One-Pot Synthesis of Some2-Amino-4H-benzo[g]chromenes

Full text of DOI:10.1080/00304948.2016.1127104

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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One-Pot Synthesis of Some2-Amino-4H-
benzo[g]chromenes
Behrooz Maleki
To cite this article: Behrooz Maleki (2016) One-Pot Synthesis of Some2-Amino-4H-
benzo[g]chromenes, Organic Preparations and Procedures International, 48:1, 81-87, DOI:
10.1080/00304948.2016.1127104
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Date: 30 January 2016, At: 09:50

Organic Preparations and Procedures International, 48:81–87, 2016
Copyright Ó Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2016.1127104
One-Pot Synthesis of Some
2-Amino-4H-benzo[g]chromenes
Behrooz Maleki
Department of Chemistry, Hakim Sabzevari University, Sabzevar, 96179-76487,
Iran
The increasing concern for the environment has led modern academic and industrial
chemists to develop chemical processes with maximize yields and minimize cost while
using non-toxic reagents and solvents. Multi-component reactions (MCRs) constitute
such processes that combine economic aspects with the environmental ones and are pow-
erful tools for the construction of novel and structurally complex molecules in a single-
pot reaction. This ensures high atom economy, good yields and low costs, in short reac-
tion times, minimization of waste, labor, energy, and avoidance of tedious purification
processes.1–7
2-Amino-4H-benzo[g]chromenes are an important class of compounds. In particular,
they are a common heterocyclic scaffold in biologically active and medicinally significant
compounds including anti-cancer,8 anti-inflammatory,9 anti-malarial,10–11 and as pesti-
cides.12 Some of hydroxynaphthalene-1,4-dione derivatives are fluorescent compounds
and are of interest as emitters for electroluminescent devices,13 as molecular probes for
biochemical research,14 and as fluorescent whitening agents.15
The diverse biological activities of some 2-amino-4H-benzo[g]chromene derivatives
have prompted considerable attention to their preparation. To the best of our knowledge,
a few procedures have been used for the synthesis of 2-amino-4H-benzo[g]chromenes
such as triethylbenzylammonium chloride (TEBA),16 DMF/AcOH under microwave irra-
diation,17 Et3N,18 DBU,19 ionic liquids,20–23 Zn(L-Proline)2,24 potassium phthalimide-N-
oxyl25 and urea.26 However, a number of these methods suffer from certain drawbacks
such as prolonged reactions times at high temperatures, the use of volatile or hazardous
organic solvents, tedious work-up procedures, utilization of alternative energy source
(microwave) and the use of corrosive, toxic and non-reusable catalysts in large amounts,
which creates difficulties in the separation of the products. Therefore, it seemed desirable
to develop a more efficient and a general method for the synthesis of these 2-amino-4H-
benzo[g]chromenes.
In continuation of our efforts toward the development of greener methodologies,27–40
we report a simple, efficient, and green synthesis of 2-amino-4H-benzo[g]chromene
derivatives 4 by reaction of various aldehydes, malononitrile, and 2-hydroxy-1,4-naph-
thoquinone in the presence of o-benzenedisulfonimide (OBS) as a reusable acid catalyst
Received August 14, 2015; in final form October 7, 2015.
Address correspondence to Behrooz Maleki, Department of Chemistry, Hakim Sabzevari Uni-
versity, Sabzevar, 96179-76487, Iran. E-mail: malekibehrooz@gmail.com
81

82
Maleki
Scheme 1
(Scheme 1). o-Benzenedisulfonimide is a stable, efficient, inexpensive, safe, non-volatile,
non-corrosive acid and re-usable catalyst. It is also highly soluble in both organic solvents
and water. Convenient work-ups when it is used and its eco-friendly nature make OBS a
green catalyst in organic synthesis.41–44
In order to carry out the preparation of 2-amino-4-phenyl-5,10-dihydro-5,10-dioxo-
4H-benzo[g]chromene-3-carbonitrile (4a) in a more efficient way, minimizing the time
and amount of catalyst, the reaction of benzaldehyde (1 equiv.), malononitrile (1.2
equiv.), and 2-hydroxy-1,4-naphthaquinone (1 equiv) was selected as a model reaction.
The effect of various parameters, such as the influence of solvents, concentration of the
catalyst and temperature, was evaluated to optimize the reaction conditions (Table 1,
Entries 1–9). As shown in the Table, the shortest time and best yield were achieved using
10 mol % of OBS (Entry 8). In the absence of o-benzenedisulfonimide, no significant
product formation was observed under the same conditions (Entry 9). Under these optimal
conditions (Table 1, Entry 8), the scope and efficiency of the reaction were explored for
Table 1
Optimization of Reaction Conditions
Entry
OBS (mol%)
Conditions
Time (min)
Yield (%)
1
2
30
30
30
30
30
30
20
10
5
Water/reflux
Methanol/reflux
Ethanol/reflux
10
15
10
10
10
60
8
82
56
80
88
86
68
89
92
80
0
3
5
Solvent-free/60ꢀC
Solvent-free/70ꢀC
Solvent-free/50ꢀC
Solvent-free/60ꢀC
Solvent-free/60ꢀC
Solvent-free/60ꢀC
Solvent-free/60ꢀC
5
6
7
8
8
9
10
15
60
0

