Self- and cross-aldol condensation of propanal catalyzed by anion-exchange resins in aqueous media

Article abstract of DOI:10.1021/op200004p

Carbon-carbon bond formation using strong and weak anion-exchange resins as green catalysts for self- and cross-aldol condensation of propanal in aqueous media was investigated. The reaction pathway followed the route of aldol condensation to a β-hydroxy aldehyde and dehydration to an α,β-unsaturated aldehyde. The resulting products were further converted to hemi-acetal, and/or acetal moieties, which were confirmed by FT-IR and NMR. In self-condensation using strong anion-exchange resin, 97% conversion of propanal was achieved with 95% selectivity to 2-methyl-2-pentenal within 1 h using 0.4 g/mL resin at 35 °C. The conversion and selectivity using weak anion exchanger was lower. During cross-aldol condensation of propanal with formaldehyde, 3-hydroxy-2-methyl-2-hydroxymethylpropanal was obtained as the main product through first and second cross-condensation followed by hydration reaction in acidic aqueous conditions. The strong anion-exchange resin provided maximal propanal conversion of 80.4% to the product with 72.4% selectivity after 7 h reaction at 35 °C and resin concentration of 1.2 g/mL. Using weak anion-exchange resin, the optimal conversion of propanal was 89.9% after 24 h at 0.8 g/mL resin and 35 °C, and the main product was 3-hydroxy-2- methylpropanal by first cross-aldol condensation along with relatively minor amounts of methacrolein and 3-hydroxy-2-methyl-2-hydroxymethylpropanal.

Full text of DOI:10.1021/op200004p

ARTICLE
pubs.acs.org/OPRD
Self- and Cross-Aldol Condensation of Propanal Catalyzed by
Anion-Exchange Resins in Aqueous Media
Sang-Hyun Pyo,*,† Martin Hedstr€om,† Stefan Lundmark,‡ Nicola Rehnberg,§ and Rajni Hatti-Kaul†
†Department of Biotechnology, Center for Chemistry and Chemical Engineering, Lund University, Box 124, 221 00 Lund, Sweden
‡Perstorp AB, 284 80 Perstorp, Sweden
§Strategic R&D, Bona AB, Box 210 74, 200 21 Malm€o, Sweden
S Supporting Information
b
ABSTRACT: Carbonꢀcarbon bond formation using strong and weak anion-exchange resins as green catalysts for self- and cross-
aldol condensation of propanal in aqueous media was investigated. The reaction pathway followed the route of aldol condensation to
a β-hydroxy aldehyde and dehydration to an R,β-unsaturated aldehyde. The resulting products were further converted to hemi-
acetal, and/or acetal moieties, which were confirmed by FT-IR and NMR. In self-condensation using strong anion-exchange resin,
97% conversion of propanal was achieved with 95% selectivity to 2-methyl-2-pentenal within 1 h using 0.4 g/mL resin at 35 °C. The
conversion and selectivity using weak anion exchanger was lower. During cross-aldol condensation of propanal with formaldehyde,
3-hydroxy-2-methyl-2-hydroxymethylpropanal was obtained as the main product through first and second cross-condensation
followed by hydration reaction in acidic aqueous conditions. The strong anion-exchange resin provided maximal propanal
conversion of 80.4% to the product with 72.4% selectivity after 7 h reaction at 35 °C and resin concentration of 1.2 g/mL. Using
weak anion-exchange resin, the optimal conversion of propanal was 89.9% after 24 h at 0.8 g/mL resin and 35 °C, and the main
product was 3-hydroxy-2-methylpropanal by first cross-aldol condensation along with relatively minor amounts of methacrolein and
3-hydroxy-2-methyl-2-hydroxymethylpropanal.
