Impregnated ruthenium on magnetite as a recyclable catalyst for the N-alkylation of amines, sulfonamides, sulfinamides, and nitroarenes using alcohols as electrophiles by a hydrogen autotransfer process

Article abstract of DOI:10.1021/jo200559h

Various impregnated metallic salts on magnetite have been prepared, including cobalt, nickel, copper, ruthenium, and palladium salts, as well as a bimetallic palladium - copper derivative. Impregnated ruthenium catalyst is a versatile, inexpensive, and simple system for the selective N-monoalkylation of amino derivatives with poor nucleophilic character, such as aromatic and heteroaromatic amines, sulfonamides, sulfinamides, and nitroarenes, using in all cases alcohols as the initial source of the electrophile, through a hydrogen autotransfer process. In the case of sulfinamides, this is the first time that these amino compounds have been alkylated following this strategy, allowing the use of chiral sulfinamides and secondary alcohols to give the alkylated compound with a diastereomeric ratio of 92:8. In these cases, after alkylation, a simple acid deprotection gave the expected primary amines in good yields. The ruthenium catalyst is quite sensitive, and small modifications of the reaction medium can change the final product. The alkylation o amines using potassium hydroxide renders the N-monoalkylated amines, and the same protocol using sodium hydroxide yields the related imines. The catalyst can be easily removed by a simple magnet and can be reused up to ten times, showing the same activity.

Full text of DOI:10.1021/jo200559h

ARTICLE
pubs.acs.org/joc
Impregnated Ruthenium on Magnetite as a Recyclable Catalyst for the
N-Alkylation of Amines, Sulfonamides, Sulfinamides, and Nitroarenes
Using Alcohols as Electrophiles by a Hydrogen Autotransfer Process†
Rafael Cano, Diego J. Ramꢀon,* and Miguel Yus
ꢀ
ꢀ
Instituto de Sintesis Orgꢀanica (ISO) and Departamento de Quimica Orgꢀanica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99,
E-03080-Alicante, Spain
S Supporting Information
b
ABSTRACT: Various impregnated metallic salts on magnetite have been prepared,
including cobalt, nickel, copper, ruthenium, and palladium salts, as well as a bimetallic
palladiumꢀcopper derivative. Impregnated ruthenium catalyst is a versatile, inexpensive,
and simple system for the selective N-monoalkylation of amino derivatives with poor
nucleophilic character, such as aromatic and heteroaromatic amines, sulfonamides,
sulfinamides, and nitroarenes, using in all cases alcohols as the initial source of the
electrophile, through a hydrogen autotransfer process. In the case of sulfinamides, this is
the first time that these amino compounds have been alkylated following this strategy,
allowing the use of chiral sulfinamides and secondary alcohols to give the alkylated
compound with a diastereomeric ratio of 92:8. In these cases, after alkylation, a simple acid
deprotection gave the expected primary amines in good yields. The ruthenium catalyst is quite sensitive, and small modifications of
the reaction medium can change the final product. The alkylation of amines using potassium hydroxide renders the N-mono-
alkylated amines, and the same protocol using sodium hydroxide yields the related imines. The catalyst can be easily removed by a
simple magnet and can be reused up to ten times, showing the same activity.
recently the use of Fe3O4 as a catalyst7 in various organic reactions
1. INTRODUCTION
has pointed out the incongruence of this idea. The impregnation of
Because of the demands of our society, recycling initiatives are
different metallic salts on magnetite has been performed for
rapidly increasing. This affects many different aspects of our day-
titanium,8 manganese,9 iron,10 cobalt,11 copper,12 ruthenium,13
to-day lives. In this context, recoverable catalysts are attracting
rhodium,14 palladium,14,15 and platinum14 derivatives. However,
increasing attention and importance under the umbrella of so-
their applications in organic chemistry have been quite limited.
called green chemistry. Heterogeneous catalyst and reagents1
On the other hand, hydrogen autotransfer16 is a reaction of
play an important role with respect to the economy and also to
great interest nowadays in CꢀC bond formation processes
the well being of society as a whole. Without effective hetero-
(Scheme 1).17 This interest is directed toward the use of amines,
geneous catalysis, the manufacture of many materials and food-
stuffs would not be possible.
There are many ways to immobilize catalysts on a solid
and other nitrogenated compounds, as nucleophiles to yield the
corresponding N-alkylated products.18 The reason for this
change is derived from the great variety of amines present in
support, depending on both the catalyst and support. One of
Nature, as well as their relevant importance in the pharmaceutical
the most used supports are the metal oxides,2 including magne-
sia, alumina, silica, zirconia, and ceria.3 There are several proto-
and agrochemical industries as usual building blocks. The
extremely high advantage of this N-alkylation process, compared
cols for the preparation of a metallic catalyst supported on metal
with classical protocols,19 is based on the simplicity of the
oxides4 such as ion exchange, grafting, depositionꢀprecipitation,
protocol, avoiding the use of either mutagenic alkyl halides,
coprecipitation, and impregnation.5 The impregnation protocol
sulfates, etc., or carbonyl compounds that are difficult to store, as
allows all metallic active species to be at the surface of the catalyst
and therefore enhances their activity. There are three standard
well as the reduction of wastes.
steps in its preparation: (a) a solution of the metallic salt contacts
the metal oxide support, (b) drying of either the solution or the
2. RESULTS AND DISCUSSION
filtered support, and (c) thermal activation.
Besides the use of impregnated ruthenium on magnetite in the
MeerweinꢀPonndorfꢀVerley type process,13c there is no report
on the use of this type of catalyst in hydrogen autotransfer
Magnetite (Fe3O4), as any other metal oxide, can be used as
support, as demonstrated in medicine, biology, and material science.6
This support introduces a new advantage due to its easy recovery by a
magnet. However, its broad use in organic chemistry has not been
attained owing to the axiomatic idea that magnetite is unstable. Very
Received: February 8, 2011
Published: May 26, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
ARTICLE
Scheme 1. General Scheme for a Hydrogen Autotransfer
Process
Figure 2. X-ray photoelectron spectroscopy and TEM image for
ruthenium, palladium, and palladium/copper catalysts.
The nickel catalyst had a total incorporation of nickel(II)
species of 1.2%, and 10.2% incorporation on the surface. The
BET area surface was 8.2 m2/g, and the distribution of nickel was
homogeneous (Figure 1, second row).
The copper catalyst had a total incorporation of copper(0) and
copper(II) species (in a 1:4 ratio, respectively) of 1.6%, and 2.6%
on the surface. The BET area surface was 6.2 m2/g, and the
distribution of copper was homogeneous (Figure 1, third row).
The ruthenium catalyst had a total incorporation of ruth-
enium(III) species from 3.0 to 2.1%, and around 15.1% incor-
poration on the surface. The BET area surface was 9.2 m2/g,
and the distribution of ruthenium species was not homogeneous
on the surface of magnetite according to the TEM images
(Figure 2, first row).
The palladium catalyst had a total incorporation of palladium-
(II) species of 2.6%, and 24.8% incorporation on the surface. The
BET area surface was 13.6 m2/g and the distribution of palladium
was homogeneous (Figure 2, second row).
The bimetallic palladiumꢀcopper catalyst had a total incor-
poration of 3.2% for Pd(0) and Pd(II) species (in a 3:2 ratio,
respectively) and 1.1% for Cu, with the incorporationof palla-
dium on the surface determined as 22.2%, and the copper layers
being placed between the palladium layer and magnetite. The
BET area surface was 19.42 m2/g, and the distribution of
palladium was homogeneous (Figure 2, third row).
Once the catalysts were prepared and characterized, we
examined their activity in various hydrogen autotransfer
processes.
Figure 1. X-ray photoelectron spectra and TEM images for cobalt,
nickel, and copper catalysts.
processes. There is only one example of N-alkylation of sulfona-
mides using bulk rutheniumꢀmagnetite catalyst,20 prepared by
coprecipitation/calcination. With this study, we aim to show the
great potential of this type of catalyst.
2.1. Synthesis and Characterization of Catalysts. All the
catalysts were easily prepared by addition of commercial microparticles
of magnetite to an aqueous solution of the corresponding metal
chloride. The corresponding impregnated magnetite catalysts were
obtained by increasing the pH of the solution up to nearly 13 by
addition of 2 M aqueous NaOH, filtering, washing with water, and
evaporation of water at 100 °C during 24 h. In the case of palladium
derivatives, a great excess of potassium chloride was added to the initial
solution in order to increase the solubility of the palladium chloride.
The cobalt catalyst had a total incorporation of cobalt(II)
species of 1.7%, and 12.8% incorporation on the surface. The
BET area surface was 8.7 m2/g, almost the same as the starting
magnetite (9.8 m2/g), and the distribution of cobalt seemed to be
homogeneous on the surface of the magnetite according to the
TEM images (Figure 1, first row).
2.2. N-Arylation of Amines. The first studied process was the
alkylation of amines using alcohols. The reaction depicted in
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ARTICLE
Table 1. Optimization of Impregnated Metal on Magnetite
Catalyst
Table 2. Optimization of Reaction Conditions
entrya
solvent
base
yield 3a (%)b
yield 4a (%)b
entry
catalyst (mol %)
yield 3a (%)a yield 4a (%)a
1c
2c
3c
dioxane
PhMe
MeCN
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
KOH
KOH
KOH
tBuOK
NaOH
K2CO3
ꢀ
KOH
KOH
KOH
KOH
KOH
22
0
22
56
0
1
2
3
4
5
6
7
8
Co(OH)2ꢀFe3O4 (1.4)b
Ni(OH)2ꢀFe3O4 (1.2)b
Cu(OH)2ꢀFe3O4 (1.3)b
Cu(OH)2ꢀFe3O4 (1.3)b,c
Ru(OH)3ꢀFe3O4 (1.3)
Pd(OH)2ꢀFe3O4 (1.2)b
Pd(OH)2ꢀFe3O4 (1.2)b,c
Pd(II/0)/CuꢀFe3O4 (1.5/0.8)b
1
48
24
40
0
16
0
0
4
0
31
0
80
40
8
5
89
42
9
45
34
10
22
6d
7d
8e
0
0
30
0
42
0
3
9f
73
0
a Isolated yield. b Reaction performed during 4 days. c Reaction per-
formed using K2CO3 (130 mol %) as base.
10g
11g,h
12g,i
99
35
97
18
0
a Reaction performed using 150 mol % of 1a. b Isolated yield. c Reaction
performed during 24 h. d Reaction performed during 5 d. e Reaction
performed at 150 °C. f Reaction performed at 90 °C. g Reaction
performed using 200 mol % of 2a. h Reaction performed using 0.26
mol % of catalyst. i Reaction performed using 2.6 mol % of catalyst.
Table 1 using aniline (1a), a low nucleophilic amine, and benzyl
alcohol (2a) was chosen as the standard in order to optimize the
different parameters of the reaction.
