Triethylamine Hydroiodide as a Bifunctional Catalyst for the Solvent-Free Synthesis of 2-Oxazolidinones

Article abstract of DOI:10.1002/ejoc.202000771

Among the wide variety of heterocycles, 2-oxazolidinones are recognized as some of the most important heterocyclic compounds in medicinal chemistry. Therefore, the development of a practical method for their synthesis would be an important development. He

Full text of DOI:10.1002/ejoc.202000771

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Triethylamine Hydroiodide as a Bifunctional Catalyst for the
Solvent-Free Synthesis of 2-Oxazolidinones
Authors: Ryuichi Nishiyori, Ken Okuno, and Seiji Shirakawa
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000771
Link to VoR: https://doi.org/10.1002/ejoc.202000771
01/2020

10.1002/ejoc.202000771
European Journal of Organic Chemistry
FULL PAPER
Triethylamine Hydroiodide as a Bifunctional Catalyst for the
Solvent-Free Synthesis of 2-Oxazolidinones
Ryuichi Nishiyori,[a] Ken Okuno,[a] and Seiji Shirakawa*[a]
[a]
R. Nishiyori, K. Okuno, Prof. Dr. S. Shirakawa
Department of Environmental Science, Graduate School of Fisheries and Environmental Sciences
Nagasaki University
1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
E-mail: seijishirakawa@nagasaki-u.ac.jp
Homepage: http://seijishirakawa.wix.com/greenchemistry
Supporting information for this article is given via a link at the end of the document.
Abstract: Among the wide variety of heterocycles, 2-oxazolidinones
are recognized as some of the most important heterocyclic
compounds in medicinal chemistry. Therefore, the development of a
practical methods for their synthesis would be an important
development. Herein, we report a practical method for the synthesis
of 2-oxazolidinones under solvent-free conditions using triethylamine
hydroiodide as a simple and effective bifunctional organocatalyst.
O
O
O
O
N
Ar
O
N
O
N
O
N
Me
CF3
Me
F
R
HO
1
AcHN
linezolid
toloxatone
O
O
O
O
N
O
N
O
Cl
O
N
H
S
HO
Introduction
N
MeO
befloxatone
N
rivaroxaban
O
N
N
Five-membered heterocycles are very important structural units
for drug design.[1] Among the wide variety of five-membered
heterocycles, 2-oxazolidinones 1 are recognized as some of the
most important heterocyclic compounds in medicinal chemistry.
Many important pharmaceuticals have been designed and
prepared based on a 2-oxazolidinone core (Scheme 1).[2] For
example, anticoagulant agent, rivaroxaban ranked as one of the
top-selling drugs. Thus, the development of an efficient and
practical method for the synthesis of 2-oxazolidinones 1 would be
important in the field of synthetic organic chemistry. In the course
of our recent study on the development of practical methods for
the synthesis of five-membered cyclic carbonates from epoxides
and carbon dioxide using triethylamine hydroiodide as a simple
and effective bifunctional catalyst,[3–5] we became interested in the
synthesis of 2-oxazolidinones 1 under a similar catalytic system.
The coupling reactions of epoxides 2 and aryl isocyanates 3 under
S
N
O
N
O
N
O
N
O
N
F
F
AcHN
sutezolid
tedizolid
HO
Triethylamine Hydroiodide as a Bifunctional Catalyst
previous work (Ref. 3)
Brønsted acidic site
O
O
C
+
Et3N
H I
O
Et
O
O
N
no solvent
N
H
Et
O
R
O
O
1
Et
I
R
2
R
Et3N
H I
Ar
O
+
O
C
no solvent
this work
Ar
nucleophilic site
N
3
R
the influence of
a
triethylamine hydroiodide provides 2-
economical catalyst, metal-free, solvent-free, atom-economical reaction
oxazolidinones 1 without the formation of by-products.[6] Herein,
we report a practical and efficient method for the synthesis of 2-
oxazolidinones under solvent and metal-free environmentally
benign conditions with an economical and readily available
triethylamine hydroiodide catalyst.
Scheme 1. Important 2-oxazolidinones and our synthetic approach.
