Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides

Article abstract of DOI:10.1039/c7gc02627g

The sustainable introduction of nitrogen moieties in the form of nitrile or amide groups in functionalized molecules is of fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report the nanoscale iron oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in the presence of 1 bar O₂ or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds to synthesise functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Additionally, applying this iron-based protocol, primary amides have also been prepared in a water medium.

Full text of DOI:10.1039/c7gc02627g

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Stable and Reusable Nanoscale Fe2O3-catalyzed Aerobic Oxidation
Process for Selective Synthesis of Nitriles and Primary Amides
Kathiravan Murugesana, Thirusangumurugan Senthamaraia, Manzar Sohailb, Muhammad Sharifb,
Narayana V. Kalevarua, and Rajenahally V. Jagadeesha*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Sustainable introduction of nitrogen moiety in the form of nitrile or amide functionality in synthetic molecules is of
fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural
products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting
materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report nanoscale iron
oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in
presence of 1 bar O2 or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds for the
synthesis of functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Further, applying this iron-
based protocol, primary amides have also been prepared in water medium.
www.rsc.org/
1. Introduction
While simple nitriles have been prepared by industrial
o
The development of iron-catalyzed reactions for the modern ammoxidation processes under drastic conditions (>300 C in
state-of-the-art organic synthesis is an actual goal of chemical gas phase) 18, functionalized and structurally diverse ones still
research.1-2 Remarkably, more abundance, cheaper price and rely on toxic cyanation reactions.19 However, the limitations of
less toxicity of iron makes it an ideal metal for catalysis ammoxidation and drawbacks of cyanation processes inspired
applications,1-2 and can be suitable candidate for the to look for alternative sustainable routes for the synthesis of
replacement of existing precious metal-based catalysts. nitriles from suitable starting materials. In this regard, catalytic
20
20a 21
,
Compared to homogeneous iron complexes, heterogeneous oxidative conversion of alcohols
or aldehydes
using
catalysts based on nanostructured iron materials constitute ammonia represents green methodology to produce various
more practical and cost-efficient catalytic systems due to their nitriles.
ease of separation, reusability and stability.1d, 2a, 3 In order to
Complementary to alcohols are aldehydes, which represent
realize more environmentally benign synthesis, iron catalyzed easily available fine and bulk chemicals, and serve as suitable
reactions should exploit the use of green and renewable starting materials for the preparation of various chemicals
Clearly, iron- such as amines,22 carboxylic acids,23 alcohols,24 esters25 and
1c-d, 4-7
reagents under mild reaction conditions.
1c-d, 4-7
catalyzed synthesis utilizing atmospheric O2 or air
8
ammonia
and heterocycles26 as well as in C-C bond forming reactions that
demonstrating exquisite selectivity constitutes enabled the preparation of array of interesting molecules24a-c,
more sustainable process that is crucial for the advancement 27. Particularly, recently reported Fe-
and Cu-23b catalyzed
23a
of academic research and industrial production. Therefore, the oxidative conversions of aldehydes to carboxylic acids are
development of iron catalyzed aerobic oxidation reactions are quite interesting. Regarding the synthesis of nitriles from
highly desired for the production of valuable chemicals, aldehydes, few methods have been reported using different
especially nitriles and amides. Noteworthy, nitriles and amides nitrogen sources such as hexamethyldisilazane (HMDS),28
represent major building blocks and central intermediates for hydroxylamine29, NaN3 30, and K3[Fe(CN)6]31 and ammonia,20a,
9-13
21,32
advanced chemicals, life science molecules and materials
.
as nitrogen sources using different catalysts.
Further, these structural motifs have been found as the Unfortunately, all of these reagents either toxic or produce
integral parts of bio-active molecules and natural products.13-17 stoichiometric amount of wastes. Therefore, ammonia is
considered to be the green and abundant nitrogen source for
the preparation of nitrogen containing compounds. With
a.Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str.
regards to the utilization of ammonia for the synthesis of
29a, 18059 Rostock, Germany.
b.The Center of Research Excellence in Nanotechnology (CENT) and Department of
Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261,
Saudi Arabia.
nitriles from aldehydes, various oxidants and catalysts have
already been disclosed.20a,b,21,34 Among these, iodine and
iodine containing compounds were commonly employed.32
However these reagents are not only sensitive and hazardous,
but also produce significant amount of wastes. Hence these
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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reagents are not suitable from green chemistry perspective.
