Superparamagnetic Fe(OH)3@Fe3O4 nanoparticles: An efficient and recoverable catalyst for tandem oxidative amidation of alcohols with amine hydrochloride salts

Article abstract of DOI:10.1021/co5001844

Magnetic Fe(OH)₃@Fe₃O₄ nanoparticles were successfully prepared and characterized. This magnetic nanocomposite was employed as an efficient, reusable, and environmentally benign heterogeneous catalyst for the direct amidation of alcohols with amine hydrochloride salts. Several derivatives of primary, secondary and tertiary amides were synthesized in moderate to good yields in the presence of this catalytic system. The catalyst was successfully recycled and reused up to six times without significant loss of its catalytic activity.

Full text of DOI:10.1021/co5001844

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Article
Superparamagnetic Fe(OH)3@Fe3O4 nanoparticles: An
efficient and recoverable catalyst for tandem oxidative
amidation of alcohols with amine hydrochloride salts
Marzban Arefi, dariush saberi, Meghdad Karimi, and Akbar Heydari
ACS Comb. Sci., Just Accepted Manuscript • DOI: 10.1021/co5001844 • Publication Date (Web): 06 May 2015
Downloaded from http://pubs.acs.org on May 12, 2015
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Superparamagnetic Fe(OH)3@Fe3O4 nanoparticles:
An efficient and recoverable catalyst for tandem
oxidative amidation of alcohols with amine
hydrochloride salts
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Marzban Arefi, † Dariush Saberi, ‡ Meghdad Karimi, † and Akbar Heydari, †*
† Chemistry Department, Tarbiat Modares University, P.O. Box 14155ꢀ4838 Tehran, Iran, Fax:
(+98)ꢀ21ꢀ 82883455; phone: (+98)ꢀ21ꢀ82883444; Email: heydar_a@modares.ac.ir
‡ Fisheries and Aquaculture Department, College of Agriculture and Natural Resources, Persian
Gulf University, Bushehr 75169, Iran
KEYWORDS Oxidative amidation, Tandem oxidation, Magnetic nanoparticles, Iron oxide,
Heterogeneous catalyst
ABSTRACT
Magnetic Fe(OH)3@Fe3O4 nanoparticles were successfully prepared and characterized. This
magnetic nanocomposite was employed as an efficient, reusable and environmentally benign
heterogeneous catalyst for the direct amidation of alcohols with amine hydrochloride salts.
Several derivatives of primary, secondary and tertiary amides were synthesized in moderate to
good yields in the presence of this catalytic system. The catalyst was successfully recycled and
reused up to six times without significant loss of its catalytic activity.
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INTRODUCTION
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Amide bond formation is one of the most important and often used reactions in the synthesis of
natural products, polymers, pharmaceuticals, and fine chemicals.1 Owing to the importance of
the amide functionality in biological systems and pharmaceutical chemistry (More than 25% of
available drugs contain an amide unit.2) the development of an efficient and practical protocol
for the amide bond formation remains a great challenge in organic chemistry. Traditionally,
amides are synthesized by the reaction of an amine with a carboxylic acid (or their derivatives)
or by using a coupling reagent.3 These methodologies are generally expensive and produce a
significant amount of chemical waste.4 However these traditional methods suffer from poor
atomꢀefficiency and/or the use of highly hazardous reagents. To circumvent these problems,
another alternative amide formation protocols have been explored. These includes, the
Staudinger reaction,5 the Schmidt reaction,6 the Beckmann rearrangement,7 dehydrogenative
amidation of alcohols,8 hydroamidation of alkynes,9 amino carbonylation of haloarenes,10 direct
amide synthesis from alcohols with amines or nitroarenes,8c, 11 transamidation of primary
amides12 and oxidative amidation of aldehydes.13 Although significant achievements were made,
most of the strategies mentioned above have not been applied in industry owing to drawbacks
such as the use of expensive transition metals and harsh reaction conditions. Among the amide
formation protocols, the tandem oxidative amidation of alcohols with amine salts has received
sustained attention over the past few years. These methods require the use of transition metals,
such as copper,14 zinc,15 ruthenium,8a, 11b, 16 rhodium17 and iridium18 or heterogeneous catalysts,
such as Au/TiO2 system,19 Au/DNA nanohybrids,8b and aluminaꢀsupported silver clusters.20
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Iron is abundant, inexpensive, safe, and environmentally benign. On the other hand, a variety of
iron salts as well as complexes are commercially available. So to compete with these methods
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involving expensive metals, studies on ironꢀcatalyzed formation of amides from aldehydes or
alcohols have been paid more attention in this area. In this context, Gaspa et al. reported the
baseꢀfree ironꢀcatalyzed oxidative amidation of alcohols with Nꢀchloroamines, generated from
toxic and non atomꢀeconomic Nꢀchlorosuccinimide.21 Recently, Ghosh et al. reported a tandem
oxidative amidation of benzyl alcohols with amine salts using Fe(NO3)3ꢀ(2,2,6,6ꢀ
Tetramethylpiperidinꢀ1ꢀyl)oxyl as catalyst, molecular oxygen and tertꢀbutyl hydroperoxide as the
oxidants.22 Other iron salts such as FeCl223 and FeSO4.7H2O24 have also been used for synthesis
of amides from aldehydes and amine hydrochloride salts. Although, these ironꢀcatalytic systems,
for the preparation of amides, promote the drawbacks existing with the other transition metal
catalytic systems, the separation of the desired product and the catalyst from the reaction mixture
can be challenging in these homogeneous catalytic methodologies.
