Synthesis and structural characterization of pyrrole heterocyclic systems bearing amino acid units: Novel pyrrol-3-ones, pyrrolo[1,2-a][3,1]benzoxazines, and pyrrolo[2,1-b][1,3]oxazoles

Article abstract of DOI:10.1002/jhet.1509

Furan-3-one derivatives 1 were converted into 2-hydroxy-pyrrole-3-ones 4 by reacting with various α- and β-amino acids. In contrast, the reaction of furan-3-ones and 1-aminocyclobutanecarboxylic acid afforded spiro-pyrrolo[2,1-b][1,3]oxazoles 5 via the pyrrole-3-one intermediate under the same reaction conditions. Some of 2-hydroxy-pyrrole-3-ones 3 derived from anthranilic acids were transformed to pyrrolo[1,2-a][3,1]benzoxazines via intramolecular esterification.

Full text of DOI:10.1002/jhet.1509

212
Synthesis and Structural Characterization of Pyrrole Heterocyclic Systems
Bearing Amino Acid Units: Novel Pyrrol-3-ones, Pyrrolo[1,2-a][3,1]
benzoxazines, and Pyrrolo[2,1-b][1,3]oxazoles
Vol 51
a
a
b
a
*
İrfan Koca, Mustafa Saçmacı, Filiz Yılmaz, and Şevket Hakan Üngören
aDepartment of Chemistry, Faculty of Arts and Sciences, Bozok University, Yozgat, Turkey
bDepartment of Chemistry, Faculty of Arts and Sciences, Anadolu University, Eskişehir, Turkey
*
E-mail: hungoren@yahoo.com
Received April 12, 2011
DOI 10.1002/jhet.1509
Published online 31 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
NH2 O
O
O
O
O
Ar
Ar
O
OH
Ar
Ar
Ar
Ar
COOR
COOR
O
R'
SOCl2, Benzene
OH
N
O
N
O
MeOH, 4h, reflux
O
RO
COOH
NH
2O
R'
R'
OH
O
O
Ar
Ar
COOR
N
O
O
Furan-3-one derivatives 1 were converted into 2-hydroxy-pyrrole-3-ones 4 by reacting with various
a- and b-amino acids. In contrast, the reaction of furan-3-ones and 1-aminocyclobutanecarboxylic acid afforded
spiro-pyrrolo[2,1-b][1,3]oxazoles 5 via the pyrrole-3-one intermediate under the same reaction conditions.
Some of 2-hydroxy-pyrrole-3-ones 3 derived from anthranilic acids were transformed to pyrrolo[1,2-a][3,1]
benzoxazines via intramolecular esterification.
J. Heterocyclic Chem., 51, 212 (2014).
INTRODUCTION
and bioactive products that were isolated from marine organ-
ism or plant. In the light of this, pyrroles including amino
acid units are interesting compounds from the viewpoint of
both their synthesis and biological applications.
In the course of our recent studies on the furan chemistry,
it was shown that pyrroles including amino acid moiety
could be prepared from the reactions of amino acids with
2-methylene-furan-3-ones [8]. In this work, we aimed to
prepare novel pyrroles, spiro-pyrrolo-oxazoles and pyrrolo-
benzoxazoles, as new amino acid heterocycles on the basis
of 2-methylene-furan-3-one chemistry.
Amino acids play crucial roles both as building blocks of
proteins and as intermediates in metabolism. Moreover,
some natural heterocycles and synthetic drugs contained cy-
clic amino acid units for instance guanin, caffeine, lukianol
A, diazepam, URB754, and cetilistat. Therefore, naturally
occurring or synthetically obtained heterocyclic amino acid
derivatives constitute an important resource for new drugs
[1–4]. Especially, synthesis of novel heterocyclic systems
provides new contributions to these research topics.
RESULTS AND DISCUSSIONS
Various anthranilic acid derivatives 2 reacted with
2-methylene-furan-3-ones 1 in methanol in the presence
of pyridine to give the corresponding 2,3-dihydro-1H-
pyrrol-3-ones (3) as described in Scheme 1. Although the
compounds 3 have an alcohol group and an acid group at
corresponding positions of the molecule, these groups did
not react to give pyrrolo[1,2-a][3,1]benzoxazin-5-one by
intramolecular esterification, spontaneously.
Pyrroles and their condensed compounds become in-
creasingly important in medicinal chemistry and organic
synthesis [5]. For instance, lamellarins, lukianols [6], and
terresoxazine [7], which possess a pyrrole ring, are natural
© 2013 HeteroCorporation

January 2014
Pyrrol-3-ones, Pyrrolo[1,2-a][3,1]benzoxazines, and Pyrrolo[2,1-b][1,3]oxazoles
213
Scheme 1. Reaction of furan-3(2H)-ones with anthranilic acid derivatives.
Figure 1. Molecular structure of 5a (hydrogen atoms have been omitted
for clarity). [Color figure can be viewed in the online issue, which is avail-
able at www.interscience.wiley.com.]
Compounds 1 also led to the corresponding pyrrole-3-
one skeleton 4 by reacting b-alanine and 1-aminocyclopro-
panecarboxylic acid (Scheme 2). On the other hand,
spiro-pyrrolo[2,1-b][1,3]oxazoles 5 were obtained from
the reaction of 1 with 1-aminocyclobutanecarboxylic acid
via the pyrrole-3-one intermediate. In the 1H NMR spectra,
the methylene protons attached to an asymmetric center of
a pyrrole ring show the signals of AB system as four lines.
The signals of these diastereotopic protons clearly revealed
the proposed pyrrole structure.
The structure of compound 5a was determined from
X-ray crystallography method [9]. The molecular structure
of 5a with the atom labeling is shown Figure 1. There
are five ring systems, which are cyclobutane [Cg1:
C(6)–C(7)–C(8)–C(9)], oxazole [Cg2: N(1)–C(4)–O(2)–C
(5)–C(6)], pyrrole [Cg3: N(1)–C(2)–C(3)–C(4)], and two
phenyl rings [Cg4: C(10)–C(11)–C(12)–C(13)–C(14)–C
(15); Cg5: C(18)–C(19)–C(20)–C(21)–C(22)–C(23)] in
molecular structure. C–C bond distances ranging from
1.518(3) Ǻ [C(7)–C(8)] to 1.549(3) Ǻ [C(6)–C(9)] and
average bond angle value is 89.94ꢀ in cyclobutane ring.
