Regioselective hydroaminomethylation of vinylarenes by a sol-gel immobilized rhodium catalyst

Article abstract of DOI:10.1021/jo402632s

In the course of our studies toward the development of new heterogeneous conditions for better controlling regioselectivity in organic reactions, we investigated the application of sol-gel immobilized organometallic catalyst for regioselective hydroaminomethylation of vinylarenes with aniline or nitroarene derivatives in an aqueous microemulsion. By immobilization of 6 mol % [Rh(cod)Cl]₂ within a hydrophobic silica sol-gel matrix we were able to perform efficient hydroaminomethylation under mild conditions and isolate 2-arylpropylamines with high regioselectivity. The regioselectivity of the reaction was found to be mainly dependent on the hydrophobicity of the catalyst support. It is also significantly affected by the electronic nature of the substrates, by the reaction temperature, and by syngas pressure. The heterogenized catalyst can be reused for several times.

Full text of DOI:10.1021/jo402632s

Article
pubs.acs.org/joc
Regioselective Hydroaminomethylation of Vinylarenes by a Sol−Gel
Immobilized Rhodium Catalyst
Zackaria Nairoukh and Jochanan Blum*
Institute of Chemistry, The Hebrew University, Jerusalem 91904, Israel
S
* Supporting Information
ABSTRACT: In the course of our studies toward the
development of new heterogeneous conditions for better
controlling regioselectivity in organic reactions, we investigated
the application of sol−gel immobilized organometallic catalyst
for regioselective hydroaminomethylation of vinylarenes with
aniline or nitroarene derivatives in an aqueous microemulsion.
By immobilization of 6 mol % [Rh(cod)Cl]2 within a
hydrophobic silica sol−gel matrix we were able to perform
efficient hydroaminomethylation under mild conditions and
isolate 2-arylpropylamines with high regioselectivity. The
regioselectivity of the reaction was found to be mainly
dependent on the hydrophobicity of the catalyst support. It is
also significantly affected by the electronic nature of the substrates, by the reaction temperature, and by syngas pressure. The
heterogenized catalyst can be reused for several times.
developed by Alper exhibited good selectivities in the
hydroaminomethylation of styrenes with primary and secon-
dary amines (b/l up to 15/1) except for aniline (b/l = 1.9/1).8
Later, Beller and co-workers suggested an improved protocol
based on the zwitterionic rhodium complexes that achieved
relatively high selectivities toward the synthesis of branched
amines (b/l various from 1.4/1 to 99/1) from the hydro-
aminomethylation of styrenes with various amines under
relatively mild conditions.9
Previously, we developed a new heterogeneous system for
the hydroformylation of vinylarenes using immobilized [Rh-
(cod)Cl]2 within sol−gel matrices which provided high
regioselectivities toward branched aldehydes.10 This heteroge-
neous system was based on combining ceramic sol−gel
materials and aqueous emulsion/microemulsion systems
(EST) and has been proven to be applicable in a wide variety
of organic reactions.11,12 The easily recyclable ceramic support
also has the ability to perform one-pot multistep reactions in
conventional organic solvents.13 Reports on the use of
microemulsions with organometallic catalysts for the hydro-
aminomethylation of olefins have, so far, been scarce.14
In this contribution we describe the application of a new
heterogeneous system based on [Rh(cod)Cl]2 immobilized
within a sol−gel matrix as a highly efficient, regioselective, and
recyclable catalyst for the hydroaminomethylation reaction of
vinylarenes with aniline derivatives under mild conditions.
Remarkably, we demonstrated for the first time, that anilines
INTRODUCTION
■
Hydroaminomethylation of olefins, originally discovered by
Reppe and co-workers,1 has attracted much attention as a
versatile tool for the synthesis of amines and has been used in
multiple applications in the pharmaceutical and chemical
industry. As described, hydroaminomethylation is a one-pot
tandem reaction involving hydroformylation of alkene, followed
by condensation of the resulting aldehyde with a primary or
secondary amine, and hydrogenation of the intermediate imine
at the final stage.