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In recent years, magnetic nanoparticlesꢀsupported catalysts have been successfully deployed in a
variety of important organic transformations.25 Because they are highly stable and they can be
separated from the reaction mixture by using an external magnet for further using. In
continuation of our efforts in using magnetic nanoparticles as a catalyst support in organic
reactions26 herein we describe an inexpensive, magnetically reusable and environmentally
friendly catalytic system (Fe(OH)3@Fe3O4) for the direct oxidative amidation of alcohols with
amine hydrochloride salts.
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RESULTS AND DISCUSSION
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As can be seen in Scheme 1, our catalytic system was prepared through a simple pathway (for
details see experimental section).
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Scheme 1. Preparation of magnetic Fe(OH)3@Fe3O4 nanoparticles.
The prepared catalyst was characterized using some instrumental techniques such as XRD, SEM,
TEM, TGA and VSM. The XRD pattern of this catalyst is shown in Figure 1. In particular, seven
characteristic peaks at 2θ equal 21.5°, 35.4°, 41.7°, 50.9°, 63.7°, 68.0° and 75.1°, which
correspond to the Miller indices values {h k l} of {111}, {220}, {311}, {400}, {422}, {511} and
{440} respectively. The XRD pattern resembles that of Fe3O4 nanoparticles and no signal is
observed from the Fe(OH)3 phase, indicating that the Fe(OH)3 compound is amorphous.
Nanoparticles morphology was evaluated by SEM (Figure 2) and TEM (Figure 3) images. Coreꢀ
shell structure and spherical in shape with a smooth surface morphology of the particles are
clearly seen in these images. On the other hand, these images confirm that the particle size is
below 40 nm. TGA recorded under nitrogen atmosphere for Fe3O4 (Figure 4(A)) and
Fe(OH)3@Fe3O4 MNPs (Figure 4(B)) determining this catalyst consisting 9.4 wt% of Fe(OH)3
and 90.6 wt% of Fe3O4 (see Supporting Information (SI)). The magnetic feature of the catalyst
was confirmed by vibrating sample magnetometry (VSM). Magnetizing (emu/g) as a function of
applied field (Oe) is depicted in Figure 5. The magnetization curve demonstrate that these
Fe(OH)3@Fe3O4 nanoparticles (Possessed magnetic saturation (Ms) about 40.0 emu/g) have
superparamagnetic properties which accounts for easy recovery of this catalyst.
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Figure 1: XRD pattern of Fe3O4 and Fe(OH)3@Fe3O4. Figure 2: SEM image of the catalyst.
Figure 3: TEM image of the catalyst.
Figure 4: TGA results of Fe3O4 and Fe(OH)3@Fe3O4.
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Figure 5: Magnetization curve of Fe3O4 and the catalyst.
The catalytic activity of Fe(OH)3@Fe3O4 MNPs was tested in tandem oxidative amidation of
alcohols with amine hydrochloride salts. Initially, the reaction of benzyl alcohol with
benzylamine hydrochloride salt was tested as the model reaction under the following conditions:
benzyl alcohol 1{1} (0.5 mmol, 1 equiv.), benzyl amine hydrochloride salt 2{5} (0.75 mmol, 1.5
equiv.), tꢀBuOOH (3.0 equiv.), CaCO3 (1.5 equiv.), CH3CN (1.0 mL), under Ar atmosphere at 25
oC. Under these conditions, after six hours of reaction time, the corresponding product, Nꢀ
benzylbenzamide 3{1,5}, was formed in just 18% yield. To increase the yield of the product,
various conditions were screened that the results are summarized in Table 1.
