Journal of CO2 Utilization 2 (2013) 4957

Contents lists available at ScienceDirect

Journal of CO2 Utilization

journal homepage: www.elsevier.com/locate/jcou

Review

Advancements in oxazolidinone synthesis utilizing carbon dioxide as a C1 source

Sharon Pulla a,1, Charlette M. Felton a,1, Punnamchandar Ramidi a, Yashraj Gartia a, Nawab Ali b,
Udaya B. Nasini a, Anindya Ghosh a,*
a
b

Department of Chemistry, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, AR 72204, USA
Department of Applied Science, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, AR 72204, USA

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 26 June 2013
Accepted 20 July 2013
Available online 27 August 2013

Carbon dioxide, a natural molecule, has been utilized in the synthesis of chemicals for several decades. Its
innocuous chemical properties make it a favorable substance to incorporate in such synthetic processes.
Recently, research is being conducted to include carbon dioxide in the production of a specic class of
cyclic urethane molecules known as oxazolidinones. Oxazolidinones are important in synthetic and
medicinal applications, which necessitate a greener method to produce them. In this review, various
synthetic methods including catalytic processes that incorporate carbon dioxide to yield oxazolidinones
have been discussed and the results of the research are presented. Emphasis is placed primarily on
reactions of carbon dioxide with a variety of aziridines, propargylamines and 2-amino alcohols for the
synthesis of oxazolidinones.
2013 Elsevier Ltd. All rights reserved.

Keywords:
Oxazolidinones
Carbon dioxide
Aziridine
Propargylamine
Amino alcohol

Contents
1.
2.

3.

Introduction . . . . . . . . . . . . . . . . . .
Oxazolidinone synthesis . . . . . . . .
2.1.
Synthesis of oxazolidinones
Synthesis of oxazolidinones
2.2.
Synthesis of oxazolidinones
2.3.
Conclusion . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . .

..................................
..................................
from aziridines and CO2 . . . . . . . . . . . . . .
from N-substituted propargylamines and
from 2-amino alcohols and CO2 . . . . . . . .
..................................
..................................
..................................

1. Introduction
The use of carbon dioxide (CO2) for the synthesis of various ne
and bulk-chemicals has attracted the interest of various research
communities over several decades. CO2, one of the major manmade greenhouse gases, is a nontoxic, nonammable, and
inexpensive molecule. It has a large atmospheric abundance of
about 2.3  1012 t [1], which makes it a viable alternative to other
substances that are being depleted. From a green chemical
standpoint, it is an invaluable chemical resource based on the
facts that CO2 can be recovered as a by-product of various
industrial processes or can be acquired from natural reservoirs and
its capability to replace toxic chemicals such as phosgene [2],

* Corresponding author. Tel.: +1 501 569 8827; fax: +1 501 569 8838.
E-mail address: axghosh@ualr.edu (A. Ghosh).
1
These authors contributed equally in the preparation of this review.
2212-9820/$ see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jcou.2013.07.005

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49
50
50
54
55
57
57
57

cyanic acid [3], and carbon monoxide [4] in various synthetic

processes. The industrial syntheses of urea, cyclic carbonates,
salicylic acid, and methanol already utilize carbon dioxide as a
reactant [5]. Within the scope of green chemistry, CO2 sequestration has called for the development of new synthetic approaches.
2-Oxazolidinones (OXZs), a class of cyclic urethane molecules
known for their synthetic and medicinal applications [6], have
attracted the interest of scientic community towards developing
new synthetic approaches, especially using CO2. Various research
efforts have been made in developing synthesis of OXZs using
carbon dioxide as a chemical source. In this review, we present a
discussion on various approaches adopted for the synthesis of
OXZs from different substrates utilizing CO2.
The 2-oxo-1,3-oxazolidine ring is a cyclic carbamate skeleton
that occupies a special place among heterocyclic compounds. OXZs
have been known to be used as chiral auxiliaries since the report of
such use of enantiomerically pure 4-substituted oxazolidin-2-ones
in asymmetric synthesis by Evans [7]. They are widely used in

