Ionic liquid-promoted three-component domino reaction of propargyl alcohols, carbon dioxide and 2-aminoethanols: A thermodynamically favorable synthesis of 2-oxazolidinones

Article abstract of DOI:10.3390/molecules23113033

To circumvent the thermodynamic limitation of the synthesis of oxazolidinones starting from 2-aminoethanols and CO₂ and realize incorporation CO₂ under atmospheric pressure, a protic ionic liquid-facilitated three-component reaction of propargyl alcohols, CO₂ and 2-aminoethanols was developed to produce 2-oxazolidinones along with equal amount of α-hydroxyl ketones. The ionic liquid structure, reaction temperature and reaction time were in detail investigated. And 15 mol% 1,5,7-triazabicylo[4.4.0]dec-5-ene ([TBDH][TFE]) trifluoroethanol was found to be able to synergistically activate the substrate and CO₂, thus catalyzing this cascade reaction under atmospheric CO₂ pressure. By employing this task-specific ionic liquid as sustainable catalyst, 2-aminoethanols with different substituents were successfully transformed to 2-oxazolidinones with moderate to excellent yield after 12 h at 80 °C.

Full text of DOI:10.3390/molecules23113033

molecules
Article
Ionic Liquid-Promoted Three-Component Domino
Reaction of Propargyl Alcohols, Carbon Dioxide and
2
-Aminoethanols: A Thermodynamically Favorable
Synthesis of 2-Oxazolidinones
Shumei Xia 1 , Yu Song , Xuedong Li , Hongru Li 1,2,* and Liang-Nian He 1,*
1
1
1
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China; 2120160737@mail.nankai.edu.cn (S.M.); songyu@mail.nankai.edu.cn (Y.S.);
xuedong-li@163.com (X.L.)
College of Pharmacy, Nankai University, Tianjin 300353, China
2
*
Correspondence: lihongru@nankai.edu.cn (H.L.); heln@nankai.edu.cn (L.-N.H.);
Tel.: +86-22-23506290 (H.L.); +86-22-23503878 (L.-N.H.)
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
Received: 15 October 2018; Accepted: 20 November 2018; Published: 20 November 2018
ꢀ
ꢁꢂꢃꢄꢅꢆ
Abstract: To circumvent the thermodynamic limitation of the synthesis of oxazolidinones starting
from 2-aminoethanols and CO and realize incorporation CO under atmospheric pressure, a protic
2
2
ionic liquid-facilitated three-component reaction of propargyl alcohols, CO and 2-aminoethanols
2
was developed to produce 2-oxazolidinones along with equal amount of
α-hydroxyl ketones.
The ionic liquid structure, reaction temperature and reaction time were in detail investigated.
And 15 mol% 1,5,7-triazabicylo[4.4.0]dec-5-ene ([TBDH][TFE]) trifluoroethanol was found to be
able to synergistically activate the substrate and CO , thus catalyzing this cascade reaction under
2
atmospheric CO pressure. By employing this task-specific ionic liquid as sustainable catalyst,
2
2
-aminoethanols with different substituents were successfully transformed to 2-oxazolidinones with
◦
moderate to excellent yield after 12 h at 80 C.
Keywords: ionic liquid; synergistic activation; aminoethanol; 2-oxazolidinone; atmospheric CO2;
sustainable catalysis
1
. Introduction
The accumulation of CO in atmosphere has aroused considerable concern due to its link to
2
the climate change; hence effective strategies are urgently needed to mitigate the increasing CO2
buildup [ ]. Among the various strategies, transforming CO to valuable chemicals has received
1–3
2
much attention by utilizing CO as economic and nontoxic C source [
4
,5
]. Nowadays, CO has
2
1
2
been employed in the synthesis of carboxylic acids [
6–
8], carbonates [9–12], carbamates [13–18],
formate [19–21], methanol [21–24], ureas [25–27] and polymers [28–30] as well.
Oxazolidinones, which are in the family of carbamates, are important chiral auxiliaries in organic
synthesis [31 32] and are also common structural units in drugs [33 34] and agrochemicals [35].
,
,
However, the conventional synthetic methods of 2-oxazolidinones rely on hazardous or expensive
reagents such as isocyanides [36] and phosgene [37]. Recently, B. Gabriele et al. reported an alternative
unconventional synthetic method to produce oxazolidinones starting from 2-amino alcohols with CO
in ionic liquids [38]. As the surrogate of CO, CO is a more desirable material. Therefore, synthesis
2
of 2-oxazolidinones using CO and appropriate substrates has attracted much attention [14,39,40],
2
among which the direct synthesis of oxazolidinones starting from 2-aminoethanols and CO is
2
considered as an ideal route because the aqueous amino alcohols have been widely utilized to capture
Molecules 2018, 23, 3033; doi:10.3390/molecules23113033
www.mdpi.com/journal/molecules

