Protic onium salts-catalyzed synthesis of 5-aryl-2-oxazolidinones from aziridines and CO2 under mild conditions

Article abstract of DOI:10.1039/c1gc15581d

Protic onium salts, e.g. pyridium iodide, proved to be highly efficient and recyclable catalysts for the selective synthesis of 5-aryl-2-oxazolidinones under a CO₂ atmosphere at room temperature, presumably due to aziridine activation assisted by hydrogen bonding on the basis of ¹H NMR and in situ FT IR under CO₂ pressure study.

Full text of DOI:10.1039/c1gc15581d

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COMMUNICATION
Protic onium salts-catalyzed synthesis of 5-aryl-2-oxazolidinones from
aziridines and CO2 under mild conditions†
Zhen-Zhen Yang, Yu-Nong Li, Yang-Yang Wei and Liang-Nian He*
Received 20th May 2011, Accepted 30th June 2011
DOI: 10.1039/c1gc15581d
Protic onium salts, e.g. pyridium iodide, proved to be highly
efficient and recyclable catalysts for the selective synthesis
of 5-aryl-2-oxazolidinones under a CO2 atmosphere at
room temperature, presumably due to aziridine activation
assisted by hydrogen bonding on the basis of 1H NMR and
in situ FT IR under CO2 pressure study.
prepared, efficient and recyclable single component catalyst
for selective formation of 5-aryl-2-oxazolidinone under mild
conditions is still highly desirable.
Because of the distinctive properties such as high thermal
stability, negligible vapor pressure, high loading capacity and
easy recyclability, ILs can potentially be used as environmentally
friendly solvents and/or efficacious catalysts and have attracted
significant attention from the scientific community.5 In the
framework of our continuous effort on the synthesis of oxa-
zolidinones from CO2,4j–m we found that a series of protic onium
salts (Scheme 2) were proved to be highly effective catalysts for
this transformation under ambient conditions. Interest in those
protic onium salts stems from facile preparation from relatively
inexpensive starting materials, gratifyingly thermal behaviour
and air/water stability. It is particularly worth mentioning
that hydrogen bonding formation between an aziridine and an
protic onium salts could lead to aziridine’s activation and thus
promote the reaction. Indeed, HPyI (N-proton pyridium iodide)
displayed excellent activity even without any additional organic
solvent/additive.
Carbon dioxide is an easily available renewable carbon resource,
which has the advantages of being nontoxic, abundant, and
economical.1 The [2 + 3] coupling reaction between CO2 and
aziridines is one of the few commercial routes using CO2 as a
raw material to afford the 5-membered materials (Scheme 1),
which are important heterocyclic compounds showing wide
applications as intermediates2a–d and chiral auxiliaries2e–g in
organic synthesis. Therefore, a growing effort has been devoted
to developing efficient methodologies for producing oxazolidi-
nones. From the viewpoint of green chemistry, the cycloaddition
procedure utilizing CO2 as a feedstock is more attractive
in comparison with those processes including carbonylation
of amino alcohols with phosgene,3a,b CO,3c and reaction of
propargylamine/propargylic alcohol with CO2.3c–g
Scheme 1 Synthesis of 2-oxazolidinones from aziridines and CO2.
In the past decades, numerous catalysts particularly Lewis
acid ionic liquids (ILs) have been proposed for this reaction.4a–m
Although significant advances have been seen, toxic organic
solvents/co-catalysts, high catalyst loading, high CO2 pressure
or longer reaction time are generally required to perform
the reaction smoothly. Therefore, development of an easily
Scheme 2 Protic onium salts used in this study.
In the preliminary study, a series of the Cl--containing protic
onium salts were examined to evaluate the cation influence by
performing the reaction of 1-ethyl-2-phenylaziridine (1a) and
CO2 at 100 ◦C and 5 MPa of CO2 for 1 h. The results listed
in Table 1 reveal that the cation has a remarkable impact on
the catalytic performance. NH4Cl was almost inactive (entry 1,
Table 1). The catalytic efficiency increased in the following order:
State Key Laboratory and Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin, 300071, People¢s Republic of China.