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

50

medicine for pharmaceutical preparations [8], in the paint and

varnish industry, and in polymer synthesis to prepare foams,
coatings, etc. [9]. The polymers containing OXZ rings are known to
have effective physicomechanical properties including high
thermal stability.
Various synthetic organic chemists have put forward considerable efforts in the synthesis of OXZs using various substrates in the
presence of CO2. Based on the class of substrate used, these can be
categorized into three major groups: (i) insertion of CO2 into the
aziridine moiety, (ii) reaction of propargylamines with CO2, and
(iii) reaction of 2-amino alcohols with CO2. This review will briey
discuss existing literature on OXZ synthesis with emphasis on
catalysis of the reactions based on these three synthetic methods.
2. Oxazolidinone synthesis
2.1. Synthesis of oxazolidinones from aziridines and CO2
Aziridines are considered to be important three-membered ring
functionalities in organic synthesis [10]. Structurally, aziridines are
analogous to epoxides with the nitrogen group replacing the
oxygen. The chemistry of aziridines has been studied over the last
few decades and their applications have been greatly expanded.
One such application of aziridines is in the synthesis of OXZs
(Fig. 1). A green approach of this synthesis in the presence of CO2
has been studied by various research groups both in catalytic and
non-catalytic pathways.
In 1976, use of iodine (I2) for the synthesis of OXZs from
aziridines and CO2 was reported by Soga et al. [11]. In a simple
synthesis of OXZs from molecules like aziridines, 2-methylaziridine was made with yields of OXZs as high as 80.5%. A
regioselective synthesis of OXZs using organoantimony halides
was reported by Nomura et al. [12]. Organoantimony halides
reportedly aided in the cycloaddition by a-cleavage. Organotin
halides were also studied in this same report. Due to their stronger
Lewis acidity as compared to organoantimony compounds, they
were reported to cause dimerization of aziridines under the
applied reaction conditions.
After over a decade, nickel (Ni) complexes of cyclam or bipyridine
ligands were studied for the efcient catalytic insertion of the carbon
dioxide into aziridines [13]. Under the electrochemical conditions,
these catalysts were found to be effective with regioselectivities of
6086%. The experimental conditions were mild, CO2 pressure at
1 atm and room temperature, which provides a greener chemical
approach from previously existing harsh methods. Another research
group led by Kawanami et al. discovered an effective use of I2 as an
active Lewis acid catalyst for the regiospecic synthesis of OXZs in
supercritical CO2 [14]. This study shows a decrease in the yield of the
OXZ product with increase in CO2 pressure. Kawanami et al. stated a
probable explanation to this anomaly was due to the variation of CO2
content in the different phases of the reaction medium (liquid or
supercritical). The source of OXZ reduction could be from the
decrease in polarity of the solvent medium. At the given temperature, the polar liquid phase containing only the co-solvent would
change to a less polar phase made up of CO2 and co-solvent. This
further increase in pressure results in increase of non-polar CO2
content, which prevents the formation of the OXZ product.

Fig. 2. Ratio of 5-substituted to 4-substituted isomers in the reaction of CO2 and Npropyl 2-phenylaziridine as a function of DMAP concentration.
Reprinted with permission from Miller and Nguyen (2004). Copyright (2004)
American Chemical Society.

In 2004, a binary complex of (salen)chromium(III) (Cr) and 4dimethylaminopyridine (DMAP) [15] was reported by Miller and
Nguyen to effectively catalyze the coupling of CO2 and aziridines
under mild reaction conditions. This study reported for the rst
time an effective catalyst for the synthesis of OXZs with the
formation of large excess, about 40:1, of the 5-substituted isomer
over the 4-substituted OXZ for a wide range of substrates. This
study indicates that contrary to the analogous epoxide/CO2, this
aziridines/CO2 coupling does not need a co-catalyst to proceed. An
interesting inuence of catalyst/co-catalyst ratio on the yield of the
5-substituted compounds was observed (Fig. 2). At the optimum
ratio of catalyst to co-catalyst (i.e. 2), the ratio of 5-substituted to
4-substituted isomers was observed to be 8:1. While in the absence
of the co-catalyst, as studied using N-propyl-2-phenylaziridine, the
ratio of isomers was found to be 40:1, favoring 5-phenyl-Npropyloxazolidinone.

O
H
N

Solvent (or) solvent-free

R
Aziridine

catalyst; CO2

NH

R
2-Oxazolidinone

Fig. 1. Synthesis of 2-oxazolidinones from aziridines.

Fig. 3. A proposed mechanism for the coupling of CO2 and aziridines by the
(salen)chromium(III)/DMAP catalyst system.
Reprinted with permission from Miller and Nguyen (2004). Copyright (2004)
American Chemical Society.

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

51

Table 1
Scope of palladium catalyzed carboxylation.

