Mild, efficient, and environmentally friendly synthesis of symmetrical N,N'-alkylidenebisamides under solvent-free conditions catalyzed by H7[(P2W17O61)FeIII(H2O)]

Article abstract of DOI:10.1039/c6ra01811d

A series of symmetrical N,N'-alkylidenebisamides were successfully synthesized via a one-pot three-component green and environmentally friendly condensation of aliphatic and/or aromatic aldehydes with benzamide by the mediation of 2.5 mol% H₇[(

Full text of DOI:10.1039/c6ra01811d

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Mild, efficient, and environmentally friendly synthesis of symmetrical N, N′ꢀ
alkylidenebisamides under solventꢀfree conditions catalyzed by
III
H [(P W O )Fe (H O)]
7
2
17 61
2
1,
∗
1
1
2
1
R. Tayebee , B. Maleki , F. M. Zonoz , R.M. Kakhki , T. Kunani
1
Department of Chemistry, School of Sciences, Hakim Sabzevari University, Sabzevar, 96179-76487,
Iran
2
Department of Chemistry, Faculty of Sciences, University of Gonabad, Gonabad, Iran
Abstract
A series of symmetrical N, N'ꢀalkylidenebisamides were successfully synthesized via a oneꢀpot
threeꢀcomponent green and environmentally friendly condensation of aliphatic and/or aromatic
III
aldehydes with benzamide by the mediation of 2.5 mol% H [(P W O )Fe (H O)] as
7
2
17 61
2
Lewis/Bronsted acid catalyst with good to excellent yields in moderately short reaction times.
This developed methodology is effective for diverse substituted aldehydes; thus, it constitutes a
general synthetic route for the preparation of symmetrical alkylidenebisamides. Findings
demonstrated that aromatic aldehydes containing electronꢀwithdrawing groups are more
effective than the electronꢀdonating counterparts.
III
Keywords: N, N'ꢀalkylidenebisamides, H [(P W O )Fe (H O)], catalytic, heteropolyacid,
7
2
17 61
2
multiꢀcomponent.
Introduction
The development of simple, effectual, and clean methodologies for the economic preparation
of extensively used pharmacophores by using readily available reagents under catalytic
conditions are the major challenges for chemists which attempt to improve the quality of the
1
,2
environment. Compounds bearing amide and bisamide groups are important intermediates in
organic synthesis and can be easily transformed into other pharmacological and
3
peptidomimetic materials. Bisamides are key fragments for the introduction of gemꢀ
4
,5
diaminoalkyl residues in retroꢀinverse pseudoꢀpeptide derivatives. Prevalence of amide
∗
Corresponding author: Reza Tayebee, Email: Rtayebee@hsu.ac.ir; Tel:+98ꢀ51ꢀ44410310; Fax: +98ꢀ51ꢀ44410300

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moieties in natural products and pharmacologically active compounds has established a diverse
array of synthetic approaches to these compounds; therefore, preparation of amides has been
6
,7
attracted considerable attention.
Symmetrical alkylidenebisamides are usually prepared by the direct reaction of an
aldehyde with the corresponding amide. So far, various Bronsted acids, such as
8
9
10
11
12
phosphotungstic acid, sulfamic acid, triflic acid, pꢀtoluene sulfonic acid, SiO ꢀMgCl ,
2
2
1
3
14
B(HSO ) , and silica supported polyphosphoric acid (SiO ꢀPPA) have been employed to
4
3
2
catalyze the reaction. Although, strong Bronsted acids showed high catalytic activity, but these
expensive materials are usually corrosive, toxic, and rare; hence, they are not beneficial to
industrial applications. Moreover, most of the introduced methods were not gratifying and need
certain restrictions with regards to scope and reaction conditions.
Due to the above comments, investigation of suitable Bronsted/Lewis acids as efficient
catalysts under mild conditions is required for the target transformation. During the course of
our investigations directed towards the development of environmentally friendly procedures
1
5ꢀ19
for several important organic transformations,
we introduce capability of the Wells-Dawson
III
H [(P W O )Fe (H O)] as an efficient acid catalyst for the synthesis of symmetrical N, N′ꢀ
7
2
17 61
2
alkylidenebisamides through condensation of aryl aldehydes with benzamide under solvent
°
free conditions at 80 C (Scheme 1). This catalyst could be easily prepared and reused for
several times without considerable loss of activity.
R
O
O
O
O
NH2
H
H [(P W O )Fe(H O)]
7
2
17 61
2
N
N
H
H
solventꢀfree, 80 °C
R
Scheme 1. General formulation for the preparation of symmetrical N, N'ꢀalkylidenebisamides.
2. Experimental
2.1. Materials and methods

