Basic ionic liquid-catalyzed multicomponent synthesis of tetrahydrobenzo[b]pyrans and pyrano[c]chromenes

Article abstract of DOI:10.1016/j.mencom.2011.09.017

Triethylenetetraammonium trifluoroacetate-catalyzed condensation of benzaldehydes, malononitrile and cyclic 1,3-dioxo compounds in aqueous medium affords the corresponding fused 2-amino-4-aryl-3-cyanopyrans.

Full text of DOI:10.1016/j.mencom.2011.09.017

Mendeleev
Communications
Mendeleev Commun., 2011, 21, 280–281
Basic ionic liquid-catalyzed multicomponent synthesis
of tetrahydrobenzo[b]pyrans and pyrano[c]chromenes
Jia Zheng and Yiqun Li*
Department of Chemistry, Jinan University, Guangzhou 510632, P. R. China.
Fax: +86 20 8522 8537; e-mail: tlyq@jnu.edu.com
DOI: 10.1016/j.mencom.2011.09.017
Triethylenetetraammonium trifluoroacetate-catalyzed condensation of benzaldehydes, malononitrile and cyclic 1,3-dioxo compounds
in aqueous medium affords the corresponding fused 2-amino-4-aryl-3-cyanopyrans.
Recently, tetrahydrobenzo[b]pyran and pyrano[c]chromene deri-
vatives have attracted increasing interest due to their wide range
of biological properties.1 A variety of technologies including
the use of microwave2 and ultrasonic3 irradiation, as well as
catalysis by tetrabutylammonium bromide (TBAB),4 fluoride anion,5
rare earth perfluorooctanoate,6 acidic ionic liquids (ILs),7 Na2SeO4,8
high surface area MgO,9 [bmim]OH10 etc. were found to be effi-
cient to promote them. In spite of the merits of these procedures,
each of them suffers at least from one of the following limitations:
low yields, unavailability of the catalyst, long reaction times,
effluent pollution, harsh reaction conditions, and tedious work-up.
As environmental friendly reaction media or designable
catalysts, ILs are receiving considerable global attention11 and
used widely in organic reactions.12 In view of the merits of ILs
such as environmental benignity, reusability and easy handling,
we are interested in use of ILs as catalysts in the synthesis of
important biologically active compounds through multicomponent
reaction (MCR) concept. We herein report the preparation of a
series of new Lewis basic task-specific ILs (Scheme 1)† and their
use as catalysts in environmentally benign MCR approach for
the synthesis of tetrahydrobenzo[b]pyran and pyrano[c]chromene
derivatives (Scheme 2).‡
hyde 1a, malononitrile 2 and dimedone 3 (Table 1, entries 1–5).
[TETA]TFA proved to have the best catalytic activity under the
optimal conditions (Table 1, entry 7).
A–
HN
NH
H2N
NH2
H
AcO–
NH2
H2N
H
[EDA]OAc
[TETA]OAc A = AcO,
[TETA]PTS A = 4-MeC6H4SO3
[TETA]BF4 A = BF4,
[TETA]TFA A = CF3COO
Scheme 1 Novel functionalized basic ILs.
O
O
Ar
R
O
CN
R
3
4
O
R
O
NH2
Ar
H
R
O
[TETA]TFA,
5 mol%
OH
O
1
+
5a–m
O
Ar
H2O–EtOH (1:1)
reflux
We initially studied the catalytic activities of the five as-pre-
pared ILs using the model reaction between 4-chlorobenzalde-
CN
CN
O
CN
O
NH2
†
Catalyst preparation. A Brønsted acid (0.05 mol, dissolved in 10.0 ml
2
ethanol) was added dropwise with vigorous stirring to a solution of
triethylenetetramine or ethylenediamine (0.05 mol) in ethanol (10.0 ml)
cooled in an ice–water bath. Then the reaction mixture was stirred for
additional 24 h. After evaporating ethanol, the crude product was washed
three times with diethyl ether, and then dried in vacuo at 60°C to afford
the desired product. All target ILs were characterized by IR, 1H NMR and
13C NMR (see Online Supplementary Materials).
6a–e
Scheme 2
Table 1 Optimization of conditions of the reaction between 1, 2 and 3.a
Time/ Yield of
Entry Solvent
Catalyst (IL) T/°C
min 5a (%)b
‡
Synthesis of 2-amino-4-aryl-3-cyano-7,7-dimethyl-4H-5,6,7,8-tetra-
hydrobenzo[b]pyran-5-ones 5a–m and 2-amino-4-aryl-3-cyano-4H,5H-
pyrano[3,2-c]chromen-5-ones 6a–e (typical procedure). An equimolar
(2.0 mmol) mixture of an aromatic aldehyde 1, malononitrile 2 and
dimedone 3 or hydroxycoumarin 4 were dissolved in H2O–EtOH (1:1,
5.0 ml). Then triethylenetetraammonium trifluoroacetate ([TETA]TFA)
(5 mol%) was added to a flask, and the mixture was vigorously stirred at
reflux for 10–240 min (TLC monitoring). After completion, water (15.0 ml)
was added to quench the reaction and to precipitate the crude product.
The crude product was collected by filtration and further purified by
recrystallization from methanol.
1
2
3
4
5
6
7
8
9
H2O
H2O
H2O
H2O
H2O
EtOH
[EDA]OAc 80
[TETA]OAc 80
[TETA]PTS 80
[TETA]BF4 80
[TETA]TFA 80
[TETA]TFA reflux
60
40
40
40
30
30
10
42
70
65
57
77
93
95
41
74
92
95
H2O–EtOH (1:1) [TETA]TFA reflux
H2O–EtOH (1:1) [TETA]TFA room temperature 120
H2O–EtOH (1:1) [TETA]TFA 60
60
45
10
For 5a: IR (KBr, n/cm–1): 3381, 3184, 2959, 2188, 1674, 1635, 1604,