Entry

Azridine

R1

R2

dr (1:2)

Time

Yield (%)a

dr (3:4)b

1
2
3
4
5
6
7
8d
9
10
11
12d
13
14d
15

1a
1b
1c
1c/2c
2c
1d
1e
1f
Ig
1h
1j
1j
1k/2k
1l
(2R,3R)-1a (98:2 er)

Ph
Ph
Ph
Ph
Ph
Ph
p-Me-C6H4
p-OMe-C6H4
p-Cl-C6H4
Ph
Ph
Cy
Ph
H
Ph

Ph
p-Me-C6H4
p-OMe-C6H4
p-OMe-C6H4
p-OMe-C6H4
p-Cl-C6H4
Ph
Ph
Ph
Me
TMS
Ph
H
H
Ph

>98:2
>98:2
97:3
52:48
2:>98
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
85:15

>98:2

2
2
4
4
4
4
4
4
2
3
24
4
0.5
0.5
2

92
86
87
62c
40
86
89
91
84
78
40
83
71e
68
89 (>99:1 er)f

>98:2
>98:2
97:3
79:21
8:92
>98:2
>98:2
>98:2
>98:2
96:4
>98:2
>98:2
85:15

>98:2

Reprinted with permission from Fontana et al. (2011). Copyright (2011) American Chemical Society.
dba = dibenzylideneacetone. TBAT = tetrabutlyammoniumdiuorotriphenylsilicate. Aziridine concentration = 6  102 M.
a
Isolated yield.
b
Determined by 1H NMR of the crude.
c
Determined by 1H NMR with 1,1,2,2-tetrachloroethane as internal standard.
d
Conducted in the absence of TBAT.
e
H NMR of the crude showed the desired oxazolidinones together with cis-aziridine 2j in a ratio of 85:15.
f
Determined by chiral HPLC.

hygroscopic nature of tetrabutylammonium chloride (TBAC), an

easily manageable uoride source, tetrabutyl-ammonium diuorotriphenylsilicate (TBAT), was used as an alternative and an
increase in the yield of the product to 92% (Table 1) was observed
with the reaction being completed in just 2 h.
High yields of products in low reaction times were achieved
with a series of diaryl substituted trans-aziridines. An interesting
change in the formation of the product was observed with change
in electron-donating nature of R1-substituents. In the case of
substrates with R1 possessing higher electron-donating character,
the addition of TBAT was found to be detrimental. Another
interesting observation was the maintenance of trans to cis ratio in
the vinyloxazolidinones as compared to the ratio of isomeric
substrates (aziridines) used. Wu et al. reported a renewable
catalyst for an efcient synthesis of 5-aryl-2-oxazolidinones from
aziridines and CO2 by using zirconyl chloride as a solid catalyst [17]
(Fig. 4). The catalyst is very effective under mild conditions and
could be easily separated by ltration and was reportedly reused
for at least ve times. The activity of the catalyst could be
attributed to the coexistence of Lewis acidic zirconium (IV) and
Lewis basic chloride species in zirconyl chloride.
The activity of the heterogeneous catalyst could be explained by
a plausible reaction mechanism (Fig. 5), where in the cationic

Miller and Nguyen proposed a reaction mechanism for their

study (Fig. 3). The aziridines coordinate with the metal center of
Crsalen complex resulting in partially cationic nitrogen. The
nucleophilic ring opening of aziridines is followed by the cocatalyst, a Lewis base. A decrease in yield of the product with an
increase in the co-catalyst amount could be due to the competitive
coordination of the Lewis base to the Lewis acid Cr site resulting in
inhibition of the reaction.
This mechanism also provided a basis for the effect of pressure
of CO2 on yields of the product. An increase in yields up to certain
pressure followed by a decrease with further increase in pressures
could be due to the reduction in the amount of co-catalyst available
for the reaction; which is known to react with CO2 to form a zwitter
ionic complex that is inactive as a co-catalyst. The catalytic activity
in the absence of the co-catalyst was observed to be due to the cocatalytic activity of aziridines themselves. With the pKb = 6.14,
aziridines may also act as Lewis bases.
Binary catalytic system composed of palladium-dibenzylideneacetone (Pd2(dba)3) [16] and quarternary ammonium salt was
reported to effectively catalyze the conversion of trans-vinylaziridines into trans-vinyloxazolidinones at 0 8C and low pressures of
CO2. An attempt to synthesize vinyloxazolidinones at room
temperature yielded 83% of the product. In the light of the

CO2

Cat.

Et

Et

Ph

Ph

1a

Ph

2a

3a

Fig. 4. Cycloaddition reaction of CO2 to aziridine into OXZ using zirconyl chloride as solid catalyst.
Reprinted from Wu et al. (2009) with permission from Elsevier.

Ph

Ph

Et

Et

Et

Et

4a

Ph

Ph

N
Et

5a

52

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

Fig. 6. General synthesis of OXZs from aziridines in the presence of alkali metal
halides (M+X) and quaternary ammonium salts (nBu4N+X).
Reprinted from Sudo et al. (2003) with permission from Elsevier.