Next, Ru-based catalysts were used at drastic conditions (130
2. Results and discussion
2.1 Preparation of nanoscale Fe2O3-based catalysts
(Fe2O3-N/C).
21
33a
oC, 6 bar air).20a,b In addition to ruthenium, Cu, Ni,
33b
and
Mg-Mn
based systems are also catalyzed aldehyde and
In 2013, we have developed nanoscale Fe2O3-based particles
activated by nitrogen doped graphene layers for catalysis
applications (Fe2O3-N/C).2a Motivated by these materials and
based on our objective to develop iron-based sustainable
chemical processes, herein we demonstrate the synthesis of all
kinds of aromatic, heterocyclic and aliphatic nitriles as well as
primary amides starting from aldehydes and aqueous
ammonia using 1 bar of molecular oxygen or air. Notably, this
ammonia reaction to obtain nitriles. Among these,
Cu/TEMPO/bipyridin catalyst system works under mild
21a
reaction conditions (25 0C, 1 bar O2) to produce nitriles.
Even though this catalyst works under mild reaction
conditions, it is a homogeneous catalyst and cannot be
21a
recycled.
In addition, the use of NaOH additive and fewer
substrate scope have hindered its practical utility for
sustainable synthesis of nitriles.21a Furthermore, other
oxidants/catalysts such as trichloroisocyanuric acid (TCCA),34a
Fe2O3-based catalyst has been prepared (Fig. 2)
by
impregnation of in situ generated Fe(II)(1,10-
tetrabutylammonium tribromide (TBATB)34b chloramine-T
phenanthroline)3(OAc)2 complex on commercial carbon
(Vulcan XC 72R) and subsequent pyrolysis at 800 °C for 2 h in
34c
(CAT)
and ceric ammonium nitrate (CAN)34d have also been
used for the preparation of nitrile from aldehydes and
ammonia. Again these compounds led to the formation of
significant amount of wastes and hence they are not
considered as green oxidants. Nevertheless, most of these
methodologies have disadvantages regarding the use of toxic
and waste generating reagents, or poor selectivity and less
substrate scope for the synthesis of functionalized and
structurally diverse nitriles. Hence, more green and efficient
methodologies for the synthesis of advanced nitriles from
aldehydes using heterogeneous iron-based catalysts under
mild reaction conditions are highly required. In this regard,
herein we report the application of reusable iron oxide catalyst
for the synthesis of a variety of nitriles starting from aldehydes
and aqueous ammonia under mild reaction conditions.
Compared to previously reported catalysts (Fig. 1), our iron-
based catalyst is more advantageous and empowers the
synthesis of functionalized and structurally diverse nitriles.
Noteworthy, the synthetic utility and practical applicability of
this catalyst have been presented by performing gram-scale
synthesis and catalyst recycling. In addition to the synthesis of
nitriles, more green protocol for the preparation of amides
using iron-based catalyst starting from aldehydes and
ammonia is also demonstrated in water medium.
argon atmosphere (Fe-Phen/C-800; Phen
phenanthroline).2a
=
1,10-
The detailed preparation and
characterization of this material by transmission electron
microscopy (TEM), X-ray photoelectron spectroscopy (XPS),
electron paramagnetic resonance (EPR), and Mössbauer
spectroscopy has been reported in our previously published
2a
paper. (see also supporting information) The Fe-Phen/C-800
catalyst system was characterized by the formation of
nanoscale Fe2O3 particles (2-5 and 20-80 nm), which are
surrounded by 3-5 nitrogen doped graphene layers (Fig. S1A).
In contrast to the active material, the inactive material,
Fe(OAC)2/C-800 prepared without phenanthroline ligand
contained much larger and well facetted big Fe2O3 particles of
100-800 nm size. In this case there is no formation of
graphene layer and hence these particles are not surrounded
by graphene layers.