The reaction was initially conducted in the absence of solvent
at 130 °C and in the presence of potassium hydroxide under an
argon atmosphere, which is one of the most typical reaction
conditions for the alkylation of aniline using the hydrogen
autotransfer strategy.7d,21 The reaction using the cobalt catalyst
gave a mixture of imine 3a (6%) and alkylated aniline 4a (22%)
after a 2 day reaction time, with an increased time of up to 4 days
not improving the results (1 and 48%, respectively, see Table 1,
entry 1). The reaction with the nickel catalyst also gave a modest
result (entry 2). The reaction with copper catalysts gave only the
expected amine 4a, although with a modest yield. Meanwhile, the
change of base to a weaker one (potassium carbonate) surpris-
ingly permitted the preparation of the corresponding imine as the
only isolated product (compare entries 3 and 4 in Table 1). The
reaction using the ruthenium derivative gave the best conversion
in only 2 days (entry 5 in Table 1). Finally, we studied the
reaction with palladium catalysts. In the case of using only
impregnated palladium on magnetite as catalyst, we obtained a
mixture of both products in a moderate yield, after a 4 day
reaction time. Whereas the change of the base to potassium
carbonate did not improve the results, only a change of the ratio
of the obtained products was observed. Then we tried the system
in which Pd(0) and Pd(II) species are on the surface of the
catalyst in order to test the activity of initial nanoparticles of
palladium(0), but they showed a behavior similar to that
obtained that with the +2 oxidation state (compare entries
6ꢀ8 in Table 1).
similar to those with KOH. Surprisingly, the reaction under
similar conditions but using sodium hydroxide gave only imine
3a in good yield (entry 5). The reaction with potassium
carbonate also gave imine 3a as the only isolated product, albeit
in lower yield, with the reaction giving a far inferior yield of imine
3a in the absence of base after 5 days (entries 6 and 7 in Table 2).
Once potassium hydroxide was found as the best base to obtain
amine 4a, the influence of temperature was tested, with higher
temperatures (150 °C) not having any accountable effect on the
yield, and lower ones (90 °C) rendering imine 3a in good yield
instead of the expected amine (entries 8 and 9 in Table 2). Then
we increased the amount of alkylating agent 2a up to 200 mol %,
and under these new reaction conditions the expected amine 4a
was obtained in practically quantitative yield (Table 2, entry 10),
with imine 3a not being detected in the crude reaction medium.
Finally, the amount of catalyst was evaluated (entries 11 and 12 in
Table 2); the decrease from 1.3 to 0.26 mol % had a great impact
not only on the chemical yield but also on the selectivity, whereas
the increase up to 2.6 mol % did not have any appreciable effect
either on the yield or on the product distribution.
After finding the best conditions (Table 2, entry 10), we
examined the problem of catalyst recycling. Once the reaction
was finished, the catalyst was trapped with a simple magnet,
washed with toluene, and reused for other cycle. The catalyst
could be reused 10-fold with no significant detrimental effect
on the excellent chemical yield obtained, being always higher
than 90% (see Supporting Information for the corresponding
graphic).
As the ruthenium derivative rendered the best conversion, we
conducted the study with this catalyst. Initially we studied the
effect of the solvent at 130 °C during 24 h under argon atmo-
sphere, finding that the reaction in dioxane gave a mixture of
products 3a and 4a in equal amounts, in toluene only amine 4a
was detected, and in acetonitrile the reaction failed (compare
entries 1ꢀ3 in Table 2 and entry 5 in Table 1). Once toluene was
discovered as the best solvent in terms of selectivity, the role of
the base was investigated. The reaction with a more basic
compound such as potassium tert-butoxide gave results (entry 4)
Then we studied the scope of the reaction using various
aromatic amines 1 and benzylic alcohol derivatives 3 (Table 3).
The reaction using various substituted anilines with electron-
donating or -withdrawing groups gave practically the same
chemical yield. Only in the case of 2-methoxyaniline did the
reaction time have to be increased in order to reach the previous
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Table 3. Alkylation of Aromatic Amines
Table 4. Optimization of Reaction Conditions for Imine 3a
Formation
entry
Ar1
Ar2
compound
yield (%)a
entrya
solvent
T (°C)
t (h)
yield 3a (%)b
1b
2c
3b
4b
5d
6d
7
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
99
71
99
99
82
94
99
99
99
99
99
99
99
90
1
dioxane
PhMe
MeCN
PhMe
PhMe
PhMe
PhMe
PhMe
130
130
130
150
90
48
48
48
48
48
24
24
24
0
4-MeOC6H4
2-MeOC6H4
3-ClC6H4
Ph
2
80
0
3
4
59
52
89
47
88
4-MeOC6H4
4-ClC6H4
Ph
5
Ph
6c
7c,d
8c,e
130
130
130
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
4-pyridyl
2-pyrimidyl
5-methylthiazol-2-yl
4g
4h
4i
8
4-MeC6H4
4-MeOC6H4
2-MeOC6H4
4-ClC6H4
Ph
9
a Reaction performed using 150 mol % of 1a. b Isolated yield. c Reaction
performed using 150 mol % of 2a. d Reaction performed using 0.26
mol % of catalyst. e Reaction performed using 2.6 mol % of catalyst.
10
11
12
13
14b
4j
4k
4l
Ph
4m
4n
hydrogenation of the imine, the one step that occurs outside the
metal coordination sphere is the condensation reaction.22
From the results shown in Table 2, we found that very small
changes of the reaction conditions could change the main
product of the reaction, the results using sodium and potassium
hydroxides being very spectacular (Table 2, entries 5 and 10). In
the case of using sodium hydroxide, the corresponding imine 3a
was isolated as the main product (see Table 4). In general, imines
have widespread applications in laboratory and industrial syn-
thetic processes,23 with their traditional synthesis implying
the condensation between amines and carbonyl compounds
(ketones or aldehydes) in acidic media with azeotropic distilla-
tion to expel the liberated water. Another interesting and
ecological alternative is the aerobic oxidation of secondary
amines,24 with the preparation of imines using alcohols and
amines as starting materials under aerobic oxidation conditions
being a more difficult task.25,26 To the best of our knowledge,
there is only one example of formation of imines using alcohols
and amines without any type of oxidant,27 which used a
sophisticated pincer-ruthenium complex28 as catalyst, liberating
hydrogen. In our case, the ruthenium-impregnated magnetite is
also able to catalyze this transformation in the absence of any
type of oxidant. For this reason, further effort was made in order
to optimize the imine preparation. Using only toluene as reaction
media, the expected imine 3a was obtained (Table 4, entries
1ꢀ3), with the optimum temperature being 130 °C (compare
entries 2, 4, and 5 in Table 4). The use of an excess of alcohol has
a beneficial impact on the chemical yield; meanwhile, the use of a
lower amount of catalyst led to a decrease in the chemical yield,
with an increase of catalyst up to 2.6 mol % not improving the
initial result (Table 4, entries 6ꢀ8).
Ph
a Isolated yield. b Reaction performed during 2 d. c Reaction performed
during 7 d. d Reaction performed during 5 d.
results (compare entries 1ꢀ4 in Table 3). The reaction also gave
excellent results in the case of 4-substituted benzylic alcohols,
independently of the electronic nature of the substitution
(compare entries 1, 5, and 6 in Table 3). Heteroaromatic amines
could also be used, obtaining in all cases practically quantitative
yields, independently of the substitution of the alcohols (Table 3,
entries 7ꢀ11), the position of the nitrogen atom (compare
entries 7 and 12 in Table 3), or the number of the nitrogen
atoms in the aromatic ring (Table 3, entry 13). Note that even
electron-rich five-membered aromatic amines could be used with
similar results (entry 14 in Table 3). However, the reaction failed
when the aliphatic tert-butylamine was used as the nucleophilic
partner in the presence of benzyl alcohol or when 1-hexanol was
used as the electrophilic partner in the presence of aniline,
showing the high selectivity of the catalyst.
The real role of the base is not clear from a mechanistic point
of view, but it seems to be connected initially with the deproto-
nation of the primary alcohol and to force the dehydrogenation
step, forming the aldehyde, because the reaction of pyridin-2-
amine with benzyl alcohol failed in the absence of KOH.
However, the same reaction using the in situ-prepared potassium
alkoxide (by deprotonation of benzyl alcohol with potassium
hydride) yields the expected product 4g in good yield. When the
reaction was performed using an equimolecular amount of
benzaldehyde and benzyl alcohol and in the absence of base,
compound 16a was not detected after 2 days, indicating that the
base also has a role in the final hydrogenation step of imines. The
reaction of an equal mixture of 4-methoxybenzyl alcohol and R,
R-dideuterobenzyl alcohol with pyridin-2-amine under standard
conditions gave a mixture of the related monodeuteated products
4i and 4g at the benzylic position, respectively, with the
incorporation of deuterium being about 70%, according to the
GC-MS spectrum. This indicates that between the ruthenium-
catalyzed steps, of the dehydrogenation of the alcohol and of the
Under the best reaction conditions (Table 4, entry 6), we studied
the recycling of the catalyst. Once the reaction was finished, the
catalyst was trapped with a simple magnet, washed with toluene, and
reused for other cycles, and the catalyst could be reused 10-fold with a
only a marginal detrimental effect on the obtained chemical yield (see
Supporting Information for the corresponding graphic). The ICP-
OES analyses showed only 0.5 ppm of ruthenium species in the
solution, which is the same amount found in the case of N-alkylation.
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Table 5. Preparation of Aromatic Imines from Amines
Table 6. Preparation of Aromatic Imines from Nitroarenes
entry
Ar1
Ar2
compound
yield (%)a
entrya
Ar1
Ar2
base (mol %) imine yield (%)b
1
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
89
91
77
83
79
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Phc
Phd
KOH (800)
KOH (300)
KOH (100)
ꢀ
K2CO3 (300)
KOH (300)
KOH (300)
KOH (300)
KOH (300)
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3d
3e
5
2
3b
4-MeOC6H4
3-ClC6H4
Ph
2
99
0
3
4
4-MeOC6H4
4
59
76
42
78
57
12e
50
44
92
5
Ph
4-ClC6H4
5
a Isolated yield. b Reaction performed during 4 d at 90 °C.
6
7
8
4-MeOC6H4 Ph
The scope of the reaction is presented in Table 5. The reaction
could be carried out with similar results using substituted
anilines, independently of the electronic nature of substitution
(Table 5, entries 1ꢀ3); for the case of chlorinated aniline, the
temperature used was lower in order to avoid the reduction of the
imine 3c to the corresponding amine 4d. It was also possible to
use various substituted benzylic alcohols 2, obtaining similar
yields for the expected imines 3 (entries 4 and 5 in Table 5).
In order to elucidate the behavior of the impregnated ruthe-
nium on magnetite, we could stop the reaction at the formation
stage of imine 3 or finish the reaction at the formation of amine 4
only by changing the cation of the hydroxide derivative. We
initially studied the BET area of the catalyst after it was used in
the presence of either potassium hydroxide or sodium hydroxide.
The area for catalyst in the first case (using KOH) was 6.2 m2/g
and in the second case (using NaOH) was 19.2 m2/g. Although
the areas are different, both are in the same range of the starting
catalyst (9.2 m2/g), indicating that there is no significant physical
change at the surface of catalyst. Moreover, the TEM images of
the three cases are quite similar. Then we saw that the nanosize
distribution of ruthenium particles at the surface of the catalyst
was similar for the three cases: 60% for particles between 0.5 and
2 nm for the initial catalyst, 79% for the catalyst used with KOH,
and 60% for the catalyst used with NaOH (see Supporting
Information for the corresponding graphics). The XPS data of
the recovered catalyst for both protocols showed the mainte-
nance of ruthenium(III) species and the adsorption of potassium
(36%) and sodium (44%) at the surface (1 nm depth). However,
this new adsorption seems to have no importance, because after
carrying out the reaction with NaOH and preparing compound
3a, the recycled catalyst was used in the presence of KOH under
standard conditions and gave the related amine 4a.
