1
80 J. CHEM. RESEARCH (S), 1997
J. Chem. Research (S),
Efficient Nucleophilic Cleavage of Oxiranes to
1
997, 180†
Chlorohydrins†
a
a
a
a
Chintamani Sarangi, Nalin B. Das,* Bhagabat Nanda, Amaendu Nayak and
b
Ram P. Sharma
a
Regional Research Laboratory, Bhubaneswar-751013, India
b
Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, India
.
SnCl 2H O–Mg and THF–H O is an efficient system for the conversion of oxiranes into chlorohydrins.
2
2
2
Epoxides are valuable intermediates in organic synthesis
partly because of their nucleophilic cleavage leading to
Table 1 Oxirane ring opening with SnCl .2H O–Mg–THF–H O
2
2
2
a
b
Entry
Oxirane
Product
Yield (%)
1
,2-difunctionalized systems and partly because such cleav-
ages usually occur specifically with trans stereochemistry. The
OH
formation of halohydrins from epoxides has been extensively
1
O
64
72
1
–8
studied with a variety of reagents. Although there is prece-
dent for the Lewis acid assisted cleavage of oxiranes to halo-
hydrins, these reactions often afford only modest yields. The
present work was undertaken in order to determine the
general applicability of the reaction with epoxides. In con-
tinuation of our earlier studies on the uses of metal
Cl
2
O
O
Cl
OH
OH
3
4
Cl
75
77
9
,10
.
reagents, we found that SnCl 2H O–Mg and THF–H O is
2
2
2
a promising system for the regioselective ring opening of
oxiranes to the corresponding chlorohydrins in good yields.
O
Cl
OH
R1
O
Cl
OH
O
SnCl2•2H2O–Mg
THF–H2O
5
6
90
78
R2
PhCH CH2
PhCHCH2OH
R1
R2
O
Cl
Cl
PhCH CHPh
PhCHCHOH
OH
1
In acidic medium there is usually a greater tendency for
nucleophilic attack at the more substituted carbon atom.
Phenyl substituents at the epoxide ring can stabilize an inter-
mediate positive charge by conjugation, and hence attack
occurs at the more substituted carbon atom. However, in the
case of epoxides with electron withdrawing substituents,
nucleophilic attack at the unsubstituted carbon is usually
favoured. Under these conditions, substituted epoxides
O
OH
7
86
74
PhOCH2CH CH2
PhOCH CHCH Cl
2
2
O
OH
8
ClCH2CH CH2
2
ClCH CHCH2Cl
a
b
All the products gave satisfactory spectral data. Total yield of
the regioisomers.
(
Table 1, entries 4, 7 and 8) reacted regioselectively affording
the primary chloride. The cyclohexene oxide and the epoxide
entries 2 and 3 respectively) opened cleanly to afford the
of the reaction (TLC), usual work-up and purification by prepara-
tive chromatography yielded the corresponding chlorohydrins.
(
1
Selected H NMR spectral data. For trans-2-chlorocyclohexanol:
trans chlorohydrins, with the tertiary chloride being the major
product in the latter case. However in the case of styrene
oxide the secondary chloride predominates. The yield of the
products corresponds to the total yield of the regioisomers.
Cleavage of the oxirane ring has also been unsuccessfully
d
H
(CDCl ) 1.1–1.95 (8 H, m), 2.65 (1 H, br s), 3.05–3.5 (2 H, m).
3
For 1-chloromethylcyclohexanol: d
2.15 (1 H, br s), 3.15 (2 H, s). For 1-chlorohexan-2-ol: d (CDCl )
H
(CDCl
3
) 1.2–1.75 (10 H, m),
H
3
1.15 (3 H, s), 1.35–1.95 (6 H, m), 2.6 (1 H, br s), 3.8 (2 H, d), 4.85
(
1 H, t). For 2-chloro-2-phenylethanol: d (CDCl ) 2.36 (1 H, s),
3.95–1.95 (2 H, d), 5.05 (1 H, t), 7.48 (5 H, m).
H
3
.
attempted using SnCl 2H O–THF alone. However, the use
2
2
of a stoichiometric amount of magnesium facilitated the
reaction. In addition, the possibility of active zero-valent tin
We thank Professor H. S. Ray, Director, and Dr Y. R. Rao,
Head, F&M Division, Regional Research Laboratory, for
their valuable suggestions. C. S. acknowledges the pool
scheme of the Government of India.
II
0
(
generated in situ by the reduction of Sn to Sn in the
presence of magnesium) could effectively induce regiose-
lective nucleophilic attack.
Owing to the general interest in the smooth and selective
cleavage of these compounds, mild reaction conditions, good
yields and some possible synthetic applications, the
Received, 18th November 1996; Accepted, 11th February 1997
Paper E/6/07796J
.
SnCl 2H O–Mg–THF system will be a useful addition to the
2
2
References
existing findings.
1
J. G. Smith, Synthesis, 1984, 629.
Experimental
2 H. O. House, Modern Synthetic Reactions, Benjamin, Menlo Park,
1
H NMR spectra were recorded on deuteriochloroform on a
1972, p. 301.
JEOL FX-90 instrument. IR spectra were recorded on a JASCO
FT/IR-5300 instrument in chloroform. Mass spectra were recorded
on an MS-30 instrument. TLC and preparative TLC were per-
formed on silica gel (E. Merck).
3 M. A. Loreto, L. Pellacani and P. A. Tardella, Synth. Commun.,
1981, 11, 287.
4 J. Kagan, B. E. Firth, N. Y. Shih and C. G. Boyajian, J. Org.
Chem., 1977, 42, 343.
General Procedure.sIn a typical procedure, a mixture of
5 E. Mincione, G. Ortaggi and A. Sirna, J. Org. Chem., 1979, 44,
.
SnCl
2
2H
2
O (442 mg, 2 mmol), Mg powder (36.5 mg, 1.5 mmol)
1569.
and oxirane (1 mmol) in THF (10 ml) was stirred at room tempera-
ture. An exothermic reaction occurred with the liberation of hydro-
gen. The reaction mixture was stirred for 30 min. After completion
6 T. W. Bell and J. A. Ciaccio, Tetrahedron Lett., 1986, 27, 827.
7 C. L. Spawn, G. J. Drtina and D. F. Weiner, Synthesis, 1986,
315.
8
C. Einhorn and J. L. Luche, J. Chem. Soc., Chem. Commun.,
1
986, 1368 and references cited therein.
*
†
To receive any correspondence.
9 C. Sarangi, A. Nayak, B. Nanda, N. B. Das and R. P. Sharma,
Tetrahedron Lett., 1995, 36, 7119.
10 C. Sarangi, A. Nayak, B. Nanda, N. B. Das and R. P. Sharma, J.
Chem. Res. (S), 1996, 28 and references cited therein.
This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).