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All starting materials and solvents were obtained from commercial sources and used as
III
20
21
22
received.
H [(P W O )Fe (H O)],
K [P W O ],
H [NaP W O ],
and
7
2
17 61
2
6
2
18 62
14
5
30 40
23
H [PMo O ], were prepared according to the reported methods. Fourier transform infrared
3
12 40
(FTꢀIR) spectra were recorded on a 8700 Shimadzu Fourier Transform spectrophotometer in
−
1
the region of 400 to 4000 cm using KBr pellets. Progress of the reactions was monitored by
thin layer chromatography (TLC). Melting points were recorded on a Bamstead electrothermal
1
type 9200 melting point apparatus. H NMR spectra were recorded on Bruker AVANCE 100
and 400 MHz instruments using TMS as internal reference. All products were identified by
2
4ꢀ26
comparison of their spectral and physical data with those previously reported.
2
.2. Synthesis of α2-K P W O .20H O
10
2
17 61
2
2
7
α2ꢀK P W O .20H O was prepared according to the literature procedure. K [αꢀ or βꢀ
10
2
17 61
2
6
P W 0 ].XH O (80 g, 1.15 mol) was dissolved in 200 ml water. Then, 20 g (200 mmol) of
2
18 62
2
potassium
hydrogen
carbonate
in
200
ml
water
was
added
while
stirring. The reaction was completed after 1 h and the white precipitate was filtered
on a coarse sintered glass frit. The solid product was dried under suction; then, reꢀdissolved in
5
00 ml hot water (95 °C). The snowꢀlike crystals appeared on cooling (after 3 h) were filtered
and dried under suction for 5 h. The final solid product (57g, 70%) was airꢀdried for 2 to 3
days.
2
.3. Preparation of K7-α2-Fe(OH )(P W O ).19H O
2
2
17 61
2
A sample containing 2.43 g (6 mmol) of Fe(NO ) .9H O was dissolved in 65 ml water, and 23
3
3
2
g (4.7 mmol) of α2ꢀK P W O .20H O was added with complete stirring. The whole
10
2
17 61
2
°
°
dissolution achieved at 30 C, and the solution was left at 6 C overnight. The appeared yellow
III
crystals were filtered and dried in air. Anal. Calcd for K [(P W O )Fe (H O)].19H O: K,
7
2
17 61
2
2
5
7
.6; P, 1.28; Fe,1.15; W, 64.4; H O, 7.42. Found: K, 5.46; P, 1.29; Fe, 1.16; W, 65.2;H O,
2 2
.41.
III
2
.4. Preparation of H [(P W O )Fe (H O)]acid catalyst
7 2 17 61 2
Wells-Dawson H [(p W O )Fe(H O)] acid catalyst (HPA) was prepared according to the
7
2
17 61
2
28
previously
reported
method.
The
iron–substituted
hetropolyanion,
K7-α2-

