Silica gel promoted highly regioselective ring opening of epoxides using NaN3 under solvent free conditions

Article abstract of DOI:10.1080/714040952

A convenient and efficient synthesis of vicinal azidohydrin has been achieved by ring opening of epoxides using SiO₂/NaN₃ under solvent free conditions. The reaction is highly regioselective and afforded the corresponding products in

Full text of DOI:10.1080/714040952

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Phosphorus, Sulfur, and Silicon and the Related
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Silica Gel Promoted Highly Regioselective Ring Opening
of Epoxides Using NaN Under Solvent Free Conditions
3
a
a
Ali Reza Kiasat & Foad Kazemi
a
Shahid Chamran University, Ahvaz, Iran
Published online: 18 Jun 2010.
To cite this article: Ali Reza Kiasat & Foad Kazemi (2003) Silica Gel Promoted Highly Regioselective Ring Opening of Epoxides
Using NaN Under Solvent Free Conditions, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:11, 2387-2392, DOI:
3
10.1080/714040952
To link to this article: http://dx.doi.org/10.1080/714040952
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Phosphorus, Sulfur, and Silicon, 178:2387–2392, 2003
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390234894
SILICA GEL PROMOTED HIGHLY REGIOSELECTIVE
RING OPENING OF EPOXIDES USING NaN UNDER
3
SOLVENT FREE CONDITIONS
Ali Reza Kiasat and Foad Kazemi
Shahid Chamran University, Ahvaz, Iran
(Received March 25, 2003)
A convenient and efficient synthesis of vicinal azidohydrin has been
achieved by ring opening of epoxides using SiO /NaN under solvent
2
3
free conditions. The reaction is highly regioselective and afforded the
corresponding products in good to excellent yields under mild and neu-
tral reaction conditions.
Keywords: Azidohydrine; azidolysis; epoxide; ring opening; silica gel;
solid state; solvent free
Oxiranes are well known electrophiles capable of reacting with a wide
1
variety of nucleophiles to generate ring-opened products. Among the
various nucleophiles employed in epoxide opening reactions the azi-
dolysis of epoxides enjoys a prominent position because the vicinal
azidohydrins obtained upon ring opening can be easily reduced to 1,2
2
3
aminoalcohols, which have been extensively used in pharmaceuticals,
2
4
carbohydrates, and in carboxylic nucleosides.
Azidation of epoxides as the most recognized method to 1,2-
aminoalcohols are often performed in aqueous solution under alkaline
5
or acidic conditions. Even though the classical protocol uses sodium
azide and ammonium chloride, the azidolysis reaction requires a long
reaction (12–48 h) and the azidohydrin is often accompanied by isomer-
6
ization, epimerization, and rearrangement of products. A great variety
of reagents or catalysts have emerged as a result of sustained efforts
by chemists to discover new and mild methods to effect azidolysis of
7
8
epoxides under non aqueous conditions. Onaka et al. reported that
sodium azide supported on three types of porous solid acids (zeolite, alu-
mina, and silica gel) can be used as reagents for azidolysis of epoxides.
They showed that the activities of the supported reagents are greatly
Address correspondence to Foad Kazemi, Chemistry Department, College of Sciences,
Shahid Chamran University, Ahvaz, Iran.
2
387

