Proline-catalyzed synthesis of 5-aryl-2-oxazolidinones from carbon dioxide and aziridines under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2010.521903

Natural a-amino acids were proven to be ecofriendly and recyclable catalysts for the carboxylation of aziridines with CO₂ without utilization of any organic solvents or additives. Notably, a series of 5-aryl-2-oxazolidinones were obtained in go

Full text of DOI:10.1080/00397911.2010.521903

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Proline-Catalyzed Synthesis of 5-Aryl-2-
oxazolidinones from Carbon Dioxide and
Aziridines Under Solvent-Free Conditions
Xiao-Yong Dou a , Liang-Nian He a & Zhen-Zhen Yang a
a State Key Laboratory and Institute of Elemento-Organic
Chemistry , Nankai University , Tianjin , China
Accepted author version posted online: 27 Jun 2011.Published
online: 14 Sep 2011.
To cite this article: Xiao-Yong Dou , Liang-Nian He & Zhen-Zhen Yang (2012) Proline-Catalyzed
Synthesis of 5-Aryl-2-oxazolidinones from Carbon Dioxide and Aziridines Under Solvent-Free
Conditions, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 42:1, 62-74, DOI: 10.1080/00397911.2010.521903
To link to this article: http://dx.doi.org/10.1080/00397911.2010.521903
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Synthetic Communications1, 42: 62–74, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.521903
PROLINE-CATALYZED SYNTHESIS OF 5-ARYL-2-
OXAZOLIDINONES FROM CARBON DIOXIDE AND
AZIRIDINES UNDER SOLVENT-FREE CONDITIONS
Xiao-Yong Dou, Liang-Nian He, and Zhen-Zhen Yang
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin, China
GRAPHICAL ABSTRACT
Abstract Natural a-amino acids were proven to be ecofriendly and recyclable catalysts for
the carboxylation of aziridines with CO2 without utilization of any organic solvents or addi-
tives. Notably, a series of 5-aryl-2-oxazolidinones were obtained in good yield together with
excellent chemo- and regioselectivity under mild conditions using proline as the catalyst.
Notably, the catalyst could be recycled more than five times after a simple separation pro-
cedure without appreciable loss of catalytic activity. This process represents a promising
strategy for homogeneous catalyst recycling.
Keywords 5-Aryl-2-oxazolidinones; aziridines; carbon dioxide; proline
INTRODUCTION
Oxazolidinones are important compounds in synthetic and medicinal chemis-
try, that can be widely used as chiral auxiliaries,[1–3] intermediates in organic syn-
thesis,[4–8] and building blocks for biologically active pharmaceutical agents.[9–14]
Currently, there are three main protocols for the synthesis of oxazolidinones from
C1 resources: (i)carbonylation of amino alcohols using phosgene, CO, etc.;[15–21]
(ii) reaction of propargylamines or propargylic alcohols with CO2; [22–26] (iii) carbox-
ylation of aziridines with CO2.[27–39] Recently, Li et al. demonstrated that the oxazo-
lidinones can be synthesized through the copper-catalyzed coupling of aldehydes,
amines, terminal alkynes, and CO2.[40] Method (iii) is a high-atom-efficiency reac-
Received February 23, 2010.
Address correspondence to Liang-Nian He, State Key Laboratory and Institute of
Elemento-organic Chemistry, Nankai University, Tianjin 300071, China. E-mail: heln@nankai.edu.cn
62

SYNTHESIS OF 5-ARYL-2-OXAZOLIDINONES
63
tion, utilizing renewable, abundant, and nontoxic CO2 as a building block, and it has
attracted much attention from the viewpoint of green chemistry. In past decades,
numerous homogeneous catalytic systems including salen Cr(III)=dimethylamino-
pyridine (DMAP),[27] phenol=DMAP,[28] alkali metal halide[29,30] or tetraalkyl-
ammonium halide system,[31] iodine,[32 33] PEG6000NBu4Br,[37] zirconyl chloride,[38]
,
and a-amino acid[39] have been reported to be effective for the coupling of aziridines
and CO2. Besides, an electrochemical procedure is an alternative for this transform-
ation.[34] Nonetheless, poisonous solvent is generally required to achieve a good
yield. Halides or other toxic components such as phenol and DMAP are required
in most of the catalysts and=or cocatalysts, thus creating a negative effect on the
environment. On the other hand, it is difficult to separate a homogeneous catalyst
from the product. Therefore, development of a biocompatible, recyclable catalytic
system for solvent-free synthesis of 5-substituted oxazolidinones is highly desirable
and still remains a challenge.
