Highly efficient synthesis of novel Morita-Baylis-Hillman adducts from activated ketones using a DABCO-based hydroxy ionic liquid (HIL) as a recyclable catalyst-solvent

Article abstract of DOI:10.1055/s-0031-1290773

A highly efficient non-imidazolium DABCO-based ionic liquid has been prepared for the synthesis of biologically active Morita-Baylis-Hillman adducts from activated ketones. The results show that the ionic liquid is very efficient in the Morita-Baylis-Hill

Full text of DOI:10.1055/s-0031-1290773

PAPER
▌1725
pHapiegr hly Efficient Synthesis of Novel Morita–Baylis–Hillman Adducts from
Activated Ketones Using a DABCO-Based Hydroxy Ionic Liquid (HIL) as a
Recyclable Catalyst-Solvent
Synthesis of Novel Morita–Baylis–Hillman Adducts Using HIL
Ali Khalafi-Nezhad,* Somayeh Mohammadi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Fax +98(711)2280926; E-Mail: khalafi@chem.susc.ac.ir
Received: 12.01.2012; Accepted after revision: 27.02.2012
In order to overcome these difficulties, we now report the
Abstract: A highly efficient non-imidazolium DABCO-based ion-
synthesis of a series of DABCO-based ionic liquids with
ic liquid has been prepared for the synthesis of biologically active
different auxiliary groups; they are a promising alterna-
tive to imidazolium analogues that may be useful as a sol-
Morita–Baylis–Hillman adducts from activated ketones. The results
show that the ionic liquid is very efficient in the Morita–Baylis–
Hillman reaction due to its operational simplicity, high yields, dual vent-catalyst in different organic reactions such as the
catalyst-solvent properties, and excellent recyclability and reusabil-
ity. This hydroxy ionic liquid acts as a protic solvent and tertiary
amine for the preparation of biologically active compounds from
been tested as additives in the Morita–Baylis–Hillman re-
isatin, ninhydrin, 1,2-acenaphthylenequinone, and benzil with high
yields and very short reaction times.
Diels–Alder reaction, Michael addition, or the Morita–
Baylis–Hillman reaction. These new ionic liquids have
action, due to their basic reaction condition properties.
Moreover, DABCO-based ionic liquids consist of a qua-
Key words: ionic liquid, Morita–Baylis–Hillman reaction,
ternary ammonium salt, tertiary amine, and protic auxilia-
DABCO, activated ketone, solvent-catalyst system
ry group, hence they can be used as a tertiary amine, protic
solvent, and accelerator in the Morita–Baylis–Hillman re-
action.
The Morita–Baylis–Hillman reaction1–4 involves a tertia-
The multifunctionalized products from the Morita–Baylis–
ry-amine-catalyzed coupling between the α-position of an
activated alkene and an aldehyde or ketone.4,5 This reac-
tion produces multifunctional molecules that are impor-
tant intermediates in a wide variety of fields.6–12 These
synthetic advantages have resulted in different basic
amines,13 phosphines,14 Lewis acid catalysts15, micro-
waves,16 ultrasound,17 salts and metals,18 organo-
catalysts19 and ionic liquids being used in the Morita–
Baylis–Hillman reaction of aldehydes with varied activat-
ed alkenes.
Hillman reaction of activated ketones such as isatin are
useful intermediates for the synthesis of biologically ac-
tive compounds such as 3-substituted 3-hydroxyindolin-
2-ones, which are valuable intermediates in the synthesis
of alkaloids and biologically active compounds such as
donaxaridine (A),29 convolutamydines (B1, B2),30 and di-
oxibrassinine (C)31 (Figure 1).
Br
OH
NHMe
HO
R
Since the discovery of air- and water-stable imidazole-
based ionic liquids by Wilkes and Zawarotko in 1992,20
they have attracted increasing interest as environmentally
benign reaction media for organic synthesis.21 Ionic liq-
uids have been widely vaunted as greener solvents, suit-
able for a range of organic reactions and providing
possibilities such as the control of product distribution,22
enhanced rates23 and/or reactivity,24 ease of product re-
covery,25 catalyst immobilization,26 and recycling.27
O
O
N
N
Br
H
H
donaxaridine (A)
convolutamydine A (B1) R = COMe
convolutamydine E (B2) R = CH2OH
S
HO
N
H
O
SMe
N
Imidazole-based ionic liquids are widely applied as sol-
vents or catalysts in different areas of chemistry, ranging
from process technology to the synthesis of fine chemi-
cals. However, the presence of an acidic C–H at position
2 of several imidazolium salts and the recently reported
thermal instability of these imidazolium salts limits the
fields of application of this interesting class of com-
pounds.28
H
dioxibrassinine (C)
Figure 1 3-Hydroxyindolin-2-one alkaloids
Despite the application of Morita–Baylis–Hillman reac-
tion in the synthesis of heterocyclic compounds, few at-
tempts have been made to accelerate the Morita–Baylis–
Hillman reaction of activated ketones.15f,32–34 The main
disadvantage of almost all existing procedures is that the
catalysts are destroyed in the workup procedure and can-
not be recovered or reused. Therefore, there is still a need
SYNTHESIS 2012, 44, 1725–1735
Advanced online publication: 04.05.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290773; Art ID: SS-2012-T0038-OP
© Georg Thieme Verlag Stuttgart · New York

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A. Khalafi-Nezhad, S. Mohammadi
PAPER
Table 1 The Combined Effects of Solvents and Amine Catalysts
on the Morita–Baylis–Hillman Reaction between N-Allylisatin and
Acrylonitrilea
for green, simple, and environmentally friendly processes
with a highly efficient and reusable catalyst.
In continuation of our interest in developing green proto-
cols for the synthesis of biologically active compounds,
we focused our attention on a simple and efficient synthe-
sis of highly reactive and recyclable non-imidazolium
DABCO-based hydroxy ionic liquids (HIL) that act as a
protic solvent and tertiary amine for the preparation of bi-
ologically active compounds from isatin, ninhydrin, 1,2-
acenaphthylenequinone, and benzil with high yields and
very short reaction times.
O
HO
CN
amine cat., solvent
O
+
O
CN
r.t.
