An efficient protocol for synthesis of tetrahydrobenzo[b]pyrans using amino functionalized ionic liquid

Article abstract of DOI:10.1016/j.crci.2011.02.007

A new functionalized basic ionic liquid, 4-amino-1-(2,3-dihydroxy propyl) pyridinium hydroxide [ADPPY] [OH], has been introduced as a catalyst for the synthesis of tetrahydrobenzo[b]pyrans under mild conditions. The desired products can be separated direc

Full text of DOI:10.1016/j.crci.2011.02.007

C. R. Chimie 14 (2011) 878–882
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Preliminary communication/Communication
An efficient protocol for synthesis of tetrahydrobenzo[b]pyrans using
amino functionalized ionic liquid
P.P. Salvi a, A.M. Mandhare a, A.S. Sartape a, D.K. Pawar a, S.H. Han b, S.S. Kolekar a,
*
a Department of Chemistry, Shivaji University, Kolhapur 416 004 (MS), India
b Inorganic Nano-Material Laboratory, Department of Chemistry, Hanyang University, Seoul 133-791, South Korea
A B S T R A C T
A R T I C L E I N F O
Article history:
A new functionalized basic ionic liquid, 4-amino-1-(2,3-dihydroxy propyl) pyridinium
Received 22 November 2010
Accepted after revision 9 February 2011
Available online 21 March 2011
hydroxide [ADPPY] [OH], has been introduced as
a catalyst for the synthesis of
tetrahydrobenzo[b]pyrans under mild conditions. The desired products can be separated
directly from the reaction mixture with high purity. Only 10 mol% catalyst was needed
with a sequestration time of 10 min. In addition, the ionic liquid used can be regenerated
and recycled several times without significant loss of activity.
Keywords:
TSIL
´
ß 2011 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Regeneration of catalyst
Tetrahydrobenzo[b]pyrans
Multicomponent synthesis
Green
1. Introduction
Tetrahydrobenzo[b]pyrans have recently attracted at-
tention as an important class of heterocyclic scaffolds in the
Ionic liquids offer the potential for ground-breaking
changes to synthesis routes and unit operations in research
as well as in the chemical industry. Although the ionic
liquid was initially introduced as an alternative green
reaction medium, today it has marched far beyond
showing its significant role in controlling the reaction as
catalyst. The large number of cations and anions allow a
wide range of physical and chemical characteristics to be
achieved, including volatile and involatile systems, and
thus the terms ‘‘designer’’ and ‘‘task-specific’’ ILs have been
developed [1–4]. The prospects for ionic liquid use are vast.
A number of ionic liquids with unique properties have
been developed and applied to catalyze many types of
reactions. Recently, basic ionic liquids have aroused
unprecedented interest because they showed more
advantages, such as catalytic efficiency and recycling of
the ionic liquid, than the combination of an inorganic base
and an ionic liquid for some base-catalyzed processes [5].
field of drugs and pharmaceuticals. These compounds are
widely used as anti-coagulant, diuretic, spasmolytic, anti-
cancer and anti-anaphylactin agents [6]. In addition, they
can be used as cognitive enhancers, for the treatment of
neurodegenerative disease, including Alzheimer’s disease,
amyotrophic lateral sclerosis, Huntington’s disease, Parkin-
son’s disease, AIDS associated dementia and Down’s
syndrome as well as for the treatment of schizophrenia
and myoclonus [7]. Some 2-amino-tetrahydrobenzo[b]pyr-
ans can be employed as photoactive materials [8]. Synthesis
of tetrahydrobenzo[b]pyrans was traditionally promoted by
harsh bases, strong acids or high temperature in the
presence of VOCs [9–17]. A little effort has been made in
view of green synthesis of tetrahydrobenzo[b]pyrans [18–
20]. Surprisingly, there have been no reports regarding the
use of the amino functionalized ionic liquids in an effort to
influence the outcome of multicomponent reactions. In this
report we will describe the synthesis of a functionalized
ionic liquid, 4-amino-1-(2,3-dihydroxy propyl) pyridinium
hydroxide [ADPPY] [OH] and its application as a mild
catalyst for the synthesis of tetrahydrobenzo[b]pyrans.
The basic idea here is to replace the scavenger reagents
by a functionalized ionic liquid. In comparison with the
* Corresponding author.
E-mail address: kolekarss2003@yahoo.co.in (S.S. Kolekar).
1631-0748/$ – see front matter ß 2011 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2011.02.007