The bond distances are typical single-bond character in
oxazole ring. The dihedral angles of the N(1)–C(4)–O
(2)–C(5)–C(6) oxazole plane with the C(6)–C(7)–C(8)–C
(9) cyclobutane plane and the N(1)–C(2)–C(3)–C(4) pyrrole
plane are 87.21ꢀ and 48.73ꢀ, respectively.
The crystal packing of 5a is a composite of C–HÁÁÁp and
C═OÁÁÁp interactions. Inter molecular C–HÁÁÁp interaction
occurs between C(25)–H(25B) and Cg(4). The H-ring
centroid (HÁÁÁCg) distance is 2.65 Å, and the g angle is
2.83ꢀ. C(25)–H(25B)ÁÁÁCg4 angles, 142ꢀ, is below the
optimal value (180ꢀ) for the strongest C–HÁÁÁp interaction,
which may be due to the steric constraints in the molecule.
In addition, there is also C═OÁÁÁp interaction between
C(5)–O(3) group and pyrrole ring center [C(5)–O(3)ÁÁÁCg
(3) = 3.838 Å].
Scheme 2. Reaction of furan-3(2H)-ones with aliphatic amino acids.
The reactions of 3 with SOCl2 in benzen at 50 ꢀC are
composed of complex crude products. According to the
NMR data, the crude products contain both intramolecular
esterification products and also b-elimination products
as by-product. The compounds 6a,l could be isolated from
some crude products by using column chromatography
method (Scheme 3).
The reaction products of 3a,l with SOCl2 do not show
the absorptions of –OH groups. This observation is clearly
revealed to intramolecular esterification of 3a,l. In addition
to this, intramolecular esterifications of 3a,l were verified
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

214
İ. Koca, M. Saçmacı, F. Yılmaz, and Ş. H. Üngören
Vol 51
Scheme 3. Products from the reaction of some 2,3-dihydro-1H-pyrrol-3-
ones attached to anthranilic acids with SOCl2.
graphite monochrometed Mo Ka radiation (l = 0.71069 Å).
Diffraction data were collected over the full sphere and were
corrected for absorption. The data reduction was performed
with the SAINT program package. We found the structure
solution with the SHELXS-97 [12] package by using the
direct methods, and we refined SHELXL-97 [13] against F2
by using first isotropic. All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were added to the structure
model at calculated positions. Geometric calculations were
performed with Platon [14]. We obtained molecular drawings
by using mercury [15].
General procedure for the preparation of 2,3-dihydro-1H-
pyrrol-3-one (3, 4) and pyrrolo[2,1-b][1,3]oxazol (5) from the
a- and b-amino acid derivatives.
Corresponding a- and b-
amino acid derivatives (1 mmol) and 1a,b (1 mmol) were refluxed
in a mixture of 50 mL methanol and about 1 mL of pyridine for
1 h. To the crude product was added 30 mL 1 M HCl solution. The
mixture was extracted with AcOEt (3 Â 20 mL), and the solvent
was removed by evaporation. The combined organic extracts were
dried (MgSO4). The solvent was removed on a rotary evaporator,
and the residue was subjected to column chromatography on Silica
gel 60 HF254. Elution with AcOEt afforded the product.
2-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]benzoic
acid (3a). This compound was obtained as pale yellow crystals,
0.351 g (66%), mp 132ꢀC; ir (KBr): 3429 (OH, acid), 3251 (OH,
by the detection of lacton C═O absorbtion of 6a,l. The
spectroscopic data of all synthesized compounds are in
agreement with the proposed structure.
1
alcohol), 1736, 1691, 1628, 1605 (C═O), 1576cmÀ1 (C═C); H
NMR (300 MHz, CDCl3): d 7.90–6.50 (m, 12H, Ar–H), 3.76,
3.74, 3.59 (3s, 9H, 3 MeO), 3.36 (A part of AB system, d,
1H, J = 15.4, CH2COOMe), 3.00 (B part of AB system, d, 1H,
J = 15.4, CH2COOMe); 13C NMR (75 MHz, CDCl3): d 195.2,
189.7, 178.7, 170.3 (4C═O), 162.9, 161.4, 145.0, 136.3, 133.1,
132.5, 132.0, 131.8, 131.4, 131.0, 128.7, 121.1, 1113.6, 113.1,
112.8 (Ar–C═C, C═C), 91.0 (N–C–OH), 55.3, 55.1, 52.2
(3 MeO), 40.5 (CH2). Anal. Calcd for C29H25NO9 (531.5 g/mol):
C, 65.53; H, 4.74; N, 2.64. Found: C, 65.18; H, 4.52; N 3.01.
5-Hydroxy-2-[2-hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-
oxoethyl)-5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-
CONCLUSIONS
We have synthesized novel 2,3-dihydro-1H-pyrrol-3-one,
pyrrolo[1,2-a][3,1]benzoxazin-5-one, and pyrrolo[2,1-b][1,3]
oxazole compounds containing amino acid units in miscel-
laneous yields from 2-methylene-furan-3-ones. This report
is the first about synthesis and crystal structure of a spiro-
pyrrolo[2,1-b][1,3]oxazole ring system. These functiona-
lized products with amino acid units are amenable to further
transformations, and we anticipate that they may have
important applications in medicinal and synthetic organic
chemistry.
yl]benzoic acid (3b).
This compound was obtained as
pale green crystals, 0.223 g (41%), mp 167 ꢀC; ir (KBr): 3393
(OH, acid), 3247 (OH, alcohol), 1730, 1692 (C═O),
1577 cmÀ1 (C═C); 1H NMR (300 MHz, DMSO-d6): d 10.07 (s,
1H, Ar–OH), 7.88–6.72 (m, 11H, Ar–H), 3.83, 3.68, 3.62 (3s,
9H, 3 MeO), 3.46 (s, 1H, COOH, br), 2.95 (A part of AB
system, d, 1H, J = 15.4, CH2COOMe), 2.69 (B part of AB
system, d, 1H, J = 15.4, CH2COOMe); 13C NMR (75 MHz,
DMSO-d6): d 194.0, 188.5, 178.6, 169.1 (4C═O), 168.5, 162.9,
161.0, 160.9, 157.4, 132.3, 132.1, 132.0, 131.6, 131.2, 126.4,
122.5, 119.1, 117.5, 113.7, 113.6 (Ar–C═C, C═C), 90.2
(N–C–OH), 55.9, 55.6, 52.3 (3 MeO), 41.0 (CH2). Anal. Calcd
for C29H25NO10 (548.5g/mol): C, 63.62; H, 4.60; N, 2.56. Found:
C, 63.84; H, 4.51; N 2.31.
