Esterification-nitration of ortho-hydroxyphenyl carboxylic acids and benzole acids with cerium(IV) ammonium nitrate (CAN)

Article abstract of DOI:10.1002/jccs.200500027

A convenient and useful esterification was realized, and this reaction proceeded without a dehydrating reagent or water removal equipment. A series of ortho -hydroxyphenyl carboxylic acids and benzoic acids were transformed to their corresponding methyl esters under CAN/CH₃OH reaction conditions. Whereas in an aprotic solvent, acetonitrile, sp³-C tethered ortho-hydroxyphenyl carboxylic acids undergo simultaneous o,p-dinitration and intramolecular esterification reactions in good yields. Also, 2-((1E)-2-nitrovinyl)-4-nitro-phenol (3e) showed selective cytotoxicities to ward MCF-7, HEP G2, and HEP 3B cell lines with IQovalues of 23.50, 7.33, and7.59ug/mL,respectively.

Full text of DOI:10.1002/jccs.200500027

Journal of the Chinese Chemical Society, 2005, 52, 173-180
173
Esterification-nitration of Ortho-hydroxyphenyl Carboxylic Acids and
Benzoic Acids with Cerium(IV) Ammonium Nitrate (CAN)
Wen-Bin Pana (
Chin-Chung Wub (
aFooyin University, Kaohsiung County 831, Taiwan, R.O.C.
), Li-Mei Weia (
), Li-Lan Weia (
),
) and Yang-Chang Wub* (
)
bGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
A convenient and useful esterification was realized, and this reaction proceeded without a dehydrating re-
agent or water removal equipment. A series of ortho-hydroxyphenyl carboxylic acids and benzoic acids were
transformed to their corresponding methyl esters under CAN/CH3OH reaction conditions. Whereas in an
aprotic solvent, acetonitrile, sp3-C tethered ortho-hydroxyphenyl carboxylic acids undergo simultaneous
o,p-dinitration and intramolecular esterification reactions in good yields. Also, 2-((1E)-2-nitrovinyl)-4-nitro-
phenol (3e) showed selective cytotoxicities toward MCF-7, HEP G2, and HEP 3B cell lines with IC50 values
of 23.50, 7.33, and 7.59 ug/mL, respectively.
Keywords: Esterification; Nitration; Carboxylic acids; Cerium(IV) ammonium nitrate.
INTRODUCTION
CAN is an unusually strong, one electron oxidant and
esterification methods of much less reactive benzoic acids.
Recently, our laboratory reported an effective and facile
method for intermolecular esterification of cis-oleic acid and
various phenylacetic acids with simple alcohols to esters us-
ing CAN.10 In the literature, the intermolecular esterification
of 2-hydroxy-5-nitrophenylacetic acid in the presence of
thionyl chloride under refluxing conditions provides an effi-
cient route to various 2-hydroxy-5-nitrophenylacetates.11
2-Hydroxyphenyl carboxylic acids have been converted to
cyclic products, 3H-benzofuran-2-one,12 chroman-2-one,13
and chromen-2-one.14 Nevertheless, there is no report dealing
with their simultaneous nitration and esterification reactions
mediated by CAN. As a reasonable extension of our work and
in view of the versatility of CAN mediated organic synthesis,
we deemed it of interest to investigate the direct nitration,
intramolecular or intermolecular esterification of 2-hydro-
xyphenyl carboxylic acids, along with the esterification of
much less reactive benzoic acids in the presence of CAN.
Herewith we wish to report for the first time a mild reaction
of 2-hydroxyphenyl carboxylic acids and benzoic acids under
CAN/CH3OH reaction conditions, and a direct synthesis of
5,7-dinitro-3-hydrobenzo[b]furan-2-one (1d) and 6,8-dini-
trochroman-2-one (2d) via the aromatic di-nitration and
chemoselective cyclization of sp3-C tethered 2-hydroxy-
phenyl carboxylic acids under a further CAN/CH3CN reac-
tion condition. We also wish to report the cytotoxicities of
has also been widely used in carbon-carbon as well as car-
bon-hetero atom bond-forming reactions via radicals.1 The
nitration of aromatic compounds can be achieved with many
nitrating reagents and is a very useful method in organic syn-
thesis.2 Aromatic nitro compounds display particularly ver-
satile chemical feedstock for a wide range of industrial prod-
ucts, such as pharmaceuticals, agrochemicals, dyestuffs, and
explosives. Traditionally, nitration has been performed by a
mixture of nitric and sulfuric acids. However, the method is
notoriously unselective for nitration of substituted aromatic
compounds and the disposal of the spent acid reagents pres-
ents a serious environmental issue.3 Nitration of phenols as a
special case has been studied using various nitrating agents
under different conditions.4 CAN coated on silica (CAN/SiO2)
has been employed on the nitration of polynuclear aromat-
ics,5 heterocycles6,7 or polymethoxyphenyl derivatives.8 Un-
fortunately 1,4-dimethoxybenzenes, which possess an addi-
tional group such as carboxylic acid and nitro groups, are not
nitrated even when the reaction time was increased to 48
hours.8 Esterification of carboxylic acids with alcohols has
wide utility in organic and bioorganic synthesis.9 Although
many effective and reliable reactions for the preparation of
esters have been reported; there is still a need for simple
* Corresponding author. Tel: +886-7-312-1101 ext. 2197; Fax: +886-7-311-4773; E-mail: yachwu@kmu.edu.tw

174 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Pan et al.
