Synthesis of methyl (E)-2-nitromethylcinnamates derived from baylis-hillman acetates and conversion into several coumarin derivatives

Article abstract of DOI:10.1055/s-2004-834916

Fast and easy access to methyl (E)-2-nitromethylcinnamates, from the corresponding Baylis-Hillman acetates with NaNO₂ in DMF is described. Several ortho-chloro-2-nitromethylcinnamates undergo intramolecular aromatic substitution reaction follow

Full text of DOI:10.1055/s-2004-834916

PAPER
33
Synthesis of Methyl (E)-2-Nitromethylcinnamates Derived from Baylis–
Hillman Acetates and Conversion into Several Coumarin Derivatives
Synthesis of Methyl
(
E
)
a
-2-Nitrome
n
thylcinnamates De
P
r
ived fromBay
y
lis–Hillman
oAcetates Hong, Kee-Jung Lee*
Organic Synthesis Laboratory, School of Chemical Engineering, Hanyang University, Seoul 133-791, South Korea
Fax +82(2)22984101; E-mail: leekj@hanyang.ac.kr
Received 4 August 2004; revised 17 September 2004
substitution reaction (SNAr) were reported. We now de-
scribe a synthesis of methyl (E)-2-nitromethylcinnamates
derived from BH acetates and conversion into coumarins
by the intramolecular SNAr reaction of several ortho-chlo-
ro-2-nitromethylcinnamates.
Abstract: Fast and easy access to methyl (E)-2-nitromethylcin-
namates, from the corresponding Baylis–Hillman acetates with
NaNO2 in DMF is described. Several ortho-chloro-2-nitromethyl-
cinnamates undergo intramolecular aromatic substitution reaction
followed by rearrangement to yield coumarin derivatives.
Key words: Baylis–Hillman reaction, sodium nitrite, methyl (E)-2-
nitromethylcinnamates, nitronate anion, coumarin
The coumarin nucleus is present in many naturally-occur-
ring pharmacologically active compounds.23 Various
methods for preparing coumarin derivatives have been de-
veloped including the classic von Pechmann,24 Claisen,25
Perkin,26 Reformatsky,27 Knoevenagel,28 and Wittig reac-
tions.29 Also, new methods of accessing these important
compounds continue to be reported. These include: the re-
action of tert-butyl isocyanide and dialkyl acetylenedicar-
boxylates in the presence of salicylaldehydes;30 the
reaction of the N-hydroxybenzotriazole ester of acetyl sal-
icylic acids and active methylene compounds followed by
cyclization;31 palladium-catalyzed reaction of phenols
with propiolic acids;32 and cyclization of protected or un-
protected BH adducts of salicylaldehyde.33
Aliphatic nitro compounds are potentially useful sub-
strates in organic synthesis due to the high electron-with-
drawing nature associated with the nitro group and the
conversion of the nitro group into other functionalities.1
Nitronate salts can act as carbon nucleophiles with a range
of electrophiles including haloalkanes,2 aldehydes3,4 and
Michael acceptors5 leading to the carbon-carbon bond for-
mation.
Much attention has recently been focused on the SN2¢ nu-
cleophilic substitution of the acetates, imines or bromo-
derivatives of the Baylis–Hillman (BH) adducts. These in-
clude nucleophilic substitution of tosyl amide,6 acryloni-
trile,7 cyanide,8,9 hydride,10 imidazole,11 acetate ion,12
phosphite,13 azide,14,15 nitronate anion,16 active methylene
anion17 and nitric acid.18 To the best of our knowledge,
there is no report in the literature19 for the conversion of
the BH adducts into the corresponding 2-nitromethyl-2-
propenoates stereoselectively. As part of our continuing
studies towards development of the BH chemistry,20,21 we
desired to have the nitro group at the allylic position of the
3-aryl-2-propenoates. In principle, such nitro compounds
might be extended further toward the building of indene
derivatives (Equation 1).