9
3-ClC6H4
Ph
10
11
12
Ph
Ph
Ph
4-MeOC6H4 KOH (300)
4-MeOC6H4 K2CO3 (300)
4-ClC6H4
KOH (300)
a Reaction performed using 800 mol % of 2. b Isolated yield. c Reaction
performed using only 300 mol % of 2a. d Reaction performed using 1600
mol % of 2a. e 49% of the amine 4d was isolated.
process using a large excess of benzyl alcohol derivatives (1700
mol %), anilines, and an iridium carbine complex (2 mol %) in
moderate to good yields (17ꢀ92%) after 1 day at 110 °C.29 On
the other hand, tertiary amines could be obtained by the same
strategy, but using in this case a large excess of alcohol (750 mol %),
catalytic amounts of a phosphaneꢀruthenium complex (7.5 mol %),
and a carbene ligand (7.5 mol %) at 150 °C during 1 day,30
with the corresponding tertiary amines being obtained in
yields ranging from 32 to 88%. We assumed that our very
selective ruthenium catalyst could perform the same trans-
formation, stopping the reaction before the final polyalkyla-
tion process.
As we anticipated, the reaction of nitrobenzene (5a) with a
large excess of benzyl alcohol (2a) and potassium hydroxide gave
a complicated mixture after a 3 day reaction time in toluene
under argon atmosphere; the corresponding imine 3a was
isolated but the related amine 4a or N,N-dibenzylaniline was
not detected. Decreasing the amount of base (300 mol %) gave a
significant improvement in the obtained yield, being practically
quantitative. These results were not improved with a further
decrease or elimination of base (compare entries 1ꢀ4 in
Table 6). The use of a weaker base such as potassium carbonate
had only a marginal effect on the chemical yield (Table 6, entry 7).
Then the amount of benzyl alcohol (2a) was changed but
resulted in no improvement in the yield (compare entries 2, 6,
and 7 from Table 6).
Finally, we considered the possibility of an extra dehydrogena-
tion step in the conversion of amine 4a to imine 3a. However, the
treatment of amine 4a with NaOH in the presence of ruthenium
catalyst under the conditions described in entry 6 of Table 4 did
not produce the expected imine 3a after a 4 day reaction time.
The same result was obtained using NaOH and 3 equiv of water,
which is the byproduct of the condensation reaction. In conclu-
sion, we do not have any satisfactory explanation for the effect of
the cation present in the base on the course of the reaction in our
experiments.
Once the best conditions were found, other substrates were
subjected to the same reaction process. Substitution on the
nitroarene derivative had an important effect on the yield, in all
cases being lower than that for simple nitrobenzene (entries 8
and 9 in Table 6). Note that in the case of 1-chloro-3-nitroben-
zene, a significant amount of monalkylated amine 4d was isolated
along with the expected imine 3c, indicating a facile reduction of
the imine 3c under these reaction conditions, as previously
highlighted in the case of aniline derivatives (Table 5, entry 3).
The reaction using 4-methoxybenzyl alcohol also gave a moderate
2.2. Reaction with Nitroarenes. Very recently, various ni-
troarenes have been used as a masked nitrogen source in the
formation of aromatic imines through the hydrogen autotransfer
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Table 7. Alkylation of Sulfonamides
Table 9. Alkylation of Sulfinamides
entrya
R1
R2
compound
yield (%)b
entry
R1
R2
compound
yield (%)a
1
2
3
4
5
6
Me
Me
Me
Me
Me
H
Ph
8a
8b
8c
8d
8e
8f
86
1
2
3
4
5
6
7
8e
H
Ph
10a
10b
10c
10d
10e
10f
76b
75
3-ClC6H4
2,3-(OCH2O)C6H3
1-naphthyl
cC6H11
99
H
4-ClC6H4
4-MeOC6H4
furan-2-yl
Me(CH2)6
iPr
99c
96c
99c
99
H
68
H
78c
67c
72
30d
28f
H
Ph
H
a Reaction performed using 200 mol % of 7. b Isolated yield. c Reaction
Me
Me
Ph
10g
10g’
performed during 4 d.
Ph
a Isolated yield. b Reaction performed during 5 h. c Reaction performed
during 48 h. d Mixture of four possible diastereoisomers. e The reaction
was performed using chiral (R)-2-methyl-2-proanesulfinamide 9. f A
92:8 mixture of two diastereoisomers was isolated.
Table 8. Optimization of Reaction Conditions
2.4. N-Alkylation of Sulfinamides. Encouraged by the suc-
cess obtained in the alkylation of various nitrogen-containing
compounds using impregnated ruthenium on magnetite, we
examined the the alkylation of sulfinamide 9 using this strategy
of hydrogen autotransfer, unknown until now (Table 8).
The reaction of 2-methylpropane-2-sulfinamide (9) with a
double amount of benzyl alcohol (2a) was chosen as a standard
in order to optimize all parameters (Table 8). The reaction in
toluene at 130 °C under argon atmosphere using potassium
hydroxide as base gave the expected compound 10a after 4 days
with a modest yield and gave a huge amount of various
byproducts. The reaction was then repeated at lower tempera-
tures in order to avoid the decomposition of the starting amide
and the final product, finding that the best result was obtained at
85 °C (compare entries 1ꢀ3 in Table 8). The change of toluene
to dioxane or acetonitrile as solvent had a very negative impact on
the yield, the reaction failing in these media (Table 8, entries 4
and 5). Other bases such as sodium hydroxide or potassium tert-
butoxide could be used to render the final compound 10a with
results similar to that obtained using potassium hydroxide
(entries 6 and 7 in Table 8). However, the reaction failed when
using a weaker base such as potassium carbonate. Finally, note
that the reaction using only a stoichiometric amount of benzyl
alcohol and either potassium or sodium hydroxide gave the
expected product 10a with slightly lower yield (entries 9 and 10
in Table 8).
More interesting is the fact that the former reaction could be
carried out using primary aliphatic alcohols with or without
substitution at the β position, such as for 1-heptanol or isobutyl
alcohol (Table 9, entries 5 and 6), in similar yields. The reaction
with secondary alcohols gave the corresponding compound 10 in
a lower yield. Thus, the reaction of racemic 9 with 1-phenyletha-
nol gave the compound 10g in a modest yield, and as a mixture of
the four possible isomers, according to the chiral-HPLC analyses
(33, 33, 17, and 17%, respectively). However, when the same
reaction was performed using the related starting chiral material
(R)-9, compound 10g0 was obtained as a mixture of only two
diastereoisomers, with the diastereoisomeric ratio being 92:8.
This last result indicated that this new reaction could be used in
entrya
solvent
base
T (°C)
t (h)
yield 10a (%)b
1
PhMe
PhMe
PhMe
Ddioxane
MeCN
PhMe
PhMe
PhMe
PhMe
PhMe
KOH
130
100
85
96
5
10
53
76
0
2
KOH
3
KOH
5
4
KOH
85
96
96
5
5
KOH
85
0
6
NaOH
tBuOK
K2CO3
KOH
85
70
69
0
7
85
5
8
85
48
5
9c
10c
85
64
58
NaOH
85
5
a Reaction performed using 200 mol % of 2a. b Isolated yield. c Reaction
performed using only 100 mol % of 2a.
yield using potassium hydroxide or potassium carbonate
(Table 6, entries 10 and 11). However, when the reaction
was performed using 4-chlorobenzyl alcohol, an excellent
yield for the corresponding imine was obtained (entry 12 in
Table 6).
The above reaction strategy is an alternative to the classical
reduction of nitroarenes without hydrogen, because the real
source of hydrogen is the alcohol. In addition, this protocol
allows the in situ protection of the amine group as an imine by
the reaction with the aldehyde formed in the dehydrogena-
tion step.
2.3. N-Alkylation of Sulfonamides. Another type of nitro-
gen-containing compound that has been very recently alkylated
using various transition metal catalysts20,21h,21m,31 through a
hydrogen autotransfer process are the sulfonamides. On the
basis of our continued interest in the synthesis and use of various
sulfonamides as ligands,32 we examined the alkylation of this type
of compound using impregnated ruthenium on magnetite cata-
lyst (see Table 7).
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Scheme 2. Liberation of Primary Amines
solvent. The product was purified by chromatography on silica gel
(hexane/ethyl acetate) to give the corresponding products 4 or 8. Yields
are included in Table 3 and 7. Physical and spectroscopic data, as well as
literature for known compounds, are as follows:
N-Benzylaniline (4a):7d. mp 37ꢀ40 °C (hexane); Rf 0.5 (hexane/
ethyl acetate: 4/1); IR (KBr): ν 3414, 1603 cmꢀ1; 1H NMR (300 MHz,
CDCl3): δ 3.98 (s, br, 1H), 4.3 (s, 2H), 6.60ꢀ6.63, 6.67ꢀ6.73,
7.13ꢀ7.19, 7.23ꢀ7.37 (4 m, 2, 1, 2, and 5H, respectively); 13C NMR
(75 MHz, CDCl3): δ 48.2, 112.8 (2C), 117.5, 127.2, 127.5 (2C), 128.6
(2C), 129.2 (2C), 139.4, 148.1; EI-MS m/z: 184 (M+ + 1, 13%), 183
(M+, 100), 182 (38), 180 (10), 106 (20), 91 (100), 77 (18), 65 (14).
N-Benzyl-4-methoxyaniline (4b):7d. Rf 0.43 (hexane/ethyl acetate:
asymmetric synthesis to prepare chiral amino derivatives, and we
are now studying the scope of this process.
4/1); IR (film): ν 3405, 1525, 1281 cmꢀ1 1H NMR (300 MHz,
;
Finally, the removal of the sulfinyl group was performed using
the typical acid protocol to give the expected primary amine 11
with good chemical yields in all three cases tested (Scheme 2).33
In the case of the sulfinamide 10g0, the absolute configuration at
the stereogenic carbon atom placed at the R-position of the
obtained amine 11c was assigned as (R), according to literature
values.34
The entire process, N-alkylation of the sulfinamide and
deprotective acid treatment, is an interesting alternative to the
direct monoalkylation of ammonia, which is a difficult task using
the hydrogen autotransfer strategy.35 Moreover, the possibility to
perform the entire transformation in an asymmetric way gives
extra value to this methodology.
CDCl3): δ 3.5ꢀ3.8 (s, br, with s at 3.68, 1 and 3H, respectively), 4.22
(s, 2H), 6.54ꢀ6.57 (m, 2H), 6.73ꢀ6.76 (m, 2H), 7.23ꢀ7.34 (m, 5H);
13C NMR (75 MHz, CDCl3): δ 49.1, 55.6, 114 (2C), 114.8 (2C), 127,
127.4 (2C), 128.5 (2C), 139.6, 142.3, 152; EI-MS m/z: 214 (M+ + 1,
16%), 213 (M+, 100), 212 (11), 198 (11), 122 (78), 91 (65), 65 (11).
N-Benzyl-2-methoxyaniline (4c):7d. Rf 0.43 (hexane/ethyl acetate:
4/1); IR (film): ν 3423, 1603, 1509, 1292 cmꢀ1; 1H NMR (300 MHz,
CDCl3): δ 3.84 (s, 3H), 4.3 (s, 2H), 4.61 (s, br, 1H), 6.57ꢀ6.86,
7.22ꢀ7.39 (2 m, 4 and 5H, respectively); 13C NMR (75 MHz, CDCl3):
δ 48, 55.4, 109.3, 110, 116.6, 121.3, 127.1, 127.5, 128.5, 138.1, 139.5,
146.7; EI-MS m/z: 214 (M+ + 1, 16%), 213 (M+, 100), 212 (21), 198
(34), 120 (12), 92 (13), 91 (70), 65 (15).
