A novel synthesis of oxazolidine-2,4-diones via an efficient fixation of CO2 with 3-aryl-2-alkynamides

Article abstract of DOI:10.1039/c0ob00550a

A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at 30 °C using a CO₂ balloon in the presence of K ₂CO₃ has been developed, which leads to an efficient assembly of oxazolidine-2,4-diones. It i

Full text of DOI:10.1039/c0ob00550a

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PAPER
A novel synthesis of oxazolidine-2,4-diones via an efficient fixation of CO2
with 3-aryl-2-alkynamides†
Guofei Chen, Chunling Fu and Shengming Ma*
Received 7th August 2010, Accepted 29th September 2010
DOI: 10.1039/c0ob00550a
A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at 30 ◦C using a CO2
balloon in the presence of K2CO3 has been developed, which leads to an efficient assembly of
oxazolidine-2,4-diones. It is observed that the regioselectivity was controlled by the aryl group.
Introduction
Recently much attention has been paid to the chemistry of
carbon dioxide as an attractive carbon resource in organic
synthesis. More and more methods for transformations of CO2
into useful organic compounds have been reported.1 In this area,
the reaction of propargyl alcohols and amines with CO2 yielding
cyclic carbonates and urethanes has already been well described
in the literature.2 However, due to the low nucleophilicity of
amide, the fixation of CO2 with amide has seldom been reported.3
On the other hand, we noticed that oxazolidine-2,4-diones are
widely used in medicine and agriculture as antiepileptic agents,4a
anti-inflammatory agents,4b–c herbicides,4f–g and the synthesis
of oxazolidine-2,4-diones is usually lengthy (Fig. 1).4 Besides
transformations from heterocyclic intermediates, the most general
methods are the cyclizations of a-hydroxy esters with urea or iso-
cyanates and a-hydroxy amides with chloroformates or carbonates
(Scheme 1).4a,5 However, the most efficient route to oxazolidine-
Scheme 1 Synthesis of oxazolidine-2,4-diones.
2,4-diones would be from the reactions of 2-alkenamide or 2-
alkynamide with CO2. Recently, we have reported the fixation
of CO2 with 2,3-allenamides under mild conditions to synthesize
1,3-oxazine-2,4-diones (eqn (1)).6 Herein, we wish to report a
simple chemical fixation of CO2 with 3-aryl-2-alkynamides for
unexpected synthesis of oxazolidine-2,4-diones.
(1)
Fig. 1 Some biologically active oxazolidine-2,4-diones.
Results and discussion
We used N-benzyl-3-phenylpropiolamide 1a as the substrate
Laboratory of Molecular Recognition and Synthesis, Department of Chem-
istry, Zhejiang University, Hangzhou 310027, Zhejiang, P. R. China.
E-mail: masm@mail.sioc.ac.cn; Fax: (+86) 21-62609305
† Electronic supplementary information (ESI) available: Spectra. CCDC
reference number 779363. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c0ob00550a
to test the reaction under the CO2 transformation conditions
for the reaction of 2,3-allenamides with CO2.6 Fortunately, we
observed the formation of a new solid compound in 16% yield
determined by 1H NMR spectroscopy (entry 1, Table 1). With the
X-ray diffraction study, we learned that the solid compound was
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Table 1 Optimization of reaction conditions for the reaction of N-benzyl-3-phenylpropiolamide 1a with carbon dioxidea
entry
solvent
base (equiv)
temp. (◦C)
time (h)
yield (%) of 2a
recovery of 1a
1
DMSO
DMSO
DMSO
DMF
1.0
1.0
1.0
2.0
2.0
2.0
3.0
2.0
2.0
70
30
30
30
30
30
30
30
30
3
16
75
0
65
40
75
77
66
0
0
9
100
22
30
0
0
0
93
2
11
11
11
11
11
11
11
11
3b
4
5
6
DMA
DMSO
DMSO
DMSO
DMSO
7
8c
9d
1
a The reaction was carried out using 0.2 mmol of 1a in dried solvent with a CO2 balloon, and the yields were determined by H NMR analysis with
CH2Br2 as the internal standard. b DMSO was commercially available and used without treatment. c The reaction was carried out under CO2 atmosphere.
d The reaction was carried out under N2 atmosphere.
Table 2 Reaction of different 2-alkynamides with carbon dioxidea
oxazolidine-2,4-dione 2a with a single Z configuration but not 1,3-
oxazine-2,4-dione3a as we were expecting(Fig. 2).7 Encouraged by
this result, we optimized the reaction conditions for the chemical
fixation of CO2 with 1a. Some typical reaction conditions are
summarized in Table 1. Due to the possible instability of product
2a, we lowered the reaction temperature to 30 ◦C, and 2a was
formed in 75% yield determined by 1H NMR spectroscopy with 9%
entry
R1
R2
time (h) isolated yield (%) of 2
recovery of starting material 1a within 11 h (entry 2, Table 1). No
reaction occurred with 100% recovery of starting material 1a when
commercial DMSO was used, which shows that a trace amount of
water in DMSO may stop this transformation in the deprotonation
step (entry 3, Table 1). When 2.0 equiv of K2CO3 were used, 2a was
obtained in 75% yield determined by 1H NMR spectroscopy with
complete conversion of the starting material 1a within 11 h (entry
6, Table 1). Increasing the concentration of K2CO3 to 3.0 equiv did
not improve the yield of 2a very much (entry 7, Table 1). Without
the CO2 balloon, the yield of 2a dropped to 66% determined by 1H
NMR spectroscopy under the CO2 atmosphere (entry 8, Table 1).