Fig. 5. A plausible reaction mechanism of OXZ synthesis using zirconyl chloride as

catalyst.
Reprinted from Wu et al. (2009) with permission from Elsevier.

cluster [Zr4(OH)8(H2O)16]8+ in the crystal of zirconyl chloride has a

strong coordinating ability towards aziridines, and, thus, forms
intermediate A via ligand exchange. The proposed ring opening of
aziridines by zirconium (Zr2+) is supposed to be performed through
two pathways, depending on the nature of R2 group while there is
an alkyl substitution at the N-position. Formation of OXZ and
subsequent regeneration of the catalyst is thought to occur after
the insertion of CO2 and subsequent cyclization via intramolecular
nucleophilic attack. Selective formation of 2 or 3 due to the nature
of R2 could also be accounted based on the fact that if R2 is an aryl
group, intermediate B is stable and, thus, favoring predominance of
2. Whereas, if R2 is an alkyl group, intermediate C is favored
resulting in predominant formation of 3.
Alkali metal halide such as lithium bromide (LiBr) was studied
for the conversion of 2-phenyl aziridine to 4-phenyl oxazolidinone.
LiBr, a catalyst known for its effectiveness in epoxide/CO2 coupling
[18] was also found to be effective in aziridines/CO2 coupling.
Using 2-methylaziridine, it was found to effectively catalyze the
formation of 4-methyl-1,3-oxazolidin-2-one as the sole product
with no regioisomer being observed [19] (Fig. 6). Other alkali metal
halides (chloride, bromide, and iodide) were also found to be
effective with the superiority of bromide counter anion, with yields
up to 76%. Solvation with 18-crown-6 in tetrahydrofuran (THF)
was needed for the activity of sodium bromide and potassium
bromide.
Alkali metal halides were found to effectively catalyze the
coupling at room temperature and under atmospheric pressures of
CO2. In this report, quaternary ammonium salts were also studied
for their activity. Sudo et al. determined tetrabuytlammonium
bromide (TBAB) to effectively catalyze the reaction. Inuence of
counter ion (X) on the yields of the product was also observed in

this case. The catalyst efciency was inuenced in the order

Br > I > Cl [19].
Hancock et al. reported a simple synthesis of N-benzyl-5phenyl isomer performed by the treatment of 2-phenyl-N-benzyl
aziridine by CO2 bubbling using lithium iodide (LiI) [20] under
reux (Fig. 7). In this study, inuence of R1 and R2 groups on the
yields of the products was of particular interest. With both R1 and
R2 being alkyl, an overall yield of 83% was obtained with the
regioisomeric ratio of 2:1 between 2 and 3. But, when R2 was
phenyl with R1 being alkyl, 3 was predominant indicating the
carboxylation at most substituted carbon. This report indicated
that fair amounts of the products could be obtained even at room
temperature.
A quaternary ammonium bromide covalently bound to
polyethylene glycol (PEG; Mw = 6000), i.e. PEG6000 (NBu3Br)2,
was found to be an efcient and recyclable catalyst for the
cycloaddition reaction of aziridines to CO2. The reaction conditions
were mild and did not require any additional organic solvents or
co-catalysts [21]. Results indicated that 5-aryl-2-oxazolidinone
was obtained in high yield possessing excellent chemo- and
regioselectivity. The catalyst worked well for a wide variety of 1alkyl-2-arylaziridines.
Du et al. tested various catalysts and their ability to synthesize
OXZs. PEG6000 (NBu3Br)2 was found to be an active catalyst when
compared to simple NBu4Br or a mixture of PEG and NBu4Br [22]. It
was found that PEG6000 (NBu3Br)2 has very high activity with a
turnover frequency (TOF) of 3394 h1 under the reaction conditions applied. This catalyst was found to be highly selective with
trace amounts of side products as indicated by mass spectrometry
and 1H nuclear magnetic resonance spectroscopy. Additionally,
the catalyst was able to be recovered via centrifugation without
any signicant loss in catalytic activity.
An eco-friendly carboxylation of aziridines with CO2 without
the addition of any organic solvents or additives was studied using
natural amino acids. Natural a-amino acids such as proline [23]
were proven to effectively catalyze the synthesis of a series of 5aryl-2-oxazolidinones in good yields with excellent chemo- and
regioselectivity under mild conditions. The catalyst could be
recycled more than ve times after a simple separation procedure
without appreciable loss of catalytic activity. This process
O

R1
N

1) LiI

R1

O
O

R1

2) CO2

R2

R2

a R1 = CH2Ph R2 = CH3
b R1 = pentyl R2 = CH3
c R1 = CH2Ph R2 = Ph
d R1 = Ph R2 = Ph
e R1 = Ph R2 = pentyl

Fig. 7. General synthesis of OXZs from aziridines using LiI/CO2.