P.P. Salvi et al. / C. R. Chimie 14 (2011) 878–882
879
Table 1
Optimization of reaction conditions for the synthesis of tetrahydrobenzo[b]pyran in different ILs as a catalyst.
Entry
Ionic Liquids
Solventb
Mol%
Time (min.)
Yield (%)a
1
2
[bmim]BF4
[bmim]OH
[bmim]PF6
[bpyr]BF4
H2O
40
40
40
40
40
40
40
10
05
10
15
30
45
480
50
0
75
46
20
35
55
61
90
78
95
92
91
91
H2O
3
H2O + C2H5OH (70:30)
120
240
180
180
180
15
4
H2O
5
[bpyr]PF6
H2O + C2H5OH (70:30)
6
[omim]BF4
[omim]PF6
[ADPPY]OH
[ADPPY]OH
[ADPPY]OH
[ADPPY]OH
[ADPPY]OH
[ADPPY]OH
H2O
7
H2O + C2H5OH (70:30)
8
H2O + C2H5OH (90:10)
9
H2O
H2O
H2O
H2O
H2O
25
10
11
12
13
10
15
15
15
a
All reactions were carried out of benzaldehyde: malononitrile: dimedone 1:1:1 (molar ratio) at room temperature in ionic liquids; yield refer to pure
isolated products.
b
Entries in bracket indicate the ratio of H2O to C2H5OH on volume basis.
other scavengers, this synthetic approach has several
outstanding advantages, including a high active site of IL,
time saving, easy monitoring and unlimited scale-up
potential in water. It is also worth noting that the used
ionic liquids could be regenerated and recycled at least five
times without significant loss of activity.
catalytic performance of [ADPPY] [OH], [BMIM] [OH] could
be much better than other ILs under the same reaction
conditions. It is evident that the yields of the desired
product in the ionic liquids containing the hydroxyl anion
are higher than those in the ionic liquids containing
tetrafluoroborate as well as hexaflurophosphate.
Furthermore, it can be seen that the conversion for
reaction with [ADPPY] [OH] as catalyst was better than
[BMIM] [OH]. These results suggest that the performance
of the IL is dependent upon the character of the side chain
of the cation and the N-heterocyclic ring. [ADPPY] [OH]
exhibited the most excellent catalytic performance with
high conversion under the same reaction conditions
(Table 2, entry 10).
2. Results and discussion
2.1. Effect of different ILs
Our efforts were focused on the synthesis of the
tetrahydrobenzo[b]pyrans using amino functionalized
ionic liquids in comparison with other ILs. The results
are summarized in Table 1.
As shown in Table 1, the molar ratio of IL/substrate and
the reaction times both have significant effects on the
reaction. It could be seen that with the increase of the
molar ratio of IL/substrate from 5 to 10%, the reaction yield
was significantly improved and then it reduces (Table 1).
Upon examination, it was found that 10 mol% of IL was
sufficient to promote the reaction. In the presence of less
than this amount, the yield dropped dramatically, even if
longer reaction times were used (Table 1, entry 9). When
the amount of IL was increased over 10 mol% equivalent,
neither the yield nor the reaction time was improved
(Table 1, entries 11–13). Experiments show that the
2.2. Reusability of [ADPPY] [OH] as catalyst
As one of the most effective functionalized IL, [ADPPY]
[OH] was selected to investigate the possibility of
reusability (Fig. 1). As the product is insoluble in water,
it was collected by simple filtration, while the ionic liquid
is completely soluble in water. So, after completion of
reaction, it became very easy to isolate the product from
the ionic liquid. The IL could be recovered easily by rotary
evaporator and directly reused for subsequent runs. As it is
shown in Fig. 1, no obvious change was observed on the
recovered catalytic and excellent yield was obtained. After
Table 2
[ADPPY] [OH] catalyzed synthesis of tetrahydrobenzo[b]pyran derivatives.
Entry
Ar
Producta
Time (min.)
R1,R2
Yield (%)b
1
2
4-Cl-C6H4
4a
4b
4c
4d
4e
4f
15
20
15
25
15
20
20
25
20
25
25
20
CH3,CH3
CH3,CH3
CH3,CH3
CH3,CH3
CH3,CH3
H,H
94
90
95
89
84
92
89
91
94
90
89
90
4-OMe-C6H4
C6H5
3
4
2,5-2Cl-C6H3
3-Pyridine
5
6
3-Pyridine
7
Thiophene
4g
4h
4i
CH3,CH3
CH3,CH3
H,H
8
3,4-2CH3-C6H3
3,4-2CH3-C6H3
4-isopropyl benzaldehyde
C6H11
9
10
11
12
4j
CH3,CH3
CH3,CH3
CH3,CH3
4k
4L
4-CN-C6H4
aAll products showed satisfactory spectroscopic data (IR, 1H and 13C NMR). bYields refer to pure, isolated products.