When the reaction was carried out in the presence of K2CO3 under
N2 atmosphere, the formation of oxazolidine-2,4-dione 2a was not
observed with 93% recovery of the starting material 1a, which
indicated that the CO2 unit in the product 2a was from the CO2
gas, not the carbonate base K2CO3 (entry 9, Table 1).
1
2
3
4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn (1a)
n-Bu (1b)
Et (1c)
allyl (1d)
i-Pr (1e)
i-Pr (1e)
H (1f)
n-Bu (1g)
n-Bu (1h)
n-Bu (1i)
Bn (1j)
n-Bu (1k)
Bn (1l)
11
11
11
11
11
11
11
12
16
11
11
11
11
11
11
11
62 (2a)
80 (2b)
66 (2c)
72 (2d)
68 (2e)
46 (2e)
0
69 (2g)
69 (2h)
67 (2i)
68 (2j)
72 (2k)
61 (2l)
55 (2m)
0
5b,c
6d
7e
8
9
4-PrC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
4-FC6H4
3-thienyl
2-thienyl
cyclohexenyl
n-Bu
10
11
12
13
14b
15f
16g
Bn (1m)
Bn (1n)
Bn (1o)
0
a The reaction was carried out using 0.2 mmol of 1 and 2.0 equiv of
K2CO3 in DMSO (distilled from CaH2) with a CO2 balloon at 30 ◦C
unless otherwise stated. b K2CO3 (3.0 equiv) was used. c Compound 1e was
recovered in 16% yield. d Cs2CO3 (2.0 equiv) was used. e Compound 1f
was recovered in 64% yield. f Compound 1n was recovered in 92% yield.
g Compound 1o was recovered in 100% yield.
the nitrogen atom of 2-alkynamides can be alkyl, benzyl and allyl
groups (entries 1–4, Table 2). When the i-propyl group substituted
2-alkynamide 1e was applied, the product 2e was afforded in 68%
yield with 16% recovery of 1e even using 3.0 equiv of K2CO3
due to the steric effect (entry 5, Table 2). Using a stronger base
such as Cs2CO3, the yield of 2e was 46% though the starting
material 1e was consumed completely (entry 6, Table 2). However,
when 3-phenylpropiolamide 1f was applied, no reaction occurred
with 64% recovery of the starting material (entry 7, Table 2).
Fig. 2 ORTEP representation of 2a.
Some typical results of different 3-aryl-2-alkynamides under the
optimized conditions are listed in Table 2. The substituent R2 on
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The substituent R1 can be phenyl groups bearing both electron-
donating and electron-withdrawing groups (entries 8–12, Table 2).
Heterocyclic aryl groups such as 2- or 3-thienyl group substituted
2-alkynamides could also be applied to the reaction with slightly
lower yields (entries 13 and 14, Table 2). It should be noted that the
reaction of cyclohexenyl substituted propiolamides 1n and n-butyl
substituted propiolamides 1o under the same reaction conditions
did not occur with recovery of starting materials, which shows
the importance of the aryl group moiety for this transformation
(entries 15–16, Table 2).
expanding the substrate scope in this area are being pursued in our
laboratory.
Experimental
Materials
DMSO was distilled from CaH2. THF was distilled from
Na/benzophenone. Et3N was distilled from KOH. The other com-
mercially available chemicals were purchased and used without
additional purification unless noted otherwise.
Based on these facts, a rational mechanism for the formation of
2 is depicted in Scheme 2. The amide 1 would lose a proton under
the basic conditions with K2CO3 to form anionic intermediate
M1, which may attack the carbon atom in carbon dioxide to form
the intermediate M2. There is an issue of regioselectivity (a vs.
b). When the R¢ is an allenyl group, the oxygen anion would
attack the central carbon atom in the allene moiety (b carbon
atom) to form six-membered product 4, which was controlled
by the carbonyl group. However, when the amide was changed
to 3-aryl-2-alkynamide, although both 5-exo-dig and 6-endo-dig
are favored according to the Baldwin’s rule, the oxygen anion in
the intermediate M2 would attack a carbon atom in the C–C
triple bond to form five-membered product 2, which was obviously
directed by the aryl group. This also explains why the aryl group
is so important in this reaction and why the alkyl substituted 2-
alkynamides fail for this reaction.
Synthesis of starting materials
Known compounds 1a,8a 1b,8b 1c,8c 1d,8d 1e,8c 1f,8a 1j,8e 1o8f and
new compounds 1g–1i, 1k–1n were prepared following the known
procedure.8a
N-(n-Butyl)-3-(4-n-propylphenyl)propiolamide (1g). To the re-
action vessel containing ethyl 3-(4-n-propylphenyl)propiolate
(1.0808 g, 5.00 mmol) were added 2 mL of H2O and 2 mL of
n-BuNH2 sequentially, Then the resulting solution was stirred at
room temperature. After 15 h, the reaction was diluted with 25 mL
of CH2Cl2, washed with water twice, and dried over anhydrous
Na2SO4. After filtration and evaporation, chromatography on
silica gel (eluent: petroleum ether/ethyl acetate = 5/1) of the crude
product afforded 1g (1.1213 g, 92%) as a solid, m.p.: 48.0–49.0 ◦C
(n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.51–7.39 (m,
2H, Ar-H), 7.22–7.10 (m, 2H, Ar-H), [5.92 (bs), 5.76 (bs), 1H,
NH], [3.49 (q, J = 6.8 Hz), 3.35 (q, J = 6.7 Hz), 2H, N-CH2], 2.70–
2.50 (m, 2H, Ar-CH2), 1.71–1.47 (m, 4H, 2¥MeCH2), 1.46–1.30
(m, 2H, CH2), 1.01–0.83 (m, 6H, 2¥Me); MS (m/z): 244 (M+ +
1, 2.47), 243 (M+, 14.26), 171 (100); IR (KBr, cm-1): 3285, 2959,
2931, 2866, 2226, 1629, 1537, 1464, 1433, 1410, 1375, 1307, 1223,
1179, 1151, 1112; Anal. Calcd. for C16H21NO: C 78.97, H 8.70, N
5.76; Found: C 79.16, H 8.72, N 6.08%.