OAc
NaNO2, DMF
r.t., 1 h
CO2Me
NO2
R
CO2Me
R
38–87%
2
1
For R see Table 1
Scheme 1
In view of the report14 that 1,4-diazabicyclo[2,2,2]octane
(DABCO) assisted fast and easy access to azides of BH
adducts from the corresponding acetates in aqueous me-
dia, we carried out the reaction of BH acetate 1a with
DABCO in aqueous THF for 10 minutes and then sodium
nitrite (NaNO2) was added and stirred at room tempera-
ture for one hour. Unfortunately, the desired 2-nitrometh-
ylcinnamic acid methyl ester 2a was produced in poor
yield (25%). But, the direct substitution reaction of 1a
with NaNO2 in DMF at room temperature for one hour af-
forded 2a in 87% yield. This success led us to transform
the representative methyl 3-acetoxy-3-aryl-2-methylene-
propanoates 1b–l into methyl (E)-3-aryl-2-nitromethyl-2-
propenoates 2b–l stereoselectively under the similar reac-
tion conditions (Scheme 1, Table 1 and Table 2). The E
geometry of the olefinic bond was established on the basis
of NOE experiment of 2d in which irradiation of either of
the allylic protons or the olefinic proton did not lead to the
X
X
CO2Me
CO2Me
Cl
NO2
NO2
Equation 1
Similar methods using Baylis–Hillman chemistry in the
construction of benzannulated compounds such as 3-quin-
olincarboxylic acid esters,6b 1,4-dihydroquinolines,22 and
naphthalenes16a via intramolecular nucleophilic aromatic
SYNTHESIS 2005, No. 1, pp 0033–0038
x
x
.
x
x
.2
0
0
4
Advanced online publication: 17.11.2004
DOI: 10.1055/s-2004-834916; Art ID: F11204SS
1
enhancement of the other peak. Also, in the H NMR
© Georg Thieme Verlag Stuttgart · New York

34
W. P. Hong, K.-J. Lee
PAPER
Table 1 Methyl (E)-3-Aryl-2-nitromethyl-2-propenoates 2
6, then tautomerized to afford oxime 7. This kind of the
formation of 7-membered ring products, 3,2-benzox-
azepin-5(4H)-one 2-oxides via intramolecular O-alkyla-
tion of the nitronate anion and rearrangement to
isocoumarin-4-one 1-oximes was reported in the litera-
ture.36 Oximes 7j–n were easily hydrolyzed using concen-
trated HCl in THF to give the corresponding coumarins
8j–n by the known method.36
React-
ant
R
Product
Yield Time Mp
(%)
87
76
86
83
64
38
70
79
82
78
80
71
(h)
(°C)
1a
1b
1c
1d
1e
1f
C6H5
2a
2b
2c
2d
2e
2f
1
oil
4-ClC6H4
2-BrC6H4
4-BrC6H4
2-IC6H4
1
64–66
1
96–97
73–74
90–91
63–64
128–130
oil
The structures of oximes 7j–n were assigned on the basis
of their spectral data. IR spectra showed absorptions at
3395–3449 cm–1 for the hydroxyl groups, absorptions at
1703–1731 cm–1 for the ester carbonyl groups, and ab-
sorptions at 1641–1655 and 1603–1613 cm–1 for the car-
1
1
2-O2NC6H4
4-O2NC6H4
4-MeOC6H4
4-AcNHC6H4
2-ClC6H4
2,6-Cl2C6H3
2,3-Cl2C6H3
1
1
1g
1h
1i
2g
2h
2i
1
bon-nitrogen and carbon-carbon double bonds. The H
NMR spectra showed signals at d = 7.62–7.78 ppm as a
singlet for the methine hydrogen, signals at d = 10.77–
11.28 ppm as a singlet for oxime hydrogen and exchange-
able in deuterium oxide, and signals corresponding to the
methoxy peak appeared as a singlet at d = 3.78–3.83 ppm.
The 13C NMR spectra showed eleven absorption peaks in-
cluding ester carbonyl absorption (162.83–163.85 ppm).
1
1
150–152
88–90
87–89
122–124
1j
2j
1
1k
1l
2k
2l
1
1
The structures of coumains 8j–n were established on the
basis of their spectral data compared with literature val-
ues.30,37 IR spectra revealed sharp bands at 1738–1779 and
1696–1720 cm–1 assigned to the carbonyl groups. The 1H
NMR spectra showed two single sharp lines readily recog-
nized as arising from methoxy (d = 3.97–4.00 ppm) and
methine (d = 8.55–8.90 ppm) protons along with multi-
plets for the aromatic protons. The 13C NMR spectra ex-
hibited signals at d = 162.54–163.69 ppm for the ester
carbonyl groups and signals at d = 153.96–155.89 ppm for
the lactone carbonyl groups.