From an economical and environmental point of view, one-
pot synthesis of amines from alkenes seems to be a superior
method over the conventional ones which comprise multistep
reactions.2 Unfortunately, multiple byproducts can be isolated
from this reaction. Consequently, many efforts have been
directed to improve the selectivity of the reaction. In particular,
methods that ensure preferential formation of either linear or
branched regioisomers have been targeted.3 Linear amines are
important intermediates and building blocks for pharmaceut-
icals, agrochemicals, and fine chemicals,4 while branched
amines are known to exhibit pharmacological activity such as
antihistaminic and sympathomimetic properties.5 For example,
Eilbracht showed that hydroaminomethylation of styrene
produces branched products with good selectivity (branched/
linear (b/l) up to 16) simply with [Rh(cod)Cl]2 without any
ligand, although it required harsh reaction conditions.6 Beller
and Kostas reported high regioselectivity of hydroaminome-
thylation of styrenes and linear alkenes with either piperidine or
morpholine (the ratio of b/l varies from 4/1 to 6.6/1 for
styrenes and up to 99/1 for linear alkenes) under high
pressures and temperatures.7 Zwitterionic rhodium complexes
Received: November 28, 2013
Published: February 14, 2014
© 2014 American Chemical Society
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a
Scheme 1. Preparation of [Rh(cod)Cl]2 Immobilized within Octylated Silica Sol−Gel Matrix
a
Stage 1: a solution of TEOOS, TDW, and EtOH was stirred for 24 h. Stage 2: to a solution of [Rh(cod)Cl]2, 2-(diphenylphosphino)-
ethyltriethoxysilane in THF were added TMOS, MeOH, and TDW. Then, the two mixtures were combined and stirring was continued for 48 h until
the gelation was complete. Stage 3: The resulting gel was aged for two days at 40 °C; dried at 80 °C and 0.1 Torr for 12 h. Then, it was washed with
CH2Cl2 and dried at 80 °C and 0.1 Torr to give a constant weight.
Table 1. Hydroaminomethylation of Styrene with Aniline by [Rh(cod)Cl]2 Immobilized within Differently Hydrophobicized
a
Sol−Gel in an Aqueous Medium
b
b
b
entry hydrophobic moiety hydrophobicity (%) yield (%) of ethylbenzene
yield (%) of branched (b) amine
yield (%) of linear (l) amine
ratio (b:l)
c,d
1
2
3
4
5
6
7
none
−
20
10
20
30
20
20
−
3
76
78
83
91
89
95
69
19
19
17
7
4:1
4:1
ethyl
propyl
propyl
propyl
octyl
−
2
5:1
13:1
13:1
32:1
3:1
4
7
2
3
phenyl
5
26
a
Reaction conditions: vinylarene (1.0 mmol, 0.8 wt % of the microemulsion), aniline (1.1 mmol), cetyltrimethylammonium bromide (CTAB, 3.3 wt
%), n-propanol (PrOH, 6.6 wt %), triply distilled water (TDW, 89.3 wt %) together with heterogenized rhodium catalyst prepared from
[Rh(cod)Cl]2 (30 mg, 0.06 mmol, 6 mol %), 2-(diphenylphosphino)ethyltriethoxysilane (45 mg, 0.12 mmol), TEOOS (or the corresponding ethyl,
propyl, or trimethoxy(phenyl)silane) (2.1 mL, 6.68 mmol, for 20% hydrophobicity) and TMOS (3.6 mL, 24.2 mmol); H2 (200 psi), CO (100 psi);
b
stirring rate 300 rpm; 60 °C, 12 h. The percentages were determined both by GC and by 1H NMR, and are the average of at least two experiments
c
d
that did not differ by more than 3%. [Rh(cod)Cl]2 immobilized within TMOS (3.6 mL, 24.2 mmol). 95% conversion.
can be prepared in situ from the corresponding nitroarenes in
one pot over the course of the hydroaminomethylation.
Any system in which the leaching per catalytic run exceeded
0.063% was discarded.
Optimization studies revolving around hydroaminomethyla-
tion of styrene with aniline using the aforementioned supports
are summarized in Table 1. The results clearly indicate that the
catalyst with the highest degree of hydrophobicity (e.g.,
octylated sol−gel prepared from 80 mol % of TMOS and 20
mol % of TEOOS) exhibits the highest selectivity (entry 6,
Table 1). The blank hydrophilic matrix (prepared from TMOS
with no alkylated comonomer), as well as matrices possessing
shorter alkyl chains, results in significantly lower selectivity
(entries 1, 2, 4 and 7, Table 1). The regioselectivity of the
hydroaminomethylation was shown to be also influenced by the
amount of the hydrophobic comonomer. For example,
introducing a high amount of propyl moiety to silica sol−gel
leads to a higher regioselectivity (entry 3 vs entry 4, Table 1).
However, no change on the regioselectivity was obtained when
higher amounts of the propyl moiety were introduced (entry 4
vs entry 5, Table 1). It should be mentioned that all the control
experiments, which have been performed under the same
conditions listed in Table 1, showed that hydroaminomethy-
lation takes place only in the presence of the sol−gel
immobilized [Rh(cod)Cl]2 coordinated to 2-
(diphenylphosphino)ethyltriethoxysilane. For example, hydro-
aminomethylation of styrene with aniline in the presence of 20
mol % of octylated sol−gel bearing physically immobilized
[Rh(cod)Cl]2 gave only the hydrogenated ethylbenzene. Also,
as anticipated, no reaction was obtained when we used the 20
RESULTS AND DISCUSSION
■
Although styrenes do not undergo hydroaminomethylation
with anilines in pure water at 60 °C by means of the
heterogenized [Rh(cod)Cl]2 catalyst system, the reaction takes
place upon the addition of a suitable surfactant that solubilizes
the substrate. Heterogenization of the catalyst by its
immobilization within a hydrophobic silica sol−gel matrix
results in the formation of the corresponding branched 2-
arylpropylamines in a highly regioselective fashion under mild
conditions.