One-Pot Synthesis of Some 2-Amino-4H-benzo[g]chromenes
83
Table 2
One-pot Synthesis of 2-Amino-4H-benzo[g]chromene Derivatives Using OBS (10 mol
%) as Catalyst
mp (ꢀC)
Products
(4a-p)
Found
Lit.
R
Yield (%)
Time (min)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
C6H5
92
91
91
92
90
90
93
90
92
89
84
82
95
90
95
82
8
6
262–264
247–248
252–254
270–272
246–249
292–294
254–256
238–240
286–288
254–256
286–288
240–242
295–297
242–244
236–238
254–257
260–26216
247–24820
248–25021
272–27323
248–25020
291–29221
250–25123
236–23920
286–28821
252–25420
286–28820
242–24420
295–29716
242–24421
234–23520
254–25621
4-CH3OC6H4
3-CH3OC6H4
3,4-CH3OC6H3
2,4-CH3OC6H3
2,3,4-CH3OC6H2
4-ClC6H4
7
6
7
9
6
2-ClC6H4
8
2,4-ClC6H3
4-BrC6H4
4-FC6H4
8
7
9
4-CH3C6H4
3-NO2C6H4
2-NO2C6H4
4-NO2C6H4
4-HOC6H4
10
5
5
5
12
the synthesis of a wide variety of substituted 2-amino-4H-benzo[g]chromenes (Table 2).
A variety of arylaldehydes, including those bearing electron-withdrawing or releasing
substituents (ortho-, meta-, and para-substituted), gave the desired products in good to
excellent yield (Table 2). When aliphatic aldehydes such as formaldehyde, acetaldehyde,
butyraldehyde, isobutyraldehyde, crotonaldehyde and cinnamaldehyde were utilized in
this reaction, none of the expected product was obtained and only starting material was
recovered.
o-Benzenedisulfonimide (OBS) may be easily recovered in better than 90% yield
from the reaction mixtures, because of its complete solubility in water. This property per-
mits its re-use in other reactions, immediately or after a quick purification step on a cat-
ion-exchange resin without any loss of catalytic activity. It was re-cycled in the model
reaction to give 4a in yields of 92%, 88%, 85% for three consecutive runs.
In order to demonstrate the effectiveness of the present method in comparison with
previously reported results in the literature, we have compared some of the results for the
preparation of 2-amino-4H-benzo[g]chromene derivatives in Table 3. They show that o-
benzenedisulfonimide (OBS) is the most efficient catalyst with respect to the reaction
time and yields of the products.
The development of methodologies that involve the use of reusable organocatalyst
under environmentally friendly (solvent-free) condition is one of the major goals in green
chemistry. From the view point of green chemistry, the use of organocatalyst in organic
reactions, good recovery and reusability of the catalyst and solvent-free conditions are
highly preferable.