spectra, the vinyl peaks appeared at 7.87–8.44 ppm, which
were well coincident with the reported data of similar
compounds.16b,18
The simplicity of this reaction yielding 2-nitromethyl-o-
chlorocinnamates 2j–l has obvious some synthetic poten-
tial due to their conversion into the cyclic derivatives via
intramolecular SNAr reaction. Thus, in our initial experi-
ment, the reaction of 2j with K2CO3 in DMF led to an ex-
tremely complex reaction mixture as indicated by thin
layer chromatography, from which we could isolate 3-
methoxycarbonylcoumarin 2-oxime 7j in 14% yield. But,
dichlorocinnamates 2k and 2l, having another electron-at-
tracting chlorine atom on benzene ring, gave coumarin 2-
oximes 7k and 7l in 66% and 50% yields, respectively. In-
terestingly, the reaction of BH acetates 1m and 1n, having
strong electron-withdrawing nitro group on benzene ring,
with NaNO2 in DMF directly gave the corresponding cou-
marin 2-oximes 7m (70%) and 7n (48%)34 within 30 min-
utes (Scheme 2).35 In all the cases indene derivatives 3
were not obtained. Although the isolation of the interme-
diate 2-nitromethylcinnamates 2m and 2n were unsuc-
cessful in these reactions we presumed that the eliminated
acetate anions could be considered as a base in this trans-
formation, possibly because of some enhancement of the
hydrogen acidity at the a-position of nitro group.
In conclusion, a simple synthesis of methyl 2-nitrometh-
ylcinnamates from readily available Baylis–Hillman ace-
tates and conversion to the several coumarin derivatives is
disclosed.
Silica gel 60 (70–230 mesh ASTM) used for column chromatogra-
phy was supplied by E. Merck. Analytical TLC was carried out on
Merck silica gel 60 F254 TLC plates. Melting points were taken us-
ing an Electrothermal melting point apparatus and are uncorrected.
Microanalyses were obtained using a Carlo Erba EA 1180 element
analyzer. Electron impact (EI) and high resolution mass spectra
(HRMS) were obtained using a Jeol SX102 mass spectrometer. IR
spectra were recorded on a Nicolet Magna 550 FTIR spectrometer.
The 1H and 13C NMR spectra were measured on a Gemini 300 spec-
trometer using CDCl3 or DMSO-d6. All chemical shifts are reported
in ppm relative to TMS and coupling constants (J) are expressed in
Hz.
Aromatic aldehydes, DABCO, THF, DMF, K2CO3, NaNO2 and
methyl acrylate were obtained from Aldrich and used without fur-
ther purification. All the required Baylis–Hillman acetates 1a–n
were prepared by the reaction of the corresponding aldehydes with
methyl acrylate in the presence of DABCO followed by acetylation
with acetic anhydride according to the literature procedures.16,38
We believe that the oximes 7 might be produced by the re-
arrangement of the intermediate 4-methoxycarbonyl-1,2-
benzoxazepine 2-oxides 4. Conversion of 4 into 7 under
the reaction condition was considered to proceed by way
of the zwitterionic tricyclic oxaziridine N-oxide interme-
diate 5, which was formed by the attack of the ring oxygen
to the imminium carbon. The resulting oxaziridine inter-
mediate 5 could be cleaved to produce nitroso compound
Preparation of Methyl (E)-3-Aryl-2-nitromethyl-2-propenoates
2a–l; General Procedure
NaNO2 (207 mg, 3 mmol) was added to the solution of the Baylis–
Hillman acetates 1a–l (2 mmol) in DMF (8 mL) and stirred at r.t. for
Synthesis 2005, No. 1, 33–38 © Thieme Stuttgart · New York

PAPER
Synthesis of Methyl (E)-2-Nitromethylcinnamates Derived from Baylis–Hillman Acetates
35
Table 2 Spectral and Elemental Analysis Data of Methyl (E)-3-Aryl-2-nitromethyl-2-propenoates 2
Product IR (KBr) (cm–1) 1H NMR (CDCl3/TMS) d, J (Hz) 13C NMR (CDCl3/TMS) d
Analysis (%)