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Fe(OH )(P W O ).19H O was converted into the corresponding acid by passing it through a
2
2
17 61
2
column of Dowexꢀ50wꢀX8 ion exchange resin. A sample of K7ꢀα2ꢀFe(OH )(P W O ).19H O
2 2 17 61 2
(2 g) was dissolved in 50 ml water; then, the solution passed through the resin column in the
+
H form. This process was repeated for two times. Slow evaporation of the final solution gave
III
the pure H [(P W O )Fe (H O)].
7
2
17 61
2
2.5. General procedure for the preparation of N, N'-alkylidenebisamides
To a mixture of aldehyde (2 mmol) and amide (4 mmol) was added 0.01 mmol of
III
°
H [(P W O )Fe (H O)]. Then, the mixture was stirred at 80 C in an oil bath and the reaction
7
2
17 61
2
was followed by TLC analysis (nꢀhexane/ethyl acetate, 3:2). After completion of the reaction,
the mass was cooled to 25 °C, and the mixture was dissolved in boiling ethanol. The liquor
involving catalyst and starting materials was concentrated and the solid product was purified
by reꢀcrystallization in ethanol 40% as the appropriate solvent. All products were characterized
1
by IR and H NMR as obtained in the supporting information.
3. Results and Discussion
To investigate easy, oneꢀpot, and environmentally benign synthetic routes to prepare different
organic aggregates, the condensation reaction of aromatic aldehydes and benzamide was
III
studied in the presence of a catalytic amount of H [(P W O )Fe (H O)] under solvent free
7
2
17 61
2
conditions.
In order to investigate the appropriate amount of catalyst, a model reaction was carried
out by applying 0ꢀ10 mol% of HPA for the preparation of N,
phenylmethylene)dibenzamide (Table 1). First, the reaction was nonꢀproductive to give the
correlative product in the absence of heteropolyacid and led to only 20% of product after 2 h
entry 1) which indicated that presence of catalyst plays an important role in the reaction
N′ꢀ
(
(
progress. It was found that 1 mol% of catalyst attained 50% yield after 20 min (entry 2). This
observation established that the HPA catalyst exhibited high catalytic activity in the desired
transformation. Then, the reaction of benzaldehyde with benzamide was conducted in the
presence of a catalytic amount of HPA (2.5 mol%). After completion of the reaction followed
by standard workꢀup and purification, the corresponding N, N
obtained in 85% yield (Table 1, entry 3).
′ꢀalkylidenebisamide was

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As is envisaged, yield% was increased with enhancing catalyst concentration and the
maximum yield of 85% was achieved with 2.5 mol% of catalyst after 20 min. However, higher
amounts of catalyst lowered yield% to 75 at the same time (entry 5). Therefore, 2.5 mol% of
catalyst was chosen as the optimal quantity to push the reaction forward.
Table 1. Effect of catalyst amount on the condensation of benzaldehyde with benzamide.
Entry
H [(p W O )Fe(H O)]
Time (min)
Yield (%)
7
2
17 61
2
(
mol%)
1
2
3
0
1
120
20
20
50
85
2.5
20
4
5
5
20
20
77
75
10
The desired amount of H [(p W O )Fe(H O)] was added to a mixture of benzaldehyde (2
7
2
17 61
2
°
mmol) and benzamide (4 mmol). Then, the mixture was stirred at 80 C in an oil bath and the
reaction was followed by TLC. After completion of the reaction, the crude product was
purified as described in the experimental section.
Organic solvents are on the top of the list of damaging chemicals, because they are
employed in enormous amounts and are usually volatile liquids that are difficult to be stored.
Search for alternative reaction media to replace volatile, flammable, and often toxic solvents
commonly used in organic synthesis is an important objective in the development of green
chemical processes. Therefore, efficacy of the solventꢀfree condition was compared with the
solvent condition by carrying out condensation of benzaldehyde with benzamide in different
solvents (Table 2). Fortunately, the best yield was achieved under solventꢀfree case with less
reaction time and found as optimum condition. However, a considerable amount of the desired
product was formed in methanol, acetonitrile, and chloroform with 35, 30, and 20% yields,
respectively.
Table 2. Effect of different solvents on the condensation of benzaldehyde with benzamide.

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Entry
solvents
acetonitrile
nꢀhexane
Time (h)
Yield (%)
1
2
17
17
30
10
3
4
5
methanol
chloroform
solvent free
17
17
35
20
85
20 min.
Reaction condition is described below Table 1.
To improve the yield% and optimize the reaction conditions, effect of temperature was
studied on the condensation reaction of benzaldehyde with benzamide (Fig. 1). At 80 °C, the
reaction proceeded smoothly and almost complete conversion of the product was observed
after 20 min. Further increase in temperature didn’t improve yield%; therefore, the reaction
temperature 80 ºC was kept for all runs. Reactions at different conditions and at various molar
III
ratios of substrates in the presence of the heterogeneous H [(P W O )Fe (H O)] revealed
7
2
17 61
2
that the best condition was solventꢀfree at 80 ºC in the presence of 2.5 mol% catalyst.
Fig. 1. Effect of reaction temperature on the condensation of benzaldehyde with benzamide.