’ INTRODUCTION
2-pentanal at 135 °C.8 The basic resins were used for aldol
condensation of 1-butanal or hexanal and gave only poor con-
version and product selectivity.9 By using benzene as solvent with
anion-exchange resin as the catalyst for self-aldol condensation of
propanal, 2-methyl-2-pentenal was obtained at 93.5% yield.10
The cross-aldol condensation of aliphatic aldehydes, especially
propanal with formaldehyde under more environmentally be-
nign conditions, has not been much studied. BASF has employed
this type of reaction to form methacrolein, which is an indust-
rially important intermediate for manufacture of methacrylic
acid, a monomer for acrylate polymers.11 Methacrolein can
be effectively synthesized from formaldehyde, syngas, and ethy-
lene using a tandem oxo-Mannich sequence of reactions.12
Butyraldehyde was aldolized with formaldehyde at 40ꢀ80 °C
over an anion-exchange resin catalyst in aqueous and methanolic
solutions to form two main products: 2-ethyl-3-hydroxy-
2-hydroxymethylpropanal (trimethylolpropane aldol) and 2-ethyl-
propenal (ethylacrolein).13,14
Inspite of the great interest in applying more environmentally
friendly approaches for new CꢀC bond formation from propanal,
there is little information available on the aldol condensation
reaction in aqueous media. Under aqueous conditions, the aldol
condensation should be more complicated due to additional
reactionssuch ashydrationand acetalization ofaldol products.15,16
Although enzymatic processes in nature must occur in an aqueous
environment by necessity, water has been a solvent to be avoided
Aldol reaction is one of the important means to form a CꢀC
bond using chemical or enzymatic catalysts.1ꢀ4 Carbonꢀcarbon
bond formation is the essence of organic synthesis and provides
the foundation for generating more complex organic compounds
from the simpler ones.5 Propanal, a building block molecule of
three carbons, is one of the important chemicals in the chemical
industry and is extensively used in rubber, plastic, coating,
pharmaceutical, pesticide, and feed additive industries.6 Conver-
sion of propanal by aldol reaction can be employed as a very
useful method for new CꢀC bond formation leading to the
synthesis of larger building blocks. A self-aldol condensation
product of propanal, 2-methyl-2-pentenal, is a commercially
important chemical intermediate used in pharmaceuticals, fra-
grances, flavors, and cosmetics industry.7 2-Methyl-2-pentenal is
produced by self-aldol condensation using a stoichiometric
amount of NaOH solution at 100 °C and 0.76ꢀ1.86 MPa with
99% conversion of propanal and 86% selectivity.7 This process
using higher than stoichiometric amount of a liquid base (KOH
or NaOH) is not eco-friendly and requires large amount of water
for removal and neutralization of the base during downstream
processing of the product.
Recently, there have been many efforts to provide a more clean
approach for the production of 2-methyl-2-pentenal.7ꢀ11 The
product was obtained with 99% selectivity by aldol condensation
using the hydrotalcite of Mg/Al, which was activated at 450 °C for
4 h.7 The self-aldol reaction in supercritical CO2 using various
catalysts like Amberlyst15 provided 76% conversion with 88%
selectivity, or 43% conversion with 99% selectivity to 2-methyl-
Received: January 5, 2011
Published: March 18, 2011
r
2011 American Chemical Society
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for common organic reactions.5 However, as a result of the
explosion of research activities in recent years in the field of Green
Chemistry, organic reactions in water have become some of the
most exciting research endeavours.
In this investigation, strong and weak anion-exchange resins
were employed in aqueous media for self- and cross-aldol con-
densation of propanal, and the reaction pathways were compared.
The degree and rate of propanal consumption increased with
an increase in the amount of the Amberlite IRA-401 used as the
catalyst; however, only at a resin concentration of 0.4 g/mL,
was the propanal converted with 95% selectivity to 2-methyl-2-
pentenal (3, retention time (RT) in HPLC of 16.2 (Supporting
Information)), which is higher than that reported earlier for the
reaction using benzene as solvent.10 Formation of 3-hydroxyl-
2-methylpentanal (2, RT11.2 (Supporting Information)) was also
noted as an intermediate product, according to Scheme 1A. At
lower resin concentration (0.2 g/mL), propanal conversion was
only 80% and maximum selectivity for the product 3 was 50% at 2 h
reaction time, while at higher resin concentration (0.6 g/mL),
although the propanal consumption was complete, only 30% ended
in product 3 after 30 min reaction. Much higher levels of product 2
were detected (up to 20%) when using 0.2 g/mL of the
resin as compared to 1ꢀ2% for the higher resin concentrations.