As readily accessible chiral molecules, natural a-amino acids possess the merits
of diverse structures, low cost, high thermal stability, biocompatibility, easy regener-
ation, and biodegradability. Many catalytic reactions have been smoothly performed
using amino acids as catalysts or auxiliaries.[41–45] In particular, proline is a remark-
able candidate for the asymmetric reactions.[46–50] Amino acid with a carbonyl and
an amino group can behave both as an acid and a base to facilitate chemical reac-
tions. Jiang et al. reported the synthesis of cyclic carbonates from CO2 and epoxides
catalyzed by amino acids.[41] In the framework of our continuous effort to chemically
fix CO2, herein we report an efficient process for the synthesis of 5-aryl-2-oxazolidi-
nones via coupling reaction of CO2 and aziridine by employing amino acids as
efficient and recyclable catalysts.
RESULTS AND DISCUSSION
The reaction of 1-ethyl-2-phenylaziridine 1a with CO2 was chosen as the
model reaction to investigate the catalytic performance of diverse a-amino acids
(Scheme 1).
As shown in Table 1, the reaction barely took place without any catalyst (entry
1, Table 1). Among the surveyed amino acids, L-proline gave the greatest yield of 2a
under identical reaction conditions (entry 13 vs. entries 2–12), which is presumably
because of its unique molecular structure.[46] As a pyrrolidine-based amino acid, pro-
line with a secondary amino group is able to be dissolved in the reaction mixture,
whereas other amino acids could act as heterogeneous catalysts, which was
confirmed by the phase behavior of the reaction visually inspected through a
sapphire window attached to the autoclave.
Scheme 1. Carboxylation of aziridine with CO2 catalyzed by different amino acids.

64
X.-Y. DOU, L.-N. HE, AND Z.-Z. YANG
Table 1. Carboxylation of 1-ethyl-2-phenylaziridine 1a with CO2 catalyzed by
different amino acidsa
Entry
Catalyst
Conv. (%)b
Yield of 2a (%)b
Regio-sel. (%)c
1
2
None
L-Arginine
L-Lysine
2
17
10
29
18
31
17
17
19
14
15
40
57
Trace
—
5
8
96:4
95:5
94:6
95:5
95:5
95:5
95:5
94:6
95:5
92:8
96:4
94:6
3
4
L-Glutamic acid
L-Valine
L-Serine
6
5
8
6
7
7
L-Alanine
5
8
L-Tryptophan
L-Phenylalanine
L-Histidine
L-Glutamine
L-Cysteine
L-Proline
5
9
4
10
11
12
13
5
8
6
32
aReaction conditions: amino acids (0.1 mmol, 5 mol% with respect to 1a), 1a
(294 mg, 2 mmol), 110 ꢀC, 6 MPa, 1 h.
bThe conversion of 1a and the yield of 2a were determined by GC using
biphenyl as an internal standard.
cMolar ratio of 2a to 3a.
The reaction conditions were also optimized with 5 mol% L-proline as the cata-
lyst. The reaction was performed at 110 ꢀC under 6 MPa CO2 pressure. The results
listed in Table 2 reveal that the reaction proceeded smoothly within first 8 h
(Table 2, entries 1–4). It is worth mentioning that within 8 h, almost full conversion
together with 91% yield of 2a was obtained, and the regioselectivity was 93:7 (2a=3a).
