Cyclization of aroylacetic acids 2-carboxyphenylamides into 2-[(Z)-2-aryl-2-hydroxy-1-ethenyl]-4H-3,1-benzoxazin-4-ones. Crystal and molecular structure of 2-[(Z)-2-hydroxy-2-phenyl-1-ethenyl]-4H-3,1-benzoxazin-4- one

Article abstract of DOI:10.1134/S1070428007020121

2-Carboxyphenylamides of aroylacetic acids undergo cyclization when treated with dehydrating agents to give 2-[(Z)-2-aryl-2-hydroxy-1-ethenyl]-4H-3,1- benzoxazin-4-ones. Crystal and molecular structure of the latter phenyl derivative was studied by X-ray

Full text of DOI:10.1134/S1070428007020121

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 2, pp. 224−227. © Pleiades Publishing, Ltd. 2007.
Original Russian Text © E.S. Vostrov, A.A. Novikov, A.N. Maslivets, Z.G. Aliev, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43,
No. 2, pp. 232−235.
Cyclization of Aroylacetic Acids 2-Carboxyphenylamides
into 2-[(Z)-2-Aryl-2-hydroxy-1-ethenyl]-4H-3,1-benzoxazin-4-ones.
Crystal and Molecular Structure
of 2-[(Z)-2-Hydroxy-2-phenyl-1-ethenyl]-4H-3,1-benzoxazin-4-one
E. S. Vostrova, A. A. Novikova, A. N. Maslivetsa, and Z. G. Alievb
aPerm State University, Perm 614990 Russia
e-mail: koh2@psu.ru
bInstitute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka
ReceivedApril 5, 2006
Abstract—2-Carboxyphenylamides of aroylacetic acids undergo cyclization when treated with dehydrating agents
to give 2-[(Z)-2-aryl-2-hydroxy-1-ethenyl]-4H-3,1-benzoxazin-4-ones. Crystal and molecular structure of the latter
phenyl derivative was studied by X-ray crystallography.
DOI: 10.1134/S1070428007020121
Heterocyclic enaminoketones, namely, 3-acylmethyl-
ene-3,4-dihydro-2H-1,4-benzoxazin-2-ones [1], 3-acyl-
methylene-1,2,3,4-tetrahydroquinoxalin-2-ones [2],
3-acylmethylene-3,4-dihydro-2-phenylquinoxalines [3],
2-acylmethylene-3-aryl-1,2,3,4-tetrahydro-4-quinazolones
[4], and 3-acylmethylenepiperazin-2-ones [5], exist in
enaminoketone form as demonstrated by X-ray diffraction
studies. In all compounds investigated an intramolecular
hydrogen bond of H-chelate type was observed between
the NH group of the heterocycle and the carbonyl of
acylmethylene fragment; therewith the hydrogen involved
into the hydrogen bond was localized at the nitrogen of
the enaminoketone moiety.
We used the former procedure for preparation of aroyl-
acetic acids 2-carboxyphenylamides, initial compounds
for investigation of intramolecular cyclization.
Boiling at 137–138°C for 15–20 min of solutions in
m-xylene of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones Ia–
If in the presence of an equivalent amount of anthranilic
acid led to the formation of aroylacetic acids 2-carboxy-
phenylamides IIa–IIf. Spectral characteristics of anilides
IIa–IIf are reported in EXPERIMENTAL and are well
consistent with those of similar in structure aroylacetic
acids amides [6–8].
Anilides IIa–IIf taken in the ratio 1:1 with dehydrating
agents, e.g., at boiling in benzene with acetic anhydride
for 1.5–2 h (method a) or at boiling in dichloroethane
with dicyclohexylcarbodiimide for 25–30 min (method b)
yielded light-yellow crystalline compounds IIIa–IIIf. For
the obtained products of the intramolecular cyclization
of anilides IIa–IIf we failed to make unambiguous choice
among isomeric structures: based only on spectral data
2-aroylmethylene-1,2-dihydro-4H-3,1-benzoxazin-4-ones
(A, B), 3-aroyl-1,2,3,4-tetrahydroquinolin-2,4-diones IV,
or 4-aryl-1,6-dihydro-2H-benzo[C][1,5]oxazocine-2,6-
diones V, and also to establish the localization in the
compounds of the hydrogen involved into the intra-
molecular hydrogen bond. Therefore the application of
X-ray crystallography was necessary. The X-ray dif-
fraction analysis showed that compound IIIa was 2-[(Z)-
2-hydroxy-2-phenyl-1-ethenyl]-4H-3,1-benzoxazin-4-one.
In extension of studies on the synthesis of new classes
of heterocyclic enaminoketones and on investigating fine
features of their structure we performed intramolecular
cyclization of aroylacetic acids 2-carboxyanilides by
treating them with dehydrating agents. The arising
benzoxazinones are polyfunctional reagents and can serve
as starting compounds for the synthesis of representatives
of new classes of extensively studied nowadays dioxo-
heterocycles and heterocumulenes based thereon.
Two convenient methods were published for
preparation of aroylacetamides: aroylacylation of amines
[6] and amides [7] with aroylketenes generated by
thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones,
and reaction of ethyl benzoylacetate with arylamines [8].
224

