Vitamin C as a green and robust catalyst for the fast and efficient synthesis of valuable organic compounds via multi-component reactions in water

Article abstract of DOI:10.1007/s13738-019-01655-w

Abstract: In the present paper, we report l-ascorbic acid (vitamin C) as an efficient and robust catalyst for the straightforward synthesis of various organic compounds, including carboxamide, benzodiazepine and benzoxazepine derivatives. These compounds with potential drug value which exhibit a broad spectrum biological and pharmacological activities were successfully accessed with vitamin C catalytic system under environmentally friendly conditions in water. The main advantages of this protocol are operational simplicity, mild reaction conditions, high yields in short reaction time and good substrate generality. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s13738-019-01655-w

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-019-01655-w
ORIGINAL PAPER
Vitamin C as a green and robust catalyst for the fast and efcient
synthesis of valuable organic compounds via multi‑component
reactions in water
Ahmad Shaabani1 · Vida Khodkari1 · Mohammad Taghi Nazeri1 · Shima Ghasemi1 · Reza Mohammadian1 ·
Shabnam Shaabani1
Received: 9 October 2018 / Accepted: 18 March 2019
© Iranian Chemical Society 2019
Abstract
In the present paper, we report l-ascorbic acid (vitamin C) as an efcient and robust catalyst for the straightforward synthesis
of various organic compounds, including carboxamide, benzodiazepine and benzoxazepine derivatives. These compounds
with potential drug value which exhibit a broad spectrum biological and pharmacological activities were successfully
accessed with vitamin C catalytic system under environmentally friendly conditions in water. The main advantages of this
protocol are operational simplicity, mild reaction conditions, high yields in short reaction time and good substrate generality.
Graphical abstract
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-019-01655-w) contains
supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Keywords Ascorbic acid · Green chemistry · Heterocyclic compounds · Multi-component reactions
hydrogen-bond donors can promote reactions through a
variety of diferent mechanisms [10]. During the course
of a reaction, hydrogen-bonding interactions can be used
as stabilizing agents for anionic intermediates and transi-
tion states. Hydrogen-bond donors containing N–H and
O–H moieties have been efectively used for electrophile
activation [11–14].
Introduction
Green chemistry is a domain of chemistry which has
concentrated on design and synthesis of environmentally
friendly products. One of the primary purposes of green
chemistry is the utilization of eco-friendly solvents and
catalysts instead of poisonous and toxic ones [1]. Bio-
based catalysts, which are usually non-toxic, biodegrad-
able and biocompatible, are in compliance with the green
chemistry principles. Therefore, many organic chemists
are always seeking a way to design efcient synthetic
methods by using such catalysts to diminish the quantity
of hazardous efects of chemical reactions [2]. In recent
years, scientists have tried to discover not only the solvents
that are compatible with environment but the ones that
do not have a hazard to human health. From this point of
view, water is utilized as a green solvent in a wide range
of chemical reactions as it has admirable features accord-
ing to green chemistry rules [3]. Furthermore, the usage
of green catalysts in many organic transformations has
been a signifcant area of green chemistry. It is obvious
that utilization of catalysts such as organocatalysts [4],
enzymes [5], ionic liquids [6, 7] and montmorillonite
K-10 [8], which do not have any detrimental efects on
health as well as the environment, is a sustainable route
for synthesis of an array of biological and pharmaceuti-
cal compounds. Organocatalyzed reactions demonstrate a
novel alternative to metal-catalyzed processes because of
not only their economical price but for their benign eco-
logical impact in comparison with metallic catalysts [4].
