ether
Acid chloride
Producta
rt, 15
rt, 15
rt, 35
90
91
90
13
14
aThe structures of the products were established from their spectral data (1H NMR, EIMS).
bIsolated yields obtained after column chromatography.

Synthesis of Chloroesters
97
carry out reaction of various cyclic and acyclic ethers with different acid
.
chlorides in the presence of 5 mol% of La(NO3)3 5H2O under solvent-free
conditions. Tetrahydropyran is considerably slower than tetrahydrofuran at
room temperature, with low yields (50%). However, at slightly elevated temp-
erature (608C), the reaction is completed in 1 h with 92% yield (Table 1,
entries 6 and 7). In the case of asymmetrical ethers, the cleavage took place
regioselectively, preferring attack on the more substitute side of the ether
(Scheme 2, Table 1, entry 10). However, in the presence of cyclic and
acyclic ethers in the same substrate, formation of products only with the
acyclic part of the substrate was observed (Table 1, entry 14).
CONCLUSION
In conclusion, we describe an efficient and facile synthesis of chloroesters in
.
the presence of a catalytic amount of La(NO3)3 6H2O under solvent-free
conditions.
EXPERIMENTAL
Typical Experimental Procedure for Preparation of Chloroesters
To a mixture of cyclic/acyclic ether (10 mmol) and acid chloride (10 mmol),
.
La(NO3)3 6H2O (5 mol%) was added at 0–58C and stirred at room tempera-
ture for an appropriate time (Table 1). After completion of the reaction, as
monitored by thin-layer chromatography (TLC), the product was extracted
into ethyl acetate (3 ꢀ 20 mL). The combined organic layer dried over
anhydrous sodium sulphate; solvent was removed under reduced pressure to
give the crude product, which was purified on a silica-gel column to yield
the corresponding chloroesters.
Table 1, entry 4. 1H NMR (CDCl3, 300 MHz), d ¼ 1.94 (m, 4H), 3.58 (t, 2H,
J ¼ 6.00 Hz), 4.36 (m, 2H), 7.28 (m, 1H), 7.40 (d, 1H, J ¼ 1.50 Hz), 7.70
(d, 1H, J ¼ 8.3 Hz); EIMS: 281 (Mþ.).
Scheme 2. Proposed mechanism.

98
V. Suresh et al.
1
Entry 5. H NMR (CDCl3, 200 MHz), d ¼ 1.97 (m, 4H), 3.60 (m, 2H), 4.40
(m, 2H), 7.31 (m, 1H), 8.13 (dd, 1H, J ¼ 2.34 Hz), 8.51 (dd, 1H,
J ¼ 1.56 Hz); EIMS: 248 (Mþ.).
1
Entry 6. H NMR (CDCl3, 200 MHz), d ¼ 1.39 (t, 3H, J ¼ 6.90 Hz), 1.90
(m, 4H), 3.58 (m, 2H), 4.31 (m, 4H), 3.58 (t, 2H, J ¼ 6.00 Hz); EIMS:
208 (Mþ.).
Entry 9a. 1H NMR (CDCl3, 200 MHz), d ¼ 1.66 (m, 2H), 1.79 (m, 2H), 2.00
(s, 3H), 3.41 (m, 2H), 4.29 (dd, 1H), 4.63 (dd, 1H), 4.79 (m, 1H), 7.47 (m, 2H),
7.73 (m, 1H), 7.6 (m, 1H); EIMS: 275 (Mþ.).
Entry 9b. 1H NMR (CDCl3, 200 MHz), d ¼ 1.72 (m, 4H), 2.02, (s, 3H), 2.15
(m, 2H), 4.00 (m, 2H), 6.67 (m, 2H), 7.50 (m, 2H), 7.61 (m, 1H), 7.87 (m, 1H);
EIMS: 275 (Mþ.).
1
Entry 12. H NMR (CDCl3, 200 MHz), d ¼ 1.22 (s, 9H), 5.18 (s, 2H) 7.33
(m, 5H); EIMS: 192 (Mþ.).
1
Entry 13. H NMR (CDCl3, 200 MHz), d ¼ 1.20 (s, 9H), 2.85 (t, 2H), 4.19
(t, 2H), 7.10 (m, 2H), 7.23 (m, 3H); EIMS: 206 (Mþ.).
Entry 14. 1H NMR (CDCl3, 300 MHz), d3.03 (t, 2H, J 6.79 Hz), 4.49 (t, 2H,
J 7.55 Hz), 7.23 (m, 8H), 7.7 (dd, 1H, J 1.51 Hz); EIMS: 260 (Mþ.).
ACKNOWLEDGMENTS
The authors are thankful to Counsil of Scientific and Industrial Research
(CSIR), University Grants Commission (UGC), and Ministry of Earth
Sciences (MEOS) and to J. S. Yadav, director of IICT, for his constant
encouragement.
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