From our previous studies, we know that hydrophobicity of
silica sol−gel matrices can affect the efficiency and the
regioselectivity of chemical reactions.10 Therefore, we inves-
tigated the influences of the hydrophobicity of the ceramic
support on the hydroaminomethylation process. Thus, [Rh-
(cod)Cl]2-containing ceramic supports modified with ethyl,
propyl, octyl, or phenyl residues have been prepared by
copolymerization of triethoxy(ethyl)silane, trimethoxy(propyl)-
silane, triethoxy(octyl)silane (TEOOS), or trimethoxy-
(phenyl)silane with tetramethyl orthosilicate (TMOS)
(Scheme 1). Leaching of the rhodium catalyst from the
modified matrices was studied by ICP analyses which indicated
that the immobilization of the rhodium complex within silica
sol−gel containing 2-(diphenylphosphino)ethyltriethoxysilane
is not leachable (0.012−0.063% of rhodium per catalytic cycle).
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mol % octylated sol−gel immobilized 2-(diphenylphosphino)-
ethyltriethoxysilane with no Rh precursor. Therefore, the
coordination of [Rh(cod)Cl]2 to the covalently bound 2-
(diphenylphosphino)ethyltriethoxysilane as a ligand is obliga-
tory for the efficient hydroaminomethylation reaction.
Furthermore, by comparing the selectivities obtained from
the nonhydrophobicized catalyst support with sol−gel con-
tained micelles formed from long-chain alkyl-substituted silica
precursors (entries 1 and 6, Table 1),15 we can unequivocally
conclude that the regioselectivity of the hydroaminomethyla-
tion originates from the hydrophobic nature of the sol−gel
matrix but not from the organometallic complex itself. On the
basis of the results of the optimization studies, we chose 20%
octylated silica sol−gel-based catalyst to study the scope and
limitation of the new method. Further experiments were also
conducted with different loadings of the rhodium catalyst. We
found that 6 mol % of [Rh(cod)Cl]2 provided efficient
hydroaminomethylation reaction. With a low-loading catalyst,
e.g. 3 mol % [Rh(cod)Cl]2, arylpropanals were isolated.
regioselectivity toward the branched amine product (entries 4
and 5). The results also indicate that optimal regioselectivity
can be obtained by 2:1 H2/CO syngas mixture (entry 2).
However, lower activity and b/l ratio were obtained by raising
the total pressure (e.g., entry 2 vs entry 5). Nevertheless, by
increasing the H2 pressure, the regioselectivity was hardly
affected (entry 3).
Under these optimized reaction conditions we carried out
the scope and limitation studies. Some typical examples of
regioselective hydroaminomethylation of some vinylarenes with
aniline by [Rh(cod)Cl]2 immobilized within octylated sol−gel
at 60 °C are summarized in Table 4. The electronic nature of
the substrates has no significant effect on the reaction rate.
However, a dramatic influence on the regioselectivity was
observed when electron-withdrawing or -donating groups were
introduced. For example, high selectivity was obtained in the
hydroaminomethylation of 4-chlorostyrene (b/l = 46/1)
compared to 4-methylsytene (b/l = 15/1) (entries 1, 4, and
5). Ortho-substituted substrates can also affect the regiose-
lectivity of the reaction due to steric hindrance. Thus, 2-
chlorostyrene gave lower selectivity compared to the para-
substituted substrate (compare entries 3 and 4). Nevertheless,
in all of the cases, including the ortho-substituted substrates
summarized in Table 4, higher regioselectivity was obtained
compared to those of the existing protocols.6,8,9 Different kinds
of substrates were also examined, such as heterocyclic
compounds, yet no satisfying regioselectivity was obtained.
Reduction of nitroarene derivatives to aniline is known to
take place under rhodium catalysis. It was thus fascinating to
test nitroarenes as “masked” anilines in the hydroaminomethy-
lation of vinylarenes. To the best of our knowledge, the use of
nitro compounds as amine precursors has never been reported
in this reaction. To our delight, essentially identical efficiencies
and selectivities were obtained by the employment of
nitrobenzene, 1-chloro-4-nitrobenzene, and 1-methyl-4-nitro-
benzene instead of their corresponding amines in the
hydroaminomethylation of 4-chlorostyrene (Table 5). For
example, introducing nitrobenzene in the hydroaminomethyla-
tion of 4-chlorostyrene led to approximately the same
selectivity ratio obtained when aniline was used (compare
entries 1 and 4). In some cases an increase in the
regioselectivity was obtained by the introduction of nitro
compounds instead of amine-based compounds (compare
entries 3 and 6).
