Efficient synthesis of 2-oxazolidinones from epoxides and carbamates catalyzed by amine-functionalized ionic liquids

Article abstract of DOI:10.1039/c5ra09838f

A series of amine-functionalized ionic liquids were prepared and their catalytic performance was tested in the synthesis of 2-oxazolidinones from epoxides and carbamates. Under optimized reaction conditions, good to excellent yields of various 2-oxazolidinones were achieved with different epoxides and carbamates. Moreover, the amine-functionalized ionic liquid catalyst could be easily recovered and reused without significant loss in activity.

Full text of DOI:10.1039/c5ra09838f

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Efficient synthesis of 2-oxazolidinones from epoxides and
carbamates catalyzed by amine-functionalized ionic liquids
Jianpeng Shang,*a Zuopeng Li,a Caina Su,a Yong Guoa and Youquan Dengb
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A series of amine-functionalized ionic liquids were prepared and their works. Since epoxides are known to produce ring-opened
catalytic performance were tested in the synthesis 2-oxazodinones from addition products with nucleophilic reagents,20 another non-
epoxides and carbamates. Under optimized reaction conditions, good to phosgene route for 2-oxazolidinones synthesis is the reaction
excellent yields of various 2-oxazolidinones were achieved with different between epoxides and carbamates, and then intramolecular
epoxides and carbamates. Moreoveer, the amine-functionalized ionic cyclization to give the expected 2-oxazolidinones,21-23 scheme
23, 24
liquid catalyst could be easily recovered and reused without significantly 1. Several alkaline agents,
such as triethylamine, have
loss in activity.
been reported as catalysts for the 2-oxazolidinones synthesis
from epoxides and carbamates. However, the volatility,
separation and recovery problems of those catalysts are still
maintained and accordingly limit their practical application.
2-oxazolidinones are important cyclic compounds in both fine
chemicals and synthetic organic chemistry. They are widely
used in the synthesis of pharmaceuticals, pesticides, cosmetics,
and so on.1-3 Since the 2-oxazolidinones preparation generally
uses highly toxic phosgene,4 and therefore involves
environmental and safety problems, much efforts have been
made to explore green alternative methods for 2-
oxazolidinones synthesis. Several non-phosgene routes for 2-
oxazolidinones synthesis have been developed: (1) oxidative
carbonylation of β-aminoalcohols with CO and O2, (2)
carbonylation of β-aminoalcohols with organic carbonate, (3)
cycloaddition of CO2 with β-aminoalcohols or aziridines.
Although the oxidative carbonylation of β-aminoalcohols
catalyzed by transition metal is an efficient way to produce 2-
oxazolidinones,5-7 such route is not eco-friendly due to the
potential explosion hazards and poisonous CO. As an
alternative, organic carbonates were used for the synthesis 2-
oxazolidinones.8-10 It should be noted that the organic
O
O
O
R
O
+
R
1 N
R3
O
R
R2
+
1 N
O
1 N
H
O
R3
R3
Scheme 1 Synthesis of 2-oxazolidinones from epoxides and carbamates
-
-
A-
A- = Cl-, BF4 , NTf2 , OTf-
N
N
N
i-Pr2NEMimA
N
Cl-
P+
N
Cl-
N
N
i-Pr2NEP444Cl
i-Pr2NEEimCl
Cl-
N
N
N
Cl-
i-Pr2NEN222Cl
+
N
i-Pr2NEBimCl
N
+
Cl-
N
N
carbonates are mainly produced by phosgenation or oxidative
carbonylation routes.11,
i-Pr2NEPyCl
12
Under these circumstances, the
direct synthesis of 2-oxazolidiones from CO2 and β- Scheme 2 The structure and abbreviation of the amine-functionalized ionic liquids used
aminoalcohols13-15 or aziridines16-19 is preferable from
in this study
environmental and economical viewpoints, however, some
Ionic liquids (ILs), defined as organic salts with melting
o
points below 100 C, have attracted considerable attention as
stoichiometrically consumed dehydrating reagents and high
pressure or high temperature are required in most of these
alternative reaction media and catalytic materials because of
their peculiar physicochemical properties. Moreover, various
functionalized ILs, incorporating different functional groups
into the ILs structure, have been explored and used as solvents
or catalysts in chemical processes.25-27 Herein, in order to avoid
the use of volatile organic amines, a series of amine-
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functionalized ILs (Scheme 2) were prepared and their catalytic corresponding 5-methyl-2-oxazolidinone. Moreover, the 4-
performances for 2-oxazodinones synthesis from epoxides and methyl-2-oxazolidinone as byproduct was observed, which was
carbamates were tested.
formed duo to the nucleophilic ring opening of the PO at
In our initial study, the reaction of propylene oxide (PO) and methyl substitute site.