X-ray photoelectron spectra for N1s electrons (Fig. S3A) of
Fe2O3-N/C (Fe-Phen/C-800) catalyst has been revealed that
there are three N1s peaks occur at 398.3 eV, 399.3 eV and
401.0 eV. The first two peaks are assigned to pyridinic nitrogen
and Fe-N centers respectively. The peak observed at at 401.0
eV, is assigned to nitrogen in a grapheme-like structure. The
XPS for Fe2P electrons, two peaks corresponding to Fe species
in the near-surface region were observed (Fig. S3B). The first
one (major) appeared at 712.4 eV and the second one (minor)
at 709.9 eV. The first peak is due to the presence of Fe+3
species (more likely Fe2O3) while the second one is assigned to
Fe+2 species. Fe+2 species are in minor proportion compared to
Fe+3. By XPS analysis, in Fe-Phen/C-800 catalyst both Fe+3
(major) and Fe+2 (minor) species are presented on the surface
of the material. However, the bulk composition is somewhat
different from the surface composition. In the bulk, we could
see the presence of mainly the Fe+3 species (in the form of
Fe2O3). The presence of Fe2O3 in bulk composition has
confirmed by EPR and Mössbauer spectral analysis (Figs. S4
and S5; See supporting information for more details). Based on
reactivity and detailed spectroscopic characterization of the
active (Fe-Phen/C-800) and non-active (Fe(OAc)/C-800)
catalysts, the active site of the catalyst consists mainly
nanoscale Fe2O3 particles, which are surrounded by nitrogen
species of the graphene layers. Both the nano-sized particles
I2 and I2 containing campounds
(Hazardous and waste-generation)
Ru (130 oC, 5 bar air)
(Harsh conditions)
Fe (40 oC, 1 bar O2) (This method)
CHO
CN
NH3
+
R
R
(Applies to the synthesis of all kinds of nitriles)
Cu (25 oC, 1 bar air), Ni, Mg-Mn
(Less substrate scope. Need additives )
TCCA, TBATB, CAT, CAN
(Not green oxidants)
Fig. 1. Synthesis of nitriles from aldehydes and ammonia using different
catalysts/oxidants: Comparison of our method with those of previously reported
methods.
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Carbon=Vulcan XC72R, Phen= phenanthroline, materials were pyrolyzed at 800 oC for 2h under argon,
and the Fe-N interactions are responsible for the remarkable
activity of this catalyst. Thus, the active sites appear to be Fe-
Nx centers that govern the catalytic acticities.
a
Bulk Fe2O3 obtained commercially (>96% Fe basis). Reaction conditions: Homogeneous catalysis
conditions: 0.5 mmol benzaldehyde, 300 µL aq. NH3 (28-30% NH3 basis), 0.015 mmol Fe(OAC)2, 0.045
mmol phenanthroline, 1 bar O2 (balloon), 2 mL t-amyl alcohol, 40 °C, 24 h, GC yields using 100 µL n-
hexadecane as standard. a Heterogeneous catalysis conditions: 0.5 mmol benzaldehyde, 300 µL aq.
NH3 (28-30% NH3 basis), weight of catalyst corresponds to 3 mol% Fe, 1 bar O2 (balloon), 2 mL t-amyl
alcohol, 40 °C, 24 h, GC yields using 100 µL n-hexadecane as standard.
2.3. Synthesis of structurally diverse aryl nitriles
Aryl nitriles, which are an important motifs found in a majority
of nitrile containing life science molecules, especially in central
14
nervous system CNS, cardiovascular and anti-HIV drugs
,
were obtained in good to excellent yields (Scheme 1).
Interestingly, halogenated benzonitriles, which encounter
selectivity problem by typical cyanation reactions, were
prepared in 89-97% yields (Scheme 1). The resulting
halogenated benzonitriles serve as precursors for
agrochemicals, pesticides and engineering materials. As an
example, 2, 6-dichlorobenzonitrile (DCBN) is an herbicide and a
key intermediate in the preparation of various potential
pesticides and high thermal resistant engineering plastics, was
obtained in 94% yield (Scheme 1; product 11). This particular
reaction is of high commercial significance and is also very
challenging topic in the field of heterogeneous catalysis under
gas phase conditions due to steric hindrance (i.e. due to
substitution of two deactivating chlorine atoms in ortho
positions).
