Can molecular sieves be used as water scavengers in microwave chemistry?

Article abstract of DOI:10.1071/CH08450

The use of sealed-vessel microwave-assisted organic synthesis in combination with 4 molecular sieves as water scavengers is investigated. Two classical model transformations, namely acetal formation and imine formation, are evaluated under both convention

Full text of DOI:10.1071/CH08450

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2009, 62, 244–249
www.publish.csiro.au/journals/ajc
Can Molecular Sieves be Used as Water Scavengers
in Microwave Chemistry?
A
A,B
Mostafa Baghbanzadeh and C. Oliver Kappe
AChristian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry,
Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
B
Corresponding author. Email: oliver.kappe@uni-graz.at
The use of sealed-vessel microwave-assisted organic synthesis in combination with 4 Å molecular sieves as water
scavengers is investigated. Two classical model transformations, namely acetal formation and imine formation, are
evaluated under both conventional heating and microwave dielectric heating. The results obtained in these studies indicate
that molecular sieves cannot be used effectively as water scavengers in microwave-assisted transformations owing to
the fact that these zeolites are generally most effective in adsorbing water at room temperature. For both acetal and imine
formation, performing these reversible reactions at a higher temperature in the presence of molecular sieves leads to
significantly reduced conversions compared with experiments at room temperature.
Manuscript received: 21 October 2008.
Final version: 18 December 2008.
Introduction
reaction for reaction monitoring can be troublesome using stan-
dard instrumentation.[ Notably, there are some instances where
the use of sealed vessel microwave technology will fail and an
open vessel microwave system must be used.[ Typically, this
is the case when one of the (volatile) products or by-products
needs to be eliminated from the reaction mixture, for example,
5]
High-speed synthesis using microwave heating technology has
attractedaconsiderableamountofattentioninrecentyears. More
than 3500 articles have been published in the area of microwave-
assisted organic synthesis (MAOS) since the first reports on
the use of microwave heating to accelerate organic chemical
transformations in 1986.[ The efficiency of ‘microwave flash
heating’ in dramatically reducing reaction times and increas-
ing product yields/purities is one of the key advantages of this
enabling technology. Most of the published applications of con-
trolled MAOS today involve the use of sealed vessel technology
in combination with single-mode microwave reactors. Here,
the advantages of rapid and direct volumetric microwave heat-
ing are combined with the capability to superheat solvents far
above their boiling points in a sealed vessel (autoclave).[
This method allows significantly higher reaction temperatures
to be reached than using conventional reflux conditions, and
therefore often results in considerable rate enhancements when
compared with experiments carried out at the boiling point of
6]
1,2]
[6]
in the case of an equilibrium process. In some important types
of synthetic transformation (e.g. acetal or imine formation from
carbonyl compounds), water is produced as a by-product that
must be removed to shift the equilibrium to the product side.
In conventional organic synthesis, there are two main physi-
cal methods to achieve this aim: azeotropic distillation with an
inert solvent (Dean–Stark apparatus), and the use of dehydrat-
ing agents, which are generally applied in small-scale experi-
ments. Although it has been recently reported that the use of a
Dean–Stark apparatus can be readily combined with microwave
heating under open-vessel conditions,[ to our knowledge
no detailed and systematic study on the use of dehydrating
agents as water scavengers in conjunction with microwave
1,2]
7]
[
1,2]
[8]
the solvent.
heating has been published. The latter technique would be
Apart from these important advantages, there are a few key
disadvantages of applying pressurized sealed-vessel microwave
technology for organic synthesis: first of all, in a closed reac-
tor, the operator is not able to visually follow the progress of the
reaction as in a conventional reflux experiment. Recent advances
in single-mode cavity design allow the interfacing of digital
cameras into the system and therefore a visual inspection of
the reaction mixture, eliminating some of the above-mentioned
particularly valuable because it would allow the successful
use of standard sealed-vessel microwave technology on small
scale.[
1,2]
Among the known dehydrating agents, molecular sieves have
a special place because of the high adsorption capacity for water,
even at very low temperatures caused by the highly polar sur-
face within the pores.[ However, the use of these materials
in conjunction with microwave heating is further complicated
because molecular sieves are known to be very strong microwave
absorbers.[ In fact, one of the best ways to dry/activate molec-
ular sieves is to irradiate them with microwaves.[ Herein,
we present a detailed study on the use of molecular sieves
as water scavengers in MAOS involving two classical model
transformations.