2
388
A. R. Kiasat and F. Kazemi
influenced by loading amounts of NaN3, amounts of adsorbed water in
the reagents, acidic properties of the solid acids, and reaction solvents.
9
10
The reactions of tributyltin and dibutyltinazide or LiN3 with epox-
ides and the reaction of epoxide with NaN3 in the presence of catalytic
amount of LiClO4,11 CAN, CeCl3, or LiBF4, trimethylsilylazide in
12
6
7
1
3
the presence of catalytic amount of Lewis acids or tetrabutylammo-
1
4
nium salt in nonaqueous solvents have been reported. Unfortunately,
some of these methods are not always fully satisfactory and suffer from
disadvantages such as acidity, relative long reaction times, low regios-
electivity, or need of application of wet solvent. Consequently, it seems
that there is still a need for development of newer methods that proceed
under mild and economically appropriate conditions.
Keeping in mind these facts as well as reports about advantages
of reaction under dry conditions in the presence of inorganic solids, we
describe our successful result that led to an efficient and simple method
for the transformation of epoxides into the corresponding azidohydrins
using NaN3/SiO2 in solvent free process in excellent isolated yields.
RESULTS AND DISCUSSION
Several ring-opening reactions of styrene oxide were performed at var-
ious temperatures and with different amounts of inorganic solid and
sodium azide in order to find the most adequate conditions for this re-
action under solvent-free conditions. In a preliminary study, the effect
of alumina and silica gel as inorganic solids on the yield of azidohydrin
was investigated with the reaction of styrene oxide as a model reaction.
The obtained results, clearly indicated, silica gel is the best solid support
for this reaction. The required mole ratio 2:1 of NaN3 and substrate,
respectively, silica gel 0.5 g, and the maximum oil bath temperature of
◦
8
0 C were found to be optimal conditions.
The procedure involves a simple mixing of neat epoxides with NaN3/
silica gel and heating the mixtures in an oil bath for the time being
specified in Table I. Different types of oxiranes carrying activated and
deactivated groups were cleanly, easily, and efficiently converted to the
corresponding azidohydrins as exclusive and virtually pure products
1
according to TLC and HNMR, in considerably short times and in ex-
cellent yields. The scope and generality of this process is illustrated with
several examples and the results are summarized in Table I. The struc-
ture of all the products were settled from their analytical and spectral
1
(
IR, H NMR) data and by direct comparison with authentic samples.
The promoting effect of silica gel was definitely confirmed by reaction
of styrene oxide with sodium azide under similar conditions, without

Azidohydrines
2389
TABLE I Regioselective Ring Opening of Epoxides to the Corresponding
◦
Azidohydrines with NaN
3
/SiO
2
at 80 C Under Solvent-Free Conditions
Time
(min) Yield (%)
Entry
1
Epoxide
Azido alcohola
b
(
I: 90%)
15 94
(
II: 10%)
2
25
94
3
4
25
25
92
92
5
6
15
30
88
86
aProducts were identified by compersion of their physical and spectral data with
those of authentic samples.
b
Isolated yield.
adding silica gel, the reaction time period was longer and the yield was
found to be considerably lower.
The regioselectivity of the ring opening of epoxides is thoroughly de-
pendent on the mechanism of the reaction and particularly on steric
and electronic factors. The reaction of styrene oxide with sodium azide
supported on silica gel was completed under solvent free condition in
◦
8
0 C after 15 min and produced 94% of 1,2-azidoalcohol as a mix-
ture of two isomers. The ratio of α-attack (2-azido-2-phenylalcohol) I to
β-attack (2-azido-1-phenylalcohol) II was found to be 90:10. Epoxides
carrying electron-withdrawing groups reacted under similar reaction
conditions and their corresponding 1,2-azidoalcohols were produced in
excellent yields and regioselectivity. In these cases, with the attack of
the azide ion on the less substituted oxirane carbon, the regioselectivity

2
390
A. R. Kiasat and F. Kazemi
is reversed and the 1,2-azidoalcohol II is obtained. It is shown that, for
epoxides carrying electron-donating groups, the electronic factor pre-
dominates and the nucleophilic attack of azide ion is strongly favored
on the more substituted carbon atom of epoxides. In contrary, epoxides
carrying electron-withdrawing groups, it is the steric factor which pre-
dominates and the nucleophilic attack of azide ion is strongly favored
on the less substituted carbon atom of epoxides (Scheme 1).
SCHEME 1
The advantage of using NaN3/SiO2 as reagent for the azidation of
epoxides is shown by comparing our results with those previously re-
ported in the literature (Table II).
Compared to some previously reported methods with major or minor
drawbacks, several noteworthy features of this reagent are apparent.
These are the easy work-up procedure, availability of the reagent, op-
erational simplicities, and use of inexpensive reagent.
CONCLUSION
We believe that the present procedure for azidation of epoxides pro-
vides an easy, mild, efficient, versatile, and general methodology for
the preparation of azidohydrins from different classes of epoxides, and
we feel that it may be a suitable addition to methodologies already
present in the literature.
EXPERIMENTAL
General
IR spectra were recorded on a Shimadzo 450 spectrophotometer;
1
and HNMR spectra in CDCI3 on a Bruker Avance DPX instrument
(
250 MHz). Required epoxides were purchased from Fluka and Merck.
Products were characterized by comparison of their physical data, IR,
and H NMR spectra with authentic samples. The purity determination
1
of the products and reaction monitoring were accomplished by TLC on
silica gel polygram SILG/UV 254 plates.