The recycling of the catalyst was also investigated. [Rh-
(cod)Cl]2 immobilized within octylated silica sol−gel can be
recycled only at 90 °C for at least 4 times. However, a drop in
the regioselectivity was obtained during the third run,
apparently, due to the enlargement of the sol−gel pores caused
by hydrolysis of some Si−O bonds in the aqueous medium
(Table 6). After the fourth run we were able to isolate only
small amounts of phenylpropanals indicating diminished
activity of the catalyst (entries 4 and 5). We assume that this
decrease in activity is associated with some morphological
changes in the sol−gel matrix (Si−O bond breaking) that takes
place in water.10,12a,d Recycling of the immobilized catalyst at
lower temperatures was less efficient. By recording the infrared
spectra of the used immobilized catalyst, metal−carbonyl peaks
were detected (1994 and 2067 cm−1 on KBr mulls) which may
cause the drop in the catalyst activity at lower temperatures
after the first catalytic run.
Further experimentation with the new catalyst showed that
selectivity can be even improved by lowering reaction
temperature (Table 2). For example, in a series of experiments
Table 2. Dependence of the Yield and of the Regioselectivity
of the Hydroaminomethylation of Styrene with Aniline on
a
the Reaction Temperature
temperature
yield (%) of branched yield (%) of linear ratio
b,c b,c
entry
1
°C
(b) amine
(l) amine
(b:l)
60
80
90
95
82
81
3
16
17
32:1
5:1
d
2
d
3
5:1
a
Reaction conditions as given in Table 1 except for the temperature.
b
The data are averages of at least two experiments that did not differ
c
d
by more than 3%. 2% of ethylbenzene was detected. Full
conversion was obtained after 5 h.
at different temperatures (60−90 °C), we found dramatic
changes in the b/l ratio and showed that, although at low
temperatures the hydroaminomethylation is slower, selectivity
is the highest (b/l = 32/1).
Another factor that influences the hydroaminomethylation of
vinylarenes is the total and partial H2 and CO pressure. The
influence derived from hydroaminomethylation of styrene with
aniline at 60 °C is shown in Table 3. The trend shows that the
higher the pressures of CO in the syngas mixture, the lower
Table 3. Effect of the Relative H2 and CO Pressure in the
Hydroaminomethylation of Styrene with Aniline on the
a
Regioselectivity and the Yield of the Products
H2:CO
(psi)
yield (%) of branched
yield (%) of linear
ratio
(b:l)
b
b
entry
(b) amine
(l) amine
c
1
100:100
200:100
300:100
100:300
300:300
93
95
94
77
68
5
3
19:1
32:1
24:1
4:1
c
2
c
3
4
d
4
20
16
e
5
4:1
a
Reaction conditions as given in Table 1 except for the pressures.
b
The data are averages of at least two experiments that did not differ
c
d
by more than 3%. 2% of ethylbenzene was detected. 3% of
ethylbenzene was detected. 3% of ethylbenzene, 2% of 2-phenyl-
e
Finally, it is notable that although many organometallic
propanal, and 11% of 3-phenylpropanal were detected.
catalysts are converted in the presence of dihydrogen or
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a
Table 4. Hydroaminomethylation of Vinylarenes with Aniline by Heterogenized [Rh(cod)Cl]2 in an Aqueous Medium
a
b
1
Reaction conditions as given in Table 1. The percentages were determined both by GC and by H NMR, and are the average of at least two
c
experiments that did not differ by more than 3%. Small amounts of ethylbenzene derivatives (2%) and acetophenone derivatives (5%) were
detected; except for entry 1, only 2% of ethylbenzene was detected. 9% of 1-chloro-2-ethylbenzene and 5% of 2′-chloroacetophenoene were
detected.
d
[HP-5]. Exact mass was measured with Q-TOF LC/MS. Transmission
electron microscopy was performed via scanning transmission electron
microscope (STEM) operated at 200 kV and equipped with EDAX-
EDS for identification of elemental compositions.
hydrogen donors into metallic nanoparticles particularly when
an aqueous medium is employed,12a,b,e we were unable to
detect Rh(0) species following the hydroaminomethylation
processes by TEM-EDAX-EDS analyses (Figure 1).