As seen in Figure 1, the concentration of 3 decreased on prolonged
reaction to give additional reaction products, which were not
detected by HPLC and hence were not aldehyde compounds
and are proposed as polyol, acetal, and hemi-acetal compounds
later in this paper.
’ RESULTS AND DISCUSSION
1. Self-Aldol Condensation of Propanal. 1.1. Self-Aldol
Condensation of Propanal Using Strong Anion-Exchange Resin.
The anion-exchange resin Amberlite IRA-401 was used as a
catalyst at low temperature for self-aldol condensation of propa-
nal in an aqueous medium. The reaction progressed quickly,
yielding high conversion of propanal within 1 h at 35 °C (Figure 1).
The effect of reaction temperature (20, 35, and 50 °C) was
evaluated using 0.4 g/mL of Amberlite IRA-401. The optimum
temperature with respect to propanal conversion and selectivity
for product 3 was 35 °C as shown above. Although the reaction
rate increased at higher reaction temperature, the selectivity was
extremely low while lower reaction temperature showed lower
reaction rate (after initial 20 min) and increasing selectivity with
the course of the reaction (Figure 2).
The possibility of the product 3 reacting with the starting
aldehyde (1) as second aldol condensation (pathway A) was
further investigated. Only two small peaks appeared at RT14 on
the HPLC chromatograms, which were predicted as isomers of
β-hydroxyaldehyde product (4) by LC-MS (Supporting In-
formation). In the presence of strong base, Cannizzaro reaction
from 3 could take place to produce an alcoholic compound
Figure 1. Self-aldol condensation of propanal at 35 °C using different
amounts of strong anion-exchange resin, Amberlite IRA-401: 0.2 g/mL
(diamond), 0.4 g/mL (square), and 0.6 g/mL (triangle). Percent
conversion of propanol is shown as filled symbols, and selectivity for
production of 2-methyl-2-pentenal is shown as empty symbols.
Scheme 1. Possible Reaction Pathway during Self- and Cross-Aldol Condensation of Propanal and Formaldehyde in Aqueous
Medium
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Figure 2. Effect of reaction temperature on self-aldol condensation of
propanal using 0.4 g/mL of Amberlite IRA-401. The temperatures used
were 20 °C (diamond), 35 °C (square), and 50 °C (triangle). Percent
conversion of propanol is shown as filled symbols, and selectivity for
production of 2-methyl-2-pentenal is shown as empty symbols.
Figure 3. Effect of the amount of strong anion-exchange resin, Amber-
lite IRA-401 on cross-aldol condensation of propanal with formaldehyde
at 35 °C. The resin was used at a concentration of 0.4 g/mL (9), 0.8 g/
mL (2), 1.2 g/mL (O) and 1.6 g/mL (/), respectively.
stage of the reaction between propanal and formaldehyde, using
Amberlite IRA-401 as catalyst, included two peaks of the starting
materials at RT9.5 and RT12.6 and a new peak at RT 6.2
corresponding to 2,2-bishydroxymethylpropanal as the main
product (8) resulting from first and second cross-aldol conden-
sation (Table 1, Scheme 1B, Supporting Information). The
product peak at RT 8.7 (6) is the intermediate, 3-hydroxy-
2-methylpropanal formed after first cross-condensation, which is
transformed to 8 by a second aldol condensation on one hand
and, on the other, undergoes dehydration to product 7, with
methacrolein appearing at RT13.8. A small amount of the
product 3 from self-condensation of propanal was also seen at
RT16.2 (Supporting Information, Pathway A). Figure 3 shows
the profiles of propanal conversion obtained at different amounts
of the ion-exchange resin. Larger amount of resin, 1.2ꢀ1.6 g/mL,
was required for the highest reaction rate that was slower than
that of self-aldol condensation. The maximum conversion of
propanal obtained was about 83% after 5 h and 91% after 24 h at
35 °C (Figure 3).