9]
[
3]
monitoring issues. Similarly, several publications have shown
thatbyusinginsituRamanspectroscopy, theprogressofavariety
of chemical transformations performed under microwave condi-
tions can be directly monitored online.[ An additional handicap
of the sealed vessel technology is that the portion or dropwise
addition of a reagent, or the withdrawal of samples during the
10]
11]
4]
©
CSIRO 2009
10.1071/CH08450
0004-9425/09/030244

RESEARCH FRONT
Molecular Sieves as Water Scavengers
245
O
100
Hϩ
BuO
OBu
H
90
H
ϩ
2
BuOH
ϪH O
80
2
Cl
Cl
7
6
5
4
3
2
0
0
0
0
0
0
1
2
3
Scheme 1.
O
NH2
N
10
0
Hϩ
0
50
100 150 200 250 300 350 400
Molecular sieve [mg]
ϩ
ϪH O
2
4
5
6
Fig. 1. Effect of molecular sieves quantities on the acetal formation shown
in Scheme 1. A mixture of 4-chlorobenzaldehyde (0.5 mmol), n-butanol
(1.2 mmol), p-toluenesulfonic acid (PTSA) (10 mol-%), molecular sieves
Scheme 2.
(
4
0–400 mg), and toluene (3 mL) were stirred in a sealed glass vial for
h at room temperature. Conversions based on gas chromatography-flame
Results and Discussion
ionisation detection monitoring.
In order to study the effect of microwave irradiation on organic
transformations requiring molecular sieves as water scavengers,
two classical model systems were selected, namely acetal forma-
tion (Scheme 1) and imine formation (Scheme 2). In both cases,
the presence of water scavengers is generally required in order
to drive the reaction to a high degree of conversion.[ We were
particularly interested to investigate these transformations both
in the presence and absence of sieves and to compare these data
with results obtained using microwave heating. For both reaction
systems, datasets obtained from runs at different tempera-
tureswerecomparedusinggaschromatography-flameionisation
detection (GC-FID) monitoring of the reaction progress.
Table 1. Effect of n-butanol:aldehyde stoichiometry on acetal
conversion (Scheme 1)
EntryA
Alcohol:aldehyde
Conversion [%]B
12]
1
2
3
4
5
6
2.0:1
2.4:1
2.8:1
3.2:1
3.6:1
4.0:1
83
90
91
95
96
100
AA mixture of 4-chlorobenzaldehyde (0.5 mmol), n-butanol,
p-toluenesulfonic acid (PTSA) (10 mol-%), toluene (3 mL), and 4 Å
molecular sieves (200 mg) was stirred in a sealed vessel for 4 h at room
temperature.
Acetal Formation
Acetal formation from an aldehyde and an alcohol component
proceeds through the nucleophilic attack of alcohol on the car-
bonyl group. The main problem in acetal formation in acidic
medium is to shift the equilibrium to the right by reducing the
concentration of the formed water in the reaction system.[13]
After some experimentation, we arrived at a suitable model
system for a reliable kinetic analysis that involved the acetal
formation from 4-chlorobenzaldehyde (1) with n-butanol (2) in
a suitable non-polar solvent (Scheme 1).The use of alcohols with
lower molecular weight such as ethylene glycol or i-propanol in
conjunction with standard 4 Å molecular sieves was not optimal,
as apparently these comparatively small alcohols can compete
with the formed water for the pores in the 4 Å molecular sieves.
Our initial experiments involved 0.5 mmol of 4-chloro-
benzaldehyde (1), 1.2 mmol n-butanol (2), 10 mol-% of
p-toluenesulfonic acid (PTSA, monohydrate) and 150 mg of
freshly activated 4 Å molecular sieves (see Experimental) in
B
Conversions based on gas chromatography-flame ionisation detection
monitoring.
on the equilibrium yield of product. Along similar lines, it was
quickly established that 10 mol-% of PTSA proved to be optimal
for obtaining high conversions.