Table 1. Esterification-nitration reaction of carboxylic acids with CAN
Entry
1
RCO2H
Time
24 h
Solvent
MeOH
Products
Yields (%)*
64
15
15
2
24 h
MeOH
35
30
25
3
24 h
MeOH
33
47
16
73
4
1
24 h
CH3CN

Esterification-nitration with CAN
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 175
5
2
24 h
24 h
CH3CN
CH3CN
77
6
3
80
15
52
36
7
8
48 h
48 h
MeOH
MeOH
9
48 h
MeOH
69
10
11
48 h
48 h
MeOH
MeOH
42
35
12
48 h
MeOH
26

176 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Pan et al.
13
48 h
MeOH
24
13
14
15
48 h
48 h
MeOH
MeOH
27
29
* Yields refer to the isolated yields. All of the compounds were characterized by 1H NMR, 13C NMR
and MS spectra data and by comparison with authentic compounds.
compounds 3e, 5a, 6a, 7a, 8a, and 12a against the cell lines of
yields, respectively. While sp2-C tethered (2E)-3-(2-hydro-
xyphenyl)prop-2-enoic acid (3) was employed in the reaction
under the same conditions, not only the mono-nitro methyl
ester, (2E)-3-(2-hydroxy-3-nitrophenyl)prop-2-enoic acid
methyl ester (3c) and methyl ester, (2E)-3-(2-hydroxyphen-
yl)prop-2-enoic acid methyl ester (3b), but also the cyclic
product chromen-2-one (3a) were obtained in 47%, 16% and
33% yields, respectively. The formation of 3a can be pro-
ceeded through isomerization of 3, followed by intramolecu-
lar esterification. Additionally, we examine the solvent ef-
fects upon the enhancement of selectivity; changing the sol-
vent system from methanol to methanol/dichloromethane
(4:1) leads in the case of 1 to the formation of 1b and 1c in
40% and 55% yields, respectively. However, the formation of
1a was not observed. When 2 was employed in the reaction
under the same conditions, 2a, 2b and 2c were formed in
20%, 40% and 36% yields, respectively. When 3 was sub-
jected to the reaction under the same conditions, 3a, 3b, and
3c were obtained in 32%, 22%, and 38% yields, respectively.
As a result, introducing dichloromethane into the methanol
solvent system may increase the production of mono-nitro
products. The sp2-C tethered 2-hydroxyphenyl carboxylic
acid 3 proceeded chemoselective intramolecular esterifica-
tion under CAN/CH3OH (or CAN/CH3OH/CH2Cl2) reaction
conditions.
Hep G2, Hep 3B, MCF-7 and MDA-MB-231.