Fig. 2. Preparation of nitrogen doped graphene activated nanoscale Fe2O3-
particle supported on carbon.
2.2. Reaction design for the synthesis of nitriles
Using our Fe-Phen/C-800 catalyst (Fe2O3-N/C), we started to
investigate the preparation of nitriles from suitable starting
materials using aqueous ammonia in presence of 1 bar
molecular oxygen under mild temperature (<50 0C) in
conventional apparatus (in glass vial using balloon); without
the use of any special equipment or autoclave. Under these
conditions, first we tested benzyl alcohol at 40 0C with 1 bar O2
in presence of Fe2O3-N/C-catalyst and found that no reaction
was occurred to produce desired benzonitrile. However, to our
surprise the reaction of benzaldehyde gave selectively
benzonitrile in 96% yield (Table 1, entry 6). Obviously
homogeneous catalyst systems based on iron acetate or iron
acetate/phenanthroline were found to be inactive (Table 1
entries 1-2). Similarly, the unpyrolyzed Fe-Phen@C material,
pyrolyzed simple iron acetate on carbon (Fe(OAc)2@C-800)
and bulk Fe2O3 were also not active (Table 1 entries 3-5). After
having excellent results using Fe2O3-N/C-catalyst and a set of
mild reaction conditions established, we explored the
applicability of this methodology for the preparation of nitriles
from aldehydes and aqueous ammonia. As seen from schemes
1-3, structurally diverse and functionalized aromatic,
heterocyclic and challenging aliphatic nitriles have been
synthesized from various aldehydes.
Table.1. Preparation of benzonitrile from benzaldehyde and
aqueous ammonia using iron catalysts: comparison of catalytic
activity
Entry
1a
Catalyst
Yield of benzonitrile (%)
Fe(OAC)2
<1
<1
<1
<3
<1
96
2 a
Fe(OAC)2+Phen
Fe-Phen@C
Fe(OAC)2@C-800
Bulk Fe2O3
Scheme 1. Fe2O3-N/C-catalyzed synthesis of structurally
diverse and functionalized benzonitrilesa. aReaction conditions : 0.5
mmol aldehyde, 200-300 µL aq. NH3 (28-30% NH3 basis), 30 mg catalyst (3 mol%
Fe), 1 bar O2 (balloon), 2 mL t-amyl alcohol, 40 °C, 24 h, isolated yields. bYields
were determined by GC using 100 µL n-hexadecane as standard.)
3 b
4 b
5 b
6 b
Fe-Phen@C-800
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Scheme 3. Synthesis of challenging aliphatic nitriles using Fe2O3-
N/C-catalysta. ( aReaction conditions: 0.5 mmol aldehyde, 200-300 µL aq. NH3 (28-30%
NH3 basis), 30 mg catalyst (3 mol% Fe), 1 bar O2 (balloon), 2 mL t-amyl alcohol, 40 °C,
24 h, isolated yields. bYields were determined by GC by using 100 µL n-hexadecane as
standard.)
The yield of DCBN achieved through the present study is much
higher compared to the state of the art (YDCBN = ca. 80% only).
Further, functionalized benzaldehydes underwent selective
reaction to produce challenging benzonitriles up to 97%
(Scheme 1).
2.6. Green Synthesis of primary amides
The creation of amide functionality35-37 is highly important in
chemistry, medicine and biology because it plays a major role
in the amplification and configuration of life science molecules,
peptides, proteins and as well as materials 13, 16-17. In general,
primary amides have been prepared by the reaction of
carboxylic acids or their activated derivatives such as acid
chlorides, anhydrides with ammonia. Nevertheless for the
synthesis of this important class of amides, more
environmentally benign procedures are required. In addition
to alcohols,37a,b the synthesis of primary amides from
aldehydes and ammonia was also been carried out using
2.4. Synthesis of heterocyclic nitriles
Next, cyano-substituted heterocycles and aryl nitriles bearing
heterocyclic backbones were synthesized in 84-96% yields
(Scheme 2). In general heterocyclic nitriles have been found to
be key starting materials for the preparation of various active
subunits of medicinal and biological molecules.