Of key importance in all transformations requiring dehy-
drating agents is the amount of molecular sieves added to the
reaction mixture. As shown in Fig. 1, we established that a quan-
tity of 200 mg of activated 4 Å molecular sieves provided a high
degree of conversion (∼90%). Increasing the amount further
only slightly increased conversion to acetal 3. We therefore used
an amount of 200 mg of sieves per 0.5 mmol of aldehyde building
block for all further experiments.
Along similar lines, the stoichiometric ratio between alde-
hyde and alcohol was investigated (Table 1). Although using
4 equiv of alcohol, full conversion was obtained after 4 h at room
temperature, we chose to work with 2.4 equiv in all subsequent
experiments in order to be able to more accurately measure any
differences between microwave heating and standard processing.
For preparative work, however, the use of 4 equiv of n-butanol
is clearly advisable.
3
mL of toluene. Although the experiment with molecular sieves
at room temperature displayed a ∼90% conversion after a few
hours, the same experiment performed without sieves reached a
maximum at ∼30% conversion, clearly demonstrating the pos-
itive effect of the molecular sieves in removing water from the
equilibrium. A solvent screen further established that toluene
was indeed one of the best solvents to perform the acetal for-
mation, with results using other solvents such as chloroform,
After the extensive reaction optimization described above, we
finally started to investigate the influence of reaction tempera-
ture on the acetal formation shown in Scheme 1. In traditional
microwave synthesis, reactions can be performed at a signifi-
1
,2-dichloroethane, 1,2-dichlorobenzene, 1,2-dimethoxyethane
or THF showing inferior conversions under otherwise identical
conditions. It has to be emphasized that none of the solvents
used in these studies were pre-dried. The amount of water ini-
tially contained in the solvent therefore will have an influence
cantly faster rate because of the comparatively high processing
temperatures employed.[
1,2]
The influence of reaction temper-
ature on any process requiring molecular sieves is therefore

RESEARCH FRONT
2
46
M. Baghbanzadeh and C. O. Kappe
1
00
Table 2. Stability of acetal 3 under different conditions at 90◦C
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
EntryA
Mol sieves
PTSA
[mol-%]
Water
[equiv]
Conversion
[%]
B
[
mg]
1
2
3
4
5
–
–
–
200
200
–
–
10
10
10
–
3
–
–
3
<1
2.8
25.7
12
rt
50°C
7
9
0°C
0°C
90
A
◦
0
1
2
3
4
5
6
7
8
0.5 mmol of acetal 3 in 3 mL toluene was used in all runs (90 C, 2 h).
Conversion of acetal 3 to 4-chlorobenzaldehyde 1 based on gas
B
Time [h]
chromatography-flame ionisation detection monitoring.
Fig. 2. Conversion over time for acetal formation in dependence on the
reaction temperature (Scheme 1). A mixture of 4-chlorobenzaldehyde
(
(
0.5 mmol), n-butanol (1.2 mmol), p-toluenesulfonic acid (PTSA)
10 mol-%), 4 Å molecular sieves (200 mg), and toluene (3 mL) stirred in a
120
3
2
00 mg
60 mg
100
sealed vessel for the given times and temperatures (oil bath temperature).
Conversions obtained based on gas chromatography-flame ionisation
detection monitoring.
200 mg
160 mg
8
6
4
0
0
0
1
00 mg
6
0 mg
of critical importance. We were surprised to find that for the
acetal formation in Scheme 1, higher reaction temperatures
usingconventionalheatingresultedinlowerconversions(Fig. 2).
Although reactions run at room temperature under our carefully
optimized conditions led to 90% conversion after 4 h, a signif-
No sieves
20
0
0
20
40
60
80
100
120
◦
icantly lower amount of acetal product 3 was formed at 50 C,
Time [s]
◦
◦
7
0 C, and90 C. Bymonitoringtheconversionovertime(Fig. 2),
we established that the reaction equilibrium was reached after
–2 h, with very little changes in reaction composition occur-
Fig. 3. Selective heating of molecular sieves suspended in carbon tetra-
chloride (3 mL) in a quartz reaction vessel using 150W of constant power
fibre-optic temperature measurement).
