Bromination of 5-substituted 3H-furan-2-ones and 3H-pyrrol-2-ones

Article abstract of DOI:10.1023/A:1022118107304

The bromination of 5-alkyl(aryl)-3H-furan-2-ones and 5-alkyl(aryl)-3H-pyrrol-2-ones and also their derivatives takes place at the ethylene bond with the formation of 4-monobromo derivatives. N-Phenyl-3H-pyrrol-2-ones are brominated simultaneously at the e

Full text of DOI:10.1023/A:1022118107304

Chemistry of Heterocyclic Compounds, Vol. 38, No. 11, 2002
BROMINATION OF 5-SUBSTITUTED
3H-FURAN-2-ONES AND 3H-PYRROL-2-ONES
A. Yu. Egorova and V. A. Sedavkina
The bromination of 5-alkyl(aryl)-3H-furan-2-ones and 5-alkyl(aryl)-3H-pyrrol-2-ones and also their
derivatives takes place at the ethylene bond with the formation of 4-monobromo derivatives. N-Phenyl-
3H-pyrrol-2-ones are brominated simultaneously at the ethylene bond of the heterocycle and at the
phenyl substituent at the nitrogen atom.
Keywords: 5-alkyl(aryl)-3H-pyrrol-2-ones, 5-alkyl(aryl)-3H-furan-2-ones, N-phenyl-3H-pyrrol-3-ones,
bromination.
Five-membered 2-carbonyl-containing O- and N-heterocycles are chemically active compounds
containing several reaction centers. We studied the reactivity of the methylene group and reaction at the ester
fragment earlier [1, 2], and we also studied the reaction at the ethylene bond for the case of the reaction with
dichlorocarbene under conditions of phase-transfer catalysis [3].
In the present work we present results on the bromination of 5-alkyl(aryl)-3H-furan-2-ones and
5-alkyl(aryl)-3H-pyrrol-2-ones and also their arylidene derivatives, the halogenation of which had not been
studied before. It seemed of interest to study the regioselectivity of bromination in order to functionalize the
obtained bromine derivatives further.
The bromination of 5-alkyl(aryl)-3H-furan-2-ones 1a-c was carried out with various brominating agents
(with a solution of bromine in acetic acid and with dioxane dibromide). The reaction was conducted under mild
conditions at 18-20°C with the reagents in an equimolar ratio.
Br
Br
R
H
Br
Br2
+
HBr
R
O
O
R
O
O
O
O
2a–c
1a–c
1, 2 a R = C5H11, b R = C6H13, c R = Ph
It was shown on the basis of elemental analysis and 1H NMR spectroscopy that bromination with bound
bromine (dioxane dibromide) and with a solution of bromine in acetic acid leads to 5-alkyl(aryl)-4-bromo-3H-
furan-2-ones 2a-c, the formation of which is possible through a stage involving addition followed by
dehydrobromination of the intermediate dibromide, which is transformed into the required products with a yield
of up to 61%.
__________________________________________________________________________________________
N. G. Chernyshevskii Saratov State University, Saratov, Russia; e-mail: TimofijiwaSU@info.sgu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1502-1506, November, 2002. Original
article submitted April 21, 2000.
0009-3122/02/3811-1319$27.00©2002 Plenum Publishing Corporation
1319

TABLE 1. The 1H NMR Spectra of the Synthesized Compounds
Chemical shifts, δ, ppm
Compound
R, m
С(3)H2 / C(4)H, s
=CH–Ar, s
0.85-1.94 (11Н)
0.82-2.01 (13Н)
7.50-7.75 (5Н)
0.82-2.00 (9Н)
0.82-2.02 (9Н)
7.30-7.72 (9H)
0.82-1.95 (9Н)
7.40-7.72 (10Н)
7.30-7.70 (10Н)
7.45-7.75 (9Н)
7.40-7.75 (7H)
4.12 (2H)
4.15 (2H)
4.20 (2H)
3.95 (2H)
3.94 (2H)
3.95 (2H)
4.05 (2H)
—
—
—
—
—
—
2а
2b
2c
4а
4b
4c
4d
8а
8b
8c
8d
—
6.05
6.10
6.16
6.65
—
—
4.35 (1H)
1
The H NMR spectra of compounds 2a-c do not contain a signal for the vinylic proton. At
4.12-4.20 ppm there is a singlet for the methylene protons at C-3, and at 0.82-2.01 ppm there is a series of
signals for the protons of the alkyl substituent at position 5 of the heterocycle (Table 1).
Analogous bromination conditions were used to study the reactivity of the ethylene bond in the
nitrogen-containing analogs – 1,5-disubstituted 3H-pyrrol-2-ones 3a-c. It was shown that the structure of the
reaction products depends on the nature of the substituent at the nitrogen atom of the heterocycle. Thus, during
the bromination of 5-alkyl-1-phenyl-3H-pyrrol-2-ones 3a,b both addition of bromine at the ethylene bond of the
heterocycle, followed by dehydrobromination, and electrophilic substitution in the phenyl fragment at the
nitrogen atom occur. The obtained 5-alkyl-4-bromo-1-(4-bromophenyl)-3H-pyrrolones 4a,b were isolated with
yields of up to 65%.
Br
+
Br2
R
O
R
O
N
N
Ph
3a,b
Br
4a,b
3, 4 a R = Bu, b R = i-Bu
5-Alkyl(aryl)-1-(4-methylphenyl)-3H-pyrrol-2-ones 3c,d were also brought into bromination. Their
bromination with a solution of bromine in benzene under mild conditions led to the production of 5-alkyl(aryl)-
4-bromo-1-(4-methylphenyl)-3H-pyrrol-2-ones 4c,d with a yield of 52%.
Br
Br2
+
– HBr
R
O
R
O
N
N
Me
Me
4c,d
3c,d
3, 4 c R = Ph, d R = Bu
1320