38b
manganese oxide,37a Rh38a KMnO4 and Iodine.38c. However,
the use of iron-based heterogeneous catalysts for the
synthesis of primary amides is obviously more advantageous.
Scheme 2. Preparation of cyano-heterocycles using Fe2O3-N/C-
a
catalyst . (aReaction conditions: 0.5 mmol aldehyde, 200-300 µL aq. NH3 (28-30%
NH3 basis), 30 mg catalyst (3 mol% Fe), 1 bar O2 (balloon), 2 mL t-amyl alcohol, 40 °C,
24 h, isolated yields. bYields were determined by GC using 100 µL n-hexadecane as
standard.)
2.5. Synthesis of challenging aliphatic nitriles
In subsequent efforts, various aliphatic aldehydes, that are
difficult to react, have been chosen as potential substrates to
produce their corresponding nitriles in good to excellent yields
(up to 96%; scheme 3). More interestingly the allylic nitriles,
important starting compounds for allylic amines, were
obtained without further oxidation of olefinic group (Scheme
3).
Scheme 4. Nanoscale Fe2O3-N/C -catalysed synthesis of amides
from aldehydes and aqueous ammoniaa. (aReaction conditions: 0.5
mmol aldehyde, 100 µL aq. NH3 (28-30% NH3 basis), 50 mg catalyst (5.0 mol%
Fe), 10 bar air 3 mL H2O, 120 °C, 24 h, isolated yields.)
After having successfully demonstrated the preparation of
important nitriles, we have further extended the potential of
Fe2O3-N/C-catalyst for direct and one-pot synthesis of primary
amides from benzaldehyde and aqueous ammonia.
Interestingly, this catalyst is also observed to be active and
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selective for the preparation of even primary amides (Scheme sustainable industrial processes. Noticeably, our Fe2O3-N@C
4). However, to achieve sufficient activity and selectivity, the catalyst is highly stable and conveniently recycled up to 5
reaction temperature and pressure had to be raised to a times without any significant loss of catalytic activity and
certain extent and also the reaction conditions need to be selectivity (Fig. 3). The recycled catalyst has been subjected to
adjusted accordingly. In water medium, we were able to ICP analysis and found that there is no leaching of iron in the
convert aldehydes into primary amides using aqueous recycled catalyst.
ammonia and air in up to 91 % yield (Scheme 4).
The reaction pathway for the formation of nitriles and
100
amides is presented in Scheme 5. In the first step, the
formation intermediate, primary imine was took place from
aledehyde and ammonia. In presence of Fe2O3-N/C-catalyst,
this unstable imine underwent oxidation to produce nitrile.
In the final step, in presence of water and ammonia the
formed nitrile was hydrolyzed to produce primary amide. The
production of amide from nitrile requires higher temperature
to proceed under forcing conditions. In order to confirm the
formation mechanism of amide, we performed the reaction of
benzonitrile in water at 120 0C in presence of aq. ammonia and
catalyst. In this case formation of benzamide in 80% yield was
observed. This result clearly evidenced that water is required
for the formation of amide from aldehyde and ammonia. Due
to the involvement of two step reaction, the obtained yields of
amides are somewhat lower than that of nitriles. In this case
the unreactive nitrile was observed as the other product.
80
60
40
20
0
1
2
3
4
5
6
Number of runs
Fig. 3. Recycling of Fe2O3-N/C-catalyst for the synthesis of
benzonitrile. (Reaction conditions: 1 mmol benzalydehyde, 60 mg catalyst (3.2
mol% Fe), 400 µL aq. NH3 (28-30% NH3 basis), 1 bar O2 (balloon), 4 mL t-amyl alcohol,
40 °C, 24 h, yields were determined by GC using n-hexadecane standard.)
Further the stability of catalyst was also tested by
performing kinetic studies (Fig. S6). The effect of ammonia
concentration, reaction time, amount of catalyst,
concentration of substrate (benzaldehyde) and pressure of O2
on the yield of benzonitrile was performed (Fig. S6).
Noticeably, the catalyst is stable and exhibited similar catalytic
activity in presence of excess of ammonia (1mL), with
prolonged reaction time and at high pressure of O2 (5 bar). As
seen from the kinetic plots (Fig. S6), on increasing the reaction
time, catalyst amount and ammonia concentration, the yeild
of benonitrile was increased and observed highest yeld for 24
h with 30mg of catalyst, in presence of 200 microl Aq.
ammonia and one bar O2.