Azidohydrines
2391
Yield
TABLE II Comparison of Azidolysis of Some Epoxides with Different
Methods
Time
Entry Epoxide Reagent and Reaction Conditions (h) α-Attack β-Attack (%)
1
LiCIO2/NaN3/CH3CN/reflux11
Mg(CIO4)2/NaN3/CH3CN/reflux
5
2
5
<1
<1
<1
<1
—
<1
—
—
<1
<1
<1
—
—
—
—
—
—
—
—
—
—
—
82
83
81
79
74
90
90
76
86
90
>99
>99
>99
>99
—
>99
—
—
>99
>99
>99
—
—
—
—
—
—
—
—
—
—
—
97
96
92
97
NR
95
NR
NR
88
85
95
99
92
95
94
92
84
91
96
89
98
86
92
78
90
94
67
98
96
84
96
94
1
1
1
1
LiOTf/NaN3/CH3CN/reflux
1
1
LiN3/CH3CN/reflux
NaN3/CH3CN/reflux
5
1
1
24
12
24
24
2
0.5
1.16
3
0.42
36
24
36
42
5
0.4
24
3
0.5
5
2
5
20
42
0.25
0.16
24
1
5
NH4CI/NaN3/MeOH/H2O/reflux
1
1
KCIO4/NaN3/CH3CN/reflux
1
1
NaCIO4/NaN3/CH3CN/reflux
1
1
Zn(OTf)2/NaN3/CH3CN/rt
1
2
CAN/NaN3/t-BuOH/reflux
7
LiBF4/NaN3/wet t-BuOH/reflux
6
CeCI3·7H2O/NaN3/CH3CN/reflux
◦
SiO2/NaN3/Solvent free/80 C
LiCIO4/NaN3/CH3CN/reflux
1
1
2
1
1
Mg(CIO4)2/NaN3/CH3CN/reflux
NH4CI/NaN3/MeOH/H2O/reflux
1
5
1
6
Zr(OTf)2/TMGA/CH3CN/rt
CAN/NaN3/t-BuOH/reflux
LiBF4/NaN3/wet t-BuOH/reflux
1
2
7
1
4
R4NCI/Me3SiN3/solvent free/r
6
CeCI3·7H2O/NaN3/CH3CN/reflux
◦
SiO2/NaN3/Solvent free/80 C
1
1
3
LiCIO4/NaN3/CH3CN/reflux
Mg(CIO4)2/NaN3/CH3CN/reflux
18
17
19
21
26
10
10
8
1
1
1
1
LiN3/CH3CN/reflux
NH4CI/NaN3/MeOH/H2O/reflux
1
5
1
6
Zr(OTf)2/TMGA/CH3CN/rt
CAN/NaN3/t-BuOH/reflux
1
2
7
LiBF4/NaN3/wet t-BuOH/reflux
R4NCI/Me3SiN3/solvent free/rt
1
4
6
CeCI3·7H2O/NaN3/CH3CN/reflux
3
0.25
10
10
◦
a
SiO2/NaN3/Solvent free/80 C
aPresent method.
GENERAL PROCEDURE FOR THE AZIDOLYSIS
OF EPOXIDES
Fine powdered sodium azide (2 mmol, 0.13 g) was mixed with 0.5 g of sil-
ica gel in a 25 ml round bottomed flask. To the resulting powder, epoxide
◦
(
1 mmol) was added and stirred at 80 C for 15–30 min. The progress
of the reaction was followed by TLC until no starting material could
be detected. The mixture was shaken with CH2CI2 (5 ml) and filtered.

2
392
A. R. Kiasat and F. Kazemi
The residue was thoroughly stirred and washed with CH2CI2 and the
solvent evaporated under reduced pressure to afford crude products.
Further purification was achieved by preparative TLC or by silica gel
column chromatography to give pure azidohydrin in 86–94% isolated
yields.
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