Silphos [PCl3-n (SiO2)n]: A heterogeneous phosphine reagent for the regioselective synthesis of vic-haloalcohols

Article abstract of DOI:10.1080/10426500600775989

Silphos as a silica-based phosphine [PCl_3-n (SiO ₂)_n] provides a practical method for the conversion of epoxides to vic-haloalcohols in the presence of molecular bromine, iodine, or N-halosuccinimides (NXS, X = Cl, Br, I) in CH₃CN or under solvent-free conditions at r.t. The simple filtration of heterogeneous Silphos oxide from the reaction mixture affords the pure vic-haloalcohols with excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500600775989

This article was downloaded by: [University of Auckland Library]
On: 09 October 2014, At: 03:13
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Silphos [PCl3- n (SiO2) n ]: A
Heterogeneous Phosphine
Reagent for the Regioselective
Synthesis of vic-Haloalcohols
Nasser Iranpoor a , Habib Firouzabadi a & Arezu
Jamalian a
a Department of Chemistry , Shiraz University ,
Shiraz, Iran
Published online: 01 Feb 2007.
To cite this article: Nasser Iranpoor , Habib Firouzabadi & Arezu Jamalian (2006)
Silphos [PCl3- n (SiO2) n ]: A Heterogeneous Phosphine Reagent for the Regioselective
Synthesis of vic-Haloalcohols, Phosphorus, Sulfur, and Silicon and the Related
Elements, 181:11, 2615-2621, DOI: 10.1080/10426500600775989
To link to this article: http://dx.doi.org/10.1080/10426500600775989
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,

and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 181:2615–2621, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600775989
Silphos [PCl3−n(SiO2)n]: A Heterogeneous Phosphine
Reagent for the Regioselective Synthesis
of vic-Haloalcohols
Nasser Iranpoor
Habib Firouzabadi
Arezu Jamalian
Department of Chemistry, Shiraz University, Shiraz, Iran
Silphos as a silica-based phosphine [PCl
for the conversion of epoxides to vic-haloalcohols in the presence of molecular
(SiO ) ] provides a practical method
2 n
3−n
bromine, iodine, or N-halosuccinimides (NXS, X = Cl, Br, I) in CH CN or under
3
solvent-free conditions at r.t. The simple filtration of heterogeneous Silphos oxide
from the reaction mixture affords the pure vic-haloalcohols with excellent yields.
Keywords Epoxide; heterogeneous phosphine; molecular halogens; N-halosuccinimide;
Silphos; vic-haloalcohol
INTRODUCTION
Supported reagents have continuously received attention from the syn-
thetic points of view for their high efficiency, environmentally benign
conditions, and convenient work-up procedures.1,2 Silica gel has been
presented to be one of the most useful inorganic solid supports for func-
tional group transformations.1,3−4 One of the major advantages of using
silica gel as a supporting reagent is its weak acidic character (pH 5.5–
7.5).1g On the other hand, vic-haloalcohol formation from epoxides has
been achieved in the presence of various catalysts and reagents.5 Fur-
thermore, phosphine-containing reagents have also been applied for
this transformation.6 However, the use of these phosphine reagents is
not always fully satisfactory and suffers from disadvantages such as the
need for time-consuming chromatographic separation of the produced
phosphine-oxide,6a,d,f the use of toxic7 dimethyl aminopyridine along
Received January 4, 2006; accepted April 13, 2006.
The authors are grateful to the Organization of Planning and Management of Iran
and Shiraz University Research Council for the support of this work.
Address correspondence to Nasser Iranpoor, Shiraz University, Department of Chem-
istry, College of Sciences, Shiraz 71454, Iran. E-mail: iranpoor@chem.susc.ac.ir
2615

2616
N. Iranpoor et al.
with the phosphine reagent,6e and the use of expensive polymeric phos-
phine reagents.6b
In connection with our interest in using heterogeneous phosphines,
we now report that Silphos [PCl3−n(SiO2)n] as a novel and easily pre-
pared heterogeneous silica-based phosphine reagent converts epoxides
to vic-haloalcohols conveniently with the ease of removal of the pro-
duced Silphos oxide by a simple filtration (Scheme 1). In this article,
the results that successfully led to presenting a versatile procedure for
the epoxide-haloalcohol transformation are described.
SCHEME 1
RESULTS AND DISCUSSION
For preliminary studies, we reacted 2,3-epoxypropylphenyl ether with
different amounts of Silphos (0.6–1.0 g) and N-bromosuccinimide (NBS)
(1.0–1.2 mmol) to optimize the reaction condition. As it is represented
in Table I, in both cases, the reaction in CH3 CN or under solvent-
free condition’s with the molar ratio of epoxide to NBS (1:1.2) and
TABLE I The Optimization of the Reaction Conditions for the
vic-Haloalcohol Formation From 2,3-Epoxypropylphenyl Ether in the
Presence of Silphos and Different Brominating Agents at R.T.
mmol
(Brominating Agent)
Entry
g of Silphos
Solvent
Time (h)
Conversion (%)a
1
2
3
4
5
6
7
8
1.0 (NBS)
1.0 (NBS)
1.0 (NBS)
1.1 (NBS)
1.2 (NBS)
1.2 (NBS)
1.2 (Br2)
0.6
0.8
1.0
1.0
1.0
1.0
1.0
1.0
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
—
24
24
24
8
30
55
70
90
1
100
100
100
100
15 min
CH3CN
CH3CN
1
8
1.2 (CBr4)
aConversion was determined by GC analysis using n-octane as an internal standard.