CYCLIZATION OF AROYLACETIC ACIDS 2-CARBOXYPHENYLAMIDES
225
Scheme.
O
O
O
Ar
N
H
IV
O
O
COOH
O
N
O
COOH
NH2
Δ, _Me2CO
O
O
O
O
Me
Me
_H2O
Ar
NHCOCH2COAr
IIa_IIf
N
.
.
.
Ia_If
H
H
.
.
.
Ar
O
Ar
Ar
B
A
IIIa_IIIf
O
O
NH
O
V
Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 4-EtOC6H4 (d), 4-ClC6H4 (e), 4-BrC6H4 (f).
A single crystal of compound IIIa was specially grown
from benzene for the X-ray diffraction study. The general
view of IIIa molecule is presented on the figure.
obviously contrasts with the structure of the formerly
studied heterocyclic enaminoketones [1–5]; the reason
of this phenomenon requires a separate study. It should
also be noted that the established localization of the
hydrogen suggests new interpretation of the abnormal
results of reactions between some heterocyclic
enaminoketones with oxalyl chloride leading to the closure
of a furandione [9, 10] and not a pyrroledione ring.
The main bond lengths in the molecule are given below.
The analysis of these interatomic distances unambiguously
shows that the hydrogen atom is localized on the oxygen.
The molecule is virtually planar containing an
...
intramolecular hydrogen bond O–H N. The distance
°
...
N H3 equals 1.71 A, and the angle at the hydrogen is
EXPERIMENTAL
146°.
°
IR spectra were recorded on a spectrophotometer
UR-20 from mulls in mineral oil. 1H and 13C NMR spectra
were registered on a spectrometer Bruker AM-400 (400
MHz), internal reference TMS. Mass spectra were taken
Bond
O1–C1
d, A
1.368(3)
O1–C2
O2–C2
O3–C3
N–C1
1.393(3)
1.199(3)
1.311(3)
1.305(3)
1.411(4)
1.366(4)
1.486(4)
C1–C4
C3–C4
C3–C5
Thus the intramolecular cyclization of anilides II
effected by dehydrating agents resulted in formation of
benzoxazinones IV. At the same time the localization of
hydrogen in the enaminoketone fragment at the oxygen
atom of the hydroxyenimine fragment tautomeric to the
enaminoketone one is not only quite unexpected, but
Structure of 2-[(Z)-2-hydroxy-2-phenyl-1-ethenyl]-4H-3,1-
benzoxazin-4-one (IIIa).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