1365, 1216. 1H NMR (DMSO-d6, 300 MHz) d: 0.93 (s, 3H), 1.02 (s, 3H),
2.10 (d, 1H, J 16.1 Hz), 2.21 (d, 1H, J 16.1 Hz), 2.50 (s, 2H), 4.19 (s, 1H),
7.05 (s, 2H), 7.18 (d, 2H, J 8.3 Hz), 7.33 (d, 2H, J 8.3 Hz).
10c H2O–EtOH (1:1) [TETA]TFA reflux
11d H2O–EtOH (1:1) [TETA]TFA reflux
a Reaction conditions: 4-chlorobenzaldehyde (2.0 mmol), malononitrile
(2.0 mmol), dimedone (2.0 mmol), ionic liquid (0.1 mmol), solvent (5.0 ml).
b Isolated yield. c1 mol% of catalyst was used. d10 mol% of catalyst was used.
For spectral characteristics of compounds 5d,f,h,l and 6a,b, see Online
Supplementary Materials.
© 2011 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2011, 21, 280–281
Table 2 [TETA]TFA catalyzed synthesis of tetrahydrobenzo[b]pyrans 5a–m
at least 8 runs without loss of its activity. In comparison with the
reported IL [bmim]OH10 and [bmim]PF617 systems, our IL catalytic
system shows comparative yields and excellent reusabilities.
In summary, we have prepared a series of new basic task-specific
ionic liquids and used them as catalysts for the synthesis of pyran-
annulated heterocyclic systems. This novel catalytic system
demonstrates the advantages of environmentally benign charac-
ter, mild reaction conditions, short reaction times, high yields,
easy handling as well as good reusability.
in aqueous media.a
Time/ Yield
min
Entry Ar
R
Product
Mp/°C
(%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
4-ClC6H4
2,4-Cl2C6H3 Me 5b
4-BrC6H4
4-O2NC6H4
3-O2NC6H4
Ph
Me 5a
10
30
5
94
94
92
87
91
85
50
88
89
83
73
69
75
211–2134(a)
114–1166
193–1953
183–1857
202–2046
213–21613
205–2078
197–1997
208–2104(a)
214–2158
228–2305
220–2229
186–1897
Me 5c
Me 5d
Me 5e
Me 5f
Me 5g
30
25
20
240
50
15
25
90
10
30
This work was supported by the National Natural Science
Foundation of China (grant nos. 21072077 and 20672046)
and the Guangdong Natural Science Foundation (grant nos.
110151063201000051 and 8151063201000016).
4-HOC6H4
4-MeOC6H4 Me 5h
4-MeC6H4 Me 5i
4-Me2NC6H4 Me 5j
2-Furyl
Ph
Me 5k
H
H
5l
5m
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2011.09.017.
4-MeOC6H4
a Reaction conditions: aldehyde (2.0 mmol), malononitrile (2.0 mmol),
dimedone (or cyclohexane-1,3-dione) (2.0 mmol), [TETA]TFA (0.1 mmol),
H2O–EtOH (1:1, 5.0 ml), reflux. b Isolated yield.
References
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Subsequently, we demonstrated the scope and generality of
the present method by the reaction of various benzaldehydes 1
with malononitrile 2 and cyclohexane-1,3-diones 3 catalyzed by
[TETA]TFA under the optimal conditions (Table 2). Benzaldehyde
and the aromatic aldehydes bearing electron-withdrawing groups
(such as nitro group, halogen) (Table 2, entries 1–6) required a
shorter reaction time and gave higher yields than those bearing
electron-donating groups (such as N,N-dimethylamino, hydroxy,
methoxy and methyl) (Table 2, entries 7–10). Note that no O-pro-
tection was required for 4-hydroxybenzaldehyde (Table 2, entry 7).
Encouraged by these results, we extended the scope of this
method towards the synthesis of pyrano[c]chromenes 6 from
4-hydroxycoumarin 4 (Scheme 2, Table 3). 3-Nitrobenzaldehyde
bearing nitro group in meta-position in the aromatic ring has
lower reactivity and required longer reaction time (Table 3, entry 5)
than p-nitro-substituted benzaldehyde (entry 1). Other benzalde-
hydes provided good yields in short time (Table 3, entries 2–4).
In view of green chemistry, reuse of the catalyst is highly
preferable. The reusability of the catalyst was exemplified on
reaction between 4-chlorobenzaldehyde, dimedone and malono-
nitrile. After the separation of products, the IL catalyst was
easily recovered and recycled by removal of the filtrate after
filtering off the products. The product was obtained in 94, 94,
95, 93, 94, 93, 91 and 90% yield in consecutive 1 to 8 runs,
respectively, which indicated that the catalyst could be reused for
12 (a) S. G. Zlotin and N. N. Makhova, Mendeleev Commun., 2010, 20, 63;
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Table 3 [TETA]TFA catalyzed synthesis of pyrano[c]chromenes 6a–e in
aqueous media.a
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104, 39.
Entry Ar
Product Time/min Yield (%)b Mp/°C
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1
2
3
4
5
4-O2NC6H4
Ph
4-MeOC6H4
4-MeC6H4
3-O2NC6H4
6a
6b
6c
6d
6e
10
20
50
20
120
94
86
85
88
75
249–25114
253–25514
238–24015
245–24716
246–24816
a Reaction conditions: aldehyde (2.0 mmol), malononitrile (2.0 mmol),
4-hydroxycoumarin (2.0 mmol), [TETA]TFA (0.1 mmol), H2O–EtOH (1:1,
5.0 ml), reflux. b Isolated yield.
Received: 17th March 2011; Com. 11/3699
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