Calcd/Found C H N
2a
2b
2c
2d
2e
1714, 1639, 1555, 3.88 (s, 3 H, OCH3), 5.36 (s, 2 H, CH2), 7.31–7.34 52.53, 71.66, 121.73, 128.69,
1387, 1357
59.73 5.01 6.33
(m, 2 H, aromatic), 7.44–7.46 (m, 3 H, aromatic), 128.90, 130.04, 133.26, 147.44, 59.51 5.14 6.06
8.19 (s, 1 H, CH)
166.03
1726, 1641, 1555, 3.80 (s, 3 H, OCH3), 5.25 (s, 2 H, CH2), 7.20
52.76, 71.61, 122.37, 129.38,
51.68 3.94 5.48
1382, 1360
(d, J = 7.6 Hz, 2 H, aromatic), 7.34 (d, J = 7.6 Hz, 130.16, 131.74, 136.40, 146.23, 51.46 3.97 5.29
2 H, aromatic), 8.05 (s, 1 H, CH) 165.86
1709, 1639, 1561, 3.90 (s, 3 H, OCH3), 5.22 (s, 2 H, CH2), 7.26–7.39 52.70, 71.57, 123.37, 123.74,
1387, 1356
44.02 3.36 4.67
(m, 3 H, aromatic), 7.67 (d, J = 7.9 Hz, 1 H, aro- 127.77, 129.31, 131.18, 133.07, 44.25 3.34 4.69
matic), 8.17 (s, 1 H, CH)
133.89, 146.43, 165.43
1718, 1641, 1554, 3.88 (s, 3 H, OCH3), 5.32 (s, 2 H, CH2), 7.20
53.25, 71.95, 122.79, 125.09,
44.02 3.36 4.67
1389, 1359
(d, J = 8.4 Hz, 2 H, aromatic), 7.59 (d, J = 8.4 Hz, 130.68, 132.54, 132.84, 146.68, 44.04 3.27 4.59
2 H, aromatic), 8.11 (s, 1 H, CH)
166.21
1709, 1637, 1562, 3.98 (s, 3 H, OCH3), 5.27 (s, 2 H, CH2), 7.20
52.89, 71.57, 98.64, 123.02,
38.06 2.90 4.04
1388, 1354
(dd, J = 7.6, 7.6 Hz, 1 H, aromatic), 7.30 (d, J = 7.6 128.64, 128.82, 131.10, 137.64, 38.31 2.91 3.93
Hz, 1 H, aromatic), 7.50 (dd, J = 7.6, 7.6 Hz, 1 H, 139.47, 150.29, 165.50
aromatic), 8.01 (d, J = 7.6 Hz, 1 H, aromatic), 8.13
(s, 1 H, CH)
2f
1724, 1649, 1555, 3.91 (s, 3 H, OCH3), 5.13 (s, 2 H, CH2), 7.42
52.44, 71.58, 122.95, 125.52,
49.63 3.79 10.52
1518, 1379, 1342 (d, J = 7.6 Hz, 1 H, aromatic), 7.63–7.78 (m, 2 H, 129.68, 130.51, 130.94, 134.75, 49.74 3.68 10.53
aromatic), 8.29 (dd, J = 8.2, 1.2 Hz, 1 H, aromatic), 144.93, 147.04, 165.25
8.44 (s, 1 H, CH)
2g
2h
1720, 1648, 1566, 3.91 (s, 3 H, OCH3), 5.30 (s, 2 H, CH2), 7.52
1519, 1384, 1347 (d, J = 8.6 Hz, 2 H, aromatic), 8.21 (s, 1 H, CH),
8.32 (d, J = 8.6 Hz, 2 H, aromatic)
53.10, 71.33, 124.29, 124.88,
129.59, 139.63, 144.85, 148.42, 49.35 3.75 10.53
165.27
49.63 3.79 10.52
1710, 1633, 1555, 3.85 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 5.40
52.31, 55.15, 71.92, 114.37,
57.37 5.22 5.58
1391, 1358
(s, 2 H, CH2), 6.96 (d, J = 8.7 Hz, 2 H, aromatic), 119.12, 125.53, 130.99, 147.07, 57.07 5.29 5.68
7.31 (d, J = 8.7 Hz, 2 H, aromatic), 8.12 (s, 1 H,
161.14, 166.36
CH)
2i
1707, 1667, 1595, 2.21 (s, 3 H, CH3), 3.87 (s, 3 H, OCH3), 5.38
24.61, 52.69, 71.96, 119.83,
56.11 5.07 10.07
1551, 1397, 1370 (s, 2 H, CH2), 7.30 (d, J = 8.6 Hz, 2 H, aromatic), 120.58, 128.88, 130.20, 139.93, 56.14 4.96 9.90
7.61 (d, J = 8.6 Hz, 2 H, aromatic), 7.69 (br s, 1 H, 147.06, 166.39, 168.80
NH), 8.11 (s, 1 H, CH)
2j
2k
2l
1726, 1641, 1555, 3.90 (s, 3 H, OCH3), 5.24 (s, 2 H, CH2), 7.25–7.50 52.80, 71.71, 123.72, 127.27,
51.68 3.94 5.48
1382, 1360
(m, 4 H, aromatic), 8.24 (s, 1 H, CH)
129.34, 129.53, 130.51, 132.10, 51.50 3.99 5.83
134.13, 144.63, 165.56
1717, 1654, 1561, 3.91 (s, 3 H, OCH3), 5.08 (s, 2 H, CH2), 7.26–7.41 52.81, 71.21, 126.80, 128.25,
45.54 3.13 4.83
1386, 1358
(m, 3 H, aromatic), 7.87 (s, 1 H, CH)
130.76, 131.02, 133.90, 141.04, 45.61 3.15 5.00
164.89
1708, 1637, 1556, 3.90 (s, 3 H, OCH3), 5.21 (s, 2 H, CH2), 7.19
52.79, 71.47, 124.30, 127.39,
45.54 3.13 4.83
1387, 1357
(d, J = 7.6 Hz, 1 H, aromatic), 7.30 (dd, J = 7.9,
7.6 Hz, 1 H, aromatic), 7.55 (d, J = 7.9 Hz, 1 H,
aromatic), 8.19 (s, 1 H, CH)
127.80, 131.59, 132.12, 133.96, 45.85 3.13 4.67
134.19, 144.01, 165.22
1 h. The reaction mixture was diluted with water (15 mL) and ex-
tracted with Et2O (3 × 30 mL). The combined organic layers were
dried over anhyd MgSO4 and the solvent was evaporated in vacuo.
