Fe(OH)3 nano solid material: An efficient catalyst for regioselective ring opening of aryloxy epoxide with amines under solvent free condition

Article abstract of DOI:10.1016/j.apcata.2013.10.003

Iron hydroxide-Fe(OH)₃and iron oxides (Fe₃O₄and Fe₂O₃) were successfully prepared and characterized. These materials were employed as efficient and environmentally benign heterogeneous catalysts for t

Full text of DOI:10.1016/j.apcata.2013.10.003

Applied Catalysis A: General 469 (2014) 442–450
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Fe(OH)3 nano solid material: An efficient catalyst for regioselective
ring opening of aryloxy epoxide with amines under solvent
free condition
Arpan K. Shaha,b, K. Jeya Prathapc, Manish Kumara,b, Sayed H.R. Abdia,b,∗
,
Rukhsana I. Kureshya,b, Noor-ul H. Khana,b, Hari C. Bajaja,b
a Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Council of Scientific and Industrial
Research (CSIR), G. B. Marg, Bhavnagar 364002, Gujarat, India
b Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar, Gujarat, India
c Shulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2013
Received in revised form 6 September 2013
Accepted 3 October 2013
Available online xxx
Iron hydroxide-Fe(OH)3 and iron oxides (Fe3O4 and Fe2O3) were successfully prepared and characterized.
These materials were employed as efficient and environmentally benign heterogeneous catalysts for
the epoxide ring opening reaction of various aryloxy, terminal and meso epoxides with aromatic and
aliphatic amines under solvent free condition at room temperature. Out of these, nano-sized Fe(OH)3
(IH-1) showed better catalytic activity to give the product ␤-amino alcohols in excellent yield (up to
∼96%) and high regioselectivity in 10–360 min. The catalyst was successfully recycled and reused eight
times with no loss in catalytic activity.
Keywords:
Nano-iron hydroxide
Heterogeneous catalyst
Aryloxy epoxide
© 2013 Published by Elsevier B.V.
Epoxide ring opening
Amino alcohol
Lewis and Brønsted acidity
1. Introduction
mesoporous silica [37–39], alumina and/or modified alumina
[40–43], nano-alumino silicates [44–48], montmorillonite-K10 clay
Epoxide ring opening (ERO) reaction with amine in general
and aryloxy epoxides in particular is an elegant strategy to pro-
duce biologically and commercially important ␤-amino alcohols
[1–6]. ERO reactions with amines are well documented [7–55],
which includes reaction subjected to specific physical parameter
like conventional heating [7,8], microwave [9–11], and ultra-
sound [11]. The use of polar reaction media like ionic liquids
[12], fluoro alcohols [13] or water at different pH conditions
[14,15] were also explored for this reaction with mixed success.
However, it is the use of a catalyst to promote this reaction
that has caught the researchers’ imagination. In this direction
several class of catalysts have been developed, e.g. Brønsted
acids and bases [12,15–20], several metal salts and/or complexes
[21–34], solids like silica gel [35], nano-silica [36], functionalized
[49], sulphated zirconia [50,51], nano-titanium dioxides [52], het-
eropoly acid [53], polyoxometalate–inorganic metal oxygen cluster
[54] and Amberlist-15 [55]. However, the use of derivatives of iron
metal which is abundant in nature, non-toxic and environmentally
benign is less explored for the ERO reaction with amines [39,54].
Hence, our present study was focused on the preparation of nano-
sized iron hydroxides for their use as catalyst particularly for the
ERO of aryloxy epoxides with amines whose ring opened prod-
ucts are used as antibacterial and ␣- and ␤-blockers in medicines
[5,33–34]. The interest in nano-sized iron hydroxide was trig-
gered by its easy synthesis, high stability and most importantly
high surface area with abundant hydroxide groups [56–57]. We
visualized its suitability as highly reactive, recyclable catalyst in
aminolytic epoxide ring opening reaction which is ongoing inter-
est of our research group [10,43,44,58]. Iron hydroxide/oxides as
catalysts in the ERO reactions with amines have not been explored
till recently where the ERO of aryloxy epoxide with aromatic thiols
[59] was reported while we were in the middle of the present study.
Seemingly straightforward synthesis of iron hydroxide is however
bit tricky as the morphology (crystalline nature/size/surface area)
of the hydroxide material which greatly influences the catalytic
∗
Corresponding author at: Discipline of Inorganic Materials and Catalysis, Central
Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), A unit of Council of
Scientific and Industrial Research (CSIR), G. B. Marg, Bhavnagar 364002, Gujarat,
India. Tel.: +91 0278 2567760; fax: +91 0278 2566970.
E-mail addresses: shrabdi@csmcri.org, raziabdi56@gmail.com (S.H.R. Abdi).
0926-860X/$ – see front matter © 2013 Published by Elsevier B.V.
http://dx.doi.org/10.1016/j.apcata.2013.10.003

A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
443
activity depends on hydrolysis protocol and iron salt used, as
different anions coordinated to Fe3+ ion show different degree
(equilibrium constant) of hydrolysis in water [60]. In view of this
we synthesized two samples of iron hydroxides IH-1 and IH-2
obtained by the hydrolysis of aqueous solutions of FeCl3·6H2O and
Fe(NO3)3·9H2O respectively by the addition of aqueous ammonia.
