Synthesis of phenylacetaldehyde from 1-phenylethan-1,2-diol by microwave-assisted dehydration in water

Article abstract of DOI:10.1007/s10562-015-1606-4

A highly efficient, simple and versatile acid catalyst is proposed for the selective dehydration of 1-phenylethan-1,2-diol to the phenylacetaldehyde as an industrial platform molecule. For the first time, common Lewis acids AlCl₃ and FeCl₃ and mineral acids HCl and H₂SO₄ had produced the acetaldehyde derivative under microwave irradiation in sub-critical water in good yield starting from the corresponding diol.

Full text of DOI:10.1007/s10562-015-1606-4

Catal Lett (2015) 145:1851–1855
DOI 10.1007/s10562-015-1606-4
Synthesis of Phenylacetaldehyde from 1-Phenylethan-1,2-diol
by Microwave-Assisted Dehydration in Water
1
1
1,2
Sarah Le Guenic
•
Claire Ceballos
•
Christophe Len
Received: 2 July 2015 / Accepted: 4 August 2015 / Published online: 19 August 2015
Ó Springer Science+Business Media New York 2015
Abstract A highly efficient, simple and versatile acid
catalyst is proposed for the selective dehydration of
1 Introduction
1
-phenylethan-1,2-diol to the phenylacetaldehyde as an
Phenylacetaldehyde is a natural product having a narcissus-
like smell. This aldehyde is a molecule found in chocolate
[1], buckwheat [2]. The chemical production of phenylac-
etaldehyde permits to use it in industry as upstream raw
material and for downstream applications like preparation
of fragrances [3] but also pharmaceuticals [4] and insecti-
cides [5]. Different strategies afford the syntheses of
phenylacetaldehyde: (i) isomerization of styrene oxide both
in liquid or in gas phase (way A); (ii) Darzens glycidic
ester condensation of benzaldehyde (way B) and (iii)
dehydration of phenylethan-1,2-diol (way C) [6]. The main
drawbacks of these methodologies were the formation of
the corresponding enal due to competitive aldol
condensation.
industrial platform molecule. For the first time, common
Lewis acids AlCl and FeCl and mineral acids HCl and
3
3
H SO had produced the acetaldehyde derivative under
2
4
microwave irradiation in sub-critical water in good yield
starting from the corresponding diol.
Graphical Abstract
In regards of green chemistry and sustainable develop-
ment, chemists can act at different levels and especially by
using safer solvents and auxiliaries and by developing
alternative technologies. Hydrothermal transformation
using conventional heating or microwave activations per-
mitted to realize the dehydration of polyols from biomass
Keywords Homogeneous catalysis Á Microwaves Á Aldol
condensation
[
7, 8] and fossil resources [9–11]. In this regards, dehy-
dration of 1-phenylethan-1,2-diol (1) at 200 °C for 6 h
without the presence of acid afforded phenylacetaldehyde
Electronic Supplementary Material The online version of this
article (doi:10.1007/s10562-015-1606-4) contains supplementary
material, which is available to authorized users.
(
2) and the enal 3 in 24 and 41 % yields, respectively [9].
Using a similar strategy, Goettmann described the forma-
tion of compounds 2 and 3 in 22 and 21 % yields,
respectively [10]. It was noteworthy that the addition of
salts such as NaCl (1 M) permitted to increase the con-
version of the diol 1 in favor of the enal derivative 3
&
Christophe Len
christophe.len@utc.fr
1
Ecole Sup e´ rieure de Chimie Organique et Min e´ rale,
Sorbonne Universit e´ s, Universit e´ de Technologie de
Compi e` gne, EA4297 Transformations Int e´ gr e´ es de la Mati e` re
Renouvelable, Centre de Recherche Royallieu, CS 60319,
(64 %). Recently, Len’s group published the double
6
0203 Compi e` gne Cedex, France
dehydration of glycerol to acrolein and the synthesis of
quinoline in sub-critical water under both conventional
heating and microwave irradiation in batch [12, 13] and in
2
Department of Chemistry, University of Hull,
Hull HU6 7RX, UK
123