Results and Discussion
Our initial aim was to clarify the catalytic activity of triethylamine
hydroiodide as a bifunctional organocatalyst in the synthesis of 2-
oxazolidinone 1a (Scheme 2). The reaction proceeds under very
simple conditions. A mixture of glycidyl phenyl ether 2a, phenyl
isocyanate 3a (1.1 equiv), and triethylamine hydroiodide (10
mol %) was heated at 100 °C. After stirring the mixture for 20 min
1
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10.1002/ejoc.202000771
European Journal of Organic Chemistry
FULL PAPER
at 100 °C, we obtained the target product 1a in an 83% yield.[7]
We next investigated the effects of anions in the bifunctional
catalyst. The catalytic activity of ammonium salts largely depends
on the halide anion, and bromide and chloride anions showed a
lower level of catalytic activity compared with that of the iodide
anion. The reaction using triethylamine hydrobromide provided
O
O
Ar
Et
O
N
R
H
I
N
2
Et
1
R
Et
Et
Et
H
N
O
product 1a in
a moderate yield (44%), but triethylamine
H
N
Et
Et
hydrochloride could only produce 1a in a low yield (12%). The use
of halide anions resulted in a similar trend during our previous
study of the cyclic carbonate synthesis.[3] It should be noted that
no target product was obtained when the reaction was performed
without a catalyst.
Et
O
O
Et
N
Ar
I
R
R
A
C
I
Et
H
N
Et
O
O
Et
C
catalyst
(10 mol %)
O
R
I
N
3
O
O
Ar
Ph
+
O
N
C
Ph
B
PhO
N
no solvent
100 ºC, 20 min
PhO
2a
3a
1a
Scheme 3. Assumed catalytic cycle.
Effect of anion
Et3N
H
I
Et3N H Br
Et3N H Cl
without catalyst
~0%
With the assumed catalytic cycle in hand, the substrate
generality of epoxides 2 was examined with phenyl isocyanate 3a
under the influence of the triethylamine hydroiodide catalyst
(Scheme 4). Epoxides containing various functional groups could
be applied to this reaction. The target 2-oxazolidinones 1a–1g
were obtained in good to high yields as a result of the reaction at
100 °C for 1 h under solvent-free conditions.[8] The present
catalytic system could be applied to the reaction with 2,2-
83%
44%
12%
Control experiments
Et3N
16%
H
I
Et4N
I
Bu4N
24%
I
6%
<5%
Scheme 2. Effect of ammonium salt catalysts.
disubstituted epoxide. We could obtain
a disubstituted 2-
oxazolidinone 1h in a moderate yield as a result of the reaction
for 20 h. It should be mentioned that several 2-oxazolidinone
products in Scheme 4 have been reported as biologically active
compounds.[9]
To clarify the importance of the bifunctional properties of
triethylamine hydroiodide, several control experiments were
examined (Scheme 2). When the reactions were performed with
either triethylamine or hydroiodic acid catalysts, target 2-
oxazolidinone 1a was obtained in low yields (16 and 6%,
respectively). In addition, the catalytic activities of
tetraalkylammonium iodides were compared with that of
Et3N
(10 mol %)
H I
O
triethylamine
hydroiodide.[6a,k]
The
reactions
using
O
O
Ph
+
O
N
C
Ph
N
no solvent
100 ºC, 1 h
tetraethylammonium and tetrabutylammonium iodide catalysts
proceeded slowly under the reaction conditions to provide 1a in
low yields (<5 and 24%, respectively). These results clearly
suggested that both an iodide counter anion and an acidic
hydrogen on the nitrogen of the triethylamine hydroiodide catalyst
were essential to achieve good catalytic performance.
R
2
3a
1
R
O
O
O
Ph
Ph
N
Ph
O
N
O
O
N
PhO
BnO
Cl
1a
1b
1c
86%
81%
87%
Based on the results listed in Scheme 2, the assumed
catalytic cycle for the present reaction using the triethylamine
hydroiodide catalyst was proposed, and it appears in Scheme 3.