Moreover, the yield and selectivity were almost invariant when the reaction time was
prolonged to 12 h (entry 4 vs. 5). In other words, a reaction time of 8 h is required to
complete the reaction. It is also interesting that the chemoselectivity of 2a also rose
from 56% to 91% as reaction time was prolonged from 1 to 8 h, which could be
explained by backbiting from the oligomers or copolymerization between aziridines
and CO2, as depicted in the literature.[36–38,51,52]
The effect of reaction temperature on the reaction was studied at the pressure
of 6 MPa for 8 h (entries 4, 6, and 7). The reaction temperature had a remarkable
effect on the reactivity. The yield of 2a was increased from 64% to 91% with tem-
perature rising from 90 to 110 ꢀC (entries 6 vs. 4). The by-products were found
to be slight amounts of 1,4-diethyl-2,5-diphenylpiperazine and 1,4-diethyl-2,3-
diphenylpiperazine (i.e., dimers of 2a,) gas chromatography–mass spectrometry
detected by (GC-MS) and 1H NMR (see the experimental section). There was no sig-
nificant change at a higher reaction temperature (entry 7). This reaction is also very
sensitive to CO2 pressure. When CO2 pressure was varied from 2 to 6 MPa, yield of
2a increased from 70% to 91% (entries 8 and 4). While higher pressure may suppress
the interaction between the substrate and the catalyst, and it may also cause a low
concentration of aziridine around the catalyst, thereby leading to lower activity
(entry 9).[37] Furthermore, a series of catalytic cycles were performed to survey the
reusability of the catalyst (entries 10–14). The particular polarity of proline could
provide a convenient protocol for the catalyst recovery. In each cycle, the catalyst

SYNTHESIS OF 5-ARYL-2-OXAZOLIDINONES
65
Table 2. Effects of reaction parameters on the reactiona
Entry
Time=h
Temp.=ꢀC
Pressure=MPa
Conv. (%)b
Yield (%)c
Regio-sel. (%)d
1
2
1
3
110
110
110
110
110
90
6
6
57
91
32
53
80
91
91
64
92
70
66
92
92
93
92
93
42
17
92:8
94:6
94:6
93:7
94:6
92:8
93:7
96:4
92:8
94:6
94:6
96:4
95:5
96:4
92:8
92:8
3
6
6
>99
>99
>99
83
4
8
6
5
12
8
6
6
6
7
8
130
110
110
110
110
110
110
110
110
110
6
>99
82
8
8
2
9
8
13
6
86
10e
11f
12g
13h
14i
15j
16k
8
100
>99
>99
>99
>99
51
8
6
8
6
8
6
8
6
8
6
8
6
37
aReaction conditions: 1a (294 mg, 2 mmol) and proline (0.1 mmol, 5 mmol% relative to 1a).
bDetermined by GC.
cThe yield of 2a.
dMolar ratio of 2a to 3a.
eThe first run of the catalyst, proline (20 mmol% with respect to 1a).
fThe second run of the catalyst.
gThe third run of the catalyst.
hThe fourth run of the catalyst.
iThe fifth run of the catalyst.
jThe catalyst loading was 1 mol%.
kThe catalyst loading was 3 mol%.
could be easily precipitated by addition of ether, recovered by simple filtration, and
reused for the next run without further purification under the same conditions. The
results listed in Table 2 indicate that no significant drop in either 2a yield or selec-
tivity was detected after five successive cycles. On the other hand, the influence of
catalyst loading on 2a synthesis was also tested. As easily seen, the catalyst amount
has a considerable influence on 2a yield in the range of 1 to 5 mol% (entries 4, 15, and
16). In particular, yield of 2a was 17% when 1 mol% catalyst was used, also indicat-
ing that catalyst leaching would be negligible. Therefore, easy recovery of the cata-
lyst (proline) from the product offers a nice strategy for homogeneous catalyst
recycling.
The utility and generality of proline were also examined. As shown in Table 3,
the cycloaddition reactions of various aziridines with CO2 were conducted under the
optimized reaction conditions (Scheme 2). It was revealed that steric hindrance of the
N-substituted group cause lower activity (Table 3, entries 1, and 3–7). A relatively
poor yield was obtained when the substrate was 1-methyl-2-phenylaziridine (1b).