Figure 4 shows the conversion of propanal and formaldehyde
with time along with the formation of different products in the
reaction catalyzed by 1.2 g/mL of resin. The selectivity of
conversion of propanal to particular aldehyde products was
estimated from the area of each peak in HPLC. From the product
profiles observed in Figure 4, it seems that all of the possible
reactions took place to give corresponding products within 1 h
from the start of the reaction. The products (2 and 3) from self-
aldol condensation (pathway A) and the product 7 from pathway
B involving first cross-condensation followed by dehydration
reaction were maintained at the same low level during the entire
reaction time. Pathway B was the main reaction giving primarily 8
within 3 h, while the intermediate 6 was increased until 1 h and
then decreased within a few hours to a basal level. Product 8
reached highest level at 4ꢀ7 h, after which it started to gradually
decrease, which may correspond to conversion to other reaction
products.
Table 1. Molecular Masses of Aldehyde Products Derivatized
by DNPH
mass
products
calculated
measureda
1
2
3
4
5
6
7
8
238.20
296.28
278.26
336.34
210.15
268.23
250.21
298.25
237.17
295.23
277.21
335.27
209.12
267.19
249.17
297.12
a The molecular masses were measured as negative mode by electrospray
ionization mass spectrometry.
(mono-ol).13 However, as in the present system, the final
reaction pH was around 5, this possibility was ruled out. On
the other hand, hydration and/or hemiacetalization of 3 could
take place in the acidic aqueous medium.
1.2. Self-Aldol Condensation of Propanal Using Weak Anion-
Exchange Resin. Using a weak anion-exchange resin as the
catalyst gave different results under similar reaction conditions
as above. The conversion of propanal was only around 70%, and
the selectivity for 2-methyl-2-pentenal (3) was very low as only a
trace amount was detected by HPLC (data not shown). Even the
other major peaks were not detected on the HPLC chromato-
gram. This was explained as the differences of reaction rates
between aldol condensation and hydration reaction. During the
time taken to reach 70% conversion (7 h), the resulting product
(3) could be quickly converted further to other products. The
intermediate (2) was maintained at a slightly higher content than
with strong anion exchanger, while there was no peak of a second
aldol condensation product.
When following the consumption of the starting materials, it
was observed that the conversion rate of propanal was slightly
higher in the initial stage perhaps due to self-condensation
reaction (Scheme 1A). However, the conversion of formalde-
hyde was continuously increased and reached 94.5%, while
conversion of propanal was 87.4% at 24 h. The higher conversion
2. Cross-Aldol Condensation of Propanal and Formalde-
hyde. 2.1. Strong Anion-Exchange Resin as a Catalyst for Cross-
Aldol Condensation between Propanal and Formaldehyde. In the
reaction between propanal and formaldehyde, both self- and
cross-aldol condensation reactions are possible (Scheme 1).
HPLC chromatograms of the samples taken from the initial
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Figure 4. Cross-aldol condensation of propanal with formaldehyde
catalyzed by 1.2 g/mL of Amberlite IRA-401 at 35 °C. The various
symbols show conversion of propanal (() and formaldehyde (9), and
selectivity for formation of 3 (b), 6 (ꢁ), 7 (/), and 8 (2).
Figure 5. Effect of reaction temperature on cross-aldol condensation of
propanal with formaldehyde using 1.2 g/mL Amberlite IRA-401 at 20
°C ((), 35 °C (9), and 50 °C (2). The inset table shows selectivity for
product 8 after 7 and 24 h reaction.
from use of an excess amount of formaldehyde explained the
second aldol condensation of 6 to produce 8.