To understand the role/effect of hydroxyl groups present on the
surface of solid iron hydroxide materials in ERO reaction, various
catalyst samples having varying degree of hydroxide ions were
prepared. Accordingly, we synthesized magnetic iron oxide-Fe3O4
(MIO-3) and non-magnetic iron oxide IO-4 (Hematite-Fe2O3) by
the precipitation of FeCl3·6H2O with ammonia under sonication
and IO-5, IO-6 and IO-7 by the calcination of IH-1, IH-2, and MIO-
3 respectively. Among all the iron materials prepared here, the
catalyst IH-1 showed highest activity in the ERO of aryloxy epox-
ides with amines to give corresponding amino alcohols with high
regioselectivity under solvent free reaction condition at room tem-
perature. The catalyst IH-1 was recycled eight times with no sign
of reduction in its performance making thereby the present ERO
protocol a green process for the preparation of amino alcohols.
untill the washings show neutral pH. After the removal of water,
the iron hydroxide samples were dried in an air oven at 373 K for
4 h giving Fe(OH)3 in ∼96% yield.
The magnetic iron oxide (MIO-3) was prepared according to the
following procedure: An aqueous solutions of FeCl2 4H2O (0.04 M,
100 mL) and FeCl3·6H2O (0.08 M, 100 mL) were mixed at room tem-
perature (Fe2+/Fe3+ = 1/2) to which aqueous ammonia (25%, 8 mL)
was added in drop-wise manner over 5 min. The resulting mixture
was stirred vigorously for about 1 h at room temperature that gave
dark brown precipitate of magnetic material. The aqueous super-
natant was decanted under the influence of a magnate and the
residue was repeatedly washed with deionized water and dried
in oven at 373 K for 4 h to get MIO-3 in 93% yield.
The catalyst IO-4 was synthesized by drop-wise addition of
aqueous ammonia (25%, 8 mL) over 5 min to an aqueous solution
of FeCl3·6H2O (0.08 M, 100 mL) under sonication. The sonication of
the resulting mass was continued for 1 h and the reddish brown
solid thus obtained was filtered and dried as described above to get
IO-4 in >86% yield.
Catalysts IO-5, IO-6 and IO-7 were obtained by the calcination
of IH-1, IH-2 and MIO-3 respectively at 773 K in air for 5 h.
Catalyst ID-1 was prepared by treating IH-1 with D2O under
reflux condition for 24 h. The liquid was removed from the resulting
mass under vacuum and dried in a desiccator and was used directly
as catalyst in the ERO reaction.
2. Experimental
2.1. Materials and methods
X-ray powder diffraction studies were carried out using a
REGAKU miniflexII desktop XRD (Japan) system in the 2 theta
range of 10–70 degrees using CuK␣1 (ꢀ = 1.54056 A) at ambient
2.3. Catalytic procedure for epoxide ring opening reaction using
iron hydroxide nano particles
˚
temperature. Surface area of as-synthesized iron hydroxides and
magnetic and non-magnetic iron oxides materials were deter-
mined by nitrogen adsorption method at 77.35 K by using ASAP
2020 (Micromeritics Inc., USA). For these iron hydroxides materi-
als were activated at 373 K and iron oxide materials were activated
at 393 K under vacuum just prior to measurements. FT-IR spectra
were recorded on a Perkin Elmer Spectrum GX spectrophotome-
ter (USA) using KBr window. JEOL, JEM-2100 microscope (Japan)
was used for transmission electron microscopic (TEM) analysis at
200 kV using carbon coated copper grids. For this, magnetic and
non-magnetic materials were dispersed in ethanol and dropped
on the grid for TEM to determine the morphology of materials.
Scanning electron microscope (SEM) image was done using LEO
1430 VP instrument (Germany) using ethanol dispersed material
which is laid on aluminum stub. TGA analysis of iron samples was
done on instrument TGA/SDTA/1822 (Mettler Toledo, USA) in the
temperature range of 70–700 ◦C. Elemental analysis was done on
a CHNS analyzer “Elementar Vario MICRO Cube (Germany)”. NMR
spectra were recorded on a Bruker F113V spectrometer (200 MHz
and 500 MHz, Switzerland) and were referenced internally with
TMS. The products were purified by flash chromatography using
silica gel 60–120 and 100–200 mesh purchased from Spectrochem
Pvt. Ltd. FeCl2·4H2O (E. Merck India Ltd., India), FeCl3·6H2O
and Fe(NO3)3·9H2O were purchased from S.D. Fine Chem. Ltd.,
India. Various aryloxy, meso and terminal epoxides, aromatic and
aliphatic amines (substituted amines) were purchased from Aldrich
chemicals (USA) and used as received.
In a typical procedure, an admixture comprising of a solid cata-
lyst (20 mg), an aryloxy epoxide (1 mmol) and an amine (1 mmol)
were taken in a 5 mL screw capped vial and stirred vigorously for
a given time period (monitored by TLC) under solvent free con-
dition. At the end of the reaction, products amino alcohols were
obtained as viscous liquids or solids. Therefore, the reaction mix-
ture was repeatedly washed with methanol (3 mL) and centrifuged.
Methanol from the combined organic layer was evaporated under
reduced pressure to get crude amino alcohol. A small sample of the
crude product was subjected to HPLC to find out regioselectivity,
while rest of the reaction mixture was subjected to flash column
chromatography (hexane/ethyl acetate, 90:10) to get the major
regioisomer in pure form. The purified product was characterized
by 1H and 13C NMR, FTIR, Microanalysis and characterization data
for all the ring opening products are given in supporting informa-
tion. The residue obtained from centrifugation was dried in air (1 h)
and then in oven at 100 ◦C for 3 h to get back the catalyst (>97%
recovery) for further use.