The resulting mixture was chromatographed on silica gel eluting
with hexane–EtOAc (4:1) to afford pure 2a–l.
Methyl 2-Hydroxyimino-2H-chromene-3-carboxylate (7j)
K2CO3 (207 mg, 1.5 mmol) was added to the solution of 2j (256 mg,
1.0 mmol) in DMF (5 mL) and stirred at r.t. for 8 h. The reaction
mixture was neutralized with dilute aq HCl solution and extracted
with CH2Cl2 (3 × 20 mL). The combined organic layers were dried
over anhyd MgSO4 and the solvent was evaporated in vacuo. The
resulting mixture was chromatographed on silica gel eluting with
hexane–EtOAc (2:1) to afford 7j (31 mg, 14%) as a yellow solid;
mp 217–219 °C.
The physical and spectral data of 2a–l prepared by this general
method are listed in Table 1 and Table 2.
IR (KBr): 3423, 1725, 1643, 1603, 1450, 1438, 1351 cm–1.
Synthesis 2005, No. 1, 33–38 © Thieme Stuttgart · New York

36
W. P. Hong, K.-J. Lee
PAPER
R3
R2
CO2Me
NO2
R3
K2CO3, DMF
r.t., 2–8 h
R1
R3
R2
CO2Me
NO2
3
Cl
R3
CO2Me
R1
R2
R2
CO2Me
2
N
O
O
N
O
R1
R1
O
4
5
R3
OAc
Cl
R3
R3
R2
CO2Me
R2
CO2Me
R2
CO2Me
NaNO2, DMF
r.t., 10–30 min
14–66%
48–70%
O
N
O
O
N OH
R1
R1
R1
7
6
1m, n
35% HCl
THF, reflux
4 h
57–68%
R3
R2
CO2Me
O
O
R1
8
R2
R3
H
1, 2, 7, 8
R1
H
j
H
k
H
H
Cl
H
Cl
H
l
m
H
NO2
H
n
NO2
Cl
H
Scheme 2
1H NMR (DMSO-d6): d = 3.78 (s, 3 H, OCH3), 7.16–7.21 (m, 2 H,
aromatic), 7.43–7.55 (m, 2 H, aromatic), 7.63 (s, 1 H, CH), 10.77 (s,
1 H, OH).
1H NMR (DMSO-d6): d = 3.80 (s, 3 H, OCH3), 7.19 (d, J = 8.2 Hz,
1 H, aromatic), 7.32 (d, J = 8.2 Hz, 1 H, aromatic), 7.46 (dd, J = 8.2,
8.2 Hz, 1 H, aromatic), 7.62 (s, 1 H, CH), 11.01 (s, 1 H, OH).
13C NMR (DMSO-d6): d = 52.47, 115.20, 118.52, 120.79, 124.09,
129.15, 132.29, 133.42, 145.33, 152.52, 163.85.
13C NMR (DMSO-d6): d = 52.76, 114.69, 116.89, 122.53, 124.76,
128.35, 131.76, 132.87, 144.76, 153.52, 163.48.
HRMS (EI): m/z calcd for C11H9NO4: 219.0532; found: 219.0530.
MS: m/z (%) = 255 (33), 253 (95) [M+], 221 (100), 191 (72), 177
(24), 163 (22), 135 (29), 114 (65).