Molecules 2018, 23, 3033
2 of 12
CO in industry [41,42]. Unfortunately, the direct reaction between amino alcohols and CO occurs
2
2
difficultly due to the thermodynamic limitation [43]. To shift the equilibrium to 2-oxazolidinones,
harsh reaction conditions [44 48], dehydrating agents or auxiliaries are often needed [13 49 52]; thus,
the generation of wasteful by-products is unavoidable. As an alternative strategy, our group has
introduced propargyl alcohols into the reaction system of amino alcohols and CO to circumvent this
–
,
–
2
thermodynamic limitation [53–55]. As descripted in Scheme 1, this three-component cascade reaction
is composed of carboxylative cyclization and the following intermolecular nucleophilic ring-opening
and further intramolecular nucleophilic cyclization. Although Ag- and Cu-based catalysts have been
developed for this three-component reaction to coproduce 2-oxazolidinones and α-hydroxyl ketones,
high CO pressure is still needed. In this context, efficient catalyst is still highly desirable to run this
2
reaction at atmospheric pressure.
R1 R2
R1 R2
O
R1 R2
CO2
OH
O
O
Sites need to be activated
O
O
Step 1: carboxylative cyclization
O
R1 R2
O
O
2
R R
1 2
R R
1
H
OH
O
N
R
N
O
OH
R
OH
O
N
R
O
O
O
O
Step 2: intermolecular nucleophilic ring-opening and further intramolecular nucleophilic cyclization
Scheme 1. Stepwise reaction in the three-component domino reaction and sites need to be activated.
It is speculated the synergistic activation of the substrate and CO may facilitate this tandem
2
reaction running at atmospheric pressure. Promisingly, the ionic liquids (ILs) show the potential
of multi-site activation in many organic syntheses by choice or functionalization of cations or
anions [56–59]. Especially, the ILs-promoted carboxylative cyclization of propargyl alcohols and
CO has been reported [60]. Considering this carboxylative cyclization reaction is the crucial step in
2
this three-component cascade reaction of propargyl alcohols, amino alcohols and CO , we envisioned
2
that the ILs-catalyzed three-component reaction is feasible.
Herein, a task-specific ILs-catalyzed three-component reaction of propargyl alcohols, CO and
2
2-aminoethanols was reported. By subtly selecting the cation and anion of the ionic liquid,
1
,5,7-triazabicylo[4.4.0]dec-5-ene trifluoroethanol ([TBDH][TFE]) was found to be the most suitable
catalyst and excellent yield of 2-oxazolidinones and -hydroxyl ketones could be obtained at
atmospheric CO pressure.
α
2
2
. Results and Discussion
2
.1. Optimization of the Reaction Conditions
The initial attempt to perform the three-component domino reaction of 2-(benzylamino)ethanol
(
1a), 2-methylbut-3-yn-2-ol (2a) and CO using ILs as catalyst was carried out under 1 atm CO
2
2
◦
at 80 C for 12 h, as summarized in Table 1. Considering the anion may play an important
role in activation of the substrate 2a, 1a and CO , the anions of ILs were firstly screened. Thus,
2
five 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1,5,7-triazabicylo[4.4.0]dec-5-ene)-based ILs with
−
different anions were investigated for this purpose (entries 1–5). As a result, the IL with anion [TFE]
presented the highest activity with 23% yield of the target product 3a (3-benzyl oxazoline-2-ketone)
and 27% yield of 4a (3-hydroxyl-3-methyl butanone) (entry 3,), which is attributed to the activation
−
capacity of [TFE] to CO [61] and to 1a as well, being consistent with the reaction mechanism as
2
depicted in Scheme 1. On the other hand, the cation of IL is supposed to activate the triple bond of
2a and also carbonyl group of the intermediate i.e., α-alkylidene cyclic carbonate, thus facilitates the

Molecules 2018, 23, 3033
3 of 12
carboxylative cyclization of 2a and the following intermolecular nucleophilic ring-opening and further
+
+
intramolecular nucleophilic cyclization. Therefore, a variety of cations, including [DBUH] , [TBDH] ,
[
+
+
−
TMGH] and [P4 ] , were further evaluated with [Im] as the anion (entries 1,6–8), and [TBDH]
444
+
was found to be the most effective cation, which may be related with its stronger interaction with the
substrate 2a and the intermediate. The above findings showed that both the anions and cations can
affect the the catalytic ability of the ILs in this reaction. We speculated that the IL with the combination
+
−
of [TBDH] and [TFE] would be an efficient catalyst for this domino reaction. As expected, the yield
of the products was improved, and 33% yield of 3a and 39% of 4a were obtained when [TBDH][TFE]
was used as the catalyst (entry 9).
Table 1. Screening ILs for the three-component domino reaction [a]
.
Yield/% [b]
Entry
IL (mol%)
3
a
4a
1
2
3
4
5
6
7
8
9
[DBUH][Im]
[DBUH][OAc]
[DBUH][TFE]
[DBUH][TFA]
[DBUH][Cl]
[TBDH][Im]
[TMGH][Im]
[P4444][Im]
14
19
23
21
13
27
22
trace
33
13
21
27
21
9
30
21
trace
39
[TBDH][TFE]
[
a]
Unless otherwise specified, the reaction conditions were: 1a (302.4 mg, 2.0 mmol), 2a (168.2 mg,
◦
[b]
1
2
.0 mmol), IL (5 mol%), CO
as the internal standard. DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, [DBUH][Im] = DBU imidazolide,
DBUH][OAc] = DBU acetate, [DBUH][TFE] = DBU trifluoroethanol, [DBUH][TFA] = DBU trifluoracetic
acid, [DBUH]Cl = DBU chloride, [TBDH][Im] = 1,5,7-Triazabicylo[4.4.0]dec-5-ene imidazolide, [TMGH][Im] =
2
(1 atm), 80 C, 12 h.
Determined by H-NMR with 1,1,2,2-tetrachloroethane
[
1
1
,1,3,3-tetramethylguanidinium imidazolide, [P4444][Im] = hexyltributylphosphonium imidazolide, [TBDH][TFE] =
,5,7-Triazabicylo[4.4.0]dec-5-ene trifluoroethanol.
Considering the IL amount may also affect the catalytic capability, the amount of the IL was
increased to further improve the reaction (Table 2). Surprisingly, the reduction of yields was
observed for most of the ionic liquids when the amount of the tested IL was increased from 5 mol%
to 10 mol% (entries 1–6). It is inferred that the interaction between the cations of ILs and the
nucleophilic sites of the substrate became dominant with the increase of the amount of the IL,
which can deactivate these nucleophilic sites and thus impedes the domino reaction. Conversely,
increasing the amount of [TMGH][Im], [P4444][Im] and [TBDH][TFE] would promote the reaction
(entries 7–9), wherein [TBDH][TFE] showed higher activity than other ionic liquids used in this
study. With [TBDH][TFE] as catalyst, the reaction time and reaction temperature were further studied.
The results showed that extending the reaction time (entry 10) or raising the reaction temperature
(entries 11,12) had no obvious impact on the reaction results. But if the loading of [TBDH][TFE] was
increased to 15 mol%, the 3a yield of up to 94% was obtained (entry 13). Further improving the loading
of [TBDH][TFE] to 20 mol% reduced the yield greatly (entry 14), which may be attributed to the solvent
+
effect of the IL and also the deactivation of the nucleophilic sites by [TBDH] . No target product was
obtained without any catalyst or with only TBD or TFE as catalyst (entries 15–17), which indicates the
importance of free anion and cation in activating substrate and CO . Therefore, 15 mol% [TBDH][TFE]
2
◦
was used as catalyst and the reactions were performed at 80 C for 12 h in subsequent studies.