Figure 5 shows the effect of reaction temperature (20, 35, and
50 °C) on the reaction using 1.2 g/mL of Amberlite IRA-401.
The reaction progressed to over 75% conversion within 2 h at 35
and 50 °C, while the rate at 20 °C was significantly low.
Selectivity for 8 was the highest (72.4%) at 35 °C at 7 h of
reaction but decreased with time as described above.
Figure 6. Conversion of propanal (A) and selectivity for product 8 (B),
and product 6 (C) during cross-aldol condensation with formaldehyde
at various ratios of formaldehyde (FA) and propanal (PA) using 1.2 g/
mL of Amberlite IRA-401 at 35 °C. FA/PA ratios were 0:1 ((), 0.57:1
(9), 1.14:1 (2), and 1.71:1 (ꢁ).
2.2. Ratio of Propanal and Formaldehyde in Cross-Aldol
Condensation Using Strong Anion-Exchange Resin. Propanal
was reacted with different concentrations of formaldehyde (0,
0.57, 1.14, and 1.71 equiv). Although the highest rate was
obtained in the reaction without formaldehyde, that is, self-aldol
condensation, all reactions reached about 80% conversion within
7 h (Figure 6A). Selectivity for 8 was 72.6, 65.9, and 32.8% at FA/
PA ratios of 1.14, 1.71, and 0.57, respectively (Figure 6B).
Considering reaction rates at ratios 1.14 and 1.71 to be similar
(Figure 6A), some different tendencies were seen with respect to
selectivity for 8 and 6 (Figure 6B,C). Reaction intermediate 6
was quickly made in the initial stage, reaching the highest level at
the highest ratio of FA/PA, and then decreased rapidly due to its
conversion to 8. The sum of 6 and 8 was increased with
increasing amount of FA as a result of increase in first and
second cross-aldol condensations. On the other hand, the
amount of 2 and 3 was decreased to 9.9, 2.2, and 0.8% for FA/
PA ratios of 0.57, 1.14, and 1.71, respectively.
2.3. Cross-Aldol Condensation of Propanal with Formalde-
hyde Using Weak Anion-Exchange Resin. The use of weak
anion-exchange resin for the reaction between propanal and
formaldehyde gave 3-hydroxy-2-methylpropanal (6) as the main
product (Figure 7). The highest selectivity for product 6 was
70.9% at 2 h reaction time (when the conversion of PA was about
50%) and decreased with time to about 60% at 24 h when the
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Table 2. Conversion and Selectivity of Cross-Aldol Con-
densation Using Weak Anion-Exchange Resin under Varying
Reaction Conditions
reaction condition
selectivity (%)
temp
resin/PA
ratio
time conversion
run (°C)
(h)
(PA, %)
6
7
8
1
2
3
4
5
6
7
8
20
20
35
35
35
35
35
35
1.2
1.2
0.4
0.8
0.8
1.2
1.2
1.2
7
24
7
72.0
84.6
45.4
76.3
89.9
81.2
89.8
95.8
51.1
56.5
79.6
55.6
56.2
55.3
49.8
42.1
2.8
3.5
4.9
6.4
8.9
6.5
11.2
5.9
7
24
5
12.8
5.2
14.2
7.6
7
5.5
11.3
11.4
Figure 7. Conversion of propanal (() and selectivity for 6 (ꢁ), 7 (/), 8
(2), 6 and 8 (9) during cross-aldol condensation using weak anion-
exchange resin (Amberlite IRA-45, 1.2 g/mL) at 35 °C.
24
11.6
1
compounds in the sample. The chemical shifts on H NMR at
2.07, 2.50, and 3.33 ppm under DMSO-d6 were assigned to the
remaining solvents of acetonitrile, DMSO, and water according
to the work of Gottlieb et al.18 The protons attached to
heteroatoms such as oxygen and a particular functional group
such as aldehyde and acetal show different chemical shifts on 1H
NMR (Supporting Information). The weak intensity of aldehyde
at around 9.5 ppm showed that remaining aldehyde was very little
in comparison to the protons of aliphatic carbon at around
0.5ꢀ1.0 ppm. Resulting alcohol, vinyl, hemi-acetal, and acetal
products appeared at the chemical shift region of 3.0ꢀ7.0 ppm.