The usage of hydrogen bonding as an activation force is
widespread in organocatalysis. Hydrogen-bond catalysis
is a type of organocatalyzed reaction that relies on the use
of hydrogen-bonding interaction to accelerate and control
organic transformations [9]. Indeed, catalytic amounts of
l-Ascorbic acid also known as vitamin C (Fig. 1) is a
rare compound containing acidic hydroxyl groups. This
naturally chiral molecule has tremendous medical appli-
cations in several diseases such as cancer, heart disease,
brain malfunction, aging, rheumatism, inflammation,
stroke emphysema and AIDS [15–17]. Vitamin C is an
electron donor compound from a double bond between the
second and third carbons, and because of this quality, it is
water soluble and an antioxidant, which has been shown
in many experiments in vitro [18].
Discovery and development of efcient strategies for syn-
thesis of a variety of complex compounds is one of the sig-
nifcant areas of organic chemistry. Multi-component reac-
tions (MCRs) are a synthetic methodology in which many
admirable compounds are constituted in a single step. There-
fore, synthesis of the heterocycles, which have been found as
the main skeleton in many medical and natural compounds,
by this route is highly admirable [19]. In this area, the com-
pounds with biological properties such as molecules-bearing
carboxamide moieties, heterocycles with two heteroatoms
and seven-membered heterocyclic systems including ben-
zoxazepines and benzodiazepines are widely found in natu-
ral products, and they exhibit a wide range of signifcant
biological and pharmacological activities (Fig. 2) [20, 21].
Therefore, the development of greener protocol and simple
synthetic methods to direct access of these compounds can
be benefcial. Due to the extraordinary catalytic abilities of
the vitamin C [22, 23], and in continuation of our interest
in developing catalytic systems for synthetic methodologies
[24–29], and multi-component reactions [30–33], herein we
report an efcient and straightforward one-pot synthesis of
carboxamide derivatives, benzodiazepines and benzoxaz-
epines by using vitamin C as an active organocatalyst under
environmentally friendly conditions in water.
Fig. 1 l-Ascorbic acid (vitamin
H
O
C)
O
O
H
O
H
O
H
O
Fig. 2 Representative examples
of biologically active com-
pounds with benzodiazepine,
benzoxazepine and carboxamide
scafolds
H
N
H
N
O
N
N
N
N
N
N
O
NH
Cl
anti cancer
anxiety disorders
analgesic and antihypertensive agents
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Journal of the Iranian Chemical Society
3.5 h, the desired product was obtained in 67% (Table 1,
Entry 1). When the reaction was examined in the presence
of vitamin C (5 mol%), the product was obtained in 52%
within 30 min (Table 2, Entry 2). The amount of vitamin
C was optimized to be 10 mol% due to higher yield and
shorter reaction times than the other amount of catalyst load-
ing (Table 2, Entry 3). As shown in Table 1, by increas-
ing the amount of catalyst, the reaction time was decreased
to 5 min and the yield increased to 96%; it is important to
note that from the energy-saving point of view, this is not
economical. The model reaction was also examined in vari-
ous media (Table 1, Entries 6–8). Results showed that water
was the most appropriate reaction solvent due to the highest
yield (91%) of the product. Therefore, the optimized reac-
tion condition for the synthesis of the carboxamide scafold
was 10 mol% of the vitamin C in water at room temperature.
Then, the optimized conditions were used for the synthe-
sis of various carboxamide derivatives. As shown in Table 2,
various aldehyde, benzoic acid and isocyanide derivatives
were successfully employed for this reaction.
Results and discussion
At the outset, on our previous investigations on Passerini
reaction [34] to access carboxamide scafolds, the catalytic
activity of the vitamin C was evaluated in the synthesis of
aforementioned compounds via reaction of benzaldehyde
3, benzoic acid 4 and cyclohexyl isocyanide 2 as the stand-
ard and model reaction under various conditions (Table 1).
Initially, the reaction was investigated in the absence of the
catalyst in water as a solvent at room temperature, and after
Table 1 Optimization of reaction conditions for the synthesis of
2-(cyclohexylamino)-2-oxo-1-phenylethyl benzoate
Entry Catalyst Solvent
(mol%)
Tempera- Time (min) Yielda (%)
ture (°C)
1
2
3
4
5
6
7
8
–
5
H2O
H2O
H2O
H2O
H2O
CH3CN r.t.
