Solvent-free, efficient, and high regioselective conversion of epoxides to symmetrical and unsymmetrical vic-dihalides using chlorodiphenylphosphine and n-halosuccinimides

Article abstract of DOI:10.1080/10426507.2010.509877

A new method is described for the efficient and high regioselective conversion of epoxides to symmetrical and unsymmetrical vic-dihalides in high yields using chlorodiphenylphosphine and N-halosuccinimides under solvent-free and neutral conditions and at room temperature. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.509877

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Solvent-Free, Efficient, and High
Regioselective Conversion of Epoxides
to Symmetrical and Unsymmetrical vic-
Dihalides Using Chlorodiphenylphosphine
and N-Halosuccinimides
Ghasem Aghapour a & Asieh Afzali a
a School of Chemistry , Damghan University , Damghan, Iran
Published online: 07 Mar 2011.
To cite this article: Ghasem Aghapour & Asieh Afzali (2011) Solvent-Free, Efficient, and High
Regioselective Conversion of Epoxides to Symmetrical and Unsymmetrical vic-Dihalides Using
Chlorodiphenylphosphine and N-Halosuccinimides, Phosphorus, Sulfur, and Silicon and the Related
Elements, 186:3, 598-605, DOI: 10.1080/10426507.2010.509877
To link to this article: http://dx.doi.org/10.1080/10426507.2010.509877
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Phosphorus, Sulfur, and Silicon, 186:598–605, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.509877
SOLVENT-FREE, EFFICIENT, AND HIGH REGIOSELECTIVE
CONVERSION OF EPOXIDES TO SYMMETRICAL
AND UNSYMMETRICAL VIC-DIHALIDES USING
CHLORODIPHENYLPHOSPHINE AND
N-HALOSUCCINIMIDES
Ghasem Aghapour and Asieh Afzali
School of Chemistry, Damghan University, Damghan, Iran
GRAPHICAL ABSTRACT
Abstract A new method is described for the efficient and high regioselective conver-
sion of epoxides to symmetrical and unsymmetrical vic-dihalides in high yields using
chlorodiphenylphosphine and N-halosuccinimides under solvent-free and neutral conditions
and at room temperature.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Chlorodiphenylphosphine; epoxide; N-halosuccinimide; solvent-free reaction; vic-
dihalide
INTRODUCTION
Syntheticchemistry continues to develop various techniques for obtaining products
with less environmental impact. One of the more promising approaches is solvent-free reac-
tions.1 The elimination of volatile organic solvents in organic syntheses is a most important
goal in “green” chemistry. Furthermore, these reactions have some other advantages such
as low costs, simplicity in process and handling, formation of cleaner products, enhanced
selectivity, much improved reaction rates, and prevention of solvent wastes, hazards, and
Received 19 May 2010; accepted 18 July 2010.
We gratefully acknowledge the support of this work by the Damghan University Research Council.
Address correspondence to Ghasem Aghapour, School of Chemistry, Damghan University, Damghan
3671641167, Iran. E-mail: Gh Aghapour@du.ac.ir
598