13C NMR spectrum showed multiple peaks in the 80ꢀ110
ppm region, also indicating hydration and/or hemiacetalization
of aldehyde, but the hydration could also take place on the β-
carbon of R,β-unsaturated aldehyde such as 3 and 7.
conversion had reached 89.9%. Both 7 and 8 were maintained at
similar low levels throughout the reaction. The combined
selectivity for 6 and 8 was maintained over 70%. The self-
condensation products (2 and 3) were not detected by HPLC.
It can thus be inferred that the reaction progressed quickly to
produce the main product (6), part of which was slowly
converted to 7 and 8, and then may be further converted to
hydrated products.
The extent of PA conversion and selectivity for different
products (6, 7, and 8) obtained at different times with different
amounts of weak anion-exchange resin are summarized in
Table 2. The reaction (runs 1 and 2) at low temperature and
high amount of resin gave lower yield and selectivity. The
maximal conversion of about 90% was obtained in the reaction
at 35 °C, 24 h, and 0.8 g/mL resin, with 6 being the major
product while 7 and 8 were formed in almost equal amounts. The
rate of second aldol condensation using weak exchanger was
slower than that with the strong exchanger, which could be due to
weak association of the resin with R-carbon to give low rate
dissociation of Hþ by its counteranion, and the longer lifetime of
6 results in increased formation of 7/8.
Hence, the pathways of self- and cross-aldol condensation are
followed by further reaction such as hydration, hemiacetalization,
and acetalization. The equilibrium between an aldehyde and its
hydrate is quickly established, resulting in higher molecular
dimers, trimers, and polymers.14ꢀ17,19
3. End Products of Pathways of Self- and Cross-Aldol
Condensation of Propanal with Formaldehyde Catalyzed
by Anion-Exchange Resins in Aqueous Media. Garland et al.
’ CONCLUSION
The work reported in this paper shows that aldol condensa-
tion using ion-exchange resin as heterogeneous catalyst in
aqueous media can provide an alternative green approach for
new CꢀC bond formation. While self-aldol condensation using
strong anion-exchange resin is extremely efficient, providing high
yields of the product rapidly, cross-aldol condensation is more
complex involving more than one condensation reactions. The
desired products of cross-aldol condensation can, however, be
obtained by proper selection of weak or strong catalyst and other
reaction conditions. The aqueous conditions promote the
formation of other reaction products on prolonged incubation,
hence termination of the reaction at a proper time is important
for obtaining high product yields. Low temperature and ab-
sence of organic solvents provide extremely energy-efficient
and eco-friendly process conditions as compared to the other
methods reported so far. Recycling of the ion-exchange resin
was, however, limited to a few cycles, perhaps due to deactivation
of the resin in the aqueous medium.20 Conditions for improved
recycling need tobeinvestigated tomakethe processeconomically
viable.
1
have earlier demonstrated by FT-IR and H NMR that the
products resulting from acid-catalyzed reaction of hexanal on
sulfuric acid particles were both aldol condensation and hemi-
acetal products.17 It seems that the aldehyde products formed by
aldol condensation in aqueous media catalyzed by the ion-
exchange resins also undergo further reaction to give alcoholic,
hemi-acetal, and acetal moieties. The reaction mixtures with
anion-exchange resins were allowed to stand at room tempera-
ture for 2 weeks. The solutions were then filtered, and the filter
rinsed with acetonitrile and pooled with filtered solution, which
was dried to give clean liquid with high viscosity. The samples
were then subjected to FT-IR and 1H and 13C NMR analyses.
