Conversion of epoxides to β-chlorohydrins with thionyl chloride and β-cyclodextrin in water

Article abstract of DOI:10.1080/00397910500182606

Several epoxides are efficiently converted to the corresponding β-chlorohydrins in impressive yields with thionyl chloride in the presence of β-cyclodextrin using water as solvent at room temperature. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500182606

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Conversion of Epoxides to
β‐Chlorohydrins with Thionyl
Chloride and β‐Cyclodextrin in
Water
K. Surendra a , N. Srilakshmi Krishnaveni a , Y. V. D.
Nageswar a & K. Rama Rao a
a Organic Chemistry Division‐1 , Indian Institute of
Chemical Technology , Hyderabad, India
Published online: 18 Aug 2006.
To cite this article: K. Surendra , N. Srilakshmi Krishnaveni , Y. V. D. Nageswar & K.
Rama Rao (2005) Conversion of Epoxides to β‐Chlorohydrins with Thionyl Chloride
and β‐Cyclodextrin in Water, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 35:16, 2195-2201
To link to this article: http://dx.doi.org/10.1080/00397910500182606
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Synthetic Communicationsw, 35: 2195–2201, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500182606
Conversion of Epoxides to b-Chlorohydrins
with Thionyl Chloride and b-Cyclodextrin
in Water
K. Surendra, N. Srilakshmi Krishnaveni, Y. V. D. Nageswar,
and K. Rama Rao
Organic Chemistry Division-1, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: Several epoxides are efficiently converted to the corresponding
b-chlorohydrinsin impressive yieldswiththionyl chloride in thepresenceofb-cyclodextrin
using water as solvent at room temperature.
Keywords: b-Chlorohydrins, b-cyclodextrin, epoxides, thionyl chloride, water
Chlorohydrins and various other halohydrins are important class of organic
compounds and versatile intermediates in the synthesis of a vast range of
biologically active natural and synthetic products, unnatural aminoacids,
and chiral auxiliaries for asymmetric synthesis.[1] They are also utilized in
the synthesis of b-adrenergic blockers and are key intermediates in the
preparation of homochiral b-blockers.[2]
Chlorohydrins are generally prepared by the ring opening of epoxides
under electrophilic conditions with TMSCI,[3] polyvinylpyrrolidone/thionyl
chloride,[4] hydrohalic acids,[5] Lewis acids such as BF3[6] and chlorosilane,[7]
metalhalides such as LiX,[8] haloboranes,[9] elemental halogens,[10] pyridine-
HCl,[11] and so forth. Some more methods involve chloroallylboration of
Received in India April 1, 2005
Address correspondence to K. Rama Rao, Organic Chemistry Division-1, Indian
Institute of Chemical Technology, Hyderabad 500 007, India. Tel.: þ 91-40-
27193164; Fax: þ91-40-27160757; E-mail: drkrrao@yahoo.com
2195

2196
K. Surendra et al.
aldehydes,[12] cleavage of cyclic ketal acids with phosphorus pentachloride,
thionyl chloride, and pivaloyl chloride,[13] and reaction of diol with dry HCl
or chlorotrimethylsilane.[14] Although various recent advances have been
made[15] there is still demand for developing newer methodologies, especially
environmentally benign and highly efficient procedures for the effective trans-
formation of epoxides to chlorohydrins. In continuation of our efforts to
develop biomimetic approaches for chemical reactions involving cyclodex-
trins, we describe herein a novel method for the regioselective ring opening
of oxiranes with thionyl chloride to form chlorohydrins under supramolecular
catalysis involving b-cyclodextrin.
Cyclodextrins are cyclic oligosaccharides possessing hydrophobic cavities,
which bind substrates selectively and catalyze chemical reactions with high
selectivity. They catalyze reactions by supramolecular catalysis involving
reversible formation of host–guest complexes by noncovalent bonding, as seen
in enzymes. Complexation depends on the size, shape, and hydrophobicity of
the guest molecule. Thus, mimicking biochemical selectivity, which is due to
orientation of the substrate by complex formation positioning and only certain
regions are for favorable attack, will be superior to chemical selectivity, which
involves random attack because of intrinsic reactivity of the substrate at
different regions. Our earlier expertise in the field of biomimetic modeling of
organic chemical reactions involving cyclodextrins[16] prompted us to attempt
the regioselective ring opening of oxiranes with thionyl chloride in the
presence of b-cyclodextrin (b-CD), because this is one of the most useful
synthetic transformations and has a variety of applications (Scheme 1).
The reactions were carried out by the in situ formation of b-cyclodextrin
complex of oxirane (1) in water followed by the addition of thionyl chloride
and stirring at room temperature to give corresponding chlorohydrins (2) in
impressive yields (Table l). The reactions did not proceed in the absence of
b-CD. Although these reactions did occur with a-CD with the same regio-
selectivity, b-CD was preferred because of its inexpensive nature and accessi-
bility. The complexes have been isolated and characterized by powder
X-ray[17] and NMR studies in D2O.[18]
The role of cyclodextrin was not only to activate the epoxide but to promote
ring opening by inclusion complex formation with impressive regioselectivity.
With the styrene epoxides (entries 8 and 9), the halide preferentially attacked
the terminal carbon, whereas cyclohexene oxide gave only the trans isomer.
A variety of epoxides such as styrene epoxides, cyclohexene epoxides,
Scheme 1.