N-(n-Butyl)-3-(p-tolyl)propiolamide (1h). Following the pro-
cedure for the preparation of 1g, the reaction of 1.0657 g
(5.67 mmol) of ethyl 3-(p-tolyl)propiolate, 2 mL of H2O and 2
mL of n-BuNH2 afforded 1.0541 g (86%) of 1h (eluent: petroleum
ether/ethyl acetate = 10/1–5/1) as a solid, m.p.: 56.9–57.4 ◦C (n-
1
hexane/CH2Cl2). H NMR (300 MHz, CDCl3) d 7.47–7.37 (m,
2H, Ar-H), 7.22–7.10 (m, 2H, Ar-H), [5.95 (bs), 5.81 (bs), 1H,
NH], [3.48 (q, J = 6.7 Hz), 3.35 (q, J = 6.7 Hz), 2H, N-CH2], [2.38
(s), 2.36 (s), 3H, Ar-CH3], 1.63–1.48 (m, 2H, CH2), 1.48–1.30 (m,
2H, MeCH2), 1.01–0.88 (m, 3H, Me); MS (m/z): 216 (M+ + 1,
1.61), 215 (M+, 10.30), 143 (100); IR (KBr, cm-1): 3271, 2961,
2932, 2872, 2216, 1630, 1534, 1464, 1377, 1353, 1303, 1222, 1209,
1182, 1023; Anal. Calcd. for C14H17NO: C 78.10, H 7.96, N 6.51;
Found: C 77.99, H 7.81, N 6.63%.
Scheme 2 Reaction mechanism.
Conclusions
In conclusion, we have developed a very mild protocol for fixation
of carbon dioxide with 2-alkynamides in DMSO at 30 ◦C using a
CO2 balloon in the presence of K2CO3, which leads to an efficient
assembly of oxazolidine-2,4-diones. The regioselectivity of this
reaction was controlled by the aryl group which is different from
the reaction of 2,3-allenamides with carbon dioxide. As a result
of the easy availability of starting materials, the usefulness of the
products and the efficient fixation of carbon dioxide, this reaction
may have potentials in organic synthesis. Further studies including
N-(n-Butyl)-3-(4-methoxyphenyl)propiolamide (1i). Following
the procedure for the preparation of 1g, the reaction of 1.0130 g
(4.97 mmol) of ethyl 3-(4-methoxyphenyl)propiolate, 2 mL of H2O
and 2 mL of n-BuNH2 afforded 1.1276 g (98%) of 1i as a solid, m.p.:
66.2–67.0 ◦C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d
7.53–7.42 (m, 2H, Ar-H), 6.92–6.80 (m, 2H, Ar-H), 6.02 (bs, 1H,
NH), [3.82 (s), 3.81 (s), 3H, OMe], [3.47 (q, J = 7.0 Hz), 3.34 (q, J =
6.8 Hz), 2H, N-CH2], 1.65–1.48 (m, 2H, CH2), 1.48–1.27 (m, 2H,
MeCH2), 1.00–0.87 (m, 3H, Me); MS (m/z): 232 (M+ + 1, 2.02),
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231 (M+, 13.76), 159 (100); IR (KBr, cm-1): 3269, 3051, 2959, 2925,
2871, 2210, 1630, 1605, 1537, 1510, 1465, 1438, 1287, 1252, 1224,
1172, 1107, 1031; Anal. Calcd. for C14H17NO2: C 72.70, H 7.41, N
6.06; Found: C 72.69, H 7.41, N 6.07%.
MeCH2), 1.00–0.83 (m, 3H, Me); MS (m/z): 206 (M+ + 1, 1.98),
205 (M+, 8.93), 133 (100); IR (neat, cm-1): 3263, 3054, 2931, 2862,
2207, 1633, 1538, 1435, 1360, 1348, 1290, 1265, 1226, 1184, 1137,
1077; Anal. Calcd. for C13H19NO: C 76.06, H 9.33, N 6.82; Found:
C 76.03, H 9.27, N 6.73%.
N-(n-Butyl)-3-(4-fluorophenyl)propiolamide (1k). Following
the procedure for the preparation of 1g, the reaction of 0.9706 g
(5.06 mmol) of ethyl 3-(4-fluorophenyl)propiolate, 2 mL of H2O
and 2 mL of n-BuNH2 afforded 1k with some minor impurity after
purification by chromatography on silica gel (eluent: petroleum
ether/ethyl acetate = 5/1). This product was further purified by
recrystallization to afford 0.9623 g (87%) of 1k (n-hexane/CH2Cl2)
as a solid, m.p.: 59.1–59.5 ◦C (n-hexane/CH2Cl2). 1H NMR
(300 MHz, CDCl3) d 7.60–7.45 (m, 2H, Ar-H), 7.15–6.98 (m, 2H,
Ar-H), [5.97 (bs), 5.85 (s), 1H, NH], [3.48 (q, J = 6.7 Hz), 3.35
(q, J = 6.6 Hz), 2H, N-CH2], 1.65–1.46 (m, 2H, CH2), 1.46–1.29
(m, 2H, MeCH2), 1.00–0.81 (m, 3H, Me); 19F NMR (282 MHz,
CDCl3) d -107.15, -107.61 (standard by frequency conversion
of CDCl3); MS (m/z): 220 (M+ + 1, 1.17), 219 (M+, 7.79), 147
(100); IR (KBr, cm-1): 3304, 2964, 2935, 2868, 2229, 1624, 1598,
1538, 1505, 1471, 1400, 1375, 1351, 1307, 1231, 1157, 1095; Anal.