This is understandable because highly active aziridine is prone to form self-oligomers
(entry 2). The aziridines with electron-withdrawing or electron-donating substituent
groups on the aryl ring were good substrates (entries 9 and 10). However, the nature
of R1 of the substrates would play a key role in dominating the selective formation of

66
X.-Y. DOU, L.-N. HE, AND Z.-Z. YANG
Table 3. Substrate scopea
Entry
Substrate
Time (h)
Conv. (%)b
Yield of 2a–k (%)b
Regio-sel. (%)c
1
2
1a
1b
1c
1d
1e
1f
8
12
10
12
12
12
12
12
8
>99
93
96
70
91
86
24
25
61
89
89
92
94
97:3
90:10
95:5
95:5
98:2
94:6
94:6
94:6
95:5
96:4
2:98
3
>99
95
4
5
26
33
6
7
1g
1h
1i
69
8
100
96
9
10
11
1j
1k
8
12
98
99
aReaction conditions: proline (0.1 mmol, 5 mol% with respect to the substrate), the
substrate (2 mmol), 110 ꢀC, 6 MPa.
bDetermined by GC.
cMolar ratio of 2 and 3.
4- or 5-substituted oxazolidinones. When R1 was altered to an alkyl-like group,
4-substituted oxazolidinone could be obtained with high regioselectivity (2:98) (entry
11), which would be explained by the proposed mechanism as outlined in Scheme 3.
In other words, the aryl group of R1 favors the formation of 5-substituted
2-oxazolidinone 2 while the alkyl group is preferable for producing 4-substituted
isomer 3, which is in good agreement with the previous literature.[27,31,37]
Based on the experimental results and previous reports,[31,37] a hypothetic reac-
tion mechanism for the coupling of CO2 with aziridines is proposed as depicted in
Scheme 3. It has three steps: first, aziridine coordinates with CO2 to form the inter-
mediate (step 1); then nucleophilic attack at the 2 or 3 position by the carboxylate
ion of the proline leads to ring opening of the aziridine (step 2), and finally oxazo-
lidinone is formed by subsequent intramolecular ringclosure and the catalyst is
Scheme 2. L-Proline-catalyzed cycloaddition reaction of CO2 to aziridines.

SYNTHESIS OF 5-ARYL-2-OXAZOLIDINONES
67
Scheme 3. Proposed mechanism.
regenerated (step 3).[41] Aziridine coordination with CO2 is the rate-dominating step,
which is in accordance with substituted group effect on the activity. Substrates bear-
ing bulk-substituted groups on the N atom could hinder interaction of aziridine and
CO2, thus leading to lower activity as a result of the steric hindrance. Interestingly,
there exist two different cycles (A or B) depending on the nature of R1. The cation
intermediate favors a more stable state, and the positive-charge center transfers to
the more substituted carbon when R1 is an aryl group or stays on the nitrogen atom
when R1 is an alkyl group, resulting in two ring-opening ways and 4- or 5-substituted
isomers.
CONCLUSIONS
In conclusion, natural a-amino acids were proven to be biocompatible catalysts
for carboxylation of aziridines with CO2 under solvent-free conditions. Proline
exhibited higher reactivity than other surveyed a-amino acids. The catalyst can be
conveniently recovered, and excellent catalyst performance was retained after five
successive recycles. This process represents a simple and green protocol for highly
efficient synthesis of oxazolidinones.
EXPERIMENTAL
Reagents
The amino acids were commercially supplied by Guangfu Chemical
Reagents Co. Ltd. Diethyl ether was freshly distilled over sodium under nitrogen.

68
X.-Y. DOU, L.-N. HE, AND Z.-Z. YANG
Dichloromethane was distilled from calcium hydride. Silica gel (particle size 200–300
mesh) in this study was commercially supplied by Qingdao Haiyang Chemical
Reagents Co. Ltd. Other reagents were analytical grade and were used as received.