The IR spectra of compounds 4a-d contain absorption bands for the lactam carbonyl in the region of
1680-1675 cm-1, for the C=C double bond in the region of 1620-1610 cm-1, and for the C–Br bond at
516-510 cm-1. In the 1H NMR spectra of compounds 4a-d the signal for the vinylic proton at position 4 is absent,
but there are signals for the protons of the methylene group at position 3 at 3.95-4.05 ppm and the methyl group
of the aryl substituent at 2.14 ppm. In the downfield region there are a series of signals for the protons of the
aromatic substituent at 7.34-7.45 ppm.
To confirm that the reaction can indeed occur at the phenyl fragment at the nitrogen atom the
N-phenylamides of the 4-oxoalkanoic acids 5a,b, which are intermediate products in the production of the
1,5-disubstituted 3H-pyrrol-2-ones and do not contain an ethylene bond, were also brought into bromination.
Their reaction with bromine under mild conditions led to the formation of N-(bromophenyl)amides of
4-oxoalkanoic acids 6a,b with yields of up to 70%.
O
O
RCCH2CH2C
RCCH2CH2C
+
Br2
– HBr
NHPh
N
Br
H
O
O
5a,b
6a,b
5, 6 a R = Ph, b R = C5H11
We also extended the bromination to the arylidene derivatives of furan-2-ones and pyrrol-2-ones, which
contain two ethylene bonds. The concurrent formation of the products from addition of bromine either at the
ethylene bond of the heterocycles or at the exocyclic ethylene bond could be expected for these compounds.
Br
Ph
Ar
CH Ar
O
CH
O
Br2
+
– HBr
Ph
X
X
8a–c
7a–c
7, 8 a,b Ar = Ph, c Ar = C6H4–NO2-3; a X = O, b,c X = NH
It should be noted that somewhat more drastic reaction conditions, i.e., heating at 45-50°C, are required
in this case. It was found that the reaction of compounds 7a-c with bromine leads to the formation of
monobromine-containing products 8a-c with yields of up to 53%.
Br
H
C
H
C
Br2
+
Br
OH
OH
Ph
Ph
O
O
N
H
N
H
7d
8d
An exception is 3-(2-hydroxybenzylidene)-5-phenyl-3H-pyrrol-2-one (7d), the bromination of which
takes place at the arylidene substituent at position 3, and this is due to the ease of halogenation of the benzene
ring activated by the hydroxyl group. The ethylene bond of the ring in this case is not affected. We isolated
3-(3,5-dibromo-2-hydroxybenzylidene)-5-phenyl-3H-pyrrol-2-one (8d) with a yield of 42%. Its structure was
1
confirmed by the H NMR spectrum. In the spectrum of this compound the singlet of the vinylic proton of the
heterocycle is retained at 4.35 ppm, and there is also a singlet for the proton of the exocyclic sp2-hybridized
carbon atom at 6.65 ppm and a series of signals for the protons of the aromatic substituents lie in the downfield
region at 7.40-7.75 ppm.
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TABLE 2. The Physicochemical Characteristics of the Synthesized
Compounds
Found, %
——————
Com-
pound
Empirical
formula
Yield,
%
20
mp, °C
nD
Calculated, %
C
H
N
Br
C9H13BrO2
46.62
46.35
5.05
5.58
33.40
34.33
1.5020
1.5050
1.5120
—
60
54
61
63
65
51
52
68
72
52
53
2а
2b
2c
4a
4b
4c
4d
6а
6b
8а
8b
C10H15BrO2
C10H7BrO2
49.04
6.25
31.80
48.62
6.12
32.35
50.45
50.21
3.04
2.93
33.67
33.47
C14H15Br2NO
C14H15Br2NO
C17H14BrNO
C15H18BrNO
C16H14BrNO2
C15H20BrNO2
C17H11BrO2
C17H12BrNO
45.10
3.95
3.60
3.75
43.10
266-268
262-264
72-73
45.04
4.02
42.89
45.15
45.04
3.96
4.02
3.65
43.05
42.89
—
3.75
62.31
4.31
4.40
4.27
24.52
—
62.19
4.27
24.39
58.74
58.44
5.96
5.84
4.72
26.70
25.97
75-76
—
4.54
58.10
4.35
4.53
4.22
24.54
130-131
125-126
158-159
—
57.83
4.22
24.09
55.35
55.21
6.23
6.13
4.10
24.35
24.54
—
4.29
62.45
3.30
25.00
—
62.38
3.36
24.46
62.70
62.57
3.52
3.68
4.09
4.29
24.85
24.54
>200
—
(dec.)
C17H11BrN2O3
C17H11Br2NO2
60.38
3.41
7.85
24.05
>230
—
—
53
42
8c
60.17
3.24
8.26
23.59
(dec.)
48.52
48.45
2.20
2.61
3.21
3.32
33.52
33.00
>250
8d
(dec.)
Thus, the bromination of 5-alkyl(aryl)-3H-furan-2-ones and 5-alkyl(aryl)-3H-pyrrol-2-ones and their
derivatives is realized under mild conditions at the ethylene bond of the heterocycle and leads to the formation
of monobromo-substituted products. N-Phenyl-3H-pyrrol-2-ones are brominated simultaneously at the ethylene
bond of the heterocycle and at the phenyl substituent.
EXPERIMENTAL
1
The IR spectra were recorded on an IKS-29 instrument. The H NMR spectra were obtained on a
Varian FT-80A instrument at 80 MHz with TMS as internal standard. The yields and characteristics of the
compounds are given in Tables 1 and 2.
5-R-3H-Furan-2-ones (1a-c) and 3-Arylidene-5-phenyl-3H-furan(pyrrol)-2-ones (7a-d). The
compounds were obtained by the method in [1]. The 1-Ar-5-R-3H-pyrrol-2-ones 3a-d and the amides of the
4-oxo acids 5a,b were obtained by the method in [2].
5-Alkyl(aryl)-4-bromo-3H-furan-2-ones (2a-c). To a solution of the compound 1a-c (6 mmol) in
dioxane with cooling to 0°C we added 6 mmole of dioxane dibromide. The reaction mixture was then poured
into cold water (30 ml), neutralized with sodium carbonate, and extracted with chloroform. The extract was
dried over calcium chloride. The product was purified on a column of aluminum oxide with hexane as eluent.
5-Alkyl(aryl)-4-bromo-1-(4-bromophenyl)-3H-pyrrol-2-ones (4a,b). To a solution of the compound
3a,b (30 mmol) in dioxane with cooling to 0°C we added dioxane dibromide (30 mmol). The mixture was kept
for 30 min. The crystals that separated were recrystallized from 2-propanol.
1322