Calcd. for C13H14FNO: C 71.21, H 6.44, N 6.39; Found: C 71.15,
H 6.45, N 6.35%.
Reactions of 2-alkynamides with CO2
(Z)-3-Benzyl-5-benzylideneoxazolidine-2,4-dione (2a). To the
reaction vessel containing K2CO3 (54.5 mg, 0.39 mmol) were
charged 1a (46.2 mg, 0.20 mmol) and 2 mL of DMSO sequentially
under CO2 atmosphere. The CO2 gas from a CO2 balloon was
dried by passing through a gas washing bottle with conc. H2SO4
and directed through a relief needle fixed with the rubber stopper
to the reaction mixture. The resulting solution was heated at 30 ◦C
with stirring. After 11 h, the reaction was quenched with 10 mL
of H2O, extracted with ether (15 mL ¥ 3), washed with brine, and
dried over anhydrous Na2SO4. After filtration and evaporation,
chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 20/1) of the crude product afforded 2a (34.0 mg, 62%)
◦
1
as a solid, m.p.: 158.2–159.2 C (n-hexane/CH2Cl2). H NMR
(300 MHz, CDCl3) d 7.79–7.70 (m, 2H, Ar-H), 7.50–7.29 (m,
8H, Ar-H), 6.78 (s, 1H, CH), 4.80 (s, 2H, N-CH2); 13C NMR
(75 MHz, CDCl3): d 162.0, 152.0, 137.4, 134.3, 131.1, 130.6, 130.5,
129.0, 128.9, 128.8, 128.5, 113.8, 43.8; MS (m/z): 280 (M+ + 1,
14.65), 279 (M+, 78.90), 118 (100); IR (KBr, cm-1): 1807, 1733,
1674, 1495, 1451, 1433, 1398, 1340, 1309, 1291, 1235, 1170, 1081,
1067; Anal. Calcd. for C17H13NO3: C 73.11, H 4.69, N 5.02; Found:
C 73.20, H 4.72, N 4.96%.
N-Benzyl-3-(3-thienyl)propiolamide (1l). Following the proce-
dure for the preparation of 1g, the reaction of 1.1863 g (6.59 mmol)
of ethyl 3-(3-thienyl)propiolate, 2.5 mL of H2O and 2.5 mL of
BnNH2 afforded 1l with some minor impurity after purification
by chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 5/1–3/1). This product was further purified by re-
crystallization to afford 0.8678 g (54%) of 1l (n-hexane/CH2Cl2)
(Z)-5-Benzylidene-3-(n-butyl)oxazolidine-2,4-dione (2b). Fol-
lowing the procedure for the preparation of 2a, the reaction of
40.1 mg (0.20 mmol) of 1b and 55.8 mg (0.40 mmol) of K2CO3 in
DMSO (2 mL) afforded 39.0 mg (80%) of 2b (eluent: petroleum
ether/ethyl acetate = 25/1) as a solid, m.p.: 82.7–83.4 ◦C (n-
◦
1
as a solid, m.p.: 111.4–112.0 C (n-hexane/CH2Cl2). H NMR
(300 MHz, CDCl3) d 7.68–7.62 (m, 1H, Ar-H), 7.42–7.27 (m, 6H,
Ar-H), 7.20–7.14 (m, 1H, Ar-H), 6.16 (bs, 1H, NH), [4.69 (d, J =
7.2 Hz), 4.54 (d, J = 5.7 Hz), 2H, N-CH2]; MS (m/z): 242 (M+ +
1, 12.00), 241 (M+, 64.86), 135 (100); IR (KBr, cm-1): 3215, 3105,
3036, 2847, 2218, 1625, 1558, 1494, 1452, 1420, 1359, 1294, 1225,
1172, 1089, 1030; Anal. Calcd. for C14H11NOS: C 69.68, H 4.59,
N 5.80; Found: C 69.79, H 4.72, N 6.03%.
1
hexane/CH2Cl2). H NMR (300 MHz, CDCl3) d 7.80–7.71 (m,
2H, Ar-H), 7.50–7.36 (m, 3H, Ar-H), 6.76 (s, 1H, CH), 3.65 (t,
J = 7.4 Hz, 2H, N-CH2), 1.78–1.62 (m, 2H, CH2), 1.46–1.30 (m,
2H, MeCH2), 0.96 (t, J = 7.4 Hz, 3H, Me); 13C NMR (75 MHz,
CDCl3): d 162.4, 152.3, 137.5, 131.0, 130.7, 130.4, 129.0, 113.3,
40.0, 29.6, 19.8, 13.5; MS (m/z): 246 (M+ + 1, 4.12), 245 (M+,
25.65), 118 (100); IR (KBr, cm-1): 1816, 1721, 1666, 1495, 1449,
1413, 1354, 1315, 1264, 1236, 1187, 1082, 1006; Anal. Calcd. for
C14H15NO3: C 68.56, H 6.16, N 5.71; Found: C 68.88, H 6.40, N
5.72%.
