First practical cross-alkylation of primary alcohols with a new and recyclable impregnated iridium on magnetite catalyst

Article abstract of DOI:10.1039/c2cc33101b

A new impregnated iridium on magnetite catalyst has been prepared, characterized, used and recycled, up to ten times with practically the same activity, for the first practical cross-alkylation of primary alcohols. The catalyst showed a wide reaction scope, is easy to prepare and handle, and it could be removed from the reaction medium just by magnetic sequestering.

Full text of DOI:10.1039/c2cc33101b

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COMMUNICATION
First practical cross-alkylation of primary alcohols with a new and
recyclable impregnated iridium on magnetite catalystw
´
Rafael Cano, Miguel Yus and Diego J. Ramon*
Received 30th April 2012, Accepted 14th June 2012
DOI: 10.1039/c2cc33101b
A new impregnated iridium on magnetite catalyst has been
prepared, characterized, used and recycled, up to ten times with
practically the same activity, for the first practical cross-alkylation
of primary alcohols. The catalyst showed a wide reaction scope, is
easy to prepare and handle, and it could be removed from the
reaction medium just by magnetic sequestering.
analysis did not provide any concluding information due to
the low iridium metal loading and its high dispersion, with
exception of the support diffraction peaks (Fe3O4). The FXR
analysis revealed a total incorporation of iridium of 0.5%. The
BET surface area of catalyst was 8.0 m2 gꢀ1, almost the same
as that of the initial magnetite, 9.6 m2 gꢀ1, and the concordant
results show that there was no significant sinterization process
under the assayed impregnation protocol and within the error of
this technique. Moreover, the TEM images showed spherical
particles for the catalyst with sizes in the range 0.1 ꢁ 0.09 mm,
similar to those obtained from the initial commercial magnetite
(size: 0.1 ꢁ 0.1 mm), with a homogenous distribution of nano-
particles of iridium (size: 0.8 ꢁ 0.2 nm; more than 95% of particles
in the range of 0.5–1.5 nm).
Alcohols are one of the most important classes of organic
compounds owing to their wide variety of uses in industrial
and laboratory chemistry. Although a plethora of methods for
the synthesis of alcohols are known,1 their simple creation by
carbon–carbon bond manipulation is very unusual. The Guerbet
reaction, a typical hydrogen autotransfer process2 (also denoted
borrowing hydrogen), is the only approach to this simple process.
Originally the reaction was only useful for the auto-alkylation of
primary alcohols.3 However, the introduction of secondary alcohols
permitted the cross-alkylation between secondary and primary
alcohols,4 with the latter ones operating as a source of electrophiles.
Besides this partial success, the trials of cross-alkylation between
primary alcohols5 were very discouraging, since it was necessary to
add an excess of one alcohol (from three to thirteen equivalents),
and to use high pressure (30 atmospheres) and temperatures (from
200 to 310 1C). In these transformations, the amount of catalyst
ranged from 3 to 175 mol%, affording the expected product in
moderate yield (from 11 to 62%), with many other by-products.
Meanwhile, we have recently developed a new, simple and
robust method to immobilize different metal oxides6 onto
magnetite.7 Along this research line, we report herein the first
immobilization of iridium on magnetite using an impregnation
protocol and its use as a reusable heterogeneous catalyst for
the cross-alkylation of primary alcohols.
The cross-alkylation of 2-phenylethanol (1a) and benzyl
alcohol (2a) was selected as a model reaction in order to
optimize the conditions (Table 1).
The influence of temperature, solvent, base, amount of
KOH, alcohol 2a, and catalyst was studied initially (see ESIw),
Table 1 Optimization of catalystsa
Entry Catalyst (mol%)