Neat
r.t.
r.t.
r.t.
r.t.
r.t.
210
30
15
10
5
360
360
360
67
52
91
94
96
23
–
10
15
20
10
10
10
Based on literature reports [22, 38], a plausible mecha-
nism for this reaction is shown in Scheme 1. Firstly, the
formation of the strong hydrogen bond between an aldehyde
and diol group in ascorbic acid activates molecule 6. Sub-
sequently, nucleophilic addition of an isocyanide to 6 leads
to intermediate 7, which is subsequently attacked by car-
boxylate 9 to produce desired compound 10. Then, Mumm
rearrangement of 10 gives rise to the fnal product 5 [37, 38].
r.t.
r.t.
EtOH
42
Reaction conditions: benzaldehyde (1.00 mmol), benzoic acid
(1.00 mmol), cyclohexyl isocyanide (1.00 mmol) and catalyst
Isolated yield
Table 2 One-pot synthesis of α-acyloxy carboxamides using ascorbic acid
R
H
O
HO
O
C
N
R2
O
Ascorbic acid (10 mol%)
H2O, r.t., 15 min
H
N
+
+
R2
O
R1
O
R
R1
5
4
2
3
Entry
R
R1
R2
Product
Yielda (%)
MP (oC)/Refs.
1
2
3
4
5
6
7
8
H
Cl
H
NO2
Me
Cl
H
H
H
H
H
OMe
Me
cyclohexyl
cyclohexyl
tert-butyl
cyclohexyl
tert-butyl
tert-butyl
cyclohexyl
cyclohexyl
5a
5b
5c
5d
5e
5f
91
88
85
92
86
83
89
90
130–133 [35]
153–155 [36]
149–151 [36]
209-210 [37]
150–152 [36]
185–187 [36]
154–156
Cl
H
5g
5h
Me
130–132
Reaction conditions: aromatic aldehyde (1.00 mmol), benzoic acid (1.00 mmol), isocyanide (1.00 mmol), catalyst (10 mol %) in water at room
temperature
aIsolated yield
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Journal of the Iranian Chemical Society
OH
HO
O
H
HO
O
C
O
O
O
O
N
+
+
R
H
O
O
R
3
3
OH
11
HO
R
1
H2O, ascorbic acid
r.t, 7 h
R2
N
O
+
O
HO
OH
O
H
O
O
H
C
HO
H
N
H
N
H
R1
+
+
9
O
H
O
H
3
R
O
R
12
O
HO
OH
R
H
R2
15 min
O
N
6
O
N
OH
R1
O
10
R
O
H
O
R
R2
N
C
H
Mumm
rearrangement
O
O
2
O-
H
N
O
H
R1 OH
H
R
H
H
O
N
Product
R2
4
7
5
R: NO2 Cl
,
O
R
13
Scheme 1 Proposed reaction mechanism for the synthesis of
α-acyloxy carboxamides
Scheme 2 Pseudo-seven-component synthesis of 2-(alkylamino)-
2-oxo-1-arylethyl 4-(alkylamino)-4-oxo-3-arylbutanoate derivatives
Furthermore, we assessed the catalytic performance
of ascorbic acid in the one-pot pseudo-seven-component
synthesis of 2-(cyclohexylamino)-2-oxo-1-arylethyl
4-(cyclohexylamino)-4-oxo-3-arylbutanoate derivatives
13a–b. Recently, we designed and reported an efcient
method for the synthesis of 4-(alkylamino)-3-aryl-4-ox-
obutanoic acid 12 via a four-component reaction of Mel-
drum’s acid 11, aldehydes 3, isocyanides 2 and water in
CH2Cl2 at room temperature [39]. Based on this report and
the proof of catalytic role of ascorbic acid, we decided to
utilize the product of mentioned reaction as acid deriva-
tives in the Passerini reaction (scheme 2).