3. Results and discussion
3.1. Catalyst characterization
3.1.1. Powder X-ray diffraction technique
The powder X-ray diffraction (PXRD) spectra of all the materi-
als are shown in Fig. 1. PXRD spectra of IH-1 and IH-2 were similar
and showed peaks typical for Fe(OH)3 (JCPDS No. 00-022-0346) but,
the broad nature of these spectra suggest their poor crystallinity
and amorphous nature. MIO-3 shows the typical peaks at 2 theta
values 18.4, 30.2, 35.6, 44.5, 53.8, 57.2 and 62.8 indicating the crys-
talline nature (JCPDS No. 001-071-6338) of the magnetite phase.
However, the peaks observed in sample MIO-3 were somewhat
broad possibly due to the presence of amorphous phase of iron
hydroxide and/or surface hydroxyl groups. Samples IO-4, IO-5, IO-
6 and IO-7 were found to be fairly crystalline and gave identical
peaks at 2 theta values of 24.2, 33.2, 35.7, 41.0, 49.6, 54.1, 57.7, 62.6
2.2. Catalyst synthesis
Modified procedure of Song et al. [56] was used to synthe-
size nano-sized Fe(OH)3. Accordingly, catalysts IH-1 and IH-2
were obtained by the addition of aqueous ammonia (25%, 8 mL)
over 5 min to a vigorously stirred aqueous solution of FeCl3·6H2O
(0.08 M, 100 mL) and Fe(NO3)3·9H2O (0.08 M, 100 mL) respectively
as brown precipitates. The brown solids so obtained were washed
repeatedly with deionized water under centrifugation at 8000 rpm

444
A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
H-bonding) respectively. Hence it can be safely concluded that
ID-1
IO-7
these materials have abundant OH groups [61,62]. These bands
were of relatively less intense in MIO-3 and IO-4 samples due to
the lesser numbers of OH groups. Expectedly, the calcined iron
samples, viz. IO-5, IO-6 and IO-7 showed no or very low intensity
band in these regions. The two absorption bands between 438-452
and 531-574 cm−1 have appeared in all the iron hydroxide and iron
oxide materials and were assigned to the fundamental vibrations
of Fe O bonds [61–64]. However, shifts in the IR spectra of ID-
1 were only marginal as compared to the IR of IH-1 possibly due
incomplete D-H exchange in IH-1 treated with D2O.
R-3c(167)
R-3c(167)
IO-6
IO-5
IO-4
R-3c(167)
R-3c(167)
Fd-3m (227)
MIO-3
IH-2
3.1.3. TGA studies
00-022-0346
00-022-0346
Thermo Gravimetric graphs recorded under nitrogen atmo-
sphere for catalysts IH-1 and IH-2 showed overall ∼14% losses in
weight due to the loss of adsorbed water on these materials and/or
removal of surface hydroxyl groups (Supporting information, Figs.
S1 and S2). The magnetic sample MIO-3 showed a weight of loss
about 7% (Supporting information, Fig. S3), whereas iron oxide-
Fe2O3 materials showed only 3–6% weight losses confirming that
these materials have very low water/hydroxyl content (Supporting
information, Fig. S4).
IH-1
10
20
30
40
50
60
70
2 Theta
Fig. 1. X-ray powder diffraction spectra of all catalysts.
and 64.2, and were identified as ␣-Fe2O3 (Hematite, JCPDS No. 33-
0664). However, the sample IO-4 (prepared by sonication method)
was found to be mixed phase material with peaks corresponding to
Hematite and amorphous phase of Fe(OH)3. The calcination prod-
ucts of IH-1, IH-2 and MIO-3, i.e. IO-5, IO-6 and IO-7 respectively,
showed intense and sharp peaks suggesting the formation of highly
crystalline non-magnetic iron oxide (Fe2O3) phase by the loss of
hydroxyl groups during calcination process. Scherrer equation was
applied to corresponding XRD peaks to calculate average particle
size of all the catalysts. The average particle size of non-crystalline,
IH-1 and IH-2 (2.5–11 nm) and semi-crystalline, MIO-3 (18 nm)
was lower than crystalline materials, IO-4 to IO-7 (∼50–60 nm).
3.1.4. Surface area and pore size distribution
N2 adsorption–desorption isotherm of all iron materials gave
type 4 isotherm showing mesoporous structure of these materi-
als. Iron hydroxides, IH-1 and IH-2 showed fairly high BET surface
area ∼350 m2/g with an average pore diameter of 2–3 nm (Table 1,
entries 1 and 2). The magnetic MIO-3 showed relatively lower
surface area (126 m2/g) but with higher average pore diameter
(7.1 nm) possibly due to the agglomeration of magnetic particles
(entry 3). The material IO-4 (formed under sonication) also showed
fairly large surface area (195 m2/g) and a pore diameter of 3.2 nm,
possibly because this material is a mixture of iron hydroxide and
Fe2O3 phases (entry 4). The calcination products IO-5, IO-6 and
IO-7 showed significant decrease in surface area (20.3–33.9 m2/g)
but increase in pore diameter (17.5–50.0 nm) suggesting the pos-
sible loss of interfacial hydrogen bonding structures between the
hydroxyl groups of the material (entries 5–7). Noticeably, sample
IO-6 (entry 6) showed very large average pore diameter (49.9 nm),
3.1.2. FT-IR studies
The IR spectra (Fig. 2) of samples IH-1 and IH-2 showed strong
absorption bands at ∼3398 (broad) and ∼1625 cm−1 which were
assigned to the fundamental stretching and bending vibrations
of hydroxyl groups and/or water molecules (adsorbed through
ID‐1
IO‐7
IO‐6
1630
558
IO‐5
439
3389
IO‐4
MIO‐3
455
536
IH‐2
IH‐1
448
536
554 445
1612
1632
448
448
548
3397
3405
531
589
1356
1464
1621
3390
3384
1620
548
431
4000
3500
1500
1000
500
cm‐1
Fig. 2. FT-IR spectra of all catalysts.