EXPERIMENTAL
The starting materials 1a,b were prepared according to
Saçmacı [8] and Üngören [10]. Melting points were deter-
mined on an Electrothermal 9200 apparatus and are uncor-
rected. We carried out elemental analyses (C, H, N) using
LECO-932 CHNS-O analyzer. We recorded IR spectra on a
Jasko Plus Model 460 FT-IR Spectrometer as KBr pellets
and Perkin Elmer Spectrum 400 FT-IR Spectrometer by using
the ATR method. We obtained 1H (300.13 MHz) and 13C
(75.47 MHz) NMR by using Bruker Ultrashield in CDCl3
and DMSO-d6. All experiments were followed by tlc using
DC Alufolien Kieselgel 60F 254 Merck and Camag TLC lamb
(254/366 nm).
2-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-
5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-5-methylbenzoic
acid (3c). This compound was obtained as pale yellow crystals,
0.454g (83%), mp 129ꢀC; ir (KBr): 3423 (OH, acid), 3224 (OH,
1
alcohol), 1737, 1690, 1631, 1605 (C═O), 1575 cmÀ1 (C═C); H
NMR (300 MHz, CDCl3): d 7.71–6.49 (m, 11H, Ar–H), 3.74,
3.72, 3.57 (3s, 9H, 3 MeO), 3.33 (A part of AB system, d, 1H,
J = 15.4, CH2COOMe), 2.96 (B part of AB system, d, 1H,
J = 15.4, CH2COOMe), 2.29 (s, 3H, Me); 13C NMR (75MHz,
Crystallographic analyses: We collected diffraction data for
complexes with a Bruker AXS APEX [11] CCD diffractome-
ter equipped with a rotation anode at 100 (2) K by using
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DOI 10.1002/jhet

January 2014
Pyrrol-3-ones, Pyrrolo[1,2-a][3,1]benzoxazines, and Pyrrolo[2,1-b][1,3]oxazoles
215
CDCl3): d 195.3, 189.7, 179.0, 170.7 (4 C═O), 162.8, 161.3, 144.8,
138.9, 133.3, 133.0, 132.3, 132.0, 131.5, 131.3, 130.7, 121.3,
113.6, 113.1, 112.7 (Ar–C═C, C═C), 90.9 (N–C–OH), 55.3,
55.1, 52.2 (3 MeO), 40.5 (CH2), 21.0 (Me). Anal. Calcd
for C30H27NO9 (545.5 g/mol): C, 66.05: H, 4.99; N, 2.57. Found:
C, 66.35; H, 4.95; N, 2.90.
135.2, 134.8, 134.4, 132.5, 131.9, 131.3, 122.4, 121.1, 113.7, 113.4,
113.1 (Ar–C═C, C═C), 90.9 (N–C–OH), 55.3, 55.1, 52.2 (3 MeO),
40.7 (CH2). Anal. Calcd for C29H24BrNO9 (610 g/mol): C,
57.06; H, 3.96; N, 2.29. Found: C, 57.22; H, 4.25; N, 2.26.
5-Chloro-2-[2-hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-
oxoethyl)-5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-
2-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-3,5-
yl]benzoic acid (3h).
This compound was obtained as pale
yellow crystals, 0.368g (65%), mp 127ꢀC; ir (KBr): 3428
(OH, acid), 3234 (OH, alcohol), 1736, 1692, 1633, 1604
dimethylbenzoic acid (3d).
This compound was obtained as
1
pale yellow crystals, 0.245g (44%), mp 136ꢀC; ir (KBr): 3437
(OH, acid), 3282 (OH, alcohol), 1804, 1742, 1706, 1647, 1600
(C═O), 1574 cmÀ1 (C═C); 1H NMR (300 MHz, DMSO-d6):
d 8.64–6.47 (m, 10H, Ar–H), 3.82, 3.67, 3.58 (3s, 9H, 3 MeO),
3.34 (s, 1H, COOH, br), 2.86 (A part of AB system, d, 1H,
J = 15.4, CH2COOMe), 2.63 (B part of AB system, d, 1H,
J = 15.4, CH2COOMe), 2.27, 2.01 (2s, 6H, 2 Me); 13C NMR
(75 MHz, DMSO-d6): d 194.9, 188.6, 179.0, 169.7 (4 C═O),
162.9, 161.1, 138.5, 138.2, 134.7, 132.4, 132.0, 131.0, 130.6,
129.3, 129.3, 122.9, 113.6, 113.6, 111.6 (Ar–C═C, C═C), 90.7
(N–C–OH), 55.9, 55.6, 52.1 (3 MeO), 40.0 (CH2) 20.8, 18.1 (2
Me). Anal. Calcd for C31H29NO9 (559 g/mol): C, 66.54; H, 5.22;
N, 2.50. Found: C, 66.15; H, 5.19; N, 2.53.
(C═O), 1575 cmÀ1 (C═C); H NMR (300MHz, CDCl3): d 8.47
(OH, br), 7.73–6.51 (m, 11H, Ar–H), 3.75, 3.72, 3.60 (3s, 9H, 3
MeO), 3.34 (A part of AB system, d, 1H, J =15.4, CH2COOMe),
2.95 (B part of AB system, d, 1H, J = 15.4, CH2COOMe); 13C
NMR (75MHz, CDCl3): d 195.2, 189.6, 178.5, 169.6 (4 C═O),
162.9, 161.5, 144.2, 135.9, 134.6, 134.5, 132.2, 132.0, 131.7,
131.3, 131.2, 126.2, 121.0, 113.7, 113.1 (Ar–C═C, C═C), 91.0
(N–C–OH), 55.3, 55.1, 52.2 (3 MeO), 40.6 (CH2). Anal. Calcd for
C29H24ClNO9 (566g/mol): C, 61.54; H, 4.27; N, 2.47. Found: C,
61.24; H, 4.16; N, 2.36.