Silphos [PCl3−n(SiO ) ]
2617
2 n
1.0 g of Silphos [PCl3−n(SiO2)n] led to the 100% conversion of 2,3-
epoxypropylphenyl ether to its corresponding vic-bromoalcohol (Table 1,
entries 5 and 6). The similar ratio was applied for Br2 and CBr4 as the
brominating agents, which needed 1 and 8 h, respectively, for the quan-
titative conversion of 2,3-epoxypropylphenyl ether to its corresponding
vic-haloalcohol (Table 1, entries 7 and 8).
We applied the optimized conditions both in CH3CN and under
solvent-free conditions for the ring opening of structurally differ-
ent epoxides to their corresponding vic-haloalcohols with molecular
bromine and iodine, and also N-halosuccinimides (NXS, Cl, Br, I) as
halogenating agents. The obtained results are summarized in Table II.
Under the optimized reaction conditions, the carbon–carbon double
bond, ester group, ethereal bonds, and aromatic ring remained un-
changed. The attack of the halide ion on the epoxides ring was influ-
enced by both the electronic and steric factors. In the case of styrene
oxide, the nucleophilic attack of the halide ion was oriented by the
electronic factors to the more substituted carbon atom. On the other
hand, the major product produced from the epoxides containing alkyl
or electron-withdrawing substituents occurred from an attack to the
less-hindered carbon atom.
Utilizing the optically active epoxide, (R)-(+)-styrene oxide as the
substrate, the epoxide ring cleavage appeared to be stereospecific, pro-
ducing the product with the inversion of the configuration. The spe-
cific rotation observed for (S)-2-bromo-2-phenylethanol was found to be
[α]D = +99.3 (c = 1, CHCl3, Lit. [α]D = + 102.1 (c = 1, CHCl3).1g
The exact mechanism of the method is not clear; however, the pro-
posed mechanism for this conversion with Silphos in the presence of
NXS (Cl, Br, I) and molecular bromine or iodine could be the same. Sim-
ilar to PPh3, Silphos can readily react with both molecular halogens or
NXS to produce partially ionic adducts, which increase the electrophilic
nature of the phosphorus atom.6a,8 However, there are some reports
that N-halosuccinimide (NXS) has acted as the source of the halide ion
and not the activating group for the phosphorus atom of the phosphine
reagents.9 We observed that Silphos reacts with molecular bromine or
NXS before the addition of epoxide to produce the positively charged
phosphorus intermediate, which is already reported in the literature.8,9
It was therefore concluded that the phosphorylation of the oxygen atom
of the epoxide by the positively charged phosphorus atom of Silphos fol-
lowed by the nucleophilic attack of the halide ion can lead to the desired
product (Scheme 2).
In conclusion, Silphos [[PCl3−n(SiO2)n] appears to be a very efficient
reagent for the conversion of epoxides to vic-haloalcohols with molecu-
lar bromine or iodine, or N-halosuccinimides both in CH3CN or under

2618
N. Iranpoor et al.
SCHEME 2
solvent-free conditions. The advantages of this regio- and stereoselective
method are high to quantitative yield of the product, easy removal of
the Silphos oxide byproduct, and the simple the preparation of Silphos
as a cheap and heterogeneous reagent.
EXPERIMENTAL
All the reagents and solvents were purchased from Fluka or Merck
Chemical Companies. FTIR spectra were recorded on a Shimadzu DR-
8001 spectrometer. NMR spectra were recorded on a Brucker Avance
DPX 250 MHz instrument. Silphos was prepared according to the
literature.4a
The Typical Procedure for the Conversion of 2,3-
Epoxypropylphenyl Ether to 1-Bromo-3-Phenoxy-Propan-2-ol
by Silphos/NBS in CH3CN
To a heterogeneous mixture of 1.0 g of Silphos and 1.2 mmol (0.21 g)
of NBS in 5 mL of CH3CN, 2,3-epoxypropylphenyl ether (1.0 mmol,
0.15 g) was added. The reaction mixture was stirred at r.t. and