84
Maleki
Table 3
Comparison of Methods for the Synthesis of 2-Amino-4H-benzo[g]chromene Derivatives
2-Amino-4H-
benzo[g]
chromenes
Time Yield
(min) (%)
Conditions
Present work
Et3N/CH3CN/rt18
8
92
1440 82
DBU/H2O/reflux19
60
12
60
87
89
91
Pyrrolidinium acetate/solvent-free/rt21
1-Butyl-3-methyl imidazolium hydroxide/EtOH/rt22
Present work
Et3N/CH3CN/rt18
6 93
1440 80
2-Hydroxyethylammonium formate/solvent-free/rt20
Pyrrolidinium acetate/solvent-free/rt21
1-Butyl-3-methyl imidazolium hydroxide/EtOH/rt22
Ttriethylammonium hydrogen sulfate/solvent-free/rt23
6
85
90
92
91
12
50
11
Present work
5
95
93
84
Triethylbenzylammonium chloride/solvent-free/85ꢀC16 210
DMF/AcOH/microwave irradiation17
Et3N/CH3CN/rt18
DBU/H2O/reflux19
2-Hydroxyethylammonium formate/solvent-free/rt20
Pyrrolidinium acetate/solvent-free/rt21
Ttriethylammonium hydrogen sulfate/solvent-free/rt23
Urea/EtOH:H2O/rt26
5
1440 75
8
8
89
85
87
88
84
12
13
360
The absence of metal in organocatalyst brings an undeniable advantage considering
the principles of green chemistry. o-Benzenedisulfonimide (OBS) is a organocatalyst and
has several advantages in comparison with other catalysts: inexpensive; readily available;
nontoxic; non-volatile, non-corrosive, inert toward moisture and oxygen. Also, Reactions
performed by organocatalysts have potential application in large scale production in
industries.
One approach to reducing the environmental impact of a reaction is to conduct them
under solvent-free conditions. Advantages of solvent-free reactions include cost savings,
reduced energy consumption, decreased reaction times, and a considerable reduction in
reactor size and, therefore, capital investment. These attributes have inspired a substantial
research effort directed toward the development of solvent-free reactions. These proper-
ties make o-Benzenedisulfonimide (OBS) attractive as novel organocatalyst for the syn-
thesis of 2-amino-4H-benzo[g]chromenes under solvent-free condition.
In conclusion, we have developed a green and simple protocol for the synthesis of 2-
amino-4H-benzo[g]chromene derivatives via a three-component condensation reaction in
the presence of o-benzenedisulfonimide (OBS) as a catalyst under solvent-free conditions.
This procedure provides several advantages such as high yields, short reaction times, non-
volatile, non-corrosive, absence of side-reactions, simple work-up procedure, non-toxic,

One-Pot Synthesis of Some 2-Amino-4H-benzo[g]chromenes
85
facile preparation and handling of the catalyst, and minimization of cost and waste gener-
ation owing to recycling of the catalyst. It is expected that the present methodology will
find application in other areas of organic synthesis.
Experimental Section
All reagents were obtained from commercial sources and were used without purification.
IR spectra were recorded as KBr pellets on a Shimadzu 435-U-04 spectrophotometer. 1H
and 13C NMR spectra were determined on a Bruker DRX-300 Avance spectrometer in
DMSO-d6 or CDCl3, and shifts are given in d downfield from tetramethylsilane (TMS) as
an internal standard. Melting points were acquired using an Electrothermal 9200 appara-
tus and are uncorrected.
General Procedure for the Synthesis of 2-Amino-4H-benzo[g]chromenes (4a-p)
To a mixture of the aldehyde (1 mmol), malononitrile (0.08 g, 1.2 mmol), and 2-hydroxy-
1,4-naphthoquinone (0.174 g, 1 mmol), was added OBS (0.022 g, 0.1 mmol) [for solid
substrates 5-10 drops of ethanol was added] and the mixture was heated on an oil bath at
60ꢀC for the time shown in Table 2. Upon completion of the reaction as indicated by
TLC (n-hexane:ethyl acetate, 4:1), EtOH (96%, 2 ml) was added and the mixture stirred
for 2 min. Then the resulting crude reaction mixture was poured onto crushed ice and the
precipitated solid was collected and recrystallized from ethanol (96%, 5 ml) to afford the
pure 2-amino-4H-benzo[g]chromene derivatives (4a-p).
To recover the catalyst (OBS), the filtrate from the isolation of the chromene (above)
was evaporated under reduced pressure. The solid residue was deposited on top of a col-
umn of acidic Dowex AG 50W-X8 ion-exchange resin (200 mg resin, 100–200 mesh)
and eluted with water (10 ml). Removal of the water under reduced pressure gave a 93%
recovery of pure o-benzenedisulfonimide as a white solid. It was dried at 80ꢀC under
reduced pressure for 1 h and re-used for subsequent reactions.
Larger Scale Preparation of 4a. Typical Procedure
To a mixture of the benzaldehyde (5.3 g, 50 mmol), malononitrile (3.96 g, 60 mmol), and
2-hydroxy-1,4-naphthoquinone (8.7 g, 50 mmol), was added OBS (0.1095 g, 5 mmol)
and the mixture was heated in an oil bath at 60ꢀC for the time 20 min. Upon completion
of the reaction as indicated by TLC (n-hexane-ethyl acetate, 4:1), 96% EtOH (95 ml) was
added and the solution was stirred for 5 min. The product was isolated as described above
and recrystallized from 96% ethanol (20 ml) to afford 12.43 g (76%) of 2-amino-4-phe-
nyl-5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile (4a).
The catalyst (OBS) was recovered as described above.
Acknowledgements
The authors thank the Research Council of Hakim Sabzevari University for partial sup-
port of this work.
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