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Effect of reaction time was also investigated to explore minimum time required to
obtain the maximum yield in the preparation of N, N ꢀalkylidenebisamide. As illustrated in Fig.
, 20 min is sufficient to get 85% yield. No important increase in yield% was detected after a
prolonged reaction time.
′
2
100
90
80
70
60
50
40
30
20
10
0
0
5
10
15
20
25
30
35
Time(min)
Fig.2. Effect of reaction time on the condensation of benzaldehyde with benzamide.
Effect of the kind of the heteropolyacid was investigated on the efficacy of the catalytic
III
system. Therefore, catalytic activity ofH [(P W O )Fe (H O)] was compared with other
7
2
17 61
2
indicative familiar heteropolyacids in the preparation of N, N′ꢀ(phenylmethylene)
dibenzamide (Table 3). Almost, all the introduced Keggin and Wells-Dawson heteropolyacids
behaved as good catalysts in the respective transformation. Although, Keggin and Wells-
Dawson heteropolyacids have different structures, however, both types behaved similar in the
preparation of N, N′ꢀalkylidenebisamide derivatives. Among different HPA’s, the Preyssler
type showed less catalytic activity and resulted in 40% yield after 20 min. Many factors such as
acidity of the heteropolyacid, negative charge density smeared over oxygen atoms, structural
composition and distortions, and approach of the substrate molecule into the bulk of the
heteropolyacid would contribute to the catalytic efficiency of the heteropolyacids under the
2
9
reaction conditions.

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Table 3. Effect of the heteropolyacid nature and structure on the efficacy of the preparation of
N, N ꢀalkylidenebisamide.
′
Catalyst
Structure type
Keggin
Time (min)
Yield (%)
H PMo O
20
20
20
20
20
20
20
68
77
81
65
85
79
40
3
12 40
H PW O
Keggin
3
12 40
H P W O
18 62
Wells-Dawson
Si-substituted Keggin
Wells-Dawson
Keggin
6
2
H SiW O
4
12 40
H [(p W O )Fe(H O)]
7
2
17 61
2
H PW V O
40
5
10
2
H NaP W O
30 110
Preyssler
1
4
5
2
.5 mol% of catalyst was used in all cases. Yield% refers to the isolated yield.
With the obtained optimal conditions and to show the generality of the reaction, the
reaction of a series of aromatic aldehydes bearing different substituents was studied with
benzamide to afford the corresponding symmetrical N, N ꢀalkylidenebisamides (Table 4). It
′
seems that substitution at the paraꢀposition of the aromatic ring produced no significant
effects; aldehydes possessing electronꢀdonating groups caused slightly lower reaction yields.
Whereas, aromatic aldehydes substituted with electronꢀwithdrawing groups reacted well to
give the corresponding products in good to excellent yields under the reaction conditions.
However, the reaction of benzaldehyde with acetamide did not occur and only starting material
was recovered (Scheme 2). Moreover, in order to synthesize the unsymmetrical N, N
′ꢀ
alkylidenebisamides, the reaction of benzaldehyde with one equivalent of benzamide and one
equivalent of acetamide was carried out. The reaction provided only symmetrical N, N
alkylidenebisamide derived from benzamide.
′ꢀ

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R
O
O
O
N N
H H
NH2
O
only proudact
H
H [(P W O )Fe(H O)]
7
2
17 61
2
and
O
solventꢀfree, 80 °C
R
R
H C
O
O
3
NH2
H C N N
3
CH3
H H
not observed
Scheme 2. reaction of benzaldehyde with one equivalent of benzamide and one equivalent of
acetamide.
Table 4. Synthesis of different N, N′ꢀalkylidenebisamides in the presence of
III
H [(P W O )Fe (H O)] under solventꢀfree conditions.
7
2
17 61
2
R
O
O
O
O
NH2
H
H [(P W O )Fe(H O)]
7
2
17 61
2
N
N
H
H
solventꢀfree, 80 °C
R
◦
◦
Aldehyde
m.p.( C) lit. m.p. ( C) Time (min) Yield (%) Product
Benzaldehyde
238ꢀ239 237ꢀ238
20
85
O
O
N
H
N
H