N-Benzyl-3-chloroaniline (4d):7d. Rf 0.5 (hexane/ethyl acetate: 4/1);
IR (film): ν 3420, 1585, 1077 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 4.2
(s, br, 1H), 4.39 (s, 2H), 6.6ꢀ6.63, 6.75ꢀ6.77, 6.88ꢀ6.89, 7.19ꢀ7.24 (4
m, 1, 1, 1 and 1H, respectively), 7.44ꢀ7.56 (m, 5H); 13C NMR (75
MHz, CDCl3): δ 47.7, 110.9, 112.3, 117, 127.2 (2C), 127.3 (2C), 128.5,
130.1, 134.8, 138.6, 149; EI-MS m/z: 219 (M+ + 1, 21%), 218 (M+, 15),
217 (64), 216 (19), 91 (100).
3. CONCLUSIONS
In conclusion, inexpensive and easily prepared impregnated
ruthenium on magnetite has been shown to be an active, stable,
versatile, and highly selective catalyst for the selective monoalk-
ylation of aromatic amines and sulfonamides through a hydrogen
autotransfer process. The protocol has been applied for the first
time successfully to sulfinamides and, in the case of chiral starting
compounds; the corresponding diastereoselective reaction was
performed. The combined alkylationꢀdeprotection process of
sulfinamide case is an alternative to the direct monoalkylation of
ammonia, which could also be applied to chiral primary amines.
The protocol of impregnation is simple and reproducible,
permitting the easy preparation of the corresponding catalysts
derived not only from ruthenium but also from cobalt, nickel,
copper, palladium, and polymetallic systems such as those
derived from palladium and copper.
N-(4-Methoxybenzyl)aniline (4e):7d. Rf 0.53 (hexane/ethyl acetate:
4/1); IR (film): ν 3412, 1603, 1259 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): δ 3.91 (s, 3H), 4.1 (s, br, 1H), 4.37 (s, 2H), 6.76ꢀ6.78,
6.86ꢀ6.91, 7.01ꢀ7.05, 7.3ꢀ7.36, 7.41ꢀ7.44 (5 m, 2, 1, 2, 2 and 2H,
respectively); 13C NMR (75 MHz, CDCl3): δ 47.5, 55, 112.7 (2C),
113.8 (2C), 117.2, 128.6 (2C), 129.1 (2C), 131.3, 148.1, 158.6; EI-MS
m/z: 213 (M+, 29%), 122 (10), 121 (100), 77 (10).
N-(4-Chlorobenzyl)aniline (4f):7d. Rf 0.43 (hexane/ethyl acetate:
4/1); IR (film): ν 3419, 1596, 1089 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): δ 4.04 (s, br, 1H), 4.3 (s, 2H), 6.58ꢀ6.62, 6.69ꢀ6.74,
7.14ꢀ7.19, 7.26ꢀ7.31 (4 m, 2, 1, 2, and 4H, respectively); 13C NMR
(75 MHz, CDCl3): δ 47.6, 112.8 (2C), 117.8, 128.7 (2C), 128.7 (2C),
129.3 (2C), 132.8, 138, 147.8; EI-MS m/z: 219 (M+ + 1, 21%), 218
(M+, 14), 217 (63), 216 (15), 182 (12), 127 (33), 125 (100), 106 (10),
89 (13), 77 (12).
4. EXPERIMENTAL SECTION
4.1. General Procedure for the Preparation of Catalysts.
To a stirred solution of the metal salt MClx (1 mmol) in deionized water
(120 mL) was added Fe3O4 (4 g, 17 mmol, powder <5 μm, BET area:
9.86 m2/g). After 10 min at room temperature, the mixture was slowly
basified with NaOH (1 M) until pH around 13. The mixture was stirred
during 1 day. Subsequently, the catalyst was filtered under vacuum and
washed several times with deionized water (3 ꢁ 10 mL). The solid
residue was dried at 100 °C during 24 h.
4.2. Representative Procedure for the Alkylation of
Amines and Sulfonamides. To a stirred solution of amine or
sulfonamide (1 or 6, 1 mmol) in toluene (3 mL) under argon atmo-
sphere were added Ru(OH)3ꢀFe3O4 (50 mg), KOH (1.3 mmol, 73
mg), and the corresponding alcohol (2 or 7, 2 mmol). The resulting
mixture was stirred at 130 °C until the end of reaction. The catalyst was
removed by a magnet, and the resulting mixture was quenched with
water and extracted with EtOAc. The organic phases were dried over
MgSO4, followed by evaporation under reduced pressure to remove the
N-Benzylpyridin-2-amine (4g):7d. mp 94ꢀ96 °C (hexane); Rf 0.2
(hexane/ethyl acetate: 4/1); IR (KBr): ν 3217, 1598, 1578, 1529 cmꢀ1
;
1H NMR (300 MHz, CDCl3): δ 4.46 (d, J = 5.8 Hz, 2H), 5.26 (s, br,
1H), 6.31ꢀ6.34 (m, 1H), 6.51ꢀ6.56 (m, 1H), 7.29ꢀ7.32 (m, 6H),
8.02ꢀ8.04 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 46.1, 106.6, 112.9,
127, 127.2 (2C), 128.5 (2C), 137.3, 139.1, 148, 158.6; EI-MS m/z: 185
(M+ + 1, 14%), 184 (M+, 100), 183 (52), 107 (18), 106 (75), 91 (36), 79
(26), 78 (20), 65 (12).
N-(4-Methylbenzyl)pyridin-2-amine (4h):7d. mp 73ꢀ77 °C (hexane);
Rf 0.17 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3210, 1599, 1570,
1521 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 2.32 (s, 3H), 4.42 (d, J =
5.7 Hz, 2H), 5.02 (s, br, 1H), 6.32ꢀ6.34 (m, 1H), 6.53ꢀ6.56 (m, 1H),
7.12 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 7.7 Hz, 2H), 7.34ꢀ7.36 (m, 1H),
8.05ꢀ8.06 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 21, 46, 106.6, 112.9,
127.3 (2C), 129.2 (2C), 136, 136.7, 137.3, 148.1, 158.6; EI-MS m/z: 199
(M+ + 1, 15%), 198 (M+, 100), 197 (45), 183 (16), 120 (71), 105 (49), 79
(22), 78 (19), 77 (14).
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N-(4-Methoxybenzyl)pyridin-2-amine (4i):7d. mp 128ꢀ130 °C
(hexane); Rf 0.07 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3231,
1603, 1574, 1531, 1506, 1238 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ
3.77 (s, 3H), 4.40 (d, J = 5.5 Hz, 2H), 5.01 (s, br, 1H), 6.33ꢀ6.36 (m,
1H), 6.54ꢀ6.58 (m, 1H), 6.86 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.6 Hz,
2H), 7.35ꢀ7.4 (m, 1H), 8.06ꢀ8.07 (m, 1H); 13C NMR (75 MHz,
CDCl3): δ 45.7, 55.2, 106.7, 112.9, 113.9 (2C), 128.6 (2C), 131.1,
137.3, 148.1, 158.6, 158.7; EI-MS m/z: 215 (M+ + 1, 10%), 214
(M+, 68), 213 (14), 136 (22), 121 (100), 78 (18).
N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-methylbenzenesulfonamide
(8c):21h. mp 134ꢀ137 °C (hexane); Rf 0.57 (hexane/ethyl acetate: 3/2);
IR (KBr): ν 3260, 1592, 1324, 1256, 1154, 1097, 1063, 1024, 922,
669 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 2.43 (s, 3H), 4.0 (d, J = 6.2
Hz, 2H), 4.9 (t, J = 6.1 Hz, 1H), 5.9 (s, 2H), 6.61ꢀ6.68 (m, 3H), 7.29 (d,
J = 8 Hz, 2H), 7.73 (d, J = 8.2 Hz, 2H); 13C NMR (75 MHz, CDCl3):
δ 21.5, 47.1, 101.1, 108.4, 121.3, 127.1 (2C), 129.7 (2C), 130.1, 136.9,
143.4, 147.2, 147.8; EI-MS m/z: 305 (M+, 12%), 150 (36), 149 (100),
148 (32), 135 (13), 91 (14), 65 (12).
N-(2-Methoxybenzyl)pyridin-2-amine (4j):7d. mp 54ꢀ56 °C
4-Methyl-N-(naphthalen-2-ylmethyl)benzenesulfonamide (8d):21h
.
(hexane); Rf 0.9 (ethyl acetate); IR (KBr): ν 3256, 1607, 1234 cmꢀ1
;
mp 159ꢀ162 °C (hexane); Rf 0.63 (hexane/ethyl acetate: 3/2); IR
1H NMR (300 MHz, CDCl3): δ 3.79 (s, 3H), 4.46 (d, J = 6.1 Hz, 2H),
5.2 (s, br, 1H), 6.33ꢀ6.35 (m, 1H), 6.48ꢀ6.51 (m, 1H), 6.82ꢀ6.91,
7.19ꢀ7.3 (2 m, 2 and 2H, respectively), 7.31ꢀ7.34 (m, 1H), 8.03ꢀ8.05
(m, 1H); 13C NMR (75 MHz, CDCl3): δ 41.4, 55.1, 106.5, 110, 112.6,
120.3, 126.9, 128.1, 128.5, 137.2, 147.9, 157.2, 158.8; EI-MS m/z: 215
(M+ + 1, 12%), 214 (M+, 77), 213 (14), 199 (27), 184 (15), 183 (100),
181 (14), 180 (13), 136 (36), 121 (27), 107 (14), 105 (12), 91 (63), 79
(19), 78 (30), 66 (13).
(KBr): ν 3293, 1596, 1339, 1158, 668 cmꢀ1; H NMR (300 MHz,
1
CDCl3): δ 2.43 (s, 3H), 4.51 (d, J = 6 Hz, 2H), 4.74 (t, J = 5.7 Hz, 1H),
7.25ꢀ7.34, 7.45ꢀ7.49, 7.74ꢀ7.76, 7.81ꢀ7.83, 7.87ꢀ7.89 (5 m, 4, 2, 3, 1
and 1H, respectively); 13C NMR (75 MHz, CDCl3): δ 21.5, 45.4, 123.2,
125.1, 126, 126.7, 126.9, 127.2 (2C), 128.7, 129, 129.7 (2C), 131.2,
131.3, 133.8, 136.5, 143.5; EI-MS m/z: 311 (M+, 14%), 156 (52), 155
(57), 154 (100), 141 (15), 129 (18), 128 (18), 127 (17), 91 (15).
N-(Cyclohexylmethyl)-4-methylbenzenesulfonamide (8e):21h. mp
78ꢀ82 °C (hexane); Rf 0.87 (hexane/ethyl acetate: 3/2); IR (KBr): ν
N-(4-Chlorobenzyl)pyridin-2-amine (4k):7d. mp 103ꢀ105 °C
(hexane), Rf 0.9 (ethyl acetate); IR (KBr): ν 3225, 1607, 1570, 1533,
1081 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 4.4 (d, J = 5.9 Hz, 2H), 5.44
(s, br, 1H), 6.28ꢀ6.30 (m, 1H), 6.51ꢀ6.55 (m, 1H), 7.22ꢀ7.32
(m, 4H), 7.33ꢀ7.34 (m, 1H), 7.99ꢀ8.01(m, 1H); 13C NMR (75 MHz,
CDCl3): δ 45.3, 106.6, 113, 128.5 (2C), 128.5 (2C), 132.6, 137.4, 137.7,
147.9, 158.4; EI-MS m/z: 220 (M+ + 1, 33%), 219 (M+, 27), 218 (100),
217 (41), 142 (32), 140 (98), 127 (16), 125 (45), 107 (11), 89 (17), 79
(31), 78 (22).