Preparation of Hydrophilic Immobilized Catalyst. Immobili-
zation of [Rh(cod)Cl]2 within hydrophilic silica sol−gel was carried
out as follows. To a solution of [Rh(cod)Cl]2 (30 mg, 0.06 mmol, 6
mol %), 2-(diphenylphosphino)ethyltriethoxysilane (45 mg, 0.12
mmol) in THF (2 mL) were added TMOS (3.6 mL, 24.4 mmol),
MeOH (2.0 mL), and TDW (2.4 mL). Stirring was continued as long
as possible (24 h), and the resulting gel was aged for two days at 40
°C, dried at 80 °C and 0.1 Torr for 12 h. The ceramic material was
washed with boiling CH2Cl2 (2 × 15 mL) to ensure the removal of any
metallic compound that was not immobilized within the sol−gel
matrix, and dried again at 80 °C and 0.1 Torr to constant weight.
Preparation of Hydrophobic Immobilized Catalyst. Immobi-
lization of [Rh(cod)Cl]2 within octylated silica sol−gel was carried out
as follows. To a solution of TEOOS (2.1 mL, 6.68 mmol)
(alternatively, corresponding triethoxy(ethyl)silane, trimethoxy-
(propyl)silane or trimethoxy(phenyl)silane), TDW (0.38 mL) and
EtOH (5.6 mL) was stirred for 24 h. Then, to a solution of
[Rh(cod)Cl]2 (30 mg, 0.06 mmol, 6 mol %), 2-(diphenylphosphino)-
ethyltriethoxysilane (45 mg, 0.12 mmol) in THF (2 mL) were added
TMOS (3.6 mL, 24.4 mmol), MeOH (2.0 mL) and TDW (2.4 mL).
The two mixtures were combined and stirring was continued for 48−
96 h until the gelation was complete. The resulting gel was aged for
two days at 40 °C, dried at 80 °C and 0.1 Torr for 12 h. The ceramic
CONCLUSION
■
Hydroaminomethylation of vinylarenes with aniline derivatives
in a highly regioselective manner can be performed at 60 °C in
the presence of [Rh(cod)Cl]2 immobilized within hydrophobic
silica sol−gel in aqueous microemulsions. We were able to
demonstrate for the first time the use of nitroarenes as
“masked” anilines in the described reaction. The efficiency and
selectivity of hydroaminomethylation depend on the hydro-
phobic moiety of the sol−gel matrix, the reaction temperature,
the H2/CO ratio, and the electronic nature of the substrates.
EXPERIMENTAL SECTION
■
General. All reagents and solvents of commercial grade were used
without further purification. H NMR and 13C NMR spectra were
1
recorded as CDCl3 solutions on a 400 MHz NMR instrument.
Infrared spectra were recorded on NaCl plates. Gas chromatography
analyses were carried with either a 30 m long column packed with 20
M poly(ethylene glycol) in fused silica or with a 15 m long column
packed with bonded cross-linked (5% phenyl) methyl polysiloxane
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Table 5. Hydroaminomethylation of 4-Chlorostyrene with Aniline and Nitroarene Derivatives by Heterogenized [Rh(cod)Cl]2
a
in an Aqueous Medium
a
b
Reaction conditions as given in Table 1, except for entries 4, 5 and 6, the reaction was performed at 70 °C. The data are the average of at least two
c
d
experiments that did not differ by more than 3%. 2% of 1-chloro-4-ethylbenzene and 5% of 4′-chloroacetophenone were detected. 5% of 1-
e
chloro-4-ethylbenzene and 6% of 4′-chloroacetophenone were detected. 5% of 1-chloro-4-ethylbenzene and 5% of 4′-chloroacetophenone were
f
detected. 4% of 1-chloro-4-ethylbenzene and 4% of 4′-chloroacetophenone were detected.
material was washed with boiling CH2Cl2 (2 × 15 mL) to ensure the
removal of any metallic compound that was not immobilized within
the sol−gel matrix, and dried again at 80 °C and 0.1 Torr to give a
constant weight.
mixture was then degassed by bubbling Ar through it for 20 min and
mixed with the heterogenized catalyst.
Emulsification of 4-Chlorostyrene and Nitrobenzene. A
mixture of the 4-chlorostyrene (0.138 g, 1 mmol, 0.8 wt.% of the
desired microemulsion), nitrobenzene (0.135 g, 1.1 mmol), TDW
(15.4 mL, 89.3 wt.%), CTAB (0.56 g, 3.3 wt.%), PrOH (1.4 mL, 6.6
wt.%) and 5−7 mg of 2,5-di-tert-butyl hydroquinone was agitated at
room temperature. The mixture was then degassed by bubbling Ar
through it for 20 min and mixed with the heterogenized catalyst.