In this cycle, epoxide 2 is activated via a hydrogen-bonding
interaction with an acidic hydrogen on the catalyst, as proven in
our previous study (intermediate A).[3] The activated epoxide then
undergoes nucleophilic attack from an iodide anion to form
intermediate B. The nucleophilic alkoxide anion in intermediate B
attacks isocyanate 3 to yield intermediate C. The intramolecular
ring-closing of intermediate C affords the target 2-oxazolidinone 1
with a regeneration of the triethylamine hydroiodide catalyst. The
positive effect of the iodide anion in comparison with other halide
anions in Scheme 2 can be explained by a lower ability to
coordinate with an acidic hydrogen (intermediate A) and by the
ability of the higher leaving groups (intermediate C).
O
O
O
Ph
Ph
Ph
O
N
O
N
O
N
O
1d
82%
1e
71%
1f
72%
O
O
Ph
Ph
O
O
N
O
N
Cl
N
Me
1h
1g
92%
O
56% (20 h)
Scheme 4. Scope of epoxides 2.
2
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10.1002/ejoc.202000771
European Journal of Organic Chemistry
FULL PAPER
The reaction was also performed with styrene oxide 2b
under standard reaction conditions (Scheme 5). Although the
reaction of styrene oxide 2b and phenyl isocyanate 3a was
efficiently promoted using a triethylamine hydroiodide catalyst, we
obtained not only the target 2-oxazolidinone 1i (51% yield) but
also regioisomer 1i’ (29% yield). Regioisomeric products such as
a 1i’ are generally observed in reactions with styrene oxide
derivatives.[6]
Et3N
(10 mol %)
H I
O
O
O
O
Ph
O
N
+
+
C
C
Ph
Ph
PhO
N
no solvent
100 ºC, 1 h
PhO
(S)-2a
(99% ee)
3a
(S)-1a
85% (99% ee)
O
Et3N
(10 mol %)
H I
O
Ph
O
N
BnO
N
no solvent
100 ºC, 1 h
BnO
(R)-2c
3a
(R)-1b
80% (99% ee)
Et3N
H I
O
O
(99% ee)
(10 mol %)
O
O
Ph
Ph
O
N
N
O
+
C
Ph
+
N
Ph
no solvent
100 ºC, 1 h
Scheme 7. Synthesis of optically active 2-oxazolidinones.
Ph
Ph
1i’
2b
3a
1i
51%
29%
Conclusion
Scheme 5. Reaction with styrene oxide 2b.
In summary, we successfully developed a practical method for the
synthesis of medicinally important 2-oxazolidinones by using
triethylamine hydroiodide as a simple, yet effective, bifunctional
organocatalyst. The atom-economical coupling reactions of
epoxides and isocyanates with triethylamine hydroiodide
proceeded under solvent-free conditions. The importance of the
bifunctional feature of the catalyst was clarified in the control
experiments. Additionally, the present catalytic system could be
applied to the asymmetric synthesis of chiral 2-oxazolidinones.
The reported reaction system is one of the most economical
processes yet documented for the efficient synthesis of 2-
oxazolidinones.
The scope of aryl isocyanates 3 was also investigated
(Scheme 6).[10] A series of aryl isocyanates 3 possessing electron-
donating and -withdrawing functionalities at the para, meta, and
ortho positions could be applied to the reaction with glycidyl
phenyl ether 2a under the influence of triethylamine hydroiodide
catalyst to provide 2-oxazolidinones 1j–1n in good yields.
Arylsulfonyl isocyanates could also be applied to this reaction
system to provide products 1o and 1p in excellent yields.
Et3N
(10 mol %)
H I
O
O
O
Ar
+
O
N
C
Ar
PhO
PhO
N
no solvent
100 ºC, 1 h
Experimental Section
PhO
2a
3
1
General Procedure for the Reaction of Epoxides 2 and Isocyanates 3
Catalyzed by Triethylamine Hydroiodide. A mixture of epoxide 2 (2.0
mmol), isocyanate 3 (2.2 mmol), and triethylamine hydroiodide (0.20 mmol,
10 mol %) was heated to 100 °C and stirred for 1 h. After cooling to room
temperature, the reaction mixture was purified by flash column
chromatography on silica gel (hexane/EtOAc or hexane/CH2Cl2 as eluent)
to afford the corresponding 2-oxazolidinone 1.