Reprinted from Hancock et al. (2003) with permission from Elsevier.

R2

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

53

Table 2
Cycloaddition of CO2 with N-protected aziridine.a
Entry

Substrate

Product

Yield (%)b

Temp.

Time

r.t.

24 h

78

50 8C

12 h

88

50 8C

24 h

95

90 8C

5h

87

90 8C

5h

87

90 8C

5h

82

6c

90 8C

5h

7d

90 8C

5h

65 (1:1.4)

8d

50 8C

24 h

38 (1:1.1)

Reprinted from Wu et al. (2011) with permission from Elsevier.

a
Reaction condition: 1 (0.2 mmol), DBN (10%), LiI (20%), toluene (1.5 mL).
b
Isolated yield.
c
58% of 1f was recovered and tosyl group on 1f was removed to afford aziridine.
d
LiI (100%).

represents a promising strategy for homogeneous catalyst

recycling. An organo-catalyzed efcient and simple process for
the xation of CO2 to aziridine was performed in the presence of
1,5-diazabicyclo[4.3.0]non-5-ene (DBN) [24] by Wu et al. The
reaction was achieved under 1 atm CO2 pressure by using DBN as
the catalyst, LiI as an additive and toluene as co-solvent (Table 2). A
representative reaction of N-butylaziridine with CO2 indicated that
considerable yields of the products (88% of OXZ) could be obtained
at 50 8C over a period of 12 h. This reaction was found to progress
even at room temperature with the formation of about 78% of the
product over a period of 24 h. A recent report by Phung et al.
suggested that considerable yields of OXZs can be obtained from
aziridines and CO2 even in the absence of catalyst while the
reactions are performed at room temperature [25]. This study
adopted the application of ball milling for an efcient synthesis of
the desired OXZ products.
Previously reported OXZ syntheses from an unactivated
aziridine precursor have required harsh conditions, such as
temperatures over 100 8C or high CO2 pressures [2629]. Phung
et al. overcame this obstacle by testing the catalytic ability of
several ionic salts [30]. By testing a previously reported theory [31]
on the necessity of lithium and iodide ions present during
cycloaddition of CO2, they determined that when paired with
ammonium, ammonium iodide (NH4I) performed with the highest

product yield of 94% (compared the LiI yield of 85%). Additionally,

excellent yield was achieved with CO2 pressure ranging from 1 to
4 atm and at room temperature in a time span of 4 h [30]. NH4I was
also effective when catalytic amounts of 5 mol% were used with
yields up to 98% when the reaction was allowed to proceed for 2 h.
This discovery helped to pave the way for additional research to be
studied on unactivated aziridine conversion to OXZs.
In a study led by Watile et al. [32], chitosan biohydrogel beads
were utilized in the synthesis of OXZs. They found that these
uniformly shaped spherical beads acted as effective catalysts in the
cycloaddition of CO2 with several aziridine derivatives under mild
conditions. Several advantages of this catalyst included recyclability, biodegradable, and heterogeneous composition. Watile et al.
were able to recover and recycle the chitosan bihydrogel beads in
ve catalytic cycles without any signicant loss in catalytic activity
and selectivity. In a similar study led by Kathalikkattil et al. [33],
chitosan-bound alkylpyridinium halides (CS-RPX) were used as
catalysts to form 4-methyl-2-oxazolidinone from a 2-methylaziridine precursor (Scheme 1 Scheme 1). Using chitosan-bound
bromoethylpyridinium bromide as the most effective catalyst,
Kathalikkattil et al. were able to synthesize OXZ with 99.8%
conversion and 93.4% selectivity (over the other minor byproducts). In order to understand the chemical reaction and
how the catalyst aided in the synthesis, Kathalikkattil et al.

54

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

Scheme 1. Schematic representation of the synthesis of chitosan supported alkyl

pyridinium halides (CS-RPX).
Reprinted from Kathalikkattil et al. (2012) with permission from Elsevier.