Molecules 2018, 23, 3033
4 of 12
Table 2. Optimization of the reaction conditions [a]
.
Yield/% [b]
Entry
IL (mol%)
3
a
4a
1
2
3
4
5
6
7
8
9
[DBUH][Im] (10)
[DBUH][OAc] (10)
[DBUH][TFE] (10)
[DBUH][TFA] (10)
[DBUH]Cl (10)
[TBDH][Im] (10)
[TMGH][Im] (10)
[P4444][Im] (10)
[TBDH][TFE] (10)
[TBDH][TFE] (10)
[TBDH][TFE] (10)
[TBDH][TFE] (10)
[TBDH][TFE] (15)
[TBDH][TFE] (20)
TBD (15)
13
7
3
9
13
5
33
25
59
57
47
56
94
11
6
5
9
16
9
37
26
55
58
47
53
97
[
c]
1
1
1
0
[
d]
1
2 [e]
1
1
1
1
1
3
4
5
6
7
44
46
trace
trace
trace
trace
trace
trace
TFE (15)
—
[
a]
◦
Reactions were carried out at 80 C for 12 h with 1a (302.4 mg, 2.0 mmol), 2a (168.2 mg, 2.0 mmol) and CO
2
[b]
1
[c]
[d]
◦
60 C.
(
1 atm).
Determined by H-NMR with 1,1,2,2-tetrachloroethane as the internal standard.
18 h.
[e]
◦
00 C.
1
2
.2. Investigation of Substrate Applicability
Having selected suitable IL as catalyst, we proceeded to investigate the substrate applicability as
listed in Table 3. The propargyl alcohols, 2-aminoalcohols and even glycols with different substituents
were employed in this cascade reaction. A wide range of propargyl alcohols with methyl, ethyl,
cyclohexyl, aryl and even other complicated substitute at the propargylic position (2a
transformed effectively to afford the corresponding 2-oxazolidinones and -hydroxyl ketones in
moderate to high yields (entries 1–5). Notably, this protocol showed its potential application in
pharmaceutical industry by realizing the transformation of ethisterone (2e) to -hydroxyprogesterone
4e) with 63% of yield and the chiral structure retained (entry 5). Subsequently, the suitability of
–e), could be
α
α
(
2-aminoalcohols with different substitutes was further examined (entries 6–11). Both aryl-substituted
and alkyl-substituted 2-aminoalcohols proceeded smoothly and generated the corresponding products
in excellent yields with the exception of aromatic 2-aminoalcohols bearing nitro group at para-position
(
entry 10). The results may be interpreted by the weakened nucleophilicity of amino caused by the
strong electron-withdrawing nitro group at benzene ring [62 63]. Besides 2-aminoalcohols, glycols (1h
were also converted to the corresponding cyclic carbonates in moderate to good yields (entries 12–14).
,
–j)
Table 3. Scope of the substrates for the reaction under optimized conditions [a]
.
Yield/% [b]
Substrate
Entry
1
2
3
4
1
1
a
2a
4a (97, 93c)
4b (79)
3
a (94, 90c)
2
1a
2b
3a (80)

Molecules 2018, 23, 3033
5 of 12
Table 3. Cont.
Yield/% [b]
Substrate
Entry
1
2
3
4
3
1a
2c
3a (73)
4c (76)
4
5
6
1
a
a
2
d
3
a (99)
a (61)
4d (99)
OHO
H
H
H
O
1
2
e
3
4e (63)
4a (89)
4a (82)
1b
2a
2a
3b (89)
7
8
1
c
3
c (85)
1
d
2a
2a
4
a (99)
a (80)
3
d (99)
9
1
e
4
3
e (82)
10
1
f
2a
2a
4
a (23)
a (92)
3
f (24)
11
1g
3g (93)
4
12
1
h
2a
4
a (97)
a (57)
3
h (95)
1
3
4
2a
4
1
i
3
i (58)
1
1j
2a
3j (94)
4a (98)
[
a]
Reactions were performed using
1
(2.0 mmol),
2
(, 2.0 mmol), [TBDH][TFE] (71.8 mg, 15 mol%) with CO
2
pressure
◦
[b]
1
of 1 atm at 80 C for 12 h.
Determined by H-NMR with 1,1,2,2-tetrachloroethane as the internal standard.
[c]
Isolated yield.

Molecules 2018, 23, 3033
6 of 12
2
.3. Recycle Tests
As ILs are non-volatile and thermal stable, they can be easily recovered by evaporating the low
boiling point components. So, we subsequently explored the recycle performance of [TBDH][TFE] for
this tandem reaction using 1a and 2a as model substrates under the optimum conditions. After reaction,
the gas was released and the reaction system was subjected to vacuum distillation for at least 1 h at
◦
1
80 C. After removing the reactant and product, the catalyst was directly used in the next round of
the reaction. As depicted in Figure 1, the IL can be reused without considerable activity loss for at least
four times. The target product could still be obtained at a 75% yield after the catalyst was reused for
5
times, suggesting that the system has a good recyclability (as shown in Figure 1).
3
a
4a
1
00
80
60
40
20
0
4
a
3
a
1
2
3
4
5
Recycling number
Figure 1. Reusability of the [TBDH][TFE] system. Reaction conditions: 1a (302.4 mg, 2.0 mmol),
◦
2
a (168.2 mg, 2.0 mmol), [TBDH][TFE] (71.8 mg, 15 mol%), CO (1 atm), 80 C, 12 h.
2
2
.4. Mechanism Study
According to our early reports [54,55], this cascade reaction is composed of carboxylative
cyclization and the following intermolecular nucleophilic ring-opening and further intramolecular
nucleophilic cyclization. To gain deeper insight on the role of [TBDH][TFE] in the catalysis, the stepwise
reactions were conducted (Table 4). To begin with, we performed the carboxylative cyclization of
2
-methylbut-3-yn-2-ol (2a) with CO using 10 mol% of IL as catalyst. A variety of DBU-based ILs such
2
as [DBUH][Im]), [DBUH][OAc], [DBUH][Cl], and Im-based ILs including [TBDH][Im], [TMGH][Im]
showed high efficiency to produce 4,4-dimethyl-5-methylene-1,3-dioxolan-2-one ( ) with excellent
m
yield under mild conditions (entries 1–2,5–7). In contrast, [TBDH][TFE] and [DBUH][TFE] showed
lower activity in the carboxylative cyclization reaction, probably due to the weaker hydrogen bond
receptors of anions (entries 3,4,9, vs. 1–2,5–7) [64–66]. The same reason may be used to explain the
low activity of [DBUH][TFA]. For [P4444][Im] (tetra butylphosphonium imidazolide), the large steric
hindrance may impede the interaction of cation and carbon-carbon triple bond and thus the substrate
can’t be activated efficiently (entry 8).
The activity of different ILs on the subsequent reaction of vinyl cyclic carbonate (m) and
aminoethanol (1a) was further examined under the otherwise identical conditions (Table 3).
Noticeably, [DBUH][Im], [DBUH][OAc] and [TBDH][TFE] exhibited similar catalytic behavior to
afford quantitative yield of 3a and 4a (entries 1,2,9, Table 3), while other ILs showed moderate activities
(entries 3–8, Table 3).
The interesting results can be obtained by comparing the results of stepwise reaction with
three-component cascade reaction. Most ionic liquids, which can promote the stepwise reaction,
display reduced performance in the three-component reaction (Tables 2 and 4). Depressingly, the reason
for the decreased catalytic activity of ILs in the three-component reaction is not clear at this stage.
Fortunately, the catalytic activity of [TBDH][TFE] is retained in the three-component reaction and its
catalytic performance can be improved by increasing the loading amount from 10 mol% to 15 mol%
(Table 2). It is inferred that
α-alkylidene cyclic carbonate is the key intermediate in this multistep
cascade reaction [53 55]. Although [TBDH][TFE] was not so efficient in the carboxylative cyclization,
–
we speculated that the added ethanolamine can act as a base to facilitate the activation of hydroxyl
in propargyl alcohol, thus efficiently promoting carboxylative cyclization of 2-methylbut-3-yn-2-ol