Silphos [PCl3−n(SiO ) ]
2619
2 n
TABLE II The Conversion of 1.0 mmol of Epoxide to vic-Haloalcohol
in the Presence of 1.0 g of Silphos [PCl3−n(SiO2)n] and 1.2 mmol of
Molecular Bromine, Iodine, or N-Halosuccinimides in CH3CN or
Under Solvent-Free Conditions
in CH3CN
Solvent-Free
Time Yield
Time
(min)
Yield
(%)a
Entry
1
Substrate
Product
Reagent (min)
(%)a
Br2
I2
40
25
50
40
35
50
30
60
55
45
40
30
60
20
20
60
60
60
50
40
55
25
30
10
10
85
87
91
88
89
90
92
88
10
5
90
94
95
91
95
93
94
94
NBS
NCS
NIS
Br2
I2
NBS
NCS
NIS
Br2
I2
NBS
NCS
NIS
Br2
I2
NBS
NCS
NIS
Br2
I2
15
10
10
10
10
15
10
10
15
10
10
5
2
3
4
5
90
91
95
95
75 (15)
74 (15)
70 (20)
72 (20)
73 (17)
88
92
91
89
94
77 (18)
80 (15)
75 (17)
81 (13)
85 (10)
95
97
94
92
94
5
15
10
15
20
20
15
15
10
5
87
93
90
86
93
96
95
94
NBS
NCS
NIS
90
5
95
6
7
Br2
I2
45
30
60
40
50
30
20
10
25
20
84 (10)
86 (10)
84 (12)
80 (11)
83 (15)
94
92
95
92
94
20
20
15
10
10
10
10
5
82 (15)
87 (10)
88 (10)
84 (11)
85 (10)
94
95
95
90
92
NBS
NCS
NIS
Br2
I2
NBS
NCS
NIS
5
5
aAll products are known compounds and are identified by their physical or spectral
data6e; Yield (%) in parenthesis shows the formation of the other regio-isomer which is
measured by GC and NMR.

2620
N. Iranpoor et al.
monitored by TLC and GC analysis. The reaction was completed after
60 min. After evaporation of the solvent, the residue was washed with
2 × 15 mL of ethyl acetate. The organic layers were combined, washed
with 20 mL of sodium thiosulfate (10%) and 20 mL of water, and
dried over anhydrous Na2SO4. Evaporation of the solvent produced
1
pure 1 bromo-3-phenoxy-propan-2-ol in a 91% yield. H NMR(CDCl3,
250 MHz): δ 2.85 (s, 1H, −OH), 3.52–3.76 (m, 2H, −CH2Br), 4.01–
4.08 (m, 2H, −CH2OPh), 4.15–4.23 (m, 1H, −CHOH), 6.75–7.65 (m,
5H, −Ph) ppm; 13C-NMR (CDCl3, 62.9 MHz): δ 35.07 (−CH2Br), 68.60
(−CHOH), 69.60 (−CH2OPh), [115.08, 121.50, 129.23, 158.23 (−Ph)],
ppm.
The Typical Procedure for the Conversion of
2,3-Epoxypropylphenyl Ether to 1-Iodo-3-Phenoxy-Propan-2-ol
by Silphos/I2 Under Solvent-Free Conditions
2,3-Epoxypropylphenyl ether (1.0 mmol, 0.15 g) was added to a solvent-
free mixture of 1.0 g of Silphos and 1.2 mmol (0.3 g) of molecular
iodine. The reaction mixture was stirred at r.t. TLC monitoring and
GC analysis showed the completion of the reaction after 15 min. The
mixture was washed with 2 × 15 mL of ethyl acetate. Then the com-
bined organic layers were washed with 20 mL of sodium thiosulfate
(10%) and 20 mL of water, respectively. Drying of the organic layer over
anhydrous Na2SO4 and evaporation of the solvent afforded 1-iodo-3-
1
phenoxy-propan-2-ol in 97% yield. H-NMR (CDCl3, 250 MHz): δ 2.65
(s, 1H, −OH), 3.37–3.43 (m, 2H, −CH2I), 4.0–4.18 (m, 2H, −CH2OPh),
4.18–4.22 (m, 1H, −CHOH), 6.96–7.56 (m, 5H, −Ph) ppm; 13C-NMR
(CDCl3, 62.9 MHz): δ 9.03 (−CH2I), 69.3 (−CHOH), 70.53 (−CH2OPh),
[(115.63, 118.2, 137.11, 139.72, −Ph)] ppm.
REFERENCES
[1] (a) A. McKillop and D. W. Young, Synthesis, 401, 481 (1979); (b) G. Bram, E. d’Incan,
and A. Loupy, Nouv. J. Chim., 6, 689 (1982); (c) P. Laszlo, Acc. Chem. Res., 19, 121
(1986); (d) J. H. Clark, A. P. Kybett, and D. J. Macquarrie, Supported Reagents: Prepa-
ration, Analysis, and Application (VCH, New York, 1992); (e) K. Smith, Solid Sup-
ports and Catalysts in Organic Synthesis; (Ellis Horwood, Chichester, England, 1992);
(f) J. H. Clark, Catalysis of Organic Reactions by Supported Inorganic Reagents (VCH,
New York, 1994); (g) H. Kotsuki, T. Shimanouchi, R. Ohshima, and S. Fujiwara,
Tetrahedron, 54, 2709 (1998).
[2] R. S. Varma, Tetrahedron, 58, 1235 (2002).
[3] (a) M. J. Hojo, Syn. Org. Chem. Jpn., 42, 635 (1984); (b) K. Smith, Bull. Soc. Chim.
Fr., 272 (1989); (c) T. Nishiguchi, J. Syn. Org. Chem. Jpn., 51, 308 (1993); (d) V. A.
Basiuk, Russ. Chem. Rev., 64, 1003 (1995); (e) A. K. Banerjee, M. S. Laya Mimo´, and
W. J. Vera Vegas, Russ. Chem. Rev., 11, 971 (2001).