N
N
1d
3d
Entry
Solvent
Catalyst
Time (h) Yield (%)
1
2
THF
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
–
192
144
12
10
7
81
80
75
75
80
85
15
5
Different studies have shown that the use of protic sol-
vents or protic additives could accelerate the Morita–Baylis–
Hillman reaction.13e,i–k,35,36 To select the appropriate protic
solvent for the Morita–Baylis–Hillman reaction, many
hydroxy ionic liquids, such as 1-(2-hydroxyethyl)-4-aza-1-
azoniabicyclo[2.2.2]octane bromide ([HEDABCO][Br],
D), 1-(2-hydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]oct-
ane chloride ([HEDABCO][Cl], E1), 1-(2-hydroxypro-
pyl)-4-aza-1-azoniabicyclo[2.2.2]octane tetrafluoroborate
([HPDABCO][BF4], E2), 1-(2,3-dihydroxypropyl)-4-aza-
1-azoniabicyclo[2.2.2]octane chloride ([DHPDABCO][Cl],
F), and 1-(2,3-dihydroxypropyl)-4-(dimethylamino)pyri-
dinium chloride ([DHPDMAP][Cl], G) were synthesized
according to literature procedures (Figure 2).37
EtOH
3
[BMIM][BF4]
HIL Db
HIL E1
HIL E2
HIL F
4
5
6
5
7
96
96
7
8
HIL G
HIL E2
THF
9
55
65
67
78
79
90
96
10
11
12
13
14
15
DBU
10
8
EtOH
DBU
N
N
N
Br
OH
BF4
OH
Cl
OH
N
[BMIM][PF6]
HIL D
DBU
6
N
N
DBU
5
HIL E1
HIL E2
DBU
2
D: [HEDABCO] [Br]
E1: [HPDABCO] [Cl]
E2: [HPDABCO] [BF4]
DBU
20 min
Me
Me
a Reactions conditions: N-allylisatin (1d, 1 mmol), acrylonitrile (2
mmol), DABCO or DBU (15% mol), r.t.
b EtOH (2 drops) was added to dissolve the substrates.
N
N
N
Cl
Cl
+
OH
OH
N
OH
OH
G as a reaction media, in the presence of DABCO, the
product 3d was formed in only 5–15% yield after stirring
for 96 hours (entries 7 and 8) and this was attributed to the
formation of an intramolecular hydrogen bond between
two hydroxy groups of alkyl chain. A control reaction us-
ing pure 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in
tetrahydrofuran and ethanol gave 3d in 65–67% yields af-
ter 8–10 hours (entries 10 and 11).
F: [DHPDABCO] [Cl]
G: [DHPDMAP] [Cl]
Figure 2 The structures of synthesized ionic liquids
To prepare the Morita–Baylis–Hillman adducts from acti-
vated ketones, the reaction between N-allylisatin (1d) and
acrylonitrile was chosen as a model reaction to find the
optimized conditions. The results are summarized in
Table 1.
It was surprising that the same reaction in the ionic liquid
[HPDABCO][BF4] E2 without the use of an amine
catalyst, such as DABCO or DBU, gave 3d in 55% yield
in seven hours (entry 9) and the same reaction in
[HPDABCO][BF4] E2 in the presence of 10 mol% of
DABCO gave 3d in 85% yield in five hours (entry 6) and
in the presence of DBU gave 3d in 96% yield in only 20
minutes (entry 15).
During our optimization studies, various molecular sol-
vents were examined. In the presence of 1,4-diazabicyc-
lo[2.2.2]octane (DABCO) in ethanol or tetrahydrofuran
as solvent, 3d was formed in ~80% yield of the products
were detected after 6–8 days as reported in literature33,34
(Table 1, entries 1 and 2). When the reaction was performed in
the ionic liquids [DHPDABCO][Cl] F or [DHPDMAP][Cl]
The analysis of the results, Table 1, showed that the best
yield and shortest reaction time was obtained in the ionic
liquid [HPDABCO][BF4] E2 in the presence of DBU, be-
cause DBU is more effective than DABCO.38 Based on
Synthesis 2012, 44, 1725–1735
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Novel Morita–Baylis–Hillman Adducts Using HIL
1727
N
N
BF4
BF4
OH
N
N
OH
O
E2
HO
HO
EWG
O
E2
EWG
O
O
+
EWG
N
r.t.
method A
DBU, r.t.
N
N
R
method B
R
R
3a–o
7–11 h
1a–f
3a–o
20–30 min
Scheme 1 Methods A and B for the synthesis of 3-substituted 3-hydroxyindolin-2-ones
R
H
O
O–
O
R33N
O
R33N
OH
O
R2CHO
H
OR1
R2
R33+N
OR1
CO2R1
R2
OR1
R33N
2
+
BF4
OH
N
N
N
R33N:
,
N
[HPDABCO] [BF4]
DBU
Scheme 2
these observations, DBU was chosen as the catalyst for
our study. Thus the ionic liquid [HPDABCO][BF4] E2 in
the presence of DBU is more suitable for the Morita–
Baylis–Hillman reaction (Scheme 1).
The above results clearly demonstrate that the Morita–
Baylis–Hillman reaction of N-allylisatin with acrylonitrile
can be performed in the ionic liquid [HPDABCO][BF4]
E2 as a protic solvent and amine catalyst without an addi-
tive in 55% yield in seven hours and also can be per-
formed in the presence of DBU in 96% yield in 20
minutes. Different research groups such as S. J. Miller et
al.39 established that the rate of Morita–Baylis–Hillman
reaction increases in protic solvents, and this has been rea-
soned as the formation of a hydrogen bond between the
hydroxy group and zwitterionic intermediate 2, produced
from the Michael addition of the nucleophilic Lewis base
to an activated alkene (Scheme 2).13a,40 it seems reason-
able to consider the ionic liquid [HPDABCO][BF4] E2 as
a good solvent.
Figure 3 The effect of DBU molar ratio on the reaction of
N-allylisatin (1d, 1 mmol) and acrylonitrile (2 mmol) in the presence
of [HPDABCO][BF4] E2 (1 mL) as solvent at r.t. for 30 min.
could synthesize [HPDABCO][BF4] as a hydroxy ionic
liquid at room temperature instead of [HEDABCO][Br],
which is solid at room temperature. Aiming to extend the
scope of our methodology, we next used ethyl acrylate,
butyl acrylate, and naphthalen-2-yl acrylate as the sub-
strates for this reaction. The results are summarized in Ta-
ble 2.
The structure of the tertiary amines as the nucleophilic
catalyst and the molar ratio of tertiary amine had a signif-
icant effect on the reaction rate. It can be seen that by in-
creasing the molar ratio of tertiary amine from 2% to 10%,
the reaction yield was significantly improved (Figure 3).
As seen from the results in Figure 3, the best result was
obtained using 8 mol% DBU.
