Efficient and Regioselective Conversion of Epoxides into Vicinal Chloroesters with TiCl4 and Imidazole in Ethyl Acetate

Article abstract of DOI:10.1039/a800145f

Epoxides can be cleaved easily in EtOAc with TiCl₄ in the presence of imidazole to afford β-chloroesters with excellent yields and regioselectivity.

Full text of DOI:10.1039/a800145f

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582 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 582±583$
Efficient and Regioselective Conversion of Epoxides
into Vicinal Chloroesters with TiCl4 and Imidazole in
Ethyl Acetate$
N. Iranpoor* and B. Zeynizadeh
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, Iran
Epoxides can be cleaved easily in EtOAc with TiCl4 in the presence of imidazole to afford ꢀ-chloroesters with excellent
yields and regioselectivity.
Regioselective ring-opening of epoxides to b-halohydrins
is a subject of interest in organic synthesis.1 Although
this matter has been widely studied in recent years, the
conversion of epoxides into b-chloroesters as important
derivatives of halohydrins has been rarely studied.
Formation of b-chloroacetates from ole®ns and epoxides
has been reported with acetyl chloride in the presence of
chromyl chloride,2,3a with low regioselectivity, or hexa-
alkylguanidium chloride.3b A similar transformation with
benzoyl chloride has also been studied in the presence of
Bun2SnCl2±PPh3 and CoCl2.5
4
Reports on the application of TiCl4 for the formation of
halohydrins6 from epoxides and our observations on the
Scheme 1
ring opening of epoxides with heteronucleophiles7 catalysed
with Lewis acids led us to explore the possibility of using
TiCl4 for such a transformation. Thus we report here that
Experimental
Products were characterized by comparison of their physical data,
IR, NMR and mass spectra with those reported in the literature.
epoxides can react with ethyl acetate in the presence of
TiCl4 and imidazole to a€ord vicinal chloroacetates in high
yields (Table 1).
The IR spectra were recorded on
a
Perkin Elmer
IR-157 G and a Perkin Elmer 781 spectrophotometer. The NMR
spectra were recorded on a Bruker Avance DPX-250. Mas spectra
were recorded on a Shimadzu GCMS-QP 1000 EX instrument.
General Procedure for Reaction of Epoxides with TiCl4 in
EtOAc.ÐIn a round-bottomed ¯ask equipped with a condenser and
magnetic stirrer, the epoxide (1 mmol) was added dropwise to a sol-
ution of TiCl4 91.5 mmol, 0.285 g) in EtOAc (8 ml) at room
temperature. The reaction mixture was then stirred vigorously for
10 min. Subsequently, imidazole (3.0 mmol, 0.204 g) was added to
the reaction mixture in small portions over a period of time shown
in Scheme 1. The reaction progress was monitored with TLC or
GLC. After completion of the reaction, solvent was evaporated
and water (10 ml) was added to the residue. ꢀ-Chloroacetate was
extracted with CHCl3 (3Â15 ml) and dried with anhydrous
Na2SO4. The product was obtained in 80±95% yield after chroma-
tography on a short column of silica-gel. Spectral data of the
products are as follows: 2a: bp 100 8C (0.3 mmHg3b), ꢁC (CDCl3),
20.2, 58.8, 67.08, 126.6, 127.6, 127.7, 136.8, 169.6; m/z (70 eV) 163
(M Cl, 0.1), 139 (M OAc, 1.2%); 2b: ꢁH (CDCl3), 1.0 (3 H, t, J
5.5 Hz), 1.26±1.7 (6 H, m), 2.1 (3 H, s), 3.6 (2 H, partially resolved
doublet), 5.1 (1 H, q); m/z (70 eV) 143 (M OAc, 1.8%); 2c: ꢁH
(CDCl3), 2.1 (3 H, s), 3.6±3.8 (2 H, m), 3.9±4.15 (2 H, partially
resolved doublet), 4.2±4.4 (1 H, m), 4.9±5.25 (2 H, m), 5.7±6 (1 H,
m); ꢁC (CDCl3), 21.2, 43.06, 68.4, 72.07, 72.68, 117.7, 134.5, 170.5;
GC and 1H NMR analysis of the crude products
showed the excellent regioselectivity with the formation
of, mostly, one isomer. The presence of di€erent sub-
stituents on the epoxide ring and the absence of side reac-
tions showed the chemoselectivity of this transformation
(Scheme 1).
In the absence of imidazole, the reactions are not
complete even after 24 h and the products that are formed
are mostly chlorohydrins. The presence of imidazole greatly
accelerates the reaction, possibly through interaction with
b-chloroalkoxytrichlorotitanate(IV) which can be formed as
an intermediate in the reaction with ethyl acetate (4).
a
Table 1 Reaction of epoxides with TiCl4 in EtOAc in the
presence of imidazoleb
Other bases, such as triethylamine, diethylamine, pyridine