ethyl carbamate (EC) was chosen as the model reaction to
Table 1. Synthesis of 5-methyl-2-oxazolidinone from PO and EC with different catalysts
and reaction conditionsa
explore the catalyst system, Table 1. Generally, the reaction
o
was carried out at 140 C for 24h in the presence of 10 mol%
O
O
catalyst. In the blank test (entry 1), the conversion of PO was
only 12%, suggested that catalyst was essential for such
reaction proceeded successfully. When the organic base
triethylamine used as catalyst, the conversion of PO reached
to 90%, entry 2. Owing to the volatility of organic amine and
the high catalytic activity toward this reaction, some amine-
functionalized ILs with different cations and anions were
prepared and investigated in such reaction, entry 3-12. From
the results, it could be found that both the cation and anion of
the investigated ILs have strong impact on the catalytic activity,
and the highest conversion of PO was achieved with i-
Pr2NEMimCl as catalyst (entry 3). The effects of the cation
structure on the catalytic performance were tested using
O
+
O
+
+
HN
O
HN
O
OH
H2N
O
5-methyl- 4-methyl-
2-oxazolidinone 2-oxazolidinone
Conv.
(%)
12
90
97
67
73
88
0
Sel.
(%)b
98
99
99
99
98
99
-
Yield
(%)c
11
88
96
64
70
84
-
Entry
Catalyst (mol%)
T(oC)
T(h)
1
2
--
140
140
140
140
140
140
140
140
140
140
140
140
140
120
130
140
140
140
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
8
Et3N
3
i-Pr2NEMimCl
i-Pr2NEPyCl
i-Pr2NEN222Cl
i-Pr2NEP444Cl
i-Pr2NEMimBF4
i-Pr2NEMimNTf2
i-Pr2NEMimOTf
NaCl
4
5
6
7
pyridinium-,
quaternary
ammonium-and
quaternary
8
0
-
-
phosphonate-based amine-functionalized ILs as catalysts
(entries 4-6), the results showed that the catalytic efficiency
decreased in the order of i-Pr2NEMimCl > i-Pr2NEP444Cl > i-
Pr2NEN222Cl > i-Pr2NEPyCl. The effects of imidazolium based
9
0
-
-
10
11
12
13
14
15
16
17
18
12
88
88
72
57
78
80
91
95
98
98
98
99
98
98
99
98
98
10
85
85
70
54
75
78
88
92
i-Pr2NEEimCl
i-Pr2NEBimCl
KF/Al2O3
-
-
amine-functionalized ILs with different anions (Cl-, BF4 , NTf2 ,
OTf-) on the reaction was also investigated. The halide anion
i-Pr2NEMimCl
i-Pr2NEMimCl
i-Pr2NEMimCl
i-Pr2NEMimCl
i-Pr2NEMimCl
-
-
Cl- gave excellent result, Whereas, BF4 , NTf2 , OTf- were found
to be inactive (entries 7-9). When the NaCl was used as
catalyst (entry 10), the conversion of PO was only 12%,
suggested that the single Cl- has no activity for this reaction
and the high activity of the i-Pr2NEMimCl may derived from
the combination effects of amine group and Cl-. Moreover, the
alkyl length of the imidazolium cation has a weak effects on
the reaction and the conversion of the PO decreased from 97%
to 88% as alkyl chain length of the cation increased from C1 to
C4 (entries 3, 11-12), probably duo to the alteration of the
solubility of the ionic liquids in the reaction mixture.
Furthermore, although the general solid base KF/Al2O3 was
found to show some catalytic activity for this reaction (entry
13), the conversion of PO was lower than that of i-Pr2NEMimCl
used as catalyst, which suggested that the ionic environment
supplied by ILs may be helpful for such reaction.
15
20
a Reaction conditions: 10 mmol PO; 15 mmol EC; 1 mmol catalysts; 120-140 °C; 8-
24 h. Conversions and selectivities were determined by gas chromatography.
b Selectivity of the 5-methyl-2-oxazolidinone.
c Isolated yield based on the charged PO.
Subsequently, the influence of the reaction temperature on
the reaction was investigated under identical reaction
condition. As is easily seen, reaction temperature has a great
influence on the reaction outcome with variation of reaction
temperature from 120 to 140 oC (entries 3, 14-15), the
conversion of PO reached 97% as the reaction temperature
was increased up to 140 oC. Additionally, the conversion of PO
was increased with increasing the reaction time and reached
97% after 24 h (entries 3, 16-18).
Fig.1 Recycling test of i-Pr2NEMimCl. Reaction conditions: 10 mmol PO; 15 mmol EC;
recovered i-Pr2NEMimCl; 140 °C; 24 h.
