A one-pot multicomponent reaction for the synthesis of 2-amino-2-chromenes promoted by N,N-dimethylamino-functionalized basic ionic liquid catalysis under solvent-free condition

Article abstract of DOI:10.1007/s00706-008-0008-3

A simple, clean, and environmentally benign three-component process to the synthesis of 2-amino-4H-chromenes using N,N- dimethylaminoethylbenzyldimethylammonium chloride, [PhCH₂Me ₂N⁺CH₂CH₂NMe₂

Full text of DOI:10.1007/s00706-008-0008-3

Monatsh Chem (2009) 140:45–47
DOI 10.1007/s00706-008-0008-3
ORIGINAL PAPER
A one-pot multicomponent reaction for the synthesis
of 2-amino-2-chromenes promoted by N,N-dimethyl-
amino-functionalized basic ionic liquid
catalysis under solvent-free condition
Lu Chen Æ Xu-Jiang Huang Æ Yi-Qun Li Æ
Mei-Yun Zhou Æ Wen-Jie Zheng
Received: 4 May 2008 / Accepted: 4 June 2008 / Published online: 6 September 2008
Ó Springer-Verlag 2008
Abstract A simple, clean, and environmentally benign
three-component process to the synthesis of 2-amino-4H-
chromenes using N,N-dimethylaminoethylbenzyldimethyl-
ammonium chloride, [PhCH2Me2N?CH2CH2NMe2]Cl-,
as an efficient catalyst under solvent-free condition is
described. A wide range of aromatic aldehydes easily
undergo condensations with a-naphthol and malononitrile
under solvent-free condition to afford the desired products
of good purity in excellent yields. Taking into account
environmental and economical considerations, the protocol
presented here has the merits of environmentally benign,
simple operation, convenient work-up and good yields.
Furthermore, the catalyst can be easily recovered and
reused for at least five cycles without losing its activities.
pigments [2], and utilized as potential biodegradable
agrochemicals [3].
2-Aminochromenes are generally prepared by refluxing
malononitrile, aldehyde, and activated phenol in the pres-
ence of hazardous organic bases like piperidine in organic
solvents such as ethanol and acetonitrile for several hours
[4]. A literature survey revealed several modified proce-
dures using cetyltrimethylammonium chloride (CTAC) [5],
tetrabutylammonium bromide (TBAB) [6], cetyltrimethyl-
ammonium bromide (CTAB) coupled with ultrasound [7],
c-alumina [8], K2CO3 [9], nanosize MgO [10], hetero-
polyacid [11], hexadecyltrimethylammonium bromide
(HTMAB)[12], triethylbenzylammonium chloride (TEBA)
[13] and TiCl4 [14]. However, some of the reported
methods require prolonged reaction time, reagents in stoi-
chiometric amounts, and toxic solvents, and generate
moderate yields of the product.
Keywords Chromene Á Multicomponent reaction Á
N,N-Dimethylaminoethylbenzyldimethylammonium
chloride Á Solvent-free condition
The increasing attention during the last decades for
environmental protection has led both modern academic
and industrial groups to develop chemical processes with
maximum yield and minimum cost while using non-toxic
reagents, solvents, and catalysts or solvent-free condition.
One of the tools used to combine economic aspects with
the environmental ones is the multicomponent reaction
(MCR) strategy; this process consists of two or more
synthesis steps which are carried out without isolation of
any intermediate thus reducing reaction time, and saving
money, energy, and raw materials [15, 16].
Introduction
2-Aminochromenes represent an important class of com-
pounds being the main components of many naturally
occurring products, and have been of interest in recent
years due to their useful biological and pharmacological
aspects, such as anticoagulant, spasmolytic, diuretic,
insecticidal, anticancer, and antianaphylactin activity [1].
Some of them can also be employed as cosmetics and
As part of our program aimed at developing useful
new selective and synthesis methods based on the use of
functionalized ionic liquids as catalysts of fine chemi-
cals preparation, we have studied using the MCR
strategy for the synthesis of substituted 2-aminochrom-
enes using the basic ionic liquid catalyst, N,N-
L. Chen Á X.-J. Huang Á Y.-Q. Li (&) Á M.-Y. Zhou Á
W.-J. Zheng
Department of Chemistry, Jinan University,
Guangzhou 510632, China
e-mail: tlyq@jnu.edu.cn
dimethylaminoethylbenzyldimethylammonium
chloride
123