Table 1. Optimization of the reaction conditions.a
Entry
Cat. (mg)
Oxidant
Base
Solvent
Temp.(°C) Yield (%)b
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2
3
4
5
6
20
20
20
20
20
20
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
CH3CN
CH3CN
CH3CN
CH3CN
DMF
25
60
80
100
80
80
18
40
87
51
10
35
H2O
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20
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20
ꢀꢀꢀ
30
15
20e
tꢀBuOOH
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
Cs2CO3
K2CO3
Na2CO3
CaCO3
CaCO3
CaCO3
CaCO3
DMSO
80
80
80
80
80
80
80
80
80
80
80
80
42
<10
<10
28
…
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48
59
<5
87
38
mꢀCPBAc
UHPd
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
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18
H2O2
ꢀꢀꢀꢀꢀ
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
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28
aReaction conditions: benzyl alcohol 1{1} (0.5 mmol, 1 equiv.), benzyl amine
hydrochloride salt 2{5}(0.75 mmol, 1.5 equiv.), oxidant (3 equiv.), base (1.5
equiv.), solvent (1 mL), under Ar atmosphere, 6 h. bYield of the isolated product
c
d
is based on the alcohol. metaꢀChloroperoxybenzoic acid. Urea hydrogen
peroxide. e20 mg of Fe3O4 nanoparticles were used.
As shown in Table 1, raising the reaction temperature to 80 oC resulted in a drastic improvement
o
in the yield (Table 1, entries 1ꢀ3). Increasing the temperature to 100 C caused a significant
decrease in the efficiency (Table 1, entry 4). We reasoned that the lower yields at higher
temperatures could be due to the partial over oxidation of benzyl alcohol to benzoic acid as a
side product. Screening the solvent indicated that acetonitrile is the best solvent among several
others (Table 1, entries 5ꢀ7). Subsequently, the other oxidants (H2O2, mꢀCPBA, and UHP) did
not give the results better than that of tꢀBuOOH (70 wt% in H2O) (Table 1, entries 8ꢀ10).
Meanwhile, the product was not observed in the absence of the oxidant (Table 1, entry 11). Other
experiments were carried out to investigate the effect of the base on the reaction. Our study
showed that lower yields are obtained when other bases such as Cs2CO3, K2CO3 and Na2CO3 are
employed (Table 1, entries 12ꢀ14). Further study showed that the catalyst was essential for this
transformation. In the absence of the catalyst only <5% of the amide product was formed (Table
1, entry 15). Finally, the effect of catalyst loading on efficiency was investigated and 20 mg per
0.5 mmol of benzyl alcohol was the best (Table 1, entries 16 and 17). In addition, the low
efficiency of the reaction in the presence of Fe3O4 nanoparticles showed that iron ions, coated on
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the magnetic nanoparticles, plays a major role as catalyst (Table 1, entry 18). Therefore, the
optimum conditions for this reaction were as follows: 20 mg of Fe(OH)3@Fe3O4 at 80 °C with
the respective acetonitrile as the solvent, CaCO3 as the base and tꢀBuOOH as the oxidant.
The above optimized protocol was extended to the direct oxidative amidation. So, various types
of amine hydrochloride salts and alcohols were subjected to this reaction and wide range of
primary, secondary and tertiary amides were synthesized in moderate to good yields (Table 2).
The diversity of alcohols and various amine hydrochloride salts is depicted in Figures 6 and 7.
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Figure 6: Diversity of alcohol 1{1ꢀ10}.
Figure 7: Diversity of amine hydrochloride salt 2{1ꢀ15}.
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Table 2. Amide bond formation in the presence of the Fe(OH)3@Fe3O4 catalyst.a
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Entry
1
Product
3{1,1}
3{2,1}
3{3,1}
3{5,1}
3{6,1}
3{9,1}
3{10,1}
3{1,2}
3{1,3}
3{1,4}
3{1,5}
3{1,6}
3{1,7}
3{1,8}
3{2,6}
3{3,6}
3{8,6}
3{5,6}
3{6,6}
3{9,6}
3{1,9}
3{1,11}
3{1,10}
3{1,12}
3{1,13}
3{1,14}
3{1,15}
3{7,15}
3{3,15}
3{8,15}
3{5,15}
3{9,15}
Yield (%)b
79
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aReaction conditions: alcohol 1{1ꢀ10}(0.5 mmol, 1 equiv), amine hydrochloride salt 2{1ꢀ15}
(0.75 mmol, 1.5 equiv.), CH3CN (1 mL), CaCO3 (1.5 equiv.), tꢀBuOOH (3 equiv.), catalyst (20
mg), 80 °C, under Ar atmosphere, 6 h. bIsolated yields.