O
O
O
OMe
PhO
NO2
O
N
O
N
O
N
O2N
PhO
N
1j
82%
1k
73%
1l
80%
O
O
Cl
O
O
N
O
O
F
5-(Phenoxymethyl)-3-phenyl-oxazolidin-2-one (1a):[6] 1H NMR (400
MHz, CDCl3) δ 7.58 (dd, J = 0.8, 8.8 Hz, 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.30
(dt, J = 1.2, 8.2 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H),
6.92 (dd, J = 0.8, 8.4 Hz, 2H), 4.96–5.01 (m, 1H), 4.18–4.27 (m, 3H), 4.08
(dd, J = 6.0, 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 158.0, 154.4, 138.1,
129.6, 129.1, 124.2, 121.7, 118.3, 114.6, 70.3, 67.8, 47.4; IR (neat): 1738,
1506, 1499, 1414, 1254, 1225, 752, 744 cm–1. (S)-1a:[6] [α]21D +59.7 (c =
0.90, CHCl3, 99% ee); HPLC analysis: Daicel Chiralpak IC-3, hexane/2-
propanol = 3:1, flow rate = 0.5 mL/min, 254 nm; retention time: 57.0 min
(minor) and 73.1 min (major).
PhO
PhO
PhO
1m
81%
1n
82%
O
O
Me
Cl
O
S
O
S
N
N
O
O
PhO
1o
99%
1p
96%
Scheme 6. Scope of isocyanates 3.
5-(Benzyloxymethyl)-3-phenyl-oxazolidin-2-one (1b):[6] 1H NMR (400
MHz, CDCl3) δ 7.54 (dd, J = 1.2, 8.4 Hz, 2H), 7.28–7.40 (m, 7H), 7.14 (t, J
= 7.2 Hz, 1H), 4.75–4.81 (m, 1H), 4.64 (d, J = 12.0 Hz, 1H), 4.60 (d, J =
11.6 Hz, 1H), 4.07 (dd, J = 8.8, 8.8 Hz, 1H), 3.93 (dd, J = 6.4, 8.8 Hz, 1H),
3.73 (d, J = 4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 154.5, 138.2, 137.3,
129.0, 128.5, 127.9, 127.7, 123.9, 118.1, 73.7, 71.2, 70.0, 47.2; IR (neat):
1743, 1504, 1408, 1223, 1129, 1104, 753 cm–1. (R)-1b:[6] [α]19D –32.3 (c =
0.80, CHCl3, 99% ee); HPLC analysis: Daicel Chiralpak IC-3, hexane/2-
propanol = 3:1, flow rate = 0.5 mL/min, 214 nm; retention time: 73.0 min
(minor) and 78.1 min (major).
To expand the utility of the present reaction system using
triethylamine hydroiodide as a bifunctional catalyst, enantiopure
epoxides (S)-2a and (R)-2c were submitted to produce optically
active 2-oxazolidinones (Scheme 7). To our delight, optically pure
2-oxazolidinones (S)-1a and (R)-1b were obtained in good yields
with retention of the chirality.
3
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10.1002/ejoc.202000771
European Journal of Organic Chemistry
FULL PAPER
5-(Chloromethyl)-3-phenyl-oxazolidin-2-one (1c):[6] 1H NMR (400 MHz,
CDCl3) δ 7.55 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 8.8 Hz, 2H), 7.17 (t, J = 8.0
Hz, 1H), 4.84–4.91 (m, 1H), 4.18 (dd, J = 8.8, 9.6 Hz, 1H), 3.97 (dd, J =
6.0, 9.6 Hz, 1H), 3.80 (dd, J = 4.4, 11.6 Hz, 1H), 3.75 (dd, J = 6.8, 11.6 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 153.9, 137.7, 129.1, 124.3, 118.3, 70.8,
70.3, 67.9, 55.5, 47.9; IR (neat): 1732, 1519, 1253, 1244, 1226, 1147,
1095, 1085, 1042, 988, 819, 755 cm–1
.
3-(4-Nitrophenyl)-5-(phenoxymethyl)-oxazolidin-2-one (1k):[11] 1H
NMR (400 MHz, CDCl3) δ 8.28 (d, J = 9.6 Hz, 2H), 7.77 (d, J = 9.6 Hz, 2H),
7.31 (t, J = 8.0 Hz, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H),
48.0, 44.6; IR (neat): 1742, 1502, 1408, 1307, 1225, 1128, 748 cm–1
.