Methyl 5-Chloro-2-hydroxyimino-2H-chromene-3-carboxylate
(7k)
HRMS (EI): m/z calcd for C11H835ClNO4: 253.0142; found:
253.0172.
K2CO3 (207 mg, 1.5 mmol) was added to the solution of 2k (290
mg, 1.0 mmol) in DMF (5 mL) and stirred at r.t. for 2 h. The reaction
mixture was neutralized with dilute aq HCl solution and extracted
with CH2Cl2 (3 × 20 mL). The combined organic layers were dried
over anhyd MgSO4 and the solvent was evaporated in vacuo. The
residue was crystallized with EtOAc to give 7k (167 mg, 66%) as a
yellow solid; mp 243–245 °C.
Methyl 8-Chloro-2-hydroxyimino-2H-chromene-3-carboxylate
(7l)
K2CO3 (207 mg, 1.5 mmol) was added to the solution of 2l (290 mg,
1.0 mmol) in DMF (5 mL) and stirred at r.t. for 6 h. The work-up
procedure was the same as described above to give 7l (127 mg,
50%) as a yellow solid; mp 217–219 °C.
IR (KBr): 3435, 1727, 1646, 1604, 1594, 1450, 1353 cm–1.
IR (KBr): 3395, 1705, 1650, 1612, 1455, 1434, 1373 cm–1.
Synthesis 2005, No. 1, 33–38 © Thieme Stuttgart · New York

PAPER
Synthesis of Methyl (E)-2-Nitromethylcinnamates Derived from Baylis–Hillman Acetates
37
1H NMR (DMSO-d6): d = 3.79 (s, 3 H, OCH3), 7.18 (dd, J = 7.9, 7.9
Hz, 1 H, aromatic), 7.50 (d, J = 7.9 Hz, 1 H, aromatic), 7.58 (d, J =
7.9 Hz, 1 H, aromatic), 7.64 (s, 1 H, CH), 10.95 (s, 1 H, OH).
13C NMR (DMSO-d6): d = 52.53, 119.20, 120.36, 121.48, 124.62,
127.91, 132.25, 132.84, 144.47, 147.99, 163.50.
MS: m/z (%) = 255 (32), 253 (100) [M+], 221 (89), 191 (48), 177
(22), 163 (12), 135 (8), 114 (20).
HRMS (EI): m/z calcd for C11H835ClNO4: 253.0142; found:
253.0151.
13C NMR (CDCl3): d = 52.89, 116.43, 117.84, 117.94, 124.88,
129.55, 134.45, 149.25, 155.21, 156.67, 163.69.
MS: m/z (%) = 204 (79) [M+], 173 (100), 146 (70), 89 (75), 63 (50).
Methyl 5-Chloro-2-oxo-2H-chromene-3-carboxylate (8k)
To a solution of oxime 7k (254 mg, 1.0 mmol) in THF (3 mL) was
added 35% HCl (0.16 mL, 1.5 mmol) and stirred at reflux tempera-
ture for 4 h. The work-up procedure was the same as described
above to afford 8k (150 mg, 63%) as a white solid after it was crys-
tallized with Et2O; mp 135–137 °C.
IR (KBr): 1746, 1720, 1608, 1563, 1450, 1294 cm–1.
Methyl 6-Nitro-2-hydroxyimino-2H-chromene-3-carboxylate
(7m)
NaNO2 (104 mg, 1.5 mmol) was added to the solution of the Baylis–
Hillman acetate 1m (314 mg, 1.0 mmol) in DMF (5 mL) and stirred
at r.t. for 30 min. The reaction mixture was quenched by water (15
mL). The precipitated solid was collected by filtration and dried in
vacuo to give 7m (185 mg, 70%) as a yellow solid; mp 259–260 °C.
1H NMR (CDCl3): d = 3.98 (s, 3 H, OCH3), 7.28 (d, J = 8.2 Hz, 1 H,
aromatic), 7.39 (dd, J = 7.9, 0.9 Hz, 1 H, aromatic), 7.58 (dd, J =
8.2, 8.2 Hz, 1 H, aromatic), 8.90 (s, 1 H, CH).
13C NMR (CDCl3): d = 53.04, 115.59, 116.53, 118.59, 125.45,
134.04, 134.35, 145.14, 155.82, 155.89, 163.24.
MS: m/z (%) = 240 (25), 238 (51) [M+], 207 (100), 180 (54), 123
(34).
HRMS (EI): m/z calcd for C11H735ClO4: 238.0033; found:
238.0047.