1,2-phenylenediamines and isocyanides (Table 5). It can
be seen that all of the products were obtained in excellent
yields.
The proposed mechanism for the reaction is suggested
in Scheme 2. At the outset, formation of hydrogen bond
between ascorbic acid and ketone 14 led to intermediate 17,
which subsequently reacted with 1,2-phenylenediamines 15
to produce compound 18; afterward, intramolecular imine-
enamine cyclization of 19 formed seven-membered ring
heterocycle 20, which was then attacked by isocyanide 2 to
form intermediate 8. Finally, nucleophilic addition of water
to the nitrilium moiety of compound 21 and subsequent tau-
tomerization led to the desired product (Scheme 3).
Furthermore, we investigated the catalytic performance
of ascorbic acid in another type of multi-component reac-
tion for the direct synthesis of benzoxazepine rings, which
are useful seven-membered heterocyclic compounds. In this
regard, we planned to perform the three-component reaction
of 2-aminophenol 23, dimedone 24 and benzaldehyde 3 in
the presence of ascorbic acid under various reaction condi-
tions to obtain 1,4-benzoxazepine derivatives (Table 6). The
best reaction condition was 10 mol% vitamin C in water at
50 °C.
According to the optimized conditions that we estab-
lished for the Passerini reaction, the reaction of various
aldehydes, Meldrum’s acid and cyclohexyl isocyanide was
investigated in the presence of ascorbic acid as a catalyst
in water at room temperature (Table 3).
Due to the importance of benzodiazepines in organic
and medicinal chemistry [40], several synthetic routes
have been reported for the synthesis of benzodiazepine
scafolds [41, 42]. To investigate the generality of this cat-
alytic system, we further examined the efciency of vita-
min C as a catalyst for the synthesis of benzodiazepines
by the pseudo-fve-component reaction of 4-nitro-1,2-phe-
nylenediamine 15, acetone 14 and cyclohexyl isocyanide
2 in water (Table 4). The best yield of product (90%) was
obtained in the presence of 10 mol% of vitamin C in water
at room temperature (Table 4, Entry 3).
With the optimized conditions established, the reaction
of various 2-aminophenols, dimedone and benzaldehyde
derivatives was examined in the presence of ascorbic acid
as a catalyst in water (Table 7).
On the basis of the previous report [43], the possi-
ble mechanism for the formation of 1,4-benzoxazepine is
shown in Scheme 4. Initially, in the presence of the catalyst,
After optimizing the reaction conditions, we inves-
tigated the scope of the reaction for the synthesis of
benzodiazepine derivatives using various ketones,
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Journal of the Iranian Chemical Society
Table 3 One-pot synthesis of 2-(cyclohexylamino)-2-oxo-1-arylethyl 4-(cyclohexylamino)-4-oxo-3-arylbutanoates using ascorbic acid
H
O
R
O
H
N
C
N
H
O
O
O
ascorbic acid (10 mol%)
H2O, r.t.
H
+
2
H
O
+
H
2
O
N
O
O
R
R
11
2
3
13
Entry
R
Time (h)
Product
Yielda (%)
1
2
Cl
NO2
7.25
7.25
13a
13b
88
93
Reaction conditions: Meldrum’s acid (1.00 mmol), isocyanide (2.00 mmol), aldehyde (2.00 mmol) and catalyst (10 mol %) in water at room tem-
perature
aIsolated yield
Table 4 Optimization of reaction conditions for the synthe-
sis of N-cyclohexyl-2, 4, 4-trimethyl-8-nitro-2,3,4,5-tetrahydro-
1H-benzo[b] [1, 4] diazepine-2-carboxamide
2-aminophenol and dimedone undergo enamine formation.
Then, intermediate 29 is produced by nucleophilic attack of
enamine to activate aldehyde 18, and then the intramolecular
cyclization led to the product (Scheme 4).