The reaction of ninhydrin, 1,2-acenaphthylenequinone,
and benzil, with acrylonitrile, ethyl acrylate and methyl
acrylate, in the presence of [HPDABCO][BF4] E2/DBU as
the reaction medium (Scheme 3) was examined, which
provided the Morita–Baylis–Hillman adducts 4 in 83–
91% isolated yield (Table 3).
It was found that more carbon atoms in the alkyl side
chain and greater anion size can lower the melting point
of the ionic liquid to room temperature. Therefore, we
© Georg Thieme Verlag Stuttgart · New York
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A. Khalafi-Nezhad, S. Mohammadi
PAPER
Table 2 Comparison of Methods A and B in the Synthesis of 3-Substituted 3-Hydroxyindolin-2-onesa
Entry
Product
Method A
Time (h)
Method B
Yield (%)
58
Time (min)
Yield (%)
92
CN
HO
1
3a
3b
8
9
22
26
O
N
H
CN
HO
O
2
3
51
52
90
89
N
CN
HO
O
3c
8
24
N
OPh
CN
HO
O
4
5
3d
3e
55
60
20
24
96
91
N
N
N
CN
O
HO
HO
10
CO2Et
CN
O
6
3f
9
50
28
89
CO2Bu
CO2Et
O
HO
HO
7
8
3g
3h
9
55
53
26
27
92
91
N
N
CO2Et
O
10
CO2Et
O
HO
9
3i
9
63
30
90
N
CO2Et
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Synthesis of Novel Morita–Baylis–Hillman Adducts Using HIL
1729
Table 2 Comparison of Methods A and B in the Synthesis of 3-Substituted 3-Hydroxyindolin-2-onesa (continued)
Entry
Product
Method A
Time (h)
Method B
Yield (%)
Time (min)
Yield (%)
CO2Et
HO
O
10
3j
8
63
24
92
N
CO2Et
HO
O
11
12
3k
9
57
59
30
28
89
90
N
OPh
CO2Bu
O
HO
3l
10
N
OPh
CO2Bu
O
HO
HO
HO
13
14
3m
3n
9
8
65
50
25
20
89
85
N
CO2Bu
O
N
CO2Et
O
O
O
15
16
3o
3p
11
11
55
60
23
25
83
85
N
O
HO
O
O
N
a Reaction conditions: Method A: 1a–f (1 mmol), activated alkene (2 mmol), [HPDABCO][BF4] E2 (1 mL), r.t.; Method B: 1a–f (1 mmol),
activated alkene (2 mmol), [HPDABCO][BF4] E2 (1 mL), DBU (8 mol%), r.t.
Next we examined the Morita–Baylis–Hillman reaction DABCO] BF4] E2 was evaluated in the following manner.
between aromatic, heteroaromatic, and aliphatic alde- The possibility of recycling the ionic liquid was tested by
hydes as the electrophile and acrylonitrile, ethyl acrylate, using the reaction of N-allylisatin (1d) with acrylonitrile
and methyl acrylate as the activated alkene (Table 4).
under optimized conditions. When the reaction was com-
plete, the ionic liquid was separated from the reaction
mixture by extraction with water. After extraction of the
product 3d with ethyl acetate, we found ~50% DBU was
One of the most important features of this ionic liquid is
its recyclable capability. The catalyst reusability of [HP-
© Georg Thieme Verlag Stuttgart · New York
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1730
A. Khalafi-Nezhad, S. Mohammadi
PAPER
Table 3 Morita–Baylis–Hillman reactions of Activated Ketones
and Activated Alkenes in HPDABCO][BF4] E2 and DBUa
O
O
O
O
OH
Entry Product
Time (min) Yield (%)
O
EWG
BF4
N
O
4a–c
2
N
OH
OH
O
O
+
1
4a
25
90
EWG
OH
CN
OH
O
O
DBU, r.t.
O
3
EWG
O
4d–e
2
3
4b
4c
35
40
87
85
OH
O
CO2Me
O
O
O
EWG
4
OH
4f–g
CO2Et
O
Scheme 3
HO
O
O
CN
Table 4 Morita–Baylis–Hillman Reaction of Aldehydes and Acti-
vated Alkenes in HPDABCO][BF4] E2 and DBUa
4
5
4d
4e
22
35
92
88
O
OH
HO
[HPDABCO][BF4] E2
+
H
EWG
R
R
DBU, r.t.
EWG
COOEt
5a–t
Entry
R
EWG
Product Time
(h)
Yield
(%)
O
OH
6
7
4f
40
50
91
83
CN
1
2
Ph
CN
5a
5b
5c
5d
5e
5f
0.83
3.0
93
85
92
81
89
75
95
87
93
90
91
88
83
93
87
90
87
78
Ph
CO2Me
CN
O
3
4-MeC6H4
4-MeC6H4
2.0
OH
4
CO2Me
CN
3.5
CO2Et
4g
5
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
4-ClC6H4
4-O2NC6H4
4-O2NC6H4
2-O2NC6H4
2-O2NC6H4
4-FC6H4
3.0
6
CO2Me
CN
7.0
a Reaction conditions: activated ketone (1.0 equiv), activated alkenes
(2.0 equiv), HPDABCO][BF4] E2 (1 mL), DBU (8 mol%), r.t.
7
5g
5h
5i
0.8
8
CO2Me
CN
3.5
9
0.25
0.75
0.25
0.75
1.5
dissolved in ethyl acetate. Therefore, the water layer
which contained 100% of ionic liquid and about 50% of
DBU was washed with diethyl ether three times. Then the
aqueous layer was heated under vacuum at 70 °C for five
hours. As seen from the results in Table 5, the best result
for the second run was obtained using 4 mol% DBU and
this indicates that only half of DBU is recyclable. The re-
cycled ionic liquid could be reused for three times without
significant loss of activity.
10
11
12
13
14
15
16
17
18
CO2Me
CN
5j
5k
5l
CO2Me
CO2Me
CN
5m
5n
5o
5p
5q
5r
2-furyl
0.16
0.58
0.20
0.25
5.0
2-furyl
CO2Me
CN
2-pyridyl
3-pyridyl
Et
CN
CO2Me
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Synthesis of Novel Morita–Baylis–Hillman Adducts Using HIL
1731
Table 4 Morita–Baylis–Hillman Reaction of Aldehydes and Acti-
vated Alkenes in HPDABCO][BF4] E2 and DBUa (continued)
Preparation and Characterization of Ionic Liquids
1-(2-Hydroxyethyl)-4-aza-1-azoniabicyclo[2.2.2]octane Bro-
mide ([HEDABCO][Br], D); Typical Procedure
O
OH
[HEDABCO][Br] D was prepared according to the literature
procedure37 with the following modifications. DABCO (10.0
mmol) and 2-bromoethanol (10.0 mmol) were dissolved in MeCN
(50 mL). The mixture was stirred at r.t. in a standard reflux appara-
tus fitted with a drying tube. After 24 h, the product appeared as
white crystals. White crystals of [HEDABCO][Br] precipitated and
then were filtered off (vacuum pump) and washed with EtOAc and
Et2O. The solid was dried under vacuum to give [HEDABCO][Br]
as white crystals; yield: 2.29 g (97%).