Aziridines Preparation
Aziridines 1a–j were prepared according to the published methods,[53] as shown
in Scheme 4.
The typical procedure is described. The bromine (32.0 g, 0.2 mol) in dry
CH2Cl2 (40 mL) was added dropwise over 30 min to an ice-cooled 40 mL CH2Cl2
solution of dimethyl sulfide (12.4 g, 0.2 mol). During the addition, light orange crys-
tals of bromodimethyl sulfonium bromide began to separate. After addition of bro-
mine, the orange crystals S1 were collected by filtration and then washed with dry
diethyl ether and dried under vacuum. Yield: 80%, mp 80 ꢀC (dec).
Olefin (160 mmol) was added dropwise to the 160 mL CH3CN solution of S1
(35.56 g, 160 mmol) in an ice-water bath. During the addition, the white solid began
to separate. The solution was further stirred for 10 min. The crystals S2 were
collected by filtration and dried under vacuum. Yield: 32–38.6%.
A solution of amine (20–50 mmol) in water was added dropwise to a stirred sol-
ution of compound S2 (10 mmol) in 20 mL of H2O at rt, and the resulting mixture
was stirred overnight. The mixture was added to 20 mL of saturated brine, extracted
with diethyl ether (3 ꢁ 20 mL), dried with anhydrous MgSO4 overnight, and evapo-
rated under reduced pressure. Aziridine was obtained by distillation under reduced
pressure. Yield: 85–100%.
Aziridine (1k) was synthesized according to the published procedure.[37]
Carboxylation of Aziridines with CO2
In a typical reaction, the carboxylation of aziridines with CO2 was carried out
in a 25-mL stainless steel autoclave. Amino acid (0.1 mmol) and aziridine (2 mmol)
were charged into the reactor at room temperature. CO2 was introduced into the
autoclave, and then the mixture was stirred at a predetermined temperature for
15 min to reach equilibration. The pressure was then adjusted to the desired pressure,
and the mixture was stirred continuously. When the reaction finished, the reactor
was cooled in ice water, and CO2 was ejected slowly. An aliquot of sample was taken
Scheme 4. Preparation of N-alkyl phenylaziridines (1a–j).

SYNTHESIS OF 5-ARYL-2-OXAZOLIDINONES
69
from the resultant mixture and dissolved in dry CH2Cl2 for GC analysis [GC analy-
ses were performed on a Shimadzu GC-2014, equipped with a capillary column
(RTX-5, 30 m ꢁ 0.25 mm ꢁ 0.25 mm) using a flame ionization detector]. The residue
was purified by column chromatography on silica gel (eluting with 8:1 to 1:1 pet-
roleum ether=ethyl acetate) to afford the product. The products were further ident-
1
ified by H NMR, 13C NMR, and MS, which are consistent with those reported in
the literature[27,37] and in good agreement with the assigned structures.
Spectral Characteristics of the Products
1H NMR and 13C NMR spectra were recorded on a Bruck 300 or Varian
Mercury-Plus 400 spectrometer in CDCl3. Chemical shifts were given as d values
referenced in parts per million (ppm) from tetramethylsilane (TMS) as an internal
standard. GC-MS was measured on a Finnigan HP G1800A. Liquid chromato-
graphy–mass spectrometry (LC-MS) was performed on a Thermo Finnigan LCQ
Advantage spectrometer in electrospray ionozation (ESI) model (ESI-MS) with
spray voltage 4.8 kV and atmospheric pressure chemical ionization (APCI-MS).