A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
445
Table 1
Particle size, surface area and pore size distribution of all catalysts.
Entry
Catalyst
Average particle size (nm)a
BET surface area (m2/g)
Total pore volume (cm3/g)
Average pore diameter (nm)
1
2
3
4
5
6
7
8
IH-1
IH-2
MIO-3
IO-4
IO-5
IO-6
IO-7
ID-1
2.5
11.2
18.2
58.3
54.3
53.4
63.8
8.1
358.20
331.99
126.38
195.48
33.98
33.32
20.32
265.50
0.215
0.236
0.272
0.197
0.168
0.177
0.148
0.200
2.755
3.078
7.082
3.252
17.450
49.960
30.980
32.500
a
Average particle size was calculated by applying Scherrer equation to each XRD peaks in the corresponding crystallograph and taking the average of them.
however a close look to BJH desorption dV/dD pore volume plot
reveals an intense peak with narrow pore size distribution cen-
tered at ∼18 nm and a very broad and low intensity pore size
distribution centered around ∼110 nm (Supporting information,
Fig. S5). This is possibly due to aggregation of nano-sized particles
under the measurement conditions creating macro-pores thereby
giving unusually high average pore diameter. Significantly, as com-
pared to its OH form, IH-1, D-exchanged iron hydroxide material
ID-1, showed lower surface area (265.5 m2/g) and pore volume
(0.2 cm3/g) but large pore diameter (entry 8). These physical
parameter changes in H/D exchange experiment are unprece-
dented and cannot occur merely by H/D exchange phenomenon.
SEM analysis of this material suggests that the deuterated material
ID-1 is largely agglomeration of nanoparticles (Supporting infor-
mation, Fig. S6).
range of particle size distribution except for IO-4, where smaller
particles in the range of 4–5 nm and larger particles of 50–60 nm
can be seen. Well-defined lattice fringes with ∼0.5 nm distance
were seen in all the iron materials and representative TEM images
of the fringes are shown in inset (Fig. 3(e) and (g)). Although
there is good correlation between average particle size (calcu-
lated by XRD) and average pore size distribution (as obtained by
N2 adsorption–desorption isotherm) for as-synthesized materials
except for samples IH-1 and IO-6 (entries 1 and 6) which is possi-
bly as a result of aggregation of nano-sized particles as explained
earlier in Section 3.1.4.
3.2. Catalytic studies
The epoxide ring opening of 1,2-epoxy-3-phenoxy propane 8a
with aniline 9a as a nucleophile was used as model reaction to test
the efficacy of the all the iron hydroxides/oxides synthesized in the
present study and the data are given in Table 2. In the absence of
a catalyst, only traces of ␤-amino alcohol product was obtained
in 24 h under solvent free condition at RT (entry-1). When iron
hydroxides IH-1 and IH-2 (20 mg/mmol of epoxide) were used as
catalysts, the ERO reaction gave the ring opened product 10aa in
86 and 84% yield respectively in 10 minutes. It is to be noted here
that in both the cases, the other possible regioisomer 10aaꢀ was
not detected on 1H and 13C NMR, instead ∼12% of the “bis-adduct”
11aa was clearly seen (entries 2 and 3). The formation of bis-adduct
during the course of the ERO reaction was due to the nucleophilic
3.1.5. Transmission electron microscopy (TEM) analysis
TEM image of each material such as iron hydroxides IH-1 and
IH-2, iron oxides magnetite MIO-3, hematite IO-4 (sonication prod-
uct) and IO-5, IO-6 and IO-7 (calcination product) are shown in
Fig. 3(a)–(g). The TEM images of amorphous IH-1 and IH-2 materials
showed the particle sizes between 3–10 and 8–10 nm respectively
which is also in good agreement with particle size estimated from
XRD spectra by applying Scherrer equation (Table 1, entries 1 and
2). The techniques, XRD and TEM showed similar trend in contin-
uous increment in particle size (∼20–60 nm) while moving from
MIO-3 to IO-7. TEM images all the materials showed the narrow
Table 2
Screening of catalysts for ERO reaction of aryloxy epoxide with aniline. a
Entry
Catalyst
Amount (mg)
Time (min)
Yieldb (%) (10aa)
Yieldc (%) (11aa)
1
2
3
4
5
6
7
8
None
IH-1
IH-2
MIO-3
IO-4
IO-5
IO-6
IO-7
ID-1
ID-1
00
20
20
20
20
20
20
20
20
1440
10
10
10
10
10
10
10
10
Trace
86
84
76
82
60
61
61
60
n.d.
12
12
13
12
16
17
13
20
24
9
10d
107
10
68
*The regioisomer 10aaꢀ was not detected on HPLC and 1H NMR in all entries.
a
All reactions were carried out using different catalysts (20 mg) with 1,2-epoxy-3-phenoxy propane 8a (1 mmol) as representative substrate and aniline 9a (1 mmol) as
nucleophile under solvent free condition at RT.
b
Isolated yield.
Bis-adduct was calculated by HPLC profile.
100 mol% catalyst was used.
c
d

446
A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
Fig. 3. Transmission electron microscope (TEM) images of catalyst (a) IH-1, (b) IH-2, (c) MIO-3, (d) IO-4, (e) IO-5, (f) IO-6 and (g) IO-7.
attack of the product 10aa on the epoxide 8a. In comparison,
magnetic MIO-3 with low surface hydroxide abundance gave the
product 10aa in ∼76% yield with ∼13% of bis-adduct 11aa in 10 min
(entry 4). The catalyst IO-4 (prepared by sonication method) which
essentially mixture of iron hydroxide and iron oxide gave relatively
higher product yield (82%, entry 5). Significantly, the calcined cat-
alysts IO-5, IO-6 and IO-7 were found to be less active for the
ERO reaction and gave the desired product 10aa in ∼60% yield

A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
447
Table 3
Screening of catalyst loading and solvent with catalyst IH-1 for ERO reaction. a
.