Epoxides to b-Chlorohydrins
2197
Table 1. Synthesis of b-chlorohydrins from epoxides and SO2Cl in the presence
of b-CD
Yieldb
(%)
Entry
1
Substrate
Producta
91[16a]
2
93[16a]
3
90
4
90
5
89[16a]
6
7
8
91
90[16a]
92[16a]
9
94[16a]
(continued)

2198
K. Surendra et al.
Table 1. Continued
Yieldb
(%)
Entry
10
Substrate
Producta
88[16a]
11
12
84[16a]
84[16a]
aAll the products were characterized by H NMR, mass, and IR spectra data.
bIsolated yields.
1
epichlorohydrin, and phenoxy epoxides with different substituents such as
chloro, methyl, methoxy, acetoxy, and metaprolol have been converted to corre-
sponding chlorohydrins. All the compounds were characterized by the 1H NMR,
mass, and IR spectra or by comparison with the reported compounds.[15a]
In conclusion, the present methodology for conversion of epoxides to
chlorohydrins is simple and efficient, and can be carried out in a biomimetic
fashion from the easily accessible epoxides and thionyl chloride in the
presence of b-CD.
EXPERIMENTAL
The b-cyclodextrin was purchased from Fluka. Epoxides were either
purchased commercially or synthesized.[19] 1H NMR spectra were obtained
on a Varian 200- or Bruker 300-MHz spectrometer. IR spectra were
recorded on a Nicolet FT-IR spectrometer. Mass spectra were observed on
V.G. Auto Spectrometer. The reaction monitoring was accomplished by
TLC on silica-gel plates.
General Method for Epoxidation
Phenol (9.4 g, 100 mmol) was dissolved in NaOH solution (1 N, 100 ml) and
cooled to 5–108C Then, epichlorohydrin (16 ml, 200 mmol) was added
dropwise (1-h duration) to the reaction mixture and the reaction mixture
stirred for 12 h, at room temperature. The product was extracted with
CH2Cl2 and washed with 5% NaOH solution; the organic layer was dried
over anhydrous sodium sulfate, and the solvent was evaporated under

Epoxides to b-Chlorohydrins
2199
reduced pressure. The product was purified by column chromatography using
chloroform–hexane (40:60) as eluent.
General Procedure for the Conversion of Epoxides
to Chlorohydrins
b-Cyclodextrin (1 mmol) was dissolved in water (15 ml) at 608C; the epoxide
(1 mmol) dissolved in acetone (1 ml) was slowly added at this temperature
with stirring and the mixture was cooled to room temperature. Then, thionyl
chloride (1.5 mmol) was added and stirring continued at room temperature
for 10 h. After completion of the reaction the organic material was extracted
with ethyl acetate; the organic phase was separated, filtered to remove any
adhering CD particles, washed with brine, dried (Na2SO4), and concentrated.
The crude product was purified by silica-gel column chromatography using
ethyl acetate–hexane (2:8) as eluent.
Spectroscopic Data of New Compounds
1-Chloro-3-(4-methylphenoxy)-2-propanol (Table 1, entry 3): pale yellow
oil, IR (neat): v ¼ 3510 Cm21; 1H NMR (CDCl3, 400 MHz,): d ¼ 2.30 (s, 3H),
2.42 (d, 1H, J ¼ 3.2 Hz), 3.66–3.80 (m, 2H), 4.00–4.10 (m, 2H), 4.12–4.20
(m, 1 H), 6.78 (d, 2H, J ¼ 8.0 Hz), 7.05 (d, 2H, J ¼ 8.0 Hz); mass (EI): m/
z ¼ 200; anal. calcd. for C10H13O2Cl: C, 59.86; H, 6.53; Cl, 17.67; found: C,
59.95; H, 6.62; Cl, 17.67.
1-Chloro-3-(4-methoxyphenoxy)-2-propanol (Table 1, entry 4): pale
;
1H NMR (CDCl3, 200 MHz,):
yellow liquid; IR (neat): v ¼ 3525 cm21
d ¼ 2.45 (brs, 1H), 3.68–3.80 (m, 5H), 3.98–4.08 (m, 2H), 4.10–4.20
(m, 1H), 6.75–6.85 (m, 4H); mass (EI): m/z ¼ 216; anal. calcd. for
C10H13O3Cl: C, 55.44; H, 6.05; Cl, 16.36; found: C, 55.36; H, 6.11; Cl, 16.42.
1-Chloro-3-[4-(2-methoxyethyl) phenoxy]-2-propanol (Table 1, entry 6):
;
1H NMR (CDCl3, 200 MHz,):
Colorless oil; IR (neat): v ¼ 3485 cm21
d ¼ 2.56 (brs, 1H), 2.80 (t, 2H, J ¼ 7.4 Hz), 3.35 (s, 3H), 3.54 (t, 2H,
J ¼ 7.4 Hz), 3.68–3.80 (m, 2H), 4.00–4.09 (m, 2H), 4.12–4.10 (m, 1 H),
6.81 (d, 2H, J ¼ 7.6 Hz), 7.12 (d, 2H, J ¼ 7.6 Hz); mass (EI): m/z ¼ 244;
anal. calcd. for C12H17O3Cl: C, 58.90; H, 7.00; Cl, 14.49; found: C, 58.98;
H, 7.05; Cl, 14.41.
ACKNOWLEDGMENT
K.S. thanks Council of Scientific Research (CSIR), New Delhi, India, for the
award of a research fellowship. IICT Communication No. 040911.

2200
K. Surendra et al.
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