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NO2
O
3
4
ꢀNO ꢀbenzaldehyde 234ꢀ236 236ꢀ237
20
97
98
2
O
N
H
N
H
NO 2
ꢀNO ꢀbenzaldehyde 240ꢀ242 241ꢀ243
15
20
2
O
O
N
H
N
H
Cl
4
ꢀClꢀbenzaldehyde 231ꢀ233 232ꢀ235
93
O
O
O
N
H
N
H
2
ꢀMeOꢀbenzaldehyde 230ꢀ232 229ꢀ230
20
20
77
98
OMe
O
N
H
N
H
Br
4
ꢀBrꢀbenzaldehyde 261ꢀ263 252ꢀ254
O
O
N
H
N
H
4
ꢀFꢀbenzaldehyde 225ꢀ227 226ꢀ228
40
76
F
O
O
N
N
H
H

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4
ꢀMeꢀbenzaldehyde 224ꢀ225 224ꢀ226
30
82
73
64
CH3
O
O
O
N
H
N
H
4
ꢀpyridylaldehyde 208ꢀ213 208ꢀ212
75
75
N
O
N
H
N
H
4
ꢀN(CH ) ꢀ
208ꢀ210 210ꢀ212
N(CH3)2
3
2
benzaldehyde
O
O
N
H
N
H
Phꢀ(CH ) ꢀCOH 249ꢀ251 248ꢀ249
75
60
67
77
2
2
O
O
N
H
N
H
C
H
CH ꢀ(CH ) ꢀCOH 171ꢀ173 172ꢀ173
3
2 2
-
(
C
H
)
O
O
N
N
H
H

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(
CH ) ꢀCHꢀCOH 126ꢀ128 126ꢀ127
75
68
3
2
O
O
N
N
H
H
Yields refer to the isolated pure products. The desired pure products were characterized by
comparison of their physical data with those of known compounds. Melting points refer to the
desired products.
III
Comparison of the efficacy of H [(P W O )Fe (H O)]catalyst with some reported
7
2
17 61
2
catalysts is presented in Table 5. The model reaction of benzamide and benzaldehyde was
considered as a representative example and the comparison was in terms of mol% or amount of
the catalyst, temperature, reaction time, and percentage yields. Evidently,
III
H [(P W O )Fe (H O)] was more effective than most of the conventional catalysts listed in
7
2
17 61
2
Table 5. The present methodology employed a very low amount of the catalyst under solventꢀ
free conditions. Although, some of the introduced additives catalyzed the reaction, even though
at a lower temperature, they required toxic and expensive solvents, higher mol% of catalyst,
and longer reaction times. The present catalytic system conveys distinct advantages in
competition with the previously reported methods, in terms of yield%, mild reaction
conditions, simple procedure and workꢀup, and lack of toxicity.
III
Table 5. Comparison of the catalytic efficiency of H [(P W O )Fe (H O)] with some reported
7
2
17 61
2
catalysts.
Entry
Catalyst and Conditions
ZnCl , Solvent, 110 ºC, 20 mol%
Time (min) Yield (%) Ref.
1
2
3
4
5
6
180
120
180
1200
40
91
74
73
70
80
81
30
31
12
8
2
SiO ꢀBaCl , Solvent free, 100 ºC, 0.025 g
2
2
SiO ꢀMgCl , Solventꢀfree , 100 °C, 0.025 g
2
2
Phosphotungstic acid, Toluene/reflux, 0.3 mmol
B(OH) , MW, 0.3 mmol
24
25
3
BF .SiO , CHCl /reflux , 0.03 g
270
3
2
3

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7
SiO ꢀPPA,Solvent free, 100 ºC, 0.025 g
70
60
32
2
8
9
Boric acid,toluene,120 ºC, 0.3 mmol
960
20
92
85
24
ꢀ
III
H
7
[(P
W
O
61)Fe (H
O)], 80 ºC, 2.5 mol%
2
17
2
III
Reusability and reproducibility of H [(P W O )Fe (H O)] was approved in the
7
2
17 61
2
synthesis of N, N′ꢀ(phenylmethylene)dibenzamide, as shown in Fig. 3. The catalyst was
recovered from the reaction mixture via eluting with ethyl acetate after each run, washed
thoroughly with ethanol, dried in an oven at 90 ºC for 4 h and tested in the subsequent run. The
catalyst was tested for six runs. It was observed that the catalyst displayed very good
reusability. Moreover, to ensure reproducibility of the transformation, repeated typical
experiments were carried out under identical reaction conditions. The obtained yields were
found to be reproducible within ±3% variation.
III
Fig. 3. Yield% as a function of reusability of H [(P W O )Fe (H O)]
.
7
2
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2