Silphos [PCl3−n(SiO ) ]
2621
2 n
[4] (a) N. Iranpoor, H. Firouzabadi, A. Jamalian, and F. Kazemi, Tetrahedron, 61, 5699
(2005); (b) N. Iranpoor, H. Firouzabadi, and A. Jamalian, Synlett, 1447 (2005);
(c) N. Iranpoor, H. Firouzabadi, and A. Jamalian, Tetrahedron Lett., 46, 7963 (2005);
(d) N. Iranpoor, H. Firouzabadi, and A. Jamalian, Tetrahedron, 62, 1823 (2006).
[5] For some of the recent references, see (a) G. Smitha and C. S. Reddy, J. Chem.
Res., 300 (2004); (b) H. Sharghi, M. M. Eskandari, and R. Ghavami, J. Mol. Cat.
A: Chemical, 215, 55 (2004); (c) H. Sharghi and M. M. Eskandari, Tetrahedron,
59, 8509 (2003); (d) K. Niknam and T. Nasehi, Tetrahedron, 58, 10259 (2002);
(e) H. Sharghi and M. M. Eskandari, Synthesis, 1519 (2002); (f) B. Tamami and H.
Mahdavi, Reactive and Functional Polymers, 51, 7 (2002); (g) H. Sharghi, K. Niknam,
and M. Pooyan, Tetrahedron, 57, 6057 (2001); (h) W. H. Leung, T. K. T. Wong, J. C. H.
Tran, and L. L. Yeung, Synlett, 677 (2000); (i) S. Munavalli, D. K. Rohrbaugh, D. I.
Rossman, L. R. McMahon, and H. D. Durst, J. Organomet. Chem., 587, 160 (1999);
(j) R. Skupin and G. Haufe, J. Fluorine Chem., 92, 157 (1998).
[6] (a) G. Palumbo, C. Ferreri, and R. Caputo, Tetrahedron Lett., 24, 1307 (1983);
(b) R. Caputo, C. Ferreri, S. Noviello, and G. Palumbo, Synthesis, 499 (1986);
(c) D. Diaz, T. Martin, and V. S. Martin, J. Org. Chem., 66, 7231 (2001); (d) N. Iran-
poor, H. Firouzabadi, and G. Aghapour, Synlett., 1176 (2001); (e) F. Sartillo-Piscil, L.
Quintero, C. Villegas, E. Santracruz-Jua´rez, and C. Anaya de Parrodi, Tetrahedron
Lett., 43, 15 (2002); (f) N. Iranpoor, H. Firouzabadi, G. Aghapour, and A. Nahid, Bull.
Chem. Soc. Jpn., 77, 1 (2004).
[7] G. Ho¨efle, W. Steglich, and H. Vorbru¨eggen, Angew. Chem. Int. Ed. Engl., 90, 569
(1978).
[8] S. Trippet, J. Chem. Soc., 2337 (1962).
[9] A. K. Bose and B. Lal, Tetrahedron Lett., 3937 (1973).