A convenient approach for the synthesis of 1,3,5-trioxanes under solvent-free conditions at room temperature

Article abstract of DOI:10.1007/s00706-014-1150-8

A series of environmentally benign bis-SO₃H-functionalized Bronsted acidic ionic liquids were synthesized by using aliphatic polyamines and 1,3-propanesultone as the source chemicals. These ionic liquids acted as efficient inexpensive and recyclable catalysts for cyclotrimerization of aliphatic aldehydes at room temperature under solvent-free conditions. The reactions proceeded smoothly with good to excellent isolated yields (66.9-97.6 %=) and were generally complete in 1.5 h when the amount of ionic liquids was 0.1 mol%. The ionic liquids could be recovered readily and reused five times without any significant loss in their catalytic activity. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-014-1150-8

Monatsh Chem
DOI 10.1007/s00706-014-1150-8
ORIGINAL PAPER
A convenient approach for the synthesis of 1,3,5-trioxanes
under solvent-free conditions at room temperature
Xinzhong Li
•
Qi Lin Rong Cao
•
Received: 25 November 2012 / Accepted: 6 January 2014
Ó Springer-Verlag Wien 2014
Abstract A series of environmentally benign bis-SO H-
3
efficient acidic catalysts have been developed, e.g., proton
acids H SO or H PO [5], Lewis acid ZnCl [6], InCl [7],
functionalized Brønsted acidic ionic liquids were synthe-
sized by using aliphatic polyamines and 1,3-propanesul-
tone as the source chemicals. These ionic liquids acted as
efficient inexpensive and recyclable catalysts for cyclotri-
merization of aliphatic aldehydes at room temperature
under solvent-free conditions. The reactions proceeded
smoothly with good to excellent isolated yields
2
4
3
4
2
3
solid acid ZrO and TiO [8], Y-zeolite [9], sulfonic cation
2
2
resin [10], and Keggin-type heteropolyacids H PMo O ,
3 12 40
H PW O , and H SiW O [11]. In addition, Ali also
4
3
12 40
12 40
reported a novel approach for the synthesis of trisubstituted
1,3,5-trioxanes by hydroformylation cyclotrimerization of
cyclopentene and cyclohexene [12]. However, on the basis
on the standards of green chemistry, these reported meth-
ods suffer from drawbacks such as corrosion of equipment,
use of volatile organic solvents, expensive catalysts which
are prone to losing activity, poor thermal stability of the
catalyst, complex experimental processes, and difficult
work-up. Therefore, there is an increasing need and interest
in developing environmentally benign, simple, and highly
efficient sustainable alternatives for the synthesis of this
class of compounds.
(
66.9–97.6 %=) and were generally complete in 1.5 h
when the amount of ionic liquids was 0.1 mol%. The ionic
liquids could be recovered readily and reused five times
without any significant loss in their catalytic activity.
Keywords Brønsted acid ꢀ Ionic liquid ꢀ Trioxane ꢀ
Aldehyde ꢀ Cyclotrimerization
Introduction
Recently, water-stable Brønsted acidic ionic liquids
[
(CH ) SO HMIM][HSO ]
2
[13],
[(CH ) SO H-
2 4 3
4
3
4
1
,3,5-Trioxanes are valuable fine chemicals with wide
MIm][CF SO ] [13], [Bis-BsPy][HSO ] [14], and [Bis-
3
3
4 2
applications in various fields, such as stabilizers in color
photography [1], burning regulators in fumigants [2], fla-
voring material carriers for scents, repellents, and
deodorants [3], insecticides [4], and so on. In general, they
are synthesized by cyclotrimerization of aliphatic alde-
hydes under acidic conditions, and a large number of
BsPy][CF SO ] [14] based on one or two sulfonic acid
3 3
groups acting as environment friendly and recyclable cat-
alysts have been applied successfully in the synthesis of
1,3,5-trioxanes. Compared to traditional synthetic approa-
ches, they demonstrated some advantages, e.g., good to
excellent isolated yields, the reactions are carried out sol-
vent-free, involve short reaction times, simple work-up,
and the ionic liquids could be reused after simple treat-
ment. However, the problem in these reports is that the
used ionic liquids are based on imidazolium, pyridinium, or
bipyridinium cations, which may hinder their potential
industrial application because of their high cost.
X. Li (&) ꢀ R. Cao
State Key Laboratory of Structure Chemistry, Fujian Institute of
Research on the Structure of Matter, Chinese Academy of
Science, 350002 Fuzhou, China
e-mail: lixinzhong77@126.com
In this paper, we report a convenient, simple, and effi-
cient new approach for the synthesis of 1,3,5-trioxanes
under solvent-free and room temperature conditions using
X. Li ꢀ Q. Lin
Department of Chemistry and Chemical Engineering, University
of Minjiang, 350108 Fuzhou, China
123