880
P.P. Salvi et al. / C. R. Chimie 14 (2011) 878–882
100
95
aldehydes (1 mmol), malononitrile (1 mmol) and 1,3-di
ketone (1 mmol) as a model. Unfortunately, as the ionic
liquid is very viscous, water (3 mL) was used as sequester.
The reaction was carried out at room temperature with
constant stirring for just 10 minutes to get a single product
in excellent yield (95%). The formation of the product was
further confirmed by IR, 1H NMR and 13C NMR spectrosco-
py. It is worthy to mention that no by-product was
detected. A variety of aldehydes and 1,3-diketone also
underwent to afford the corresponding tetrahydroben-
zo[b]pyrans in moderate to high yields. Aromatic alde-
hydes with either electron donating or electron
withdrawing groups underwent the reaction smoothly.
Having obtained favourable results with aromatic alde-
hydes, we then examined heterocyclic aldehydes such as
pyridine-3-carboxylaldehyde and 2-furaldehyde. The
results are summarized in Table 2. A conceivable mecha-
nism for the multicomponent synthesis of tetrahydroben-
zo[b]pyran using [ADPPY] [OH] is proposed (Schemes 2
and 3).
90
85
80
1
2
3
4
5
Number of Runs
Fig. 1. Reusability of [ADPPY] [OH].
five times reusability, the IL remains stable and has less
impact on the catalytic activity.
3. Conclusion
In summary, we have introduced
a new amino
functionalized ionic liquid ([ADPPY] [OH]) that can be
used as an efficient catalyst for tetrahydrobenzo[b]pyrans.
The heterocycles synthesized in this study were obtained
in high regioselectivity, good yields and short reaction
times.
4.3. Spectral data
4.3.1. Spectral data for TSIL (4-amino-1-(2,3-dihydroxy
propyl) pyridinium, hydroxide)
1H NMR (300 MHz, DMSO-d6):
d 3.179 (m, 2H), 3.725
4. Experimental
(s, 1H), 3.953–4.024 (m, 1H), 4.229–4.284 (m, 1H), 5.067
(t, 1H, OH), 5.425 (d, 1H, OH), 6.854 (d, J = 7.2 Hz, 2H),
8.090 (d, J = 7.2 Hz, 2H), 8.316 (bs, 2H, NH2). 13C NMR
4.1. Synthesis of the ionic liquids (ILs)
(75 MHz, DMSO):
159.15.
d 60.24, 63.07, 70.78, 109.24, 144.03,
A novel amino functionalized ionic liquid 4-amino-1-
(2,3-dihydroxy propyl) pyridinium, hydroxide [ADPPY]
[OH] (Fig. 2) was synthesized from commercially available
4-amino pyridine and 3-Chloro-1,2-propanediol, followed
by anion exchange with Amberlite IRA 400 Cl resin
(Scheme 1) [21]. The product (87% yield) was characterized
by 1H and 13C NMR spectroscopy.
4.3.2. Spectral data for unknown tetrahydrobenzo[b]pyran
derivatives
˚
Table-2, Entry 4e: mp 184–186 C; IR (KBr): 3377, 3313,
2959, 2184, 1683, 1653, 1373, 1216, 1035, 712 cmÀ1 1H
NMR (300 MHz, CDCl3): 1.019 (s, 3H, CH3), 1.107 (s, 3H,
;
d
CH3), 2.209 (s, 2H, CH2), 2.460 (s, 2H, CH2), 4.433 (s, 1H,
Benzylic CH), 4.992 (s, 2H, NH2), 7.268 (s, J = 12 Hz, 1H, Ar-
CH), 7.656 (s, J = 7.8 Hz, 1H, Ar-CH), 8.455 (d, 2H, Ar-CH);
13C NMR (75 MHz, CDCl3):
d 27.71, 28.74, 32.21, 33.65,
4.2. Synthesis of tetrahydrobenzo[b]pyran
To demonstrate the utility of [ADPPY][OH] in multi-
component reaction, we began with
a
mixture of
40.63, 50.54, 61.57, 113.08, 118.38, 123.61, 136.06, 139.12,
147.75, 148.71, 158.08, 162.17, 195.79. M/z = 296 (M + 1);
Purity by LC-MS = 98.16%.
˚
Table-2, Entry 4f: mp 204–205 C; IR (KBr): 3360, 3329,
3036, 2192, 1665, 1524, 1366, 1214, 1028, 714 cmÀ1 1H
NMR (300 MHz, CDCl3): 1.989 (s, 2H, CH2), 2.253 (s, 2H,
;
d
CH2), 2.516 (s, 2H, CH2), 4.306 (s, 1H, Benzylic CH), 6.298 (s,
2H, NH2), 7.238 (s, J = 12.6 MHz, 1H, Ar-CH), 7.577 (s,
J = 14.1, 1H, Ar-CH), 8.360 (d, 2H, Ar-CH); 13C NMR
(75 MHz, CDCl3):
d 20.06, 27.05, 33.74, 36.64, 58.49,
113.81, 119.38, 123.85, 136.30, 140.23, 147.23, 148.25,
158.91, 164.48, 195.91. M/z = 268 (M + 1); Purity by LC-
MS = 74.78%.
˚
Table-2, Entry 4 h: mp 201–202 C; IR (KBr): 3451, 3329,
2964, 2193, 1670, 1600, 1365, 1206, 1039, 773 cmÀ1 1H
NMR (300 MHz, DMSO-d6 in CDCl3):
1.060 (s, 3H, CH3),
;
d
1.113 (s, 3H, CH3), 2.222 (s, 2H, CH2), 2.222 (s, 3H, Ar-CH3),
2.222(s, 3H, Ar-CH3), 2.459 (s, 2H, CH2), 4.325 (s, 1H,
Benzylic CH), 4.572 (s, 2H, NH2), 6.949 (d, J = 16 MHz, 2H,
Ar-CH), 7.057 (s, 1H, Ar-CH); 13C NMR (75 MHz, DMSO in
Fig. 2. Images of TSILs.