Yieldb 3a (%) Yieldb 4 (%)
1
2
IrO2–Fe3O4 (0.14)
Fe3O4 (65)
—
IrCl4 (0.14)
[IrCl(cod)]2 (0.07)
IrO2 (0.14)
CoO–Fe3O4 (1.4)
NiO–Fe3O4 (1.0)
CuO–Fe3O4 (1.3)
Ru2O3–Fe3O4 (1.4)
PdO–Fe3O4 (1.2)
NiO/CuO–Fe3O4 (0.9/1.1)
96
35
14
59
47
67
0
3
3
10
7
12
9
0
0
1
5
2
The catalyst was prepared by the classical impregnation method
and characterized by XPS and XRD analyses. The XPS spectra
showed two peaks placed at 62.1 and 64.5 eV, which correspond
to the binding energies of IrO2 4f7/2 and 4f5/2 levels,8 with the
superficial incorporation (1 nm depth) being 18%. The XRD
3c
4c
5c
6c
7
8
9
10
11
12
13
0
11
26
41
28
Dpto. Quı´mica Orga´nica and Instituto de Sı´ntesis Orga´nica,
Universidad de Alicante, Apdo. 99, E-03080 Alicante, Spain.
E-mail: djramon@ua.es; Fax: +34-965903549; Tel: +34-965903986
w Electronic supplementary information (ESI) available: General
procedure for the preparation of catalyst and products, XPS, TEM,
EDS, and XRD analyses, particle size distribution, and 1H and
13C NMR spectra. See DOI: 10.1039/c2cc33101b
4
8
Pd(0,II)/CuO–Fe3O4 (1.5/0.8) 32
a
Reactions were carried out using 1a (1.0 mmol) and 2a (2.0 mmol) in
b
toluene (1.5 mL). Isolated yield after column chromatography.
c
Reactions were performed for 5 days.
c
7628 Chem. Commun., 2012, 48, 7628–7630
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Table 2 Cross-alkylation of primary alcoholsa
Entry
R
Ar
Alcohol
Yieldb (%)
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
96
72
73
71
75
72
79
68
80
89
98
87
83
93
97
88
90
86
82
2c
4-ClC6H4
4-MeC6H4
4-tBuC6H4
4-MeOC6H4
3,5-(MeO)2C6H3
Ph
3c
4c
Fig. 1 Recycling of IrO2–Fe3O4 catalyst.
5c
6c
with the conditions presented in entry 1 of Table 1 showing
the maximum yield of product 3a. (E)-Prop-1-ene-1,3-diyldi-
benzene (4), which formed from the dehydrogenation of the
starting alcohol 1a, an auto-condensation process and final
decarbonylation,9 was also detected as a by-product. The effect
of the commercial micro-magnetite support was also tested
(entry 2), which gave a modest yield in the cross-alkylation
process. The reaction using 200 mol% of magnetite rendered
compound 3a in 70% yield, after 7 days. Even some amount of
product 3a could be detected when the reaction was performed in
the absence of any transition salt (entry 3). Then, other sources of
iridium catalyst were checked and both soluble and insoluble
catalysts gave similar results (entries 4–6). Finally, other
impregnated metals on magnetite were used as catalyst, but in
all trials the yields were appreciably lower (entries 7–13).
Once the optimal reaction conditions were established, the
problem of recycling was examined. The catalyst recovered from
the reaction by using a magnet (entry 1, Table 1) was washed
with toluene and re-used under the same reaction conditions,
which resulted in the expected product 3a (Fig. 1). The iridium
catalyst could be re-used up to ten times without practically
losing its activity, with the lower yield obtained being 71%. The
phenomenon of leaching was studied by ICP-MS analysis of the
resulting reaction solution mixture, and 3.3% of the initial
amount of iridium was detected (0.4% for iron). All these data
demonstrate the possible structural integrity of the catalyst.
Moreover, the TEM images of the ten-times recycled catalyst
showed a homogenous distribution of nano-particles of iridium
(size: 1.0 ꢁ 0.4 nm; more than 90% of particles in the range of
0.5–1.5 nm), which is similar to the initial one, with the BET
surface area being 7.5 m2 gꢀ1 and the XPS spectra being exactly
the same as those obtained from the fresh catalyst.
7c
4-BrC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
2-ClC6H4
3-ClC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
Et
8c
Ph
9c
4-ClC6H4
4-MeOC6H4
Ph
Ph
Ph
4-ClC6H4
4-MeOC6H4
Ph
4-ClC6H4
4-MeOC6H4
Ph
10c
11
12c
13c
14c
15c
16c
17
18
19c
Et
Et
Me(CH2)9
a
Reactions were carried out using 1 (1.0 mmol) and 2 (2.0 mmol),
b