5.03–5.09 (m, 1H), 4.23–4.30 (m, 3H), 4.17 (dd, J = 5.6, 8.8 Hz, 1H); 13
C
5-(Allyloxymethyl)-3-phenyl-oxazolidin-2-one (1d):[6] 1H NMR (400
MHz, CDCl3) δ 7.56 (dd, J = 0.8, 8.8 Hz, 2H), 7.38 (t, J = 8.0 Hz, 2H), 7.14
(t, J = 7.6 Hz, 1H), 5.84–5.94 (m, 1H), 5.20–5.32 (m, 2H), 4.75–4.81 (m,
1H), 4.06–4.10 (m, 3H), 3.95 (dd, J = 6.4, 8.8 Hz, 1H), 3.67–3.74 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 154.5, 138.2, 133.9, 129.0, 123.9, 118.1,
117.7, 72.6, 71.2, 70.0, 47.2; IR (neat): 1744, 1503, 1409, 1223, 1131,
NMR (100 MHz, CDCl3) δ 157.8, 153.8, 143.6, 143.4, 129.7, 125.0, 122.0,
117.4, 114.6, 70.6, 67.6, 47.0; IR (neat): 1741, 1597, 1515, 1505, 1491,
1403, 1329, 1304, 1214, 1146, 753 cm–1
.
3-(2-Nitrophenyl)-5-(phenoxymethyl)-oxazolidin-2-one (1l): 1H NMR
(400 MHz, CDCl3) δ 8.04 (d, J = 8.8 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.46–
7.50 (m, 2H), 7.32 (t, J = 8.4 Hz, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.96 (d, J =
8.0 Hz, 2H), 5.06–5.12 (m, 1H), 4.24–4.30 (m, 3H), 4.09 (dd, J = 5.6, 8.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 157.9, 155.3, 145.3, 133.9, 131.1,
129.6, 128.0, 127.6, 125.8, 121.6, 114.5, 71.9, 67.6, 49.1; IR (neat): 1752,
1529, 1490, 1413, 1354, 1225, 1153, 747, 733 cm–1; HRMS (FAB) calcd
for C16H14N2O5: 314.0903 ([M]+), found 314.0903.
1107, 754 cm–1
.
5-(3-Buten-1-yl)-3-phenyl-oxazolidin-2-one (1e):[11] 1H NMR (400 MHz,
CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.38 (t, J = 8.0 Hz, 2H), 7.14 (t, J = 7.6
Hz, 1H), 5.78–5.89 (m, 1H), 5.04–5.14 (m, 2H), 4.63–4.70 (m, 1H), 4.09
(dd, J = 8.4, 8.8 Hz, 1H), 3.67 (dd, J = 6.8, 8.8 Hz, 1H), 2.20–2.36 (m, 2H),
1.94–2.03 (m, 1H), 1.78–1.87 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 154.7,
138.2, 136.5, 128.9, 123.8, 118.0, 115.9, 72.2, 50.3, 34.1, 28.7; IR (neat):
3-(4-Chlorophenyl)-5-(phenoxymethyl)-oxazolidin-2-one (1m):[6] 1H
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 9.6 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H),
7.30 (t, J = 8.0 Hz, 2H), 7.01 (t, J = 7.6 Hz, 1H), 6.91 (d, J = 7.6 Hz, 2H),
4.96–5.03 (m, 1H), 4.23 (d, J = 4.4 Hz, 2H), 4.18 (dd, J = 8.8, 8.8 Hz, 1H),
4.06 (dd, J = 6.0, 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 157.9, 154.2,
136.7, 129.6, 129.4, 129.1, 121.8, 119.4, 114.5, 70.4, 67.7, 47.2; IR (neat):
1741, 1503, 1407, 1218, 1130, 912, 754, 729 cm–1
.
5-Hexyl-3-phenyl-oxazolidin-2-one (1f):[11] 1H NMR (400 MHz, CDCl3) δ
7.54 (dd, J = 0.8, 8.8 Hz, 2H), 7.38 (t, J = 8.0 Hz, 2H), 7.13 (t, J = 7.2 Hz,
1H), 4.60–4.67 (m, 1H), 4.08 (dd, J = 8.4, 8.8 Hz, 1H), 3.66 (dd, J = 6.8,
8.4 Hz, 1H), 1.68–1.91 (m, 2H), 1.25–1.55 (m, 8H), 0.90 (t, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 154.9, 138.3, 128.9, 123.8, 118.1, 73.0, 50.4,
35.0, 31.5, 28.8, 24.4, 22.4, 14.0; IR (neat): 2953, 2917, 2855, 1738, 1721,
1737, 1498, 1251, 1224, 1146, 1096, 754 cm–1
.