1
(
ring after that time. Only for the room temperature run, where
the equilibrium is apparently reached more slowly, an increased
formation of acetal 3 was observed after 4 h.
We ascribe the lower conversions reached at higher temper-
atures to the fact that water is more effectively adsorbed to
established that molecular sieves are indeed strong microwave
absorbers. IntheexperimentsshowninFig. 3, weighedquantities
of molecular sieves were suspended in a microwave-transparent
solvent (carbon tetrachloride) contained in a transparent quartz
reaction vessel and exposed to microwave irradiation at constant
power for 2 min.[ As shown in Fig. 3, even small quantities
of molecular sieves are able to raise the bulk temperature of
the mixture significantly. It should be emphasized that in the
absence of molecular sieves, no heating occurs and that it can be
assumed that the temperature of the molecular sieves is signifi-
cantly higher than the monitored bulk temperature of the solvent
under these specific conditions.[ This would in principle open
up the possibility to use molecular sieves as passive heating
elements for otherwise low-absorbing reaction mixtures.[
Based on the data obtained using conventional heating for the
acetalization reaction (Fig. 2), we ultimately performed an iden-
[9]
molecular sieves at lower temperatures. At higher tempera-
tures, most of the water will be outside the sieves and therefore
will be able to hydrolyze the acetal back to the aldehyde and alco-
hol components. In order to demonstrate the reversible nature of
this process, we performed an experiment where the acetaliza-
tion was initially performed at room temperature for 4 h, giving
the expected ∼90% conversion. The reaction mixture was then
14]
◦
heated to 90 C for an additional 4 h, which led to a reduced con-
15]
version back to 50% in agreement with the data shown in Fig. 2.
This experiment clearly shows the equilibrium-type behaviour
of the acetalization and again demonstrated the effectiveness
of molecular sieves to remove water at ambient conditions. At
higher temperatures, the water-scavenging ability of molecular
sieves is apparently reduced.
16]
◦
tical experiment using controlled microwave irradiation at 70 C.
The results presented above are in good agreement with stud-
ies on the hydrolytic stability of acetal 3 at higher temperatures.
As shown in Table 2, acetal 3 is stable towards hydrolysis in the
absence of an acidic catalyst (PTSA), even in the presence of
an excess of water (entries 1 and 2). By introducing 10 mol-%
of the catalyst in the monohydrate form, significant hydrolysis
takes place (entry 3), which cannot be fully suppressed by the
A comparison of the kinetic data obtained for microwave and
conventional heating revealed that, within experimental error,
the same results were obtained: at higher temperature, the con-
version in the acetalization is lower and the use of molecular
sieves becomes ineffective, regardless if microwave or con-
ventional heating is employed (Fig. 4). Owing to the fact that
molecular sieves are strong microwave absorbers and will heat
rapidly under microwave conditions (Fig. 3), the use of these
materials as water scavengers in microwave-assisted reactions
is probably not practical. However, it may be possible to affix
the molecular sieves in the upper region of a modified 10 mL
Pyrex vial, which typically remains cold during the microwave
heating process, being outside the actual microwave cavity and
not in contact with the microwave-heated solvent. If the reaction
◦
molecular sieves at 90 C (entry 4). By adding an excess amount
of water (∼3 equiv, 27 mg, one drop), the capacity of the sieves is
exceeded and almost full hydrolysis to the aldehyde is observed
(
entry 5).
Having all these data in hand, we finally investigated the
influence of microwave irradiation on acetal formation in the
presence of molecular sieves. In a first series of experiments, we

RESEARCH FRONT
Molecular Sieves as Water Scavengers
247
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
Table 3. Solvent effect on the reaction of cyclohexylamine and cyclo-
hexanone (Scheme 2)
EntryA
Solvent
Conversion [%]B
1
2
3
4
5
6
Toluene
DCB
DCE
CHCl3
DME
THF
52
34
82
70
–
–
AA mixture of cyclohexanone (0.5 mmol), cyclohexylamine (0.6 mmol),
p-toluenesulfonic acid (PTSA) (10 mol-%), and solvent (3 mL) was stirred
Oil bath heating
in a sealed vessel for 4 h at room temperature.