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]benzoic
acid (3i). This compound was obtained as pale yellow crystals,
0.197 g (36%), mp 111ꢀC; ir (KBr): 3429 (OH, acid), 3378 (OH,
alcohol), 1732, 1691, 1631, 1602 (C═O), 1575 (C═C). 1H NMR
2-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-5-
3
methoxybenzoic acid (3e).
This compound was obtained as
(300 MHz, CDCl3): 7.79–6.51 (m, 12H, Ar–H), 4.21 (q, J = 6.9,
pale yellow crystals, 0.433g (77%), mp 105ꢀC; ir (KBr): 3451
2H, OCH2), 3.77, 3.60 (2s, 6H, 2 MeO), 3.35 (A part of AB
system, d, 1H, J = 15.4, CH2COOEt), 2.98 (B part of AB
system, d, 1H, J = 15.4, CH2COOEt), 1.25 (t, 3J = 6.9, Me);
13C NMR (75MHz, CDCl3): d 195.1, 189.6, 178.9, 170.7
(4C═O), 162.9, 161.3, 144.5, 136.2, 133.6, 132.4, 132.0, 131.5,
131.3, 131.0, 128.6, 121.1, 113.58, 113.6, 113.1, 112.9
(Ar–C═C, C═C), 91.0 (N–C–OH), 61.2 (OCH2CH3), 55.3, 55.1
(2 MeO), 40.8 (C–CH2COEt), 14.1 (OCH2CH3). Anal. Calcd for:
C30H27NO9 (545 g/mol): C, 66.05; H, 4.99; N, 2.57. Found:
C, 65.97; H, 5.14; N, 2.84.
(OH, acid), 3217 (OH, alcohol), 1737, 1688, 1631, 1604 (C═O),
1573cmÀ1 (C═C); 1H NMR (300 MHz, CDCl3):
d 7.81
(br, 2H, 2 OH,), 7.76–6.49 (m, 11H, Ar–H), 3.76, 3.75, 3.72, 3.59
(4s, 12H, 4 MeO), 3.32 (A part of AB system, d, 1H, J = 15.4,
CH2COOMe), 2.96 (B part of AB system, d, 1H, J = 15.4,
CH2COOMe); 13C NMR (75 MHz, CDCl3): d 195.2, 189.6,
179.0, 170.4 (4 C═O), 162.8, 161.3, 159.1, 134.5, 132.1, 132.0,
131.4, 131.3, 128.7, 128.3, 121.3, 118.3, 116.0, 113.6, 113.1
(Ar–C═C, C═C), 90.8 (N–C–OH), 55.6, 55.3, 55.1, 52.2 (4
MeO), 40.4 (CH2). Anal. Calcd for C30H27NO10 (561 g/mol):
C, 64.17; H, 4.85; N, 2.49. Found: C, 64.22; H, 5.00; N, 2.20.
2-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-4,5-
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-5-
hydroxybenzoic acid (3j).
This compound was obtained as
pale green crystals, 0.320 g (57%), mp 155 ꢀC; ir (KBr): 3380
dimethoxybenzoic acid (3f).
This compound was obtained
(OH, acid), 3208 (OH, alcohol), 1729, 1692, 1604 (C═O),
1
as pale yellow crystals, 0.162 g (27%), mp 107 ꢀC; ir (KBr):
3446–3352 (OH, acid), 3135 (OH, alcohol), 1735, 1688, 1627,
1603 (C═O), 1574 cmÀ1 (C═C); 1H NMR (300 MHz, CDCl3):
d 7.74–6.22 (m, 10H, Ar–H), 4.00, 3.87, 3.83, 3.77, 3.74
(5s, 15H, 5 MeO), 3.37 (A part of AB system, d, 1H, J = 15.4,
CH2COOMe), 3.00 (B part of AB system, d, 1H, J = 15.4,
CH2COOMe); 13C NMR (75 MHz, CDCl3): d 194.8, 189.5,
178.8, 169.9 (4 C═O), 162.9, 161.4, 152.3, 144.5, 131.9, 131.3,
130.9, 130.3, 128.7, 124.4, 113.7, 113.7, 113.5, 113.1, 112.7
(Ar–C═C, C═C), 90.9 (N–C–OH), 56.4, 56.1, 55.3, 55.1, 52.3
(5 MeO), 41.0 (CH2). Anal. Calcd for C31H29NO11 (591 g/mol):
C, 62.94; H, 4.94; N, 2.37. Found: C, 62.88; H, 5.24; N, 2.52.
5-Bromo-2-[2-hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-
oxoethyl)-5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-
1-yl]benzoic acid (3g). This compound was obtained as pale
yellow crystals, 0.452g (74%), mp 146ꢀC; ir (KBr): 3452 (OH,
acid), 3394 (OH, alcohol), 1736, 1704, 1608 (C═O), 1575 cmÀ1
(C═C); 1H NMR (300 MHz, CDCl3): d 9.66 (OH, br), 7.84–6.51
(m, 11H, Ar–H), 3.77, 3.73, 3.62 (3s, 9H, 3 MeO), 3.35 (A part
of AB system, d, 1H, J = 15.4, CH2COOMe), 3.00 (B part of AB
system, d, 1H, J= 15.4, CH2COOMe); 13C NMR (75 MHz, CDCl3):
d 195.1, 189.4, 178.3, 170.1 (4 C═O), 162.9, 161.4, 145.6, 136.9,
1573cmÀ1 (C═C); H NMR (300 MHz, DMSO-d6): d 7.97–6.61
(m, 11H, Ar–H), 4.09 (q, 3J = 7.1, 2H, OCH2), 3.83, 3.68 (2s, 6H,
2 MeO), 3.40 (OH, alcohol, br), 2.94 (A part of AB system,
d, 1H, J = 15.4, CH2COOEt), 2.68 (B part of AB system, d,
1H, J = 15.4, CH2COOEt), 1.15 (t, 3J = 7.1, 3H, Me); 13C
NMR (75 MHz, DMSO-d6): d 194.0, 188.5, 178.7, 168.6 (4C═O),
163.0, 161.0, 157.4, 132.9, 132.4, 132.0, 131.3, 129.2, 122. 5,
119.2, 118,2, 117.6, 115.7, 113.7, 113.6 (Ar–C═C, C═C), 90.3
(N–C–OH), 61.1 (OCH2CH3), 55.9, 55.6 (2 MeO), 41.4
(C–CH2COEt), 14.4 (OCH2CH3). Anal. Calcd for C30H27NO10
(561 g/mol): C, 64.17; H, 4.85; N, 2.49. Found: C, 64.22; H, 5.00;
N, 2.20.