Entry
Catalyst
(mol%)
Temperature Time (h)
(°C)
Yielda (%)
1
2
3
4
5
–
5
10
15
20
100
r.t.
r.t.
r.t.
24
12
5
4.5
4.5
Trace
46
90
92
Conclusions
In summary, vitamin C was successfully used as a highly ef-
cient H-bond donor organocatalyst for the multi-component
synthesis of various compounds with fairly good yields in
water. Moreover, in view of the simplicity and non-hazardous
nature of the catalyst and its commercial availability, vitamin
C might be a useful catalyst for the synthesis of a variety of
r.t.
96
Reaction conditions: 4-nitro-1,2-phenylenediamine (1.00 mmol), ace-
tone (2.00 mmol), cyclohexyl isocyanide (1.00 mmol) and catalyst in
water
Bold values indicate the best condition
aIsolated yield
Table 5 Synthesis of benzodiazepines derivativesSynthesis of benzodiazepines derivatives
R4
R3
R4
R3
HN
O
HN
R5
R1
R2
NH2
NH2
O
NH
C
N
R5
2
Ascorbic acid (10 mol%), H O, r.t
+
+
2
R3 R4
5 h
R1
R2
15
14
2
16
Entry Diamine
Ketone
Isocyanide
Time (h) Product Yielda (%) MP (°C)/Refs.
1
2
3
4
1,2-phenylenediamine
4-nitro-1,2-phenylenediamine
4-nitro-1,2-phenylenediamine
Cyclopentanone Cyclohexyl isocyanide
5
5
5
5
16a
16b
16c
16d
84
90
87
88
157–160
Acetone
Acetone
Cyclohexyl isocyanide
Tert-butyl isocyanide
Cyclohexyl isocyanide
186–188 [42]
223–225 [42]
170–172 [42]
4,5-dichloro-1,2-phenylenediamine Acetone
Reaction conditions: 1, 2-phenylenediamines (1.00 mmol), ketone (2.00 mmol), isocyanide (1.00 mmol) and catalyst (10 mol %) in water
aIsolated yield
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Journal of the Iranian Chemical Society
R2
R2
spectra were recorded on a Bruker DRX-300 Avance spec-
trometer at 300.13 and 75.47 MHz using CDCl3 and DMSO-
d6 as solvents and tetramethylsilane (TMS) as an internal
standard. The melting points of the products were measured
by an electrothermal 9100 apparatus.
R1
N
R3
R1
HN
OH
NH
tautomerization
Product
16
22
O
HO
OH
R2
H
2O
2
R1
O
R2
R2
14
R1
R1
HN
N
R3
HO
OH
O
1
NH
General procedure for the synthesis of the α‑acyloxy
carboxamides (5a‑f)
O
H
HO
HO
H
R2
O
O
21
17
R1
NH2
NH2
To a magnetically stirred solution of an aromatic aldehyde
(1.00 mmol), benzoic acid derivatives (1.00 mmol) and
ascorbic acid (0.017 g, 10 mol%) in H2O (5 mL) was added
dropwise a solution of an alkyl isocyanide (1.00 mmol). The
reaction mixture was allowed to stir at room temperature;
after 15 min, a white precipitate formed. After fltration and
washing with water, the pure product was obtained.
C
N
R3
2
15
H
H
R1
R2
R2
R2
R2
R1
HN
N
N
OH
OH
H
O
R1
H
R1
O
OH
OH
N
H
O
O
O
18
H
HO
OH
O
O
20
1
O
O
R2
1
General procedure for the synthesis
of the 2‑(cyclohexylamino)‑2‑oxo‑1‑arylethyl
4‑(cyclohexylamino)‑4‑oxo‑3‑arylbutanoates
(13a‑b)
H
H
R
R2
H
N
NH
R1
19
Scheme 3 Proposed reaction mechanism for the synthesis of benzo-
To a magnetically stirred solution of Meldrum’s acid (0.14 g,
1.00 mmol), an aromatic aldehyde (1.00 mmol) and ascorbic
acid (0.017 g, 10 mol%) in H2O (5 mL) was added dropwise
a solution of cyclohexyl isocyanide (0.109 g, 1.00 mmol).