1
3285, 1596, 1314, 1154, 676 cmꢀ1; H NMR (300 MHz, CDCl3): δ
0.83ꢀ0.88, 1.07ꢀ1.25 (2 m, 2 and 3H, respectively), 1.36ꢀ1.41 (m,
1H), 1.61ꢀ1.72 (m, 5H), 2.42 (s, 3H), 2.75 (t, J = 6.7 Hz, 2H), 4.78 (s,
br, 1H), 7.3 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 8.9 Hz, 2H); 13C NMR (75
MHz, CDCl3): δ 21.5, 25.6 (2C), 26.2, 30.5 (2C), 37.7, 49.3, 127 (2C),
129.6 (2C), 137.1, 143.2; EI-MS m/z: 267 (M+, 7%), 186 (11), 185
(10), 184 (100), 155 (100), 96 (10), 91 (60), 65 (13), 55 (11).
N-Benzylbenzenesulfonamide31a (8f). mp 85ꢀ87 °C (hexane); Rf
0.13 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3325, 1611, 1586, 1318,
1161, 676 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 4.13 (d, J = 6.2 Hz,
2H), 5.38 (t, J = 6.1 Hz, 1H), 7.18ꢀ7.28, 7.45ꢀ7.5, 7.54ꢀ7.6,
7.85ꢀ7.88 (4 m, 5, 2, 1 and 2H, respectively); 13C NMR (75 MHz,
CDCl3): δ 47, 126.9 (2C), 127.6, 127.7 (2C), 128.5 (2C), 129 (2C),
132.5, 136.2, 139.7; EI-MS m/z: 247 (M+, 0.2%), 106 (100), 104 (12),
91 (14), 79 (15), 78 (13), 77 (37), 51 (11).
4.3. Representative Procedure for the Preparation of
Aromatic Imines from Amines. To a stirred solution of amine
(1, 1 mmol) in toluene (3 mL) under argon atmosphere were added
Ru(OH)3ꢀFe3O4 (50 mg), NaOH (1.3 mmol, 52 mg), and the
corresponding alcohol (2, 1.5 mmol). The resulting mixture was stirred
at 130 °C until the end of reaction. The catalyst was removed by a
magnet, and the resulting mixture was quenched with water and
extracted with EtOAc. The organic phases were dried over MgSO4,
followed by evaporation under reduced pressure to remove the solvent.
The product was purified by chromatography on silica gel (hexane/ethyl
acetate) to give the corresponding products 3. Yields are included in
Table 4. Physical and spectroscopic data, as well as literature for known
compounds, are as follows:
N-Benzylpyridin-4-amine (4l):7d. Rf 0.07 (ethyl acetate); IR (film): ν
3246, 1604, 1524 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 4.35 (d, J = 5.2
Hz, 2H), 5.24 (s, br, 1H), 6.46 (d, J = 6.3 Hz, 2H), 7.26ꢀ7.35 (m, 5H),
8.12 (d, J = 5.4 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 46.7, 107.6,
127.2 (2C), 127.5 (2C), 128.7 (2C), 137.7, 149.1 (2C), 153.6; EI-MS
m/z: 185 (M+ + 1, 12%), 184 (M+, 86), 183 (23), 91 (100), 65 (11).
N-Benzylpyrimidin-2-amine (4m):7d. mp 70ꢀ75 °C (hexane); Rf
0.73 (ethyl acetate); IR (KBr): ν 3242, 1597, 1527 cmꢀ1; 1H NMR (300
MHz, CDCl3): δ 4.60 (d, J = 6.1 Hz, 2H), 6.38 (t, J = 4.8 Hz, 1H), 7.04
(s, br, 1H), 7.24ꢀ7.36 (m, 5H), 7.99 (s, br, 2H); 13C NMR (75 MHz,
CDCl3): δ 45.5, 110.4, 127.2, 127.8 (2C), 128.6 (2C), 139.2, 157.9
(2C), 162.4; EI-MS m/z: 186 (M+ + 1, 13%), 185 (M+, 100), 184 (71),
108 (11), 106 (45), 91 (23), 80 (10), 79 (14).
N-Benzyl-5-methylthiazol-2-amine (4n):7d. mp 86ꢀ91 °C (hexane);
Rf 0.3 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3188, 1589, 1560 cmꢀ1
;
1H NMR (300 MHz, CDCl3): δ 2.2 (s, 3H), 4.38 (s, 2H), 6.43 (s, br,
1H), 6.58 (s, 1H), 7.24ꢀ7.35 (m, 5H); 13C NMR (75 MHz, CDCl3): δ
11.9, 49.7, 120.8, 127.4, 127.6 (2C), 128.5 (2C), 135.4, 137.9, 169; EI-
MS m/z: 205 (M+ + 1, 10%), 204 (M+, 63), 203 (23), 106 (11), 91
(100), 65 (13).
N-Benzyl-4-methylbenzenesulfonamide (8a):21h. mp 118ꢀ120 °C
(hexane); Rf 0.27 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3278, 1600,
1328, 1169, 715 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 2.43 (s, 3H),
4.11 (d, J = 6.2 Hz, 2H), 4.73 (t, J = 6 Hz, 1H), 7.17ꢀ7.32, 7.74ꢀ7.78 (2
m, 7 and 2H, respectively); 13C NMR (75 MHz, CDCl3): δ 21.5, 47.2,
127.2 (2C), 127.8 (2C), 127.9, 128.7 (2C), 129.7 (2C), 136.2, 136.8,
143.5; EI-MS m/z: 261 (M+, 0.2%), 106 (100), 92 (13), 91 (38), 79
(10), 65 (11).
N-Benzylideneaniline (3a):26. Rf 0.37 (hexane/ethyl acetate: 4/1); IR
(film): ν 1621, 1597 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 7.23ꢀ7.49,
7.89ꢀ7.92 (2 m, 8 and 2H, respectively), 8.46 (s, 1H); 13C NMR (75
MHz, CDCl3): δ 120.9 (2C), 125.9, 128.8 (2C), 128.8 (2C), 129.1
(2C), 131.4, 136.2, 152, 160.4; EI-MS m/z: 182 (M+ + 1, 11%), 181
(M+, 100), 104 (8), 77 (35), 51 (12).
N-Benzylidene-4-methoxyaniline (3b):24k. mp 66ꢀ68 °C (hexane);
Rf 0.53 (hexane/ethyl acetate: 4/1); IR (KBr): ν 1609, 1581,
1247 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ 3.85 (s, 3H), 6.95ꢀ6.99,
7.26ꢀ7.29, 7.49ꢀ7.5, 7.91ꢀ7.93 (4 m, 2, 2, 3 and 2H, respectively), 8.51
(s, 1H); 13C NMR (75 MHz, CDCl3): δ 55.4, 114.3 (2C), 122.1 (2C),
128.5 (2C), 128.7 (2C), 131, 136.4, 144.8, 158.2, 158.3; EI-MS m/z: 212
(M+ + 1, 14%), 211 (M+, 88), 210 (15), 197 (15), 196 (100), 167 (22).
N-Benzylidene-3-chloroaniline (3c):36. Rf 0.87 (hexane/ethyl acet-
N-(3-Chlorobenzyl)-4-methylbenzenesulfonamide (8b):21h
. mp
70ꢀ73 °C (hexane); Rf 0.23 (hexane/ethyl acetate: 4/1); IR (KBr): ν
3262, 1597, 1571, 1321, 1158, 1089, 687 cmꢀ1; 1H NMR (300 MHz,
CDCl3): δ 2.37 (s, 3H), 4.0 (d, J = 6.5 Hz, 2H), 4.55 (s, 1H), 7.03ꢀ7.26
(m with d at 7.21, J = 8.2 Hz, 6H), 7.66 (d, J = 8.3 Hz, 2H); 13C NMR (75
MHz, CDCl3): δ 21.3, 46.2, 125.8, 126.8 (2C), 127.5, 127.6, 129.5 (2C),
129.6, 134, 136.5, 138.4, 143.4; EI-MS m/z: 295 (M+, 0.7%), 142 (32),
140 (100), 92 (18), 91 (32), 65 (10).
1
ate: 4/1); IR (film): ν 1622, 1582, 1067 cmꢀ1; H NMR (300 MHz,
CDCl3): δ 7.06ꢀ7.09, 7.18ꢀ7.21, 7.29ꢀ7.32, 7.43ꢀ7.51, 7.87ꢀ7.9
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ARTICLE
(5 m, 1, 2, 1, 3, and 2H, respectively), 8.4 (s, 1H); 13C NMR (75 MHz,
CDCl3): δ 119.4, 120.9, 125.8, 128.8 (2C), 128.9 (2C), 130, 131.7,
134.7, 135.8, 153.3, 161.3; EI-MS m/z: 217 (M+ + 1, 31%), 216 (M+,
45), 214 (100), 111 (26), 89 (10), 75 (15).
1060 cmꢀ1; 1H NMR (300 MHz, CDCl32): δ 1.22 (s, 9H), 3.52 (t, br, J =
1
5.5 Hz, 1H), 4.29 (dq, J = 15.9 Hz, J = 6.1 Hz, 2H), 6.27ꢀ6.28,
6.32ꢀ6.33, 7.37ꢀ7.38 (3 m, 1, 1 and 1H, respectively); 13C NMR (75
MHz, CDCl3): δ 22.5 (3C), 42.2, 56, 107.8, 110.3, 142.4, 151.8; EI-MS
m/z: 201 (M+, 0.1%), 145 (33), 82 (14), 81 (100), 77 (11), 57 (47),
53 (12).
N-Heptyl-2-methylpropane-2-sulfinamide (10e). Rf 0.1 (hexane/
ethyl acetate: 4/1); IR (film): ν 3213, 1361, 1057 cmꢀ1; 1H NMR (300
MHz, CDCl3): δ 0.88 (t, J = 6.9 Hz, 3H), 1.21 (s, 9H), 1.28ꢀ1.4 (m,
8H), 1.52ꢀ1.59 (m, 2H), 3.03ꢀ3.09 (m, 1H), 3.19ꢀ3.23 (m, 2H); 13C
NMR (75 MHz, CDCl3): δ 13.9, 22.5, 22.5 (3C), 26.6, 28.8, 31, 31.6,
45.6, 55.4; EI-MS m/z: 219 (M+, 0.2%), 163 (67), 146 (47), 114 (18), 78
N-(4-Methoxybenzylidene)aniline (3d):24k. mp 45ꢀ48 °C (hexane);
Rf 0.2 (hexane/ethyl acetate: 4/1); IR (KBr): ν 1679, 1600, 1245 cmꢀ1
;
1H NMR (300 MHz, CDCl3): δ 3.78 (s, 3H), 6.92ꢀ6.94, 7.16ꢀ7.18,
7.32ꢀ7.36, 7.76ꢀ7.82 (4 m, 2, 3, 2 and 2H, respectively), 8.32 (s, 1H);
13C NMR (75 MHz, CDCl3,): δ 54.8, 113.6 (2C), 120.4 (2C), 125,
128.6 (2C), 128.7, 130 (2C), 151.8, 159.1, 161.7; EI-MS m/z: 213 (M+,
1), 212 (13), 211 (88), 210 (100), 167 (12), 77 (20).