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To confirm that the catalytic activity was generated from the heterpolyacid catalyst, and
not from the decomposed components of the heteropolyacid in the reaction mixture, a hot filtration
test was planned. In this technique, to a mixture of aldehyde (2 mmol) and amide (4 mmol) was
III
added 0.01 mmol of H [(P W O )Fe (H O)] and the reaction was continued as described in the
7
2
17 61
2
experimental section. At this stage, the yield of the product was 75%. Then, the catalyst was
filtered off under hot conditions and with the filtrate obtained after separation of the catalyst, the
reaction was continued for another 15 min at the same reaction temperature. However, no
corresponding increase in yield beyond 75% was attained. This result clearly confirmed the
stability of the heteropolyacid in this condensation reaction and no degradation of the
heteropolyacid occurred during the course of the reaction. This result was also confirmed by
3
1
reusability and reproducibility studies of the catalyst as mentioned above. Moreover, P NMR
spectrum of the reꢀused catalyst was very similar to the fresh one and no change was occurred in
the structure of the heteropolyacid after six reꢀusing.
Finally, a plausible reaction pathway for the preparation of N, N
′
ꢀalkylidenebisamides
III
+
in the presence of H [(P W O )Fe (H O)] is proposed in Scheme 3. It is conceivable that H
7
2
17 61
2
from the heteropolyacid first bound to the carbonyl oxygen of the aromatic aldehyde and
increased its Lewis acidity. Then, benzamide attaches to the carbonyl group of aldehyde and
led to the generation of (I) and followed by loss of H O affords (II). As reported in the
2
literature, the Knoevenagel type coupling of benzamide with an active carbonyl compound
3
3
such as benzaldehyde gives N, N′ꢀalkylidenebisamide.

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H [(P W O61 )Fe(H O)]
7
2
17
2
O
R1
H+
Fe 3+
R
O
NH 2
H
O
H
OH
H
HO
N
H
R1
R
R
R
OH
(I)
H+
Fe 3+
O
R
O
R1
H+
N
H
N
N
H
ꢀ
H O
R1
2
R1
R1
O
H
R
H N
O
2
(
II)
Scheme 3. Proposed mechanism for the synthesis of N,N′ꢀalkylidenebisamide.
Conclusion
III
A green and easily available H [(P W O )Fe (H O)] was used as a strong, effective, and
7
2
17 61
2
selective Lewis/Bronsted acid catalyst for the preparation of symmetrical N, N′ꢀ
alkylidenebisamides under solventꢀfree conditions. The present protocol has some advantages
over the previously reported methods, such as good to excellent product yields, short reaction
times, low toxicity, low cost, and simple scaleꢀup. The workꢀup procedure is very clearꢀcut;
that is, the products were isolated and purified by simple filtration and reꢀcrystallization from
aqueous ethanol.
Acknowledgements
Partial financial support from the Research Councils of Hakim Sabzevari University is greatly
appreciated.