[HPDABCO][BF4] E2
+
H
EWG
R
R
DBU, r.t.
EWG
5a–t
Entry
R
EWG
Product Time
(h)
Yield
(%)
19
20
Pr
i-Pr
CO2Me
CN
5s
5t
7.0
7.0
76
73
1H NMR (250 MHz, D2O): δ = 3.42 (t, J = 4.8 Hz, 6 H, 3 CH2), 3.72
(t, J = 4.8 Hz, 6 H, 3 CH2), 4.06–4.08 (m, 2 H, CH2), 4.65–4.67 (m,
2 H, CH2).
a Reaction conditions: aldehyde (1.0 equiv), activated alkene (2.0
equiv), [HPDABCO][BF4] E2 (1 mL), DBU (8 mol%), r.t.
13C NMR (62.5 MHz, D2O): δ = 44.2, 51.9, 64.0, 66.4.
Anal. Calcd for C8H17BrN2O: C, 40.52; H, 7.23; N, 11.81. Found:
C, 40.12; H, 7.00; N, 11.01.
1-(2-Hydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane Chlo-
ride ([HPDABCO][Cl], E1)
a
Table 5 Recyclability of [HPDABCO][BF4] E2
Following the typical procedure for [HEDABCO][Br] D using 3-
chloropropanol gave [HPDABCO] Cl as a viscous liquid; yield:
1.87 g (91%).
1H NMR (250 MHz, D2O): δ = 1.95–2.05 (m, 2 H, CH2), 3.22 (t,
J = 4.8 Hz, 6 H, 3 CH2), 3.34 (t, J = 4.8 Hz, 6 H, 3 CH2), 3.63–3.69
(m, 2 H, CH2), 4.05–4.66 (m, 2 H, CH2).
Run
DBU (mol%)
8
Time (min)
20
Yield (%) of 3d
1
2
96
2
4
6
20
20
20
84
94
94
13C NMR (62.5 MHz, D2O): δ = 22.9, 42.8, 51.0, 60.5, 66.1.
3
4
25
90
Anal. Calcd for C9H19BrN2O: C, 43.04; H, 7.62; N, 11.15. Found:
C, 42.12; H, 7.00; N, 11.05.
a Reaction conditions: N-allylisatin 1d (1 mmol), acrylonitrile (2
mmol), [HPDABCO][BF4] E2 (1 mL), r.t.
1-(2-Hydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane Tet-
rafluoroborate ([HPDABCO][BF4], E2)
–
An anion exchange reaction from Br– to BF4 was completed by
mixing [HPDABCO][Cl] E1 and excess NaBF4 (1.2 equiv) accord-
ing to the literature procedure.37 The reactants were gently stirred
together for 12 h in acetone at r.t. (29 °C). Precipitated NaCl was fil-
tered off and [HPDABCO][BF4] was dried under reduced pressure.
As unreacted NaBF4 was dissolved in the ionic liquid [HP-
DABCO][BF4], the product was a pale oil with low viscosity. The
NaBF4 was removed easily by redissolving the ionic liquid in
CH2Cl2, which caused the precipitation of NaBF4. Subsequent fil-
tration gave the product of ionic liquid [HPDABCO][BF4] as a pale
oil; yield: 2.37 g (92%).
In summary, a highly efficient method for the preparation
of biologically active multifunctional compounds such as
Morita–Baylis–Hillman adducts by using the hydroxy
ionic liquid [HPDABCO][BF4] as solvent-catalyst media
has been developed. The ionic liquid [HPDABCO][BF4]
is applicable to the Morita–Baylis–Hillman reactions of a
variety of aldehydes and activated ketones. The advan-
tages of this environmentally benign and safe protocol in-
clude simple and very mild reaction conditions, high
efficiency, and very short reaction times, as well as the re-
usability of the ionic liquid, which makes it a useful and
practical method for the synthesis of Morita–Baylis–
Hillman adducts.
1-(2,3-Dihydroxypropyl)-4-aza-1-azoniabicycle[2.2.2]octane
([DHPDABCO][Cl], F)
Following the typical procedure for [HEDABCO][Br] gave [DHP-
DABCO][Cl] as white crystals; yield: 2.00 g (91% overall).
1H NMR (250 MHz, D2O): δ = 3.27 (t, J = 4.8 Hz, 6 H, 3 CH2), 3.43
(t, J = 4.0 Hz, 6 H, 3 CH2), 3.60 (m, 2 H, CH2), 3.72–3.76 (m, 2 H,
CH2), 4.13–4.76 (m, 1 H, CH).
Chemicals were purchased from Fluka, Merck, and Aldrich Chem-
13C NMR (62.5 MHz, D2O): δ = 44.1, 51.5, 64.8, 66.0, 66.4.
1
ical Companies. COSY and H NMR spectra Bruker (400 MHz)
Avance DRX were recorded in DMSO-d6 and CDCl3 with TMS as
internal standard. FT-IR spectroscopy employed a Shimadzu FT-IR
8300 spectrophotometer. Melting points were determined in open
capillary tubes in a Barnstead Electrothermal 9100 BZ circulating
oil melting point apparatus. Monitoring of the reactions was accom-
plished by TLC on silica gel PolyGram SILG/UV254 plates. Col-
umn chromatography was carried out using silica gel 60 (70–230
mesh).
Anal. Calcd for C9H19ClN2O2: C, 48.54; H, 8.60; N, 12.58. Found:
C, 48.16; H, 8.50; N, 11.92.
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium
([DHPDMAP][Cl], G)
Following the typical procedure for [HEDABCO][Br] gave [DHP-
DMAP][Cl] as a white solid. The solid was redissolved in MeCN,
the soln was cooled, and crystals of [DHPDMAP][Cl] were ob-
tained; yield: 2.00 g (86%).