RESULTS AND DISCUSSION
Initial experiments were conducted on sp3-C tethered
2-(2-hydroxyphenyl) acetic acid (1). When a solution of this
compound in methanol was treated with a methanol solution
of CAN at room temperature, intermolecular esterification
product 2-hydroxyphenylacetic acid methyl ester (1a), and
two simultaneous mono-nitration and intermolecular ester-
ification products 2-hydroxy-3-nitrophenylacetic acid meth-
yl ester (1b) and 2-hydroxy-5-nitrophenylacetic acid methyl
ester (1c) were obtained in 64%, 15% and 15% yields, respec-
tively (Table 1, Entry 1). This reaction gave no intramolecu-
lar esterification products. The structures of 1a, 1b and 1c
were assigned on the basis of spectral analysis. Similar re-
sults were obtained by employing the other 2-hydroxyphenyl
carboxylic acid (Entry 2). sp3-C tethered 3-(2-Hydroxyphen-
yl)propanoic acid (2) afforded methyl ester, 3-(2-hydroxy-
phenyl)propanoic acid methyl ester (2a) and two esterifica-
tion-nitration products, 3-(2-hydroxy-3-nitrophenyl)pro-
panoic acid methyl ester (2b), 3-(2-hydroxy-5-nitrophenyl)-
propanoic acid methyl ester (2c) in 35%, 30% and 25%

Esterification-nitration with CAN
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 177
In order to achieve the desired cyclic products and avoid
the formation of methyl esters by intermolecular esterifica-
tion, we decided to use acetonitrile instead of methanol. In
one successive step, simultaneous di-nitration and intramo-
lecular esterification of 1 gave o,p-dinitrobenzofuran-2-one
(1d) as the sole product in 73% yield (Entry 4). Another
2-hydroxyphenyl carboxylic acid 2 has also been success-
fully employed in this cyclization reaction. 2 afforded the
o,p-dinitrochroman-2-one (2d) as the sole product in 77%
yield (Entry 5). However, the reaction of 3 under the same re-
action conditions gave no cyclic products; only the major
di-nitration product (2E)-3-(2-hydroxy-3,5-dinitrophenyl)-
prop-2-enoic acid (3d) and the minor nitrodecarboxylation
product 2-((1E)-2-nitrovinyl)-4-nitrophenol (3e) were ob-
tained in 80%, 15% yields, respectively (Entry 6). The forma-
tion of 3d indicated that the di-nitration of sp2-C tethered 3
proceeded in acetonitrile, but the cyclic product was not ob-
served.
chroman-2-one, 5,7-dinitro-3-hydrobenzo[b]furan-2-one,
and chromen-2-one. This method also allows esterificaton of
much less reactive benzoic acids under the CAN/CH3OH re-
action conditions. This esterification method demands no de-
hydrating reagents or water removal equipment. Further-
more, compound 3e showed selective activities on MCF-7,
HEP G2, and HEP 3B cancer cell lines.
EXPERIMENTAL SECTION
General
NMR spectra were acquired on a Varian Germini 200
MHz FT-NMR running at 200 Mz (1H) or 50 MHz (13C), re-
spectively. Chemical shifts (d) were reported in ppm relative
1
to residual solvent signals. The multiplicities of H signals
are designated by the following abbreviations: s = singlet; d
= doublet; t = triplet; q = quartet; br = broad; m = multiplet,
app = apparent. All coupling constants, J, are reported in
Hertz. 13C NMR spectra were acquired on a broad band de-
coupled mode and the multiplicities were obtained using
DEPT sequences. The following symbolisms are used for
the multiplicities in 13C spectra: q = primary methyl; t = sec-
ondary methylene; d = tertiary methine; s = quaternary.
Melting points were determined using a Fargo MP-1D melt-
ing point apparatus and are uncorrected. Mass spectra were
recorded on a JEOL TMSD-100 Mass spectrometer. Flash
column chromatography was carried out using Fluka
Kieselgel 60 (230-400 mesh). Analytical thin layer chroma-
tography (TLC) was performed using precoated aluminium-
backed plates (Merck Kieselgel 60 F254) and visualized by
ultraviolet irradiation. Analytical grade solvents were used
as received.
When esterification of benzoic acids with methyl alco-
hol in the presence of CAN were investigated, the corre-
sponding methyl esters were obtained in 13-69% yields. (En-
tries 7-15) Thus, these reaction conditions also provide an al-
ternative esterification method for converting benzoic acids
to methyl esters. The results showed that methanol behaves
as a reactant and a solvent in these esterifications. Numerous
functionalities (e.g.; -OCH3, -OH, -CH3, -Cl, -NO2) were tol-
erated in the reaction conditions.
The cytotoxicities of compounds 3e, 5a, 6a, 7a, 8a, and
12a were evaluated against the cell lines of human hepato-
cellular carcinoma Hep G2 and Hep 3B, human breast carci-
noma MCF-7 and MDA-MB-231. Compound 3e showed se-
lective activities to MCF-7, HEP G2, and HEP 3B cancer cell
lines with IC50 values 23.50, 7.33, and 7.59 mg/mL, respec-
tively. However, compounds 5a, 6a, 7a, 8a, and 12a exhib-
ited no effect on the growth inhibition of Hep G2, Hep 3B,
MCF-7, and MDA-MB-231 cell lines.
