Reactivity of unsaturated 5(4H)-oxazolones with Hg(II) acetate: Synthesis of methyl N-benzoylamino-3-arylacrylates

Article abstract of DOI:10.1080/00397911.2010.523157

An efficient and high-yield procedure to prepare methyl N-benzoylamino-3-arylacrylates from unsaturated (Z)-2-aryl-4-arylidene-5-(4H)- oxazolones and Hg(OAc)₂ in methanol is described herein. The observed reactivity of mercury(II) acetate here

Full text of DOI:10.1080/00397911.2010.523157

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Reactivity of Unsaturated 5(4H)-
Oxazolones with Hg(II) Acetate:
Synthesis of Methyl N-Benzoylamino-3-
arylacrylates
Gheorghe-Doru Roiban a b , Tatiana Soler c , Maria Contel d , Ion
Grosu a , Carlos Cativiela b & Esteban P. Urriolabeitia e
a Organic Chemistry Department , Faculty of Chemistry and
Chemical Engineering, Babeş Bolyai University , Cluj Napoca ,
Romania
b Departamento de Química Orgánica , Instituto de Ciencia de
Materiales de Aragón, CSIC-Universidad de Zaragoza , Zaragoza ,
Spain
c Servicios Centrales de Investigación , Facultad Ciencias , Alicante ,
Spain
d Chemistry Department, Brooklyn College and the Graduate
Center , City University of New York , New York , USA
e Departamento de Compuestos Organometálicos , Instituto de
Ciencia de Materiales de Aragón, CSIC-Universidad de Zaragoza ,
Zaragoza , Spain
Accepted author version posted online: 26 Jul 2011.Published
online: 14 Sep 2011.
To cite this article: Gheorghe-Doru Roiban , Tatiana Soler , Maria Contel , Ion Grosu , Carlos
Cativiela & Esteban P. Urriolabeitia (2012) Reactivity of Unsaturated 5(4H)-Oxazolones with Hg(II)
Acetate: Synthesis of Methyl N-Benzoylamino-3-arylacrylates, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:2, 195-203, DOI:
10.1080/00397911.2010.523157
To link to this article: http://dx.doi.org/10.1080/00397911.2010.523157
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Synthetic Communications1, 42: 195–203, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.523157
REACTIVITY OF UNSATURATED 5(4H)-OXAZOLONES
WITH Hg(II) ACETATE: SYNTHESIS OF METHYL
N-BENZOYLAMINO-3-ARYLACRYLATES
Gheorghe-Doru Roiban,1,2 Tatiana Soler,3 Maria Contel,4
Ion Grosu,1 Carlos Cativiela,2 and Esteban P. Urriolabeitia5
1Organic Chemistry Department, Faculty of Chemistry and Chemical
Engineering, Babes¸ Bolyai University, Cluj Napoca, Romania
2
´
Departamento de Quımica Organica, Instituto de Ciencia de Materiales de
Aragon, CSIC-Universidad de Zaragoza, Zaragoza, Spain
´
´
3
´
Servicios Centrales de Investigacion, Facultad Ciencias, Alicante, Spain
4Chemistry Department, Brooklyn College and the Graduate Center,
City University of New York, New York, USA
5
´
Departamento de Compuestos Organometalicos, Instituto de Ciencia de
Materiales de Aragon, CSIC-Universidad de Zaragoza, Zaragoza, Spain
´
GRAPHICAL ABSTRACT
Abstract An efficient and high-yield procedure to prepare methyl N-benzoylamino-3-
arylacrylates from unsaturated (Z)-2-aryl-4-arylidene-5-(4H)-oxazolones and Hg(OAc)2
in methanol is described herein. The observed reactivity of mercury(II) acetate here is dif-
ferent than its usual metallating behavior and it cleaves the unsaturated oxazolone ring
without change of stereochemistry.
Keywords Alcoholysis; azalactone ring opening; mercury(II) acetate; 5-(4H)-oxazolones
INTRODUCTION
The most important reaction in the chemistry of oxazolones is the nucleophilic
opening of the heterocyclic ring,[1] hydrolysis, and alcoholysis of 5(4H)-oxazolones,
which gives the respective N-acylamino acids and esters, which are used to prepare
a variety of new synthetic amino acids.[2] The use of N-acylamino alkyl esters as
the starting a-dehydroamino acid derivatives also enables the selective formation
Received August 15, 2010.
Address correspondence to Gheorghe-Doru Roiban, Organic Chemistry Department, Faculty of
Chemistry and Chemical Engineering, Babes¸ Bolyai University, Arany Janos 11, 400028, Cluj Napoca,
Romania. E-mail: gdroiban@chem.ubbcluj.ro
195