IR (KBr): 3423, 1703, 1655, 1613, 1570, 1531, 1514, 1377, 1340,
1292 cm–1.
1H NMR (DMSO-d6): d = 3.83 (s, 3 H, OCH3), 7.41 (d, J = 9.2 Hz,
1 H, aromatic), 7.78 (s, 1 H, CH), 8.29 (dd, J = 9.2, 2.8 Hz, 1 H, ar-
omatic), 8.52 (d, J = 2.8 Hz, 1 H, aromatic), 11.18 (s, 1 H, OH).
13C NMR (DMSO-d6): d = 52.76, 116.55, 119.56, 122.71, 124.80,
127.19, 131.68, 143.36, 144.46, 156.63, 163.45.
Methyl 8-Chloro-2-oxo-2H-chromene-3-carboxylate (8l)
To a solution of oxime 7l (254 mg, 1.0 mmol) in THF (3 mL) was
added 35% HCl (0.16 mL, 1.5 mmol) and stirred at reflux tempera-
ture for 4 h. The work-up procedure was the same as described in
the preparation of 8j to afford 8l (150 mg, 63%) as a white solid af-
ter it was crystallized with Et2O; mp 133–135 °C.
MS: m/z (%) = 264 (100) [M+], 232 (92), 202 (63), 186 (35), 158
(36), 114 (41).
HRMS (EI): m/z calcd for C11H8N2O6: 264.0382; found: 264.0380.
IR (KBr): 1758, 1698, 1614, 1561, 1452, 1316 cm–1.
Methyl 5-Chloro-8-nitro-2-hydroxyimino-2H-chromene-3-car-
boxylate (7n)
1H NMR (CDCl3): d = 3.97 (s, 3 H, OCH3), 7.29 (dd, J = 7.9, 7.6
Hz, 1 H, aromatic), 7.54 (dd, J = 7.6, 1.2 Hz, 1 H, aromatic), 7.73
(dd, J = 7.9, 1.2 Hz, 1 H, aromatic), 8.55 (s, 1 H, CH).
13C NMR (CDCl3): d = 53.13, 118.75, 119.06, 121.81, 125.03,
128.01, 134.64, 148.61, 150.88, 155.42, 163.36.
MS: m/z (%) = 240 (7), 238 (22) [M+], 207 (100), 180 (60), 123 (36).
HRMS (EI): m/z calcd for C11H735ClO4: 238.0033; found:
NaNO2 (104 mg, 1.5 mmol) was added to the solution of the Baylis–
Hillman acetate 1n (348 mg, 1.0 mmol) in DMF (5 mL) and stirred
at r.t. for 10 min. The reaction mixture was quenched by water (10
mL) and extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were dried over anhyd MgSO4 and the solvent was evaporat-
ed in vacuo. The residue was crystallized with EtOAc to give 7n
(143 mg, 48%) as a yellow solid; mp 235–236 °C.
238.0028.
IR (KBr): 3449, 1731, 1641, 1613, 1590, 1571, 1449, 1345, 1255
cm–1.
1H NMR (DMSO-d6): d = 3.82 (s, 3 H, OCH3), 7.49 (d, J = 9.2 Hz,
1 H, aromatic), 7.64 (s, 1 H, CH), 8.07 (d, J = 9.2 Hz, 1 H, aromatic),
11.28 (s, 1 H, OH).
13C NMR (DMSO-d6): d = 52.91, 119.28, 123.47, 124.35, 127.50,
127.64, 135.59, 136.38, 142.82, 146.24, 162.83.
Methyl 6-Nitro-2-oxo-2H-chromene-3-carboxylate (8m)
To a solution of oxime 7m (264 mg, 1.0 mmol) in THF (3 mL) was
added 35% HCl (0.16 mL, 1.5 mmol) and stirred at reflux tempera-
ture for 4 h. The work-up procedure was the same as described in
the preparation of 8j to afford 8m (160 mg, 64%) as a white solid
after it was crystallized with MeOH; mp 219–220 °C. (lit.37 220–
221).
MS: m/z (%) = 300 (33), 298 (100) [M+], 266 (86), 236 (45), 222
IR (KBr): 1779, 1696, 1619, 1570, 1523, 1478, 1349, 1307 cm–1.
(23), 192 (15), 148 (30).
HRMS (EI): m/z calcd for C11H735ClN2O6: 297.9993; found:
297.9985.
