Novel synthetic routes of 3-methoxypropanal from glycerol

Article abstract of DOI:10.1080/00397911.2010.486502

A new synthesis of 3-methoxypropanal from glycerol was presented. With this new approach, the conversion of glycerol to 3-methoxypropanal can be effected in moderate yield using catalysts of copper sulfate and polyethylene glycol (PEG).

Full text of DOI:10.1080/00397911.2010.486502

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Novel Synthetic Routes of 3-
Methoxypropanal from Glycerol
Jin Chen a & Xiaohua Du a
a State Key Laboratory Breeding Base of Green Chemistry–Synthesis
Technology, Zhejiang University of Technology, Hangzhou, China
Published online: 30 Mar 2011.
To cite this article: Jin Chen & Xiaohua Du (2011) Novel Synthetic Routes of 3-Methoxypropanal from
Glycerol, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:9, 1376-1380, DOI: 10.1080/00397911.2010.486502
To link to this article: http://dx.doi.org/10.1080/00397911.2010.486502
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Synthetic Communications1, 41: 1376–1380, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.486502
NOVEL SYNTHETIC ROUTES OF
3-METHOXYPROPANAL FROM GLYCEROL
Jin Chen and Xiaohua Du
State Key Laboratory Breeding Base of Green Chemistry–Synthesis
Technology, Zhejiang University of Technology, Hangzhou, China
GRAPHICAL ABSTRACT
Abstract A new synthesis of 3-methoxypropanal from glycerol was presented. With this new
approach, the conversion of glycerol to 3-methoxypropanal can be effected in moderate
yield using catalysts of copper sulfate and polyethylene glycol (PEG).
Keywords Copper sulfate; dehydration; glycerol; 3-methoxypropanal; PEG
Glycerol has been a well-known chemical made fats and oils by saponification for
more than two centuries. Recently, a large surplus of glycerol has been formed as
a by-product in manufacturing biodiesel fuel by transesterification of seed oils with
methanol. About 100 kg of pure glycerol is obtained from one ton of biodiesel
production.[1] Studies have shown that the glycerol commodity market is very
limited, and any increase in biodiesel production will cause a sharp decline in price.
Obviously, how this additional glycerol can be used wisely has become an urgent
issue, particularly how glycerol itself or some of its derivatives can find new applica-
tions in the chemical industry. In recent years, new opportunities for the conversion
of glycerol into value-added chemicals have attracted intensive interest.[2]
Compound 3-methoxypropanal is a valuable intermediate in organic synthesis
and has been used to synthesize agricultural chemical, such as imazamox.[3] It is also
useful for the synthesis of a series of N-(3-methoxypropyl)-N-arylmethylpiperidin-
4-amines, which are inhibitors of both serotonin and norepinephrine reuptake.[4]
Received June 15, 2009.
Address correspondence to Xiaohua Du, State Key Laboratory Breeding Base of Green
Chemistry–Synthesis Technology, Zhejiang University of Technology, Hangzhou, 310014, China.
E-mail: duxiaohua@zjut.edu.cn
1376