1H NMR (250 MHz, D2O): δ = 3.06 (s, 6 H, 2 CH3), 3.52–3.47 (m,
2 H, CH2), 3.92–3.96 (m, 2 H, CH2), 4.15–4.57 (m, 1 H, CH), 6.74
(d, J = 5.0 Hz, 2 H, 2 CH), 7.84 (d, J = 4.8 Hz, 2 H, 2 CH).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1725–1735

1732
A. Khalafi-Nezhad, S. Mohammadi
PAPER
13C NMR (62.5 MHz, D2O): δ = 39.5, 58.9, 62.0, 71.5, 107.8, 142.3,
157.3.
Butyl 3-[3-(1-Cyanovinyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-in-
dol-1-yl]propanoate (3f)
Brown oil; yield: 2.6 g (89%); Rf = 0.51 (EtOAc–hexane, 1:3).
Anal. Calcd for C10H17ClN2O2: C, 51.61; H, 7.36; N, 12.04. Found:
C, 49.78; H, 7.00; N, 12.00.
IR (liquid film): 3444, 3054, 2916, 1743, 1635, 1604, 867, 950, 731
cm–1.
Morita–Baylis–Hillman Reaction; General Procedure
A soln of aldehyde or activated ketone (1.0 mmol) and activated al-
kene (2.0 mmol) in ionic liquid (1 mL) was stirred at r.t. (25–29 °C)
for method A; for method B, DBU (8 mol%) was added (TLC mon-
itoring). Upon completion, the mixture was extracted with EtOAc.
The combined EtOAc fractions were evaporated. The crude product
thus obtained was purified by column chromatography (silica gel,
200–300 mesh, EtOAc–hexane, 1:5–1:3). All products were charac-
terized by IR and 1H and 13C NMR.
1H NMR (250 MHz, CDCl3): δ = 0.90 (t, J = 7.5 Hz, 3 H, CH3),
1.28–1.37 (m, 2 H, CH2), 1.50–1.59 (m, 2 H, CH2), 2.72 (t, J = 7.2
Hz, 2 H, CH2), 3.95 (t, J = 7.3 Hz, 2 H, CH2), 4.04 (t, 2 H, CH2),
4.22 (s, 1 H, OH), 6.15 (s, 1 H, Hvinyl), 6.36 (s, 1 H, Hvinyl), 7.63–6.67
(complex, 4 H, 4 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 13.6, 19.0, 30.4, 31.2, 32.1, 38.9,
65.0, 109.4, 115.4, 122.9, 124.0, 125.4, 127.3, 131.0, 133.4, 142.1,
171.0, 174.4.
Compounds 3a,32 3d,32 4a–c,32 5a,b,13l,35e 5c,13l 5d,35e,41 5e,13l 5f,41
5g,h,35e,41 5i,j,13l,35e 5l,13l 5m,35d,e 5n,35d 5o,35d,e and 5p–t13l are
known compounds, and the spectroscopic data of new synthesized
compounds are reported below.
Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found: C,
65.78; H, 6.09; N, 8.50.
Ethyl 2-(1-Ethyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-
yl)acrylate (3g)
Yellow crystals; yield: 2.5 g (92%); mp 109–110 °C; Rf = 0.63
(EtOAc–hexane, 1:1).
2-(1-Butyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acrylo-
nitrile (3b)
Brown oil; yield: 2.0 g (90%); Rf = 0.63 (EtOAc–hexane, 1:1).
IR (solid film): 3423, 3020, 2934, 1762, 1614, 1602, 950, 879, 699
cm–1.
IR (liquid film): 3384, 2960, 2224, 1743, 1679, 1467, 1364, 947,
754 cm–1.
1H NMR (250 MHz, CDCl3): δ = 0.93 (t, J = 5.0 Hz, 3 H, CH3),
1.31–1.40 (m, 2 H, CH2), 1.54–1.60 (m, 2 H, CH2), 3.31 (t, J = 7.5
Hz, 2 H, CH2), 4.92 (s, OH), 6.25 (s, 1 H, Hvinyl), 6.34 (s, 1 H, Hvinyl),
7.05–7.75 (complex, 4 H, 4 Harom).
1H NMR and COSY NMR (400 MHz, DMSO-d6): δ = 0.96 (t,
J = 7.0 Hz, 3 H, NCH2CH3), 1.93 (t, J = 6.5 Hz, 3 H, OCH2CH3),
3.70 (q, J = 6.9 Hz, 2 H, OCH2), 3.86–3.92 (2 q, J = 25.0 Hz, 2 H,
NCH2), 6.45 (s, 1 H, Hvinyl), 6.49 (s, 1 H, Hvinyl), 6.59 (s, 1 H, OH),
6.97 (t, J = 7.3 Hz, 1 H, Harom), 7.03 (d, J = 7.9 Hz, 2 H, 2 Harom),
7.30 (t, J = 7.4 Hz, 1 H, Harom).
13C NMR (62.5 MHz, DMSO-d6): δ = 14.6, 20.1, 39.8, 42.1, 76.1,
110.2, 116.3, 122.3, 122.8, 124.4, 129.0, 130.3, 132.0, 141.9, 175.1.
13C NMR (62.5 MHz, DMSO-d6): δ = 12.5, 13.9, 41.4, 53.8, 109.6,
120.7, 123.6, 128.5, 129.3, 131.9, 139.4, 144.2, 164.2, 175.6.
Anal. Calcd for C15H16N2O2: C, 70.29; H, 6.29; N, 10.93. Found: C,
70.21; H, 6.23; N, 10.90.
Anal. Calcd for C15H17NO4: C, 65.44; H, 6.22; N, 5.09. Found: C,
64.67; H, 6.10; N, 5.00.
2-[3-Hydroxy-2-oxo-1-(2-phenoxyethyl)-2,3-dihydro-1H-indol-
3-yl]acrylonitrile (3c)
Brown oil; yield: 2.7 g (89%); Rf = 0.52 (EtOAc–hexane, 1:1).
Ethyl 2-(1-Butyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-
yl)acrylate (3h)
White crystals; yield: 2.5 g (91%); mp 106–107 °C; Rf = 0.65
(EtOAc–hexane, 1:1).
IR (liquid film): 3454, 3096, 2916, 1743, 1635, 1604, 899, 787
cm–1.
IR (solid film): 3424, 3021, 2936, 1763, 1615, 1604, 950, 879, 699
cm–1.
1H NMR (250 MHz, CDCl3): δ = 2.12 (t, J = 5.0 Hz, 2 H, CH2),
3.54 (t, J = 5.0 Hz, 2 H, CH2), 6.34 (s, 1 H, Hvinyl), 6.42 (s, 1 H,
Hvinyl), 7.63–6.67 (complex, 9 H, 9 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 19.3, 42.2, 111.2, 117.6, 123.8,
125.3, 126.3, 126.4, 127.9, 130.9, 131.8, 135.7, 138.4, 150.9, 158.2,
168.1, 173.2.