Molecules 2018, 23, 3033
7 of 12
1
(
2a) with CO . To verify our conjecture, H NMR (400 MHz, DMSO-d6) measurement was performed
2
to characterize the interaction between propargyl alcohol and 2-aminoalcohol. The results showed
that the peak shape for hydroxylic hydrogen in 2-methylbut-3-yn-2-ol (2a) altered after addition of
2-(benzylamino)ethanol (1a), proving the formation of hydrogen bond between propargyl alcohol and
2
-aminoalcohol (see Figure S1 in Supplementary Materials).
Table 4. Catalytic effect of ionic liquids to stepwise reactions in the domino reaction [a].
O
O
O
ionic liquid
ionic liquid
H
O
O
OH
+
OH
+
CO2
O
N
Ph
(1 atm)
Ph
N
OH
2a
m
1a
3a
4a
Step 1
Step 2
Yield/% [b]
3a
Entry
IL
m
4a
1
2
3
4
5
6
7
8
9
[DBUH][Im]
[DBUH][OAc]
[DBUH][TFE]
[DBUH][TFA]
[DBUH]Cl
[TBDH][Im]
[TMGH][Im]
[P4444][Im]
87
88
46
54
75
75
76
34
43
97
90
63
55
50
57
49
44
99
99
93
62
54
50
54
46
43
99
[TBDH][TFE]
[
[
a]
b]
◦
Reaction conditions: 1a (302.4 mg, 2.0 mmol), 2a (168.2 mg, 2.0 mmol), IL (47.8 mg, 10%), CO
Determined by H-NMR with 1,1,2,2-tetrachloroethane as the internal standard.
2
(1 atm), 80 C, 12 h.
1
On the basis of the experimental studies and previous reports [54], the possible mechanism
for the [TBDH][TFE]-catalyzed three-component reaction was proposed as depicted in Scheme 2.
This cascade reaction includes the initial carboxylative cyclization of 2-methylbut-3-yn-2-ol (2a) with
CO and the subsequent nucleophilic addition of
α
-alkylidene cyclic carbonate with 2-aminoalcohol.
, propargyl alcohol is simultaneously activated by the coordination of the C C bond with
, while CO2
2
In step
I
≡
+
cation [TBDH] and hydrogen bonding with 2-aminoethanol to form the intermediate
A
−
is activated through the formation of the anion [TFECOO] . Then the
α
-alkylidene cyclic carbonate
to CO and
intermediate is generated by the nucleophilic attack of O atom in the intermediate
subsequent intramolecular cyclization. In step II, the nucleophilic N atom of 2-aminoethanol attacks
-alkylidene cyclic carbonate to form the corresponding -oxopropylcarbamate species C [54]. Finally,
A
2
α
β
2
-oxazolidinones and equal amount of
α
-hydroxyl ketones are formed through the intramolecular
+
cyclization of intermediate C facilitated by [TBDH] .
Scheme 2. Plausible mechanism.