46
L. Chen et al.
Scheme 1
Me
OH
[Ph N CH CH NMe ]
Cl
2
2
2
CN
CN
Me
solvent-free, 80oC
O
NH2
CN
ArCHO
+
+
Ar
1
2
3
4
Table 1 Synthesis of 2-amino-2-chromene using N,N-dimethylaminoethylbenzyldimethylammonium chloride as catalyst under solvent-free
condition
Entry
Ar–
Product
Time/min
Yieldsa/%
Mp/°C
Lit. Mp/°C
1
C6H5
4a
4b
4c
4d
4e
4f
35
30
91
93
70
82
95
94
53
82
46
65
62
56
210–212
231–232
237–238
220–222
230–231
208–210
195–197
205–206
245–247
190–192
136–138
169–171
210–211 [7]
231–232 [10]
236–237 [7]
222–224 [12]
231–234 [10]
208–211 [10]
203–205 [6]
205–206 [13]
245 [14]
2
4-Cl-C6H4
3
2-Cl-C6H4
100
50
4
2,4-Cl2-C6H3
4-NO2-C6H4
3-NO2-C6H4
4-Me2N-C6H4
4-Me-C6H4
4-HO-C6H4
4-MeO-C6H4
3-MeO-4-OH-C6H3
2-Furyl
5
40
6
80
7
4g
4h
4i
60
8
100
40
9
10
11
12
a
4j
120
130
120
191 [11]
4k
4l
137–139 [7]
169–172 [10]
Isolated yields
([PhCH2Me2N?CH2CH2NMe2]Cl-), under solvent-free
condition.
The ionic liquid catalyst is in favor of melting of the
reaction mixture and plays a crucial role in the success of
the reaction in terms of the rate and the yields. Reacting
benzaldehyde with 2 and 3 as a reference, the reaction
could not be carried out in the absence of the catalyst at
80 °C. When 1 mol% of the catalyst was used, the yield
of the product reached 70% at 80 °C under solvent-free
condition for 2 h. Increasing the amount of catalyst from
5 to 10 mol%, the reaction yields rose from 83 to 92%.
Therefore, 10 mol% of the catalyst was enough to push the
reaction to completion.
Results and discussion
The model reaction was carried out simply by mixing
benzaldehyde, malononitrile (2), a-naphthol (3), and the
ionic liquid catalyst at 80 °C for 35 min without any sol-
vent to afford the desired product in good yield. The scope
and the generality of the present method were then further
demonstrated by the reaction of 1 with 2 and 3 (Scheme 1).
In all cases, good yields with good selectivity were
obtained. All the results are shown in Table 1.
In view of the green chemistry, the catalyst was further
explored for the reusability by a model reaction of 4-
chlorobenzaldehyde and reactants 2 and 3 under similar
conditions in the presence of 10 mol% catalyst. The cata-
lyst was easily recovered by washing the reaction mixture
with distilled water and directly reused for the next turn
after evaporation of water under reduced pressure. The
recycled catalyst has been reused five times to catalyze the
model reaction affording the corresponding chromene in
91, 88, 90, 87, and 89% yields, and without appreciable
decreases of yield.
As can be seen from Table 1, electronic effects and the
nature of substituents on the aromatic ring did show strong
effects in terms of reaction time under the reaction
conditions mentioned above. When aromatic aldehydes
containing electron-donating groups (such as hydroxyl,
alkoxyl, or methyl group) were employed (Table 1, entries
7–11), a longer reaction time was required than those of
electron-withdrawing groups (such as nitro group, halide)
on aromatic rings (Table 1, entries 2–6). It is worthy of
note that the reaction proceeded without the protection of
acidic hydroxyl substituents (Table 1, entries 9 and 11).
In conclusion, we describe a practical and efficient
procedure for the preparation of 2-amino-2-chromenes
through the three-component reaction of aromatic
123

A one-pot multicomponent reaction for the synthesis of 2-amino-2-chromenes
47
aldehydes, malononitrile (2), and a-naphthol (3) using a
catalytic amount of N,N-dimethylaminoethylbenzyldime-
thylammonium chloride as catalyst under solvent-free
condition. This procedure offers several advantages
including mild reaction conditions, cleaner reaction, and
satisfactory yields of products, as well as a simple exper-
imental and isolated procedure, which makes it a useful
and attractive protocol for the synthesis of these
compounds.
reused another cycle after evaporation of water. All of the
products are known and the data are found to be identical
with those that reported in literature (Table 1).
Acknowledgments We are grateful to the National Natural Science
Foundation of China (No 20672046) and the Guangdong Natural
Science Foundation (No 04010458) for financial support.
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¨
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123