196
G.-D. ROIBAN ET AL.
of the corresponding isoquinolines.[3] Some esters can be used as plant growth
regulators,[4] while other acrylic acid derivatives have herbicidal activity[5] or are use-
ful intermediates for the synthesis of anti-inflammatory agents.[6] The methods used
to synthesize methyl N-benzoylamino-3-arylacrylates include alcoholysis of 5(4H)-
oxazolones in the presence of MeONa,[7] KOH,[8] triethylamine (TEA),[3,9] NEt3,[10]
P(OEt)3,[11] and cyclooligosaccharides.[12] In some cases, sonication has been also
used to promote the nucleophilic ring opening.[13] Recently, we have shown that
unsaturated 5(4H)-oxazolones can be ortho-paladated to give dimers, which evolve
after photocycloaddition to unprecedent oxazolones.[14] Palladated oxazolones can
be also regioselectively functionalized, which leads to a series of clean products that
are easy to isolate.[15] Still, certain unsaturated oxazolone substrates resisted the
action of different palladation agents, while for others, harsher conditions[14] were
needed. To extend oxazolone C-H bond activation and functionalization, we focused
on finding milder synthetic routes involving a metal activator such as mercuriation.
Many aromatic substrates that refuse to react with Pd(OAc)2 were derivatized using
an organomercury route followed by transmetallation.[16] Mercury’s unique abilities
to mediate organic transformations and to transfer organic ligands to different
transition-metal centers provide a convenient entry to different substrates that are
difficult to prepare using classic synthetic methods.[17] In particular, Hg(OAc)2 is
known to attack easily aromatic compounds[17] and gives many interesting complexes
by direct mercuriation.[18] However, the increased Lewis acid character of Hg com-
pared to Pd sometimes may induce a different reactivity behavior of metal, as noticed
in metallation of 1,5-bis(dimethylamino)naphthalene, when Hg(OAc)2 and Pd(OAc)2
gave different metallated products.[19] Another example is 3,4,5-trimethoxybenzalde-
hyde, which does not react with Pd(OAc)2 but is easily mercuriated in the presence of
mercury(II) acetate.[20] To our knowledge, the treatment of unsaturated oxazolones
with mercuric derivatives has not been investigated until now, and therefore we
report here the reactivity of 5(4H)-oxazolones toward mercury(II) acetate.
RESULTS AND DISCUSSION
With this aim, we prepared (Z)-2-phenyl-4-arylidene-5(4H)-oxazolones 1a–e
according to known literature procedures (Scheme 1).[9] Two geometric isomers
Scheme 1. Synthesis of methyl N-benzoylamino-3-arylacrylates.