Molecules 2018, 23, 3033
8 of 12
3
. Materials and Methods
3
.1. Materials and General Analytic Methods
Unless otherwise noted, carbon dioxide (99.999%), commercially available DBU (99%), TBD (98%),
TMG (99%), Imidazole (99.5%), TFE (99.5%) and TFA (99.5%) were obtained from Shanghai Aladdin
Bio-Chem Technology Co., LTD. (Shanghai, China). All starting materials including propargyl alcohols,
monoethanolamine and aromatic aldehydes, were obtained from Aladdin, Alfa Aesar (Haverhill, MA,
USA), and Heowns (Tianjin, China) and used as received. All operations were carried out by using
1
standard high vacuum and Schlenk technique unless otherwise noted. H NMR spectra were recorded
on Bruker AVANCE III HD 400 spectrometer (Bruker BioSpin, Rheinstetten, Germany) using CDCl3
(
99.8%, Wilmad, Beijing, China) or DMSO-d6 (99.9%, Wilmad, Beijing, China) as solvent referenced to
13
CDCl (7.26 ppm) or DMSO-d6 (2.50 ppm). C NMR was recorded at 100.6 MHz in CDCl (77.00 ppm).
3
3
Multiples were assigned as singlet, doublet, triplet, doublet of doublet, multiplet and broad singlet.
Mass spectra were recorded on a Shimadzu GCMS-QP2010 (Restek, Shimadzu, Japan) equipped with
a RTX-5MS capillary column (Restek, Shimadzu, Japan) at an ionization voltage of 70 eV. The data are
given as mass units per charge (m/z).
3
.2. General Procedure for the Synthesis of 2-Aminoethanol Derivatives [33]
A mixture of an aromatic aldehyde (10 mmol), 2-aminoethanol (0.61 g, 10 mmol) and Na SO
2
4
(
1.42 g, 10 mmol) in CH OH (20.0 mL) was added into a 100 mL round bottom flask and stirred for 2 h
3
at room temperature. Then, the solution was obtained after removing the drying agent. The solution
was treated with the addition of NaBH (0.19 g, 5 mmol) in ice water and stirred for 1 h. The mixture
4
was concentrated under vacuum, and the residue was extracted with CH Cl (3
×
20 mL), washed with
2
2
water (20.0 mL), and dried with Na SO . The CH Cl solution was concentrated under vacuum and
2
4
2
2
the residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate
v/v, 10:1–1:2) as eluent to give the desired products.
(
3
.3. General Procedure for the Synthesis of ILs [67]
All ionic liquids (ILs) were synthesized based on the procedure’s reported [59]. Typically, for the
synthesis of [TBDH][TFE], TBD was added to the methanol solution of CF CH OH by using the
3
2
anion-exchange resin method. Then the mixture was stirred at room temperature for 24 h. Subsequently,
◦
methanol was distilled off at 70 C under vacuum for 24 h. The as-synthesized ILs were characterized
by NMR spectroscopy. The NMR data are listed in Supplementary Material.
3
.4. General Procedure for the Synthesis of 2-Oxazolidinones and α-Hydroxyl Ketones
TBDH][TFE] (69.9 mg, 15 mol%), propargylic alcohol 1a (2.0 mmol) and 2-aminoethanol
2.0 mmol) were added successively to a 10 mL Schlenk tube equipped with a magnetic stir bar.
[
(
Then the flask was capped and attached to a CO balloon with purity of 99.95%. Subsequently,
2
◦
the reaction mixture was stirred at 80 C for 12 h. When the reaction completed, the vessel was cooled
with an ice-bath, and remove the balloon. The residue was flushed with 2
by column chromatography on silica gel (n-butylamine saturation) using petroleum ether/ethyl acetate
v/v, 50:1–1:1) as eluent to give the desired products.
×
3 mL CH Cl and purified
2 2
(

Molecules 2018, 23, 3033
9 of 12
4
. Conclusions
In summary, we have developed a new strategy to promote the three-component cascade reaction
of propargyl alcohols, atmospheric CO and 2-aminoethanols efficiently under mild conditions by
2
utilizing ILs as both catalyst and solvent, which successfully addresses the thermodynamic issue in
the synthesis of 2-oxazolidinones starting from 2-aminoethanols with CO and avoids the generation
2
of wasteful by-products. The protic IL [TBDH][TFE] showed the best performance amongst the tested
ILs due to its ability to synergistically activate the substrate by its cation and anion. Besides, it can
be easily recovered and reused at least for 5 times without obvious loss of its activity. A wide range
of propargyl alcohols and 2-aminoethanols, were successfully transformed to 2-oxazolidinones and
◦
α
-hydroxyl ketones with moderate to excellent yield after 12 h at 80 C. We believe that employing
easily recyclable ILs as catalyst and CO as starting material renders the synthesis of 2-oxazolidinones
2
in sustainable mode.
1
Supplementary Materials: The following are available online, Figure S1: H NMR for propargyl alcohol and
mixtures of propargyl alcohol and 2-aminoalcohol.
Author Contributions: Conceptualization, L.-N.H. and X.L.; methodology, X.L. and Y.S.; software, S.X.; validation,
X.L.; formal analysis, X.L.; investigation, X.L. and Y.S.; resources, L.-N.H.; data curation, X.L.; writing—original
draft preparation, H.L. and S.X.; writing—review and editing, S.X. and H.L.; visualization, H.L. and S.X.;
supervision, L.-N.H.; project administration, L.-N.H. and H.L.; funding acquisition, L.-N.H.
Funding: This research was funded by National Key Research and Development Program (2016YFA0602900),
the National Natural Science Foundation of China (21672119), the Natural Science Foundation of Tianjin
Municipality (16JCZDJC39900).
Acknowledgments: We thank the Ministry of Science and Technology of China (National Key Research and
Development Program), the National Natural Science Foundation of China, the Natural Science Foundation of
Tianjin Municipality for financial support.
Conflicts of Interest: All authors declare no conflict of interest.
References
1.
2.
3.
4.
Choi, S.; Drese, J.H.; Jones, C.W. Adsorbent materials for carbon dioxide capture from large anthropogenic
point sources. ChemSusChem 2009, 2, 796–854. [CrossRef] [PubMed]
D’Alessandro, D.M.; Smit, B.; Long, J.R. Carbon dioxide capture: Prospects for new materials. Angew. Chem.
Int. Ed. 2010, 49, 6058–6082. [CrossRef] [PubMed]
Le Quéré, C.; Raupach, M.R.; Canadell, J.G.; Marland, G. Trends in the sources and sinks of carbon dioxide.
Nat. Geosci. 2009, 2, 831–836. [CrossRef]
Cokoja, M.; Bruckmeier, C.; Rieger, B.; Herrmann, W.A.; Kühn, F.E. Transformation of carbon dioxide with
homogeneous transition-metal catalysts: A molecular solution to a global challenge? Angew. Chem. Int. Ed.
2
011, 50, 8510–8537. [CrossRef] [PubMed]
5
6
7
8
9
1
1
.
.
.
.
.
Mikkelsen, M.; Jørgensen, M.; Krebs, F.C. The teraton challenge. A review of fixation and transformation of
carbon dioxide. Energy Environ. Sci. 2010, 3, 43–81. [CrossRef]
Börjesson, M.; Moragas, T.; Gallego, D.; Martin, R. Metal-catalyzed carboxylation of organic (pseudo)halides
with CO . ACS Catal. 2016, 6, 6739–6749. [CrossRef] [PubMed]
2
Yu, D.; Teong, S.P.; Zhang, Y. Transition metal complex catalyzed carboxylation reactions with CO2.
Coord. Chem. Rev. 2015, 293, 279–291. [CrossRef]
Yu, B.; Diao, Z.-F.; Guo, C.X.; He, L.N. Carboxylation of olefins/alkynes with CO to industrially relevant
2
acrylic acid derivatives. J. CO Util. 2013, 1, 60–68. [CrossRef]
2
Shaikh, R.R.; Pornpraprom, S.; D’Elia, V. Catalytic strategies for the cycloaddition of pure, diluted, and waste
CO to epoxides under ambient conditions. ACS Catal. 2017, 8, 419–450. [CrossRef]
2
0. North, M.; Pasquale, R.; Young, C. Synthesis of cyclic carbonates from epoxides and CO . Green Chem. 2010
,
2
1
2, 1514–1539. [CrossRef]
1. Gao, X.F.; Yuan, G.Q.; Chen, H.J.; Jiang, H.F.; Li, Y.W.; Qi, C.R. Efficient conversion of CO2 with
olefins into cyclic carbonates via a synergistic action of I and base electrochemically generated in situ.
2
Electrochem. Commun. 2013, 34, 242–245. [CrossRef]