N-(4-Chlorobenzylidene)aniline (3e)25e. mp 51ꢀ54 °C (hexane); Rf
0.7 (hexane/ethyl acetate: 4/1); IR (KBr): ν 1621, 1578, 1092 cmꢀ1; 1H
NMR (300 MHz, CDCl3): δ 7.17ꢀ7.2, 7.35ꢀ7.41, 7.75ꢀ7.82 (3 m, 3, 4
and 2H, respectively), 8.37 (s, 1H); 13C NMR (75 MHz, CDCl3): δ
120.8 (2C), 128.9 (2C), 129.1 (2C), 129.3, 129.8 (2C), 134.6, 137.2,
151.5, 158.6; EI-MS m/z: 217 (M+ + 1, 32%), 216 (M+, 46), 215 (95),
214 (100), 104 (10), 77 (43), 51 (13).
4.4. Representative Procedure for the Preparation of
Aromatic Imines from Nitroarenes. To a stirred solution of
nitroarene (5, 1 mmol) in toluene (3 mL) under argon atmosphere
were added Ru(OH)3ꢀFe3O4 (50 mg), KOH (3 mmol, 168 mg), and
the corresponding alcohol (2, 8 mmol). The resulting mixture was
stirred at 130 °C until the end of reaction (see Table 6). The catalyst was
removed by a magnet, and the resulting mixture was quenched with
water and extracted with EtOAc. The organic phases were dried over
MgSO4, followed by evaporation under reduced pressure to remove the
solvent. The product 3 was purified by chromatography on silica gel
(hexane/ethyl acetate). Yields are included in Table 6.
(17), 77 (11), 57 (100); HRMS calcd (%) for C11H25NOS C4H10:
3
163.1031; found: 163.1050.
N-Isobutyl-2-methylpropane-2-sulfinamide (10f). Rf 0.1 (hexane/
ethyl acetate: 3/2); IR (film): ν 3234, 1361, 1050 cmꢀ1; 1H NMR (300
MHz, CDCl3): δ 0.92 (d, J = 2.7 Hz, 3H), 0.94 (d, J = 2.8 Hz, 3H), 1.22
(s, 9H), 1.78 (m, 1H), 2.81ꢀ2.9, 3.01ꢀ3.09 (2 m, 1 and 1H,
respectively), 3.3 (t, br, J = 5.7 Hz, 1H); 13C NMR (75 MHz, CDCl3):
δ 19.9, 20, 22.6 (3C), 29.5, 53.2, 55.6; EI-MS m/z: 177 (M+, 0.3%), 121
(90), 78 (36), 65 (22), 57 (100); HRMS calcd (%) for C8H19NOS
C4H10: 121.0561; found: 121.0558.
3
2-Methyl-N-(1-phenylethyl)propane-2-sulfinamide (10g):41. Rf
0.03 (hexane/ethyl acetate: 4/1); IR (film): ν 3213, 1603, 1389, 1357,
1049 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 1.23 (s, 9H); 1.51 (d, J =
6.6 Hz, 3H), 3.46 (s, br, 1H), 4.55 (dq, 1J = 6.5 Hz, 2J = 2.8 Hz, 1H),
7.26ꢀ7.36 (m, 5H); 13C NMR (75 MHz, CDCl3): δ 22.5 (3C), 22.7,
53.9, 55.4, 126.5 (2C), 127.7, 128.7 (2C), 144; EI-MS m/z: 225
(M+, 0.1%), 169 (24), 106 (10), 105 (100), 57 (14).
(R,R)-2-Methyl-N-(1-phenylethyl)propane-2-sulfinamide (10g0):41.
Rf 0.03 (hexane/ethyl acetate: 4/1); [R]D20 = ꢀ14 (c = 1 in EtOAc);
IR (film): ν 3213, 1603, 1389, 1357, 1049 cmꢀ1; 1H NMR (300 MHz,
CDCl3): δ 1.23 (s, 9H); 1.51 (d, J = 6.6 Hz, 3H), 3.46 (s, br, 1H), 4.55
4.5. Representative Procedure for the Alkylation of Sulfi-
namides. To a stirred solution of sulfinamide (9, 1 mmol) in toluene
(3 mL) under argon atmosphere were added Ru(OH)3ꢀFe3O4 (50 mg),
KOH (1.3 mmol, 73 mg), and the corresponding alcohol (11, 2 mmol).
The resulting mixture was stirred at 85 °C until the end of reaction. The
catalyst was removedbyamagnet, andtheresultingmixturewasquenched
with water and extracted with EtOAc. The organic phases were dried over
MgSO4, followed by evaporation under reduced pressure to remove the
solvent. The product was purified by chromatography on silica gel
(hexane/ethyl acetate) to give the corresponding products 10. Yields
are included in Table 9. Analytical, physical and spectroscopic data, as well
as literature for known compounds, follow:
1
2
(dq, J = 6.5 Hz, J = 2.8 Hz, 1H), 7.26ꢀ7.36 (m, 5H); 13C NMR
(75 MHz, CDCl3): δ 22.5 (3C), 22.7, 53.9, 55.4, 126.5 (2C), 127.7,
128.7 (2C), 144; EI-MS m/z: 225 (M+, 0.1%), 169 (24), 106 (10), 105
(100), 57 (14).
4.6. Representative Procedure for the Preparation of
Amines. To a solution of the corresponding sulfinamide (10, 1 mmol)
in 0.42 mL of MeOH was added 0.41 mL (1.64 mmol) of 4 M HCl 1,
4-dioxane solution at room temperature. The mixture was stirred for 30
min. The mixture was extracted with diethyl ether. The aqueous phases
were basified with NaOH solution and extracted again with diethyl ether.
The organic phases were evaporated under reduced pressure, and the
corresponding amine 11 was obtained pure. Yields are included in
Scheme 2. Physical and spectroscopic data, as well as literature for
known compounds, are as follows:
N-Benzyl-2-methylpropane-2-sulfinamide (10a):37. mp 58ꢀ63 °C
(hexane), Rf 0.13 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3205, 1607,
1392, 1370, 1040 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 1.24 (s, 9H),
1
2
3.61 (t, br, J = 6 Hz, 1H), 4.3 (dq, J = 15.6 Hz, J = 6.3 Hz, 2H),
7.27ꢀ7.35 (m, 5H); 13C NMR (75 MHz, CDCl3): δ 22.6 (3C), 49.3,
58.6, 127.5, 128 (2C), 128.5 (2C), 138.4; EI-MS m/z: 211 (M+, 0.1%),
155 (45), 92 (12), 91 (100), 77 (22), 57 (31).
Phenylmethanamine (11a):42. Rf 0.1 (hexane/ethyl acetate: 3/2);
IR (film): ν 3372, 1604 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 1.39 (s,
2H), 3.79 (s, 2H), 7.17ꢀ7.32 (m, 5H); 13C NMR (75 MHz, CDCl3): δ
46.1, 126.3, 126.7 (2C), 128.1 (2C), 143; EI-MS m/z: 108 (M+ + 1,
0.1%), 107 (M+, 100), 106 (100), 104 (11), 91 (31), 89 (10), 79 (90), 78
(32), 77 (56), 65 (11), 63 (10).
N-(4-Chlorobenzyl-2-methylpropane-2-sulfinamide (10b):38. mp
113ꢀ115 °C; Rf 0.17 (hexane/ethyl acetate: 4/1); IR (KBr): ν 3187,
1
1592, 1357, 1089, 1031 cmꢀ1; H NMR (300 MHz, CDCl3): δ 1.24
1
2
(s, 9H), 3.64 (s, br, 1H), 4.25 (dq, J = 14.7 Hz, J = 6.2 Hz, 2H),
7.26ꢀ7.32 (m, 4H); 13C NMR (75 MHz, CDCl3): δ 22.5 (3C), 48.6,
55.8, 128.6 (2C), 129.3 (2C), 133.3, 136.9; EI-MS m/z: 245 (M+, 0.1%),
189 (25), 139 (10), 138 (12), 127 (33), 125 (100), 77 (22), 57 (61).
N-(4-Methoxybenzyl)-2-methylpropane-2-sulfinamide (10c):39. Rf
0.1 (hexane/ethyl acetate: 4/1); IR (film): ν 3209, 1611, 1578, 1389,
1368, 1245, 1049 cmꢀ1; 1H NMR (300 MHz, CDCl3): δ 1.23 (s, 9H),
3.58 (s, br, 1H), 3.78 (s, 3H), 4.22 (dq, 1J = 15.7 Hz, 2J = 6.1 Hz, 2H),
6.85 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz,
CDCl3): δ 22.5 (3C), 48.6, 55, 55.6, 113.7 (2C), 129.2 (2C), 130.4,
158.9; EI-MS m/z: 241 (M+, 0.1%), 122 (10), 121 (100), 57 (12).
N-(Furan-2-ylmethyl)-2-methylpropane-2-sulfinamide (10d):40. Rf
0.1 (hexane/ethyl acetate: 3/2); IR (film): ν 3212, 1603, 1506, 1361,
(4-Methoxyphenyl)methanamine (11b):42. Rf 0.07 (hexane/ethyl
acetate: 3/2); IR (film): ν 3372, 1610, 1585, 1245, 1033 cmꢀ1; 1H NMR
(300 MHz, CDCl3): δ 1.47 (s, 2H), 3.73 (s, 3H), 3.74 (s, 2H), 6.84 (d, J
= 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ
45.4, 54.7, 113.4 (2C), 127.8 (2C), 135.1, 158; EI-MS m/z: 137 (M+,
96%), 136 (100), 122 (18), 121 (76), 120 (22), 119 (13), 109 (42), 108
(10), 106 (73), 104 (10), 94 (36), 93 (25), 92 (10), 91 (18), 79 (13), 78
(22), 77 (37), 66 (16), 65 (18), 63 (14).
(R)-1-Phenylethanamine (11c):34. Rf 0.3 (hexane/ethyl acetate:
3/2); [R]D20 = +23 (c = 1 in CHCl3); IR (film): ν 3365, 1604 cmꢀ1; 1H
NMR (300 MHz, CDCl3): δ 1.36 (d, J = 6.6 Hz, 3H), 1.53 (s, br, 2H),
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The Journal of Organic Chemistry
ARTICLE
4.08 (q, J = 6.6 Hz, 1H), 7.20ꢀ7.34 (m, 5H); 13C NMR (75 MHz,
CDCl3): δ 25.5, 51.1, 125.5 (2C), 126.6, 128.3 (2C), 147.6; EI-MS m/z:
121 (M+, 1%), 106 (100), 104 (18), 79 (29), 78 (11), 77 (23), 51 (13).
von Rechenberg, B. J. Magn. Magn. Mater. 2005, 293, 483–496.
(e) Majewski, P.; Thierry, B. Crit. Rev. Solid State Mater. Sci. 2007,
32, 203–215. (f) Lu, A.-H.; Salabas, E. L.; Sch€uth, F. Angew. Chem., Int.
Ed. 2007, 46, 1222–1244. (g) Shylesh, S.; Sch€unemann, V.; Thiel, W. R.
Angew. Chem., Int. Ed. 2010, 49, 3428–3459. (h) Polshettiwar, V.;
Varma, R. S. Green Chem. 2010, 12, 743–754.
’ ASSOCIATED CONTENT
ꢀ
(7) (a) Martinez, R.; Ramꢀon, D. J.; Yus, M. Adv. Synth. Catal. 2008,
S
Supporting Information. General information, catalyst
b
350, 1235–1240. (b) Mojtahedi, M. M.; Abaee, M. S.; Eghtedari, M.