E-mail: heln@nankai.edu.cn; Fax: (+86)-22-2350-1493;
Tel: (+86)-22-2350-1493
† Electronic supplementary information (ESI) available: General experi-
mental methods, characterization for ionic liquids, aziridines, oxazolidi-
nones and piperazines and copies of NMR, ESI-MS spectra. See DOI:
10.1039/c1gc15581d
HHMTA+ < HTBD+ < HDBU+ ~ HDABCO+ < HMIm+
<
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Table 1 Cation effect of the protic onium salts on the reactiona
Table 3 Reaction conditions screeninga
Entry
Catalyst
Conv./%b
Yield/%b,c
Regio-sel.d
Cat./
CO2 pressure/ Time/
Entry mol% T/◦C MPa
min
Conv./%b Yield/%b
1
2
3
4
5
6
7
8
NH4Cl
10
89
87
94
99
95
97
73
8
88 : 12
93 : 7
92 : 8
90 : 10
92 : 8
88 : 12
93 : 7
93 : 7
HHMTACl
HTBDCl
HDBUCl
HDABCOCl
HMImCl
HPyCl
43
77
90
92
94
97
45
1
2
3
4
5
6
7
8
9
0.25
1
3
1
1
1
1
1
1
100
100
100
25
120
25
25
25
25
25
5
5
5
5
5
0.1
3
7
9
15
15
15
15
15
300
15
15
15
5
86
82
98
97
98
76
85
98
98
84
91
>99
>99
>99
>99
89
>99
99
C4DABCOCl
a Reaction conditions: 1a (1 mmol, 0.147 g); catalyst loading (3 mol%);
CO2 (5 MPa); 100 ◦C; 1 h. b Determined by GC. c Total yield of 2a and
3a. d Molar ratio of 2a to 3a.
85
>99
10
1
3
a Reaction conditions: 1a (1 mmol, 0.147 g). b Determined by GC.
HPy+ (entries 2–7). This is understandable because those delo-
calized cations could help stabilize the intermediate (Scheme 3)
and thus gave better results. The HDABCO+ cation with a ter-
tiary nitrogen able to activate CO2 showed high catalytic activity
(entry 5).4l Whereas, N-butyl protic onium salt i.e. C4DABCOCl,
incapable of forming hydrogen bonds with the aziridine, showed
much lower activity (entry 5 vs. 8). Therefore, hydrogen bonding
formation could play a crucial role in facilitating the reaction. On
the other hand, low efficiency of HHMTA+ would presumably be
ascribed to its steric hindrance (entry 2). Table 2 shows the anion
effect of HPyA on the reaction. HSO4 , H2PO4 and NO3 were
found to be ineffective due to poor nucleophilicity and leaving
ability (entries 1–3,Table 2). Interestingly, the halide activity
follows the order of Cl- < Br- < I- (entries 4–6), consistent
with the trend of nucleophilicity and leaving ability. As a result,
HPyI gave a quantitative result even within 15 min and was
therefore chosen as the model catalyst for further investigation.
Influence of the reaction parameters on the reaction was
also examined. The results are summarized in Table 3. When
0.25 mol% catalyst was used, 82% yield of 2a+3a was obtained
alongside small amounts of 1,4-diethyl-2,5-diphenyl-piperazine
(4a) and 1,4-diethyl-2,3-diphenyl-piperazine (5a) being detected
by GC-MS and 1H NMR (see electronic supplementary
information†). Nearly quantitative yield was attained in the
presence of 1 mol% HPyI. A further increase in the catalyst
amount to 3 mol% has little influence on the reaction outcome
(entries 1–3). Notably, high regio-selectivity was kept in the
range of 0.25 to 3 mol% HPyI. To our delight, HPyI worked
very well even at r.t. (entries 2, 4, 5). Temperatures over 120 ◦C
caused a slight decrease in the yield due to facile formation of
piperazines 4a and 5a. On the other hand, an almost quantitative
yield together with excellent selectivity could be retained in the
range of 3–7 MPa CO2, demonstrating the preferential effect of
the hydrogen-bonding for accelerating the reaction (entries 4,
7, 8). Moreover, 85% yield could also be attained even at 1 atm
CO2 when prolonging the reaction time to 5 h (entry 6). However,
CO2 pressure over 9 MPa caused the yield to decrease because of
CO2’s dilution effect, whereas chemo-selectivity was still > 99%
(entry 9).6 Therefore, the suitable CO2 pressure would be ca. 3
MPa. Notably, excellent results can also be obtained within 5
min under mild reaction conditions (entry 10). To test catalyst
stability, a subsequent cycle was run by adding fresh substrate to
the reaction mixture upon completion of the reaction without
product separation. The total product was separated after 5
cycles. The results indicate that no substantial drop in catalytic
activity was detected after five successive cycles (Table 4).
-
-
-
The generality of this protocol was also examined. Various
oxazolidinones were selectively formed in good yields (Table 5).