General procedure for the preparation of products
The presented reactions are as follows: to a solution of
aromatic carboxylic acids (1.6 mmol) in solvent was added a
solution of CAN (0.99 g, 1.8 mmol) in solvent (10 mL) at
room temperature and stirred. After 24 h (or 48 h), the solvent
was removed on a rotary evaporator and the residue was sub-
jected to flash column chromatography on silica gel using
ethyl acetate as eluent. After the removal of the solvent, the
residue was subjected to column chromatography on silica
gel to afford the corresponding products.
In conclusion, the cerium(IV) ammonium nitrate pro-
moted aromatic mono-nitration, and esterification of 2-hy-
droxyphenyl carboxylic acids provides a one-step synthesis
of corresponding mono-nitro methyl esters, methyl esters,
and chromen-2-one in methanol at room temperature. This
method enables the simultaneous di-nitration and intra-
molecular esterification of an sp3-C tethered 2-hydroxyphen-
yl carboxylic acid, whereas the sp2-C tethered carboxylic
acid was stable in intramolecular esterification under the
CAN/CH3CN reaction conditions. This protocol provides a
practical method for the simple condensation reaction to pre-
pare nitro esters, as well as the cyclic products, 6,8-dinitro-
Cytotoxicity Assays
Compounds were assayed for cytotoxicity against Hep
G2, Hep 3B, MCF-7, and MDA-MB-231 cells using the MTT

178 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Pan et al.
method. Freshly trypsinized cell suspensions were seeded in
96-well microtitre plates at densities of 5,000-10,000 cells
per well with tested compounds added from DMSO-diluted
stock. After 3 days in culture, attached cells were incubated
with MTT (0.5 mg/mL, 1 hr) and subsequently solubilized in
DMSO. The absorbency at 550 nm was then measured using a
microplate reader. The IC50 is the concentrations of agent that
reduced cell growth by 50% under the experimental condi-
tions.
3-(2-Hydroxy-3-nitrophenyl)propanoic acid methyl ester
(2b)
Compound 2b was prepared according to general pro-
cedure and after 24 h the product was isolated as yellow green
1
oil. H NMR (200 MHz, CDCl3) 10.93 (s, 1H, 2-OH), 7.97
(dd, 1H, J = 8.6, 1.6 Hz), 7.49 (dd, 1H, J = 7.4, 1.0 Hz), 6.89
(dd, 1H, J = 8.6, 7.4 Hz), 3.65 (s, 3H), 3.04 (t, 1H, J = 7.4 Hz),
2.68 (t, 1H, J = 7.4 Hz); 13C NMR (50 MHz, CDCl3) 173.0,
153.4, 137.8, 133.6, 131.4, 123.3, 119.5, 51.6, 33.0, 25.5;
EI-MS m/z 225 (M+, 9), 194 (22), 175 (94), 148 (74), 118
(100).
2-Hydroxyphenylacetic acid methyl ester (1a)
Compound 1a was prepared according to general pro-
cedure and after 24 h the product was isolated as white crys-
tals. mp 73-74 °C; 1H NMR (200 MHz, CDCl3) 7.35 (s, 1H,
2-OH), 7.17-7.08 (m, 2H), 6.94-6.88 (m, 2H), 3.75 (s, 2H),
3.69 (s, 3H); 13C NMR (50 MHz, CDCl3) 174.2, 155.0, 131.0,
129.1, 120.8, 120.6, 117.4, 52.6, 37.4; EI-MS m/z 166 (M+,
11), 179 (69), 152 (25), 151 (25), 106 (51), 77 (95), 57 (100).
3-(2-Hydroxy-5-nitrophenyl)propanoic acid methyl ester
(2c)
Compound 2c was prepared according to general proce-
dure and after 24 h the product was isolated as white needles.
mp 106-107 °C; 1H NMR (400 MHz, CDCl3) 8.61 (br s, 1H,
2-OH), 8.03 (d, 1H, J = 2.8 Hz), 8.02 (dd, 1H, J = 8.4, 2.8 Hz),
6.93 (d, 1H, J = 8.4 Hz), 3.73 (s, 3H), 2.96 (t, 1H, J = 6.8 Hz),
2.78 (t, 1H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) 176.3,
160.7, 141.2, 127.7, 126.7, 124.4, 117.3, 52.7, 34.4, 24.7;
EI-MS m/z 216 (M+, 16), 193 (12), 165 (8), 89 (100), 61 (59).