3-(3-Fluorophenyl)-5-(phenoxymethyl)-oxazolidin-2-one (1n): 1H NMR
(400 MHz, CDCl3) δ 7.48 (td, J = 2.4, 11.2 Hz, 1H), 7.28–7.37 (m, 4H),
7.01 (t, J = 7.6 Hz, 1H), 6.91 (dd, J = 0.8, 8.8 Hz, 2H), 6.86 (ddt, J = 0.8,
2.4, 8.0 Hz, 1H), 4.97–5.03 (m, 1H), 4.23 (d, J = 4.4 Hz, 2H), 4.19 (dd, J =
8.8, 8.8 Hz, 1H), 4.06 (dd, J = 6.0, 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 163.0 (d, J = 244 Hz), 157.9, 154.1, 139.6 (d, J = 10.7 Hz), 130.2 (d, J =
9.1 Hz), 129.6, 121.8, 114.6, 113.2 (d, J = 3.3 Hz), 110.8 (d, J = 21.4 Hz),
105.8 (d, J = 27.2 Hz), 70.4, 67.7, 47.2; IR (neat): 1735, 1590, 1496, 1405,
1252, 1227, 1093, 756 cm–1; HRMS (FAB) calcd for C16H14FNO3:
287.0958 ([M]+), found 287.0958.
1505, 1416, 1233, 1147, 756, 747 cm–1
.
3-Phenyl-5-(phthalimidomethyl)-oxazolidin-2-one (1g):[6] 1H NMR (400
MHz, CDCl3) δ 7.86–7.90 (m, 2H), 7.73–7.78 (m, 2H), 7.52 (d, J = 7.6 Hz,
2H), 7.37 (t, J = 8.0 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 4.95–5.02 (m, 1H),
4.12–4.18 (m, 2H), 3.98 (dd, J = 5.6, 14.4 Hz, 1H), 3.92 (dd, J = 5.6, 9.2
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.9, 153.9, 137.8, 134.3, 131.6,
128.9, 124.1, 123.5, 118.2, 69.5, 48.2, 40.7; IR (neat): 1750, 1742, 1709,
1414, 1398, 1389, 1225, 1138, 1040, 754, 725, 713 cm–1
.
5-(Chloromethyl)-5-methyl-3-phenyl-oxazolidin-2-one (1h): 1H NMR
(400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.16
(t, J = 7.2 Hz, 1H), 4.11 (d, J = 9.2 Hz, 1H), 3.77 (d, J = 9.2 Hz, 1H), 3.74
(d, J = 11.2 Hz, 1H), 3.63 (d, J = 11.2 Hz, 1H), 1.67 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 153.5, 137.9, 129.0, 124.2, 118.2, 77.3, 53.4, 49.2, 24.1;
IR (neat): 1739, 1503, 1405, 1319, 1216, 1146, 1094, 751 cm–1; HRMS
(FAB) calcd for C11H12ClNO2: 225.0557 ([M]+), found 225.0557.
5-(Phenoxymethyl)-3-tosyl-oxazolidin-2-one (1o):[6] 1H NMR (400 MHz,
CDCl3) δ 7.97 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.26 (t, J = 8.4
Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H), 4.83–4.87 (m,
1H), 4.21 (dd, J = 8.8, 9.2 Hz, 1H), 4.06–4.14 (m, 3H), 2.47 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 157.6, 151.3, 145.8, 134.1, 129.9, 129.5, 128.2,
121.9, 114.5, 71.5, 67.3, 46.2, 21.7; IR (neat): 1773, 1372, 1245, 1173,
1145, 1095, 1044, 814, 747 cm–1
.