O
CN
CHO
NH3
Fe2O3-N/C
O2
Fe2O3-N/C
H2O, NH3
NH
NH2
R
R
R
R
Scheme 5. Reaction pathway for the Fe2O3-N/C -catalyzed synthesis
of nitriles and amides from aldehydes and ammonia.
2.7. Scale up studies for gram scale synthesis
In order to demonstrate the synthetic and practical utility of
this approach using our iron-catalyzed synthetic protocol, we
further performed the gram scale (i.e. 1 to 5 g) reactions. In
the direction of scale up, a few grams of some selected
aldehydes have been converted to their corresponding nitriles
under identical reaction conditions. The yields of desired
nitriles obtained from these tests are very much comparable
and quite consistent with those obtained from 0.5 mmol
(small) scale tests (Scheme 6).
3. Experimental section
3.1. Procedure for the reparation of Fe2O3-N/C (Fe-Phen/C-
800) catalyst (1 g) [2a]
F
Cl
CN
F
F
Appropriate amounts of Fe(OAc)2 and 1,10-phenanthroline
corresponds to 3 wt% of Fe in 1:3 molar ratio of Fe to
phenathroline were stirred in ethanol for 30 minutes at room
temperature. Then, carbon powder (VULCAN® XC72R, Cabot
Corporation Prod. Code XVC72R; CAS No. 1333-86-4) was
added and the whole reaction mixture was stirred at 60 °C for
12-15 hours. The reaction mixture was cooled to room
temperature and the ethanol was removed in vacuo. The solid
material thus obtained was dried at 60 °C for 12 hours, after
which it was grinded to a fine powder. Then, the powdered
material was pyrolyzed at 800 °C for 2 hours under an argon
atmosphere and then cooled to room temperature.
CN
CN
Cl
CN
Br
CN
CN
O
O
O
O
NO2
1: 93%
2 g scale
F
F
33: 93%
(5 g scale)
4: 92%
(2 g scale)
11: 93%
34: 88%
(5 g scale)
F
(2 g scale)
9: 92%
(1 g scale)
Scheme 6. Demonstrating gram scale reactions for synthesis of
some selected nitriles over Fe2O3-N/C catalyst. (Reaction conditions: 2-5 g
substrate, weight of catalyst corresponds to 3 mol% Fe, 200 µL Aq. NH3 for every 0.5
mmol substrate, 40 0C, 10-50 mL t-amyl alcohol, 1 bar O2 (balloon), 24-30 h. Isolated
yields.)
2.8. Stability and Recycling of Fe2O3-N/C-catalyst.
In general, stability, recycling and reusability features of any
catalyst are very important features for the advancement of
Elemental analysis of Fe2O3-N/C (pyrolyzed Fe-phen/C at 800
oC) (Wt%): C = 91.1, H = 0.19, N = 2.69, Fe = 2.95.
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3.2. General procedure for the preparation of nitriles
solvent from the filtrate containing reaction products was
The 8 mL oven dried glass vial was charged with magnetic removed in vacuo. The corresponding nitrile was purified by
stirrer bar and 0.5 mmol corresponding aldehyde and then 2 column chromatography (silica; n-hexane-ethyl acetate
mL t-amyl alcohol was added. Next, 30 mg Fe2O3-N/C (i.e. Fe- mixture). All products were analyzed by GC-MS and NMR
Phen/C-800) catalyst (3 mol% Fe) was added followed the by analysis.