X. Li et al.
Fig. 1 Cyclotrimerization of
aliphatic aldehydes in bis-
3
SO H-functionalized Brønsted
acidic ionic liquids at room
temperature under solvent-free
conditions
a novel series of bis-SO H-functionalized Brønsted acidic
3
BAILs-5, BAILs-6, BAILs-9, and BAILs-10 were isolated
as viscous liquids after the water was removed under
reduced pressure. BAILs-3, BAILs-5, and BAILs-11 could
be solidified slowly to wax-like solids at room temperature.
These BAILs were partially immiscible with ethyl esters,
n-hexane, and toluene but readily soluble in water. The
content of water in BAILs-1–12 ranges from 5.0 to 9.8 %
ionic liquids BAILs-1–12 (Fig. 1), which have two alkyl
sulfonic acid side chains in their cations and act as reusable
catalysts.
Results and discussion
(
by Karl Fischer titration). The acidity of BAILs-1–12 was
measured using UV–Vis spectrophotometer with
-nitroaniline as basic indicator according to methods
Synthesis of BAILs-1–12
a
4
BAILs-1–12 were synthesized using commercially avail-
0 0
reported in the literature [15]. The acidity of those BAILs
depends on the number of acidic groups and relative acidity
of the anion; BAILs-9 showed the highest acidity owing to
able
N,N,N ,N -tetramethylethylenediamaine,
0
00 00
triethylenediamine, and N,N,N ,N ,N -pentamethyldiethy-
lenetriamine as starting substrate via a quaternization and
acidification two-step process (Fig. 2). The advantage of
choosing these polyamines are as follows: (1) they are all
fine chemicals commercially available in large scale and
can be obtained easily and cheaply; (2) compared to aro-
matic amines such as dipyridine and imidazole they exhibit
stronger basicity, which may allow the quaternization
reaction to be performed smoothly under mild conditions
with relative short reaction times and satisfactory yields;
-
its three HSO4 anions.
Cyclotrimerization of aliphatic aldehydes catalyzed
by BAILs-1–12
In order to develop a convenient, simple, and efficient new
synthetic strategy for the cyclotrimerization of aliphatic
aldehydes, the cyclotrimerization of isobutyraldehyde
using the bis-SO H-functionalized Brønsted acidic ionic
3
(
3) multiple sulfonic acid groups and acidic anions can be
BAILs-1–12 as catalyst under solvent-free conditions at
room temperature was chosen as the model reaction. The
results of the experiments under optimum reaction
introduced easily into the structure of ionic liquids which
result in higher acidity. The resulting BAILs-1, BAILs-2,
1
23

A convenient approach for the synthesis of 1,3,5-trioxanes
3
Fig. 2 Synthesis of bis-SO H-
functionalized Brønsted acidic
ionic liquids
conditions are listed in Table 1. All investigated BAILs in
this study were found to be active, and gave moderate to
excellent isolated yields (ranging from 70.1 to 97.6 %).
The activity of these ionic liquids follows the order BAILs-
towards the aldehyde side with increasing reaction tem-
perature. As shown in Table 2, for straight-chain aldehydes
the yields decreased with the length of carbon chain and
also the reaction became difficult to proceed and needed
prolonged reaction times; for branched-chain aldehydes
which gave better results compared with straight-chain
ones with the same number of carbon, the reason lies in the
fact that the mechanism of aldehyde cyclotrimerization is a
nucleophilic addition process. The reaction therefore
depends dramatically on the steric hindrance and the sta-
bilization of the carbenium ion; when the length the carbon
chain was increased the steric hindrance also increased, but
this may favor the formation of a stable carbenium ion for
the branched chain aldehydes.
1
1 [ BAILs-3 [ BAILs-9 [ BAILs-7 * BAILs-1 [
BAILs-12 * BAILs-5[BAILs-10 * BAILs-4[BAILs-
* BAILs-6 [ BAILs-8, which is consistent with their
2
acidity. The reason for BAILs-11 giving the best results
might be ascribed to its stronger acidity and good dispersity
in aldehydes. On the basis of this success, we further
expanded the range of substrates; these results are listed in
Table 2. All of the investigated straight-chain and bran-
ched-chain aldehydes reacted smoothly with moderate to
excellent isolated yields. These good results could be
explained by the following facts: (1) the stronger acidity of
these ionic liquids effectively promoted the formation of
the intermediate carbenium ions; (2) for the reversible
cyclotrimerization of aldehydes, the equilibrium shifts
For the purpose of comparison, the cyclotrimerization of
isobutyraldehyde catalyzed by BAILs-13 and BAILs-14
(Fig. 1, both synthesized according to the method reported
in the literature [13]), which each have one SO H group in
3
123