5-Alkyl(aryl)-4-bromo-1-(4-methylphenyl)-3H-pyrrol-2-ones (4c,d). The compounds were obtained
similarly to compounds 4a,b. The products were recrystallized from chloroform.
N-(4-Bromophenyl)amides of 4-Oxo Acids (6a,b). The compounds were obtained similarly to
compounds 4a-d. The products were recrystallized from a 3:1 mixture of 2-propanol and hexane.
3-Arylidene-4-bromo-5-phenyl-3H-furan(pyrrol)-2-ones (8a-d). To a solution of the compound 7a-d
(5 mmol) in chloroform we added an equimolar amount of bromine. The mixture was heated on a water bath
(45-50°C) for 30 min. The crystals that separated on cooling were recrystallized from hexane.
REFERENCES
1.
V. A. Sedavkina, N. A. Morozova, A. Yu. Egorova, and I. G. Ostroumov, Khim. Geterotsikl. Soedin.,
451 (1987).
2.
3.
N. A. Morozova, V. A. Sedavkina, and A. Yu. Egorova, Khim. Geterotsikl. Soedin., 349 (1994).
V. A. Sedavkina, N. A. Morozova, A. Yu. Egorova, and R. G. Savkin, Izv. Akad. Nauk, Ser. Khim., 1995
(1995).
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