Molecules 2018, 23, 3033
10 of 12
1
1
2. Wan Isahak, W.N.R.; Che Ramli, Z.A.; Mohamed Hisham, M.W.; AmbarYarmo, M. The formation of a series
of carbonates from carbon dioxide: Capturing and utilisation. Renew. Sustain. Energy Rev. 2015, 47, 93–106.
CrossRef]
3. Farshbaf, S.; Fekri, L.Z.; Nikpassand, M.; Mohammadi, R.; Vessally, E. Dehydrative condensation of
-aminoalcohols with CO : An environmentally benign access to 2-oxazolidinone derivatives. J. CO Util.
[
β
2
2
2
018, 25, 194–204. [CrossRef]
1
1
1
1
4. Pulla, S.; Felton, C.M.; Ramidi, P.; Gartia, Y.; Ali, N.; Nasini, U.B.; Ghosh, A. Advancements in oxazolidinone
synthesis utilizing carbon dioxide as a C1 source. J. CO Util. 2013, 2, 49–57. [CrossRef]
2
5. Yu, B.; He, L.N. Upgrading carbon dioxide by incorporation into heterocycles. ChemSusChem 2015, 8, 52–62.
[CrossRef] [PubMed]
6. Yang, Z.-Z.; He, L.N.; Gao, J.; Liu, A.H.; Yu, B. Carbon dioxide utilization with C–N bond formation:
Carbon dioxide capture and subsequent conversion. Energy Environ. Sci. 2012, 5, 6602–6639. [CrossRef]
7. Vessally, E.; Mohammadi, R.; Hosseinian, A.; Edjlali, L.; Babazadeh, M. Three components coupling of
amines, alkyl halides and carbon dioxide: An environmentally benign access to carbamate esters (urethanes).
J. CO Util. 2018, 24, 361–368. [CrossRef]
2
1
1
8. Arshadi, S.; Vessally, E.; Hosseinian, A.; Soleimani-amiric, S.; Edjlali, L. Three-component coupling of CO2,
propargyl alcohols, and amines: An environmentally benign access to cyclic and acyclic carbamates (A
Review). J. CO Util. 2017, 21, 108–118. [CrossRef]
2
9. Wang, W.H.; Himeda, Y.; Muckerman, J.T.; Manbeck, G.F.; Fujita, E. CO hydrogenation to formate and
2
methanol as an alternative to photo- and electrochemical CO reduction. Chem. Rev. 2015, 115, 12936–12973.
2
[CrossRef] [PubMed]
2
0. Gunasekar, G.H.; Park, K.; Jung, K.D.; Yoon, S. Recent developments in the catalytic hydrogenation of CO2
to formic acid/formate using heterogeneous catalysts. Inorg. Chem. Front. 2016, 3, 882–895. [CrossRef]
1. Álvarez, A.; Bansode, A.; Urakawa, A.; Bavykina, A.V.; Wezendonk, T.A.; Makkee, M.; Gascon, J.; Kapteijn, F.
Challenges in the greener production of formates/formic acid, methanol, and DME by heterogeneously
2
catalyzed CO hydrogenation processes. Chem. Rev. 2017, 117, 9804–9838. [CrossRef] [PubMed]
2
2
2
2. Du, X.L.; Jiang, Z.; Su, D.S.; Wang, J.Q. Research progress on the indirect hydrogenation of carbon dioxide to
methanol. ChemSusChem 2016, 9, 322–332. [CrossRef] [PubMed]
3. Shi, L.; Yang, G.H.; Tao, K.; Yoneyama, Y.; Tan, Y.S.; Tsubaki, N. An introduction of CO conversion by dry
2
reforming with methane and new route of low-temperature methanol synthesis. Accounts Chem. Res. 2013
,
4
6, 1838–1847. [CrossRef] [PubMed]
2
4. Khusnutdinova, J.R.; Garg, J.A.; Milstein, D. Combining low-pressure CO capture and hydrogenation to
2
form methanol. ACS Catal. 2015, 5, 2416–2422. [CrossRef]
2
5. Paz, J.; Pérez-Balado, C.; Iglesias, B.; Muñoz, L. Carbon dioxide as a carbonylating agent in the synthesis of
2
-oxazolidinones, 2-oxazinones, and cyclic ureas: Scope and limitations. J. Org. Chem. 2010, 75, 3037–3046.
[CrossRef] [PubMed]
2
6. Jin, S.J.; Khan, Y.; Maeng, J.H.; Kim, Y.J.; Hwang, J.; Cheong, M.; Lee, J.S.; Kim, H.S. Efficient catalytic systems
for the carboxylation of diamines to cyclic ureas using ethylene urea as a promoter. Appl. Catal. B Environ.
2
017, 209, 139–145. [CrossRef]
2
7. Anderson, J.C.; Moreno, R.B. Synthesis of ureas from titanium imido complexes using CO as a C1 reagent
2
at ambient temperature and pressure. Org. Biomol. Chem. 2012, 10, 1334–1338. [CrossRef] [PubMed]
2
8. Zhou, Q.H.; Gu, L.; Gao, Y.G.; Qin, Y.S.; Wang, X.H.; Wang, F.S. Biodegradable CO -based polycarbonates
2
with rapid and reversible thermal response at body temperature. J. Polym. Sci. Part A 2013, 51, 1893–1898.
[CrossRef]
2
9. Li, C.; Sablong, R.J.; Koning, C.E. Chemoselective alternating copolymerization of limonene dioxide and
carbon dioxide: A new highly functional aliphatic epoxy polycarbonate. Angew. Chem. Int. Ed. 2016, 55,
1
1572–11576. [CrossRef] [PubMed]
3
3
3
0. Geschwind, J.; Wurm, F.; Frey, H. From CO -based multifunctional polycarbonates with a controlled number
2
of functional groups to graft polymers. Macromol. Chem. Phys. 2013, 214, 892–901. [CrossRef]
1. Heravi, M.M.; Zadsirjan, V. Oxazolidinones as chiral auxiliaries in asymmetric aldol reactions applied to
total synthesis. Tetrahedron Asymmetry 2013, 24, 1149–1188. [CrossRef]
2. Heravi, M.M.; Zadsirjan, V.; Farajpour, B. Applications of oxazolidinones as chiral auxiliaries in the
asymmetric alkylation reaction applied to total synthesis. RSC Adv. 2016, 6, 30498–30551. [CrossRef]