X. Li et al.
Table 1 Results of cyclotrimerization of isobutyraldehyde catalyzed
by different SO H-functionalized Brønsted acidic ionic liquids
Table 3 Reuse of BAILs-11/BAILs-3 for cyclotrimerization of
isobutyraldehyde
3
a,c
a
Entry
BAILs
Yield/%
Run Ratio of aldehyde/ Reaction
BAILs
Yield/%
BAILs-3
BAILs-11/
time/h
1
2
3
4
5
6
7
8
9
BAILs-1
BAILs-2
BAILs-3
BAILs-4
BAILs-5
BAILs-6
BAILs-7
BAILs-8
BAILs-9
BAILs-10
BAILs-11
BAILs-12
BAILs-13
BAILs-14
87.2
76.4
92.3
78.4
82.4
72.5
85.8
70.1
89.6
80.3
97.6
83.5
83.0
78.2
1
2
3
4
5
a
1:0.01
1:0.01
1:0.01
1:0.01
1:0.01
1.5
1.5
1.5
1.5
1.5
96.5/91.7
95.6/90.9
96.3/90.5
96.2/89.9
96.1/90.6
Isolated yield
The catalytic activity has no noticeable decrease after
BAILs-11 and BAILs-3 were reused five times.
1
1
1
1
1
a
0
1
2
3
4
b
b
Conclusion
Reaction conditions: BAILs/isobutyraldehyde = 0.1 % (molar
ratio); reaction temperature, room temperature; reaction time, 1.5 h
unless indicated otherwise)
A simple, convenient, and eco-friendly new approach for
the cyclotrimerization of aliphatic aldehydes was devel-
(
b
oped using a series novel bis-SO H-functionalized BAILs
3
Reaction time, 2.0 h
Isolated yields
c
as efficient and recyclable catalysts under solvent-free and
room temperature conditions. Several noteworthy features
of this alternative are (1) the used ionic liquids can be
prepared easily using commercially available chemicals as
starting material via a two-step reaction; (2) the reaction
could be carried out smoothly with high yield and purity
after simple exaction; (3) BAILs could be reused five times
after simple treatments. These advantages make this
methodology a green alternative for the synthesis of trial-
kyl-1,3,5-trioxanes.
Table 2 Results of cyclotrimerization of aliphatic aldehydes cata-
lyzed by bis-SO
BAILs-11
3
H-functionalized Brønsted acidic ionic liquid
a,b
Entry
Aldehyde
Time/h
Yield/%
1
2
3
4
5
6
7
8
a
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
CH
2
CHO
1.5
1.5
2
91.3
84.2
79.7
75.4
71.8
66.9
97.6
71.4
(CH
(CH
(CH
(CH
(CH
2
)
2
)
2
)
2
)
2
)
2
CHO
3
CHO
4
CHO
6
CHO
8
CHO
2
2
Experimental
2.5
1.5
2
(CH
(CH
3
)
)
2
CHCHO
CHCH CHO
IR spectra were recorded on a Perkin-Elmer FT-IR 240-c
1
spectrophotometer using KBr optics. H NMR (400 MHz)
3
2
2
1
and C NMR (100 MHz) spectra were recorded on a
3
Reaction conditions: BAILs/aldehyde = 0.1 % (molar ratio); reac-
tion temperature, room temperature
Bruker 400 MHz spectrometer in D O with TMS as
2
b
Isolated yields
internal standard. All chemicals were commercially avail-
able and used as received without further purification.
the side chain, was also carried out under the same reaction
conditions; prolonging the reaction time to 2 h afforded the
triisopropyl-1,3,5-trioxane in 83.0 and 78.2 % isolated
yield. As is evident, the catalytic performances of BAILs-
General procedures for synthesis of Brønsted acidic
ionic liquids
A mixture of aliphatic polyamines (1 mol) and 1,3-pro-
panesultone (2.1 mol) in acetonitrile was stirred for 24 h at
room temperature. On completion of the reaction, the
obtained white solid was filtered off and washed with
acetonitrile and diethyl ester, then dried under vacuum at
70 °C for 8 h to give the ionic liquid precursor zwitterionic
salts. After the obtained zwitterionic salts were dissolved
1
1 and BAILs-3 are better than those of BAILs-13 and
BAILs-14; the reason may be ascribed to their stronger
acidity than that of BAILs-13 and BAILs-14.
In order to investigate the recycling of BAILs-11 and
BAILs-3 the cyclotrimerization of isobutyraldehyde was
chosen as a model reaction; the results are listed in Table 3.
1
23