proposed a reaction mechanism (Fig. 8). Additionally, they were

able to recover and reuse the catalyst in four continuous cycles
with only 26% conversion loss and 13% selectivity loss per
catalytic cycle (Fig. 9). These reactions were also performed under
mild reaction conditions, such as 2 MPa CO2 pressure and 100 8C.
Watile et al. [34] studied the efciency of polymer supported
diol functionalized ionic liquids (PS-DFILXs) in the conversion of 1alkyl-2-arylaziridines with CO2 to 5-aryl-2-oxazolidinones. With
the advantage of its heterogeneous character, this catalyst was able
to be recovered and recycled for four consecutive catalytic cycles.
The hydroxyl groups present on the PS-DFILX yielded a more
effective catalyst, leading to good yields and regioselectivity. This
OXZ synthetic method also uses solvent-free conditions, which
shows the impact it has in the eld of green chemistry and OXZ
synthesis incorporating a chemical xation pathway of CO2.
Seayad et al. [35] studied the cycloaddition of CO2 to Ntosylaziridines. Using various imidazolium and triazolium salts,
they determined diisopropylphenylimidazolium chloride (IPrCl) to
be the most efcient in the OXZ synthesis reaction. Under
conditions of 20 atm CO2 pressure and 80 8C, yields up to 60%
were recorded. By changing the previously used solvent from
tetryhydrofuran (THF) to dichloromethane (DCM), 83% yield of 2oxazolidinone was achieved. Seayad et al. further studied the
regioselectivity of the catalyst and found regioisomeric ratios high
as 88:12 and yields up to 80%.

Fig. 9. Catalyst recycle test for chitosan-bound bromoethylpyridinium bromide.

Reprinted from Kathalikkattil et al. (2012) with permission from Elsevier.

2.2. Synthesis of oxazolidinones from N-substituted propargylamines

and CO2
N-substituted propargylamines are a class of terminal alkynes
that have also been considered as other favorable substrates for the
synthesis of OXZs in the presence of CO2 (Fig. 10). In 1987, Mitsudo
et al. reported the use of (4-1,5-cyclooctadiene)(6-1,3,5-cyclooctatriene)ruthenium [Ru(COD)(COT)] and tertiary phosphine binary
system in toluene to give OXZs with high regio- and stereoselectivity. 5-Methylene-2-oxazolidinones were obtained from Nsubstituted propargylamines and CO2 in high yields [36].
Costa et al., in 1996, reported the use of strong organic bases as
catalysts for the efcient synthesis of 5-substituted OXZs using Nalkylprop-2-ynylamine substrates [37]. An extensive study on the
synthesis of oxazolidinones from propargyl amines was reported
by Shi et al. [38]. Various palladium (Pd) based catalysts were
studied for the synthesis under mild reaction conditions. 5 mol% of
Pd(OAc)2 was reported to be the best catalytic amount for the
synthesis under given conditions. Pd(0) metal and tertiary
phosphine system were also studied for the efcient synthesis
using toluene as the solvent.
A study led by Kayanoki et al. patented an autoclave method for
the synthesis of 3-methyl-5-methylidene-2-oxazolidinone [39].

Fig. 8. Proposed reaction mechanism for the cycloaddition of 2-methylaziridine with CO2 catalytic and non-catalytic pathways.
Reprinted from Kathalikkattil et al. (2012) with permission from Elsevier.

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

Fig. 10. Synthesis of oxazolidinones from N-substituted propargylamines.

Using supercritical CO2 (scCO2) at pressures above 1.0 MPa,

N-methylproparagylamine was converted to the OXZ product
with yields up to 88%. The advantage of this method removes the
need for additional solvents or catalysts. Another novel noncatalytic synthesis of OXZs from propargylamines was reported
by Kayaki et al. [40]. The scCO2 medium was used for the
synthesis with high selectivity toward the formation of (Z)-5alkylidene-1,3-oxazolidin-2-ones from the respective substrates.
Use of basic alumina as heterogeneous catalyst [41] toward the
effective and highly selective synthesis of OXZs from propargylamines was reported in 2007. This heterogeneous catalyst was
reported to be recyclable with high activity up to seven times,
even without thermal activation. Using terminal propargylamines, the corresponding OXZs with exocyclic double bonds
were obtained in acceptable to good yields (6696%) and with
excellent selectivities (9399%). However, when a di-substituted
alkyne was used, the desired product was not detected,
suggesting that the present process could be specic for terminal
propargylamines.
2.3. Synthesis of oxazolidinones from 2-amino alcohols and CO2
2-Amino alcohols, derivatives of various amino acids, have been
reported to be easily available, simple and economic substrates
toward the synthesis of 2-oxazolidinones. In 1959, Steele [42]
reported the synthesis of 3-alkyl and 3-hydroxyalkyl-5-methyloxazolidinones from the corresponding amino alcohols at elevated
temperatures ranging from 120 8C to 175 8C and at super
atmospheric pressures of 175700 psi. An aqueous solution of
the substrate (e.g. N-methylisopropanolamine) was pressurized
with required amount of CO2 resulting in the formation of OXZs at
elevated temperatures via the formation of a carbonate. It was also
reported that a non-aqueous solutions of the substrates (e.g. in
ethylene glycol) resulted in carbamic acid when it was subjected to
reaction conditions [42].
After about a period of over two decades, Nomura et al. reported
the rst organometallic [43] catalyzed synthesis of OXZs from
amino alcohols in the presence of CO2. Triphenylstibine oxide
(Ph3SbO) was reported to effectively catalyze the synthesis of 2oxazolidinones at 160 8C for 24 h resulting in about 94% of the
product (Fig. 10). It was reported that no other side products
besides the cyclic urethanes were detected.
The use of dehydrating agents in the form of 3A molecular
sieves was necessitated by the sensitivity of the catalyst to the
water formed in the reaction. Antimony 2-aminoethoxides,
resulting from the reaction of triphenylstibine oxide with alcohol,
was found to be a key intermediate in the synthetic process. This
intermediate formed a carbamic acid in the presence of CO2, which
further cyclized to corresponding OXZ.
The use of electrochemically generated [44] tetraethylammoniumperoxydicarbonate (TEAPC) or tetraethylammonium carbonate (TEAC) solutions for the synthesis of OXZs under mild reaction
conditions was reported by Feroci et al. TEAPC and TEAC were used
as carboxylating agents in the synthesis from 2-amino alcohols and
CO2. In this process, addition of slight excess of tosyl chloride
played a major role resulting in moderate to high yields of

