Ionic Liquid [BDBDMIm](Br3)2 As a New Efficient Brominating Agent in the Synthesis of γ-Butyrolactones

Article abstract of DOI:10.1134/S1070363218050286

γ-Butyrolactones can be synthesized by a solvent free multicomponent reaction of aldehydes with ethylpyruvate followed by an intramolecular cyclization using the new brominating agent, ionic liquid [BDBDMIm](Br₃)₂. This is the first synthesis of γ-butyrolactones starting with aldehydes via the Knovenagel condensation and halogenation, followed by multicomponent cyclization reaction. The present method offers several advantages such as solvent free mild conditions, simple procedure, excellent yields, and environmental friendliness. All synthesized compounds were characterized by their IR, ¹H and ¹³C NMR spectra.

Full text of DOI:10.1134/S1070363218050286

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 5, pp. 1009–1014. © Pleiades Publishing, Ltd., 2018.
Ionic Liquid [BDBDMIm](Br3)2 As a New Efficient Brominating
Agent in the Synthesis of γ-Butyrolactones1
L. Z. Fekria*
a Department of Chemistry, Payame Noor University, Tehran, 19395-3697 Iran
*e-mail: chem_zare@yahoo.com; chem_zare@pnu.ac.ir
Received September 8, 2017
Abstract—γ-Butyrolactones can be synthesized by a solvent free multicomponent reaction of aldehydes with
ethylpyruvate followed by an intramolecular cyclization using the new brominating agent, ionic liquid
[BDBDMIm](Br3)2. This is the first synthesis of γ-butyrolactones starting with aldehydes via the Knovenagel
condensation and halogenation, followed by multicomponent cyclization reaction. The present method offers
several advantages such as solvent free mild conditions, simple procedure, excellent yields, and environmental
friendliness. All synthesized compounds were characterized by their IR, 1H and 13C NMR spectra.
Keywords: multicomponent reaction, butyrolactones, ionic liquid, solvent free
DOI: 10.1134/S1070363218050286
INTRODUCTION
butyrolactones using aryl aldehydes, ethylpyruvate and
[BDBDMIm]Br3 as a brominating ionic liquid.
γ-Butyrolactones, are found in some plant
hormones and demonstrate various biological activities
[1]. Their synthesis has been the focus of intensive
efforts, including phosphine-catalyzed substitution of
Morita–Baylis–Hillman acetates [2], Au-Catalyzed
tandem cycloisomerization–oxidation of homopro-
pargyl alcohols [3], selective benzylic C–H abstraction
of carboxylic and benzoic acid in the presence of
hypervalent iodine(III) reagents and KBr [4], direct
preparation of lactones from keto alcohols in the
presence of Noyori’s asymmetric transfer hydro-
genation catalyst [5], and some others [6–9]. Up to
now the only example of approach to γ-butyrolactone
by the multicomponent reaction of isocyanides with
glyoxals and acetophosphonic acid diethylesters has
been published [10].
RESULTS AND DISCUSSION
The current study started with optimization of the
reaction of benzaldehyde 1a with ethylpyruvate 2 in
the presence of the ionic liquid [BDBDMIm](Br3)2
targeting butenolide derivative 4a (Scheme 1).
The optimized conditions were applied to a number
of possible reactive substrates. The reaction that
involved aryl aldehydes containing the electron
withdrawing groups on the aromatic ring, such as Cl
Scheme 1. Multicomponent synthesis of butyrolactones.
O
O
O
H
+
Based on the above and in continuation of our
earlier efforts of preparation of pharmaceutical and
heterocyclic compounds [11–18], we report a simple,
one pot multicomponent method for the construction
of butyrolactones 4a–4i or 6a–6d from aldehydes 1 or
5, ethylpyruvate 2 and [BDBDMIm](Br3)2 as a safe
source of bromine and an oxidant. To the best of our
knowledge, the current study is the first report on a
multicomponent reaction leading to the synthesis of
R
O
2
1
[BDBDMIm](Br3)2
3
Br
OH
O
O
R
1 The text was submitted by the author in English.
4
1009

1010
FEKRI
Scheme 2. Mechanistic pathway to butyrolactone.