VOSTROV et al.
226
on MKh-1320, ionizing electrons energy 70eV. The homo-
geneity of compounds synthesized was confirmed by TLC
on Silufol plates, eluent benzene−ethyl acetate, 5:1,
development in iodine vapor.
NH), 13.58 br.s (1H, COOH). Found, %: C 60.50; H 3.80;
Cl 11.20; N 4.42. C16H12ClNO4. Calculated, %: C 60.48;
H 3.81; Cl 11.16; N 4.41.
4-Bromobenzoylacetic acid N-(2-carboxyphenyl)-
amide (IIf). Yield 1.38 g (78%), mp 190–191°C
(ethanol). IR spectrum, ν, cm–1: 3335 br (NH, COOH),
1698 (COOH), 1680 br (CONH, COC6H4), 1533
(“amide II”). 1H NMR spectrum (CDCl3), δ, ppm: 4.12 s
(2H, CH2), 7.13–8.76 group of signals (8H, 2C6H4),
11.38 s (1H, NH). Found, %: C 53.04; H 3.35; Br 22.10;
N 3.85. C16H12BrNO4. Calculated, %: C 53.06; H 3.34;
Br 22.06; N 3.87.
Benzoylacetic acid N-(2-carboxyphenyl)amide
(IIa). Asolution of 4.9 mmol of dioxinone Ia and 4.9 mmol
of anthranilic acid in 2 ml of m-xylene was boiled for 10–
15 min, cooled, the precipitate was filtered off. Yield
1.10 g (79%), mp 177–178°C (ethanol). IR spectrum, ν,
cm–1: 3160 br (NH, COOH), 1698 (COOH), 1685 br
(CONH, COPh), 1540 (“amide II”). 1H NMR spectrum
(DMSO-d6), δ, ppm: 4.31 s (2H, CH2), 7.18–8.44 group
of signals (9H, C6H4 + Ph), 11.26 s (1H, NH), 13.60 br.s
(1H, COOH). Found, %: C 67.76; H 4.60; N 5.00.
C16H13NO4. Calculated, %: C 67.84; H 4.63; N 4.94.
2-[(Z)-2-Hydroxy-2-phenyl-1-ethenyl]-4H-3,1-
benzoxazin-4-one (IIIa). a. A solution of 3.35 mmol of
anilide IIa and 3.35 mmol of acetic anhydride in 10 ml of
benzene was boiled for 2 h, evaporated, and the residue
was crystallized from 2-propanol. Yield 0.89 g(100%).
Compounds IIb–IIf were similarly obtained.
4-Toluoylacetic acid N-(2-carboxyphenyl)amide
(IIb). Yield 1.12 g (77%), mp 157–158°C (ethanol). IR
spectrum, ν, cm–1: 3150 br (NH, COOH), 1700 (COOH),
b. A solution of 3.35 mmol of anilide IIa and
3.35 mmol of dicyclohexylcarbodiimide in 20 ml of
1,2-dichloroethane was boiled for 39 min, cooled, the
precipitate of dicyclohexylurea was filtered off, the filtrate
was evaporated, and the residue was crystallized from
2-propanol. Yield 0.89 g (100%), mp 141–142°C
(2-propanol). IR spectrum, ν, cm–1: 3050 br (OHbound),
1
1675 br (CONH, COC6H4), 1535 (“amide II”). H NMR
spectrum (CDCl3), δ, ppm: 2.40 s (3H, Mε), 4.16 s (2H,
CH2), 7.11–8.69 group of signals (8H, 2C6H4), 11.38 s
(1H, NH). Found, %: C 68.70; H 5.08; N 4.73.
C17H15NO4. Calculated, %: C 68.68; H 5.09; N 4.71.
1
1762 (C4=O), 1634 (C=N). H NMR spectrum (CDCl3),
4-Methoxybenzoylacetic acid N-(2-carboxy-
phenyl)amide (IIc). Yield 1.07 g (70%), mp 175–176°C
(ethanol). IR spectrum, ν, cm–1: 3145 br (NH, COOH),
1703 (COOH), 1670 br (CONH, COC6H4), 1533
δ, ppm: 5.96 s (1H, CH), 7.37–8.15 group of signals
(9H, Ph + C6H4), 14.26 s (1H, OH). Found, %: C 72.39;
H 4.15; N 5.30. C16H11NO3. Calculated, %: C 72.45;
H 4.18; N 5.28.
1
(“amide II”). H NMR spectrum (DMSO-d6), δ, ppm:
3.86 s (3H, MeO), 4.22 s (2H, CH2), 7.05–8.44 group of
signals (8H, 2C6H4), 11.26 C (1H, NH), 13.58 br.s (1H,
COOH). Found, %: C 65.25; H 4.80; N 4.45. C17H15NO5.
Calculated, %: C 65.17; H 4.83; N 4.47.
X-ray crystallography. Crystals of compound IIIa,
C16H11NO3, monoclinic, a 14.182(3), b 9.443(2), c 9.404
°
(2) A°
,
β 97.86(3)°, V 1247.6(5) A , M 265.26, dcalc
3
1.412 g/cm3, Z 4, space group P21/n. The set of experi-
mental reflections was obtained on an automatic four-
circle diffractometer QM-4 (KUMA DIFFRACTION)
with κ-geometry by ω/2Θ scanning on MoKα-radiation
with a monochromator (2Θ ≤ 50.1°). Overall 2349 reflec-
tions were measured, 2206 among them independent
(Rint 0.0495). The correction for extinction was not done
(μ 0.10 mm–1). The structure was solved by the direct
method by the program SIR92 [11] followed by calculation
of a series of electron density charts. Hydrogen atoms
were revealed from the difference synthesis of the
electron density. Full-matrix refining in anisotropic
approximation for nonhydrogen atoms was performed by
the least-mean-squares method using SHELXL-97 soft-
ware[12] and was completed at R1 0.0393, wR2 0.1070
using 1027 reflections with I ≥ 2σ(I) and R1 0.1340, wR2
0.1744 using all 2206 reflections.
4-Ethoxybenzoylacetic acid N-(2-carboxy-
phenyl)amide (IId). Yield 1.11 g (69%), mp 192–193°C
(ethanol). IR spectrum, ν, cm–1: 3145 br (NH, COOH),
1680 (COOH), 1660 br (CONH, COC6H4), 1533
(“amide II”). 1H NMR spectrum (CDCl3), δ, ppm: 1.44 t
(3H, MeCH2O, J 7.0 Hz), 4.10 q (2H, MeCH2O, J 7.0 Hz),
4.10 s (2H, CH2), 6.91–8.71 group of signals (8H, 2C6H4),
11.41 s (1H, NH). Found, %: C 66.04; H 5.24; N 4.30.
C18H17NO5. Calculated, %: C 66.05; H 5.23; N 4.28.
4-Chlorobenzoylacetic acid N-(2-carboxyphenyl)-
amide (IIe). Yield 1.18 g (76%), mp 170–171°C
(ethanol). IR spectrum, ν, cm–1: 3225 br (NH, COOH),
1718 (COOH), 1685 br (CONH, COC6H4), 1536
1
(«amide II»). H (DMSO-d6), δ, ppm: 4.31 s (2H, CH2),
7.18–8.40 group of signals (8H, 2C6H4), 11.23 s (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

