Mild and efficient method for the cleavage of cyclic and acyclic ethers by iodine under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2005.10.017

Ethers undergo smooth cleavage with acyl chlorides in the presence of a catalytic amount of elemental iodine under extremely mild conditions to give the corresponding halo esters. This new procedure offers significant advantages such as high conversions, short reaction times and enhanced selectivity together with mild reaction conditions, which makes it an attractive strategy.

Full text of DOI:10.1016/j.tetlet.2005.10.017

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8493–8495
Mild and efficient method for the cleavage of cyclic and
acyclic ethers by iodine under solvent-free conditionsI
J. S. Yadav,* B. V. S. Reddy, P. Murali Krishna Reddy and Manoj K. Gupta
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 19April 2005; revised 27 September 2005; accepted 6 October 2005
Available online 21 October 2005
Abstract—Ethers undergo smooth cleavage with acyl chlorides in the presence of a catalytic amount of elemental iodine under extre-
mely mild conditions to give the corresponding halo esters. This new procedure offers significant advantages such as high conver-
sions, short reaction times and enhanced selectivity together with mild reaction conditions, which makes it an attractive strategy.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The cleavage of ethers is a versatile reaction in organic
synthesis, mainly in degradation or transformation of
complex molecules especially in biologically active natu-
ral products such as carbohydrates and macrolide anti-
biotics. Additionally, aliphatic, benzylic and allylic
ethers are frequently used as protecting groups for
hydroxyl functions,1 which then require subsequent
cleavage to release polyfunctional molecules useful in
organic synthesis.2 The cleavage of ethers with acyl chlo-
rides has been reported using Lewis acids such as SmI2,3
ZnCl2,4 FeCl3,5 Mo(CO)6,6 MoCl5,7 PdCl2(PPh3)2,8
CoCl2,1 NaI,9 lanthanide salts,10 Zn,11 graphite,12 alu-
minium complexes13 and others.14 However, many of
these methods often involve the use of toxic or expensive
reagents and the formation of mixtures of products
resulting in low yields. Therefore, the development of
simple, convenient and practical procedures for the
cleavage of cyclic and acyclic ethers continues to be a
challenge. Recently, iodine15 has been used in acid
mediated and other organic transformations. However,
there have been no reports on the use of elemental
iodine for the cleavage of ethers with acyl chlorides.
O
10 mol% Iodine
r.t.
O
Cl
+
Me
Cl
Me
O
O
1
2
3a
Scheme 1.
as the catalyst under solvent-free conditions.17 Firstly,
we attempted the cleavage of tetrahydrofuran with acet-
yl chloride in the presence of elemental iodine. The reac-
tion went to completion within 2 h and the product was
obtained in 91% yield (Scheme 1).
Encouraged by this result, we examined benzoyl chlo-
ride, 3-methylbenzoyl chloride, 2-chlorobenzoyl chlo-
ride and the acid chloride derived from cyhalothrin,
again using tetrahydrofuran, and obtained the corre-
sponding halo esters in good to excellent yields (Table
1, entries b–e). Like tetrahydrofuran, several other cyclic
and acyclic ethers were cleaved with a range acyl chlo-
rides to afford the corresponding halo esters in good
yields (Table 1, entries f–m). In the cases of entries f
and h (Table 1), 10% and 20%, respectively, of the
regioisomers were observed, which was confirmed by
GC analysis. Using 10 mol % of iodine under solvent
free-conditions afforded higher yields with reduced reac-
tion times as compared to some other cheap reagents
such as FeCl3,5 ZnCl24 and NaI9 for the cleavage of cyc-
lic and acyclic ethers.
In continuation of our interest on the catalytic applica-
tion of elemental iodine,16 we disclose herein a mild, effi-
cient and practical methodology for the cleavage of
cyclic and acyclic ethers with acyl chloride using iodine
Keywords: Ethers; Acyl chloride; Iodine.
q IICT Communication No. 051004.
In summary, we have described a simple, convenient,
efficient and practical method for the cleavage of
cyclic and acyclic ethers with acyl chlorides using
*
Corresponding author. Tel.: +91 40 271 93030; fax: +91 40 2716
0387; e-mail: yadavpub@iict.res.in
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.017