UNSATURATED 5(4H)-OXAZOLONES
197
are possible for 1a–e, but the Erlenmeyer synthesis proceeds stereoselectively, favor-
ing the thermodynamically more stable (Z) isomer.[21] Arguments are based on
NMR studies,[22] chromatographic behavior,[23] and previous x-ray determinations
of molecular structures of related oxazolones.[24] With azlactones 1a–e in hand,
the next step was the study of their reactivity toward Hg(OAc)2 in methanol, because
it was known that different C, N-complexes have been prepared in these con-
ditions.[18] Therefore, substrate 1a[25] was refluxed in methanol in the presence of
equimolar quantities of Hg(OAc)2. However, after workup, only 2-benzoylamino-3-
phenylmethylacrylate 2a[26] was isolated in 98% yield (Scheme 1). The presence of the
expected metallated product could not be detected.
The same reaction occurred when oxazolones 1b[27] and 1c[28] were treated with
Hg(OAc)2, because ester derivatives 2b and 2c[29] (Table 1) were obtained in good
yields. (Z)-2-Phenyl-4-(4-methoxybenzylidene)-5(4H)-oxazolone 1d[30] afforded, after
treatment with Hg(OAc)2, 2-benzoylamino-3-(4-methoxyphenyl)methyl acrylate
2d.[31] It is evident that in these processes the Hg(OAc)2 did not behave as a metalla-
tion agent, but hydrolyzed the oxazolone ring, affording methyl N-benzoylamino-3-
arylacrylates 2a–d. Curiously, the electron-activated substrate 1e[32] could not be
hydrolyzed in these conditions even if the reaction time was increased to 24 h. In
addition, it is widely accepted that the mercuriation occurs mainly through an elec-
trophilic substitution SEAr pathway,[33] but no metallating product was detected
after workup when activated substrate 1e was employed.
It should be noted that compound 1a remained practically unchanged when
refluxed in methanol alone for 20 hs, as noted also by Shabana et al.[11] Under the
same reaction conditions, Pd(OAc)2 leaves the oxazolone ring intact, as we observed
in our initial attempts to get cyclopalladated derivatives.[15] To see if the reaction can
be catalytically driven, 1d was refluxed in MeOH using 3 mol% of Hg(OAc)2. How-
ever, the observed conversion of 1d into 2d was only 12% after more than 36 h.
In the 1H NMR spectrum of 2d, the shielding of the aromatic protons shows that
the delocalization of the electron density occurs to a lesser extent in comparison with
starting oxazolone. The presence of a broad peak around 7.70ppm, in 2d, assigned to
the acidic proton from the NH group is in keeping with the oxazolone cleavage. In the
aliphatic area of the spectrum, the existence of the methyl ester group is confirmed by
a sharp peak at d 3.79ppm. Methyl N-benzoylamino-3-arylacrylates 2a–d have been
also characterized using infrared (IR) spectroscopy. Absorptions assigned to the
stretch of the C¼O group were detected at about 1700cmꢀ1, and shifted to lower
energy in all studied cases with respect to the two-component band appearing in the
1740–1780 cmꢀ1 region in starting oxazolones.[14] Bands due to NH vibrations appear
Table 1. Alcoholysis of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones 1a–d
Oxazolone
X
Product
Yield (%)
1a
1b
1c
1d
1e
H
2-Br
2a
2b
2c
2d
—
98
96
97
94
—
4-Cl
4-OMe
3,4-OMe

198
G.-D. ROIBAN ET AL.
Figure 1. ORTEP plot of 2c with thermal ellipsoids drawn at the 50% probability level.
around 3300cmꢀ1 in products 2a–d while the C¼N stretching vibration appears at
1652cmꢀ1. Mass spectra performed on compounds 2a–d are strongly in the favor of
the drawn structures. When compound 2b is analyzed under mass spectrometry–
electrospray ionization (MS-ES) conditions, the protonated molecule is detected at
m=z 359.9 and 361.8, while the cationic [MNa]þ species appear at m=z 381.8 and 383.8.
The structure of 2-benzylamino-3-(4-chlorophenyl)methyl acrylate (2c) was
also confirmed by the determination of its molecular structure by x-ray diffraction
methods. From the structure of 2c, the cleavage of the heterocyclic ring and the
incorporation of a methanol molecule (Fig. 1) is obvious. In comparison with start-
ing oxazolones 1a–d, which are planar,[24] the molecule planarity is destroyed by the
ring opening. The crystal structure of 2c displays a Z configuration about the C8C9
double bond. This is the same configuration as that found in the oxazolone 1c, mean-
ing that the reaction occurs with stereochemical retention of the configuration.
The molecular conformation is stabilized by an intramolecular and several
intermolecular hydrogen bonds (Table 2). The intramolecular H-bonds are formed
o
)
˚
Table 2. Hydrogen-bonding geometry (A,
D-H ꢁ ꢁ ꢁ A
D-H
H ꢁ ꢁ ꢁ A
D ꢁ ꢁ ꢁ A
D-H ꢁ ꢁ ꢁ A
C13-H13A ꢁ ꢁ ꢁ N1
C6-H6A ꢁ ꢁ ꢁ Cl1a
C14-H14A ꢁ ꢁ ꢁ Cl1b
N1-H1A ꢁ ꢁ ꢁ O1b
C17-H17A ꢁ ꢁ ꢁ O3c
C9-H9A ꢁ ꢁ ꢁ O3c
C11-H11A ꢁ ꢁ ꢁ O2c
0.9296(16)
0.9302(29)
0.9304(14)
0.8603(14)
0.9303(14)
0.9301(14)
0.9604(21)
2.5266(14)
3.1497(5)
3.0643(5)
1.9868(10)
2.539(1)
3.0942(22)
3.9372(24)
3.5805(18)
2.8278(18)
3.3020(17)
3.4668(19)
3.4707(23)
119.686(103)
143.592(155)
116.725(97)
165.459(102)
139.482(99)
149.623(103)
147.902(124)
2.6324(11)
2.6193(13)
a1 ꢀ x, 2 ꢀ y, 1 ꢀ z.
b1 þ x, 1 þ y, z.
c2 þ x, 1 þ y, z.