2-Hydroxy-3-nitrophenylacetic acid methyl ester (1b)
Compound 1b was prepared according to general pro-
cedure and after 24 h the product was isolated as yellow nee-
dles. mp 115-116 °C; 1H NMR (200 MHz, CDCl3) 10.92 (s,
1H, 2-OH), 8.05 (dd, 1H, J = 8.6, 1.6 Hz), 7.52 (dd, 1H, J =
7.4, 1.6 Hz), 6.96 (dd, 1H, J = 8.6, 7.4 Hz), 3.75 (s, 2H), 3.72
(s, 3H); 13C NMR (50 MHz, CDCl3) 170.9, 153.4, 138.7,
133.7, 125.7, 124.2, 119.5, 52.2, 34.9; EI-MS m/z 211 (M+,
12), 179 (61), 152 (43), 135 (37), 105 (59), 77 (100).
Chromen-2-one (3a)
Compound 3a was prepared according to general pro-
cedure and after 24 h the product was isolated as colorless
needles. mp 193-194 °C; 1H NMR (400 MHz, CDCl3) 7.71 (d,
1H, J = 9.6 Hz), 7.54 (dd, 1H, J = 8.0, 3.6 Hz), 7.49 (dd, 1H, J
= 7.6, 1.6 Hz), 7.35 (d, 1H, J = 8.0 Hz), 7.28 (dd, 1H, J = 7.6,
1.6 Hz), 6.43 (d, 1H, J = 9.6 Hz); 13C NMR (50 MHz, CDCl3)
160.7, 154.1, 143.4, 131.8, 127.8, 124.4, 118.9, 116.9, 116.8;
EI-MS m/z 146 (M+, 41), 118 (100), 90 (62), 63 (25).
2-Hydroxy-5-nitrophenylacetic acid methyl ester (1c)
Compound 1c was prepared according to general proce-
dure and after 24 h the product was isolated as a white solid.
mp 183-184 °C; 1H NMR (200 MHz, CDCl3) 8.61 (br s, 1H,
2-OH), 8.08 (dd, 1H, J = 7.4, 2.8 Hz), 8.06 (d, 1H, J = 2.8 Hz),
6.96 (d, 1H, J = 7.4 Hz), 3.80 (s, 3H), 3.76 (s, 3H); 13C NMR
(50 MHz, CDCl3) 173.7, 161.2, 141.2, 127.2, 125.4, 121.0,
117.5, 53.2, 37.3; EI-MS m/z 211 (M+, 16), 179 (69), 152
(25), 151 (25), 106 (51), 77 (95), 57 (100).
(2E)-3-(2-Hydroxyphenyl)prop-2-enoic acid methyl ester
(3b)
Compound 3b was prepared according to general pro-
cedure and after 24 h the product was isolated as a yellow
1
amorphous solid. mp 176-177 °C; H NMR (200 MHz,
CDCl3) 11.30 (br s, 1H, 2-OH), 8.15 (dd, 1H, J = 8.6, 1.6 Hz),
8.00 (d, 1H, J = 16.0 Hz), 7.81 (ddd, 1H, J = 7.6, 1.6, 0.4 Hz),
7.02 (dd, 1H, J = 8.6, 7.6 Hz), 6.64 (d, 1H, J = 16.0 Hz), 3.82
(s, 3H); 13C NMR (50 MHz, CDCl3) 167.1, 153.9, 137.3,
136.3, 134.3, 126.4, 126.0, 121.3, 119.8, 51.9; EI-MS m/z
223 (M+, 7), 191 (11), 174 (9), 147 (18), 117 (24), 89 (100).
3-(2-Hydroxyphenyl)propanoic acid methyl ester (2a)
Compound 2a was prepared according to general pro-
cedure and after 24 h the product was isolated as yellow oil.
1H NMR (200 MHz, CDCl3) 7.30 (br s, 1H, 2-OH), 7.15-7.06
(m, 2H), 6.89-6.82 (m, 2H), 3.68 (s, 3H), 2.94 (t, 2H, J = 6.6
Hz), 2.72 (t, 2H, J = 6.6 Hz); 13C NMR (50 MHz, CDCl3)
175.6, 154.1, 130.3, 127.8, 127.0, 120.6, 116.5, 52.0, 34.6,
24.9; EI-MS m/z 180 (M+, 36), 148 (93), 120 (100), 107 (33),
91 (49).