1
852
S. Guenic et al.
continuous flow [14]. Following our continued interest in
developing dehydration of alcohol in water, we now report
a novel and efficient synthesis of phenylacetaldehyde and
derivatives in sub-critical water under microwave
technology.
2
Experimental
2
.1 General
Substrate and product (1-phenylethan-1,2-diol and pheny-
lacetaldehyde) were purchased from Acros. Catalysts were
purchased from Acros [MnSO , FeCl , AlCl , FeSO ,
4
3
3
4
CaCl and H SO (96 %)], from Normapur [Fe (SO ) ,
4 3]
2
2
4
2
from Merck (ZnSO ) and from Carlo Erba [hydrochloric
4
acid (37 %) and NaCl]. All materials were used without
further purification. Distilled H O was used for preparation
2
1
13
of all aqueous solutions. H and C NMR spectra were
recorded on a 400 MHz Bruker UltraShield 400 MHz/
Scheme 1 Proposed mechanism for the dehydration of diol 1 to
aldehyde 2 with the AlCl catalyst in water
3
5
4 mm Ultra long hold. Chemical shifts (d) are quoted in
ppm and are referenced to TMS as an internal standard.
Coupling constants (J) are quoted in Hz. All reactions were
monitored by HPLC. The column used is a GRACE Prevail
C18. The detector used is a SPD-M20A photo diode array
detector (Shimadzu). The mobile phase is a mixture of
water and MeOH (20:80). Reactant and product concen-
trations were determined using calibration curves that were
obtained from references samples. The product yield (Yi),
2
.2 General Procedure for the Synthesis
of Phenylacetaldehyde (2) in Water Starting
from 1-Phenylethan-1,2-diol (1)
In a typical experiment, a 10 mL glass vessel was charged
with an aqueous solution (2 g) of 1-phenylethan-1,2-diol (1,
5
wt%) and a catalyst (20 mol%). The vessel was sealed
with a septum, placed in the microwave apparatus (An-
tonPaar Monowave 300) and heated to the desired temper-
ature under magnetic stirring (600 rpm) for the desired time.
Temperature in the vessel was measured by means of an IR
sensor. At the end of the reaction, the vessel was cooled down
to 40 °C using compressed air. Then, the reaction mixture
the conversion (X), the selectivity (S ) and the ratio 2/
i
(
2 1 3) were calculated by the following equations:
Final amount of product i ðmolÞ
Product yield Y ¼
i
Initial amount of reactant ðmolÞ
 100 %
ðInitial reactant amount ðmolÞ À Final reactant amount ðmolÞÞ
Initial amount of reactant ðmolÞ
Conversion X ¼
 100 %
was diluted in 100 mL of acetonitrile. An aliquot of the
diluted solution was taken (ca. 1.5 mL) and filtered prior to
analysis through a syringe filter (PTFE, 0.45 lm, VWR).
Yield of product i
Selectivity Si ¼
Ratio 2=ð2 þ 3Þ
 100 %
Conversion of reactant
3
Results and Discussion
Final amount of product 2ðmolÞ
Final amounts of product 2 þ product 3ðmolÞ
The initial dehydration reaction was performed using
¼
 100%
1
-phenylethan-1,2-diol (1) in the presence of AlCl3
(20 mol%) as a model reaction in neat water at 170 °C
1
23