A convenient approach for the synthesis of 1,3,5-trioxanes
completely in deionized water, a stoichiometric amount of
the corresponding mineral or organic acid was added
dropwise within 1 h under vigorous stirring. Then the
mixture was heated to 60 °C and kept for 8 h in an oil bath.
After the water was removed under vacuum the target ionic
liquid was obtained an as off-white viscous liquid or wax-
like solid with yields of 90–95 %.
(100 MHz, D
2
O): d = 32.13, 48.14, 51.09, 63.67, 64.04,
64.56 ppm; FT-IR (KBr): mꢀ = 3,443, 2,976, 2,871, 1,470,
1,186, 1,042, 793, 610 cm
-
1
.
0
00 00
00
N,N,N ,N ,N -Pentamethyl-N,N -bis(3-sulfopropyl)-
diethylenetriaminium tris(dihydrogenphosphate)
(
BAILs-10, C H N O P S )
15 40 3 18 3 2
1
13
H and C NMR spectra are identical to those of BAILs-9.
0
0
0
N,N,N ,N -Tetramethyl-N,N -bis(3-sulfopropyl)ethylenedia-
minium bis(hydrogensulfate) (BAILs-1, C H N O S )
0
00 00
00
N,N,N ,N ,N -Pentamethyl-N,N -bis(3-sulfopropyl)-
diethylenetriaminium tris(trifluoromethanesulfonate)
1
2 32 2 14 4
1
H NMR (400 MHz, D O): d = 2.26–2.30 (m, 4H, 2 CH ),
.01 (t, J = 4.0 Hz, 4H, 2 CH ), 3.27 (s, 12H, 4 CH ), 3.62
2 3
2
2
(
1
BAILs-11, C H F N O S )
18 37 9 3 15 5
13
H and C NMR spectra are identical to those of BAILs-9.
3
1
3
(
t, J = 4.4 Hz, 4H, 2 CH ), 3.98 (s, 4H, 2 CH ) ppm;
2
C
2
0
00 00
00
NMR (100 MHz, D O): d = 31.85, 47.86, 50.81, 63.33,
4.17 ppm; FT-IR (KBr): mꢀ = 3,435, 2,945, 2,857, 1,645,
N,N,N ,N ,N -Pentamethyl-N,N -bis(3-sulfopropyl)-
diethylenetriaminium trinitrate
2
6
-
1
1
,493, 1,182, 1,046, 800, 610 cm
.
(BAILs-12, C15H N O S )
37 6 15 2
13
H and C NMR spectra are identical to those of BAILs-9.
1
0
0
0
N,N,N ,N -Tetramethyl-N,N -bis(3-sulfopropyl)-
ethylenediaminium bis(dihydrogenphosphate)
General procedure for cyclotrimerization of aliphatic
aldehydes
(
1
BAILs-2, C H N O P S )
12 34 2 14 2 2
13
H and C NMR spectra are identical to those of BAILs-1.
0
0
0
N,N,N ,N -Tetramethyl-N,N -bis(3-sulfopropyl)-
ethylenediaminium bis(trifluoromethanesulfonate)
A mixture of aliphatic aldehyde (0.3 mol) and BAILs
(0.0003 mmol) was stirred vigorously under a nitrogen
atmosphere at room temperature. The progress of the
reaction was monitored by TLC. On completion, the
reaction mixture was extracted with n-hexane; after the
removal of n-hexane under vacuum the desired compounds
were obtained by recrystallization or silica gel column
chromatography. The BAILs were reused directly after
washing with diethyl ether.
(
1
BAILs-3, C H F N O S )
14 30 6 2 12 4
13
H and C NMR spectra are identical to those of BAILs-1.
0
0
0
N,N,N ,N -Tetramethyl-N,N -bis(3-sulfopropyl)-
ethylenediaminium dinitrate (BAILs-4, C H N O S )
1
13
H and C NMR spectra are identical to those of BAILs-1.
2 30 4 12 2
1
0
N,N -Bis(3-sulfopropyl)triethylenediaminium bis-
(
1
hydrogensulfate) (BAILs-5, C H N O S )
12 28 2 14 4
Acknowledgments This project was supported by Research Project
of Fujian Province Education Department (JA13252, JK2010044) and
Natural Science Foundation of Fujian Province (J01053).
H NMR (400 MHz, D O): d = 2.20–2.30 (m, 4H, 2 CH ),
2
2
2
1
4
1
.98 (t, J = 7.2 Hz, 4H), 3.74 (t, J = 4.8 Hz, 4H), 4.03 (s,
1
3
2H, 6 CH ) ppm; C NMR (100 MHz, D O): d = 32.46,
2
2
9.14, 64.21, 65.26 ppm; FT-IR (KBr): mꢀ = 3,062, 2,918,
-
1
,684, 1,608, 1,572, 1,492, 759, 693 cm
.
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0
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1
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0
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2
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1
13
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1
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0
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1
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