High-resolution mass spectrometry (HRMS) was conducted using an Ionspec
7.0 T spectrometer by the ESI-FTICR technique. Melting points were measured
on an X4 apparatus and uncorrected. Spectral characteristics of the products (oxa-
zolidinones 2a–k) in Table 3 were provided as follows:
3-Ethyl-5-phenyloxazolidin-2-one (2a). Colorless liquid; 1H NMR
(300 MHz, CDCl3): d 1.17 (t, J ¼ 7.2 Hz, 3H), 3.29–3.45 (m, 3H), 3.92 (t, J ¼ 8.7 Hz,
1H), 5.48 (t, J ¼ 7.8 Hz, 1H), 7.34–7.42 (m, 5H). 13C NMR (75 MHz, CDCl3): d 12.4,
38.8, 51.5, 74.2, 125.4, 128.6, 128.8, 138.8, 157.5. MS (ESI) calcd. for C11H13NO2
191.09 found 192.29 (M þ H)þ, 214.38 (M þ Na)þ, 405.01 (2M þ Na)þ.
3-Ethyl-4-phenyloxazolidin-2-one (3a). Colorless liquid; 1H NMR
(300 MHz, CDCl3): d 1.05 (t, J ¼ 5.4 Hz, 3H), 2.79–2.88 (m, 1H), 3.48–3.57(m,
1H), 4.10 (t, J ¼ 6.0 Hz, 1H), 4.62 (t, J ¼ 6.6 Hz, 1H), 4.81 (t, J ¼ 5.4 Hz, 1H), 7.30
ꢂ7.44 (m, 5H). 13C NMR (75 MHz, CDCl3): d 12.1, 36.9, 59.4, 69.8, 127.0, 129.0,
129.2, 137.9, 158.1. MS (ESI) calcd. for C11H13NO2 191.09; found 192.29 (M þ H)þ,
214.38 (M þ Na)þ.
3-Methyl-5-phenyloxazolidin-2-one (2b). White crystals. Mp. 50–52 ꢀC. 1H
NMR (300 MHz, CDCl3): d 2.89 (s, 3H), 3.42 (t, J ¼ 8.4 Hz, 1H), 3.90 (t, J ¼ 8.4 Hz,
1H), 5.45 (t, J ¼ 8.0 Hz, 1H), 7.33–7.38 (m, 5H). 13C NMR (75 MHz, CDCl3): d 30.7,
54.0, 73.0, 125.3, 128.5, 128.6, 138.4, 157.9. ESI-MS calcd. for C10H11NO2 177.08,
found 178.21 (M þ H)þ, 200.25 (M þ Na)þ, 377.00 (2M þ Na)þ.
5-Phenyl-3-propyloxazolidin-2-one (2c). Colorless liquid. 1H NMR
(300 MHz, CDCl3): d 0.91 (t, J ¼ 7.2 Hz, 3H), 1.52–1.61 (m, 2H), 3.18–3.31 (m,
2H), 3.40 (t, J ¼ 8.0 Hz, 1H), 3.90 (t, J ¼ 8.8 Hz, 1H), 5.46 (t, J ¼ 8.0 Hz, 1H),
7.31–7.37 (m, 5H). 13C NMR (75 MHz, CDCl3): d 10.7, 20.3, 45.5, 51.8, 74.0,
125.2, 128.4, 128.5, 138.7,157.6. ESI-MS calcd. for C12H15NO2 205.11; found
206.30 (M þ H)þ, 228.30 (M þ Na)þ, 433.04 (2M þ Na)þ.

70
X.-Y. DOU, L.-N. HE, AND Z.-Z. YANG
3-Butyl-5-phenyloxazolidin-2-one (2d). Colorless liquid. 1H NMR
(300 MHz, CDCl3): d 0.94 (t, J ¼ 7.2 Hz, 3H), 1.31–140 (m, 2H), 1.51–1.58 (m,
2H), 3.23–3.38 (m, 2H), 3.43 (t, J ¼ 8.0 Hz, 1H), 3.92 (t, J ¼ 8.8 Hz, 1H), 5.49 (t,
J ¼ 8.0 Hz, 1H), 7.28–7.42 (m, 5H). 13C NMR (75 MHz, CDCl3): d 13.4, 19.5,
29.1, 43.6, 51.8, 74.1, 125.2, 128.4,128.5, 138.7, 157.7. ESI-MS calcd. for
C13H17NO2 219.13; found 220.34 (M þ H)þ, 259.48 (MþK)þ, 461.05 (2M þ Na)þ.