Br3
Br3
N+
N+
O
O
O
O
O
3
H
+
O
O
1
2
5
−Br2
[DBDBMIm](Br3)2
OH
[DBDBMIm]2Br2
O
Br
Br
Br+
O
O
O
O
O
O
O
4
7
6
Scheme 3. Synthesis of pyrazolyl butyrolactones.
OH
O
Br
O
CHO
O
[BDBDMIm](Br3)2
N
+
N
O
N
N
O
5
2
6
and Br (2, 3, 6-8), provided the corresponding
butenolide smoothly in high yields. Aldehydes with
electron releasing groups, such as 4-methyl and
4-methoxy and 2-hydroxy, also afforded the
correspond-ing butenolide (4, 5, 9) in high yields.
EXPERIMENTAL
Chemicals were purchased from Merck and Fluka.
All solvents used were dried and distilled according to
the standard procedures. Melting points were measured
on an Electrothermal 9100 apparatus. IR spectra (KBr
discs) were recorded on a Shimadzu FT-IR 8600
The probable mechanism of the reaction could be
expressed as follows (Scheme 2). Initially, acidic bis
ionic liquid 3 supports activation of aldehyde 1 and
deprotonation of ethylpyruvate 2 leading to chalcone 5.
Bromination of chalcone 5 results in lactone 7,
followed by its enolization and formation of butyro-
lactone 4.
1
spectrophotometer. H and 13C NMR spectra were
measured on a Bruker 400 DRX Avance spectrometer
at 400 and 100 MHz in DMSO-d6.
Preparation of [BDBDMIm]Br ionic liquid. The
ionic liquid was prepared according to the earlier
developed method [19–21].
The following study targeted synthesize of a new
library of pyrazolyl butyrolactone (Scheme 3, Table 2).
General procedure for γ-butyrolactones 4a–4i or
6a–6d. A mixture of an aldehyde (1 mmol) with
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 5 2018

IONIC LIQUID [BDBDMIm](Br3)2 AS A NEW EFFICIENT BROMINATING AGENT
Table 1. Butyrolactones one-pot multicomponent synthesis dataa
1011
Comp.
no.
Yieldb,c,
%
Comp.
no.
Yieldb,c,
%
Formula
OH
mp, °C
Formula
OH
mp, °C
Br
4a
87
151–153
4f
89
142–143
Br
Cl
O
O
O
O
OH
Br
4b
83
124–125
110–112
178–180
4g
82
139–141
OH
Br
O
Cl
O
O
O
O
Cl
OH
OH
Br
Br
4c
86
85
4h
4i
89
84
164–165
178–180
Cl
Br
O
O
O
Br
Cl
OH
OH
Br
4d
OH
O
O
O
O
H3CO
OH
Br
4e
81
165–167
O
O
H3C
a
All products were characterized by IR and NMR data. b Yields based upon starting aldehyde. c In all cases the product was isolated after
stirring for 1 h.
ethylpyruvate (1 mmol) and [BDBDMIm](Br3)2
(1 mmol) was stirred for 20 min. After completion of
the reaction, as indicated by TLC, the product was
extracted by CHCl3–H2O. Upon evaporation of the
organic solvent, the crude product was recrystallized
from EtOH and dried to afford white solid compounds
4a–4i or 6a–6d, respectively.
4-Bromo-5-(4-chlorophenyl)-3-hydroxyfuran-2(5H)-
one (4b). FT-IR spectrum, ν, cm–1: 1089 (C–Br), 1157
(C–Cl), 1250 (C–O), 1492, 1600, 1766 (C=O), 3525
1
(O–H). H NMR spectrum, δ, ppm: 6.1 s (1H), 7.66 d
(J = 8.4 Hz, 2H), 7.97 d (J = 8.5 Hz, 2H), 11.4 s (1H).