Emulsification of 4-Chlorostyrene and 1-Methyl-4-nitro-
benzene or 1-Chloro-4-nitrobenzene. A mixture of the 4-
chlorostyrene (0.138 g, 1 mmol, 0.8 wt.% of the desired micro-
emulsion), either 1-methyl-4-nitrobenzene (0.15 g, 1.1 mmol) or 1-
chloro-4-nitrobenzene (0.172 g, 1.1 mmol), TDW (15.4 mL, 89.3 wt.
%), CTAB (0.56 g, 3.3 wt.%), PrOH (1.4 mL, 6.6 wt.%) and 5−7 mg
of 2,5-di-tert-butyl hydroquinone was agitated at 70 °C. The mixture
Emulsification of the Substrates. A mixture of the vinylarene (1
mmol, 0.8 wt.% of the desired microemulsion), aniline derivative (1.1
mmol), TDW (89.3 wt.%), CTAB (3.3 wt.%), cosurfactant (PrOH, 6.6
wt.%) and 5−7 mg of 2,5-di-tert-butyl hydroquinone was agitated at
room temperature. The mixture was then degassed by bubbling Ar
through it for 20 min and mixed with the heterogenized catalyst.
Emulsification of 4-Chlorostyrene and p-Toluidine or 4-
Chloroaniline. A mixture of the 4-chlorostyrene (0.138 g, 1 mmol,
0.8 wt.% of the desired microemulsion), either p-toluidine (0.12 g, 1.1
mmol) or 4-chloroaniline (0.14 g, 1.1 mmol), TDW (15.4 mL, 89.3
wt.%), CTAB (0.56 g, 3.3 wt.%), PrOH (1.4 mL, 6.6 wt.%) and 5−7
mg of 2,5-di-tert-butyl hydroquinone was agitated at 50 °C. The
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MHz, CDCl3) δ 161.5 (d, J = 244.2 Hz), 147.9, 140.1 (d, J = 3.2 Hz),
129.2, 128.6 (d, J = 7.8 Hz), 117.4, 115.4 (d, J = 21.1 Hz), 112.9, 50.9
(d, J = 0.8 Hz), 38.5 (d, J = 0.5 Hz), 19.8 (d, J = 0.7 Hz); IR (NaCl,
chloroform, νmax, cm−1): 3409, 2963, 2932, 2870, 1601, 1505, 1319,
1256, 1223, 1096, 832; HRMS (ESI) calcd for C15H17FN, (M + H)+
230.1345, found 230.1344.
Table 6. Effect of Catalyst Recycling in the
Hydroaminomethylation of Styrene on the Yield and on the
a
Regioselectivity in an Aqueous Medium
yield of
yield of
bbranched
linear (l)
run conversion
yield of
ethylbenzene(%)
(b) amine
amine
ratio
2-Chloro-β-methyl-N-phenyl-benzene Ethanamine (3ca):
b
b
b
no.
(%)
(%)
(%)
(b:l)
1
yield 78% (0.191 g); H NMR (400 MHz, CDCl3) δ 7.37 (dd, J =
1
2
3
100
100
100
98
2
2
3
4
4
81
80
63
31
24
17
16
34
48
44
5:1
4:1
2:1
1:2
1:2
0.3, 1.3 Hz, 1H), 7.26 (m, 2H), 7.15 (m, 3H), 6.68 (tt, J = 1.0, 7.3 Hz,
1H), 6.60 (dd, J = 1.0, 8.6 Hz, 2H), 3.64 (br sextet, J = 7.0 Hz, 2H),
3.37 (m, 1H), 3.26 (m, 1H), 2.22 (s, 3H), 1.33 (d, J = 6.9 Hz, 3H);
13C NMR (400 MHz, CDCl3) δ 148.1, 141.7, 134.1, 129.7, 129.2,
127.6, 127.3, 127.2, 117.3, 112.8, 49.7, 35.3, 18.7; IR (NaCl,
chloroform, νmax, cm−1): 3398, 2929, 2868, 1600, 1502, 1444, 1254,
1096, 1022, 840, 669; HRMS (ESI) calcd for C15H17ClN, (M + H)+
246.1049, found 246.1045.
c
4
d
5
88
a
Reaction conditions as given in Table 1 except the hydro-
b
aminomethylation was performed at 90 °C. The data are the average
of at least two experiments that did not differ by more than 3%. 8%
c
4-Chloro-β-methyl-N-phenylbenzene Ethanamine (3da).9
Reaction with aniline or nitrobenzene afforded yields of 91% (0.223
d
of 2-phenylpropanal and 7% of 3-phenylpropanal was detected. 11%
of 2-phenylpropanal and 5% of 3-phenylpropanal was detected.