8494
J. S. Yadav et al. / Tetrahedron Letters 46 (2005) 8493–8495
Table 1. Iodine catalyzed cleavage of cyclic and acyclic ethers by aryl chlorides under solvent-free conditions
Entry
a
Ether
Acyl chloride
Producta
Time (h)
2.0
Yield (%)b
91
O
O
Cl
O
Me Cl
Me
O
O
O
Cl
b
c
2.0
3.5
3.0
93
83
88
Cl
O
O
O
O
O
O
O
Cl
Cl
Cl
Me
O
Me
O
d
Cl
Cl
O
Cl
H
O
H
O
Cl
Cl
Cl
e
f
4.5
7.0
92
Cl
O
O
CF
CF
3
3
OAc
OAc
O
Cl
O
Me
Cl
O
65 (9:1)c
OAc
O
O
OAc
Me Cl
O
OAc
g
h
i
4.0
6.0
2.5
4.5
3.5
85
Cl
Cl
Cl
Me Cl
OCOPh
Cl
O
Cl
Cl
71 (8:2)c
O
Cl
Cl
Cl
OCOPh
O
O
O
O
80
78
88
Cl
Cl
O
O
O
O
j
O
O
O
O
k
Cl
O
O
O
O
Me
Cl
Me
Cl
H
H
l
4.5
5.0
87
80
O
Cl
O
CF
CF
3
3
O
O
m
Cl
O
O
Cl
Cl
a All products were characterized 1H NMR and IR spectra and mass spectrometry.
b Yields obtained after column chromatography.
c By GC analysis.
elemental iodine as the catalyst, under solvent free-
conditions.
References and notes
1. Iqbal, J.; Srivastava, R. R. Tetrahedron 1991, 47, 3155–
3182, and references cited therein.
2. (a) Amouroux, R.; Ejjiyar, S. Tetrahedron Lett. 1991, 32,
3059–3062; (b) Nystrom, J.-E.; McCanna, T. D.; Helquist,
P.; Amouroux, R. Synthesis 1988, 56–58; (c) Guindon, Y.;
Therien, M.; Girard, Y.; Yoakim, C. J. Org. Chem. 1987,
52, 1680–1686; (d) Guindon, Y.; Anderson, P. C. Tetra-
hedron Lett. 1987, 28, 2485–2488.
Acknowledgements
B.V.S. and M.K.G. thank the CSIR New Delhi, and
P.M.R. thanks UGC New Delhi, for the award of
fellowships.