13C NMR spectrum, δ, ppm: 56.3, 94.6, 112.4, 118.2,
123.4, 138.1, 159.1, 165.9. Found, %: C 41.47; H 2.07.
C10H6BrClO3. Calculated, %: C 41.49; H 2.09.
4-Bromo-3-hydroxy-5-phenylfuran-2(5H)-one (4a).
FT-IR spectrum, ν, cm–1: 1117 (C–Br), 1236 (C–O),
1496, 1602, 1762 (C=O), 3324 (O–H). 1H NMR spectrum,
δ, ppm: 6.1 s (1H), 7.98–8.09 m (5H), 11.3 s (1H). 13C
NMR spectrum, δ, ppm: 56.5, 92.1, 112.1, 124.2, 127.8,
136.7, 152.2, 168.2. Found, %: C 47.11; H 2.77.
C10H7BrO3. Calculated, %: C 47.09; H 2.77.
4-Bromo-5-(4-bromophenyl)-3-hydroxyfuran-2(5H)-
one (4c). FT-IR spectrum, ν, cm–1: 1163 (C–Br), 1286
(C–O), 1488, 1620 (aromatic C=C stretch), 1760
1
(C=O), 3242 (O–H). H NMR spectrum, δ, ppm: 5.8 s
(1H), 7.44 d (J = 8.5 Hz, 2H), 7.77 d (J = 8.5 Hz, 2H),
11.35 s (1H). 13C NMR spectrum, δ, ppm: 56.3, 94.6,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 5 2018

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Table 2. The library of the synthesized pyrazolylbutyrolactones 6
Comp.
no.
Yield,
%
Comp.
no.
Yield,
%
Formula
Br
mp, °C
Formula
Br
mp, °C
OH
O
H3CO
OH
O
6a
93
223–225
6c
89
190–191
O
O2N
O
N
N
N
N
OH
Cl
OH
HO
6b
91
187–189
6d
96
254–256
Br
N
Br
N
O
O
O
O
N
N
112.5, 115.6, 127.8, 133.3, 156.6, 168.2. Found, %: C
35.91; H 1.88. C10H6Br2O3. Calculated, %: C 35.96; H 1.81.
δ, ppm: 6.41 s (1H), 7.84 d (J = 8.4 Hz, 1H), 7.86 d.d
(J = 8.4, 7.8 Hz, 1H), 7.99 d.d (J = 8.4, 7.6 Hz, 1H),
8.04 d (J = 7.6 Hz, 1H), 11.27 s (1H). 13C NMR
spectrum, δ, ppm: 56.3, 94.6, 110.8, 113.6, 118.9,
123.8, 135.9, 137.2, 158.1, 169.3. Found, %: C 41.53;
H 2.12. C10H6BrClO3. Calculated, %: C 41.49; H 2.09.
4-Bromo-3-hydroxy-5-(4-methoxyphenyl)furan-
2(5H)-one (4d). FT-IR spectrum, ν, cm–1: 1157 (C–
Br), 1249 (C–O), 1515, 1608 (aromatic C=C stretch),
1
1742 (C=O), 3295 (O–H). H NMR spectrum, δ, ppm:
3.87 s (3H), 5.82 s (1H), 6.97 d (J = 8.5 Hz, 2H), 7.26
d (J = 8.5 Hz, 2H), 11.23 s (1H). 13C NMR spectrum,
δ, ppm: 56.3, 63.2, 94.6, 110.8, 123.7, 125.7, 136.9,
156.9, 167.8. Found, %: C 41.53; H 2.12. C10H6BrClO3.
Calculated, %: C 41.49; H 2.09.