Molecules 2018, 23, 3033
11 of 12
3
3. Mallesham, B.; Rajesh, B.M.; Reddy, P.R.; Srinivas, D.; Trehan, S. Highly efficient CuI-catalyzed coupling of
aryl bromides with oxazolidinones using Buchwald’s protocol: A short route to linezolid and toloxatone.
Org. Lett. 2003, 5, 963–965. [CrossRef] [PubMed]
3
4. Surmaitis, R.M.; Nappe, T.M.; Cook, M.D. Serotonin syndrome associated with therapeutic metaxalone in a
patient with cirrhosis. Am. J. Emerg. Med. 2016, 34, 346. [CrossRef] [PubMed]
3
5. Quayle, W.C.; Oliver, D.P.; Zrna, S. Field dissipation and environmental hazard assessment of clomazone,
molinate, and thiobencarb in Australian rice culture. J. Agric. Food Chem. 2006, 54, 7213–7220. [CrossRef]
[PubMed]
3
3
6. Buyck, T.; Pasche, D.; Wang, Q.; Zhu, J. Synthesis of oxazolidin-2-ones by oxidative coupling of isonitriles,
phenyl vinyl selenone and water. Chem. Eur. J. 2016, 22, 2278–2281. [CrossRef] [PubMed]
7. Hamdach, A.; Hadrami, E.M.E.; Gil, S.; Zaragozá, R.J.; Zaballos-Garcíaa, E.; Sepúlveda-Arquesa, J. Reactivity
difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols. Tetrahedron 2006
2, 6392–6397. [CrossRef]
,
6
3
8. Mancuso, R.; Raut, D.S.; Della Ca’, N.; Fini, F.; Carfagna, C.; Gabriele, B. Catalytic oxidative carbonylation of
amino moieties to ureas, oxamides, 2-oxazolidinones, and benzoxazolones. ChemSusChem 2015, 8, 2204–2211.
[CrossRef] [PubMed]
3
4
4
4
9. Mei, C.; Zhao, Y.; Chen, Q.; Cao, C.; Pang, G.; Shi, Y. Synthesis of oxazolidinones and derivatives through
three-component fixation of carbon dioxide. Chem. Cat. Chem. 2018, 10, 3057–3068. [CrossRef]
0. Takada, Y.; Foo, S.W.; Yamazaki, Y.; Saito, S. Catalytic fluoride triggers dehydrative oxazolidinone synthesis
from CO . RSC Adv. 2014, 4, 50851–50857. [CrossRef]
2
1. Inagaki, F.; Okada, Y.; Matsumoto, C.; Yamada, M.; Nakazawa, K.; Mukai, C. Energyless CO absorption,
2
generation, and fixation using atmospheric CO . Chem. Pharm. Bull. 2016, 64, 8–13. [CrossRef] [PubMed]
2
2. Park, S.H.; Lee, K.B.; Hyun, J.C.; Kim, S.H. Correlation and prediction of the solubility of carbon dioxide
in aqueous alkanolamine and mixed alkanolamine solutions. Ind. Eng. Chem. Res. 2002, 41, 1658–1665.
[CrossRef]
4
4
3. Foo, S.W.; Takada, Y.; Yamazaki, Y.; Saito, S. Dehydrative synthesis of chiral oxazolidinones catalyzed by
alkali metal carbonates under low pressure of CO . Tetrahedron Lett. 2013, 54, 4717–4720. [CrossRef]
2
4. Fujita, S.I.; Kanamaru, H.; Senboku, H.; Arai, M. Preparation of cyclic urethanes from amino alcohols and
carbon dioxide using ionic liquid catalysts with alkali metal promoters. Int. J. Mol. Sci. 2006, 7, 438–450.
[
CrossRef]
5. Matsuda, H.; Baba, A.; Nomura, R.; Kori, M.; Ogawa, S. Improvement of the process in the synthesis of
-oxazoiidinones from 2-amino alcohols and carbon dioxide by use of triphenylstibine oxide as catalyst.
Ind. Eng. Chem. Prod. Res. Dev. 1985, 24, 239–242. [CrossRef]
6. Bhanage, B.M.; Fujita, S.I.; Ikushimabc, Y.; Arai, M. Synthesis of cyclic ureas and urethanes from alkylen e
4
4
2
diamines and amino alcohols with pressurized carbon dioxide in the absence of catalysts. Green Chem. 2003
,
5
, 340. [CrossRef]
4
7. Juárez, R.; Concepción, P.; Corma, A.; García, H. Ceria nanoparticles as heterogeneous catalyst for CO2
fixation by omega-aminoalcohols. Chem. Commun. 2010, 46, 4181–4183. [CrossRef] [PubMed]
4
8. Pulla, S.; Felton, C.M.; Gartia, Y.; Ramidi, P.; Ghosh, A. Synthesis of 2-oxazolidinones by direct condensation
of 2-aminoalcohols with carbon dioxide using chlorostannoxanes. ACS Sustain. Chem. Eng. 2013, 1, 309–312.
[CrossRef]
4
5
9. Niemi, T.; Fernández, I.; Steadman, B.; Mannisto, J.K.; Repo, T. Carbon dioxide-based facile synthesis of
cyclic carbamates from amino alcohols. Chem. Commun. 2018, 54, 3166–3169. [CrossRef] [PubMed]
0. Paz, J.; Pérez-Balado, C.; Iglesias, B.; Muñoz, L. Carbonylation with CO and phosphorus electrophiles: A
2
convenient method for the synthesis of 2-oxazolidinones from 1,2-amino alcohols. Synlett 2009, 3, 395–398.
[CrossRef]
5
1. Dinsmore, C.J.; Mercer, S.P. Carboxylation and Mitsunobu reaction of amines to give carbamates: Retention vs
inversion of configuration is substituent-dependent. Org. Lett. 2004, 6, 2885–2888. [CrossRef] [PubMed]
5
2. Tamura, M.; Honda, M.; Nakagawa, Y.; Tomishige, K. Direct conversion of CO with diols, aminoalcohols
2
and diamines to cyclic carbonates, cyclic carbamates and cyclic ureas using heterogeneous catalysts. J. Chem.
Technol. Biotechnol. 2014, 89, 19–33. [CrossRef]