The reaction mixture was allowed to stir at room tempera-
ture for 7 h. Then, an aldehyde (1.00 mmol) and cyclohexyl
isocyanide (0.109 g, 1.00 mmol) were added to the above
mixture and the reaction was stirred at room temperature.
After completion of the reaction, the precipitate was fltered
of and washed with water to give product as a white solid.
diazepines derivatives
Table 6 Optimization of reaction conditions for the synthesis of
3,3-dimethyl-11-phenyl-3,4,5,11-tetrahydrodibenzo [b, e] [1, 4] oxaz-
epin-1(2H)-one
Entry
Catalyst (mol Temperature Time (h)
Yielda (%)
%)
(°C)
1
2
3
4
5
6
–
100
r.t.
40
50
60
50
24
12
12
12
12
12
Trace
41
67
88
92
10
10
10
10
15
General procedure for the synthesis
of the 4,5,6,7‑tetrahydro‑1H‑1,4‑diazepine‑5‑car‑
boxamide derivatives (16a–d)
91
Reaction conditions: 2-aminophenol (1.00 mmol), dimedone
(1.00 mmol), benzaldehyde (1.00 mmol) and catalyst in water
A mixture of o-phenylene diamine derivatives (1.00 mmol),
a ketone (2.00 mmol) and an alkyl isocyanide (1.00 mmol) in
the presence of ascorbic acid (0.017 g, 10 mol%) was stirred
for 5 h in water (5.00 ml) at room temperature. After com-
pletion of the reaction as indicated by TLC (ethyl acetate/n-
hexane, 2/1; Rf =0.50), the precipitate was fltered of and
washed with water, and then crystallized from acetone to
give product as colorless crystals.
Bold values indicate the best condition
aIsolated yield
heterocyclic compounds. Short reaction times, high product
yields, ease of the experimental procedure and environmentally
benign methodology are the advantages of this catalytic system.
General procedure for the synthesis of the 1,4‑ben‑
zoxazepine derivatives (25a–e)
Experimental
A mixture of 2-aminophenol derivatives (1.00 mmol),
dimedone (0.140 g, 1.00 mmol) and ascorbic acid (0.017 g,
10 mol%) in water (5.00 ml) was heated at 50 °C for 4 h.
After completion of this step as indicated by TLC, an
Materials and methods
All reagents were purchased from Sigma-Aldrich and used
without further purifcation. The H NMR and 13C NMR
1
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Journal of the Iranian Chemical Society
Table 7 One-pot three-component synthesis of 1, 4-benzoxazepine derivatives using ascorbic acid
H
N
R1
1: ascorbic acid (10 mol%)
O
OH
O
H2O, 50 oC, 4h
O
+
O
R1
NH2
R3
R4
CHO
,50 oC, 8h,
R2
R3
R2
2:
24
23
R4
25
3
Entry
R1
R2
R3
R4
Time (h)
Product
Yielda (%)
MP (°C)/Refs.
1
2
3
4
5
6
7
H
H
H
H
Cl
H
H
H
H
H
H
H
H
OMe
H
H
H
H
H
OMe
OMe
H
Cl
NO2
Me
NO2
H
12
12
12
12
12
12
12
25a
25b
25c
25d
25e
25f
88
91
93
85
89
90
85
269–271 [34]
269–270 [34]
278–280 [34]
270–272 [34]
275–277
261–263
267–268
H
25g
Reaction conditions: 2-aminophenol (1.00 mmol), dimedone (1.00 mmol), aldehyde (1.00 mmol), H2O (1.00 mmol) catalyst (10 mol %) at 50 °C
aIsolated yield
HO
OH
Acknowledgements We gratefully acknowledge fnancial support
of the Research Council of Shahid Beheshti University and the Iran
National Science Foundation (INSF).