4-Bromo-3-hydroxy-5-(3-chlorophenyl)furan-
2(5H)-one (4g). FT-IR spectrum, ν, cm–1: 1076 (C–Br),
1096 (C–Cl), 1208 (C–O), 1459, 1609 (aromatic C=C
stretch), 1711 (C=O), 3413 (O–H). 1H NMR spectrum,
δ, ppm: 6.41 s (1H), 7.67 d.d (J = 8.2, 7.4 Hz, 1H),
7.85 d (J = 8.4 Hz, 1H), 7.85 d (J = 8.2 Hz, 1H), 8.63 d
4-Bromo-3-hydroxy-5-(4-methylphenyl)furan-
2(5H)-one (4e). FT-IR spectrum, ν, cm–1: 1037 (C–Br),
1139 (C–Cl), 1234 (C–O), 1475, 1609 (aromatic C=C
stretch), 1748 (C=O), 3446 (O–H). 1H NMR spectrum,
δ, ppm: 2.36 s (3H), 6.40 s (1H), 7.86 d (J = 8.0 Hz,
1H), 7.99 d (J = 8.4 Hz, 1H), 11.52 s (1H). 13C NMR
spectrum, δ, ppm: 32.4, 56.3, 94.6, 115.7, 123.9,
128.2, 138.3, 158.9, 169.6. Found, %: C 41.53; H 2.12.
C10H6BrClO3. Calculated, %: C 41.49; H 2.09.
13
(J = 2.4 Hz, 1H), 11.52 s (1H). C NMR spectrum, δ,
ppm: 56.3, 94.6, 111.6, 112.9, 117.8, 126.9, 134.2,
139.1, 158.0, 167.9. Found, %: C 37.11; H 1.52.
C10H5BrCl2O3. Calculated, %: C 37.06; H 1.54.
4-Bromo-3-hydroxy-5-(2,4-dichlorophenyl)furan-
2(5H)-one (4h). FT-IR spectrum, ν, cm–1: 1080 (C–
Br), 1095 (C–Cl), 1296 (C–O), 1463, 1585, 1610
1
(aromatic C=C stretch), 1712 (C=O), 3618 (O–H). H
4-Bromo-3-hydroxy-5-(2-chlorophenyl)furan-
2(5H)-one (4f). FT-IR spectrum, ν, cm–1: 1037 (C–Br),
1139 (C–Cl), 1234 (C–O), 1475, 1609 (aromatic C=C
stretch), 1748 (C=O), 3446 (O–H). 1H NMR spectrum,
NMR spectrum, δ, ppm: 6.40 s (1H), 7.86 d (J =
8.2 Hz, 1H), 7.98 d (J = 8.2 Hz, 1H), 8.21 s (1H),
11.51 s (1H). 13C NMR spectrum, δ, ppm: 56.3, 94.6,
111.7, 112.8, 114.5, 123.2, 132.8, 138.1, 157.6, 169.1.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 5 2018

IONIC LIQUID [BDBDMIm](Br3)2 AS A NEW EFFICIENT BROMINATING AGENT
1013
Found, %: C 37.11; H 1.52. C10H5BrCl2O3. Calculated,
%: C 37.06; H 1.54.
4-Bromo-3-hydroxy-5-[3-(5-chlorophenyl)-1-
phenyl-1H-pyrazol-4-yl]furan-2(5H)-one (6d). FT-
IR spectrum, ν, cm–1: 1282 (C–O stretch), 1492, 1595
(aromatic C=C stretch), 1726 (C=O stretch), 2923
4-Bromo-3-hydroxy-5-(2-hydroxyphenyl)furan-
2(5H)-one (4i). FT-IR spectrum, ν, cm–1: 1109 (C–Br
stretch), 1278 (C–O stretch), 1497, 1608 (aromatic
C=C stretch), 1726 (C=O stretch), 3245 (O–H stretch).