Entry
Amount (mg)
Solvent
Time (min)
Yieldb (%) (10aa)
Yieldc (%) (11aa)
1
2
3
4
10
20
30
20
20
20
20
None
None
None
DCM
Acetonitrile
Toluene
H2O
15
10
10
1440
1440
1440
1440
82
86
84
73
70
65
60
12
12
13
8
9
18
25
5
6
7d
a
All reactions were carried out using catalyst IH-1 with 1,2-epoxy-3-phenoxy propane 8a (1 mmol) and aniline 9a (1 mmol) under solvent/solvent free condition at RT.
Isolated yield.
Bis-adduct was calculated by HPLC profile.
Trace of diol observed.
b
c
d
with ∼16% bis-adduct 11aa in 10 min (entries 6–8). These observa-
higher product yield (entries 26 and 27) than branched amine 9h
(entry 28) possibly due to steric reasons. The use of heterocyclic
secondary amines, such as piperidine 9i and morpholine 9j for the
ERO reaction of 8a gave excellent product yields 96% (entries 29
and 30) in shorter time. Noticeably, with aliphatic primary amines
corresponding bis-adduct was not formed. Under this optimized
condition, ERO reaction of epoxide 8a with different nucleophiles
such as methanol 9k, ethanol 9l, water 9m and phenol 9n was
also conducted. In these experiments, unfortunately, for unknown
reasons, no epoxide ring opened product formation was observed
(entries 31–34), not even at higher temperature (70 ◦C) both under
conventional and microwave (900 W) heating (entries 35 and 36
respectively).
Next, the above optimized protocol was extended to the ERO
reaction of enantiomerically pure (S)-1-naphthyl glycidyl ether 8f
[65] with isopropyl amine 9h and 1-(2-methoxyphenyl)piperazine
9o to get potent ␤- and ␣1-blockers (S)-Propranolol and (S)-
Naftopidil respectively in high yields 86 and 92% (entries 37 and
38).
In order to check the general applicability of the catalyst IH-1,
various other epoxides, viz. cis-stilbene oxide 8g, epichlorohydrin
8h, styrene oxide 8i and 1,2-hexene oxide 8j were subjected to
ERO reaction with aniline 9a under the above optimized condi-
tions (Table 5, entries 1–4). Significantly in all these cases only
single regioisomer was obtained in excellent yield with no traces
of bis-adduct. Barring cis-stilbene oxide that reacted rather slowly
(300 min, entry 1) while ERO reaction with other epoxides was
fairly fast (20–60 min, entries 2–4). Noticeably, with epichlorohy-
drin as a substrate no chlorine substituted product was formed
under our reaction conditions (entry 2).
To check whether hydrogen on the surface hydroxyl group in the
material, only makes the H-bond with substrates or it actually take
part in the reaction, the deuterated iron hydroxide, Fe(OD)3, ID-1
was used as catalyst. To rule out any ambiguity, the catalyst (ID-1)
loading of 18.7 and 100 mol% was used for the ERO of 1,2-epoxy-3-
phenoxy propane 8a with aniline 9a which gave the product amino
alcohol in 63 and 69% yields respectively (Table 2, entries 9 and
10). Contrary to our expectations, the 1H NMR of the reaction mix-
ture using catalyst ID-1 showed no sign of deuterium exchange
between the product hydroxyl group with deuteroxyl group on cat-
alyst. A similar observation was also reported by Song et al. [56,57].
Although, it cannot be stated in clear term a possible reason for this
behavior lies in lower Brønsted acidity (pKa = ∼6.6) of iron hydrox-
ide with low H/D mobility under solvent free reaction condition
tions clearly indicate the possibility of interfacial hydrogen bonding
between the surface OH (Brønsted acidity) on iron hydroxide cat-
alysts and oxygen atom of the epoxide ring at the solid–liquid
interface [56,57]. Nevertheless, involvement of Lewis acidic sites
in the ERO reaction cannot be entirely ruled out as even calcined
samples showed fairly good catalytic activity. In fact we observed
that catalysts with higher surface OH population (as determined
by IR and PXRD) showed higher catalytic activity and follows the
catalytic activity order of IH-1 = IH-2 > IO-4 = MIO-3 > IO-5/IO-6/IO-
7 (Table 2, entries 2–8). It is worth mentioning here that in none of
our catalytic runs we observed the presence of diol, thereby ruling
out the possibility of involvement of free/adsorbed water molecules
during ERO reaction.
Due to the relatively better performance of the catalyst IH-1,
it was taken forward for the optimization of reaction parameters
(Table 3).
We studied 10, 20 and 30 mg catalyst (IH-1) loadings per 1 mmol
of aryloxy epoxide 8a in the ERO reaction with aniline 9a (entries
1–3) and found that 20 mg (∼18.7 mol%) catalyst loading is opti-
mum under the solvent free reaction condition at RT (entry 2).
The use of different solvents (entries 4–6) for this reaction was
found to be counterproductive in terms of drastic increase in the
reaction time to attain moderate product yields (∼70%). A possi-
ble explanation for this observation is the masking or competitive
binding of solvent molecules with the catalytically active sites. Sim-
ilar trend was also observed with water as a solvent (entry 7, 60%
yield), besides the reaction mixture also showed the presence of
trace amount of diol and higher bis-adduct 11aa formation. There-
fore, solvent free condition with 20 mg of catalyst IH-1 per mmol
of substrate loading would be the best option for ERO reaction.