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-5-
methylbenzoic acid (3k). This compound was obtained as pale
yellow crystals 0.419 g (75%), mp 135ꢀC; ir (KBr): 3428 (OH,
acid), 3378(OH, alcohol), 1732, 1690, 1631, 1605 (C═O),
1
1575cmÀ1 (C═C); H NMR (300 MHz, DMSO-d6): d 7.80–6.71
(m, 11H, Ar–H), 4.09 (q, 3J = 7.1, 2H, OCH2), 3.83, 3.67 (2s, 6H,
2 MeO), 2.97 (A part of AB system, d, 1H, J =15.4, CH2COOEt),
2.63 (B part of AB system, d, 1H, J = 15.4, CH2COOEt), 2.31
(s, 3H, Me), 1.15 (t, 3J = 7.1, 3H, Me); 13C NMR (75MHz,
Journal of Heterocyclic Chemistry
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İ. Koca, M. Saçmacı, F. Yılmaz, and Ş. H. Üngören
Vol 51
1
DMSO-d6): d 193.9, 188.5, 178.3, 168.6 (4 C═O), 163.0, 161.1,
149.9, 138.6, 133.2, 133.2, 132.3, 132.0, 131.7, 131.3, 129.2,
122.3, 113.9, 113.6, 112.2 (Ar–C═C, C═C), 90.4 (N–C–OH),
61.1 (OCH2CH3), 55.9, 55.6 (2 MeO), 41.5 (C–CH2CO2Et),
20.9 (Ar–CH3), 14.4 (OCH2CH3). Anal. Calcd for C31H29NO9
(559 g/mol): C, 66.54; H, 5.22; N, 2.50. Found: C, 66.15; H,
5.19; N, 2.53.
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-3,5-
dimethylbenzoic acid (3l). This compound was obtained as pale
yellow crystals, 0.253g (44%), mp 120ꢀC; ir (KBr): 3425 (OH,
acid), 3240 (OH, alcohol), 1734, 1691, 1631, 1604 (C═O),
1575 cmÀ1 (C═C). 1H NMR (300 MHz, DMSO-d6): d 7.82–6.73
(m, 10H, Ar–H), 4.04 (q, 3J = 7.1, 2H, –OCH2), 3.82, 3.66
(2s, 6H, 2 MeO), 2.63 (A part of AB system, d, 1H, J = 15.4,
CH2COOEt), 2.17 (B part of AB system, d, 1H, J = 15.4,
CH2COOEt), 2.27 (2s, 6H, 2 Me), 1.16 (t, 3J=7.1, 3H, Me);
13C NMR (75 MHz, DMSO-d6): d 194.7, 188.6, 179.2, 169.7
(4 C═O), 162.9, 161.2, 138.8, 138.4, 136.9, 132.4, 132.0, 131.0,
130.7, 129.5, 129.2, 122.8, 113.7, 113.6, 111.6 (Ar–C═C, C═C),
90.6 (N–C–OH), 60.9 (OCH2CH3), 55.9, 55.6 (2 MeO), 20.8, 18.1
(2 Ar–CH3), 14.4 (OCH2CH3). Anal. Calcd for C32H31NO9
(573 g/mol): C, 67.01; H, 5.45; N, 2.44. Found: C, 66.98; H,
5.40; N, 2.70.
(C═O), 1575 cmÀ1 (C═C); H NMR (300 MHz, DMSO-d6): d
3
7.99–6.75 (m, 11H, Ar–H), 4.08 (q, J = 7.1, 2H, OCH2), 3.84,
3.68 (2s, 6H, 2 MeO), 2.98 (A part of AB system, d, 1H,
J = 15.4, CH2COOEt), 2.67 (B part of AB system, d, 1H,
J = 15.4, CH2COOEt), 1.14 (t, 3J = 7.1, 3H, Me); 13C NMR
(75 MHz, DMSO-d6): d 193.9, 188.6, 178.0, 168.6 (4 C═O),
163.1, 161.3, 149.5, 137.4, 135.7, 135.2, 133.8, 132.1, 132.0,
131.4, 122.0, 121.7, 114.0, 113.9, 113.7 (Ar–C═C, C═C),
90.6 (N–C–OH), 61.2 (OCH2CH3), 55.9, 55.7 (2 MeO), 41.7
(C–CH2COEt), 14.3 (OCH2CH3). Anal. Calcd fo C30H26BrNO9
(624 g/mol): C, 57.70; H, 4.20; N, 2.24. Found: C, 57.76; H,
4.21; N, 2.18.
5-Chloro-2-[2-(2-ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-
5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]benzoic
acid (3p). This compound was obtained as pale yellow crystals,
0.161 g (28%), mp 101 ꢀC, ir (KBr): 3413 (OH, acid), 3234 (OH,
alcohol), 1732, 1692, 1631, 1604 (C═O), 1575 cmÀ1 (C═C); H
1
NMR (300 MHz, CDCl3): d 7.75–6.53 (m, 11H, Ar–H), 4.19
(q, 3J = 7.1, 2H, OCH2), 3.76, 3.62 (2s, 6H, 2 MeO), 3.32 (A part
of AB system, d, 1H, J = 15.4, CH2COOEt), 2.92 (B part of
AB system, d, 1H, J = 15.4, CH2COOEt), 1.24 (t, 3J = 7.1,
3H, Me); 13C NMR (75 MHz, CDCl3): d 195.1, 189.6, 178.8,
169.1 (4 C═O), 132.9, 161.5, 143.8, 135.1, 134.8, 134.5,
132.2, 132.0, 131.7, 131.34, 131.3, 126.4, 120.9, 113.8, 113.1
(Ar–C═C, C═C), 91.1 (N–C–OH), 61.3 (OCH2CH3), 55.3, 55.1
(2 MeO), 40.8 (C–CH2COEt), 14.1 (OCH2CH3). Anal. Calcd
for C30H26ClNO9 (580 g/mol): C, 62.13; H, 4.52; N, 2.42.