the addition of 200-300 µL aq. NH3 (28-30% NH3 basis). The
glass vial was fitted with septum and screw cap. Then 1 bar O2 3.5. Procedure for catalyst recycling
containing balloon was connected to the reaction vial though The recycling of the catalyst was carried out for the synthesis
needle and then the reaction was allowed to proceed for 24 of benzonitrile under the same procedure given in the section
o
hrs at 40 C under continuous stirring. After completion of the 3.2 under reaction conditions: 1 mmol benzalydehyde, 60 mg
reaction, the reaction vial was cooled down to room Fe2O3-N/C (Fe-Phen/C-800) (3% Fe), 400 µL aq. NH3, 1 bar O2,
o
temperature and the excess O2 was gradually discharged. 4mL t-amyl alcohol, 40 C, 24 hrs, yields were determined by
Then, the catalyst was filtered-off, and washed with ethyl GC using 100 µL n-hexadecane standard. In each run, after the
acetate. The solvent from the filtrate containing the reaction reaction the catalyst was separated by centrifugation, washed
products and unreacted substrate (if any?) was removed in thoroughly with ethyl acetate and dried by vacuum. Then, the
vacuo and the target nitrile was purified by column dried catalyst was used further, without any purification or re-
chromatography. In case of yields determined by GC, 100 µL n- activation. The recycled catalyst and centrifugate containing
hexadecane was added to the reaction vial containing reaction products were subjected to ICP analysis. This analysis
products and diluted with ethyl acetate. Then, filtered through showed that the content of Fe in recycled catalysts has not
plug of silica and the filtrate containing products was analysed been decreased (2.94) and also not detected in centrifuate.
by GC (HP-6890, column HP-5 (30 m x 250 mm x 0.25 μm)
equipped with FID. Conversion and yields were determined on Conclusions
the basis of GC area counts using pre-calibrations. All products In conclusion, we have demonstrated green methodology for
were analyzed by GC, GC-MS and NMR analysis.
preparation nitriles and primary amides starting from easily
accessible various aldehydes by make use of combination of
earth abundant Fe-based nano-catalyst and green reagents
3.3. General procedure for the preparation of amides
A magnetic stirrer bar and the corresponding aldehydes were such as atmospheric O2 or air and inexpensive aqueous
transferred to 8 mL glass vial and then the 3 mL H2O was ammonia. Under operationally simple and mild reaction
added. Later on, 50 mg Fe2O3-N/C (i.e. Fe-Phen/C-800) catalyst conditions, this iron-based catalyst is highly reactive and
(5 mol% Fe) was added followed by the addition of 100 µL aq. selective for the synthesis of series of functionalized and
NH3. Then, the vial was fitted with septum, cap and needle. structurally diverse aromatic, heterocyclic and aliphatic
The reaction vials (i.e. 8 vials in each test) were placed into a nitriles. Further, this aerobic green oxidative methodology has
300 mL autoclave (PARR Instrument Company, USA) and then been applied for the preparation of primary amides. Moreover
autoclave was pressurized with 10 bar of air. The autoclave synthetic utility and and practical applicability of this
was placed into an aluminium block and the temperature of methodology were demonstrated by up scaling the reactions
the aluminium block was set to measure 120 oC inside the to gram scales (1-5 g scale) and recycling of the catalyst.
autoclave and reactions were allowed to progress under
o
continuous stirring for required time at 120 C. In this set-up
Conflicts of interest
the temperature of the aluminium block was set more than
o
o
0
120 C (130-140 C) in ordered to attain exactly 120 C inside
the autoclave). After completion of the reaction, the excess air
remained in the autoclave was slowly depressurized and then
the samples were removed from the autoclave. Afterwards,
the catalyst was filtered-off, washed with methanol. The
solvent from the filtrate containing the reaction products was
removed in vacuo and the corresponding amide was purified
by column chromatography. All products were analyzed by
GC-MS and NMR analysis.
There are no conflicts to declare.
Acknowledgements
We thank Prof. Matthias Beller, the Director of Leibniz
Institute for Catalysis for his helpful discussions. The European
Research Council for financial support and the State of
Mecklenburg-Vorpommern for general support are gratefully
acknowledged. We also thank analytical staff of LIKAT for their
excellent service.
3.4. Procedure for the gram scale reactions
The reactions were performed similar to the procedure
mentioned in section 3.2 in 100 or 300 mL glass fitted
autoclave with the conditions, 2-5 g aldehyde, corresponds to
3 mol% Fe, 200 µL Aq. NH3 for every 0.5 mmol substrate, 40
oC, 10-50 mL t-amyl alcohol, 24-30 h. After completion of the
reaction, the autoclave was cooled to room temperature and
remaining air was discharged. The catalyst from the reaction
mixture was filtered off and washed with ethyl acetate. The
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