O
O
product 25
O
24
HO
OH
1
Compliance with ethical standards
NH
HO
OH
O
OH
HO
Conflicts of interest All authors declare that they have no confict of
O
H
O
interest.
O
H
O
O
H
H
O
O
29
HO
HO
References
O
26
1. J.H. Clark, Green Chem. 1, 1 (1999)
2. D.T. Allen, K.S. Rosselot, Pollution prevention for chemical pro-
cesses (Wiley-Interscience, Hoboken, 1997)
NH2
OH
H
H
O
H
N
O
3. M.B. Gawande, V.D. Bonifácio, R. Luque, P.S. Branco, R.S.
Varma, Chem Soc Rev 42, 5522 (2013)
H
23
O
HO
OH
OH
OH
OH
4. N. Marion, S. Díez-González, S.P. Nolan, Angew Chem Int Ed
46, 2988 (2007)
O
O
28
O
27
HO
OH
5. D. Yao, G. Li, T. Kuila, P. Li, N.H. Kim, S.I. Kim, J.H. Lee, J.
Appl. Polym. Sci. 120, 1114 (2011)
1
6. H.-P. Zhu, F. Yang, J. Tang, M.-Y. He, Green Chem. 5, 38 (2003)
7. S. Noura, M. Ghorbani, M.A. Zolfgol, M. Narimani, M. Yarie,
M. Oftadeh, J. Mol. Liq. 271, 778 (2018)
Scheme 4 Proposed reaction mechanism for the synthesis of 1,
4-benzoxazepine derivatives
8. T.-K. Huang, R. Wang, L. Shi, X.-X. Lu, Catal. Commun. 9, 1143
(2008)
9. W. Yang, D.-M. Du, Org. Lett. 12, 5450 (2010)
10. J.P. Malerich, K. Hagihara, V.H. Rawal, J. Am. Chem. Soc. 130,
14416 (2008)
aromatic aldehyde (1.00 mmol) was added to the above
mixture and then the reaction was heated for 8 h at 50
°C. After completion of the reaction, the precipitate was
fltered of and washed with water to give product as a
white solid.
11. Ł. Albrecht, G. Dickmeiss, F.C. Acosta, C. Rodríguez-Escrich,
R.L. Davis, K.A. Jørgensen, J. Am. Chem. Soc. 134, 2543 (2012)
1 3

Journal of the Iranian Chemical Society
12. S. Schenker, A. Zamfr, M. Freund, S.B. Tsogoeva, Eur. J. Org.
Chem. 2011, 2209 (2011)
28. A. Shaabani, R. Mohammadian, S.E. Hooshmand, A. Hashemza-
deh, M.M. Amini, ChemistrySelect 2, 11906 (2017)
29. A. Shaabani, A. Rashidi Vahid, S. Shaabani, R. Mohammadian,
M.T. Nazeri, M. Keramati Nejad, Appl. Organomet. Chem. e4510
(2018)
13. Y. Takemoto, Org. Biomol. Chem. 3, 4299 (2005)
14. J. Wang, H. Li, X. Yu, L. Zu, W. Wang, Org. Lett. 7, 4293 (2005)
15. B. Frei, S. Lawson, Proc. Natl. Acad. Sci. 105, 11037 (2008)
16. M.L. Heaney, J.R. Gardner, N. Karasavvas, D.W. Golde, D.A.
Scheinberg, E.A. Smith, O.A. O’Connor, Cancer Res 68, 8031
(2008)
30. A. Shaabani, A. Maleki, J. Moghimi-Rad, J. Org. Chem. 72, 6309
(2007)
31. A. Shaabani, H. Mofakham, A. Maleki, F. Hajishaabanha, J. Com-
bin. Chem. 12, 630 (2010)