Generally speaking, electron donating groups such as methoxy or methyl, on the benzyl alcohol,
give the better yields than the electron withꢀdrawing groups such as bromo, chloro, fluoro or
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nitro. Under the optimized conditions, a variety of aryl alcohols were reacted with ammonium
hydrochloride salt and the corresponding primary amides were prepared in moderate to good
yields (Table 2, entries 1ꢀ5). Heteroaromatic alcohols (e.g. furfuryl alcohol and thiophenꢀ2ꢀ
ylmethanol) were also efficiently transformed, affording the corresponding amides in moderate
yields (Table 2, entries 6, 7, 20 and 32). To further establish the general utility of this
transformation, we were encouraged to test the synthesis of secondary amides. As shown in
Table 2, secondary amides were obtained in good yields under these conditions. The reaction is
sensitive to steric hindrance as the reaction with tertꢀbutylamine hydrochloride salt gave the
corresponding amide in moderate yield (Table 2, entry 10). In the case of enantiomerically pure
amines, according to chiral HPLC data (on products in Table 2, entries 12ꢀ14 and 15ꢀ20), no
racemization was observed. The reaction is compatible with several functional groups such as
alcohol (Table 2, entry 13), ester (Table 2, entry 14) and ether (Table 2, entries 27ꢀ32).
Following the successful synthesis of primary and secondary amides with this heterogeneous
catalytic system, we were encouraged to extend the scope of this protocol to the formation of
more challenging tertiary amides. Delightfully, various salts of secondary amines carried out this
reaction and the corresponding tertiary amides obtained in good yields (Table 2, entries 21ꢀ32).
Finally, several alkyl alcohols were employed as the substrates but their corresponding amides
could not be detected.
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On the basis of the results and literature reports,13c, 27 we propose a plausible free radical
mechanism for this tandem reaction as shown in Scheme 2.
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Scheme 2: Proposed mechanism for Fe(OH)3@Fe3O4 catalyzed tandem oxidative amidation of
alcohols with amine hydrochloride salts.
Initially, the aldehyde is generated from the alcohol in the presence of tertꢀbutylperoxyl and tertꢀ
butoxyl radicals that can be formed from eq. (1) and (2) respectively (Scheme 3).28
Scheme 3. Decomposition of tꢀBuOOH assisted by an iron compound.
Subsequently, this generated aldehyde can react with the free amine, obtained from the reaction
of the amine salt with CaCO3, to form hemiaminal intermediate (III).24, 29 The tertꢀbutylperoxyl
radical, formed by the FeIIIꢀtꢀBuOOH catalytic system, abstracts hydrogen from hemiaminal (III)
to give intermediate (IV). Finally, hydrogen abstraction by tertꢀbutoxyl radical leads to formation
of the corresponding amide. Being radical reaction pathway was confirmed by adding free
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radical inhibitor, 2,4ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol to the reaction mixture and lack of product
formation.
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After establishing the activity and versatility of the Fe(OH)3@Fe3O4 catalyst for synthesis of
amides from alcohols and amine hydrochloride salts, the recyclability and reusability of it was
tested in the preparation of compound 3{1,5} under the optimized reaction conditions. After
completion of the reaction, the catalyst was removed from the reaction mixture by simple
decantation using an external magnet, washed with ethanol, dried at ambient temperature and
reused for the next cycle. The catalyst recycled up to six times in this amidation reaction without
any significant loss of its catalytic activity (Figure 8). The TEM and SEM images as well as
XRD pattern of the reused catalyst showed that the morphology and size of the catalyst after
recycling six times does not change significantly (see SI page S27).
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Figure 8: Recycling of the catalyst in the preparation of compound 3{1,5}.
CONCLUSIONS
In conclusion, we have demonstrated a novel protocol for the formation of amides in the
presence of the cheap and magnetically separable Fe(OH)3@Fe3O4 catalyst. This catalyst
exhibited high catalytic activity for amide bond formation. By using this catalytic system, all
types of amides (primary, secondary and tertiary amides) were obtained in moderate to good
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yields. Its advantages include a straightforward preparation, facile separation from the reaction
medium and recyclability up to six times.