Found: C, 62.40; H, 4.25; N, 2.60.
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-5-
methoxybenzoic acid (3m). This compound was obtained as pale
yellow crystals, 0.317 g (55%), mp 120 ꢀC, ir (KBr): 3433 (OH,
acid), 3256 (OH, alcohol), 1732, 1687, 1627, 1606 (C═O),
3-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-(4-
methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]propanoic acid
1
1577cmÀ1 (C═C); H NMR (300 MHz, DMSO-d6): d 7.79–6.72
(m, 11H, Ar–H), 4.08 (q, 3J = 7.1, 2H, OCH2), 3.84, 3.77,
3.68 (3s, 9H, 3 MeO), 2.95 (A part of AB system, d, 1H, J =15.4,
CH2COOEt), 2.61 (B part of AB system, d, 1H, J =15.4,
CH2COOEt), 1.15 (t, 3J = 7.1, 3H, Me); 13C NMR (75 MHz,
DMSO-d6): d 193.9, 188.5, 178.6, 168.6 (4 C═O), 163.0,
161.1, 158.8, 136.9, 133.0, 132.3, 132.1, 132.0, 129.2, 128.0,
122.4, 117.9, 115.9, 113.8, 113.6 (Ar–C═C, C═C), 90.4
(N–C–OH), 61.1 (OCH2CH3), 56.0, 55.9, 55.6 (3 MeO), 41.5
(C–CH2COEt), 14.4 (OCH2CH3). Anal. Calcd for C31H29NO10
(575 g/mol): C, 64.69; H, 5.08; N, 2.43. Found: C, 64.85; H,
5.16; N, 2.82.
(4a).
This compound was obtained as white crystals, 0.227 g
(46%), mp 152 ꢀC; ir (KBr): 3384 (OH, acid), 3178 (OH, alcohol),
1735, 1713, 1692, 1608 (C═O), 1571 cmÀ1 (C═C); 1H NMR
(300 MHz, DMSO-d6): d 12.36 (s, 1H, COOH), 7.66–6.90 (m, 8H,
Ar–H), 4.08 (q, 3J=7.1, 2H, OCH2), 3.81 (2s, 6H, 2 MeO),
3.69–3.47 (m, 2H, CH2N), 3.12 (A part of AB system, d, 1H,
J= 15.4, CH2COOEt), 2.93 (B part of AB system, d, 1H, J= 15.4,
3
CH2COOEt), 2.64–2.35 (m, 2H, CH2CO2H), 1.16 (t, J=7.1, 3H,
Me); 13C NMR (75 MHz, DMSO-d6): d 193.7, 187.3, 179.6, 172.4
(4 C═O), 162.8, 161.1, 132.2, 131.8, 129.6, 122.5, 114.5, 113.4,
110.6 (Ar–C═C, C═C), 89.0 (N–C–OH), 61.0 (OCH2CH3), 55.9,
55.7 (2 MeO), 34.5 (CH2COOH) 14.4 (OCH2CH3). Anal. Calcd
for C26H27NO9 (497 g/mol): C, 62.77; H, 5.47; N, 2.82. Found:
C, 62.61; H, 5.40; N, 3.00.
2-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]-4,5-
dimethoxybenzoic acid (3n). This compound was obtained as
pale yellow crystals, 0.162g (27%), mp 118 ꢀC, ir (KBr): 3437
(OH, acid), 3258 (OH, alcohol), 1730, 1691, 1636, 1604 (C═O),
1577cmÀ1 (C═C); 1H NMR (300 MHz, CDCl3): d 7.77–6.54 (m,
1-[2-Hydroxy-4-(4-methoxybenzoyl)-2-(2-methoxy-2-oxoethyl)-
5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]
cyclopropanecarboxylic acid (4b).
This compound was
3
10H, Ar–H), 4.19 (q, J = 7.1, 2H, OCH2), 4.00, 3.84, 3.77, 3.63
obtained as white crystals, 0.312 g (63%), mp 137 ꢀC; ir (KBr):
(4s, 12H, 4 MeO), 3.35 (A part of AB system, d, 1H, J = 15.4,
CH2COOEt), 2.97 (B part of AB system, d, 1H, J= 15.4,
CH2COOEt), 1.23 (t, 3J=7.1 3H, Me); 13C NMR (75MHz,
CDCl3): d 194.7, 189.4, 179.2, 169.7 (4 C═O), 162.9, 161.4,
152.2, 145.3, 132.0, 131.5, 130.9, 130.2, 128.6, 124.5, 121.3,
113.7, 113.5, 113.1, 112.7 (Ar–C═C, C═C), 91.1 (N–C–OH), 61.4
(OCH2CH3), 56.4, 56.1, 55.3, 55.1 (4 MeO), 41.3 (C–CH2COEt),
14.1 (OCH2CH3). Anal. Calcd for C32H31NO11 (605 g/mol):
C, 63.47; H, 5.16; N, 2.31. Found: C, 63.20; H, 4.90; N, 2.60.