CYCLIZATION OF AROYLACETIC ACIDS 2-CARBOXYPHENYLAMIDES
227
group of signals (8H, 2C6H4), 14.24 s (1H, OH). Found,
%: C 64.10; H 3.37; Cl 11.85; N 4.65. C16H10ClNO3.
Calculated, %: C 64.12; H 3.36; Cl 11.83; N 4.67.
Analogously were prepared compounds IIIb–IIIf.
2-[(Z)-2-Hydroxy-2-(4-methylphenyl)-1-ethenyl]-
4H-3,1-benzoxazin-4-one (IIIb). Yield 98 (a), 100%
(α), mp 178–179°C (2-propanol). IR spectrum, ν, cm–1:
3080 br (OHbound), 1770 (C4=O), 1640 (C=N). 1H NMR
spectrum (CDCl3), δ, ppm: 2.42 s (3H, Me), 5.93 s (1H,
CH), 7.26–8.14 group of signals (8H, 2C6H4), 14.25 s
(1H, OH). Found, %: C 73.10; H 4.67; N 5.03.
C17H13NO3. Calculated, %: C 73.11; H 4.69; N 5.01.
2-[(Z)-2-Hydroxy-2-(4-bromophenyl)-1-ethenyl]-
4H-3,1-benzoxazin-4-one (IIIf). Yield 95 (a), 100%
(b), mp 204–205°C (2-propanol). IR spectrum, ν, cm–1:
1
3340 br (OHbound), 1760 (C4=O), 1625 (C=N). H NMR
spectrum (CDCl3), δ, ppm: 5.91 s (1H, CH), 7.35–8.14
group of signals (8H, 2C6H4), 14.23 s (1H, OH). Found,
%: C 55.83; H 2.95; Br 23.25; N 4.05. C16H10BrNO3.
Calculated, %: C 55.84; H 2.93; Br 23.22; N 4.07.
2-[(Z)-2-Hydroxy-2-(4-methoxyphenyl)-1-
ethenyl]-4H-3,1-benzoxazin-4-one (IIIc). Yield 100%
(a, b), mp 164–165°C (2-propanol). IR spectrum, ν,
cm–1: 3040 br (OHbound), 1750 (C4=O), 1615 (C=N).
1H NMR spectrum (CDCl3), δ, ppm: 3.88 s (3H, MeO),
5.88 s (1H, CH), 6.96–8.13 group of signals (8H, 2C6H4),
14.27 s (1H, OH). 13C NMR spectrum (100 MHz,
CDCl3), δ, ppm: 55.48 (MeO), 83.93 (C2=CH), 114.10
(C4a), 121.25–129.35 (ArH), 137.00 (C8a), 162.12 (C4),
162.56 (C2), 177.30 (COC6H4). Mass spectrum, m/z (Irel,
%): 265 (32) [M]+, 188 (6) [M – C6H5]+, 146 (3) [M –
C6H5COCH2]+, 119 (19) [C6H5COCH2]+, 105 (100)
[C6H5CO]+, 77 (29) [C6H5]+. Found, %: C 69.17; H 4.48;
N 4.75. C17H13NO4. Calculated, %: C 69.15; H 4.44;
N 4.74.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grants
nos. 04-03-33024, 04-03-96033).
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CH), 6.94–8.12 group of signals (8H, 2C6H4), 14.27 s
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2-[(Z)-2-Hydroxy-2-(4-chlorophenyl)-1-ethenyl]-
4H-3,1-benzoxazin-4-one (IIIe). Yield 96 (a), 100%
(b), mp 205–206°C (2-propanol). IR spectrum, ν, cm–1:
3170 br (OHbound), 1757 (C4=O), 1628 (C=N). 1H NMR
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007