However, increasing steric hindrance of the N-substituted group
R1 gave rise to a reactivity decrease (entries 9–11). High
regioselectivity could be attained from 97 : 3 (2/3) to >99 : 1
with variation of the alkyl substituent at the nitrogen atom. On
Scheme 3 The proposed mechanism.
Table 2 Anion effecta
Table 4 Catalyst reusabilitya
Entry
Catalyst
Conv./%b
Yield/%b,c
Regio-sel.d
Cycle
t/min
Conv./%b
Yield/%b,c
Regio-sel.d
1
2
3
4
5
6
HPyHSO4
HPyH2PO4
HPyNO3
HPyCl
HPyBr
HPyI
4
13
49
48
>99
>99
0
0
6
34
70
97
—
—
96 : 4
90 : 10
97 : 3
97 : 3
1
2
3
4
5
15
15
30
30
30
>99
>99
99
98
99
98
97
95
94
95
98 : 2
97 : 3
98 : 2
98 : 2
98 : 2
a Reaction conditions: 1a (1 mmol, 0.147 g); catalyst loading (3 mol%);
CO2 (5 MPa); 100 ◦C; 15 min. b Determined by GC. c Total yield of 2a
and 3a. d Molar ratio of 2a to 3a.
a Reaction conditions: 1a (1 mmol, 0.147 g); catalyst loading (1 mol%);
CO2 (3 MPa); 25 ◦C. b Determined by GC. c Total yield of 2a and 3a.
d Molar ratio of 2a to 3a.
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Table 5 Various oxazolidinones synthesisa
Entry R1, R2 T/◦C Time Conv./%b Yield/%b Regio-sel.c
and regenerate the catalyst. The main product 2 could originate
from ring-opening of the aziridine through nucleophilic attack at
the most substituted carbon (path b), in agreement with typical
ring-opening of the 3-membered heterocycles.7
1
2
3
4
5
6
7
8
Et, Ph
25
25
70
25
25
25
25
80
25
15 min >99
15 min >99
15 min >99
15 min 98
98
97 : 3
98 : 2
99 : 1
98 : 2
99 : 1
97 : 3
97 : 3
97 : 3
Et, p-Cl-Ph
Et, p-Me-Ph
n-Pr, Ph
i-Pr, Ph
n-Bu, Ph
i-Bu, Ph
Bn, Ph
c-Hex, Ph
c-Hex, p-Cl-Ph 60
c-Hex, p-Me-Ph 55
>99
>99
94
71
98
98
98
45
>99
73
In summary, protic onium salts, such as HPyI proved to
be highly efficient and stable catalysts for the cycloaddition of
CO2 to aziridines without utilization of any organic solvent or
additive under modest reaction conditions. The protic onium
salts used in this study represent cheap, easily synthesized,
robust etc. protic onium-based catalysts, which can effectively
activate aziridine through hydrogen bonding formation. Further
extending the application of protic onium salt towards broad
reactions is currently under investigation in our laboratory.
This work was financially supported by the National Natural
Science Foundation of China (No. 20672054, 20872073), the 111
project (B06005), and the Committee of Science and Technology
of Tianjin.
2 h
30 min >99
4 h >99
15 min >99
72
9
10
11
48 h
48 h
48 h
46
>99
73
>99 : 1
>99 : 1
>99 : 1
a Reaction conditions: 1 (1 mmol); catalyst loading (1 mol%); CO2
(3 MPa). b Determined by GC. c Molar ratio of 2 to 3.
the other hand, an electron-withdrawing group on the benzene
ring showed higher activity than an electron-donating group
(entry 10 vs. 11).
References
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peak of the carbonyl group was migrated from 1770 cm-1 (1a-
CO2 carbamate salt, Scheme 3) to 1740 cm-1 (oxazolidinone),
when 1a was used as the substrate (Fig. S1, see electronic
supplementary information†), implying the activation of CO2
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Fig. 1 The 1H NMR (CDCl3, 400 MHz) of HPyI without and with 1a.
On the basis of previous reports4c,j and the experimental
results herein, a possible mechanism for the HPyI-catalyzed
cycloaddition of CO2 with aziridine was proposed as shown in
Scheme 3. Firstly, aziridine could coordinate with CO2 to afford
the carbamate salt, which was detected by in situ FT-IR.4l,m
Simultaneously, the aziridine itself could also interact with
HPy+ through hydrogen bonding, thus resulting in aziridine’s
activation. Subsequent nucleophilic attack by the iodide anion
and the final intra-molecular ring-closure, form oxazolidinone
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