CONVERSION OF EPOXIDES TO VIC-DIHALIDES
599
toxicity. These factors are especially important in industry. The development of solvent-free
organic synthetic methods has thus become an important and popular research area.1
Additionally, epoxides are important intermediates in organic synthesis,2 and, due
to their particular polarity and strain in their three-membered ring, a large variety of
nucleophiles are known to effect the ring opening of these compounds.3,4 Although there
are many methods reported for the conversion of epoxides into β-halohydrins,5–8 their
conversion to symmetrical or especially unsymmetrical vic-dihalides as other important
halogenated compounds is rarely found in the literature. The use of reagents such as
PPh3/CCl4,9 PPh3/X2 (X = Cl, Br),10a,b and PPh3/N-halo imides in acetonitrile under reflux
conditions7b is reported for the preparation of symmetrical vic-dihalides and HCl/THF
as highly acidic conditions in first step to produce chlorohydrin, followed by treatment
with PPh3/Br2 in the second step10b and PPh3/N-halo imides via a two-step procedure in
acetonitrile under reflux conditions7b for the preparation of unsymmetrical vic-dihalides.
RESULTS AND DISCUSSION
Recently, we have reported on the application of PPh3/DDQ/tetraalkylammonium
halides in refluxing acetonitrile in the conversion of the epoxides to β-halohydrins and
vic-dihalides,11 and also the application of chlorodiphenylphosphine in the conversion
of epoxides to chlorohydrins under mild and solvent-free conditions.12 Also, we have
shown additional abilities of trivalent phosphorus in organic synthesis,13–16 including con-
version of aldehydes and ketones to gem-dichlorides using chlorodiphenylphosphine/N-
chlorosuccinimide (ClPPh2/NCS).17
In continuation of this work, with respect to rarity of methods for preparation of sym-
metrical and especially unsymmetrical vic-dihalides from epoxides, and also the advantages
of solvent-free reactions, we report in this article a new, more facile, and milder method
for the efficient, regioselective, and solvent-free conversion of epoxides to symmetrical
or unsymmetrical vic-dihalides using ClPPh2 and N-halosuccinimides (NXS; X = Cl, Br,
I) under neutral and one-pot conditions at room temperature in good to excellent yields
(Scheme 1).
Scheme 1 Solvent-free conversion of epoxides to symmetrical and unsymmetrical vic-dihalides using
chlorodiphenylphosphine and N-halosuccinimides (ClPPh2 and NXS, X = Cl, Br, I) under neutral conditions
at room temperature.
Initially we tried to convert glycidyl phenyl ether to 1,2-dichloro-3-phenoxy propane
using ClPPh2 and NCS under solvent-free conditions. In this connection, grinding of this
epoxide with ClPPh2 (1 eq.) alone for about 20 min gave 1-chloro-3-phenoxy-2-propanol,
which was isolable by column chromatography.12 We also found that the use of ClPPh2
and NCS simultaneously is highly exothermic and vigorous for this purpose. Thus, for ease
and mild performing of this transformation, first glycidyl phenyl ether was ground with
ClPPh2 (1 eq.) in a glass test tube until TLC showed the disappearance of the epoxide
(20 min), and then NCS (1.2 eq.) was gradually added to the reaction mixture over a period
of 3 min. The reaction mixture was magnetically agitated for 9.5 h so that TLC showed

600
G. AGHAPOUR AND A. AFZALI
Table 1 Solvent-free conversion of epoxides to vic-dichlorides using ClPPh2 and NCS at room temperaturea,b
Entry
1
Epoxides
vic-Dichlorides
Time (h)
Yield (%)c
90
9.85
2
3
10
9
87
85
4
5
10
83
97
5.25
6
7
4.5
7.5
70d
75
Cl
O
Cl
Cl
O
CH3(CH2)11
CH3(CH2)11
Cl
Cl
8
9.5
82
Cl
O
Cl
aMolar ratio 1:1:1.2 of epoxide:ClPPh2:NCS was used in these reactions.
bFirst epoxide was ground with ClPPh2 (1 eq.) in a glass test tube until TLC showed the disappearance of the
epoxide (15–40 min), and then NCS was gradually added to the reaction mixture over a period of 3 min. The
reaction mixture was magnetically agitated for appropriate time.
cIsolated yield.
dA mixture of cis:trans (1:2) was obtained in this case on the basis of NMR analysis.
the completion of the reaction. Column chromatography of the crude product afforded
1,2-dichloro-3-phenoxy propane in 90% yield. Then, we extended this procedure to other
structurally different epoxides to obtain vic-dichlorides. The results of this investigation are
shown in Table 1.
As shown in Table 1, epoxides are efficiently converted to their corresponding vic-
dichlorides using ClPPh2 and NCS in low molar ratio (1:1.2) under solvent-free condi-
tions at room temperature. Under these reaction conditions, the activated aromatic ring,