1H NMR (250 MHz, DMSO-d6): δ = 0.93 (t, J = 5.0 Hz, 3 H, CH3),
1.31–1.40 (m, 2 H, CH2), 1.54–1.6o (complex, 5 H, CH2, CH3), 3.31
(t, J = 7.5 Hz, 2 H, CH2), 3.85–3.90 (q, 2 H, CH2), 4.92 (s, 1 H, OH),
6.42 (s, 1 H, Hvinyl), 6.53 (s, 1 H, Hvinyl), 7.05–7.75 (complex, 4 H, 4
Harom).
Anal. Calcd for C19H16N2O3: C, 71.24; H, 5.03; N, 8.74. Found: C,
71.20; H, 5.00; N, 8.68.
13C NMR (62.5 MHz, DMSO-d6): δ = 13.5, 13.6, 19.4, 28.8, 60.1,
74.8, 108.2, 121.7, 122.9, 127.1, 129.3, 130.9, 139.9, 143.9, 163.9,
175.1.
Ethyl 2-[3-(1-Cyanovinyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-in-
dol-1-yl]propanoate (3e)
Brown oil; yield: 2.6 g (91%); Rf = 0.61 (EtOAc–hexane, 1:1).
Anal. Calcd for C17H21NO4: C, 67.31; H, 6.98; N, 4.62. Found: C,
67.25; H, 6.91; N, 4.60.
IR (liquid film): 3474, 3096, 2848, 1753, 1625, 1604, 1382, 1062,
1025, 858, 721 cm–1.
Ethyl 2-{1-[1-(Ethoxycarbonyl)ethyl]-3-hydroxy-2-oxo-2,3-di-
hydro-1H-indol-3-yl}acrylate (3i)
Brown oil; yield: 3.0 g (90%); Rf = 0.63 (EtOAc–hexane, 1:1).
1
COSY NMR and H NMR (400 MHz, DMSO-d6): δ = 1.20 (d,
J = 3.7 Hz, 3 H, NCHCH3), 2.00 (t, J = 6.1 Hz, 3 H, OCH2CH3),
4.14–4.55 (q, J = 6.9 Hz, 1 H, NCH), 4.72–5.35 (q, J = 6.8 Hz, 2 H,
OCH2), 6.40 (s, 1 H, Hvinyl), 6.63 (s, 1 H, Hvinyl), 6.72 (s, 1 H, OH),
6.75–7.41 (complex, 4 H, 4 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 13.7, 14.2, 49.4, 62.1, 110.3,
115.8, 124.1, 124.9, 126.1, 126.4, 127.4, 130.6, 131.9, 135.5, 141.0,
164.8.
IR (liquid film): 3464, 3096, 2938, 2898, 1743, 1635, 1604, 1018,
831, 747 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 1.06 (t, J = 7.0 Hz, 3 H,
NCHCH3), 1.28 (d, J = 3.7 Hz, 3 H, NCHCH3), 2.15 (t, J = 6.2 Hz,
3 H, OCH2CH3), 3.70 (q, J = 6.8 Hz, 2 H, OCH2), 4.18–4.49 (q,
J = 6.8 Hz, 1 H, NCH), 4.74–5.40 (q, J = 6.8 Hz, 2 H, OCH2), 6.42
(s, 1 H, Hvinyl), 6.66 (s, 1 H, Hvinyl), 6.72 (s, 1 H, OH), 6.95 (t, J = 7.4
Hz, 1 H, Harom), 7.11 (d, J = 7.9 Hz, 2 H, 2Harom), 7.35 (t, J = 7.4 Hz,
1 H, Harom).
Anal. Calcd for C16H16N2O4: C, 63.99; H, 5.37; N, 9.33. Found: C,
63.93; H, 5.30; N, 9.30.
Synthesis 2012, 44, 1725–1735
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Novel Morita–Baylis–Hillman Adducts Using HIL
1733
13C NMR (62.5 MHz, CDCl3): δ = 13.5, 13.8, 13.9, 48.4, 60.9, 61.0,
84.7, 110.3, 123.8, 124.1, 127.7, 129.8, 130.7, 139.1, 142.1, 164.7,
170.3, 175.65.
Hz, 2 H, CH2), 4.33 (t, J = 7.2 Hz, 2 H, CH2), 5.26 (dd, J = 1.3, 10.2
Hz, 2 H, CH2), 5.80–5.92 (m, 1 H, CH), 6.41 (s, 1 H, Hvinyl), 6.55 (s,
1 H, Hvinyl), 6.70–7.40 (complex, 4 H, 4 Harom).
Anal. Calcd for C18H21NO6: C, 62.24; H, 6.09; N, 4.03. Found: C,
62.18; H, 6.00; N, 4.00.
13C NMR (62.5 MHz, CDCl3): δ = 13.6, 18.9, 31.5, 42.5, 64.8,
109.7, 117.8, 122.2, 123.8, 127.0, 128.8, 129.5, 129.5, 129.9, 131.1,
139.3, 143.6, 164.5, 176.0.
Ethyl 2-(1-Allyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-
yl)acrylate (3j)
Yellow crystals; yield: 2.6 g (92%); mp 136–137 °C; Rf = 0.52
(EtOAc–hexane, 1:1).
Anal. Calcd for C18H21NO4: C, 68.55; H, 6.71; N, 4.44. Found: C,
68.50; H, 6.67; N, 4.40.
Butyl 2-{1-[1-(Ethoxycarbonyl)ethyl]-3-hydroxy-2-oxo-2,3-di-
hydro-1H-indol-3-yl}acrylate (3n)
Yellow oil; yield: 2.9 g (85%); Rf = 0.61 (EtOAc–hexane, 1:1).
IR (liquid film): 3434, 3043, 2896, 1767, 1635, 1608, 898, 798, 741
cm–1.
1H NMR and COSY NMR (400 MHz, CDCl3): δ = 1.00 (t, J = 6.4
Hz, 3 H, OCH2CH3), 3.78 (q, J = 6.8 Hz, 2 H, OCH2), 4.27 (d,
J = 4.7 Hz, 2 H, NCH2), 5.20 (dd, J = 1.2, 10.3 Hz, 1 H, =CH), 5.31
(dd, J = 1.2, 10.3 Hz, 1 H, =CH), 5.70–5.90 (m, 1 H, CH=), 6.53 (s,
1 H, Hvinyl), 6.79 (s, 1 H, Hvinyl), 6.89 (s, 1 H, OH), 7.00–7.76 (com-
plex, 4 H, 4 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 13.86, 42.7, 60.9, 109.1, 117.5,
122.9, 123.8, 127.6, 129.5, 129.9, 131.2, 139.3, 143.7, 164.5, 167.4,
176.4.