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EXPERIMENTAL
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All experiments were carried out under argon. All chemicals and solvents were purchased from
commercial suppliers and used without further purification. FTꢀIR spectra were obtained over
the region 400–4000 cm−1 with a Nicolet IR100 FTꢀIR with spectroscopic grade KBr. The
powder Xꢀray diffraction spectrum was recorded at room temperature using a Philips XꢀPert
1710 diffractometer with Co Kα (α=1.79285 Å) voltage: 40 kV, current: 40 mA and in the range
20°–80° (2θ) with a scan speed of 0.02°/s. The morphology of catalyst was studied with scanning
electron microscopy using SEM (Philips XL 30 and Sꢀ4160) on gold coated samples. The
magnetic properties of Fe(OH)3@Fe3O4 were obtained by a vibrating magnetometer/Alternating
Gradient Force Magnetometer (VSM/AGFM, MDK Co., Iran, www.mdkꢀmagnetic.com).
Transmission electron microscopy (TEM) were carried out at 120 kV (Philips model CM120).
Thermal gravimetric analysis (TGA) was performed on a Thermal Analyzer with a heating rate
of 20 °C min−1 over a temperature range of 25–1100 °C under flowing compressed N2. 1H NMR
and 13C NMR spectra were recorded on a Bruker Avance (DPX 250 MHz and DRX 400 MHz) in
pure deuterated CDCl3 solvent with tetramethylsilane (TMS) as internal standard.
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Catalyst Preparation
The nanoꢀsized Fe(OH)3@Fe3O4 was synthesized via a modified procedure reported by Song et
al.30. The Superparamagnetic catalyst was prepared by dissolving the mixture of 4 mmol
FeCl3·6H2O and 2 mmol FeCl2·4H2O salts in 40 mL deionized water under vigorous stirring. An
ammonia solution (25% (w/w)) was added in dropꢀwise manner over 5 min to the stirring
mixture to maintain the reaction pH about 11. The resulting black dispersion was stirred
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vigorously for 1h at room temperature and then was refluxed for 1h. Fe3O4 nanoparticles were
magnetically gathered and the residue was repeatedly washed with water and ethanol.
Subsequently, asꢀprepared Fe3O4 nanoparticles and 15 mmol of FeCl3·6H2O were ultrasonically
dispersed into 10 ml of ethanol. After totally dissolution and dispersion, the nanoparticles were
separated from the ethanol solution by magnetic decantation and dried at 80 °C for 4h.
Fe(OH)3@Fe3O4 nanoparticles were obtained by dropꢀwise addition of aqueous ammonia (25%
(w/w), 5 mL) to the dried brown nanoparticles under vigorous stirring. Finally, the products of
Fe(OH)3@Fe3O4 were magnetically separated, washed with water, and dried in an oven at 373 K
overnight for further usage.
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General procedure for the direct amidation of alcohols with amine hydrochloride salts
To a mixture of catalyst (20 mg, 3.5 mol%), amine hydrochloride salt (0.75 mmol, 1.5 equiv.)
and CaCO3 (75.1 mg, 1.5 equiv.) in CH3CN (1 mL) were added alcohol (0.5 mmol, 1 equiv.),
and tꢀBuOOH (70 wt% in H2O, 3 equiv.) under argon atmosphere. The mixture was stirred at 80
°C for 6 h. After completion, the reaction mixture was allowed to cool to room temperature. It
was then diluted with EtOAc and the catalyst was separated with an external magnet and
washing twice with EtOAc. The mixture was extracted with EtOAc, the volatiles were removed
under reduced pressure, and the crude product was purified by column chromatography to afford
the desired product.
ASSOCIATED CONTENT
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13
Supporting Information. Experimental details, HꢀNMR, CꢀNMR, mass spectra and Chiral
HPLC data of selected amides. This material is available free of charge via the Internet at
http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail: heydar_a@modares.ac.ir
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Present Addresses
†Department of Chemistry, Tarbiat Modares University, P.O. Box 14155ꢀ4838 Tehran, Iran,
Fax: (+98)ꢀ21ꢀ 82883455; phone: (+98)ꢀ21ꢀ82883444.
ACKNOWLEDGMENT
We acknowledge Tarbiat Modares University for partial support of this work.
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For Table of Contents Use Only
Superparamagnetic Fe(OH)3@Fe3O4 nanoparticles: An efficient and recoverable catalyst
for tandem oxidative amidation of alcohols with amine hydrochloride salts
Marzban Arefi, † Dariush Saberi, ‡ Meghdad Karimi, † and Akbar Heydari, †*
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