Microwave heating
B
Conversions based on gas chromatography-flame ionisation detection
monitoring.
0
50
100
150
200
250
Time [min]
Table 4. Effect of amine to ketone stoichiometry on imine formation
(Scheme 2)
Fig. 4. Conversion in acetal formation (Scheme 1) comparing microwave
and oil-bath heating at 70 C.A mixture of 4-chlorobenzaldehyde (0.5 mmol,
◦
7
0 mg), n-butanol (1.2 mmol, 110 µL), p-toluenesulfonic acid (PTSA)
EntryA
Conversion [%]B
Amine:ketone
(
10 mol-%), molecular sieves (200 mg), and toluene (3 mL) stirred in sealed
vessel for given times and temperatures. Both sets of experiments were
performed in the same reaction vessel using internal fibre-optic probe
temperature measurement. Conversions obtained based on gas chromato-
graphy-flame ionisation detection monitoring.
1
2
3
4
5
6
1:1
83
90
91
93
94
97
1.2:1
1.4:1
1.6:1
1.8:1
2:1
is performed above the boiling point of the solvent, the formed
water may be (azeotropically) distilled to the upper parts of the
vial where the sieves are located. Under these conditions, the
use of sieves may be possible (J. T. Shaw, pers. comm.). In our
AA mixture of cyclohexanone, cyclohexylamine, p-toluenesulfonic acid
(PTSA) (10 mol-%), and 1,2-dichloroethene (3 mL) was stirred in a sealed
vessel for 4 h at room temperature.
B
Conversions based on gas chromatography-flame ionisation detection
◦
monitoring.
hands, an acetalization experiment at 130 C in toluene (in the
absence of sieves) did not provide a satisfactory result, leading
to 30% conversion after 1 h. Although the formation of small
water droplets at the top part of the vial could be observed, in
the absence of an effective water scavenging mechanism, this
method apparently is ineffective.
9
0
80
7
6
5
4
0
0
0
0
Imine Formation
To verify the results obtained for acetalization (Scheme 1), we
additionally studied the acid-catalyzed formation of imines from
ketones and amines. Primary amines can add to aldehydes and
ketones to produce imines, which are often sensitive to hydro-
lysis, in particular if derived from aliphatic aldehydes.[ In
general, ketones react more slowly than aldehydes, and higher
temperatures and longer reaction times are required. In addi-
tion, the equilibrium must often be shifted, usually by removal
of water, either azeotropically by distillation, or by use of a
30
2
1
0
0
0
rt
50°C
70°C
17]
0
50
100
Time [min]
150
200
250
Fig. 5. Conversion over time for imine formation in dependence on the
reaction temperature (Scheme 2). A mixture of cyclohexanone (0.5 mmol),
cyclohexylamine (0.6 mmol), p-toluenesulfonic acid (PTSA) (10 mol-%),
1,2-dichloroethene (3 mL), and 4 Å molecular sieves (200 mg) were stirred
in sealed vessel for the given times and temperatures. Conversions are based
on gas chromatography-flame ionisation detection monitoring.
water scavenger such as TiCl4,[ or molecular sieves.
18]
[19]
For
our model studies, we selected the reaction between cyclohex-
anone and cyclohexylamine, again employing PTSA as a catalyst
(Scheme 2). Initial investigations in toluene at room temper-
ature confirmed that the use of 4 Å molecular sieves for this
reaction was required in order to obtain an acceptable degree of
conversion.
Similarly to the investigations described above for acetaliza-
tion, the reaction was subsequently optimized at room tempera-
ture using different solvents (Table 3), molar ratios of building
blocks (Table 4), and amounts of sieves. After considerable
experimentation, we arrived at conditions that employed 1,2-
dichloroethane (DCE) as a solvent, 1.2 equiv of amine, 10 mol-%
of PTSA catalyst and 200 mg of 4 Å molecular sieves.