1
g) and 90% (0.221 g), respectively; H NMR (400 MHz, CDCl3) δ
7.29 (d, J = 8.5 Hz, 2H), 7.15 (m, 4H), 6.69 (tt, J = 1.0, 7.3 Hz, 1H),
6.56 (dd, J = 1.0, 8.7 Hz, 2H), 3.53 (br s, 1H), 3.33 (m, 1H), 3.19 (m,
1H), 3.04 (sextet, J = 7.1 Hz, 1H), 1.31 (d, J = 6.9 Hz, 3H); 13C NMR
(400 MHz, CDCl3) δ 147.9, 143.0, 132.2, 129.2, 128.7, 128.6, 117.5,
112.9, 50.8, 38.6, 19.6; IR (NaCl, chloroform, νmax, cm−1): 3417, 2964,
1603, 1505, 1320, 1256, 1218, 1094, 1013, 828, 772, 746, 693.
β-Methyl-N-phenylbenzene Ethanamine (3ea):16 yield 87%
1
(0.196 g); H NMR (400 MHz, CDCl3) δ 7.11 (m, 6H), 6.67 (t, J =
7.3 Hz, 1H), 6.56 (d, J = 8.7 Hz, 3H), 3.56 (br s, 1H), 3.31 (m, 1H),
3.19 (m, 1H), 3.01 (sextet, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.31 (d, J =
7.0 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 148.1, 141.4, 129.3,
129.2, 127.1, 117.2, 112.9, 50.8, 38.7, 21.0, 19.8; IR (NaCl, chloroform,
νmax, cm−1): 3419, 2963, 2950, 1603, 1505, 1320, 1220, 818, 639.
4-Chloro-N-(2-(4-chlorophenyl)propyl)aniline (3db). Reaction
with 4-chloroaniline or 1-chloro-4-nitrobenzene afforded yields of 79%
(0.221 g) and 78% (0.218 g), respectively; 1H NMR (400 MHz,
CDCl3) δ 7.29 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.09 (d, J
= 8.9 Hz, 2H), 6.46 (d, J = 8.9 Hz, 2H), 3.53 (br s, 1H), 3.29 (m, 1H),
3.16 (m, 1H), 3.01 (sextet, J = 7.1 Hz, 1H), 1.30 (d, J = 6.9 Hz, 3H);
13C NMR (400 MHz, CDCl3) δ 145.6, 143.1, 132.2, 129.7, 128.7,
Figure 1. TEM micrograph of a typical 20% octylated silica sol−gel
support immobilized Rh complex (A) before and (B) after the
hydroaminomethylation reaction of styrene and aniline at the same
conditions listed in Table 1
128.6, 126.7, 113.1, 51.2, 38.6, 20.3, 19.6; IR (NaCl, chloroform, νmax
,
was then degassed by bubbling Ar through it for 20 min and mixed
with the heterogenized catalyst.
cm−1): 3415, 2964, 2874, 1598, 1499, 1247, 1092, 1010, 818, 690, 543;
HRMS (ESI) calcd for C15H16Cl2N, (M + H)+ 280.0659, found
280.0655.
General Procedure for Catalytic Hydroaminomethylation.
The emulsion or microemulsion containing the substrate (usually 15−
20 mL) was placed in a glass-lined Parr bomb equipped with a
mechanical stirrer, together with the immobilized rhodium catalyst.
The autoclave was sealed and purged three times with hydrogen and
then pressurized to the desired pressure of H2 and CO. The reaction
mixture was kept at the desired temperature for the required period of
time. The reaction vessel was cooled to room temperature, the gases
were released and the remaining mixture was filtered. The filtrate was
treated with NaCl (1 g), which caused the mixture to separate into two
phases. The sol−gel material, as well as the aqueous layer, were
extracted with CH2Cl2 (2 × 10 mL) to ensure complete removal of the
products. The combined organic solutions were dried (MgSO4),
filtrated over silica column, concentrated and analyzed by GC, 1H
NMR and 13C NMR. The heterogenized catalyst was dried at 80 °C
and 0.1 Torr for 5 h in order to be ready for use in the next run.
β-Methyl-N-phenylbenzene Ethanamine (3aa):9 yield 95%
4-Chloro-N-(3-(4-chlorophenyl)propyl)aniline (4db). Reaction
with 4-chloroaniline or 1-chloro-4-nitrobenzene afforded yields of 10%
(0.028 g) and 11% (0.030 g), respectively; mp = 89 °C; 1H NMR (400
MHz, CDCl3) δ 7.25 (m, 2H), 7.10 (m, 4H), 6.48 (d, J = 8.9 Hz, 2H),
3.60 (br s, 1H), 3.09 (t, J = 7.0 Hz, 2H), 3.17 (t, J = 7.6 Hz, 2H), 1.90
(pentet, J = 7.4 Hz, 2H); 13C NMR (400 MHz, CDCl3) δ 146.7, 139.8,
131.7, 129.7, 129.1, 128.5, 121.8, 113.7, 43.3, 32.6, 30.8; IR (NaCl,
chloroform, νmax, cm−1): 3335, 2927, 2868, 1601, 1490, 1448, 1365,
1251, 1094, 1018, 830, 690; HRMS (ESI) calcd for C15H16Cl2N, (M +
H)+ 280.0659, found 280.0653.