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DOI: 10.1039/C6RA01811D
References
1
W. Bannwarth and B. Hinzen, in Combinatorial Chemistry: FromTheory to Application
,
Wiley NCH, Weinheim, 2006.
2
3
K. Tanaka and G. Kaupp, in Solvent-free organic synthesis, Wiley VCH, Weinheim, 2009.
(a) R. S. Varma, Green Chem., 1999, 43; (b) H. R. Shaterian, M. Ghashang and M. Feyzi,
Appl. Catal. A: Gen 345, 2008, 128; (c) H. R. Shaterian, M. Ghashang and A. Hassankhani,
Dyes Pigments 76, 2008, 564.
P. Pallai, R. Struthers, M. Goodman, L. Moroder and E. Wunsch, Biochem.
,
4
5
6
, 24, 1985, 1933.
M. Rodriguez, P. Dubreuil, J. P. Bali and J. Martinez , J. Med. Chem. 30, 1987,758.
(a) E.E. Magat, B.F. Faris, I.E. Reith, L.F. Salisbury, J. Am. Chem. Soc. 73, 1951, 1028; (b)
H. R. Shaterian, A. Hosseinian, M. Ghashang, Can. J. Chem. 86, 2008, 376.
7
8
9
1
1
A. H.Fernandez , R. M. Alvarez and T.M. Abajo, Synthesis, 1996, 1299.
G. Harichandran, S. D. Amalraj and P. Shanmugam. Ind. J. Chem. 50, 2011, 77.
N.P. Selvam, S. Saranya and P.T. Perumal. Can. J. Chem. 86, 2008, 32.
0 J. Pernak, B. Mrowczynski and J. Weglewski, Synthesis 12, 1994, 1415.
1 M. AnaryꢀAbbasinejad, M. H. Mosslemin, A. Hassanabadi and S. T. Safa,
40, 2010, 2209.
2 M.R.M. Shafiee, Lett. Org. Chem.
3 Z. KarimiꢀJaberi and B. Pooladian, Monatsh. Chem.
4 M. AnaryꢀAbbasinejad, M. Mosslemin and A. Hassanzbadi, J. Chem. Res., 2009, 218.
,
,
,
Synth. Commun.
,
1
1
1
1
5
1
1
, 8, 2011, 562.
,
144, 2013, 659.
5 R. Tayebee, M. M. Amini, S. Pouyamanesh and A. Aliakbari, Dalton Trans., 44, 2015,
888.
6 R. Tayebee, M. M. Amini, M. Akbariu and A. Aliakbari, Dalton Trans., 2015, 44, 9596.
7 R. Tayebee, M. Jarrahi, B. Maleki, M. KargarRazi, Z. B. Mokhtari and S. M. Baghbanian,
RSC Adv.
,
5
, 2015, 10869.
8 R. Tayebee, M. Jarrahi, RSC Adv.
9 R. Tayebee, M. M. Amini, H. Rostamian and A. Aliakbari, Dalton Trans.
1
1
2
5
2
, 5, 2015, 21206.
,
43, 2014, 1550.
0 M.ꢀC. Kuo, R.J. Stanis, J.R. Ferrell Iii, J.A. Turner and A.M. Herring, Electrochim. Acta,
2, 2007, 2051.
1 R. Contant, Inorg. Synth., 27, 1990, 104.

Page 17 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01811D
2
2 H. M. Alizadeh, P. Subhash, H. Y. Jeannin, J. M. Frere, T. Michael and J. Pope, J. Am.
Chem. Soc. 107, 1985, 2662.
3 J. A. Dias, S. C. L. Dias , E. Caliman, J. Bartis and L. Francesconi, Inorg. Synth., 36, 2014,
,
2
2
2
2
2
2
2
2
10.
4 G. Harichandran , S. D. Amalraj and P. Shanmugam, J. Iran. Chem. Soc., 8, 2011, 298.
5 B. B. F Mirjalili, A. Bamoniri, S. A. Fazeli Attara, Iran. J. Catal., 3(3), 2013, 157.
6 Z. KarimiꢀJaberi and B. Pooladian, Monatsh Chem. 144, 2013, 659.
7 B. Dawson, Acta Crystallogr. , 1953, 113.
8 S Matkovic, G Valle, L Briand .Mater. Res., 8, 2005 , 351ꢀ355
9 R. Tayebee, F. Nehzat, E. RezaeiꢀSeresht, F. Z. Mohammadi and E. Rafiee, J. Mol. Catal.
,
,
6
.
R
.
.
M
.
.E.
A: Chem., 351, 2011, 154.
3
3
0 X. X. Shen, Y.L. Shen, Y.F. Han and Q. Liu, Adv. Mater. Res., 441, 2012, 421.
1 M R Mohammad Shafie, M P Zakaria, P.Aberomand Azar. Biological and Environmental
Engineering, 2, 2010,172
2 M.R. Mohammad Shafiee, Lett. Org. Chem., 8, 2011, 562.
3
3
6
3 F. Tamaddon , H. KargarꢀShooroki, A. A. Jafari, J. Mol. Catal. A: Chem. 368–369, 2013,
6.
Graphical Abstract
III
H [(P W O )Fe (H O)] is introduced as an effective catalyst for the oneꢀpot synthesis of N,
7
2
17 61
2
N
′
ꢀalkylidenebisamides. The catalyst could be easily separated without noticeable reduction in
activity.

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DOI: 10.1039/C6RA01811D
Na WO4
2
KHCO3
H PO4
3
KCl
WellsꢀDawson α− P W O
α2ꢀP
W
O
2
18 62
2
17 61
R
O
O
O
O
NH3
H [(P W O )Fe(H O)]
7 2 17 61 2
H
N
N
H
H
solventꢀfree, 80 °C
R