UNSATURATED 5(4H)-OXAZOLONES
199
between the proton on the aromatic bond C13H13 and the N1 atom [H13A ꢁ ꢁ ꢁ N1
˚
2.5266 (14) A] and have parameters similar to those found in isobutyl
N-benzoylamino-3-(4-chlorophenyl)
acrylate[34]
and
N-benzoylamino-3-(4-
chlorophenyl) acrylic acid.[35] In the structure, Cl atom forms weak C-H ꢁ ꢁ ꢁ Cl
˚
hydrogen bonds [C6-H6A ꢁ ꢁ ꢁ Cl1 3.1497(5) A respectively C14-H14A ꢁ ꢁ ꢁ Cl1
[36]
˚
3.0643(5) A] that are shorter than the sum of the Van der Waals radii of carbon
˚
and chlorine (3.60 A).
A closer check of the crystal structure revealed further
˚
N-H ꢁ ꢁ ꢁ O intermolecular interactions [N1-H1A ꢁ ꢁ ꢁ O1 1.9868(10) A], with the
N1-H1A ꢁ ꢁ ꢁ O1 angle tending to be close to linear [165.459(102)]. In addition to this,
˚
the C-H ꢁ ꢁ ꢁ O interactions [C17-H17A ꢁ ꢁ ꢁ O3 2.539(1) A, C11-H11A ꢁ ꢁ ꢁ O22.6193(13)
˚
˚
A, and C9-H9A ꢁ ꢁ ꢁ O3 2.6324(11) A] are also stabilizing the structure.
In conclusion, we observed that reaction of unsaturated 5(4H)-oxazolones with
Hg(OAc)2 in methanol did not lead to any metallated product. Instead mercury(II)
acetate showed low Lewis acid behavior when reacted with unsaturated oxazolones.
In the given reaction conditions, the oxazolone ring was cleaved and methyl
N-benzoylamino-3-arylacrylates were obtained in good yields. The reaction did
not occur in catalytic amounts of mercury(II) acetate while electron-activated
substrates could not be hydrolyzed.
EXPERIMENTAL
Chemicals of commercial grade were used without further purification. 1H and
1
13Cf Hg NMR spectra were recorded in CDCl3, at room temperature, on a Bruker
Avance 400 spectrometer (d in ppm, J in Hz) at 1H operating frequency of
1
400.13 MHz. H and 13C NMR spectra were referenced using the solvent signal as
internal standard. MS-ES mass spectra were recorded using an Esquire 3000
ion-trap mass spectrometer (Bruker Daltonic GmbH) equipped with a standard
ESI=APCI source. Infrared spectra (4000–380 cmꢀ1
) were recorded on a
Perkin-Elmer Spectrum One IR spectrophotometer, using nujol mulls between poly-
ethylene sheets. Data collection was performed at room temperature on an Oxford
Diffraction Xcalibur2 diffractometer using graphite-monocromated Mo-Ka radi-
˚
ation (k ¼ 0.71073 A). A hemisphere of data was collected based on three x-scan
or u-scan runs. The diffraction frames were integrated using the program CrysAlis
RED,[37] and the integrated intensities were corrected for absorption with
SADABS.[38]
Structure Solution and Refinement
The structure was solved and developed by Patterson and Fourier methods.[39]
All nonhydrogen atoms were refined with anisotropic displacement parameters. The
hydrogen atoms were placed at idealized positions and treated as riding atoms.
Each hydrogen atom was assigned an isotropic displacement parameter equal to
1.2 times the equivalent isotropic displacement parameter of its parent atom. The
structure was refined to F2o, and all reflections were used in the least-squares
calculations.[40] Elemental analyses were carried out on a Perkin-Elmer 2400-B
microanalyzer.