KOH (1 mmol) in toluene (1.5 mL). Isolated yield after column
c
chromatography. Reactions were performed for 5 days.
The usual cross-alkylation process using alcohol 1a and
IrO2–Fe3O4, after seven days and final treatment with trifluoro-
acetic acid, did not produce the expected compound 3. More-
over, the standard reaction mixture was filtered off at 110 1C
after one-day reaction (21% of compound 3a), and the resulting
solution was kept at this temperature for three more days,
which resulted in only a 26% yield of compound 3a. In a
similar experiment, after the hot-filtration, magnetite (65 mol%),
compound 1f, benzyl alcohol (2a), and KOH were added and
after 4-day reaction only compound 3a (29%) was detected, and
compound 3m was not formed.
The optimized protocol was applied to other substrates in order
to study the scope of the reaction (Table 2). The protocol gave
homogenous results in the case of using functionalized benzyl
alcohols (2) independent of electron-withdrawing or electron-
donating groups (Table 2, entries 1–6). The methodology could
be applied to different 1-arylethanol reagents (1) with practically
the same yields (entries 7–15), even it was possible to carry out the
reaction with an aliphatic alcohol (1), which gave the expected
product with similar results (entries 16–19). The reaction failed
when two different aliphatic alcohols were used, resulting in the
recovery of the starting materials.
To know whether the reaction was carried out by the iridium
leached into the organic medium, we performed the standard
reaction between compounds 1a and 2a (Table 1, entry 1). After
that, the catalyst was removed by a magnet and washed with
toluene. The solvents of the above solution, without catalyst, were
removed under low pressure and 2-(4-methoxyphenyl)ethanol (1f),
benzyl alcohol (2a), KOH and toluene were added to the above
residue. The resulting mixture was heated again at 110 1C for
5 days. The analysis of the crude mixture, after hydrolysis, revealed
the formation of compound 3a in 91% (catalyzed process) and
product 3m in only 32% yield (compare with entry 13 in Table 2).
Therefore, we could exclude that the final leached iridium was
responsible for the reaction results. The three-phase test10
was performed in order to exclude a possible dynamic metal
leach and return process. So, a benzylic alcohol moiety was
attached to a NovaSyn-amino resin by reaction with phthalide.
The last part of this study was focused on the possible
catalytic pathway of the reaction, for the standard reaction
between 2-phenylethanol and benzyl alcohol. The same reaction
was performed with different combinations of labelled reagents, in
all cases, it was found that the product 30a was labelled in different
ratios but always at the same positions. Thus, the reaction using
only deuterated alcohol 10a gave the expected product 30a with a
poor incorporation of deuterium at the a-position (19%) and at
the g-position (40%), with respect to the hydroxy group. When the
alcohol 20a was used as the only deuterated compound, the same
product 30a was obtained with an incorporation of deuterium of
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 7628–7630 7629

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In conclusion, impregnated iridium on magnetite is an
excellent heterogeneous and recyclable catalyst for the first
real cross-alkylation of primary alcohols. The catalyst is very
robust, easy to prepare, handle and store, and the general
process shows a reasonable scope. All these facts, together with
the simple recovery of catalyst by sequestering it with a simple
magnet, without losing its activity, permit us to anticipate a
good future for the process shown in this study not only in the
laboratory but also in the industry.
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c
7630 Chem. Commun., 2012, 48, 7628–7630
This journal is The Royal Society of Chemistry 2012