Appl. Organometal. Chem. 2008, 22, 529–532. (c) Mojtahedi, M. M.;
Abaee, M. S.; Alishiri, T. Tetrahedron Lett. 2009, 50, 2322–2325.
characterization data, XPS data, TEM images of catalysts, size
particle distribution for Ru(OH)3ꢀFe3O4 (after and before the
reactions), graphics of the obtained yields for the reused catalyst,
and copies of 1H and 13C NMR for compounds 3, 4, 8, 10, and
11. This material is available free of charge via the Internet at
http://pubs.acs.org.
ꢀ
(d) Martinez, R.; Ramꢀon, D. J.; Yus, M. Org. Biomol. Chem. 2009,
7, 2176–2181. (e) Zhang, Z.-H.; L€u, H.-Y.; Yang, S.-H.; Gao, J.-W.
J. Comb. Chem. 2010, 12, 643–646. (f) L€u, H.-F.; Yang, S.-H.; Deng, J.;
Zhang, Z.-H. Aust. J. Chem. 2010, 63, 1290–1296. (g) Gooβen, L. J.;
Mamone, P.; Oppel, C. Adv. Synth. Catal. 2011, 353, 57–63.
(h) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M.; Hoseini, J. Adv.
Synth. Catal. 2011, 353, 125–132.
’ AUTHOR INFORMATION
(8) (a) Beydoun, D.; Amal, R.; Low, G. K.-C.; McEvoy, S. J. Phys.
Chem. B 2000, 104, 4387–4396. (b) Xuan, S.; Jiang, W.; Gong, X.; Hu,
Y.; Chen, Z. J. Phys. Chem. C 2009, 113, 553–558.
(9) Shu, Z.; Wang, S. J. Nanomater. 2009, ID 340217 (5 p).
(10) Niu, F.; Zhang, L.; Luo, S.-Z.; Song, W.-G. Chem. Commun.
2010, 46, 1109–1111.
Corresponding Author
*djramon@ua.es
Notes
†In memory of our friend Prof. Dr. Josꢀe M. Concellꢀon.
(11) Uheida, A.; Salazar-Alvarez, G.; Bj€orkman, E.; Yu, Z.;
Muhammed, M. J. Colloid Interface Sci. 2006, 298, 501–507.
(12) (a) Aliaga, M. J.; Ramꢀon, D. J.; Yus, M. Org. Biomol. Chem.
2010, 8, 43–46. (b) Cano, R.; Ramꢀon, D. J.; Yus, M. J. Org. Chem. 2010,
75, 3458–3460.
(13) (a) Basiꢀnska, A.; Jꢀoꢀzwiak, W. K.; Gꢀoralski, J.; Domka, F. Appl.
Catal. A: Gen. 2000, 190, 107–115. (b) Basiꢀnska, A.; Klimkiewicz, W. R.;
Domka, F. Appl. Catal. A: Gen. 2001, 207, 287–294. (c) Kotani, M.;
Koike, T.; Yamaguchi, K.; Mizuno, N. Green Chem. 2006, 8, 735–741.
(14) Uheida, A.; Iglesias, M.; Fontꢁas, C.; Hidalgo, M.; Salvadꢀo, V.;
Zhang, Y.; Muhammed, M. J. Colloid Interface Sci. 2006, 301, 402–408.
(15) (a) Liu, J.; Peng, X.; Sun, W.; Zhao, Y.; Xia, C. Org. Lett. 2008,
10, 3933–3936. (b) Ranganath, K. V. S.; Kloesges, J.; Schꢀafer, A. H.;
Glorius, F. Angew. Chem., Int. Ed. 2010, 49, 7786–7789.
’ ACKNOWLEDGMENT
This work was supported by the Spanish Ministerio de Ciencia
ꢀ
y Tecnologia (Consolider Ingenio 2010 CSD2007-00006,
CTQ2007-65218/BQU) and the Generalitat Valenciana
(Prometeo 2009/03, FEDER). R.C. thanks G.V. for a fellowship
through the PROMETEO program. We gratefully acknowledge
the refinement of our English by Mrs. Oriana C. Townley.
’ REFERENCES
(1) For various aspects, see: (a) Mizuno, N.; Misono, M. Chem. Rev.
1998, 98, 199–217. (b) Lipshutz, B. H. Adv. Synth. Catal. 2001,
343, 313–326. (c) Gladysz, J. A. Chem. Rev. 2002, 102, 3215–3216.
(16) (a) Guillena, G.; Ramꢀon, D. J.; Yus, M. Angew. Chem., Int. Ed.
2007, 46, 2358–2364. (b) Hamid, M. H. S. A.; Slatford, P. A.; Williams,
J. M. J. Adv. Synth. Catal. 2007, 349, 1555–1575. (c) Nixon, T. D.;
Whittlesey, M. K.; Williams, J. M. J. Dalton Trans. 2009, 753–762.
(d) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010, 110, 681–703.
ꢀ
(introduction of a thematic issue).(d) Corma, A.; Garcia, H. Chem. Rev.
2003, 103, 4307–4365. (e) Astruc, D.; Lu, F.; Ruiz Aranzaes, J. Angew.
Chem., Int. Ed. 2005, 44, 7852–7872. (f) Lauritsen, J. V.; Vang, R. T.;
Besenbacher, F. Catal. Today 2006, 111, 34–43. (g) Matsumoto, T.;
Ueno, M.; Wang, N.; Kobayashi, S. Chem. Asian J. 2008, 3, 196–214.
(h) Newton, M. A. Chem. Soc. Rev. 2008, 37, 2644–2657. (i) Hutchings,
G. J. J. Mater. Chem. 2009, 19, 1222–1235. (j) Sch€atz, A.; Reiser, O.;
Stark, W. J. Chem.—Eur. J. 2010, 16, 8950–8967.
ꢀ
(e) Alonso, F.; Foubelo, F.; Gonzꢀalez-Gꢀomez, J. C.; Martinez, R.;
Ramꢀon, D. J.; Riente, P.; Yus, M. Mol. Divers. 2010, 14, 411–424.
ꢀ
(17) For recent examples from our laboratory, see: (a) Martinez, R.;
Brand, G. J.; Ramꢀon, D. J.; Yus, M. Tetrahedron Lett. 2005,
ꢀ
(2) Metal Oxides Chemistry and Applications; Fierro; J. L. G., Ed.;
CRC Press: Boca Raton, 2006.
46, 3683–3686. (b) Martinez, R.; Ramꢀon, D. J.; Yus, M. Tetrahedron
ꢀ
2006, 62, 8982–8987. (c) Martinez, R.; Ramꢀon, D. J.; Yus, M. Tetra-
(3) For instance, see: (a) Santra, A. K.; Goodman, D. W. J. Phys.:
Condens. Matter 2002, 14, R31–R62. (b) Carrier, X.; Marceau, E.;
Carabiniero, H.; Rodriguez-Gonzꢀalez, V.; Che, M. Phys. Chem. Chem.
Phys. 2009, 11, 7527–7539. (c) Minakata, S.; Komatsu, M. Chem. Rev.
2009, 109, 711–724. (d) Yamaguchi, K.; Mizuno, N. Synlett 2010,
2365–2382.
hedron 2006, 62, 8988–9001.
(18) (a) Guillena, G.; Ramꢀon, D. J.; Yus, M. Chem. Rev. 2010,
110, 1611–1641. (b) Yamaguchi, R.; Fujita, K.-i.; Zhu, M. Heterocycles
2010, 81, 1093–1140. (c) Watson, A. J. A.; Williams, J. M. J. Science
2010, 329, 635–636.
ꢀ
(19) For reviews on the synthesis of amines, see: (a) Malpass, J. R. In
Comprehensive Organic Chemistry; Barton, D.; Ollis; W. D., Eds.;
Pergamon: Oxford, 1979; Vol. 2, pp 3ꢀ59. (b) Gladych, J. M. Z.;
Hartley, D. In Comprehensive Organic Chemistry; Barton, D.; Ollis, W. D.,
Eds.; Pergamon: Oxford, 1979; Vol. 2, pp 61ꢀ130. (c) Lindsay, R. J. In
Comprehensive Organic Chemistry; Barton, D.; Ollis, W. D., Eds.;
Pergamon: Oxford, 1979; Vol. 2, pp 131ꢀ184. (d) Mitsunobu, O. In
Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.;
Pergamon Press: Oxford, 1991, Vol. 6, pp 65ꢀ101. (e) Gilchrist,
T. L. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 8, pp 381ꢀ402. (f) Salvatore,
R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron 2001, 57, 7785–7811.
(g) Schlummer, B.; Scholz, U. Adv. Synth. Catal. 2004, 346, 1599–
1626. (h) Mu~niz, K.; H€ovelmann, C. H.; Streuff, J.; Campos-Goꢀmez, E.
Pure Appl. Chem. 2008, 80, 1089–1096. (i) M€uller, T. E.; Hultzsch, K. C.;
(4) Wong, M. S. In Metal Oxides Chemistry and Applications; Fierro,
J. L. G., Ed.; CRC Press: Boca Raton, 2006; pp 31ꢀ54.
(5) For instance, see: (a) Lambert, J.-F.; Che, M. J. Mol. Catal. A:
Chem. 2000, 162, 5–18. (b) Arurault, L.; Bes, R.; Bonino, J.-P. Met.
Finish. 2003, 101, 36–37. (c) van Dillen, A. J.; Ter€orde, R. J. A. M.;
Lensveld, D. J.; Geus, J. W.; de Jong, K. P. J. Catal. 2003, 216, 257–264.
(d) Jiang, S. P. Mater. Sci. Eng., A 2006, 418, 199–210.(e) Geus, J. W. In
Catalyst Preparation; Regalbuto, J., Ed.; CRC Press: Boca Ratꢀon, 2007;
pp 341ꢀ372.
(6) For instance, see: (a) Pankhurst, Q. A.; Connolly, J.; Jones, S. K.;
Dobson, J. J. Phys. D: Appl. Phys. 2003, 36, R167–R181. (b) Graham,
D. L.; Ferreira, H. A.; Freitas, P. P. Trends Biotechnol. 2004, 22, 455–
462. (c) Gptar, A. K.; Gupta, M. Biomaterials 2005, 26, 3995–
4021. (d) Neuberger, T.; Sch€opf, B.; Hofmann, H.; Hofmann, M.;
5556
dx.doi.org/10.1021/jo200559h |J. Org. Chem. 2011, 76, 5547–5557

The Journal of Organic Chemistry
ARTICLE
Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795–3892.
(j) Hartwig, J. F. H. Acc. Chem. Res. 2008, 41, 1534–1544.
(28) Gnanaprakasam, B.; Zhang, J.; Milstein, D. Angew. Chem., Int.
Ed. 2010, 49, 1468–1471.
(20) Shi, F.; Tse, M. K.; Zhou, S.; Pohl, M.-M.; Radnik, J.; H€ubner,
S.; J€ahnisch, K.; Br€uckner, A.; Beller, M. J. Am. Chem. Soc. 2009,
131, 1775–1779.
(29) Zanardi, A.; Mata, J. A.; Peris, E. Chem.—Eur. J. 2010,
16, 10502–10506.
(30) Feng, C.; Liu, Y.; Peng, S.; Shuai, Q.; Deng, G.; Li, C.-J. Org.
(21) For instance, see: (a) Pratt, E. F.; Frazza, E. J. J. Am. Chem. Soc.