IR (solid film): 3454, 3034, 2945, 1743, 1635, 1605, 1584, 1078,
897, 767, 725 cm–1.
1H NMR (250 MHz, DMSO-d6): δ = 0.73 (t, J = 7.2 Hz, 3 H, CH3),
1.12 (t, J = 4.5 Hz, 3 H, CH3), 1.15–1.30 (m, 2 H, CH2), 1.45–1.87
(m, 2 H, CH2), 2.0 (d, J = 7.3 Hz, 3 H, CH3), 3.79 (t, J = 7.2 Hz, 2
H, CH2), 3.84–3.93 (q, 2 H, CH2), 4.09–4.15 (q, J = 7.3 Hz, 1 H,
CH), 6.42 (s, 1 H, Hvinyl), 6.85 (s, 1 H, Hvinyl), 6.95–7.25 (complex,
4 H, 4 Harom).
13C NMR (62.5 MHz, DMSO-d6): δ = 13.2, 13.3, 13.8, 18.2, 30.1,
56.8, 60.8, 63.8, 84.53, 109.5, 120.2, 123.2, 127.3, 129.1, 139.8,
142.0, 163.6, 166.5, 169.7, 174.6.
Anal. Calcd for C16H17NO4: C, 66.89; H, 5.96; N, 4.88. Found: C,
66.83; H, 5.91; N, 4.80.
Anal. Calcd for C20H25NO6: C, 63.99; H, 6.71; N, 3.73. Found: C,
63.90; H, 6.65; N, 3.68.
Ethyl 2-[3-Hydroxy-2-oxo-1-(2-phenoxyethyl)-2,3-dihydro-1H-
indol-3-yl]acrylate (3k)
Yellow crystals; yield: 2.9 g (89%); mp 90–91 °C; Rf = 0.59
(EtOAc–hexane, 1:1).
Naphthalen-2-yl 2-(1-Allyl-3-hydroxy-2-oxo-2,3-dihydro-1H-
indol-3-yl)acrylate (3o)
Yellow crystals; yield: 3.0 g (83%); mp 118–119 °C; Rf = 0.11
(EtOAc–hexane, 1:3).
IR (solid film): 3472, 3049, 2896, 1779, 1665, 1601, 989, 763, 730
cm–1.
1H NMR (250 MHz, CDCl3): δ = 1.08 (t, J = 7.2, 3 H, CH3), 2.94 (t,
J = 5.0 Hz, 2 H, CH2), 3.85 (t, J = 5.0 Hz, 2 H, CH2), 4.01 (q, 2 H,
CH2), 6.25 (s, 1 H, Hvinyl), 6.46 (s, 1 H, Hvinyl), 7.63–6.67 (complex,
9 H, 9 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 13.3, 33.3, 41.7, 60.9, 108.7,
122.8, 124.3, 126.6, 127.5, 128.6, 128.9, 129.5, 130.8, 138.4, 139.3,
143.6, 147.3, 163.9, 176.2.
IR (solid film): 3467, 3043, 2946, 1765, 1675, 1609, 987, 785,
745.6 cm–1.
1H NMR and COSY NMR (400 MHz, DMSO-d6): δ = 4.27 (d,
J = 4.8 Hz, 2 H, NCH2), 5.03 (dd, J = 1.1, 10.4 Hz, 1 H, =CH), 5.31
(dd, J = 1.1, 10.4 Hz, 1 H, =CH), 5.69–5.77 (m, 1 H, CH=), 6.79 (s,
1 H, Hvinyl), 6.88 (s, 1 H, Hvinyl), 6.91 (s, 1 H, OH), 6.94–8.97 (com-
plex, 2 H, 2 Harom), 7.07 (t, J = 7.4 Hz, 1 H, Harom), 7.22 (d, J = 7.2
Hz, 1 H, Harom), 7.34 (t, J = 7.66 Hz, 1 H, Harom), 7.34 (d, J = 1.90
Hz, 1 H, Harom), 7.48–7.50 (m, 2 H, 2 Harom), 7.84–7.92 (m, 3 H, 3
Anal. Calcd for C21H21NO5: C, 68.65; H, 5.76; N, 3.81. Found: C,
68.60; H, 5.70; N, 3.78.
Harom).
13C NMR (62.5 MHz, CDCl3): δ = 42.7, 109.8, 118.0, 118.6, 120.8,
123.2, 123.9, 125.2, 125.9, 126.6, 127.6, 127.7, 129.4, 129.6, 129.9,
130.2, 131.0, 131.4, 133.6, 139.1, 143.7, 147.5, 163.4, 176.1.
Butyl 2-[3-Hydroxy-2-oxo-1-(2-phenoxyethyl)-2,3-dihydro-1H-
indol-3-yl]acrylate (3l)
Yellow oil; yield: 3.3 g (90%); Rf = 0.65 (EtOAc–hexane, 1:1).
IR (liquid film): 3558, 3016, 1743, 1665, 1604, 989, 763, 730 cm–1.
Anal. Calcd for C24H19NO4: C, 74.79; H, 4.97; N, 3.63. Found: C,
74.70; H, 4.90; N, 3.58.
1H NMR (250 MHz, CDCl3): δ = 0.77 (t, J = 7.2 Hz, 3 H, CH3),
1.13–1.19 (m, 2 H, CH2), 1.38–1.44 (m, 2 H, CH2), 2.93 (t, J = 5.0
Hz, 2 H, CH2), 3.84 (t, J = 5.0 Hz, 2 H, CH2), 3.92 (t, J = 7.2 Hz, 2
H, CH2), 6.25 (s, 1 H, Hvinyl), 6.46 (s, 1 H, Hvinyl), 6.70–7.40 (com-
plex, 9 H, 9 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 13.6, 18.9, 30.3, 33.3, 41.7, 64.9,
108.7, 122.8, 124.0, 126.6, 127.6, 128.6, 129.9, 130.0, 138.8, 139.3,
143.6, 144.5, 164.7, 176.0.
Naphthalen-2-yl 2-(1-Ethyl-3-hydroxy-2-oxo-2,3-dihydro-1H-
indol-3-yl)acrylate (3p)
Yellow crystals; yield: 3.9 g (85%); mp 109–110 °C; Rf = 0.23
(EtOAc–hexane, 1:3).
IR (liquid film): 3462, 2896, 1765, 1665, 1604, 978, 843, 756 cm–1.