1H NMR spectrum, δ, ppm: 6.42 s (1H), 6.55 d (J =
6.4 Hz, 2H), 7.68–7.89 m (2H). 13C NMR spectrum, δ,
ppm: 56.3, 71.8, 94.6, 112.6, 118.2, 123.3, 127.9,
135.4, 138.0, 156.1, 167.6. Found, %: C 44.36; H 2.57.
C10H7BrO4. Calculated, %: C 44.31; H 2.60.
1
(aliphatic C–H stretch), 3267 (O–H stretch). H NMR
spectrum, δ, ppm: 4.44 s (1H), 7.42 d (J = 6.4 Hz, 2H),
7.56–7.59 m (5H), 7.92 d (J = 6.4 Hz, 2H), 7.98 s
(1H). 13C NMR spectrum, δ, ppm: 71.9, 93.9, 119.4,
119.8, 127.8, 127.9, 128.6, 128.9, 129.2, 131.6, 133.7,
137.4, 148.3, 168.4, 197.8. Found, %: C 52.86; H 2.87;
N 6.44. C19H12BrClN2O3. Calculated, %: C 52.87; H
2.80; N 6.49.
4-Bromo-3-hydroxy-5-[3-(4-methoxyphenyl)-1-
phenyl-1H-pyrazol-4-yl]furan-2(5H)-one (6a). FT-
IR spectrum, ν, cm–1: 1284 (C–O stretch), 1490, 1596
(aromatic C=C stretch), 1726 (C=O stretch), 2960
CONCLUSIONS
We have studied the first three component synthesis
of butyrolactones from aryl aldehydes, ethyl pyruvate
and [BDBDMIm](Br3)2 under mild conditions. The
simple process, easy workup, inexpensive materials,
and environmentally friendly brominating agent used
in the aqueous media, are the advantages of this
procedure. To the best of our knowledge, this is the
first report of application of ionic liquid [BDBDMIm]·
(Br3)2 as a brominating ionic liquid.
1
(aliphatic C–H stretch), 3302 (O–H stretch). H NMR
spectrum, δ, ppm: 3.94 s (3H), 6.48 s (1H), 6.55 d.d
(J = 6.4, 1.6 Hz, 2H), 7.48–7.55 m (2H), 7.59 s (2H),
7.71 m (2H), 7.92 d.d (J = 6.4, 1.9 Hz,1H), 8.19 d (J =
1.9 Hz, 1H). 13C NMR spectrum, δ, ppm: 62.4, 71.2,
95.8, 110.4, 118.4, 122.6, 124.7, 126.7, 128.9, 131.6,
132.5, 135.8, 138.9, 145.3, 164.8, 193.6. Found, %: C
56.26; H 3.57; N 6.54. C20H15BrN2O4. Calculated, %:
C 56.22; H 3.54; N 6.56.
ACKNOWLEDGMENTS
4-Bromo-3-hydroxy-5-[3-(4-hydroxyphenyl)-1-
phenyl-1H-pyrazol-4-yl]furan-2(5H)-one (6b). FT-
IR spectrum, ν, cm–1: 1282 (C–O stretch), 1465, 1600
(aromatic C-C stretch), 1728 (C=O stretch), 2960
(aliphatic C–H stretch), 3068 (aromatic C–H stretch),
3419 (O–H stretch). 1H NMR spectrum, δ, ppm: 4.49 s
(1H), 7.51–7.55 m (5H), 7.68–7.74 m (4H), 8.26 s
(1H). 13C NMR spectrum, δ, ppm: 71.8, 97.2, 110.6,
118.2, 125.8, 128.7, 128.8, 130.9, 132.4, 132.5, 135.1,
141.2, 148.3, 164.6, 199.8. Found, %: C 55.19; H 3.17;
N 6.81. C19H13BrN2O4. Calculated, % C 55.23; H 3.17;
N 6.78.
Financial support from the Research Council of
Payame Noor University of Rasht branch is sincerely
acknowledged.
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