5-Bromo-2-[2-(2-ethoxy-2-oxoethyl)-2-hydroxy-4-(4-
methoxybenzoyl)-5-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-
pyrrol-1-yl]benzoic acid (3o). This compound was obtained
as pale yellow crystals, 0.270 g (43%), mp 124 ꢀC, ir (KBr):
3414 (OH, acid), 3232 (OH, alcohol), 1731, 1692, 1631, 1603
3393, 3154 (OH, alcohol, and acid), 1738, 1698, 1631 cmÀ1
1
(C═O). H NMR (300 MHz, DMSO-d6): d 12.66 (b, 1H, OH),
7.80–6.91 (m, 8H, Ar–H), 3.82, 3.78 (2s, 6H, 2 MeO), 3.44 (b,
1H, OH), 3.08 (A part of AB system, d, 1H, J = 15.4,
CH2COOMe), 2.99 (B part of AB system, d, 1H, J = 15.4,
CH2COOMe), 1.39–0.84 (m, 2Â CH2, cyclopropane); 13C
NMR (75 MHz, DMSO-d6): d 194.4, 187.8, 181.0, 174.0
(4 C═O), 163.1, 162.9, 132.2, 132.0, 131.9, 130.1, 123.4,
113.7, 113.5, 111.7 (Ar–C═C, C═C), 89.6 (N–C–OH), 55.9,
55.6, 51.9 (3 MeO), 37.2 (CH2), 20.5 (CH2, cyclopropane).
Anal. Calcd for C26H25NO9 (495 g/mol): C, 63.03; H, 5.09; N,
2.83. Found: C, 63.19; H, 5.00; N, 2.86.
1-[2-(2-Ethoxy-2-oxoethyl)-2-hydroxy-4-(4-methoxybenzoyl)-5-
(4-methoxyphenyl)-3-oxo-2,3-dihydro-1H-pyrrol-1-yl]
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DOI 10.1002/jhet

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Pyrrol-3-ones, Pyrrolo[1,2-a][3,1]benzoxazines, and Pyrrolo[2,1-b][1,3]oxazoles
217
cyclopropanecarboxylic acid (4c).
This compound was
(m, 12H, Ar–H), 3.86, 3.83, 3.67 (3s, 9H, 3 MeO), 3.48 (A part
of AB system, d, 1H, J = 15.4, CH2COOMe), 3.14 (B part of
AB system, d, 1H, J = 15.4, CH2COOMe); 13C NMR (75 MHz,
CDCl3): d 189.4, 187.1, 176.5, 167.2 (4 C═O), 163.7, 161.7,
160.4, 136.1, 135.1, 132.1, 131.2, 130.8, 130.4, 130.0, 126.5,
122.6, 119.7, 116.0, 114.1, 113.5 (Ar–C═C, C═C), 88.5
(N–C–O), 55.5, 55.4, 52.3 (3 MeO), 38.3 (CH2). Anal. Calcd
for C29H23NO8 (513 g/mol): C, 67.83; H, 4.51; N, 2.73. Found:
C, 67.80; H, 4.50; N, 2.62.
obtained as white crystals, 0.295 g (58%), mp 105 ꢀC; ir (KBr):
3421 (OH, alcohol, and acid), 1733, 1698, 1633 cmÀ1 (C═O);
1H NMR (300 MHz, DMSO-d6): d 12.82 (b, 1H, OH), 7.80–6.91
(m, 8H, Ar–H), 4.21–3.99 (m, 2H, OCH2), 3.82, 3.78 (2s, 6H,
2 MeO), 3.38 (b, 1H, OH), 3.06 (A part of AB system, d,
1H, J = 15.4, CH2COOEt), 2.97 (B part of AB system, d,
1H, J = 15.4, CH2COOEt), 2.40–2.30, 0.99–0.85 (m, 4H,
2Â CH2, cyclopropane), 1.20 (t, 3J = 7.1, 3H, CH3); 13C
NMR (75 MHz, DMSO-d6): d 194.4, 187.8, 181.1, 174.0
(4 C═O), 162. 9, 160.6, 132.2, 132.0, 130.0, 123.5, 115.1,
113.7, 113.4, 111.6 (Ar–C═C, C═C), 89.6 (N–C–OH),
60.6 (OCH2), 55.9, 55.6 (2 MeO), 37.3 (CH2), 15.4 (Me),
14.4 (CH2, cyclopropane). Anal. Calcd for C27H27NO9
(509 g/mol): C, 63.65; H, 5.34; N, 2.75. Found: C, 63.56;
H, 5.39; N, 2.81.
Ethyl [2-(4-methoxybenzoyl)-1-(4-methoxyphenyl)-7,9-dimethyl-
3,5-dioxo-5H-pyrrolo[1,2-a][3,1]benzoxazin-3a(3H)-yl]
acetate (6l).
This compound was obtained as pale yellow
crystals, recrystallized from AcOEt, 0.263 g (47%), mp 95 ꢀC;
ir (KBr): 1741, 1711, 1645 cmÀ1 (C═O); H NMR (300 MHz,
1
CDCl3): d 7.96–6.78 (m, 10H, Ar–H), 4.14 (q, 3J = 7.1, 2H,
OCH2), 3.88, 3.81 (2s, 6H, 2 MeO), 3.50 (A part of AB
system, d, 1H, J = 15.4, CH2COOEt), 2.95 (B part of AB
system, d, 1H, J = 15.4, CH2COOEt), 2.42, 1.45 (2s, 6H, 2 Ar–
CH3), 1.26 (t, 3J = 7.1, 3H, Me); 13C NMR (75 MHz, CDCl3): d
189.8, 187.7, 176.7, 167.1 (4 C═O), 163.7, 161.9, 160.9,
138.5, 138.0, 134.1, 132.5, 132.2, 131.0, 130.3, 129.3,
120.8, 120.5, 114.1, 113.9, 113.5 (Ar–C═C, C═C), 89.1
(N–C–O), 61.5 (OCH2) 55.5, 55.4 (2 MeO), 37.2 (CH2),
21.0, 17.1 (2 Ar–CH3), 14.1 (Me). Anal. Calcd for
C32H29NO8 (555 g/mol): C, 69.18; H, 5.26; N, 2.52. Found:
C, 69.33; H, 5.21; N, 2.71.