17. H.H. Ting, F.K. Timimi, K.S. Boles, S.J. Creager, P. Ganz, M.A.
Creager, J. Clin. Investig. 97, 22 (1996)
32. A. Shaabani, E. Soleimani, A.H. Rezayan, A. Sarvary, H.R.
Khavasi, Org. Lett. 10, 2581 (2008)
18. G.R. Buettner, B.A. Jurkiewicz, Radiat. Res. 145, 532 (1996)
19. M. Shiri, Chem. Rev. 112, 3508 (2012)
33. S. Shaabani, A. Shaabani, S.W. Ng, ACS Combin. Sci. 16, 176
(2014)
20. C. Dittrich, V. Dieras, P. Kerbrat, C. Punt, R. Sorio, F. Caponigro,
X. Paoletti, C. de Balincourt, D. Lacombe, P. Fumoleau, Investig
New Drugs 21, 347 (2003)
34. A. Shaabani, S.E. Hooshmand, M.T. Nazeri, R. Afshari, S. Gha-
semi, Tetrahedron Lett. 57, 3727 (2016)
21. N. Willand, T. Beghyn, G. Nowogrocki, J.-C. Gesquiere, B.
Deprez, Tetrahedron Lett 45, 1051 (2004)
35. L.A. Polindara-García, E. Juaristi, Eur. J. Org. Chem. 2016, 1095
(2016)
22. S. Arayachukiat, C. Kongtes, A. Barthel, S.V. Vummaleti, A.
Poater, S. Wannakao, L. Cavallo, V. D’Elia, A.C.S. Sustain,
Chem. Eng. 5, 6392 (2017)
36. T. Bousquet, M. Jida, M. Soueidan, R. Deprez-Poulain, F. Agbos-
sou-Niedercorn, L. Pelinski, Tetrahedron Lett. 53, 306 (2012)
37. M. Adib, E. Sheikhi, M. Azimzadeh, Tetrahedron Lett. 56, 1933
(2015)
23. A.A. Napoleon, F.-R.N. Khan, E.D. Jeong, E.H. Chung, Tetrahe-
dron Lett 55, 5656 (2014)
38. R. Ramozzi, K. Morokuma, J. Org. Chem. 80, 5652 (2015)
39. A. Shaabani, M.B. Teimouri, J. Chem. Res. 2002, 433 (2002)
40. J.N. Sangshetti, A.S. Zambare, F.A. Kalam Khan, I. Gonjari, Z.
Zahir, Mini Rev. Med. Chem. 14, 988 (2014)
24. M. Mahyari, M.S. Laeini, A. Shaabani, Chem. Commun. 50, 7855
(2014)
25. R. Mohammadian, M.K. Alavijeh, N. Kamyar, M.M. Amini, A.
Shaabani, Polyhedron 156, 174 (2018)
41. G.A. Archer, L.H. Sternbach, Chem. Rev. 68, 747 (1968)
42. A. Shaabani, A. Maleki, H. Mofakham, J. Combin. Chem. 10, 595
(2008)
26. A. Shaabani, R. Mohammadian, H. Farhid, M.K. Alavijeh, M.M.
Amini, Ind. Eng. Chem. Res. 58, 2784 (2019)
27. A. Shaabani, R. Mohammadian, A. Hashemzadeh, R. Afshari,
M.M. Amini, New J. Chem. 42, 4167 (2018)
43. M. Ghandi, T. Momeni, M.T. Nazeri, N. Zarezadeh, M. Kubicki,
Tetrahedron Lett. 54, 2983 (2013)
Afliations
Ahmad Shaabani1 · Vida Khodkari1 · Mohammad Taghi Nazeri1 · Shima Ghasemi1 · Reza Mohammadian1 ·
Shabnam Shaabani1
1
* Ahmad Shaabani
Faculty of Chemistry, Shahid Beheshti University, G.C., P.O.
a-shaabani@sbu.ac.ir
Box 19396-4716, Tehran, Iran
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