55

2-oxazolidinones. Absolute chirality of the compounds used was

reported to be unchanged in this study.
Another synthetic method using an electrogenerated base was
reported by Casadei et al. [45]. In the presence of plantium (Pt)
anode and cathode, under galvanostatic control, 2-pyrrolidone was
electrolyzed in an acetonitrile-tetraethylammonium perchlorate
solution. Upon the addition of this electrolyzed solution to 1,2amino alcohol, the solution was bubbled with CO2 for 1 h and,
nally, tosyl chloride was added and stirred. Tosylchoride (TsCl)
may react with carbamate group and form a mixed anhydride that
can act as an acylating agent. The yields of the products were
inuenced by parameters such as number of Faradays per mole of
2-pyrrolidone supplied to the electrodes, the mole ratio 2pyrrolidone/1,2-amino alcohol, and the nature of the solvent. It
was also reported that it is the nature of only the amine group that
inuences the yields of 2-oxazolidinone but not the hydroxyl
group. This synthetic process reported the retention of chirality of
the 2-oxazolidinones formed.
In 2002, Tominaga and Sasaki reported [46] the use of dibutyltin
oxide catalyst toward the synthesis of 2-oxazolidinones from 2amino alcohols. N-methylprrolidone was used as solvent for this
dehydrative condensation. Many substrates under the investigation showed high percentage of conversion but the reaction
conditions adopted were relatively harsh at 180 8C for about 16 h.
Electrospray ionization-mass spectrometry studies of the reaction
indicated a stannoxazolidine intermediate formed as a result of
reaction between catalyst and the substrates. The SnN bond of
this intermediate is susceptible to CO2 insertion, which resulted in
the formation of cyclic tin carbamate. Formation of OXZ
regeneration of the catalyst could possibly occur due to the
intramolecular nucleophilic attack of alkoxy group on carbonyl
carbon of the carbamate.
Kawanami et al. reported several studies toward the synthesis
of 2-OXZs by using 2-amino alcohols as starting material and N,N0 dicyclohexylcarbodiimide [47] (DCC) as dehydrating and condensation agent. 4-Phenyl-2-oxazolidinone was synthesized at 40 8C
with acetonitrile being used as the solvent to provide a medium for
the dissolution of carbamate intermediate. A yield of about 96.5%
was observed when the reaction was performed at 40 8C for 12 h in
the presence of acetonitrile. In the absence of any solvent, a yield of
about 58% was observed at 40 8C and 8.6 MPa of CO2.
Ionic liquids are another class of catalysts that have recently
been studied toward their ability to catalyze the dehydration
condensation of 2-amino alcohols and CO2. Various ionic liquids
were studied. Tertiary-butylphosphonium bromide (TBPB) was
found to be more active than TBAB. Similar yield of the major
product was obtained when TBAB and 1-butyl-3-methylimidazolium bromide (BMIM-Br) was studied [48].
Presence of alkali metal promoter such as potassium carbonate
(K2CO3) was found to enhance the yield of the product. Catalytic
system comprising of BMIM-Br with a promoter of K2CO3 was
reported to be effective. The performance of the system was found
to be dependent upon the nature of the substrates. For 1-amino-2propanol (1c) under optimized conditions, a high yield of the cyclic
urethane (2c) of 40% was obtained along with the substituted
cyclic urea (3c) in a yield of 10%. Whereas, for 3-amino-1-propanol
(1d), considerable yield of desired product (2d) was obtained with
smaller yields of the cyclic urea (3d) (Fig. 11).
Phosphorylating agents [49] such as diphenylphosphoryl azide
(DPPA) and diphenyl chlorophosphate (DPPCl) were reported to
yield excellent amounts of 2-oxazolidinones and 2-imidazolidinones from corresponding 2-amino alcohols and diamines, respectively. Under basic conditions, treatment of primary or scondary
amines with phosphorylating agents resulted in transient carbamate anion, which, by intramolecular trapping by hydroxyl group,
forms 2-oxazolidinones in high yields (Table 3). Various other

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

56

Fig. 11. Reactions of CO2 with various amino alcohols.