200
G.-D. ROIBAN ET AL.
Synthesis of the Starting Compounds
Unsaturated 5-(4H)-oxazolones 1a,[25] 1b,[27] 1c,[28] 1d,[30] and 1e[32] were
previously prepared and characterized. Also, alcoholysis products 2a,[26] 2c,[29] and
2d[31] have been spectroscopically characterized elsewhere.
General Procedure for Preparation of Methyl N-Benzoylamino-3-
Arylacrylates
(Z)-2-Arylidene-4-phenyl-5(4H)-oxazolone (1.0 equiv) and mercury(II) acetate
(1.0 equiv) were added in MeOH (10–30 mL). The mixture was heated for 3 to 4 h at
70 ꢂC until the monitoring of the reaction using thin-layer chromatography (TLC)
showed completion and then was allowed to cool at room temperature. The solvent
was evaporated, and the residue was purified on a chromatographic column (ethyl
acetate) to give 2a–d.
Synthesis of Methyl N-Benzoylamino-3-(2-bromophenyl)acrylate
(Z)-2-(2-Bromobenzylidene)-4-phenyl-5(4H)-oxazolone 1b (1.27 g, 3.89 mmol)
and mercury(II) acetate (1.24 g, 3.89 mmol) were added in MeOH (30 mL). The mix-
ture was heated for 3 h at 70 ꢂC and, after reaction completion as shown by TLC,
allowed to cool at room temperature. The solvent was evaporated to dryness, and
then the solid was washed three times with cold diethyl ether. The united ether
1
phases were evaporated to give 2b as a white solid (yield 1.34 g, 96%). H NMR
(400 MHz, CDCl3) d ppm: 3.85 (s, 3H, COOCH3), 7.12 (td, 3J ¼ 7.7 Hz, 4J ¼ 1.7 Hz,
3
3
00
00
0
0
1H, H4 ), 7.18 (t, J ¼ 6.8 Hz, 1H, H5 ), 7.39 (t, J ¼ 7.6 Hz, 2H, H3 , H5 ), 7.47
3
4
0
00
00
(m, 2H, H4 , H6 ), 7.52 (s, 1H, H7 ), 7.57–7.62 (dd, J ¼ 8.0 Hz, J ¼ 1.2 Hz, 1H,
H3 ), 7.77 (d, J ¼ 7.4 Hz, 2H, H2 , H6 ), 7.97 (broad s, 1H, NH). 13C NMR
3
00
0
0
(101 MHz, CDCl3) d ppm: 52.84 (1C, COOCH3), 124.34, 126.06, 133.21, 134.54
00
(4C, C1 , C2 , C1 , C2), 127.14 (1C, C5 ), 127.33 (2C, C2 , C6 ), 128.56 (2C, C3 ,
00
0
00
0
0
0
0
0
00
00
C5 ), 129.34, 129.37 (2C, C4 , C7 ), 130.09 (1C, C4 ), 132.07 (1C, C6 ), 132.83 (1C,
00
þ
00
C3 ), 165.38, 165.43 (2C, CO, COOCH3). MS-ES m=z: 359.9, 361.8 [MH] , 381.8,
383.8 [MNa]þ. Anal. calc. for C17H14BrNO3: C, 56.69; H, 3.92; N, 3.89. Found:
C, 56.84; H, 3.76; N, 3.56.
ACKNOWLEDGMENTS
Funding from CNCSIS TD87=2007 (Romania), the Ministerio de Ciencia e
Innovacion (Projects CTQ2008-01784 and CTQ2007-62245, Spain), and Gobierno
de Aragon (PI071-09) is gratefully acknowledged. D. R. also thanks the World
Federation of Scientists (WFS) for financial support.
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