(2E)-3-(2-Hydroxy-3-nitrophenyl)prop-2-enoic acid
methyl ester (3c)
Compound 3c was prepared according to general proce-

Esterification-nitration with CAN
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 179
dure and after 24 h the product was isolated as a yellow amor-
Methyl benzoate (4a)
1
phous solid. mp 120-121 °C; H NMR (200 MHz, CDCl3)
Compound 4a was prepared according to general pro-
8.05 (d, 1H, J = 16.0 Hz), 7.47 (dd, 1H, J = 7.8, 1.6 Hz), 7.24
(td, 1H, J = 7.8, 1.6 Hz), 6.92 (td, 1H, J = 7.8, 1.6 Hz), 6.86
(dd, 1H, J = 7.8, 1.6 Hz), 6.64 (d, 1H, J = 16.0 Hz), 3.83 (s,
3H); 13C NMR (50 MHz, CDCl3) 168.9 (s), 155.4 (s), 140.9
(d), 131.5 (d), 129.2 (d), 121.6 (s), 120.7 (d), 118.0 (d), 116.4
(d), 51.8 (q); EI-MS m/z 178 (M+, 5), 146 (21), 118 (100), 103
(21), 91 (60).
cedure and after 48 h the product was isolated as colorless liq-
1
uid. H NMR (CDCl3, 200 MHz): 8.08-8.02 (m, 2H), 7.60-
7.39 (m, 3H), 3.91 (s, 3H). 13C NMR (CDCl3, 50 MHz):
167.1, 132.9, 130.1, 129.5, 129.5, 128.3, 128.3, 52.0.
Methyl 3-methoxybenzoate (5a)
Compound 5a was prepared according to general pro-
cedure and after 48 h the product was isolated as colorless liq-
1
5,7-Dinitro-3-hydrobenzo[b]furan-2-one (1d)
uid. H NMR (CDCl3, 400 MHz) 7.63 (d, 1H, J = 8.0 Hz),
Compound 1d was prepared according to general pro-
cedure and after 24 h the product was isolated as pale yellow
7.55 (s, 1H), 7.34 (t, 1H, J = 8.0 Hz), 7.10 (d, 1H, J = 8.0 Hz),
3.91 (s, 3H), 3.84 (s, 3H); 13C NMR (CDCl3, 100 MHz)
167.0, 159.5, 131.4, 129.3, 121.9, 119.5, 113.9, 55.4, 52.1;
EI-MS m/z 166 (M+, 80), 135 (100), 107 (50), 92 (39), 77
(31).
1
oil. H NMR (400 MHz, CD3OD) 8.92 (d, 1H, J = 2.8 Hz),
8.47 (d, 1H, J = 3.2 Hz), 3.72 (s, 2H); 13C NMR (100 MHz,
CD3OD) 173.7, 138.5, 131.8, 123.5, 30.7, quaternary carbon
signals were absent; EI-MS m/z 224 (M+, 100), 197 (18), 69
(24).
Methyl 3-methylbenzoate (6a)
Compound 6a was prepared according to general pro-
cedure and after 48 h the product was isolated as colorless liq-
uid. 1H NMR (CDCl3, 200 MHz) 7.78 (s, 1H), 7.76 (d, 1H, J =
6,8-Dinitrochroman-2-one (2d)
Compound 2d was prepared according to general pro-
cedure and after 24 h the product was isolated as pale yellow
7.6 Hz), 7.26 (d, 1H, J = 7.6 Hz), 7.23 (t, 1H, J = 7.6 Hz); 13
C
1
oil. H NMR (200 MHz, CD3OD) 8.85 (d, 1H, J = 2.8 Hz),
NMR (CDCl3, 50 MHz) 167.2, 138.0, 133.6, 133.6, 130.0,
128.2, 126.6, 51.9, 21.1; EI-MS m/z 150 (M+, 24), 119 (100),
91 (61), 65 (29), 43 (96).
8.42 (d, 1H, J = 2.8 Hz), 3.10 (t, 2H, J = 7.4 Hz), 2.72 (t, 2H, J
= 7.4 Hz); 13C NMR (50 MHz, CD3OD) 176.5, 158.8, 141.0,
135.8, 135.3, 132.2, 121.3, 34.0, 27.2; EI-MS m/z 238 (M+,
26), 220 (91), 210 (63), 193 (95), 177 (100).
Methyl 3-chlorobenzoate (7a)
Compound 7a was prepared according to general pro-
cedure and after 48 h the product was isolated as colorless liq-
uid. 1H NMR (CDCl3, 400 MHz) 8.01 (s, 1H), 7.91 (dd, 1H, J
= 7.6, 1.2 Hz), 7.53 (dd, 1H, J = 7.6, 1.2 Hz), 7.37 (t, 1H, J =
7.6 Hz), 3.92 (s, 3H); 13C NMR (CDCl3, 50 MHz) 166.2,
134.5, 133.0, 131.8, 129.7, 129.7, 127.7, 52.4; EI-MS m/z
170 (M+, 16), 139 (60), 111 (39), 88 (28), 70 (57), 61 (100).