CONVERSION OF EPOXIDES TO VIC-DIHALIDES
601
Table 2 Solvent-free conversion of epoxides to unsymmetrical vic-halides using ClPPh2 and NXS (X = Br, I)
at room temperaturea,b
Entry
1
Epoxides
Unsymmetrical vic-dihalides
Time (h)
10
Yield (%)c
65
2
3
12
9
73
70
4
5
15
14
72
83
6
7
8
15
17
15
92
69
75
aMolar ratio 1:1:1.2 of epoxide:ClPPh2:NXS was used in these reactions.
bFirst epoxide was ground with ClPPh2 (1 eq.) in a glass test tube until TLC showed the disappearance of the
epoxide (15–40 min), and then NXS was gradually added to the reaction mixture over a period of 3 min. The
reaction mixture was magnetically agitated for the appropriate time.
cIsolated yield.
carbon–carbon double bonds, ester group, and ethereal bonds as functional groups that
are present in the epoxide molecules remain intact. In addition, it is possible to obtain
unsymmetrical vic-dihalides by exchanging NCS with N-bromosuccinimide (NBS) or N-
iodosuccinimide (NIS) in the present method. The results of this exchange are shown in
Table 2.

602
G. AGHAPOUR AND A. AFZALI
Table 3 Comparison of the efficiency of the presented method with our previously reported method based on
using PPh3/DDQ/tetraalkyl ammonium halide11
Reagent
(molar ratio)
Temp.
(◦C)
Yield
(%)a
Entry
1
Epoxide
vic-Dihalide
Solvent
–
ClPPh2/NCS (1:1.2)
r.t.
90
2
PPh3/DDQ/(n-
butyl)4NCl.H2O
(4:4:2.2)
CH3CN
reflux
78b
3
4
ClPPh2/NIS (1:1.2)
–
r.t.
73
PPh3/DDQ/(n-
butyl)4NCl.H2O/
(n-butyl)4NI
CH3CN
reflux
40b
(4:4:1.2:1.2)
aIsolated yield.
bIn these reactions (entries 2 and 4), first the epoxide is treated with PPh3:DDQ (1.2:1.2) in the presence
of (n-butyl)4NCl.H2O producing vic-chloro alcohol. Then, the reaction mixture is transferred to another flask
containing PPh3:DDQ (2.8:2.8) alone or together with tetra alkyl ammonium iodide for obtaining symmetrical or
unsymmetrical vic-dihalides, respectively.
As shown in Table 2, epoxides are efficiently converted to their corresponding vic-
chlorohalides via a one-pot procedure using ClPPh2 and then the appropriate NXS (X = Br,
I) in low molar ratio (1:1.2) under solvent-free conditions at room temperature. In addition,
in this transformation, it was observed that the epoxide ring is regioselectively opened from
its less-hindered side due to steric factor by the reaction with ClPPh2 so that the product
contains a chlorine atom attached to a primary carbon atom and another halogen (Br or I)
to a secondary one.
In order to obtain deeper insight into the advantages and merit of the current method
compared to previously reported methods, we compared the efficiency of ClPPh2 and
NXS with, for example, triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/tetra
alkyl ammonium halide system (PPh3/DDQ/R4NX)11 in this conversion. The results of this
comparison are shown in Table 3.
As shown in Table 3, ClPPh2 and NXS convert the epoxides to vic-dihalides in low
molar ratio at room temperature in high yields under solvent-free conditions and in a one-
pot manner. However, this conversion is operated using PPh3/DDQ/R4NX but in high molar
ratio and in refluxing acetonitrile. In addition, the operation of this method is somewhat
difficult, so that the first epoxide is treated with PPh3/DDQ (1.2:1.2) in the presence of (n-
butyl)4NCl.H2O producing vic-chloro alcohol. Then, the reaction mixture is transferred to
another flask containing PPh3/DDQ (2.8:2.8) alone or together with tetra alkyl ammonium
iodide for obtaining symmetrical or unsymmetrical vic-dihalides, respectively.
Also, the use of PPh3 and NXS (or N-halo saccharine = NXSac)7b for this conversion
contains some disadvantages compared to the presented method, such as performing in

