An efficient one-pot synthesis of dihydropyrano[c]chromenes and amino-2-chromenes under solvent-free conditions

Article abstract of DOI:10.3184/174751913X13639572643562

1,8-Diazabicyclo[5.4.0]-undec-7-en-8-ium acetate, a basic ionic liquid, showed excellent catalytic activity in the three-component condensation reaction of aldehydes and malononitrile with α- or β-naphthol or 4-hydroxycoumarin. The products, amino-4H-chro

Full text of DOI:10.3184/174751913X13639572643562

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 253
APRIL, 253–255
An efficient one-pot synthesis of dihydropyrano[c]chromenes and
amino-2-chromenes under solvent-free conditions
Davood Habibi* and Atefeh Shamsian
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
1,8-Diazabicyclo[5.4.0]-undec-7-en-8-ium acetate, a basic ionic liquid, showed excellent catalytic activity in the three-
component condensation reaction of aldehydes and malononitrile with α- or β-naphthol or 4-hydroxycoumarin. The
products, amino-4H-chromenes and dihyropyrano[c]chromenes respectively, were obtained under mild conditions
without any additional organic solvents in good to excellent yields and short reaction times. The catalyst could be
recycled several times with only slight loss of activity.
Keywords: ionic liquid, chromenes, multi-component reaction, solvent-free reaction, green chemistry
The principles of green chemistry have been introduced to
eliminate or at least to reduce the use of hazardous materials
in chemical processes. Since one of the key areas of green
chemistry is the replacement of hazardous solvents with
environmentally benign ones or the elimination of solvents
altogether,1,2 development of new solid phase (solvent-free)
reactions and transferring solution phase reactions to solid
phase are subjects of recent interest.
Ionic liquids (ILs) are salt-like compounds, which are liq-
uids at room temperature and possess low vapour pressures.
ILs are considered as “green solvents” since unlike the con-
ventional solvents which are volatile, they do not evaporate
and are not harmful to the environment.3–7 These compounds
are known as environmentally benign solvents or catalysts
and much attention has currently been focused on the organic
reactions with ILs as catalysts or solvents and many organic
reactions were performed in ILs with high performance.8,9
Modern synthesis needs access to fast and very efficient
methods to avoid isolation during the reaction. This feature
is perfectly exemplifieded by multi-component reactions
(MCRs).10–12 The first MCR was initiated by Strecker in 1850
for the synthesis of amino acids.13
Since 2-amino-2-chromenes and dihydropyrano[c]chromen
es are known as spasmolytic, diuretic, anticancer, anti-coagu-
lant and anti-HIV agents, much research has been done on
them recently.14
Benzochromenes are widely used as pigments and agro-
chemicals and exhibit interesting biological activities.15 Also,
they are cognitive enhancers for the treatment of neurodegen-
erative diseases including Parkinson’s disease, Down’s
syndrome, schizophrenia, Alzheimer’s disease and AIDS
associated dementia.16
Results and discussion
The reaction of 4-chlorobenzaldehyde (1.0 mmol) and malo-
nonitrile (1.2 mmol) with β- or α- naphthol (1.0 mmol) or
4-hydroxycoumarin (1.0 mmol) in the presence of DBU[Ac] at
80 °C was selected as a model to optimise the reaction
conditions and it wasfound that the best yield was obtained
with 10 mol% of the catalyst (Table 1). When these reactions
were carried out at room temperature or in the absence of the
catalyst, the yield was very low.
Amino-4H-benzo[h]chromenes (2a–h and 3a–h) and 3,4-di
hydropyrano[c]chromenes (4a–h) were synthesised through
the three-component one-pot condensation reaction of alde-
hydes, malononitrile and β-naphthol/α-naphthol or 4-hydroxy-
coumarin in the presence of DBU[Ac] under mild conditions
without any additional organic solvents in good to excellent
yields and short reaction times (Scheme 1, Table 2 ). All the
synthesised compounds are known and were characterised by
comparison of their melting points and spectral data with those
reported in literature.
Aromatic aldehydes with electron-withdrawing groups such
as nitro or halogen (Table 2, entries 3–4, 6–9, 12–14 and 18–
22), reacted faster, while those containing the electron-releas-
ing groups such as methyl or methoxy needed longer reaction
times (Table 2, entries 2, 5, 11, 15 and 23–24). Electron-with-
drawing groups decrease the electron density of the carbon of
the carbonyl group, so facilitating the nucleophilic attack on it,
while the electron-releasing groups act in the opposite way.
Additionally, 4-dimethylaminobenzaldehyde (Table 2, entry
16) failed to give the corresponding product. This may be due
to the strong electron-releasing character of the dimethylamino
group.
The catalyst was recovered from the aqueous medium, dried
under vacuum and reused for consecutive four runs. The yields
obtained were sequentially 94, 93, 91 and 89%, which shows
that the catalyst may be reused without significant loss of
activity.
Recently, relatively benign catalysts such as KF/Al2O3,17
basic alumina,18 triethylamine,19 tetrabutylammonium bromide
(TBAB) and sodium dodecyl sulfate were employed for their
synthesis. However, some of these procedures are limited
due to the use of toxic organic solvents, expensive catalysts
and tedious workup. Thus, here we report an efficient method
for the synthesis of different chromenes using 1,8-diazabicy-
clo[5.4.0]-undec-7-en-8-ium acetate (DBU[Ac]), an ionic liquid.
In Table 3, the capability of the DBU[Ac] catalyst was com-
pared with other literature catalytic systems in the synthesis of
chromenes. It is clear that the ionic liquid catalyst is quicker
than the others and, moreover is solvent-free.
Table 1 Effect upon the yields of different amounts of DBU[Ac] catalyst on the three-component model reaction of
4-chlorobenzaldehyde (1.0 mmol) and malononitrile (1.2 mmol) and α- or β-naphthol or 4-hydroxycoumarin (1.0 mmol) at 80 °C
Entry
Catalyst/mol%
Time/min
Yield % with β-naphthola Yield/% with α-naphthola Yield % with 4-hydroxycoumarina
1
2
3
4
None
240
30
30
5
Trace
70
Trace
67
Trace
60
1
5
10
82
80
75
95
94
93
a Isolated yields.
* Correspondent. E-mail: davood.habibi@gmail.com