3,5-Diphenyl-oxazolidin-2-one (1i):[6] 1H NMR (400 MHz, CDCl3) δ 7.56
(d, J = 8.4 Hz, 2H), 7.36–7.45 (m, 7H), 7.15 (t, J = 7.6 Hz, 1H), 5.64 (dd, J
= 7.6, 8.4 Hz, 1H), 4.38 (dd, J = 8.8, 8.8 Hz, 1H), 3.97 (dd, J = 7.6, 9.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 154.6, 138.03, 138.00, 128.98. 128. 91,
125.6, 124.0, 118.2, 73.9, 52.5; IR (neat): 1744, 1502, 1400, 1369, 1222,
3-(4-Chlorobenzenesulfonyl)-5-(phenoxymethyl)-oxazolidin-2-one
(1p): H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz, 2H), 7.55 (d, J =
1
8.8 Hz, 2H), 7.27 (t, J = 8.0 Hz, 2H), 7.00 (t, J = 7.2 Hz, 1H), 6.69 (d, J =
8.0 Hz, 2H), 4.85–4.91 (m, 1H), 4.22 (dd, J = 8.8, 9.2 Hz, 1H), 4.06–4.16
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 157.5, 151.2, 141.3, 135.5, 129.62,
129.57, 121.9, 114.4, 71.8, 67.3, 46.1; IR (neat): 1779, 1371, 1172, 1145,
1084, 751, 730 cm–1; HRMS (FAB) calcd for C16H15ClNO5S: 368.0359
([M+H]+), found 368.0359.
1210, 1136, 984, 751 cm–1
.
3,4-Diphenyl-oxazolidin-2-one (1i’):[6] 1H NMR (400 MHz, CDCl3) δ
7.23–7.40 (m, 9H), 7.06 (t, J = 7.6 Hz, 1H), 5.39 (dd, J = 5.6, 8.8 Hz, 1H),
4.77 (dd, J = 8.8, 8.8 Hz, 1H), 4.19 (dd, J = 5.6, 8.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 155.9, 138.2, 137.0, 129.3. 128.85, 128.77, 126.2, 124.6,
120.8, 69.8, 60.6; IR (neat): 1744, 1500, 1394, 1354, 1209, 1125, 1046,
Acknowledgements
756 cm–1
.
We thank Professor Satoshi Minakata (Osaka University) for
valuable comments regarding the present work. This work was
supported by JSPS KAKENHI Grant Number JP19K05480, by the
Cooperative Research Program of "Network Joint Research
Center for Materials and Devices" (20201298), and by Takahashi
Industrial and Economic Research Foundation. This work was the
result of using research equipment shared in MEXT Project for
3-(4-Methoxyphenyl)-5-(phenoxymethyl)-oxazolidin-2-one (1j):[6] 1H
NMR (400 MHz, CDCl3) δ 7.47 (d, J = 9.2 Hz, 2H), 7.31 (t, J = 8.4 Hz, 2H),
7.00 (t, J = 7.6 Hz, 1H), 6.90–6.95 (m, 4H), 4.94–4.99 (m, 1H), 4.15–4.25
(m, 3H), 4.03 (dd, J = 5.6, 8.8 Hz, 1H), 3.81 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.0, 156.4, 154.7, 131.2, 129.6, 121.7, 120.3, 114.6, 114.3,
4
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10.1002/ejoc.202000771
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Kuo, S. M. Sur, G. D. Hartman, Bioorg. Med. Chem. Lett. 2010, 20, 3129–
promoting public utilization of advanced research infrastructure
(Program for supporting introduction of the new sharing system)
Grant Numbers JPMXS0422500320 and JPMXS0422300120.
3133.
[10] Unfortunately, alkyl isocyanates provided the target 2-oxazolidinone
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Keywords: Bifunctional catalysts • Green chemistry •
Heterocycles • Organocatalysis • Sustainable chemistry
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10.1002/ejoc.202000771
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Entry for the Table of Contents
(Key topic) Oxazolidinone Synthesis
O
O
Et3N
H I
R
Ar
O
N
+
O
no solvent
C
Ar
N
R
Brønsted acidic site
Et
economical catalyst
metal-free
solvent-free
N
H
Et
O
Et
atom-economical
I
R
nucleophilic site
This efficient synthesis of 2-oxazolidinones from epoxides and isocyanates features the use of triethylamine hydroiodide as a simple
and effective bifunctional organocatalyst.
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