3-Isopropyl-5-phenyloxazolidin-2-one (2e). Colorless liquid. 1H NMR
(300 MHz, CDCl3): d 1.16 (d, J ¼ 6.8 Hz, 3H), 1.22 (d, J ¼ 6.8 Hz, 3H), 3.37 (t,
J ¼ 8.0 Hz, 1H), 3.87 (t, J ¼ 8.8 Hz, 1H), 4.13–4.23 (m, 1H), 5.48 (t, J ¼ 8.0 Hz,
1H), 7.34–7.42 (m, 5H). 13C NMR (75 MHz, CDCl3): d 19.1, 19.6, 44.5, 47.0, 74.2,
125.1, 128.3, 128.5, 138.7,156.7. ESI-MS calcd. for C12H15NO2 205.11; found
206.29 (M þ H)þ, 433.08 (2M þ Na)þ.
3-Cyclopropyl-5-phenyloxazolidin-2-one
(2f). White
crystals;
mp
1
52–55 ꢀC. H NMR (300 MHz, CDCl3) d 0.75 (s, 4H), 2.55–2.59 (m, 1H), 3.43 (t,
J ¼ 8.1 Hz, 1H), 3.88 (t, J ¼ 8.7 Hz, 1H), 5.42 (t, J ¼ 8.1 Hz, 1H), 7.28–7.37 (m,
5H). 13C NMR (75 MHz, CDCl3) d 5.4, 5.8, 25.7, 53.3, 74.3, 125.4, 128.6, 128.7,
138.5, 157.9. ESI-MS calcd. for C12H13NO2 203.09; found 429.27 (2M þNa)þ,
631.80 (3M þ Na)þ.
3-Isobutyl-5-phenyloxazolidin-2-one (2g). White crystals; mp 38–42 ꢀC.
1H NMR (300 MHz, CDCl3): d 0.91 (d, J ¼ 4.8 Hz, 3H), 0.93 (d, J ¼ 4.8 Hz, 3H),
1.81–1.95 (m, 1H), 3.02–3.16 (m, 2H), 3.42 (dd, J ¼ 8.7 Hz, J ¼ 7.5 Hz, 1H), 3.91
(t, J ¼ 8.7 Hz, 1H),5.48 (t, J ¼ 8.4 Hz, 1H), 7.32–7.41 (m, 5H). 13C NMR (75 MHz,
CDCl3): d 19.7, 19.8,26.7, 51.6, 52.6, 74.1, 125.3, 128.5, 128.7, 138.8, 158.0. ESI-MS
calcd. for C13H17NO2 219.13; found 461.22 (2M þ Na)þ, 679.70 (3M þNa)þ.
HRMS: calcd. for C13H17NO2 (M þH)þ 220.1332; found 220.1339.
3-Isopentyl-5-phenyloxazolidin-2-one (2h). Colorless liquid. 1H NMR
(300 MHz, CDCl3): d 0.92 (d, J ¼ 3.3 Hz, 3H), 0.94 (d, J ¼ 3.3 Hz, 3H), 1.43 (q,
J ¼ 7.5 Hz, 2H), 1.54–1.65 (m, 1H), 3.22–3.36 (m, 2H), 3.41 (t, J ¼ 7.8 Hz, 1H),
3.91 (t, J ¼ 8.7 Hz, 1H), 5.46 (t, J ¼ 8.1 Hz, 1H), 7.33–7.39 (m, 5H). 13C NMR
(75 MHz, CDCl3): d 22.2, 22.3,25.6, 35.9, 42.4, 52.0, 74.2, 125.3, 128.6, 128.7,
138.8, 157.7. ESI-MS calcd. for C14H19NO2 233.14; found 489.17 (2M þ Na)þ,
721.97 (3M þ Na)þ. HRMS: calcd. for C14H19NO2 (M þ H)þ 234.1489; found
234.1489.