3-METHOXYPROPANAL FROM GLYCEROL
1377
Furthermore, it also found its application in synthesizing the flavor methyl jasmo-
nate.[5] The methods of preparing this compound include oxidation of 3-methoxypro-
panol with pyridinium chlorochromate,[6] hydroformylation of methoxy-ethene using
catalysts of low-valent cobalt and rhodium,[7] rearrangement of 2-methoxymethyl-
oxirane under erbium triflate catalysis in dichloromethane,[8] and addition reaction
of acrolein with saturated alcohols in the presence of catalysts.[9]
However, studies on converting 3-methoxy-1,2-propanediol to 3-methoxypro-
panal are seldom performed. Herein we report a new method for the synthesis of
3-methoxypropanal from glycerol (Scheme 1). The reaction was carried out in two
steps. First, we prepared 3-methoxy-1,2-propanediol by a literature procedure.[10]
Then it was converted to 3-methoxypropanal by dehydration. Some efforts have
been made to choose the proper catalysts to obtain better results.
This study first focused on the feasibility of producing 3-methoxypropanal by
dehydration of 3-methoxy-1,2-propanediol using heterogeneous catalyst in a single-
stage reaction. The products were distilled when the reactions were completed. The
results for the dehydration of 3-methoxy-1,2-propanediol are summarized in Table 1.
In our study, catalysis of sulfuric acid, p-toluene sulfonic acid, sodium bisulfate
monohydrate, and copper sulfate were examined. A trace amount of product was
observed. Copper-chromite catalyst showed high selectivity in the dehydration of
glycerol to acetol,[11] but it was not effective in this reaction (Table 1, entry 1).
Conventional dehydration catalysts such as sulfuric acid and p-toluene sulfonic acid
were active for dehydrating 3-methoxy-1,2-propanediol, but low selectivity showed
in this reaction (Table 1, entries 2 and 3). Then we investigated the performance
of acidic ionic liquids in the absence of any solvents, but most reactions did not occur
at all (Table 1, entries 10 and 11) and some showed low selectivity (Table 1, entries
12–15). On the other hand, sodium bisulfate monohydrate and copper sulfate
catalysts are superior to the other screened catalysts, and the corresponding yields
reached 21% and 30%, respectively. So copper sulfate and sodium bisulfate monohy-
drate catalysts were selected for further studies.
In an attempt to improve the method, we also tried adding phase-transfer
catalysts to the system to facilitate the migration of the reactant in the heterogeneous
system, such as polyethylene glycol (PEG), b-cyclodextrins (b-CD), tetrabutylammo-
nium bromide (TBAB), or using the mixture of two phase-transfer catalysts. The
reactions were carried out using the present reaction conditions, and the results
are presented in Table 2.
As expected, better concentrations and yields were achieved when adding 2.5%
b-CD or PEG400 into sodium bisulfate monohydrate catalyst (Table 2, entries 2 and
3), while lower selectivity was shown when adding TBAB into the reaction (Table 2,
entry 1). When more PEG400 (15%) was added, we obtained higher concentration
and yield (Table 2, entry 4). Similarly, 15% b-CD or PEG400 were added into copper
sulfate catalyst (Table 2, entries 5 and 6); particularly PEG displayed an apparent
Scheme 1. Synthetic route of 3-methoxypropanal from glycerol.

1378
J. CHEN AND X. DU
Table 1. Synthesis of 3-methoxypropanal catalyzed by various catalysts
Entry
Catalyst (15 wt%)
Distillatea (g)
Concentrationb (%)
Yield (%)
1
2
CuCr2O4
p-MeC6H4SO3H
H2SO4
0
0
12
11
44
0
0
6
1.77
2.05
1.89
0
3
5
4
NaHSO4 ꢀ H2O
Na2HPO4
21
0
5
6
CuSO4 ꢀ 5H2O
CuSO4
Cu(HSO4)2
2.01
2.3
41
51
36
27
0
20
30
17
8
7
8
1.92
1.13
0
9
KHSO4
10
11
12
13
14
15
[BMIM][HSO4]
[HSO3-PMIM][HSO4]
[HSO3-BMIM][HSO4]
[HSO3-BPy][HSO4]
[BMIM][CF3SO3]
[TEPSA][HSO4]c
0
0
0
0
0.51
1.65
1.02
1.77
31
24
12
30
4
10
3
13
aThe amount of distillate.
bThe concentration of 3-methoxypropanal in the distillate was analyzed by GC.
cN,N,N-Triethyl-N-propanesulfonic acid ammonium hydrogen sulfate.
Table 2. Concentration and yield of 3-methoxypropanal by mixed catalysts
Entry
Catalyst (wt%)
Distillatea (g)
2.07
Concentrationb (%)
Yield (%)
1
2
NaHSO4 ꢀ H2O (15)
TBAB (2.5)
12
42
6
NaHSO4 ꢀ H2O (15)
1.37
15
b-CD (2.5)
3
4
NaHSO4 ꢀ H2O (15)
PEG400 (2.5)
NaHSO4 ꢀ H2O (15)
PEG400 (15)
CuSO4 (15)
2.08
2.26
1.96
2.07
2.4
44
48
28
59
20
63
21
53
23
27
14
31
12
39
12
28
5
b-CD (15)
CuSO4 (15)
6
PEG400 (15)
CuSO4 (15)
7
PEG200 (15)
CuSO4 (15)
8
2.48
2.35
2.12
PEG600 (15)
CuSO4 (15)
9
PEG800 (15)
NaHSO4 ꢀ H2O (15)
PEG600 (7.5)
b-CD (7.5)
10
11
12
CuSO4 (15)
PEG600 (7.5)
b-CD (7.5)
2.05
2.07
54
38
28
19
NaHSO4 ꢀ H2O (7.5)
CuSO4 (7.5)
aThe amount of distillate.
bThe concentration of 3-methoxypropanal in the distillate was analyzed by GC.