N-Benzyl-3-(2-thienyl)propiolamide (1m). Following the pro-
cedure for the preparation of 1g, the reaction of 0.4535 g
(2.52 mmol) of ethyl 3-(2-thienyl)propiolate, 1 mL of H2O and
1 mL of BnNH2 afforded 0.2171 g (36%) of 1m (eluent: petroleum
ether/ethyl acetate = 5/1–3/1) as a solid, m.p.: 107.3–107.6 ◦C
(n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.47–7.21 (m,
7H, Ar-H), 7.07–6.95 (m, 1H, Ar-H), [6.22 (bs), 6.05 (bs), 1H,
NH], [4.67 (d, J = 6.3 Hz), 4.54 (d, J = 5.7 Hz), 2H, N-CH2]; MS
(m/z): 242 (M+ + 1, 9.74), 241 (M+, 50.45), 135 (100); IR (KBr,
cm-1): 3273, 3088, 2207, 1625, 1583, 1552, 1496, 1453, 1425, 1366,
1277, 1231, 1180, 1061, 1029, 1009; Anal. Calcd. for C14H11NOS:
C 69.68, H 4.59, N 5.80; Found: C 69.74, H 4.60, N 6.12%.
(Z)-5-Benzylidene-3-ethyloxazolidine-2,4-dione (2c). Follow-
ing the procedure for the preparation of 2a, the reaction of
34.2 mg (0.20 mmol) of 1c and 55.4 mg (0.40 mmol) of K2CO3
in DMSO (2 mL) afforded 28.4 mg (66%) of 2c (eluent: petroleum
ether/ethyl acetate = 25/1) as a solid, m.p.: 123.6–124.3 ◦C (n-
1
hexane/CH2Cl2). H NMR (300 MHz, CDCl3) d 7.85–7.68 (m,
N-(n-Butyl)-3-cyclohexenylpropiolamide (1n). Following the
procedure for the preparation of 1g, the reaction of 0.9073 g
(5.10 mmol) of ethyl 3-cyclohexenylpropiolate, 2 mL of H2O and 2
mL of n-BuNH2 afforded 0.9200 g (88%) of 1n (eluent: petroleum
ether/ethyl acetate = 3/1) as a liquid. 1H NMR (300 MHz, CDCl3)
d 6.41–6.27 (m, 1H, CH), 5.80 (bs, 1H, NH), [3.38 (q, J =
6.7 Hz), 3.29 (q, J = 6.7 Hz), 2H, N-CH2], 2.21–2.02 (m, 4H,
CH2-C C-CH2), 1.69–1.45 (m, 6H, 3¥CH2), 1.44–1.25 (m, 2H,
2H, Ar-H), 7.52–7.35 (m, 3H, Ar-H), 6.75 (s, 1H, CH), 3.71 (q,
J = 7.2 Hz, 2H, N-CH2), 1.32 (t, J = 7.2 Hz, 3H, Me); 13C NMR
(75 MHz, CDCl3): d 162.1, 152.0, 137.5, 131.0, 130.7, 130.4, 129.0,
113.2, 35.3, 13.0; MS (m/z): 218 (M+ + 1, 5.78), 217 (M+, 43.70),
118 (100); IR (KBr, cm-1): 1813, 1735, 1682, 1496, 1452, 1441,
1415, 1372, 1347, 1320, 1246, 1211, 1169, 1115, 1080, 1045; Anal.
Calcd. for C12H11NO3: C 66.35, H 5.10, N 6.45; Found: C 66.31,
H 5.33, N 6.46%.
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(Z)-3-Allyl-5-benzylideneoxazolidine-2,4-dione (2d). Follow-
ing the procedure for the preparation of 2a, the reaction of 36.7 mg
(0.20 mmol) of 1d and 56.2 mg (0.41 mmol) of K2CO3 in DMSO (2
mL) afforded 32.6 mg (72%) of 2d (eluent: petroleum ether/ethyl
acetate = 15/1) as a solid, m.p.: 79.7–80.5 ◦C (n-hexane/CH2Cl2).
1H NMR (300 MHz, CDCl3) d 7.84–7.68 (m, 2H, Ar-H), 7.50–
7.36 (m, 3H, Ar-H), 6.78 (s, 1H, CH-Ar), 6.00–5.78 (m, 1H,
CH-CH2), 5.45–5.25 (m, 2H, CH2), 4.25 (d, J = 5.7 Hz, 2H,
N-CH2); 13C NMR (75 MHz, CDCl3): d 161.8, 151.8, 137.4, 131.1,
130.6, 130.5, 129.5, 129.0, 119.6, 113.6, 42.2; MS (m/z): 230 (M+
+ 1, 6.03), 229 (M+, 41.47), 118 (100); IR (KBr, cm-1): 1816, 1740,
1682, 1452, 1433, 1403, 1351, 1238, 1176, 1101; Anal. Calcd. for
C13H11NO3: C 68.11, H 4.84, N 6.11; Found: C 68.47, H 5.01, N
5.99%.
cm-1): 2959, 2877, 1817, 1735, 1675, 1608, 1514, 1440, 1404, 1362,
1345, 1318, 1288, 1239, 1161, 1094, 1065, 1042; Anal. Calcd. for
C15H17NO3: C 69.48, H 6.61, N 5.40; Found: C 69.43, H 6.66, N
5.35%.