Similarly to acetal formation, the reaction of cyclohexyl-
amine with cyclohexanone (Scheme 2) was then performed at
different temperatures using oil-bath and microwave heating. In
agreement with the results described above for acetal formation,
we found that also in the case of imine formation, the molecu-
lar sieves worked best at room temperature, and were not really
effective at higher temperatures, although the effects were not as
pronounced as with acetal formation (Fig. 5). At room tempera-
ture, an 86% conversion to imine was obtained after 8 h, whereas

RESEARCH FRONT
2
48
M. Baghbanzadeh and C. O. Kappe
◦
at 90 C, the conversion was significantly lower (55%). For imine
formation at higher temperatures, side products were seen after
prolonged reaction times by GC-MS monitoring, which further
contributed to the low product yields. As expected, the mode of
heating had no significant influence on imine product formation
Kinetic Study of Acetal Formation (Scheme 1)
A 5 mL Pyrex vessel equipped with a stir bar was charged
with 4-chlorobenzaldehyde (1) (70 mg, 0.5 mmol), n-butanol
(
0
2) (110 µL, 90 mg, 1.2 mmol), PTSA monohydrate (9 mg,
.05 mmol), 3 mL of solvent, and the appropriate amount of 4 Å
◦
and kinetic studies at 70 C revealed no significant difference
between microwave heating and conventional heating (data not
shown).
molecular sieves. The vessel was sealed with a septum and the
reaction mixture was either exposed to microwave irradiation
or immersed in a preheated oil bath at different temperatures
and times as shown in Tables 1 and 2, and Figs 1–3. After
being cooled to ambient temperature, the mixture was imme-
diately quenched with triethylamine (1 mL), washed with 2 M
KOH solution (5 mL), and dried over potassium sulfate before
injection into a GC-FID.
Conclusions
In the present publication, we have evaluated the performance
of molecular sieves as water scavengers in microwave-assisted
transformations.Aftercarefulkineticanalysisoftwomodelreac-
tions (acetal and imine formation), it appears that molecular
sieves cannot be used efficiently as water scavengers under stan-
dard sealed-vessel microwave conditions. The reasons for this
are not so much connected to the strong microwave absorbance
of these zeolite-based materials but rather to the fact that the
effectiveness of molecular sieves as water scavengers is gener-
ally highest at ambient temperatures. As shown for both acetal
and imine formation, performing these reversible reactions at
a higher temperature (microwave or conventional heating) in
the presence of molecular sieves leads to significantly reduced
conversions compared with experiments at room temperature.
Kinetic Study of Imine Formation (Scheme 2)
A 5 mL Pyrex vessel equipped with a stir bar was charged with
cyclohexylamine (5) (69 µL, 59 mg, 0.6 mmol), cyclohexanone
(
4) (50 µL, 47 mg, 1.2 mmol), 3 mL of solvent, PTSA mono-
hydrate (9 mg, 0.05 mmol), and the appropriate amount of 4 Å
molecular sieves. The vessel was sealed with a septum and the
reaction mixture was either exposed to microwave irradiation or
immersed in a preheated oil bath at different temperatures and
times shown in Tables 3, 4 and in Fig. 4. After being cooled to
ambient temperature, the mixture was immediately quenched
with triethylamine (1 mL), washed with 2 M KOH solution
(
5 mL), and dried over potassium sulfate before injection into
Experimental
a GC-FID.
General Instrumentation
Microwave experiments (Figs 3 and 4) were recorded using a
Discover Labmate single-mode microwave reactor (CEM Corp.)
employing custom-made high-purity quartz vessels (capacity
1
-Chloro-4-(dibutoxymethyl)benzene 3
A mixture of 4-chlorobenzaldehyde (1) (1.4 g, 10 mmol),
n-butanol (2) (3.8 mL, 2.96 g, 40 mmol), PTSA monohydrate
(190 mg, 1 mmol), 30 mL of toluene, and 4 g of 4 Å molecu-
lar sieves was stirred in a sealed 100 mL round-bottom flask at
room temperature for 4 h. After completion of the reaction (GC-
FID monitoring), the mixture was quenched with triethylamine
(5 mL), washed with 2 M KOH solution (20 mL), and dried over
potassium sulfate. The solvent was evaporated under reduced
pressure and the pure acetal product was isolated as a colourless
[
14]
1
0 mL).
For comparison experiments between oil-bath and
microwave heating (Fig. 4), the temperature profiles for both sets
of experiments were monitored with a fibre-optic probe inserted
[
14]
into the vessel protected by a sapphire immersion well.