254 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 1
Table 2 Synthesis from β- or α-naphthol of variously subsituted aminochromenes (2a–h or 3a–h) and from 4-hydroxycoumarin of
dihydropyranochromenes (4a–h) by a three-component reaction with araldehydes (ArCHO) and malononitrile in the presence of
DBU[Ac] at 80 °C
Entry
R-CHO
Hydroxy compound
Product
Time/min
Yielda/%
M.p./°C
Found
Reported
1
2
C6H4
4-Me-C6H4
4-Cl-C6H4
2-Cl-C6H4
4MeO-C6H4
4-F-C6H4
2,4Cl2-C6H3
3NO2-C6H4
4-Cl-C6H4
C6H5
β-Naphthol
β-Naphthol
2a
2b
2c
2d
2e
2f
2g
2h
3a
3b
3c
3d
3e
3f
4
15
2
96
85
93
95
89
91
95
95
94
93
88
92
95
95
86
–
85
93
91
90
91
93
85
82
287–290
269–271
208–210
270–273
188–191
231–232
221–223
186–188
230–232
210–212
192–194
252–254
214–215
240–243
205–208
–
200–202
214–215
257–259
262–260
257–260
237–235
234–236
230–233
288–28921
270–27222
207–208.523
272–27321
190–191.523
232–23322
222–22421
188–18924
231–232.523
218–21921
195–19621
250–25121
214–21624
214.5–21625
205–20726
–
3
β-Naphthol
4
β-Naphthol
2
5
β-Naphthol
10
2
6
β-Naphthol
7
β-Naphthol
2
8
β-Naphthol
2
9
α-Naphthol
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
α-Naphthol
3
4MeO-C6H4
2-Cl-C6H4
2,4-Cl2-C6H3
3NO2-C6H4
4-Me-C6H4
4-Me2N-C6H4
3-Br-C6H4
4-Cl-C6H4
C6H5
α-Naphthol
7
α-Naphthol
2
α-Naphthol
1
α-Naphthol
1
α-Naphthol
3g
–
5
α-Naphthol
–
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4-Hydroxycoumarin
4a
4b
4c
4d
4e
4f
5
198–19627
212–20928
258–26028
260–26229
262–26430
255–25628
232–23431
228–23029
5
7
4-F-C6H4
5
3NO2-C6H4
4NO2-C6H4
4-OMe-C6H5
3,4-(OMe)2C6H3
4
6
4g
4h
10
15
a Isolated yield.
Table 3 Comparison of the DBU[Ac] with other literature catalysts in the in the synthesis of chromenes
Entry
Catalyst/mol%
Conditions
Time
Yield/%
1
2
3
4
5
Et3N (10)
CuO nanoparticle (15)
TEBA (10)
Triethyamine (10)
DBU[Ac] (10)
CH3CN, room temperature
H2O, reflux
24 h
8032
5 min
3.5 h
3 h
9333
Solvent-free, 80 °C
Ethanol/reflux
Solvent-free, 80 °C
9334
8235
4 min
82–96 (Present work)
Conclusions
very short reaction times, which make it a useful and attractive
strategy for the synthesis of different chromenes.
We report an efficient procedure for the synthesis of 2-amino-
4H-chromenes (2a–h and 3a–h) and 3,4-dihyropyrano[c]-
chromenes (4a–h) through the three-component condensation
reaction of aldehydes, malononitrile and β-naphthol/α-naph-
thol or 4-hydroxycoumarin in the presence of DBU[Ac] as a
reusable, nontoxic and inexpensive catalyst at 80 °C. The
major advantage of this method is the ease of the work-up; so
the products can be isolated without chromatography. The
method also offers some other advantages such as clean reac-
tion, simple synthesis of catalyst, high yields of products and
Experimental
All chemicals were purchased from Aldrich or Merck with high-grade
quality, and used without further purification. Melting points were
taken in open capillary tubes with a BUCHI 510 melting point appa-
ratus and were uncorrected. NMR spectra were recorded in DMSO-d6
on a Bruker 300 MHz spectrometer. FT-IR (KBr) spectra were
recorded on a Perkin-Elmer 781 spectrophotometer. DBU[Ac] was
prepared as a weak basic ionic liquid catalyst according to the reported
procedure.20

JOURNAL OF CHEMICAL RESEARCH 2013 255
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Received 13 December 2012; accepted 14 February 2013
Paper 1201679 doi: 10.3184/174751913X13639572643562
Published online: 19 April 2013
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