(Z)-3-(n-Butyl)-5-(4-methoxybenzylidene)oxazolidine-2,4-dione
(2i). Following the procedure for the preparation of 2a, the
reaction of 45.7 mg (0.20 mmol) of 1i and 55.1 mg (0.40 mmol)
of K2CO3 in DMSO (2 mL) afforded 36.7 mg (67%) of 2i (eluent:
petrol◦eum ether/ethyl acetate = 25/1–15/1) as a solid, m.p.: 106.0–
106.6 C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.73–
7.65 (m, 2H, Ar-H), 6.98–6.88 (m, 2H, Ar-H), 6.70 (s, 1H, CH),
3.84 (s, 3H, OMe), 3.63 (t, J = 7.4 Hz, 2H, N-CH2), 1.75–1.61
(m, 2H, CH2), 1.45–1.27 (m, 2H, MeCH2), 0.95 (t, J = 7.5 Hz,
3H, Me); 13C NMR (75 MHz, CDCl3): d 162.5, 161.3, 152.4,
136.0, 132.9, 123.4, 114.4, 113.3, 55.3, 39.9, 29.6, 19.8, 13.5; MS
(m/z): 276 (M+ + 1, 6.32), 275 (M+, 36.31), 148 (100); IR (KBr,
cm-1): 2979, 2952, 2867, 2835, 1814, 1740, 1678, 1603, 1514, 1447,
1408, 1345, 1307, 1257, 1163, 1095, 1064, 1027; Anal. Calcd. for
C15H17NO4: C 65.44, H 6.22, N 5.09; Found: C 65.38, H 6.30,
N 5.03%.
(Z)-5-Benzylidene-3-isopropyloxazolidine-2,4-dione (2e). Fol-
lowing the procedure for the preparation of 2a, the reaction of
37.6 mg (0.20 mmol) of 1e and 82.9 mg (0.60 mmol) of K2CO3 in
DMSO (2 mL) afforded 31.5 mg (68%) of 2e (eluent: petroleum
ether/ethyl acetate = 25/1) as a solid, m.p.: 123.8–125.0 ◦C (n-
hexane/CH2Cl2). The reaction of 37.0 mg (0.20 mmol) of 1e and
132.7 mg (0.41 mmol) of Cs2CO3 in DMSO (2 mL) afforded
(Z)-3-Benzyl-5-(4-methoxybenzylidene)oxazolidine-2,4-dione
(2j). Following the procedure for the preparation of 2a, the
reaction of 53.3 mg (0.20 mmol) of 1j and 55.6 mg (0.41 mmol)
of K2CO3 in DMSO (2 mL) afforded 42.2 mg (68%) of 2j (eluent:
petrol◦eum ether/ethyl acetate = 20/1–10/1) as a solid, m.p.: 117.8–
118.7 C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.75–
7.65 (m, 2H, Ar-H), 7.50–7.40 (m, 2H, Ar-H), 7.40–7.27 (m, 3H,
Ar-H), 6.98–6.88 (m, 2H, Ar-H), 6.73 (s, 1H, CH), 4.78 (s,
2H, N-CH2), 3.84 (s, 3H, OMe); 13C NMR (75 MHz, CDCl3):
d 162.1, 161.3, 152.1, 135.9, 134.5, 133.0, 128.81, 128.77, 128.4,
123.3, 114.5, 113.8, 55.3, 43.6; MS (m/z): 310 (M++1, 13.88), 309
(M+, 68.64), 148 (100); IR (KBr, cm-1): 1805, 1735, 1666, 1601,
1572, 1512, 1455, 1443, 1430, 1401, 1348, 1312, 1259, 1174, 1091,
1070, 1025; Anal. Calcd. for C18H15NO4: C 68.89, H 4.89, N 4.53;
Found: C 69.75, H 5.01, N 4.64%.
1
20.8 mg (46%) of 2e. H NMR (300 MHz, CDCl3) d 7.80–7.69
(m, 2H, Ar-H), 7.50–7.36 (m, 3H, Ar-H), 6.72 (s, 1H, CH),
4.44 (heptet, J = 7.0 Hz, 1H, N-CH), 1.49 (d, J = 7.0 Hz, 6H,
2¥Me); 13C NMR (75 MHz, CDCl3): d 162.2, 151.5, 137.2, 131.0,
130.8, 130.3, 129.0, 112.9, 45.3, 19.4; MS (m/z): 232 (M+ + 1,
5.15), 231 (M+, 34.78), 118 (100); IR (KBr, cm-1): 1815, 1738,
1686, 1666, 1496, 1452, 1403, 1388, 1371, 1347, 1249, 1207, 1181,
1071, 1021, 1002; Anal. Calcd. for C13H13NO3: C 67.52, H 5.67, N
6.06; Found: C 67.48, H 5.73, N 6.11%.
(Z)-3-(n-Butyl)-5-(4-n-propylbenzylidene)oxazolidine-2,4-dione
(2g). Following the procedure for the preparation of 2a, the
reaction of 48.2 mg (0.20 mmol) of 1g and 56.0 mg (0.41 mmol)
of K2CO3 in DMSO (2 mL) afforded 39.3 mg (69%) of 2g (eluent:
petroleum ether/ethyl acetate = 25/1) as a liquid. 1H NMR
(300 MHz, CDCl3) d 7.66 (d, J = 8.4 Hz, 2H, Ar-H), 7.23 (d,
J = 8.4 Hz, 2H, Ar-H), 6.74 (s, 1H, CH), 3.64 (t, J = 7.4 Hz,
2H, N-CH2), 2.61 (t, J = 7.7 Hz, 2H, Ar-CH2), 1.78–1.57 (m, 4H,
2¥MeCH2), 1.46–1.30 (m, 2H, CH2), 1.02–0.89 (m, 6H, 2¥Me);
13C NMR (75 MHz, CDCl3): d 162.4, 152.3, 145.8, 136.9, 131.1,
129.1, 128.2, 113.5, 40.0, 37.9, 29.6, 24.2, 19.8, 13.7, 13.5; MS
(m/z): 288 (M+ + 1, 6.70), 287 (M+, 34.43), 160 (100); IR (neat,
cm-1): 2960, 2925, 2873, 1822, 1738, 1674, 1608, 1511, 1442, 1404,
1371, 1345, 1301, 1246, 1192, 1162, 1092, 1042; HRMS Calcd for
C17H21NO3 (M+): 287.1521, Found: 287.1521.