Synthesis of Phenylacetaldehyde from 1-Phenylethan-1,2-diol by Microwave-Assisted Dehydration…
1853
under microwave irradiation. As expected the dehydration
reaction in presence of AlCl in water is believed to be
3
initiated by the hydrolysis of AlCl which forms under
3
microwave irradiation a cationic species [Al(OH)(H
2
-
2
?
?
2?
O) ] and H . It is notable that [Al(OH)(H O) ] and
5
2
5
?
H
could react as a potential electrophile with the diol 1
and as acid catalyst, respectively (Scheme 1). Using these
initial conditions, study of the rate of aldehyde 2 formation
as a function of time was realized (Table 1). Conversion of
the diol 1 increased with the time of the microwave irra-
diation and better yield of compound 2 was obtained after
1
13
Fig. 1 Structure of enal 3 by H and C NMR determination
structure. The configuration of the enal 3 was assigned to
the E configuration since an NOE interaction between the
C(3)H and the C(1)H was detected (Fig. 1).
3
0 min of reaction (Table 1, entry 3). After this time, the
yield of compound 2 and selectivity between compounds 2
and 3 decreased due to the formation of the aldehyde 3.
Consequently, 30 min of reaction have been selected for
the next steps.
Based on these results, dehydration of diol 1 was carried
out using AlCl (20 mol%) as catalyst in water for 30 min
3
at different temperatures (Table 2). Conversion increased
till 100 % after 30 min under microwave irradiation at
180 °C. With a temperature higher than 180 °C, the yield
of aldehyde 2 decreased from 55 to 31 % and the aldol
condensation furnishing compound 3 was preferred
(Table 2, entries 6–8). Considering the results, temperature
of 170 °C has been selected.
In contrast with previous reports [9, 10], aldol conden-
sation of aldehyde 2 afforded the (E)-2,4-diphenylbut-2-
enal (3). The structure of compound 3 was established by
1
13
NMR spectroscopy. H NMR and
C spectroscopy
1
experiments were performed at 296 K in CDCl . The H
3
NMR spectrum showed that (i) the C(1)H gave one singlet
at 9.67 ppm indicating no coupling with another hydrogen
atom; (ii) the C(3)H gave one triplet at 6.88 ppm and (iii)
the C(4)H gave one doublet at 3.71 ppm with an integral
value for two hydrogen atoms. The coupling constant
J = 7.6 Hz for C(3)H and C(4)H proved that the CH and
The next step consisted in studying variable catalyst
concentrations of AlCl for maximizing the aldehyde 2
3
yield (Table 3). Acid concentration had some influence on
the conversion of the diol 1 to the aldehyde 2 since 5 mol%
of AlCl gave 60 % of conversion (Table 3, entry 1) and
3
50 mol% of AlCl gave 91 % of conversion (Table 3, entry
3
1
3
CH2 groups were neighbors. The C NMR spectrum
showed the presence of an enal structure with the C(1)H at
6). In contrast, AlCl concentration had a lower influence
3
on the yield of aldehyde 2 (46–60 % yields) but a higher
concentration of AlCl increased the yield of compound 3.
1
1
1
93.51 ppm,
a
disubstituted carbon atom C(2) at
3
53.47 ppm and an electron deficient carbon atom C(4) at
1 13
38.02 ppm. The H and C NMR experiments confirmed
In the next steps, the amount of AlCl3 was fixed at
20 mol % due to a good equilibrium between yield of
compound 2, global selectivity and 2/(2 ? 3) balance.
that compound 3 had a 2,4-disubstituted-but-2-enal
Table 1 Acid catalyzed dehydration of diol 1 to aldehyde 2 under microwave irradiation at different time of reaction
a
a
Entry
Time(min)
Conversion (%)
Yield 2 (%)
Yield 3 (%)
Selectivity 2 (%)
2/(2 ? 3) (%)
1
2
3
4
5
6
a
10
20
30
40
50
60
51
64
80
86
94
98
36
48
55
53
53
48
1
71
75
69
61
56
49
97
98
95
88
82
83
1
3
7
12
10
The yield was calculated from HPLC analysis with a calibration curve
123