and DABCO, also enhance the reaction, but imidazole is
the most ecient. The stereochemistry of the cyclic products
was determined by di€erent procedures.8
These results show that this method is very suitable for
the direct conversion of epoxides into b-chloroacetates.
High yields, high regio- and chemoselectivities, easy work-
up and the availability of the reagents can be considered as
advantages of this method.
Epoxide
Time (h)
Yield (%)c Products
2:3d
1a
1b
1c
1d
1e
1f
3.5
2
7
2.5
1.5
1
95
89
93
94
80
92
87
95
2a‡3a
2b‡3b
2c‡3c
2d‡3d
2e‡3e
2fe
96:4
80:20
95:5
91:9
90:10
Ð
1g
1h
2
2.5
2gf
Ð
Ð
2hg
a1.5 Molar equivalents of TiCl4 were used. b3 Molar equivalents
of imidazole were used. cIsolated yield after chromatography.
dThe ratio of compounds 2 and 3 was determined by GC and
1H NMR analysis. etrans-1-Chloro-2-acetoxycyclohexane.
ftrans-1-Chloro-2-acetoxycyclopentane. gtrans-1-Chloro-2-
acetoxycyclooctane.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1998 583
m/z (70 eV) 133 (M OAc, 1.2), 98 (M 133 Cl, 4.2%); 2d: ꢁH
(CDCl3), 1.05 (6 H, d, J 6 Hz), 2.01 (3 H, s), 3.4±3.8 (5 H, com-
plex), 4.9 (1 H, m); ꢁC (CDCl3), 20.58, 21.64, 42.62, 65.78, 71.68,
72.13, 169.86; m/z (70 eV) 159 (M Cl, 1.8), 135 (M OAc, 3.9%);
2e: ꢁH (CDCl3) (3 H, s), 3.6±3.8 (4 H, m), 5.1±5.4 (1 H, m); ꢁC
(CDCl3), 20.57, 40.80, 66.12, 169.09, m/z (70 eV) 101 (M 2Cl,
18.9%); 2f: (trans-1-chloro-2-acetoxycyclohexane) ꢁH (CDCl3), 1±1.5
(4 H, m), 1.5±1.8 (4 H, m), 2.01 (3 H, s), 3.65±4.1 (1 H, m), 4.6±4.9
(1 H, m); ꢁC (CDCl3), 23.01, 25.91, 26.54, 32.74, 36.8, 62.69, 77.82,
172.1; m/z (70 eV) 141 (M Cl, 10.7%), 117 (M OAc, 1.9%); 2h:
(trans-1-chloro-2-acetoxycyclooctane) ꢁH (CDCl3) 1.4±1.9 (8 H,
complex), 2.1 (3 H, s), 1.96±2.2 (4 H, m), 4.16 (1 H, m), 5.1 (1 H,
m); ꢁC (CDCl3), 19.8, 22.2, 23.9, 24.2, 24.3, 29.8, 30.3, 63.01, 77.4,
168.8; m/z (70 eV) 169 (M Cl, 1.8%), 145 (M OAc, 1.8%); 2g:
(trans-1-chloro-2-acetoxycyclopentane) ꢁH (CDCl3), 1±1.5 (2 H, m),
1.5±1.8 (4 H, m), 2.05 (3 H, s), 3.6±4.05 (1 H, m), 4.5±4.85 (1 H,
m), m/z (70 eV) 127 (M Cl, 8.5%), 103 (M OAc, 1.4%).
2 J. E. Backwell, M. W. Young and K. B. Sharpless, Tetrahedron
Lett., 1977, 40, 3523.
3 (a) K. B. Sharpless, A. Y. Teranishi and J. E. Backvall, J. Am.
Chem. Soc., 1977, 99, 3120; (b) P. Gros, P. Le Perchec and J. P.
Senet, J. Org. Chem., 1994, 59, 4925.
4 I. Shibata, A. Baba and H. Matsuda, Tetrahedron Lett., 1986,
27, 3021.
5 J. Igbal, Khan M. Amin and R. R. Srivastav, Tetrahedron Lett.,
1988, 29, 4985.
6 (a) M. Shimizu, A. Yoshida and T. Fujisawa, Synlett, 1992, 204;
(b) J. J. Eisch, Z. Liu, X. Ma and G. Zhen, J. Org. Chem., 1992,
57, 5140.
7 (a) N. Iranpoor and P. Salehi, Tetrahedron, 1995, 51, 909;
(b) N. Iranpoor and F. Kazemi, Synthesis, 1996, 821;
(c) N. Iranpoor, T. Tarrian and Z. Movahedi, Synthesis, 1996,
1473; (d) N. Iranpoor and F. Kazemi, Tetrahedron, 1997, 53,
11377.
8 The stereochemistry of the cyclic products were determined
according to the following procedures: (a) the corresponding
trans-halohydrins which are formed as intermediates from the
reaction of epoxides with TiCl4 in the absence of imidazole
were separated and their physical data were compared with the
data reported in the literature.9 (b) The acetate or benzoate
derivatives of the obtained cyclic chlorohydrins were also
prepared and their physical data were compared with those
reported in the literature.10 (c) The spectral data obtained from
the acetate derivative of halohydrins in procedure (b) were
found to be identical with those obtained with our method.
9 (a) M. Mousseron and F. Winternitz, Bull. Soc. Chim. Fr., 1946,
604; (b) S. J. Lapporte and L. L. Ferstandig, J. Org. Chem.,
1961, 26, 3681.
We are thankful to the Shiraz University Research
Council for partial support of this work. The assistance of
Mr. N. Maleki for running the NMR spectra and Dr. A. A.
Jarahpoor for running mass spectra is also acknowledged.
Received, 5th January 1998; Accepted, 21st May 1998
Paper E/8/00145F
References and notes
1 (a) For a review see C. Bonini and G. Righi, Synthesis, 1994,
225; (b) J. G. Smith, Synthesis, 1984, 629; (c) N. Iranpoor,
F. Kazemi and P. Salehi, Synth. Commun., 1997, 27, 1247 and
references therein.
10 (a) L. N. Owen and P. N. Smith, J. Chem. Soc., 1952, 4026;
(b) Y. Ganoni, Bull. Soc. Chim. Fr., 1959, 701; (c) J. G.
Traynham and J. Schneller, J. Am. Chem. Soc., 1965, 87, 2398.