The above optimized reaction protocol was then extended to the
ERO of different aryloxy epoxides, viz. glycidyl 2-methyl phenyl
ether 8b, glycidyl 4-tert butyl phenyl ether 8c, glycidyl-4-chloro
phenyl ether 8d, benzyl glycidyl ether 8e with aniline 9a and sub-
stituted anilines such as 4-methyl aniline 9b, 4-methoxy aniline
9c, 4-chloro aniline 9d and 2-methoxy aniline 9e. The results are
summarized in Table 4 (entries 1–25). In most of the cases, catalyst
IH-1 was proved to be highly efficient and the reaction proceeded
smoothly to afford the desired product ␤-amino alcohol in high
isolated yield (80–90%) within short reaction time (10–20 min).
Further, the ring opening reactions of 8a with aliphatic primary
amines was also conducted. Although the reaction was found to be
sluggish (360 min.), linear primary amines 9f and 9g tend to give

448
A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
Table 4
ERO reaction of various aryloxy epoxides with different anilines using IH-1 as catalyst. a
.
Entry
1
Epoxide
Nucleophiles
Time (min)
10
Yieldb (%) (10)
Aniline 9a
86
2
3
4
5
4-Me-aniline 9b
4-MeO-aniline 9c
4-Cl-aniline 9d
10
15
10
15
89
86
87
80
8a
2-MeO-aniline 9e
6
Aniline 9a
10
84
7
8
9
4-Me-aniline 9b
4-MeO-aniline 9c
4-Cl-aniline 9d
15
15
12
88
85
82
10
11
8b
8c
2-MeO-aniline 9e
Aniline 9a
15
15
82
88
12
13
14
4-Me-aniline 9b
4-MeO-aniline 9c
4-Cl-aniline 9d
15
15
20
86
90
86
15
16
2-MeO-aniline 9e
Aniline 9a
20
10
85
90
17
18
19
20
4-Me-aniline 9b
4-MeO-aniline 9c
4-Cl-aniline 9d
15
12
10
15
90
89
86
87
8d
8e
2-MeO-aniline 9e
21
22
23
24
25
Aniline 9a
10
15
12
10
15
88
86
88
84
85
4-Me-aniline 9b
4-MeO-aniline 9c
4-Cl-aniline 9d
2-MeO-aniline 9e
26
Propan-1-amine 9f
360
70
27
28
29
30
Hexane-1-amine 9g
Propan-2-amine 9h
Piperidine 9i
360
360
180
150
95
54
96
96
8a
8a
Morpholine 9j
31
32
33
Methanol 9k
Ethanol 9l
Water 9m
Phenol 9n
Phenol 9n
Phenol 9n
1440
1440
1440
1440
1440
30
00
00
00
00
00
00
34
35c
36d
37
9h
360
86(S)-Propranolol

A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
449
Table 4 (Continued)
Entry
Epoxide
Nucleophiles
Time (min)
Yieldb (%) (10)
38e
8f
9o
360
92(S)-Naftopidil
a
All reactions were carried out using IH-1 (20 mg) as catalyst with various aryoxy epoxides 8a–f (1 mmol) and different nucleophiles 9a–o (1 mmol) under solvent free
condition at RT.
b
Isolated yield.
c
70 ◦C.
d
e
Micro-wave 900 W.
Reaction was performed in 0.5 mL DCM.
Table 5
ERO reaction of different epoxides with aniline as nucleophile using IH-1 as catalyst.a
.
Entry
1
Substrate
Time (min)
300
Yieldb (10) (%)
8g
8h
90
2
3
20
45
60
88
92
90
Fig. 5. Recycling data of ERO reaction of aryloxy epoxide (8a, 1 mmol) with aniline
(9a, 1 mmol) using IH-1 (20 mg) as a catalyst under solvent free condition at RT.
8i
8j
ability of ERO reaction. Hence, the plausible reaction mechanism
considering the role of both Lewis and Brønsted acid aspects of
iron hydroxide as a catalyst for ERO reaction with amine is shown
in Fig. 4.
Finally we checked catalyst reusability and for this iron hydrox-
ide (IH-1) was used as catalyst in the ERO of 1,2-epoxy-3-phenoxy
propane 8a with aniline 9a as model reaction under the optimized
reaction condition (Fig. 5). The catalyst showed no sign of dete-
rioration over eight reuse experiments. After each catalytic run
the catalyst was separated from the product by centrifugation. The
recovered catalyst was washed with methanol (3 × 2 mL) and dried
at 100 ◦C for 2 h before it is applied to next catalytic run.
4
a
All reactions were carried out using catalyst IH-1 (20 mg) with various epoxides
(1 mmol) and aniline 9a (1 mmol) under solvent free condition at RT.
b
Isolated yield.
and surface hydroxyl groups of iron hydroxide are involved only in
making interfacial hydrogen bonds with the O-atom of the organic
molecules at solid-liquid interface. Notwithstanding these experi-
ments, the experimental results as given Table 2 (entries 9 and 10)
and associated statements conclusively suggest a synergetic role of
surface hydroxyl groups on the catalyst in enhancing the catalytic
4. Conclusion
Iron hydroxides and oxides were prepared by simple precipita-
tion and calcination methods using inexpensive iron sources and
used as catalysts in the epoxide ring opening reaction with var-
ious amines under solvent free condition. Among magnetic and
non-magnetic materials used in the present study, Fe(OH)3 IH-
1 was found to be highly efficient, stable and reusable catalyst
and was effectively used for the preparation of potent ␤-blocker
(S)-Propranolol and a selective ␣1-blocker (S)-Naftopidil in high
yields in 6 h at RT. The Lewis acidity of the catalyst plays significant
role in catalysis; however, Brønsted acidity enhances the rate and
yield of the ERO reaction by making the interfacial hydrogen bonds
between the substrates and catalyst. Further investigations to sur-
vey the scope and limitation of this system as well as to apply it to
other reactions are in progress.