1
13
H and C NMR spectra were recorded on a Bruker AMX
60 in CDCl3. Low-resolution mass spectra were obtained
3
on an Agilent 1100 LC/MS instrument using atmospheric
pressure chemical ionization (APCI) in positive or nega-
tive mode. GC-FID analysis was performed on a Trace-GC
[20]
oil
in quantitative yield and >98% purity (GC-FID). δH 0.94
(
ThermoFisher) with a flame ionization detector using an HP5
(6H, t, J 7.3, 2CH3), 1.42 (4H, tq, J 7.3, 7.1, 2CH2CH3), 1.61
(4H, tt, J 7.3, 7.1, 2CH2CH2), 3.51 (4H, m, 2OCH2), 5.50 (1H,
s, CH), 7.34 (2H, d, J 8.4, 2ArH), 7.43 (2H, d, J 8.4, 2ArH).
δC 13.7, 19.4, 31.8, 65.0, 100.8, 128.1, 128.2, 133.9, 137.7. m/z
(APCI) 197 (100, [M − C4H9O ] ), 140 (65, [M − C7H16O ] ).
◦
column (30 m × 0.250 mm × 0.025 µm). After 1 min at 50 C,
◦
−1
◦
the temperature was increased in 25 C min steps up to 300 C
◦
and kept at 300 C for 4 min. The detector gas for the flame
ionization was H2 and compressed air (5.0 quality).
•
+
• +
4
ÅMolecularsieveswerepurchasedfromAldrichChem. Co.
(
Cat. No. 20860–4). All solvents and chemicals were obtained
from standard commercial vendors and were used without any
further purification.
Synthesis of N-Cyclohexylidenecyclohexanamine 6
A mixture of cyclohexylamine (5) (2.3 mL, 1.98 g, 20 mmol),
cyclohexanone (4) (1.0 mL, 0.94 g, 10 mmol), PTSA mono-
hydrate (190 mg, 1 mmol), 30 mL of DCE, and 4 g of 4 Å
molecular sieves was stirred in a sealed 100 mL round-bottom
flask at room temperature for 4 h. After completion of the
reaction (GC-FID monitoring), the mixture was quenched with
triethylamine (5 mL), washed with 2 M KOH solution (20 mL),
and dried over potassium sulfate. The solvent was evaporated
under reduced pressure and the pure imine product was isolated
as a colourless oil[ in 95% yield and >98% purity (GC-FID).
δH 1.20–1.38 (6H, m), 1.53–1.93 (10H, m), 2.18–2.30 (4H, m),
3.20–3.28 (1H, m). δC 24.7, 25.6, 27.5, 29.0, 34.1, 40.2, 57.9,
General Procedure for Activating 4 Å Molecular Sieves
under Microwave Irradiation
Asampleof30 gof4 Åmolecularsieves(freshbottle)wasplaced
in a 100 mL round-bottom flask and irradiated in a domestic
microwaveovenwithfullpower(800W)for∼80 s, whichcaused
◦
the temperature to rise to ∼250 C (temperature measurement
21]
immediately after irradiation by a standard thermometer). Imme-
diately after switching off the microwave power, the sieves were
put under vacuum (900 Pa, membrane pump) for 15 min. This
cycle was repeated five times.
•
+
170.8 (C=N). m/z (APCI) 180 (100, [M + 1 ] ).

RESEARCH FRONT
Molecular Sieves as Water Scavengers
249
Acknowledgement
(c) W. S. Bremner, M. G. Organ, J. Comb. Chem. 2008, 10, 142.
doi:10.1021/CC700159U
M.B. thanks Shahid Beheshti University and the Ministry of Science,
Research and Technology of Iran for a scholarship. We gratefully acknowl-
edge Professor Minoo Dabiri for facilitating M.B.’s leave.
(
2
(
d) V. Gududuru, V. Nguyen, J. T. Dalton, D. D. Miller, Synlett 2004,
357.
e) G. F. Manbeck, A. J. Lipman, R. A. Stockland, Jr, A. L. Freidl,
A. F. Hasler, J. J. Stone, I. A. Guzei, J. Org. Chem. 2005, 70, 244.
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