Methyl [6′-(4-methoxybenzoyl)-5′-(4-methoxyphenyl)-2′,7′-
dioxospiro[cyclobutane-1,3′-pyrrolo[2,1-b][1,3]oxazol]-7a′(7′H)-
yl]acetate (5a). This compound was obtained as yellow crystals,
recrystallized from acetic acid, 0.285 g (58%), mp 91ꢀC; ir (KBr):
1797, 1744, 1690, 1637 cmÀ1 (C═O); 1H NMR (300 MHz,
CDCl3): d 7.82–6.85 (m, 8H, Ar–H), 3.86, 3.75 (3s, 9H, 3 MeO),
3.13 (A part of AB system, d, 1H, J = 15.4, CH2COOMe), 3.06
(B part of AB system, d, 1H, J = 15.4, CH2COOMe), 2.89–1.54
(m, 6H, 3Â CH2, cyclobutane); 13C NMR (75MHz, CDCl3):
d 191.5, 188.7, 179.2, 175.4 (4 C═O), 163.9, 163.3, 132.1,
130.7, 130.0, 123.3, 120.9, 114.7, 113.6 (Ar–C═C, C═C), 93.9
(N–C–O), 64.5 (N–C–COOH), 55.6, 55.5, 52.3 (3 MeO), 39.6
(CH2COOMe), 36.3, 30.3, 13.9 (CH2, cyclobutane). Anal. Calcd
for C27H25NO8 (491g/mol): C, 65.98; H, 5.13; N, 2.85. Found:
C, 65.76; H, 5.29; N, 2.91.
Acknowledgments. We wish to dedicate this article to Prof. Dr
Yunus Akçamur. The authors are grateful to The Medicinal Plants
and Medicine Research Centre of Anadolu University for the use
of the X-ray diffractometer. This study was financially supported
by The Scientific and Technological Research Council of Turkey
(TÜBİTAK), project no. TBAG 107T140.
Ethyl [6′-(4-methoxybenzoyl)-5′-(4-methoxyphenyl)-2′,7′-
dioxospiro[cyclobutane-1,3′-pyrrolo[2,1-b][1,3]oxazol]-7a′(7′H)-yl]
acetate (5b).
This compound was obtained as yellow crystals,
recrystallized from acetic acid, 0.320 g (63%), mp 180 ꢀC; ir (KBr):
1797, 1739, 1693, 1637cmÀ1 (C═O); 1H NMR (300 MHz,
CDCl3): d 7.84–6.86 (m, 8H, Ar–H), 4.19 (q, 3J = 7.1, 2H,
OCH2), 3.87 (2s, 6H, 2 MeO), 3.13 (A part of AB system, d, 1H,
J = 15.4, CH2COOEt), 3.03 (B part of AB system, d, 1H, J = 15.4,
CH2COOEt), 2.89–1.57 (m, 6H, 3Â CH2, cyclobutane), 1.28
(t, 3J = 7.1, 3H, Me); 13C NMR (75MHz, CDCl3): d 191.4, 188.7,
179.3, 175.4 (4C═O), 163.9, 163.3, 132.1, 130.7, 130.1, 123.3,
120.8, 114.7, 113.6 (Ar–C═C, C═C), 94.0 (N–C–O), 64.5
(N–C–COOH), 61.5 (OCH2), 55.5, 55.4 (2 MeO), 39.8(CH2),
36.3, 36.2 (2 CH2, cyclobutane), 14.1 (Me). Anal. Calcd for
C28H27NO8 (505g/mol): C, 66.53; H, 5.38; N, 2.77. Found: C,
66.22; H, 5.50; N, 2.52.
REFERENCES AND NOTES
[1] Clayden, J.; Read, B.; Hebditch, K. R. Tetrahedron, 2005, 61,
5713.
[2] Betler, B.; Mulle, C. Neuropharmacology 1995, 34, 123.
[3] Schoepp, D.; Smith, C.; Lodge, D.; Millar, J.; Leander, D.;
Sacaan, A.; Lunn, W. Eur J Pharmacol 1991, 203, 237.
[4] Dunnil, P. M.; Fowden, L. Phytochemistry, 1965, 4, 933.
[5] Basurto, J. C.; Raya, J. E.; May, M. G.; Fonseca, L. M. E.;
Alcantara, I. V.; Ferrara, J. T. J Enzym Inhib Med Ch 2006, 21, 133.
[6] Fan, H.; Peng, J.; Hamann, M. T.; Hu, J. F. Chem Rev
2008, 108, 264; Yasui, E.; Wada, M.; Takamura, N. Tetrahedron
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[7] Huang, J. W.; Tan, C. H.; Jiang, S. H.; Zhu, D. Y. Chinese
Chem Lett 2004, 15, 305.
[8] Saçmacı, M.; Üngören, Ş. H.; Akçamur, Y.; Arıcı, C.; Ülkü, D.
Heteroatom Chem 2005, 16, 235; Saçmacı, M., Üngören, Ş. H., Akçamur,
Y. Amino Acids 2006, 31, 397.
[9] Crystallographic data for the structural analysis of com-
pound 5a has been deposited at the Cambridge Crystallographic
Data Centre as deposition no. CCDC 799885. Copies of the data
can be obtained, free of charge, on applicant to the Cambridge
Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge,
CB2 1EZ UK (fax: +44(1223)336033); email:deposit@ccdc@cam.
ac.uk
General procedure for preparation of pyrrolo[1,2-a][3,1]
benzoxazin (6) and 2-methylene pyrrol-3-one (7). Corresponding
pyrrol-3-one derivatives (3a,l,n) (1 mmol) and excess of
equivalent amount of SOCl2 (about three to four drops) were
stirred at RT in 50 mL benzene for 15 min. Then, the solution
was refluxed for 45 min. The solvent was removed by
evaporation. The oily residue was subjected to column
chromatography on Silica gel 60 HF254. Elution with AcOEt/
hexane (5:1) afforded the product.
Methyl [2-(4-methoxybenzoyl)-1-(4-methoxyphenyl)-3,5-dioxo-
5H-pyrrolo[1,2-a][3,1]benzoxazin-3a(3H)-yl]acetate (6a). This
compound was obtained as pale yellow crystals, recrystallized
from AcOEt, 0.210 g (41%), mp 180 ꢀC; ir (KBr): 1734, 1705,
1645 cmÀ1 (C═O); 1H NMR (300 MHz, CDCl3): d 8.13–6.46
[10] Üngören, Ş. H.; Saçmacı, M.; Akçamur, Y.; Arıcı, C.; Ülkü, D.
J Heterocyclic Chem, 2004, 41, 141.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

218
İ. Koca, M. Saçmacı, F. Yılmaz, and Ş. H. Üngören
Vol 51
[11] APEX2 and SAINT; Bruker AXS Inc.: Madison, Wisconsin,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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