3-Ethyl-5-p-tolyloxazolidin-2-one (2i). White crystals; mp 49–53 ꢀC. 1H
NMR (300 MHz, CDCl3): d 1.18 (t, J ¼ 7.2 Hz, 3H), 2.36 (s, 3H), 3.29–3.45 (m,
3H), 3.89 (t, J ¼ 8.7 Hz, 1H), 5.45 (t, J ¼ 8.1 Hz, 1H), 7.19–7.24 (m, 4H). 13C
NMR (75 MHz, CDCl3): d12.6, 21.2, 38.9, 51.6, 74.4, 125.6, 129.5, 135.9, 138.7,
157.7. ESI-MS calcd. for C12H15NO2 205.11; found 206.15 (M þ H)þ, 433.92
(2M þ Na)þ.
5-(4-Chlorophenyl)-3-ethyloxazolidin-2-one (2j). White crystals; mp
1
73–77 ꢀC. H NMR (300 MHz, CDCl3): d 1.18 (t, J ¼ 15 Hz, 3H), 3.32–3.42 (m,
3H), 3.92 (t, J ¼ 9 Hz, 1H), 5.46 (t, J ¼ 6 Hz, 1H), 7.28–7.40 (m, 4H). 13C NMR
(75 MHz, CDCl3): d 12.5, 38.9,51.5, 73.5, 126.9, 129.1, 134.6, 137.4, 157.3, 162.3.
ESI-MS calcd. for C11H12NO2Cl 225.06; found 226.17 (M þ H)þ.

SYNTHESIS OF 5-ARYL-2-OXAZOLIDINONES
71
3-Benzyl-4-(chloromethyl)oxazolidin-2-one (2k). Colorless liquid. 1H
NMR (300 MHz, CDCl3): d 3.52 (d, 2H), 3.86–3.94 (m, 1H), 4.17 (d, J ¼ 15.3 Hz,
1H), 4.24 (t, J ¼ 8.9 Hz, 1H), 4.23 (q, J ¼ 9.0 Hz, J ¼ 5.3 Hz, 1H), 4.82 (d,
J ¼ 15.3 Hz, 1H), 7.29–7.37 (m, 5H). 13C NMR (75 MHz, CDCl3): d 43.4, 46.5,
54.8, 65.3, 128.1, 128.3, 129.0, 135.5, 158.0. ESI-MS calcd for C11H12NO2Cl
225.67; found 472.90 (2M þ Na)þ. HRMS: calcd. for C11H12NO2Cl (M þ Na)þ
248.0449; found 248.0454.
1,4-Diethyl-2,5-diphenylpiperazine. White crystals; mp 115–119 ꢀC. 1H
NMR (400 MHz, CDCl3) d 0.91 (t, J ¼ 7.2 Hz, 6H), 1.99–2.05 (m, 2H), 2.30 (t,
J ¼ 10.8 Hz, 2H), 2.54–2.62 (m, 2H), 3.08 (dd, J ¼ 11.6 Hz, J ¼ 2.4 Hz, 2H), 3.45
(dd, J ¼ 2.0 Hz, J ¼ 12.0 Hz, 2H), 7.29–7.43 (m, 10H). LC-MS calcd. for C20H26N2
294.21; found 295.35 (M þ H)þ.
1
1,4-Diethyl-2,3-diphenylpiperazine. Colorless liquid. H NMR (400 MHz,
CDCl3) d 1.01 (t, J ¼ 7.2 Hz, 6H), 2.17–2.26 (m, 2H), 2.26–2.33 (m, 2H), 2.65–2.69
(m, 2H), 2.95–2.99 (q, J ¼ 6.0 Hz, 2H), 3.73 (s, 2H), 7.27–7.38 (m, 6H), 7.69–7.71
(d, J ¼ 7.2 Hz, 4H). LC-MS calcd. for C20H26N2 294.21; found 295.31(M þ H)þ.
ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation of China
(Grant Nos. 20421202, 20672054, and 20872073), the 111 Project (B06005), and
the Committee of Science and Technology of Tianjin is gratefully acknowledged.
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