Reprinted with permission from Fujita et al. (2006).

substituents on the two tin (Sn) centers, we determined that

chlorostannoxanes performed most efciently with butyl substituents (Fig. 12). A plausible reason could be due to the electronic
and steric environment provided by the substituents on the Sn
centers. When the Lewis acidity and catalyst solubility were
changed, the effect of catalysts on OXZ production was found to be
more pronounced. The chlorostannoxane catalyst with phenyl
substituents was found to have the lowest catalytic conversion to
OXZ. Additionally, we successfully reported the efcient synthesis
of OXZs which were found to retain the chirality (up to 99%) of the
starting amino alcohols under the reaction conditions and high
turnover numbers (TON = 138).

electrophiles such as thionyl chloride (SOCl2) and tosyl chloride

(TsCl) were also studied for their activity. Most of the N-alkyl
derivatives studied in this report were found to retain the chirality.
In the presence of chlorostannoxanes as robust, recyclable
catalysts, using diethyl carbonate, a congener of CO2, our research
group reported an efcient synthesis of OXZs from 2-amino
alcohols. High yields of 2-oxazolidinones were obtained within
60 min of reaction time [50]. Due to their effectiveness in the
synthesis of OXZs from 2-amino alcohols, and their ability in
activating CO2 toward cyclic carbonate synthesis [51], we tested
the catalytic ability of chlorostannoxanes to synthesize OXZs from
2-amino alcohols and CO2 [52]. Using both phenyl and butyl

Table 3
Synthesis of 2-oxazolidinones using electrophiles.

Entry

1
2
3
4
5
6
7
8
9
10
11

R1

Ph
Bn
i-Pr
t-Bu
s-Bu
1H-indol-3-ylmeth yl
CO2Et
CO2Et
Me
CO2Me
CO2Et

R2

H
H
H
H
H
H
H
Me
Ph
H
H

OH
OH
OH
OH
OH
OH
OH
OH
OH
SH
SH

a (2R)
b (2R)
c (2S)
d (2S)
e (2S,3S)
f (2S)
g (2S)
h (2S,3R)
i (1S,2R)
j (2R)
k (2R)

Reprinted with permission from Paz et al. (2010). Copyright (2010) American Chemical Society.
a
PhTMG as a base (100200 mol%).
b
Et3N as a base (200250 mol%).

a (4R)
b (4R)
c (4S)
d (4S)
e (4S,10 S)
f (4S)
g (4S)
h (4S,5S)
i (4R,5S)
j (4R)
k (4R)

Yield (%)
DPPA

DPPC1

AcCl

80a
75a
75a
74a
73a
94b
73a
75a
97b
95a
73a

95b
97b
97b
85a
94b
92b
76a
78a
96b

94b
89b
86a
97b
82b
94a
96a
97b

S. Pulla et al. / Journal of CO2 Utilization 2 (2013) 4957

57

Fig. 12. Structure of chlorostannoxane catalysts.

Reprinted with permission from Pulla et al. (2013). Copyright (2013) American Chemical Society.

3. Conclusion
The synthesis of OXZs from various substrates in the presence of
CO2 is a promising procedure based on the low toxicity of CO2 and
low cost of production. Development of renewable catalytic
system is also vital in a green chemical perspective. By using
CO2 as a renewable feedstock source in chemical reactions, the
necessity for other harmful chemicals can be eliminated.
Additionally, capturing naturally occurring CO2 and utilizing it
in chemical synthesis may help reduce its abundance in the
atmosphere.
For the production of OXZs, CO2 is an obvious and efcient C1
source for cycloaddition to various precursors, like aziridines,
propargylamines, and 2-amino alcohols. Improvements from past
research to recent reports are being conducted to help advance the
efciency of carbon dioxide in OXZ synthesis. Although these
approaches have been known for over few decades, not many
advancements have been made in recent years. There still
continues to be a clear need of more efcient catalytic processes
which can result in high yields under milder conditions and with
low catalyst loading.
Acknowledgements
A.G. likes to thank Kathleen Thomsen Hall Charitable Trust for
nancial support and National Science Foundation (Grant CHE1229149) major research instrument grant to complete this work.
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