Photodimerization of 4-Aryl-1,4-dihydropyridines in 1-Butyl-3-methylimidazolium tetrafluoroborate

Article abstract of DOI:10.1246/cl.140513

A simple, efficient, and convenient method for the photodimerization of 4-aryl-1,4-dihydropyridine in room-temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]) has been developed. By this way, head-to-tail syn-di

Full text of DOI:10.1246/cl.140513

CL-140513
Received: May 21, 2014 | Accepted: June 19, 2014 | Web Released: June 26, 2014
Photodimerization of 4-Aryl-1,4-dihydropyridines
in 1-Butyl-3-methylimidazolium Tetrafluoroborate
Jing-Yu He,* Hui-Zhen Jia, Qing-Guo Yao, Si-Jie Liu, Hong-Kun Yue, Wei-Yan Liu, Xiao-Hong Wang, and Jing-Chao Tian
College of Chemical Engineering, Shijiazhuang University, Shijiazhuang 050035, Hebei, P. R. China
(E-mail: jyhe@emails.bjut.edu.cn)
A simple, efficient, and convenient method for the photo-
dimerization of 4-aryl-1,4-dihydropyridine in room-temperature
ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate
([Bmim][BF4]) has been developed. By this way, head-to-tail
syn-dimers and 3,9-diazatetraasteranes were obtained in good to
excellent yields. In addition, [Bmim][BF4] can be reused at least
5 times as the medium without obvious decrease in reaction time
and yield.
occurs in solid state or in organic solution, but there have been
few reports on photodimerizaiton in ionic lquid.1-3,6 In the
framework of our investigations on the development of green
chemical procedures,7 we would like to herein report a novel and
environmentally safe procedure for photodimerization of 4-aryl-
1,4-dihydropyridines in room-temperature ionic liquid 1-butyl-
3-methylimidazolium tetrafluoroborate ([Bmim][BF4]), which is
designed to overcome the limitations previously encountered in
the reaction.
Ionic liquid [Bmim][BF4] has been used as a convenient,
economic, and user-friendly reaction medium for synthesizing
1,4-dihydropyridines.8 In search of the best experimental
reaction conditions, the photodimerization of 4-phenyl-1,4-
dihydropyridine (1a) in IL [Bmim][BF4] was considered as a
standard model reaction to obtain photodimer intermediate and
corresponding cage-dimeric 3,9-diazatetraasterane. We tested the
effects of different concentration of 4-phenyl-1,4-dihydropyr-
idine (1a) (0.08-0.16 mmol mL¹1) and various power (400-
500 W) of unfiltered light from a medium pressure mecury lamp
at -max > 313 nm on the photodimerization (Table 1). Results
Photodimerization of 4-aryl-1,4-dihydropyridines has at-
tracted some attention because its major products 3,9-diazatetra-
asteranes have been suggested as interesting pharmacological
targets with potential anticancer or anti-HIV activity.1 A solid-
state method has been initially developed through the photo-
dimerization of 4-aryl-1,4-dihydropyridine 1 under solvent-free
condition by Hilgeroth and co-workers.1b,2 Although the method
can produce syn-dimer intermediate 2 and 3,9-diazatetraasterane
3, it could hardly been used on a industrial scale due to the
small-scale production, a long reaction time, and low yield.
Later, the solution-dimerization of 4-aryl-1,4-dihydropyridines
has been reported to give anti-dimer intermediate 4 and 3,9-
diazatetraasterane 3. However, a large amount of organic
solvent, harsh reaction condition, a long reaction time, and
low yields still represent main disadvantages (Scheme 1).3
Recently, ionic liquids (ILs) have emerged as a set of green
solvents with unique properties such as tunable polarity, high
thermal stability and immiscibility with a number of organic
solvents, negligible vapor pressure, and recyclability.4 Their
high polarity and the ability to solubilize both organic and
inorganic compounds can result in enhanced rates of chemical
processes and can provide higher selectivities than conventional
solvents. Accordingly they are emerging as novel replacements
for volatile organic solvents in organic synthesis. They are
particularly promising as solvents for catalysis.5 Because of
distinct advantages of ILs as environmentally benign reaction
media for catalytic processes, much attention has currently
focused on organic reactions promoted by ionic liquids. To the
best of our knowledge, [2 + 2] photocycloaddition usually
showed that saturated9 4-phenyl-1,4-dihydropyridine (1a)
¹1
0.16 mol L
and a medium pressure mecury lamp 450 W
provided the best conditions to give intermediate 2a and cage
dimer 3a in 92 and 89% yield within 15 and 30 min, respectively
(Table 1, Entries 6 and 12). The structure of intermediate 2a
(CCDC No. 992512) was finally determined to be a head-to-tail
syn-dimer by single-crystal X-ray diffraction as shown in
Figure 1.10 Moreover we found that the formed subsequence
was syn-dimer 2 before cage photodimer 3, so the reaction path
Table 1. Photodimerization of 4-phenyl-1,4-dihydropyridine
(1a) in [Bmim][BF4]a
Concentration Power of UV Time Yieldb
Entry Product
¹1
/mmol mL
lamp/W
/min
/%
1
2
3
4
5
6
7
8
9
10
11
12
13
2a
2a
2a
2a
2a
2a
2a
3a
3a
3a
3a
3a
3a
0.08
0.1
400
400
400
400
400
450
500
400
400
400
400
450
500
180
100
60
40
25
65
77
80
81
85
92
80
68
76
80
81
89
68
0.12
0.14
0.16
0.16
0.16
0.08
0.10
0.12
0.14
0.16
0.16
MeO2
C
CO2Me
MeO2
C
CO2Me
NH
15
10
R
R
HN
NH
HN
R
R
+
MeO2C
CO2Me
240
200
180
100
30
R
MeO2C
CO2Me
CO2Me
MeO2C
CO2Me
2
3
N
H
MeO2
HN
C
NH
R
R
3
+
1
CO2Me
CO2Me
30
4
aReaction condition: 1a (0.8-1.6 mmol), [Bmim][BF4]
(10 mL), light (400-500 W medium pressure mecury lamp
with -max > 313 nm). Isolated yields.
Scheme 1. Photodimerization of 4-aryl-1,4-dihydropyridine
under solid-state and solution conditions.
b
1596 | Chem. Lett. 2014, 43, 1596–1598 | doi:10.1246/cl.140513
© 2014 The Chemical Society of Japan