(2E)-3-(2-Hydroxy-3,5-dinitrophenyl)prop-2-enoic acid
(3d)
Compound 3d was prepared according to general pro-
cedure and after 24 h the product was isolated as an orange
red solid. mp 209-210 °C; 1H NMR (200 MHz, CD3OD) 8.94
(d, 1H, J = 2.6 Hz), 8.72 (d, 1H, J = 2.6 Hz), 7.97 (d, 1H, J =
16.0 Hz), 6.79 (d, 1H, J = 16.0 Hz); 13C NMR (50 MHz,
CD3OD) 169.6, 159.3, 139.8, 137.8, 136.3, 130.0, 129.0,
124.2, 123.4; EI-MS m/z 254 (M+, 27), 219 (22), 193 (100),
163 (25).
Methyl 3-nitrobenzoate (8a)
Compound 8a was prepared according to general pro-
cedure and after 48 h the product was isolated as a white
1
solid. mp 77-78 °C; H NMR (CDCl3, 200 MHz) 8.85 (dd,
2-((1E)-2-Nitrovinyl)-4-nitrophenol (3e)
1H, J = 2.2, 1.6 Hz), 8.44-8.33 (m, 2H), 7.65 (t, 1H, J = 8.0
Hz); 13C NMR (CDCl3, 50 MHz) 164.9, 135.2, 131.9, 129.6,
127.3, 124.6, 52.8; EI-MS m/z 181 (M+, 14), 150 (92), 104
(44), 76 (100).
Compound 3e was prepared according to general proce-
dure and after 24 h the product was isolated as yellow oil. 1H
NMR (200 MHz, CDCl3) 8.38 (d, 1H, J = 2.6 Hz), 8.22 (dd,
1H, J = 9.0, 2.6 Hz), 8.11 (d, 1H, J = 13.4 Hz), 7.97 (d, 1H, J =
13.4 Hz), 7.01 (d, 1H, J = 9.0 Hz); 13C NMR (50 MHz,
CD3OD) 164.5, 139.4, 138.7, 133.2, 127.5, 127.2, 117.5,
116.2; EI-MS m/z 210 (M+, 12), 163 (100), 117 (50), 89 (86).
Methyl 5-hydroxy-2-nitrobenzoate (9a)
Compound 9a was prepared according to general pro-
cedure and after 48 h the product was isolated as pale yellow

180 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Pan et al.
needles. mp 114-115 °C; 1H NMR (CDCl3, 200 MHz) 10.50
(s, 1H, -OH), 8.17 (d, 1H, J = 8.8 Hz), 7.82 (d, 1H, J = 1.4
Hz), 7.61 (dd, 1H, J = 8.8, 1.4 Hz), 3.96 (s, 3H); 13C NMR
(CDCl3, 50 MHz) 164.8, 154.6, 138.0, 136.0, 125.2, 121.6,
120.6, 52.9; EI-MS m/z 197 (M+, 78), 166 (100), 136 (15),
119 (16), 108 (12).
ACKNOWLEDGEMENT
We thank the National Science Council of the Republic
of China for financial support of this program.
Received July 22, 2004.
Methyl 2-hydroxy-3-nitrobenzoate (10a)
Compound 10a was prepared according to general pro-
cedure and after 48 h the product was isolated as white nee-
dles. mp 142-143 °C; 1H NMR (CDCl3, 400 MHz) 12.00 (s,
1H, -OH), 8.17 (dd, 1H, J = 8.0, 2.0 Hz), 8.14 (dd, 1H, J = 8.0,
2.0 Hz), 7.01 (t, 1H, J = 8.0 Hz), 4.02 (s, 3H); 13C NMR
(CDCl3, 50 MHz) 169.1, 155.7, 135.7, 131.4, 128.3, 118.4,
116.0, 53.1; EI-MS m/z 197 (M+, 45), 165 (64), 107 (100), 91
(55), 63 (96).
REFERENCES
1. Nair, V.; Mathew, J.; Prabhakaran. J. Chem. Soc. Rev. 1997,
127.
2. Gu, S.; Jing, H.; Wu, J.; Ling, Y. Synth. Commun. 1997, 27,
2793.
3. Smith, K.; Almeer, S.; Black, S. J. Chem. Commun. 2000,
1571.
4. (a) Delaude, L.; Laszlo, P.; Smith, K. Acc. Chem. Res. 1993,
26, 607. (b) Laszlo, P. Acc. Chem. Res. 1986, 19, 121. (c)
Cornelis, A.; Laszlo, P.; Pennetreau, P. Bull. Soc. Chim.