3-METHOXYPROPANAL FROM GLYCEROL
1379
positive effect (Table 2, entry 6). A series of PEG200–800 was investigated (Table 2,
entries 7–9), and we found the greatest enhancement was recorded with adding
PEG600 (Table 2, entry 8), which afforded 63% content and 39% yield. Moreover,
we used the mixture of copper sulfate and sodium bisulfate monohydrate catalysts
(Table 2, entry 12) and added the mixture of PEG600 and b-CD into copper sulfate
or sodium bisulfate monohydrate catalysts (Table 2, entries 10 and 11). However, the
results were not improved. The possible reason for this phenomenon is the metal
cation coordination ability of PEG causes heterogeneous catalysts to have better
solubility.
CONCLUSION
In summary, we have developed a novel and simple method for the synthesis of
3-methoxypropanal from glycerol in the presence of copper sulfate and PEG600.
Although it affords a moderate yield (39%) now, this methodology provides a new
application of glycerol, and such conversion can facilitate the replacement of
petroleum by renewable resources.
EXPERIMENTAL
General Procedure for the Preparation of 3-Methoxy-1,
2-propanediol
A three-necked flask equipped with a stirrer, a thermometer, and a distillatory
was charged with glycerol and 50% aqueous sodium hydroxide in the molar ratio of
glycerol=NaOH 3:1. The mixture was heated to about 120 ꢁC under reduced pressure
to distill water formed in the synthesis. Then dimethyl sulfate (DMS) was added
dropwise to the resulting sodium glycerate at 120–125 ꢁC in the molar ratio DMS=
NaOH 0.5:1. The resulting Na2SO4 was filtered off. After distillation of the bottom
in a vacuum and repeated fractionation, 3-methoxy-1,2-propanediol was isolated by
vacuum distillation, yield 59%.
General Procedure for the Preparation of 3-Methoxypropanal
3-Methoxy-1,2-propanediol (4 g) and catalyst were added into a 25-ml,
magnetically stirred reactor equipped with a thermometer, a condenser, and a distil-
latory. The reaction mixture was heated to about 200 ꢁC under atmospheric pressure,
and then the product was distilled. The reaction was completed in 30 min to an
hour, and dark residues were left. At the end of the reaction, the distillates were
weighed and analyzed with a gas chromatograph. The products were purified by frac-
tional distillation in vacuum. The structures of the products were confirmed by
1
1H NMR, 13C NMR, and HRMS. H NMR and 13C NMR spectra were obtained
on Bruker Avance III 500-MHz instrument for 1H at 500 MHz and for 13C at
125 MHz using CDCl3 as solvent and TMS as internal standard. High-resolution
mass spectra (HRMS) were recorded on a Waters Premier TOF-MS instrument with
CI source.

1380
J. CHEN AND X. DU
Data for 3-Methoxypropanal
1H NMR (CDCl3), d: 9.78–9.79 (t, J ¼ 1.8 Hz, 1H, CHO), 3.72–3.75
(t, J ¼ 6.0 Hz, 2H, CH2), 3.36 (s, 3H, CH3), 2.66–2.69 (td, J ¼ 6.0, 1.8 Hz, 2H,
CH2). 13C NMR (CDCl3), d: 201.07, 66.08, 58.70, 43.65. HRMS (CIþ) calculated
for C4H8O2: 88.0524. Found: 88.0515.
ACKNOWLEDGMENT
We thank Dr. Xu Zhang of Wuhan University for helpful discussions.
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