Table 2. Preparation syn-dimers 2 and cage dimers 3 in
[Bmim][BF4]a
Time
/min
Yieldb
/%
Entry
Product
R
1
2
3
4
5
6
7
8
9
2a
H
4-Me
4-OMe
4-Cl
4-OH
3-OMe, 4-OH
H
4-Me
4-OMe
4-Cl
4-OH
15
15
10
15
15
20
35
30
35
40
35
30
92
90
92
89
88
90
89
85
81
84
86
85
2bc
2c
2dc
2ec
2fc
3a
3bc
3c
3dc
3ec
3fc
10
11
12
Figure 1. ORTEP diagram of the crystal structure of com-
pound 2a (Drawn at the 50% thermal ellipsoids).
3-OMe, 4-OH
aReaction condition: 1 (1.6-1.8 mmol), [Bmim][BF4] (10 mL)
(saturated concentration), light (450 W medium pressure
mecury lamp with -max > 313 nm). bIsolated yields. cNew
compound.
CO2Me
NH
MeO2C
MeO2C
CO2Me
NH
hv
hv
MeO2C
CO2Me
HN
HN
[Bmim][BF4]
[Bmim][BF4]
N
H
MeO2C
CO2Me
MeO2C
CO2Me
1a
2a
3a
CO2Me
NH
MeO2C
MeO2C
CO2Me
NH
Scheme 2. Photodimerization of 4-phenyl-1,4-dihydropyri-
dine (1a) under ionic liquid conditions.
R
R
R
HN
HN
R
R
hv
[Bmim][BF4]
hv
[Bmim][BF4]
MeO2C
CO2Me
MeO2C
CO2Me
3
MeO2C
CO2Me
N
H
was presumed to be 4-aryl-1,4-dihydropyridine 1 producing the
syn-dimer 2 through [2 + 2] cycloaddition, then 3,9-diazate-
traasterane 3 being obtained by the photodimerization of the syn-
dimer intermediate 2 in [Bmim][BF4] (Scheme 2). Solid-state
photodimerization yielded the same products syn-dimer 2a and
cage dimer 3a as the IL method, but it had some disadvantages
such as a long reaction time (3 to 4 days), tedious process, and
low yield.3 Results in Table 1 showed that the photodimerization
of 4-phenyl-1,4-dihydropyridine in IL could not only be used
as a substitute for the solid-state method, but also has distinct
advantages such as a short reaction time, easy purification, and
higher yield.
For assessing the generality of reaction condition, we next
investigated the photodimerizaiton of different substituted 4-
phenyl-1,4-dihydropyridines under the IL reaction conditions
(Table 2). It seemed that there was little difference between
yields of photodimer products with electron-donating groups
and electron-withdrawing groups, and all the photodimerization
showed high reactivity and exclusive selectivity. Various 4-
phenyl-1,4-dihydropyridines 1 gave syn-dimer intermediates 2
within 10-20 min and in 88-92% yields, and the corresponding
3,9-diazatetraasteranes 3 within 30-40 min and in 81-89%
yields (Scheme 3).
2
1
R =a: H; b: 4-Me; c: 4-OMe; d: 4-Cl; e: 4-OH; f: 3-OMe, 4-OH
Scheme 3. Photodimerization of 4-aryl-1,4-dihydropyridines
in [Bmim][BF4].
[Bmim][BF4] as reaction medium gave 2a in 90-92% yield and
3d in 81-84% yield. The use of IL [Bmim][BF4] as reaction
medium for this transformation avoids the use of organic
solvents and also avoids aqueous workup to isolate the products.
The simple experimental and product isolation procedures
combined with the ease of recovery and reuse of the novel
reaction medium is expected to contribute to the development of
a green strategy for the synthesis of syn-dimers and correspond-
ing 3,9-diazatetraasteranes.
In summary, we developed an efficient and environmentally
benign method for the photodimerization of 4-aryl-1,4-dihydro-
pyridines in ionic liquid [Bmim][BF4]. syn-Dimers and corre-
sponding 3,9-diazatetraasteranes were obtained in high yields
within a short time, and the reaction medium [Bmim][BF4] ionic
liquid can be reused five times without distinct decrease in
yields.
To check the reusability of IL as solvent, when the
photodimerization of 4-phenyl-1,4-dihydropyridines was com-
pleted, the mixture was poured into water, and the crude product
was obtained by filtration. The product was recrystallized
from alcohol. The aqueous layer containing IL was subjected
to vacuum distillation to remove water, leaving the IL
[Bmim][BF4]. The residual IL was washed with a small amount
of ethyl acetate, dried under vacuum at 80 °C for 4 h and
recycled. It was found that the medium [Bmim][BF4] can be
recycled at least five times with no significant decrease in yields
of products. For example, photodimerization in the fifth reuse of
The project was supported by the Shijiazhuang National
Natural Science Foundation (No. 12120453) and the Hebei
National Natural Science Foundation (No. B2014106034).
Supporting Information is available electronically on J-STAGE.
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1598 | Chem. Lett. 2014, 43, 1596–1598 | doi:10.1246/cl.140513
© 2014 The Chemical Society of Japan