(Z)-3-(n-Butyl)-5-(4-fluorobenzylidene)oxazolidine-2,4-dione
(2k). Following the procedure for the preparation of 2a, the
reaction of 43.2 mg (0.20 mmol) of 1k and 56.2 mg (0.41 mmol)
of K2CO3 in DMSO (2 mL) afforded 37.2 mg (72%) of 2k (eluent:
petrol◦eum ether/ethyl acetate = 25/1) as a solid, m.p.: 102.6–
103.8 C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.81–
7.69 (m, 2H, Ar-H), 7.18–7.05 (m, 2H, Ar-H), 6.71 (s, 1H, CH),
3.65 (t, J = 7.4 Hz, 2H, N-CH2), 1.78–1.60 (m, 2H, CH2), 1.46–
1.28 (m, 2H, MeCH2), 0.95 (t, J = 7.4 Hz, 3H, Me); 13C NMR
(75 MHz, CDCl3): d 163.6 (d, J = 251.4 Hz), 162.3, 152.2, 137.2
(d, J = 2.7 Hz), 133.1 (d, J = 8.4 Hz), 127.0 (d, J = 3.2 Hz), 116.2
(d, J = 22.7 Hz), 112.0, 40.1, 29.6, 19.8, 13.5; 19F NMR (282 MHz,
CDCl3): d -108.0 (standard by frequency conversion of CDCl3);
MS (m/z): 264 (M+ + 1, 3.56), 263 (M+, 21.57), 136 (100); IR
(KBr, cm-1): 2959, 2873, 1819, 1728, 1674, 1602, 1511, 1447, 1416,
1373, 1356, 1310, 1292, 1239, 1186, 1163, 1085, 1058, 1010; Anal.
Calcd. for C14H14FNO3: C 63.87, H 5.36, N 5.32; Found: C 63.98,
H 5.41, N 5.23%.
(Z)-3-(n-Butyl)-5-(4-methylbenzylidene)oxazolidine-2,4-dione
(2h). Following the procedure for the preparation of 2a, the
reaction of 43.3 mg (0.20 mmol) of 1h and 56.6 mg (0.41 mmol)
of K2CO3 in DMSO (2 mL) afforded 35.8 mg (69%) of 2h (eluent:
petroleum ether/ethyl acetate = 25/1) as a solid, m.p.: 87.0–88.4 ◦C
1
(n-hexane/CH2Cl2). H NMR (300 MHz, CDCl3) d 7.64 (d, J =
8.1 Hz, 2H, Ar-H), 7.23 (d, J = 8.1 Hz, 2H, Ar-H), 6.73 (s, 1H,
CH), 3.64 (t, J = 7.4 Hz, 2H, N-CH2), 2.38 (s, 3H, Ar-Me),
1.77–1.61 (m, 2H, CH2), 1.46–1.25 (m, 2H, MeCH2), 0.95 (t, J =
7.2 Hz, 3H, Me); 13C NMR (75 MHz, CDCl3): d 162.4, 152.3,
141.0, 136.9, 131.0, 129.7, 127.9, 113.4, 39.9, 29.6, 21.5, 19.8, 13.5;
MS (m/z): 260 (M+ + 1, 4.24), 259 (M+, 25.13), 132 (100); IR (KBr,
(Z)-3-Benzyl-5-(thiophen-3-ylmethylene)oxazolidine-2,4-dione
(2l). Following the procedure for the preparation of 2a, the
reaction of 47.9 mg (0.20 mmol) of 1l and 55.1 mg (0.40 mmol)
of K2CO3 in DMSO (2 mL) afforded 34.8 mg (61%) of 2l
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(eluent: petr◦oleum ether/ethyl acetate = 15/1) as a solid, m.p.:
155.9–156.4 C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3)
d 7.83–7.75 (m, 1H, Ar-H), 7.52–7.41 (m, 3H, Ar-H), 7.40–7.28
(m, 4H, Ar-H), 6.84 (s, 1H, CH), 4.78 (s, 2H, N-CH2); 13C NMR
(75 MHz, CDCl3): d 161.9, 151.9, 136.6, 134.4, 132.0, 130.7, 128.9,
128.8, 128.6, 128.5, 126.7, 107.8, 43.8; MS (m/z): 286 (M+ + 1,
16.21), 285 (M+, 100); IR (KBr, cm-1): 3102, 3031, 2947, 1808,
1735, 1674, 1518, 1495, 1456, 1438, 1406, 1354, 1343, 1322, 1249,
1212, 1156, 1090, 1069; Anal. Calcd. for C15H11NO3S: C 63.14, H
3.89, N 4.91; Found: C 63.18, H 4.09, N 4.99%.
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Ikeno and T. Yamada, Eur. J. Org. Chem., 2007, 2604; (h) M. Yoshida, T.
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chia and A. Inesi, Lett. Org. Chem., 2005, 2, 731; (b) M. A. Casadei, F.
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Tetrahedron, 1995, 51, 5891; (e) Using strong bases LDA or n-BuLi,
see: G. M. Coppola and R. E. Damon, J. Heterocycl. Chem., 1995, 32,
1133; (f) A. R. Katritzky, W.-Q. Fan, A. E. Koziol and G. J. Palenik,
Tetrahedron, 1987, 43, 2343; (g) A. R. Katritzky and W.-Q. Fan, Org.