J. S. Yadav et al. / Tetrahedron Letters 46 (2005) 8493–8495
8495
3. Kwon, D. W.; Kim, Y. H. J. Org. Chem. 2002, 67, 9488–
9491.
4. Cloke, J. B.; Pilgrim, F. J. J. Am. Chem. Soc. 1939, 61,
2667–2669.
5. Ganem, B.; Small, V. R., Jr. J. Org. Chem. 1974, 39, 3728–
3730.
6. Alper, H.; Huang, C.-C. J. Org. Chem. 1973, 38, 64–71.
7. Guo, Q.; Miyaji, T.; Gao, G.; Hara, R.; Takahashi, T.
Chem. Commun. 2001, 1018–1019.
8. Pri-Bar, I.; Stille, J. K. J. Org. Chem. 1982, 47, 1215–1220.
9. (a) Oku, A.; Harada, T.; Kita, K. Tetrahedron Lett. 1982,
23, 681–684; (b) Mimero, P.; Saluzzo, C.; Amourous, R.
Tetrahedron Lett. 1994, 35, 1553–1556.
10. Taniguchi, Y.; Tanaka, S.; Kitamura, T.; Fujiwara, Y.
Tetrahedron Lett. 1998, 39, 4559–4560.
11. Bhar, S.; Ranu, B. C. J. Org. Chem. 1995, 60, 745–747.
12. Suzuki, Y.; Matsushima, M.; Kodomari, M. Chem. Lett.
1998, 319–320.
B. V. S.; Reddy, E. J.; Yadav, J. S. Chem. Lett. 1999, 857–
858; (h) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand,
P. K.; Prasad, A. R. Synlett 2001, 1638–1640.
17. General procedure for cleavage of THF, ethers and epox-
ides: To a mixture of (6.90 mmol) of cyclic/acyclic ether
and (0.69mmol) of acyl chloride, a catalytic amount of
iodine (10 mol %) was added. The reaction mixture was
stirred at room temperature under a nitrogen atmosphere
for an appropriate time (Table 1). After completion of the
reaction as indicated by TLC, the reaction mixture was
quenched with saturated aq sodium bicarbonate solution
(15 ml) and extracted with ethyl acetate (2 · 15 ml).
Evaporation of the solvent followed by purification on
silica gel (Merck, 100–200 mesh, ethyl acetate–hexane,
0.5:9.5) afforded the pure ester derivative. Spectroscopic
data for selected products: 3d: 4-Chlorobutyl 2-chloro-
benzoate: Liquid. IR (KBr): mmax 3070, 2959, 1731, 1592,
1472, 1436, 1293, 1250, 1120, 1050, 771, 749 cmÀ1 1H
.
13. Green, L.; Hemeon, L.; Singer, R. D. Tetrahedron Lett.
2000, 41, 1343–1346.
NMR (CDCl3, 400 MHz) d: 7.77 (d, J = 8.7 Hz, 1H),
7.45–7.23 (m, 3H), 4.35 (t, J = 5.8 Hz, 2H,), 3.58 (t,
J = 5.8 Hz, 2H), 1.94 (quin, J = 5.8 Hz, 4H). LCMS: m/z:
247 (M+, 10%), 230 (7), 221 (5), 156 (8), 149(5), 139(10),
116 (5), 91 (7). HRMS calcd for C11H13Cl2O2: 247.0292.
Found: 247.0294. Compound 3e: 4-Chlorobutyl 3-[(E)-
2-chloro-3,3,3-trifluoro-1-propenyl]-2,2-dimethyl-1-cyclo-
propanecarboxylate: Liquid, IR (KBr): mmax 3079, 2961,
1727, 1654, 1453, 1416, 1275, 1201, 1140, 1087, 955,
14. (a) Machrouhi, F.; Namy, J.-L.; Kagan, H. B. Tetrahedron
Lett. 1997, 38, 7183–7186; (b) Souppe, J.; Namy, J.-L.;
Kagan, H. B. Tetrahedron Lett. 1984, 25, 2869–2872; (c)
Goldsmith, D. J.; Kennedy, E.; Campbell, R. G. J. Org.
Chem. 1975, 40, 3571–3574.
15. (a) Bhosale, R. S.; Bhosale, S. V.; Bhosale, S. V.; Wang,
T.; Zubaidha, P. K. Tetrahedron Lett. 2004, 45, 7187–
7188; (b) Lipshutz, B. H.; Keith, J. Tetrahedron Lett. 1998,
39, 2495–2498; (c) Deka, N.; Kalita, D. J.; Borah, R.;
Sharma, J. C. J. Org. Chem. 1997, 62, 1563–1564; (d)
Vaino, A. R.; Szarek, W. A. Synlett 1995, 1157–1158.
16. (a) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy,
T. Tetrahedron Lett. 2005, 46, 2687–2690; (b) Yadav, J. S.;
Reddy, B. V. S.; Srinivas, M.; Sathaiah, K. Tetrahedron
Lett. 2005, 46, 3489–3492; (c) Yadav, J. S.; Reddy, B. V.
S.; Shubashree, S.; Sadashiv, K. Tetrahedron Lett. 2004,
45, 2951–2954; (d) Yadav, J. S.; Reddy, B. V. S.; Reddy,
M. S.; Prasad, A. R. Tetrahedron Lett. 2002, 43, 9703–
9706; (e) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J.
Chem. Soc., Perkin Trans. 1 2000, 3082–3084; (f) Yadav, J.
S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K.
Synthesis 2000, 1532–1534; (g) Kumar, H. M. S.; Reddy,
772 cmÀ1 1H NMR (CDCl3, 400 MHz) d: 6.90 (d, J =
.
9.4 Hz, 1H), 4.10 (t, J = 5.8 Hz, 2H), 3.55 (t, J = 5.8 Hz,
2H), 2.14 (t, J = 9.4 Hz, 1H), 1.95–1.82 (m, 5H), 1.30 (d,
J = 3.6 Hz, 6H). LCMS: m/z: 334 (M+1, 5%), 301 (89),
279(68), 205 (15), 149(28), 116 (12), 107 (5), 69(5), 57 (5).
HRMS calcd for C13H18Cl2F3O2: 333.0635 (M+H)+.
Found: 333.0642. Compound 3m: Ethyl 2-chlorobenzoate:
Liquid, IR (KBr): mmax 3072, 2983, 2935, 2873, 1731, 1593,
1473, 1436, 1389, 1366, 1293, 1252, 1116, 1051, 854,
748 cmÀ1
.
1H NMR (CDCl3, 400 MHz) d: 7.76 (d,
J = 7.2 Hz, 1H), 7.43–7.22 (m, 3H), 4.39(q, J = 7.2 Hz,
2H), 1.40 (t, J = 7.2 Hz, 3H). LCMS: m/z: 185 (M+1,
78%), 177 (25), 157 (58), 149(18), 139(40), 127 (10), 116
(8), 103 (5), 88 (10). HRMS calcd for C9H10ClO2:
185.0369(M+H) +. Found: 185.0371.