1
854
S. Guenic et al.
Table 2 Acid catalyzed dehydration of diol 1 to aldehyde 2 under microwave irradiation varying the temperature
a
a
Entry
T (°C)
Conversion (%)
Yield 2 (%)
Yield 3 (%)
Selectivity 2 (%)
2/(2 ? 3) (%)
1
2
3
4
5
6
7
8
a
130
140
150
160
170
180
190
200
5
0
0
0
0
6
4
0
66
81
77
69
45
39
31
100
100
97
95
67
58
53
16
44
80
100
100
100
13
34
55
45
39
31
0
1
3
22
28
27
The yield was calculated from HPLC analysis with a calibration curve
Table 3 Acid catalyzed dehydration of diol 1 to aldehyde 2 under microwave irradiation varying the concentration of AlCl
3
a
Entry
AlCl
3
(mol %)
Conversion (%)
Yield 2 (%)
Yield 3 (%)
Selectivity 2 (%)
2/(2 ? 3) (%)
1
2
3
4
5
6
a
5
60
73
80
81
91
91
46
51
55
49
58
60
1
2
3
4
6
9
77
70
69
60
64
66
98
96
95
92
91
87
10
20
30
40
50
The yield was calculated from HPLC analysis with a calibration curve
Afterwards, different acids such as Lewis acid, Brønsted
acid, metal sulfate and salts were tested in sole water at
of different alcohols, metal sulfates (Table 1, entries 5–8)
and chloride salts (Table 1, entries 9 and 10) did not permit
to furnish aldehyde 2 in good yield. In our hands, opti-
mized dehydration of the diol 1 in sub-critical water under
microwave irradiation was realized in the presence of
AlCl , FeCl , HCl or H SO at 170 °C for 30 min. In these
conditions, the target aldehyde 2 was selectively obtained
in 55–63 % yields with both good global selectivity and
excellent selectivity for aldehyde 2 over aldehyde 3
(Table 4, entries 1–4). To the best of our knowledge, this is
the first time that phenylacetaldehyde (2) was produced in
liquid phase in yield higher than 45 % starting from the
corresponding diol (1).
170 °C for 30 min under microwave irradiations in order to
isolate selectively the target aldehyde 2 (Table 4). From
those experiments one could see that Lewis acids AlCl3
and FeCl (Table 1, entries 1, 2) and Brønsted acids HCl
3
3
3
2
4
and H SO (Table 1, entries 3, 4) had a major impact on
2
4
the dehydration. Using FeCl , HCl and H SO , a full
3
2
4
conversion of the starting material 1 was detected and
aldehyde 2 was obtained with higher yields than with
AlCl . However, the global selectivity was more important
3
when AlCl was used. In contrast with the results obtained
3
by Vogel [15, 16] and Goettmann [10] for the dehydration
1
23

Synthesis of Phenylacetaldehyde from 1-Phenylethan-1,2-diol by Microwave-Assisted Dehydration…
1855
Table 4 Acid catalyzed dehydration of diol 1 to aldehyde 2 under microwave irradiation varying the nature of the catalyst
a
Entry
Acid (20 mol %)
Conversion (%)
Yield 2 (%)
Yield 3 (%)
Selectivity 2 (%)
2/(2 ? 3) (%)
1
2
3
4
5
6
7
8
9
AlCl
FeCl
HCl
3
3
80
99
96
97
0
55
59
63
62
0
3
6
4
4
0
0
0
0
0
0
69
60
66
64
0
95
91
94
H
2
SO
MnSO
ZnSO
FeSO
Fe (SO
NaCl
CaCl
4
94
4
0
4
3
2
67
50
48
100
100
100
100
100
100
100
4
2
1
2
4
)
3
54
1
26
1
1
0
2
4
4
a
The yield was calculated from HPLC analysis with a calibration curve
2
3
4
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4
Conclusion
In conclusion, AlCl , FeCl , HCl and H SO are excellent
4
3
3
2
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2
4
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3
3
1
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by aldol condensation was detected.
1
1
Acknowledgments S.L.G. thanks the Ministere de la Recherche de
France for MENRT financial support.
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