1954, 76, 6174–6179. (b) Sprinzak, Y. J. Am. Chem. Soc. 1956,
78, 3207–3208. (c) Watanabe, Y.; Morisaki, Y.; Kondo, T.; Mitsudo,
T.-a. J. Org. Chem. 1996, 61, 4214–4218. (d) Fujita, K.-i.; Li, Z.; Ozeki, N.;
Yamaguchi, R. Tetrahedron Lett. 2003, 44, 2687–2690. (e) Blank, B.;
Madalska, M.; Kempe, R. Adv. Synth. Catal. 2008, 350, 749–758.
(f) Shimizu, K.; Nishimura, M.; Satsuma, A. ChemCatChem 2009,
1, 497–503. (g) Likhar, P. R.; Arundhathi, R.; Kantam, M. L.; Prathima,
Lett. 2010, 12, 4888–4891.
(31) For examples of N-alkylation of various sulfonamides using a
hydrogen autotrasfer process, see: (a) Hamid, M. H.; Allen, C. L.; Lamb,
G. W.; Maxwell, A. C.; Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J.
J. Am. Chem. Soc. 2009, 131, 1766–1774. (b) Shi, F.; Tse, M. K.; Cui, X.;
G€ordes, D.; Michalik, D.; Thurow, K.; Deng, Y.; Beller, M. Angew. Chem.,
Int. Ed. 2009, 48, 5912–5915. (c) Cui, X.; Shi, F.; Tse, M. K.; G€ordes, D.;
Thurow, K.; Beller, M.; Deng, Y. Adv. Synth. Catal. 2009,
351, 2949–2958. (d) Cui, X.; Shi, F.; Zhang, Y.; Deng, Y. Tetrahedron
Lett. 2010, 51, 2048–2051. (e) Zhu, M.; Fujita, K.-i.; Yamaguchi, R. Org.
Lett. 2010, 12, 1336–1339.
(32) For the use of sulfonamides as catalysts from our laboratory, see
for instance: (a) Forrat, V. J.; Ramꢀon, D. J.; Yus, M. Tetrahedron:
Asymmetry 2005, 16, 3341–3344. (b) Forrat, V. J.; Prieto, O.; Ramꢀon,
D. J.; Yus, M. Chem.—Eur. J. 2006, 12, 4431ꢀ4445 [Corrigendum:
Chem.—Eur. J. 2006, 12, 6720]. (c) Forrat, V. J.; Ramꢀon, D. J.; Yus, M.
Tetrahedron: Asymmetry 2006, 17, 2054–2058. (d) Forrat, V. J.; Ramꢀon,
ꢀ
P. S. Eur. J. Org. Chem. 2009, 5383–5389. (h) Martinez-Asencio, A.;
Ramꢀon, D. J.; Yus, M. Tetrahedron Lett. 2010, 51, 325–327. (i) Corma, A.;
Rꢀodenas, T.; Sabater, M. J. Chem.—Eur. J. 2010, 16, 254–260.
(j) Gonzꢀalez-Arellano, C.; Yoshida, K.; Luque, R.; Gai, P. L. Green Chem.
2010, 12, 1281–1287. (k) Saidi, O.; Blacker, A. J.; Farah, M. M.; Marsden,
S. P.; Williams, J. M. J. Chem. Commun. 2010, 46, 1541–1543. (l) He, L.;
Lou, X.-B.; Ni, J.; Liu, Y.-M.; Cao, Y.; He, H.-Y.; Fan, K.-N. Chem.—Eur. J.
2010, 16, 13965–13969.(m) Cui, X.; Zhang, Y.; Shi, F.; Deng, Y. Chem.—
Eur. J. 2011, 17, 1021ꢀ1028 (Corrigendum: Chem.—Eur. J. 2011, 17, 1382).
ꢀ
ꢀ
(22) Martinez-Asencio, Ramꢀon, D. J.; Yus, M. Tetrahedron 2011,
D. J.; Yus, M. Tetrahedron: Asymmetry 2007, 18, 400–405. (e) Martinez,
67, 3140–3149.
R.; Zoli, L.; Cozzi, P. G.; Ramꢀon, D. J.; Yus, M. Tetrahedron: Asymmetry
2008, 19, 2600–2607. (f) Forrat, V. J.; Ramꢀon, D. J.; Yus, M. Tetra-
hedron: Asymmetry 2009, 20, 65–67.
(23) Gawronski, J.; Wascinska, N.; Gajewy, J. Chem. Rev. 2008,
108, 5227–5252.
(24) For instance, see: (a) Nishinaga, A.; Yamada, T.; Fujisawa, H.;
Ishizaki, K.; Ihara, H.; Matsuura, T. J. Mol. Catal. 1988, 48, 249–264. (b)
Porta, F.; Crotti, C.; Cenini, S.; Palmisano, G. J. Mol. Catal. 1989,
50, 333–341. (c) Shimizu, M.; Orita, H.; Hayakawa, T.; Suzuki, K.;
Takehira, K. Heterocyles 1995, 41, 773–779. (d) Bailey, A. J.; James, B. R.
Chem. Commun. 1996, 2343–2344. (e) Minakata, S.; Oshima, Y.;
Takemiya, A.; Ryu, I.; Komatsu, M.; Ohshiro, Y. Chem. Lett.
1997, 311–312. (f) Mori, K.; Yamaguchi, K.; Mizugaki, T.; Ebitani,
K.; Kaneda, K. Chem. Commun. 2001, 461–462. (g) Maeda, Y.;
Nishimura, T.; Uemura, S. Bull. Chem. Soc. Jpn. 2003, 76, 2399–2403.
(h) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2003, 42, 1480.
(i) Yamaguchi, K.; Mizuno, N. Chem.—Eur. J. 2003, 9, 4353–4361.
(j) Samec, J. S. M.; Ell, A. H.; B€ackvall, J.-E. Chem.—Eur. J. 2005,
11, 2327–2334. (k) Wang, J.-R.; Fu, Y.; Zhang, B.-B.; Cui, X.; Liu, L.;
Guo, Q.-X. Tetrahedron Lett. 2006, 47, 8293–8297. (l) Murahashi, S. I.;
Okano, Y.; Sato, H.; Nakae, T.; Komiya, N. Synlett 2007, 1675–1678.
(m) Zhu, B. L.; Angelici, R. J. Chem. Commun. 2007, 2157–2159.
(n) Li, F.; Chen, J.; Zhang, Q.; Wang, Y. Green Chem. 2008,
10, 553–562. (o) Zhu, B. L.; Lazar, M.; Trewyn, B. G.; Angelici, R. J.
(33) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997,
119, 9913–9914.
(34) Chi, Y.; Zhou, Y.-G.; Zhang, X. J. Org. Chem. 2003,
68, 4120–4122.
(35) For some examples, see: (a) Richardson, J. T.; Lu, W.-C.
J. Chem. 1976, 42, 275–28. (b) Hamada, H.; Kuwahara, Y.; Sato, T.;
Wakabayashi, K. Bull. Chem. Soc. Jpn. 1987, 60, 55–60. (c) Ohtani, B.;
Osaki, H.; Nishimoto, S.-i.; Kagiya, T. Tetrahedron Lett. 1986,
27, 2019–2022. (d) Yamaguchi, R.; Kawagoe, S.; Asai, C.; Fujita, K.-i.
Org. Lett. 2008, 10, 181–184. (e) Gunanathan, C.; Milstein, D. Angew.
Chem., Int. Ed. 2008, 47, 8661–8664. (f) Yamaguchi, K.; He, J.; Oishi, T.;
Mizuno, N. Chem.—Eur. J. 2010, 16, 7199–7207. (g) Imm, S.; B€ahn, S.;
Neubert, L.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010,
49, 8126–8129. (h) Pingen, D.; M€uller, C.; Vogt, D. Angew. Chem., Int.
Ed. 2010, 49, 8130–8133. (i) Kawahara, R.; Fujita, K.-i.; Yamaguchi, R.
J. Am. Chem. Soc. 2010, 132, 15108–15111.
(36) Naeimi, H.; Sharghi, H.; Salimi, F.; Rabiei, K. Heteroat. Chem.
2008, 19, 43–47.
(37) Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A. J. Am.
Chem. Soc. 1998, 120, 8011–8019.
ꢀ
J. Catal. 2008, 260, 1–6. (p) Grirrane, A.; Corma, A.; Garcia, H. J. Catal.
2009, 264, 138–144. (q) Aschwanden, L.; Mallat, T.; Grunwaldt, J. D.;
Krumeich, F.; Baiker, A. J. Mol. Catal. A: Chem. 2009, 300, 111–115.
(r) Aschwanden, L.; Mallat, T.; Krumeich, F.; Baiker, A. J. Mol. Catal. A:
Chem. 2009, 309, 57–62. (s) Aschwanden, L.; Panella, B.; Rossbach, P.;
Keller, B.; Baiker, A. ChemCatChem 2009, 1, 111–115. (t) So, M. H.; Liu,
Y. G.; Ho, C. M.; Che, C. M. Chem. Asian J. 2009, 4, 1551–1561.
(u) Aschwanden, L.; Mallat, T.; Maciejewski, M.; Krumeich, F.; Baiker,
A. ChemCatChem 2010, 2, 666–673.
(38) Gobi, L.; Knust, H.; Malherbe, P.; Nettekoven, M.; Pinard, E.;
Roche, O.; Roger-Evans M. PTC Int. Appl., WO 2008107335, 2008.
(39) Solꢁa, J.; Revꢀes, M.; Riera, A.; Verdaguer, X. Angew. Chem., Int.
Ed. 2007, 46, 5020–5023.
(40) Furkert, D. P.; Husbands, S. M. Org. Lett. 2007, 9, 3769–3771.
(41) Petrovic, A. G.; Polavarapn, P. L.; Drabowicz, J.; Lyzwa, P.;
Mikolajczyk, M.; Wieczorek, W.; Balisnka, A. J. Org. Chem. 2008,
73, 3120–3129.
(25) (a) Blackburn, L.; Taylor, R. J. Org. Lett. 2001, 3, 1637–1639.
(b) Sithambaram, S.; Kumar, R.; Son, Y. C.; Suib, S. L. J. Catal. 2008,
253, 269–277. (c) Kwon, M. S.; Kim, S.; Park, S.; Bosco, W.; Chidrala,
R. K.; Park, J. J. Org. Chem. 2009, 74, 2877–2879. (d) Kim, J. W.; He, J.;
Yamaguchi, K.; Mizuno, N. Chem. Lett. 2009, 38, 920–921. (e) Sun, H.;
Su, F.-Z.; Ni, J.; Cao, Y.; He, H.-Y.; Fan, K.-N. Angew. Chem., Int. Ed.
2009, 48, 4390–4393.
(42) Addis, D.; Enthaler, S.; Junge, K.; Wendt, B.; Beller, M.
Tetrahedron Lett. 2009, 50, 3654–3656.
(26) For the alternative process using only amines as starting
material, see for instance: Kodama, S.; Yoshida, J.; Nomoto, A.;
Ueta, Y.; Yano, S.; Ueshima, M.; Ogawa, A. Tetrahederon Lett. 2010,
51, 2450–2452.
(27) For an example of MeerweinꢀPonndorfꢀVerley reduction
ꢀ
without a transition metal catalyst, see: Martinez, R.; Ramꢀon, D. J.;
Yus, M. J. Org. Chem. 2008, 73, 9778–9780.
5557
dx.doi.org/10.1021/jo200559h |J. Org. Chem. 2011, 76, 5547–5557