H
R1
N
H
R
O
O
Br
Ønsted acid
catalyzed
H
O
NH-R1
OH
H
Fe
O
O
H
O
R
H
O
R1
N
O
Lewis acid
catalyzed
Acknowledgements
R
H
The authors are thankful to DST and CSIR Network Projects on
Catalysis for financial assistance, and also the “Analytical Section” of
Fig. 4. Plausible reaction mechanisms for iron hydroxide catalyzed ERO reaction
with amine.

450
A.K. Shah et al. / Applied Catalysis A: General 469 (2014) 442–450
the Institute for providing instrumentation facilities. Arpan K. Shah
and Manish kumar are also thankful to AcSIR for Ph.D. enrollment.
[32] M.J. Bhanushali, N.S. Nandurkar, M.D. Bhor, B.M. Bhanage, Tetrahedron Letters
49 (2008) 3672–3676.
[33] J.S. Yadav, A. Ramesh Reddy, A. Venkat Narsaiah, B.V.S. Reddy, Journal of Molec-
ular Catalysis A: Chemical 261 (2007) 207–212.
Appendix A. Supplementary data
[34] Shivani, B. Pujala, A.K. Chakraborti, Journal of Organic Chemistry 72 (2007)
3713–3722.
[35] A.K. Chakraborti, S. Rudrawar, A. Kondaskar, Organic and Biomolecular Chem-
istry 2 (2004) 1277–1280.
[36] B. Sreedhar, P. Radhika, B. Neelima, N. Hebalkar, Journal of Molecular Catalysis
A: Chemical 272 (2007) 159–163.
[37] L. Saikia, J.K. Satyarthi, D. Srinivas, P. Ratnasamy, Journal of Catalysis 252 (2007)
148–160.
Supplementary material related to this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.apcata.
2013.10.003.
References
[38] A. Kumar, D. Srinivas, Journal of Catalysis 293 (2012) 126–140.
[39] M.M. Heravi, B. Baghernejad, Catalysis Letter 130 (2009) 547–550.
[40] L-j. Meng, B.V.D. Vijaykumar, H. Zuo, Z.-B. Li, G. Dupati, K. Jang, D.-S. Shin,
Tetrahedron: Asymmetry 23 (2012) 1029–1037.
[41] Y. Harrak, M.D. Pujol, Tetrahedron Letters 43 (2002) 819–822.
[42] S. Ramesh Kumar, P. Leelavathim, Journal of Molecular Catalysis A: Chemical
266 (2007) 65–68.
[43] M. Maheswara, K.S.V. Krishna Rao, J.Y. Do, Tetrahedron Letters 49 (2008)
1795–1800.
[44] R.I. Kureshy, S. Agrawal, M. Kumar, N.H. Khan, S.H.R. Abdi, H.C. Bajaj, Catalysis
Letters 134 (2010) 318–323.
[1] D.J. Ager, I. Prakash, D.R. Schaad, Chemical Reviews 96 (1996) 835–875.
[2] M. Pastor, M. Yus, Current Organic Chemistry 9 (2005) 1–29.
[3] V.A. Soloshonok, K. Izawa, Asymmetric Synthesis and Application of ␣-Amino
Acids. ACS Symposium Series, ACS, Washington, DC, 2009.
[4] A.K. Ghosh, G. Bilcer, G. Schiltz, Synthesis 15 (2001) 2203–2229.
[5] C. Clarkson, C.C. Musonda, K. Chibale, W.E. Campbell, P. Smith, Bioorganic and
Medicinal Chemistry 11 (2003) 4417–4422.
[6] C. Palomo, M. Oiarbide, A. Laso, Angewandte Chemie International Edition 44
(2005) 3881–3884.
[7] P. Barbaro, C. Bianchini, V. Sernau, Tetrahedron: Asymmetry 7 (1996) 843–850.
[8] R. Torregrosa, I.M. Pastor, M. Yus, Tetrahedron 63 (2007) 469–473.
[9] A. Robin, F. Brown, N. Bahamontes-Rosa, B. Wu, E. Beitz, J.F.J. Kun, S.L. Flitsch,
Journal of Medicinal Chemistry 50 (2007) 4243–4249.
[10] R.I. Kureshy, I. Ahmad, K. Pathak, N.H. Khan, S.H.R. Abdi, H.C. Bajaj, E. Suresh,
Research Letters in Organic Chemistry 2009 (2009), 1-5 (Article ID 109717).
[11] G. Palmisano, S. Tagliapietra, A. Barge, A. Binello, L. Boffa, G. Cravotto, Synlett
13 (2007) 2041–2044.
[12] J.S. Yadav, B.V.S. Reddy, A.K. Basak, A. Venkat Narsaiah, Tetrahedron Letters 44
(2003) 1047–1050.
[13] U. Das, B. Crousse, V. Kesavan, D. Bonnet-Delpon, J.-P. Bégué, Journal of Organic
Chemistry 65 (2000) 6749–6751.
[14] N. Azizi, M.R. Saidi, Organic Letters 7 (2005) 3649–3651.
[15] S. Bonollo, D. Lanari, L. Vaccaro, European Journal of Organic Chemistry 2011
(2011) 2587–2598.
[16] M. Hosseini-Sarvari, H. Sharghi, Journal of the Iranian Chemical Society 5 (2008)
384–393.