Very similar results from self- and cross-aldol reactions
using strong and weak anion-exchange resin were obtained
(Supporting Information). The FT-IR spectrum showed a strong
band in the OH stretching region of 3000ꢀ3500 cmꢀ1 ascribed
to alcoholic compounds, while very weak or no band for the band
stretching of carbonyl and water was seen at around 1700 and
1650 cmꢀ1, respectively, suggesting the absence of carbonyl
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Organic Process Research & Development
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’ EXPERIMENTAL SECTION
Scheme 2. Formation of Aldehyde Derivatives by 1,3-Dini-
trophenylhydrazine (DNPH)
Materials. Propanal (97%), 2,4-dinitrophenylhydrazine (99%,
DNPH), 2-methyl-2-pentenal (97%), and methacrolein (95%)
were purchased from Sigma-Aldrich (St. Louis, MO). Formal-
dehyde (37%, aqueous solution in 10% methanol) and acetoni-
trile (HPLC grade) were purchased from Merck (Germany). All
chemicals were used without further treatment. Amberilte IRA-
401 (strong anion-exchange resin with quaternary amino group-
s) and Amberlite IRA-45 (weak anion-exchange resin with
primary, secondary, and tertiary amino groups), based on
styrene-divinylbenzene matrix, were purchased from BDH Che-
micals (Poole, England).
General Reaction Procedure. For the self-condensation
reaction, 64.8 mmol (4.5 mL) propanal was mixed with 60 mL
of deionized water on a magnetic stirrer for 30 min at room
temperature in a 250 mL flask attached with a water condenser.
The reaction was started by adding strong anion-exchange resin
(Amberlite IRA-401) or weak anion-exchange resin (Amberlite
IRA-45), which were preactivated by treatment with 10% sodium
hydroxide, followed by washing with deionized water to pH
7.5ꢀ8.0.
(Perkin-Elmer, Norwalk, CT) and spiking method using stan-
dard materials. Elucidations of product structure were performed
1
using FT-IR (Bruker, ALPHA-P, Germany) and H and 13C
NMR (Bruker, UltraShield Plus 400, Germany).
’ ASSOCIATED CONTENT
S
Supporting Information. Additional figures. This materi-
b
al is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Phone: þ46-46-222-8157. Fax: þ46-46-222-4713. E-mail:
As a general method of cross-aldol condensation, 65 mmol
(4.5 mL) propanal and 74 mmol (6 mL) formaldehyde
(37%, aqueous solution) were mixed with 54 mL of deionized
water under the same conditions as above. The reaction was
started by addition of strong or weak anion-exchange resin.
Effects of the amount of ion-exchange resin, ratio of propanal
and formaldehyde, and temperature on reaction yield and
product selectivity were investigated. The reaction temperature
was controlled by using a water bath. Aliquots were taken at
different time intervals to analyze the contents of the substrates
and products. Blank reactions without using ion-exchange resin
were also run, which did not show any substrate conversion.
Analyses Using HPLC, LC-MS, FT-IR, and 1H and 13C NMR.
Quantitative analyses of the substrates and products were
performed using high-performance liquid chromatography
(Jasco, Tokyo, Japan) on a RP-18 column (4.6 ꢁ 250 mm, pore
diameter 5 μm, Merck, Germany). The column was eluted by a
gradient of solvent A (30% acetonitrile/water) and B (100%
acetonitrile) starting from 90 vol A/10 vol B to 10 vol A/90 vol B
for 15 min, and then 10 vol A/90 vol B for 5 min at a flow rate of
1.0 mL/min. All samples were derivatized with DNPH for
detection by UV detector (Scheme 2).21 One hundred microliter
samples diluted 40 times were reacted with 50 μL of 0.1 M
DNPH stock solution (prepared in a solvent system composed of
1:1 2 N HCl/acetonitrile) at room temperature for 20 min,
followed by two extractions using 250 μL of ethyl acetate. One
hundred microliters of the extract solution was dried and
dissolved in 0.5 mL of acetonitrile for injection into HPLC.