P.P. Salvi et al. / C. R. Chimie 14 (2011) 878–882
881
NH2
Ehanol
60 - 65 0
48 hrs
NaOH
H2N
OH
N
OH
H2N
Cl
OH
N
+
C
Ion Exchange
Cl
OH
OH
OH
OH
N
[ADPPY] [Cl]
[ADPPY] [OH]
Scheme 1. Synthesis of TSIL [ADPPY] [OH].
O
Ar
O
O
CN
CN
Ionic Liquid
R1
+
+
Ar-CHO
R1
R.T.
NH2
O
CN
R2
R2
4
1
2
3
Scheme 2. Synthesis of tetrahydrobenzo[b]pyran.
OH-
O
H
CN
NC
NC
HC
C
CH
OH
H2N
N+
+
+
CN
R
H
OH
OH-
N+
O
R
O
H
OH
H2N
CN
NH
H
R
OH
NC
NC
+
O
H
O
R
O
O
OH-
N+
R
O
CN
H
OH
H2N
CN
OH
NH2
NH
Scheme 3. A conceivable mechanism for formation of tetrahydrobenzo[b]pyran.
O
CDCl3):
d
19.4, 19.9, 27.72, 28.29, 32.21, 35.09, 40.68,
NMR (75 MHz, DMSO in CDCl3):
d
13.39, 19.96, 20.23,
50.69, 63.76, 114.10, 118.83, 124.76, 128.77, 129.87,
135.35, 136.61, 140.71, 157.35, 161.46, 196.00. M/
z = 323 (M + 1); Purity by LC-MS = 91.00%.
27.05, 35.37, 36.84, 60.00, 114.81, 120.11, 124.94, 128.70,
129.65, 134.66, 136.12, 142.31, 158.72, 163.98, 195.90. M/
z = 317 (M + Na); Purity by LC-MS = 100%.
˚
Table-2, Entry 4i: mp 198–200 C; IR (KBr): 3396, 3329,
2918, 2192, 1680, 1657, 1364, 1207, 1021, 795 cmÀ1 1H
NMR (300 MHz, DMSO-d6 in CDCl3):
6.93 (s, 1H, Ar-CH),
Acknowledgment
;
d
The authors P.P.S. and S.S.K. thanks to DAE–BRNS, New
Delhi (India) for the financial assistance and a research
fellowship respectively.
6.84 (d, J = 13.8 MHz, 2H, Ar-CH), 6.57 (s, 2H, NH2), 4.11 (s,
1H, Benzylic CH), 2.62 (s, 2H, CH2), 2.35 (s, 2H, CH2), 1.95 (s,
2H, CH2), 2.12 (s, 3H, Ar-CH3), 2.15 (s, 3H, Ar-CH3); 13C

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P.P. Salvi et al. / C. R. Chimie 14 (2011) 878–882
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