[17] S. Singhal, S.L. Jain, B. Sain, Synthetic Communications 41 (2011) 1829–1837.
[18] A.Z. Halimehjani, H. Gholami, M.R. Saidi, Green Chemistry Letters and Reviews
5 (2012) 1–5.
[19] V.T. Kamble, N.S. Joshi, Green Chemistry Letters and Reviews 3 (2010) 275–281.
[20] K. Surendra, N.S. Krishnaveni, K.R. Rao, Synlett 3 (2005) 506–510.
[21] N. Tan, S. Yin, Y. Li, R. Qiu, Z. Meng, X. Song, S. Luo, C.-T. Au, W.-Y. Wong, Journal
of Organometallic Chemistry 696 (2011) 1579–1583.
[22] M.M. Khodaei, A.R. Khosropour, K. Ghozati, Tetrahedron Letters 45 (2004)
3525–3529.
[23] G. Sekar, V.K. Singh, Journal of Organic Chemistry 64 (1999) 287–289.
[24] Y. Li, Y. Tan, E. Herdtweck, M. Cokoja, F.E. Kühn, Applied Catalysis A: General
384 (2010) 171–176.
[25] D. Bradley, G. Williams, M. Lawton, Tetrahedron Letters 47 (2006) 6557–6560.
[26] D. Bradley, G. Williams, A. Cullen, Journal of Organic Chemistry 74 (2009)
9509–9512.
[45] R.I. Kureshy, S. Singh, N.H. Khan, S.H.R. Abdi, E. Suresh, R.V. Jasra, Journal of
Molecular Catalysis A: Chemical 264 (2007) 162–169.
[46] M.W.C. Robinson, A.M. Davies, I. Mabbett, T.E. Davies, D.C. Apperley, S.H. Taylor,
A.E. Graham, Journal of Molecular Catalysis A: Chemical 329 (2010) 57–63.
[47] R. Chakravarti, H. Oveisi, P. Kalita, R.R. Pal, S.B. Halligudi, M.L. Kantam, A. Vinu,
Microporous and Mesoporous Materials 123 (2009) 338–344.
[48] M.W.C. Robinson, D.A. Timms, S.M. Williams, A.E. Graham, Tetrahedron Letters
48 (2007) 6249–6251.
[49] A.K. Chakraborti, A. Kondaskar, S. Rudrawar, Tetrahedron 60 (2004) 9085–9091.
[50] B.M. Reddy, M.K. Patil, B.T. Reddy, S.-E. Park, Catalysis Communications 9 (2008)
950–954.
[51] C.X. Hernández-Reyes, D. Angeles-Beltrán, L. Lomas-Romero, E. González-
Zamora, R. Gavin˜o, J. Cárdenas, J.A. Morales-Serna, G.E. Negrón-Silva, Molecules
17 (2012) 3359–3369.
[52] X. Chen, H. Wu, S. Wang, S. Huang, Synthetic Communications 42 (2012)
2440–2452.
[53] N. Azizi, M.R. Saidi, Tetrahedron 63 (2007) 888–891.
[54] N. Aramesh, B. Yadollahi, V. Mirkhani, Inorganic Chemistry Communications
28 (2013) 37–40.
[55] M. Vijender, P. Kishore, P. Narender, B. Satyanarayana, Journal of Molecular
Catalysis A: Chemical 266 (2007) 290–293.
[56] F. Niu, C.-C. Liu, Z.-M. Cui, J. Zhai, L. Jianga, W.-G. Song, Chemical Communication
(2008) 2803–2805.
[57] F. Niu, L. Zhang, S.-Z. Luo, W.-G. Song, Chemical Communication 46 (2010)
1109–1111.
[58] R.I. Kureshy, K. Jeya Prathap, S. Agrawal, M. Kumar, N.H. Khan, S.H.R. Abdi, H.C.
Bajaj, European Journal of Organic Chemistry 2009 (2009) 2863–2871.
[59] M.M. Mojtahedi, M.S. Abaee, A. Rajabi, P. Mahmoodi, S. Bagherpoor, Journal of
Molecular Catalysis A: Chemical 361–362 (2012) 68–71.
[60] B. Voigt, A. Gobler, Crystal Research and Technology 21 (1986) 1177–1183.
[61] H.A. Khalaf, Monatshefte für Chemie 140 (2009) 669–674.
[62] G. Nauer, P. Strecha, N. Brinda-Konopik, G. Liptay, Journal of Thermal Analysis
30 (1985) 813–830.
[27] E. Ertürk, A.S. Demir, Arkivoc ii (2008) 160–171.
[63] T. Li, Y. Deng, X. Song, Z. Jin, Y. Zhang, Bulletin of the Korean Chemical Society
24 (2003) 957–960.
[64] H. Liu, Y. Weia, P. Li, Y. Zhang, Y. Sun, Materials Chemistry and Physics 102
[28] J. Augé, F. Leroy, Tetrahedron Letters 37 (1996) 7715–7716.
[29] A. Venkat Narsaiah, S.B. Wadavrao, A. Ramesh Reddy, J.S. Yadav, Synthesis 3
(2011) 485–489.
[30] A.A. Jafari, Moradgholi, Synthetic Communications 41 (2011) 594–602.
[31] B. Pujala, S. Rana, A.K. Chakraborti, Journal of Organic Chemistry 76 (2011)
8768–8780.
(2007) 1–6.
[65] S. Jovanovic´, M. Vico-Stevenovic´, D. Ugljesˇic´-Kilibarda, D. Popadic´, S. Simic´, D.
Dzˇeletovic´, Journal of Serbian Chemical Society 71 (2006) 867–877.