1H NMR (CDCl3): d = 4.00 (s, 3 H, OCH3), 7.51 (d, J = 9.1 Hz, 1 H,
aromatic), 8.50 (dd, J = 9.1, 2.5 Hz, 1 H, aromatic), 8.57 (d, J = 2.5
Hz, 1 H, aromatic), 8.62 (s, 1 H, CH).
13C NMR (DMSO-d6): d = 52.71, 117.77, 118.17, 119.18, 126.09,
128.65, 143.65, 147.94, 154.99, 158.09, 162.62.
Methyl 2-Oxo-2H-chromene-3-carboxylate (8j)
To a solution of oxime 7j (219 mg, 1.0 mmol) in THF (3 mL) was
added 35% HCl (0.16 mL, 1.5 mmol) and stirred at reflux tempera-
ture for 4 h. The reaction mixture was concentrated under reduced
pressure and the residue was partitioned between CH2Cl2 (20 mL)
and water (5 mL). The organic layer was separated, dried and evap-
orated in vacuo. The resulting residue was chromatographed on sil-
ica gel eluting with hexane–EtOAc (2:1) to afford 8j (138 mg, 68%)
as a white solid after it was crystallized with Et2O; mp 107–109 °C
(lit.30 107–109).
IR (KBr): 1738, 1703, 1613, 1566, 1459, 1261 cm–1.
1H NMR (CDCl3): d = 3.97 (s, 3 H, OCH3), 7.35–7.39 (m, 2 H, ar-
omatic), 7.62–7.67 (m, 2 H, aromatic), 8.58 (s, 1 H, CH).
MS: m/z (%) = 249 (50) [M+], 218 (100), 191 (51), 172 (48), 88 (31),
62 (25).
Methyl 5-Chloro-8-nitro-2-oxo-2H-chromene-3-carboxylate
(8n)
To a solution of oxime 7n (299 mg, 1.0 mmol) in THF (3 mL) was
added 35% HCl (0.16 mL, 1.5 mmol) and stirred at reflux tempera-
ture for 4 h. The work-up procedure was the same as described in
the preparation of 8j to afford 8n (162 mg, 57%) as a white solid af-
ter it was crystallized with MeOH; mp 210–212 °C.
IR (KBr): 1775, 1711, 1608, 1563, 1536, 1453, 1356, 1266 cm–1.
Synthesis 2005, No. 1, 33–38 © Thieme Stuttgart · New York

38
W. P. Hong, K.-J. Lee
PAPER
1H NMR (CDCl3): d = 4.00 (s, 3 H, OCH3), 7.51 (d, J = 8.6 Hz, 1 H,
aromatic), 8.19 (d, J = 8.6 Hz, 1 H, aromatic), 8.89 (s, 1 H, CH).
13C NMR (DMSO-d6): d = 53.33, 118.30, 119.73, 125.39, 130.41,
135.76, 138.74, 143.85, 148.15, 153.96, 162.54.
MS: m/z (%) = 285 (38), 283 (100) [M+], 252 (87), 225 (34), 206
(17), 178 (21), 150 (16), 122 (14), 87 (34).
HRMS (EI): m/z calcd for C11H635ClNO6: 282.9884; found:
282.9871.
(19) For previously reported synthesis of b-nitro acrylic esters by
means of NaNO2–CAN mediated conversion of Baylis–
Hillman derived acrylic esters, see: Jayakanthan, K.;
Madhusudanan, K. P.; Vankar, Y. D. Tetrahedron 2004, 60,
397.
(20) For reviews of the Baylis–Hillman reaction, see:
(a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
4653. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001. (c) Ciganek, E. In Organic
Reactions, Vol. 51; Paquette, L. A., Ed.; Wiley: New York,
1997, 201. (d) Langer, P. Angew. Chem. Int. Ed. 2000, 39,
3049. (e) Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002, 6,
627. (f) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem.
Rev. 2003, 103, 811.
(21) (a) Song, Y. S.; Lee, C. H.; Lee, K.-J. J. Heterocycl. Chem.
2003, 40, 939. (b) Park, J. B.; Ko, S. H.; Kim, B. G.; Hong,
W. P.; Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25, 27.
(c) Park, J. B.; Ko, S. H.; Hong, W. P.; Lee, K.-J. Bull. Kor.
Chem. Soc. 2004, 25, 927. (d) Lee, C. H.; Lee, K.-J.
Synthesis 2004, 1941.
Acknowledgment
This study was supported by a grant of the Korea Health 21 R & D
Project, Ministry of Health & Welfare, Republic of Korea (01-PJ1-
01CH03-0003).
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Synthesis 2005, No. 1, 33–38 © Thieme Stuttgart · New York