Elution was monitored at 356 nm, λmax of derivatized propanal.22
The selectivity was estimated by comparing the peak area of the
products on the chromatogram. The concentrations of propanal
and formaldehyde in the samples taken during the reaction were
calculated from their respective standard curves prepared in the
range of 0.05 to 2.0 mg/mL. The percent conversion of the
substrates was then calculated by comparison with the respective
concentration at time zero.
sang-hyun.pyo@biotek.lu.se.
’ ACKNOWLEDGMENT
The work was financially supported by Vinnova (The Swedish
Agency for Innovation Systems).
’ REFERENCES
(1) Eꢀge, S. N. Organic Chemistry, 4th ed.; Houghton Mifflin: Boston,
MA, 1999; p 666.
(2) Sharma, S. K.; Parikh, P. A.; Jasra, R. V. J. Mol. Catal. A 2009,
301, 31.
(3) Khan, S. S.; Shah, J.; Liebscher, J. Tetrahedron 2010, 66, 5082.
(4) Siyutkin, D. E.; Kucherenko, A. S.; Zlotin, S. G. Tetrahedron
2010, 66, 513.
(5) Li, C.-J. Chem. Rev. 2005, 105, 3095.
(6) Market analysis of propanal, propanol, and propionic acid.
(Organics), China Chemical Reporter, 26-SEP-04; http://goliath.ec-
next.com/coms2/gi_0199-2329431/Market-analysis-of-propanal-pro-
panol.html.
(7) Sharma, S. K.; Parikh, P. A.; Jasra, R. V. J. Mol. Catal. A 2007,
278, 135.
(8) Stevens, J. G.; Bourne, R. A.; Poliakoff, M. Green Chem. 2009,
11, 409.
(9) Astle, M. J.; Zaslowsky, J. A. Ind. Eng. Chem. 1952, 44, 2869.
(10) Tang, S. P.; Li, Q. H.; Yin, D. L. Acta Sci. Nat. Univ. Norm.
Hunan 2001, 24, 42.
(11) Merger, F.; Foerster, H. J. EP 58927, 1982.
(12) Deshpande, R. M.; Diwakar, M. M.; Mahajan, A. N.; Chaudhari,
R. V. J. Mol. Catal. A 2004, 211, 49.
(13) Serra-Holm, V.; Salmi, T.; Multam€aki, J.; Reinik, J.; M€aki-
Arvela, P.; Sj€oholm, R.; Lindfors, L. P. Appl. Catal. A 2000, 198, 207.
(14) Serra-Holm, V.; Salmi, T.; M€aki-Arvela, P.; Paatero, E.; Lindfors,
L. P. Org. Process Res. Dev. 2001, 5, 368.
(15) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry: Part A
Structure and Mechanisms, 4th ed.; Plenum Press: New York, 2000;
p 228.
(16) Jang, M.; Czoschke, N. M.; Northcross, A. L. Environ. Sci.
Technol. 2005, 39, 164.
The derivatized aldehyde compounds were also elucidated by
electrospray ionization mass spectrometry using a QSTAR
hybrid Pulsar instrument (Applied Biosystems, CA, USA)
equipped with series 200 liquid chromatography system
(17) Garland, R. M.; Elrod, M. J.; Kincaid, K.; Beaver, M. R.;
Jimenez, J. L.; Tolbert, M. A. Atmos. Environ. 2006, 40, 6863.
636
dx.doi.org/10.1021/op200004p |Org. Process Res. Dev. 2011, 15, 631–637

Organic Process Research & Development
ARTICLE
(18) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997,
62, 7512.
(19) Solomons, T. W. G. Organic Chemistry; 4th ed.; John Wiley &
Sons: New York, 1988; p 791.
(20) Malshe, V. C.; Sujatha, E. S. React. Funct. Polym. 1997, 35, 159.
(21) Lipari, F.; Swarin, S. J. J. Chromatogr. 1982, 247, 297.
(22) Cordis, G. A.; Das, D. K.; Riedel, W. J. Chromatogr. A 1998,
798, 117.
637
dx.doi.org/10.1021/op200004p |Org. Process Res. Dev. 2011, 15, 631–637