Molecules 2018, 23, 3033
12 of 12
5
5
5
5
3. Li, X.D.; Cao, Y.; Ma, R.; He, L.N. Thermodynamically favorable protocol for the synthesis of 2-oxazolidinones
via Cu(I)-catalyzed three-component reaction of propargylic alcohols, CO and 2-aminoethanols. J. CO Util.
2
2
2
018, 25, 338–345. [CrossRef]
4. Song, Q.W.; Zhou, Z.H.; Wang, M.Y.; Zhang, K.; Liu, P.; Xun, J.Y.; He, L.N. Thermodynamically
favorable synthesis of 2-oxazolidinones through silver-catalyzed reaction of propargylic alcohols, CO2,
and 2-aminoethanols. ChemSusChem 2016, 9, 2054–2058. [CrossRef] [PubMed]
5. Li, X.D.; Song, Q.W.; Lang, X.D.; Chang, Y.; He, L.N. Ag(I) /TMG-promoted cascade reaction of propargyl
alcohols, carbon dioxide, and 2-aminoethanols to 2-oxazolidinones. Chemphyschem 2017, 18, 3182–3188.
[CrossRef] [PubMed]
6. Alvim, H.G.O.; Correa, J.R.; Assumpção, J.A.F.; da Silva, W.A.; Rodrigues, M.O.; de Macedo, J.L.;
Fioramonte, M.; Gozzo, F.C.; Gatto, C.C.; Neto, B.A.D. Heteropolyacid-containing ionic liquid-catalyzed
multicomponent synthesis of bridgehead nitrogen heterocycles: Mechanisms and mitochondrial staining.
J. Org. Chem. 2018, 83, 4044–4053. [CrossRef] [PubMed]
5
5
7. Wang, M.Y.; Song, Q.W.; Ma, R.; Xie, J.N.; He, L.N. Efficient conversion of carbon dioxide at atmospheric
pressure to 2-oxazolidinones promoted by bifunctional Cu(II)-substituted polyoxometalate-based ionic
liquids. Green Chem. 2016, 18, 282–287. [CrossRef]
8. Tang, S.K.; Baker, G.A.; Zhao, H. Ether- and alcohol-functionalized task-specific ionic liquids:
Attractive properties and applications. Chem. Soc. Rev. 2012, 41, 4030–4066. [CrossRef] [PubMed]
9. Giernoth, R. Task-specific ionic liquids. Angew. Chem. Int. Ed. 2010, 49, 2834–2839. [CrossRef] [PubMed]
0. Zhao, Y.; Yang, Z.; Yu, B.; Zhang, H.; Xu, H.; Hao, L.; Han, B.; Liu, Z. Task-specific ionic liquid and
5
6
CO -cocatalysed efficient hydration of propargylic alcohols to α-hydroxy ketones. Chem. Sci. 2015, 6,
2
2
297–2301. [CrossRef] [PubMed]
6
6
1. Zhao, Y.; Yu, B.; Yang, Z.; Zhang, H.; Hao, L.; Gao, X.; Liu, Z. A protic ionic liquid catalyzes CO conversion
2
at atmospheric pressure and room temperature: Synthesis of quinazoline-2,4-(1H,3H)-diones. Angew. Chem.
Int. Ed. 2014, 53, 5922–5925. [CrossRef] [PubMed]
2. Della Cà, N.; Gabriele, B.; Ruffolo, G.; Veltri, L.; Zanetta, T.; Costa, M. Effective guanidine-catalyzed
synthesis of carbonate and carbamate derivatives from propargyl alcohols in supercritical carbon dioxide.
Adv. Synth. Catal. 2011, 353, 133–146. [CrossRef]
6
6
6
6
3. Song, Q.W.; Yu, B.; Li, X.D.; Ma, R.; Diao, Z.F.; Li, R.G.; Li, W.; He, L.N. Efficient chemical fixation of CO2
promoted by a bifunctional Ag WO /Ph P system. Green Chem. 2014, 16, 1633–1638. [CrossRef]
2
4
3
4. Li, X.D.; Ma, R.; He, L.N. Fe(NO3)3 9H O-catalyzed aerobic oxidation of sulfides to sulfoxides under mild
·
2
conditions with the aid of trifluoroethanol. Chin. Chem. Lett. 2015, 26, 539–542. [CrossRef]
5. Shuklov, I.A.; Dubrovina, N.V.; Börner, A. Fluorinated alcohols as solvents, cosolvents and additives in
homogeneous catalysis. Synthesis 2007, 19, 2925–2943. [CrossRef]
6. Ravikumar, K.S.; Kesavan, V.; Crousse, B.; Bonnet-Delpon, D.; Bégué, J.P. Mild and selective oxidation of
sulfur compounds in trifluoroethanol: Diphenyl disulfide and methyl phenyl sulfoxide. Org. Synth. 2003, 80,
1
84–189. [CrossRef]
7. Ying, A.G.; Liu, L.; Wu, G.F.; Chen, G.; Chen, X.Z.; Ye, W.D. Aza-Michael addition of aliphatic or
aromatic amines to -unsaturated compounds catalyzed by a DBU-derived ionic liquid under solvent-free
conditions. Tetrahedron Lett. 2009, 50, 1653–1657. [CrossRef]
6
α,β
Sample Availability: Samples of the compounds are not available from the authors.
©
2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).