1H NMR and COSY NMR (400 MHz, CDCl3): δ = 1.00 (t, J = 7.0
Hz, 3 H, NCH2CH3), 3.80 (q, J = 6.8 Hz, 2 H, NCH2), 6.75 (s, 1 H,
Anal. Calcd for C23H25NO5: C, 69.86; H, 6.37; N, 3.54. Found: C,
69.80; H, 6.31; N, 3.49.
H
vinyl), 6.88 (s, 1 H, Hvinyl), 6.91 (s, 1 H, OH), 6.94–6.97 (complex,
2 H, 2 Harom), 7.12 (t, J = 7.3 Hz, 1 H, Harom), 7.25 (d, J = 7.2 Hz, 1
H, Harom), 7.34 (t, J = 7.6 Hz, 1 H, Harom), 7.35 (d, J = 1.9 Hz, 1 H,
Butyl 2-(1-Allyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-
yl)acrylate (3m)
Harom), 7.48–7.53 (m, 2 H, 2 Harom), 7.84–7.92 (m, 3 H, 3 Harom).
13C NMR (62.5 MHz, CDCl3): δ = 33.2, 60.7, 109.8, 118.0, 118.6,
120.8, 123.2, 123.9, 125.2, 125.9, 126.6, 127.6, 127.7, 129.4, 129.6,
129.9, 130.2, 131.0, 131.4, 133.6, 139.1, 138.2, 143.7, 147.5, 163.4,
171.2, 176.1.
Orange crystals; yield: 3.0 g (89%); mp 79–80 °C; Rf = 0.63
(EtOAc–hexane, 1:1).
IR (solid film): 3435, 3019, 2934, 1723, 1615, 1601, 967, 876, 756
cm–1.
1H NMR (250 MHz, CDCl3): δ = 0.85 (t, J = 7.2 Hz, 3 H, CH3),
1.21–1.27 (m, 2 H, CH2), 1.45–1.51 (m, 2 H, CH2), 4.05 (d, J = 4.38
Anal. Calcd for C23H19NO4: C, 73.98; H, 5.13; N, 3.75. Found: C,
73.01; H, 5.00; N, 3.61.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1725–1735

1734
A. Khalafi-Nezhad, S. Mohammadi
PAPER
(9) de Souza, R. O. M. A.; Meireles, B. A.; Aguiar, C. S.;
2-(1-Hydroxy-2-oxo-1,2-dihydroacenaphthylen-1-yl)acryloni-
trile (4d)
Brown solid; yield: 2.1 g (92%); mp 220–221 °C; Rf = 0.70
(EtOAc–hexane, 1:1).
Vasconcellos, M. Synthesis 2004, 1595.
(10) Kundu, M. K.; Sundar, N.; Kumar, S. K.; Bhat, S. V.;
Biswas, S.; Valecha, N. Bioorg. Med. Chem. Lett. 1999, 9,
731.
IR (solid film): 3425, 1760, 1710, 1689, 1604 cm–1.
(11) de Souza, R. O. M. A.; Pereira, V. L. P.; Muzitano, M. F.;
Falcao, C. A. B.; Rossi-Bergmann, B.; Filho, E. B. A.;
Vasconcellos, M. Eur. J. Med. Chem. 2007, 42, 99.
(12) Vasconcellos, M.; Silva, T. M. S.; Camara, C. A.; Martins,
R. M.; Lacerda, K. M.; Lopes, H. M.; Pereira, V. L. P.; de
Souza, R. O. M. A.; Crespo, L. T. C. Pest Manage. Sci. 2006,
62, 288.
1H NMR (CDCl3): δ = 3.44 (br s, 1 H, OH), 6.67 (s, 1 H, Hvinyl), 6.83
(s, 1 H, Hvinyl), 7.13–7.42 (m, 6 H, 6 Harom).
13C NMR (CDCl3): δ = 104.49, 118.41, 122.21, 124.72, 128.00,
128.43, 128.88, 129.50, 129.98, 130.29, 131.65, 132.65, 133.14,
133.87, 197.45.
Anal. Calcd for C15H9NO2: C, 76.59; H, 3.86; N, 5.95. Found: C,
76.40; H, 3.72; N, 5.65.
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Ethyl 2-(1-Hydroxy-2-oxo-acenaphthen-1-yl)acrylate (4e)
Yellow solid; yield: 2.4 g (88%); mp 231–232 °C; Rf = 0.74
(EtOAc–hexane, 1:1).
IR (solid film): 3423, 1762, 1713, 1690, 1602 cm–1.
1H NMR (CDCl3): δ = 1.13 (t, J = 7.2 Hz, 3 H, CH3), 4.12 (q, J =
7.2 Hz, 2 H, CH2), 3.52 (br s, 1 H, OH), 6.69 (s, 1 H, Hvinyl), 6.88 (s,
1 H, Hvinyl), 7.25–7.61 (m, 6 H, Harom).
13C NMR (CDCl3): δ = 22.51, 60.90, 104.49, 118.41, 122.21,
124.72, 128.00, 128.43, 128.88, 129.50, 129.98, 130.29, 131.65,
132.65, 133.14, 133.87, 197.45.
Anal. Calcd for C17H14O4: C, 72.33; H, 5.00; Found: C, 72.01; H,
4.82.
3-Hydroxy-2-methylene-4-oxo-3,4-diphenylbutyronitrile (4f)
Yellow oil; yield: 2.4 g (91%); Rf = 0.69 (EtOAc–hexane, 1:1).
IR (liquid film): 3421, 1764, 1715, 1681, 1600 cm–1.
1H NMR (CDCl3): δ = 3.31 (br s, 1 H, OH), 6.22 (s, 1 H, Hvinyl), 6.54
(s, 1 H, Hvinyl), 7.17–7.19 (m, 5 H, 5 Harom), 7.31–7.40 (m, 5 H, 5
Harom).
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2001, 6, 852. (e) Basavaiah, D.; Sreenivasulu, B.; Reddy, R.
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13C NMR (CDCl3): δ = 90.50, 123.72, 127.00, 128.26, 128.65,
128.85, 129.36, 130.62, 131.59, 133.54, 135.97, 136.72, 141.02,
195.97.
Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C,
77.43; H, 4.53; N, 5.11.
Acknowledgment
(16) Kundu, M. K.; Mukherjee, S. B.; Balu, N.; Padmakumar, R.;
Bhat, S. V. Synlett 1994, 444.
We acknowledge the financial support from Shiraz University.
(17) Coelho, F.; Almeida, W. P.; Veronese, D.; Mateus, C. R.;
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