Prep. Proced. Int., 1987, 19, 263; (h) G. M. Coppola and R. E. Damon,
J. Heterocycl. Chem., 1995, 32, 1133.
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T. Connor, W. A. Cetenko, R. J. Sorenson, C. R. Kostlan, J. C. Sircar,
C. D. Wright, D. J. Schrier and R. D. Dyer, J. Med. Chem., 1994, 37,
322; (c) D. A Heerding, L. T. Christmann, T. J. Clark, D. J. Holmes, S.
F. Rittenhouse, D. T. Takata and J. W. Venslavsky, Bioorg. Med. Chem.
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Clark, B. Hulin and R. W. Stevenson, J. Med. Chem., 1991, 34, 1538;
(e) Y. Momose, T. Maekawa, T. Yamano, M. Kawada, H. Odaka, H.
Ikeda and T. Sohda, J. Med. Chem., 2002, 45, 1518; (f) Y.-L. Li, Y.-X.
Song and T.-J. Guo, Cont. Chem. Indu., 2003, 32, 18; (g) Y.-L. Li, W.-R.
Miao and Y.-H. Zhou, Chin. J. Pest., 2005, 44, 503.
(Z)-3-Benzyl-5-(thiophen-2-ylmethylene)oxazolidine-2,4-dione
(2m). Following the procedure for the preparation of 2a, the
reaction of 47.1 mg (0.20 mmol) of 1m and 81.6 mg (0.59 mmol)
of K2CO3 in DMSO (2 mL) afforded 30.7 mg (55%) of 2m (eluent:
petrol◦eum ether/ethyl acetate = 15/1) as a solid, m.p.: 177.2–
178.0 C (n-hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 7.59
(d, J = 4.8 Hz, 1H, Ar-H), 7.53–7.40 (m, 3H, Ar-H), 7.40–7.28 (m,
3H, Ar-H), 7.12 (t, J = 4.4 Hz, 1H, Ar-H), 7.01 (s, 1H, CH),
4.78 (s, 2H, N-CH2); 13C NMR (75 MHz, CDCl3): d 161.5, 151.6,
135.6, 134.4, 133.5, 133.1, 132.0, 128.9, 128.8, 128.5, 128.1, 107.4,
43.8; MS (m/z): 286 (M+ + 1, 13.07), 285 (M+, 74.61), 124 (100); IR
(KBr, cm-1): 3104, 1810, 1728, 1668, 1495, 1457, 1435, 1398, 1344,
1318, 1247, 1231, 1167, 1071, 1051; Anal. Calcd. for C15H11NO3S:
C 63.14, H 3.89, N 4.91; Found: C 63.11, H 3.97, N 5.01%.
5 (a) T. L. Patton, J. Org. Chem., 1967, 32, 383; (b) A. Oku, S. Nakaoji,
T. Kadono and H. Imai, Bull. Chem. Soc. Jpn., 1979, 52, 2966; (c) A.
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Acknowledgements
Financial support from the Major State Basic Research and
Development Program (2009CB825300) and Project for Basic
Research in Natural Science Issued by Shanghai Municipal
Committee of Science (No. 08dj1400100). Shengming Ma is a
Qiu Shi Adjunct Professor at Zhejiang University. We thank Mr.
Suhua Li in this group for reproducing the results presented in
entries 3, 9, and 13 in Table 2.
6 G. Chen, C. Fu and S. Ma, Org. Lett., 2009, 11, 2900.
7 Crystal data for compound 2a: C17H13NO3, MW = 279.28, monoclinic,
space group P2(1)/c, final R indices [I > 2s(I)], R1 = 0.0411, wR2 =
˚
0.0979, R indices (all data) R1 = 0.0487, wR◦2 = 0.1027, a = 6.◦4285(4) A,
◦
˚
˚
b = 31.4664(18) A, c = 7.0702(4) A, a = 90 , b = 106.517(2) , g = 90 ,
V = 1371.16(14) A , T = 173(2) K, Z = 4, reflections collected/unique
3
˚
15862/2426 (Rint = 0.0299), number of observations [I > 2s(I)]
2086, parameters: 190. Supplementary crystallographic data have been
deposited at the Cambridge Crystallographic Data Center. CCDC
779363.
8 (a) S. A. Jr. Lang and E. Cohen, J. Med. Chem., 1975, 18, 441; (b) Y.
Iwanami, Nippon Kagaku Zasshi, 1962, 83, 600; (c) A. Yokoyama, K.
Ashida and H. Tanaka, Chem. Pharm. Bull., 1964, 12, 690; (d) H.
Jiang, S. Ma, G. Zhu and X. Lu, Tetrahedron, 1996, 52, 10945; (e) H.
Imase, K. Noguchi, M. Hirano and K. Tanaka, Org. Lett., 2008,
10, 3563; (f) G. T. Crisp and M. J. Millan, Tetrahedron, 1998, 54,
637.
Notes and references
1 For a most recent review, see: T. Sakakura, J.-C. Choi and H. Yasuda,
Chem. Rev., 2007, 107, 2365.
2 For recent reports, see: (a) M. Yoshida and M. Ihara, Angew. Chem.,
Int. Ed., 2001, 40, 616; (b) M. Shi and Y.-M. Shen, J. Org. Chem., 2002,
67, 16; (c) M. Yoshida, M. Fujita, T. Ishii and M. Ihara, J. Am. Chem.
Soc., 2003, 125, 4874; (d) M. Yoshida, M. Fujita and M. Ihara, Org.
110 | Org. Biomol. Chem., 2011, 9, 105–110
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The Royal Society of Chemistry 2011
©