CONVERSION OF EPOXIDES TO VIC-DIHALIDES
603
Scheme 2 Suggested mechanism for the conversion of epoxides to symmetrical and unsymmetrical vic-dihalides
using ClPPh2 and NXS (X = Cl, Br, I).
refluxing acetonitrile, the use of reagent in high molar ratio (up to 3.7:3.7), and the need
to transfer the reaction mixture to the second reaction flask again for completion of the
reaction. In addition, in the synthesis of chloroiodides using the present procedure, contrary
to previous works,7b,11 alkene formation is not an important competing pathway, and these
products are obtained in good to excellent yields (Table 2, entries 2, 4, 6, and 8; Table 3,
please compare entry 3 with entry 4).
Although the exact mechanism of these reactions is not clear, on the basis of the
indicated mechanisms in this area,7b,12 we may suggest that at first, the epoxide ring
is regioselectively opened from its less-hindered side due to steric factor by reaction with
ClPPh2 affording adduct (I)12 (Scheme 2). The addition of N-halosuccinimide to the reaction
mixture converts the adduct (I) to the intermediate (II) with concomitant releasing of the
halide anion.7b The desired symmetrical or unsymmetrical vic-dihalide is produced via
attacking of the present halide anion to intermediate (II). This mechanism is in accordance
with the formation of unsymmetrical vic-dihalides containing a chlorine atom attached to
a primary carbon atom and bromine or iodine to a secondary one in the present method.
CONCLUSIONS
In conclusion, the present investigation has demonstrated that the use of ClPPh2
and then NXS offers a solvent-free, simple, and convenient method, avoiding the use of
molecular halogen10a,b with respect to its harsh handling and also halogenated hydrocarbon
solvents such as dichloromethane, for the mild conversion of epoxides to their corresponding
vic-dihalides. This method containing the ability of the synthesis of both symmetrical and
unsymmetrical vic-dihalides, especially in a one-pot procedure, offers advantages such as
commercial availability, ease of handling and inexpensiveness of the reagent, the use of

604
G. AGHAPOUR AND A. AFZALI
reagent in low molar ratio, reduced pollution, easy work up, excellent regioselectivity, high
yields even for chloroiodides, and operation at room temperature in neutral media. Further
studies toward the other applications of this reagent in organic synthesis are in progress in
our laboratory.
EXPERIMENTAL
Solvents, reagents, and chemicals were obtained from Merck (Germany) and Fluka
(Switzerland) chemical companies. The products are known compounds,7b,11 and were
characterized by comparison of their physical data, IR, NMR, and mass spectra with those
prepared according to procedures reported in the literature. FT-IR spectra were recorded on
a Perkin Elmer RXI spectrophotometer. Nuclear magnetic resonance spectra were recorded
on a Brucker Avance DPX-250 or Brucker Avance DRX-500 spectrometers. Mass spectra
were determined on a Shimadzu GCMS-QP 1000 EX at 70 ev. Thin layer chromatography
was carried out on silica gel 254 analytical sheets obtained from Fluka.
General Procedure for the Conversion of Epoxides to Symmetrical
or Unsymmetrical vic-Dihalides
Epoxide (1 mmol) was thoroughly mixed with ClPPh2 (0.18 mL, 1 mmol) in a
glass test tube. The resulting mixture was ground at room temperature for the appropriate
time, which TLC showed complete disappearance of epoxide (15–40 min), and then NXS
(X = Cl, Br, I) (1.2 mmol) was gradually added to the reaction mixture over a period of
3 min. The reaction mixture was magnetically agitated untile TLC showed the completion
of the reaction. Column chromatography of the crude product gave pure symmetrical or
unsymmetrical vic-dihalide in 70–97% and 65–92% yields, respectively (Tables 1 and 2).
The spectral data of some of the products can be found in the Supplemental Materials
(available online).
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