Belg. 1984, 93, 961. (d) Zeegers, P. J. J. Chem. Ed. 1993, 70,
1036. (e) Gigante, B.; Prazeres, A. O.; Marcelo-Curto, M. J.
J. Org. Chem. 1995, 60, 3445. (f) Rodrigues, J. A. R.; de O.
Filho, A. P.; Moran, P. J. S.; Custodio, R. Tetrahedron 1999,
55, 6733. (g) Nonoyama, N.; Chiba, K.; Hisatome, K.;
Suzuki, H.; Shintani, F. Tetrahedron Lett. 1999, 40, 6923. (h)
Lehnig, M. Tetrahedron Lett. 1999, 40, 2299.
5. Chawla, H. M.; Mittal, R. S. Synthesis 1985, 70.
6. Del Mar Blanco, M.; Avendano, C.; Cabezas, N.; Menendez,
J. C. Heterocycles 1993, 36, 1387.
7. Chakrabarty, N.; Batabyal, A. Synth. Commun. 1994, 24, 1.
8. Grenier, J.-L.; Catteau, J.-P.; Cotelle, P. Synth. Commun.
1999, 29, 1201.
9. (a) Beaz, G. In Comprehensive Organic Synthesis; Trost, B.
M.; Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 6, p. 323.
(b) Franklin, A. S. J. Chem. Soc. Perkin Trans. 1 1998, 2451
and 1999, 3537. (c) Otera, J. Chem. Rev. 1993, 93, 1449. (d)
Greene, T. W.; Wuts, P. G. Protective Groups in Organic
Synthesis; 3rd ed.; Wiley-Interscience: New York, 1999; p.
372.
Methyl 2-hydroxy-5-nitrobenzoate (10b)
Compound 10b was prepared according to general pro-
cedure and after 48 h the product was isolated as a white
solid. 1H NMR (CDCl3, 400 MHz) 11.44 (s, 1H), 8.80 (d, 1H,
J = 2.8 Hz), 8.34 (dd, 1H, J = 9.2, 2.8 Hz), 7.09 (d, 1H, J = 9.2
Hz), 4.04 (s, 3H); 13C NMR (CDCl3, 50 MHz) 169.3, 166.3,
130.6, 126.7, 121.9, 118.7, 112.2, 53.1; EI-MS m/z 197 (M+,
38), 165 (55), 70 (55), 61 (100).
Methyl 4-hydroxybenzoate (11a)
Compound 11a was prepared according to general pro-
cedure and after 48 h the product was isolated as a white
solid. mp 144-145 °C; 1H NMR (CDCl3, 200 MHz) 7.94 (d,
2H, J = 8.8 Hz), 6.88 (d, 2H, J = 8.8 Hz), 6.55 (br s, 1H, -OH),
3.90 (s, 3H); 13C NMR (CDCl3, 50 MHz) 167.4, 160.2, 131.9,
122.3, 115.3, 52.0; EI-MS m/z 152 (16), 121 (100), 93 (62),
65 (56).
Methyl naphathalenecarboxylate (12a)
Compound 12a was prepared according to general pro-
cedure and after 48 h the product was isolated as colorless liq-
10. Pan, W. B.; Chang, F. R.; Wei, L. M.; Wu, M. J.; Wu, Y. C.
Tetrahedron Lett. 2003, 44, 331.
11. Chen, H.; Boiziau, J.; Parker, F.; Mailliet, P.; Commercon, A.
J. Med. Chem. 1994, 37, 845.
12. EI-Sayrafi, S.; Rayyan, S. Molecules 2001, 6, 279.
13. Yang, D.; Wong, M. K.; Yan, Z. J. Org. Chem. 2000, 65,
4179.
1
uid. H NMR (CDCl3, 200 MHz) 8.92 (d, 1H, J = 8.8 Hz),
8.22 (dd, 1H, J = 7.4, 1.4 Hz), 8.02 (d, 1H, J = 8.0 Hz), 7.89
(dd, 1H, J = 7.8, 1.8 Hz), 7.67-7.46 (m, 3H), 4.01 (s, 3H); 13
C
NMR (CDCl3, 50 MHz) 168.0, 133.8, 133.4, 131.8, 130.2,
128.5, 127.7, 127.0, 126.2, 125.8, 124.5, 52.1; EI-MS m/z
186 (M+, 38), 155 (92), 127 (100), 101 (10), 77 (15), 75 (15).
14. Vaidya Proc. R. Soc. London A 1930, 129, 304.