The recycling performance of i-Pr2NEMimCl was also
investigated in the reaction of EC and PO, Fig.1. The results
showed a slight decrease in the activity after each run, which
could be ascribed to the fact that i-Pr2NEMimCl was recovered
only 95% of the charged amount after each run by extracted
Notably, the 5-methyl-2-oxazolidinone was preferentially
formed with high selectivity in all cases listed in Table 1. The
major product corresponds to the nucleophilic ring opening of
the PO at the less substitute site under basic conditions,28
followed by intramolecular cyclization to produce the
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with diethyl ether, suggesting that the i-Pr2NEMimCl catalyst investigated, the results shown in Table 3. The carbamates
could be reused without significantly loss in activity.
with different alkyl or benzyl substituent on oxygen atom
(entries 1-4) gave good to excellent yields of the corresponding
2-oxazolidinones, however, the much lower yield of the
corresponding 2-oxazolidinones was obtained when the
phenyl substituent on the oxygen atom (entry 5), which could
be ascribed to the weaker leaving ability of the phenoxy than
the alkoxy or benzyloxy during the intramolecular cyclization
step. Additionally, the substituent on the nitrogen atom of
carbamates gave lower yield of the corresponding 2-
oxazolidinones, entries 6-7, which could be duo to the high
hindrance of substituent on the nitrogen atom and
unfavorable for the nucleophilic addition to the PO.
Table 2. Synthesis of 2-oxazolidinones from various epoxides and ECa
Conv.
(%)
Sel.
Yield
(%)c
Entry
1
Epoxide
Major product
(%)b
97
96
95
99
96
95
93
Table 3. Synthesis of 2-oxazolidinones from various carbamates and POa
2
3
100
98
4
5
97
98
99
98
95
95
Conv.
(%)
Yield
(%)b
Entry
1
carbamate
Major product
O
97
98
96
95
46
72
76
96
96
94
93
43
70
74
HN
O
O
O
2
3
4
5
6
7
HN
O
6
96
98
94
O
O
HN
O
7
8
95
82
74
93
81
100
a Reaction conditions: 10 mmol epoxides; 15 mmol EC; 1 mmol catalysts; 140 °C;
24 h. Conversions and selectivities were determined by gas chromatography.
b Selectivity of the 5-substituted-2-oxazolidinone.
c Isolated yield based on the charged PO.
To demonstrate the utility and generality of this approach to
formation 2-oxazolidinones, the reaction of EC with different
epoxides were carried out under the optimized conditions, the
results shown in Table 2. Excellent yields of the corresponding
2-oxazolidinones were obtained with terminal epoxides
(entries 1–7), while the disubstituted epoxide, cyclohexene
oxide (entry 8), gave lower activity towards the production of
the corresponding 2-oxazolidinones, which might be due to
the high hindrance of cyclohexene oxide. However, the
selectivity of the 5-substituted-2-oxazolidinones for the
styrene oxide (entry 7) was much lower than that of other
epoxides, which might be ascribed to the conjugative effect
derived from the benzene ring, which should favourably attack
at the carbon atom at which phenyl substitute was connected
to afford 4-substituted-2-oxazolidinones.29
a Reaction conditions: 10 mmol PO; 15 mmol carbamates; 1 mmol catalysts; 140
°C; 24 h. Conversions were determined by gas chromatography.
b Isolated yield based on the charged PO.
Based on the reaction mechanism reported in the previous
literature,23 the 2-oxazolidinone was formed in two
consecutive steps, scheme 3. The first is the formation of
compound I by nucleophilic addition between epoxide and
carbamate, followed by the formation of the 2-oxazolidinone II
in the second step by intramolecular cyclization.
Moreover, the reaction of PO and different carbamates with
various substituents on nitrogen or oxygen atom were also Scheme 3 Illustration for the formation of hydroxyl functionalized 2-oxazolidinones
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It is worth to note that during the reaction processes, we the hydroxyl functionalized 2-oxazolidinones were successfully
never detected the presence of the compound I. This fact synthesized when the epoxides were in excess.
indicated that the rate-limiting step for the conversion of
epoxide into 2-oxazolidinone is the ring-opening step of
Acknowledgements
epoxide. Thus, we supposed that if the epoxide is in excess,
the further ring opening of epoxide with the formed 2-
oxazolidinone II could be occurred and generate the hydroxyl
functionalized 2-oxazolidinone III which also represent an
important class of compounds have wide utility in
pharmaceutical chemistry. So, we carried out the reaction
This work has been financially supported with Doctoral
Scientific Research Foundation of Shanxi Datong University.
Notes and references
under the optimized condition with the mole ratio of EC
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oxazolidinones were obtained with various epoxides.
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5
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carbamate
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O
OH
98
97
97
97
96
95
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O
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,
Conclusions
In conclusion, an amine-functionalized ILs catalyst was
developed for the synthesis of 2-oxazolidinones from epoxides
and carbamates. Under the optimized reaction conditions,
good to excellent yields of various 2-oxazolidinones were
obtained with different epoxides and carbamates. Meanwhile,
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The amine-functionalized ionic liquids can be an efficient catalyst for 2-oxazolidinones
synthesis from epoxides and carbamates