N-(2-(4-Chlorophenyl)propyl)-4-methylaniline (3dc). Reac-
tion with p-toluidine or 1-methyl-4-nitrobenzene afforded yields of
1
80% (0.207 g) and 82% (0.213 g), respectively; H NMR (400 MHz,
CDCl3) δ 7.28 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 6.97 (d, J
= 8.5 Hz, 2H), 6.49 (d, J = 8.5 Hz, 2H), 3.41 (br s, 1H), 3.30 (m, 1H),
3.17 (m, 1H), 3.03 (sextet, J = 7.2 Hz, 1H), 2.22 (s, 3H), 1.30 (d, J =
6.8 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 145.6, 143.1, 132.2,
129.7, 128.7, 128.6, 126.7, 113.1, 51.2, 38.6, 20.3, 19.6; IR (NaCl,
chloroform, νmax, cm−1): 3411, 2929, 2870, 1615, 1519, 1489, 1370,
1094, 1011, 827; HRMS (ESI) calcd for C16H19ClN, (M + H)+
260.1206, found 260.1201.
1
(0.200 g); H NMR (400 MHz, CDCl3) δ 7.32 (m, 2H), 7.23 (m,
3H), 7.15 (t, J = 7.8 Hz, 2H), 6.68 (t, J = 7.3 Hz, 1H), 6.56 (dd, J =
0.9, 8.6 Hz, 2H), 3.56 (br s, 1H), 3.34 (m, 1H), 3.22 (m, 1H), 3.05
(sextet, J = 7.1 Hz, 1H), 1.33 (d, J = 7.0 Hz, 3H); 13C NMR (400
MHz, CDCl3) δ 148.1, 144.5, 129.2, 128.6, 127.2, 126.6, 117.3, 112.9,
50.9, 39.2, 19.7; IR (NaCl, chloroform, νmax, cm−1): 3422, 3009, 2967,
1599, 1501, 1311, 1244, 760, 682.
N-(3-(4-Chlorophenyl)propyl)-4-methylaniline (4dc). Reac-
4-Fluoro-β-methyl-N-phenylbenzene Ethanamine (3ba):
yield 88% (0.201 g); H NMR (400 MHz, CDCl3) δ 7.16 (m, 4H),
tion with p-toluidine or 1-methyl-4-nitrobenzene afforded yields of
10% (0.025 g) and 8% (0.020 g), respectively; H NMR (400 MHz,
1
1
7.00 (t, J = 8.8 Hz, 2H), 6.68 (dt, J = 1.1, 7.3 Hz, 1H), 6.55 (dd, J =
1.1, 7.9 Hz, 2H), 3.53 (br s, 1H), 3.32 (m, 1H), 3.19 (m, 1H), 3.02
(sextet, J = 7.2 Hz, 1H), 1.30 (d, J = 6.9 Hz, 3H); 13C NMR (400
CDCl3) δ 7.27 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 6.99 (d, J
= 8.4 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 3.54 (br s, 1H), 3.13 (t, J = 7.0
Hz, 2H), 3.17 (t, J = 7.6 Hz, 2H), 1.93 (pentet, J = 7.5 Hz, 2H); 13C
2402
dx.doi.org/10.1021/jo402632s | J. Org. Chem. 2014, 79, 2397−2403

The Journal of Organic Chemistry
Article
NMR (400 MHz, CDCl3) δ 145.6, 140.1, 131.6, 129.7, 128.5, 126.6,
113.0, 43.6, 32.7, 31.0, 20.3; IR (NaCl, chloroform, νmax, cm−1): 3358,
2930, 2872, 1605, 1499, 1436, 1250, 1022, 830; HRMS (ESI) calcd for
C16H19ClN, (M + H)+ 260.1206, found 260.1197.
(14) Gall, B.; Bortenschlager, M.; Nuyken, O.; Weberskirch, R.
Macromol. Chem. Phys. 2008, 209, 1152.
(15) Park, M.; Komarneni, S.; Lim, W. T.; Heo, N. H.; Choi, J. J.
Mater. Res. 2000, 15, 1437.
(16) Kubiak, R.; Prochnow, I.; Doye, S. Angew.Chem., Int. Ed. 2010,
49, 2626.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org
AUTHOR INFORMATION
Corresponding Author
*Tel.: +972-2-6585329. Fax: +972-2-6513832. E-mail:
jochanan.blum@mail.huji.ac.il.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We acknowledge the Israel Science Foundation through Grant
No. 299/10 for its generous financial support.
■
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