Design of a bifunctional Ir-Zr based metal-organic framework heterogeneous catalyst for the N-alkylation of amines with alcohols

Article abstract of DOI:10.1002/cctc.201402101

The direct N-alkylation of amines with alcohols was performed with an Ir-Zr-based metal-organic framework multifunctional heterogeneous catalyst. This system is efficient and environmentally benign for the synthesis of various organic amines in air in the absence of a base. The catalyst was recovered and reused without significant loss of activity, and only water was produced as a byproduct. Better be direct than elusive: The direct N-alkylation of amines with alcohols is performed with an Ir-Zr-based metal-organic framework multifunctional heterogeneous catalyst. This system is efficient and environmentally benign for the synthesis of various organic amines in air in the absence of a base. The catalyst is recovered and reused without significant loss of activity, and only water is produced as a byproduct.

Full text of DOI:10.1002/cctc.201402101

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DOI: 10.1002/cctc.201402101
Design of a Bifunctional Ir–Zr Based Metal–Organic
Framework Heterogeneous Catalyst for the N-Alkylation of
Amines with Alcohols
A. M. Rasero-Almansa,[a] A. Corma,*[b] M. Iglesias,*[a] and F. Sꢀnchez[c]
The direct N-alkylation of amines with alcohols was performed
with an Ir-Zr-based metal–organic framework multifunctional
heterogeneous catalyst. This system is efficient and environ-
mentally benign for the synthesis of various organic amines in
air in the absence of a base. The catalyst was recovered and
reused without significant loss of activity, and only water was
produced as a byproduct.
Introduction
The N-alkylation of amines is a reaction of fundamental impor-
tance in organic synthesis because the resulting higher amines
are widely used as synthetic intermediates for pharmaceuticals,
agrochemicals, fine chemicals, dyes, surfactants, and function-
alized materials.[1] The most frequently used method for the
preparation of N-alkyl amines is the coupling of amines with
alkyl halides[2] in the presence of stoichiometric amounts of in-
organic bases. An alternative environmentally benign approach
to these methods is the N-alkylation of amines with alcohols
as alkylating agents. The advantages of the use of alcohols in-
stead of alkyl halides/carbonyl compounds are the availability
of the former that produces only water as a byproduct, has
high atom efficiency, and avoids toxic reagents and stoichio-
metric reducing agents.[3,4] Although there are efficient homo-
geneous catalytic systems using metal salts and Ir,[5] Ru,[6] Rh,[7]
Pd,[8] Au,[9] Ni,[10] Cu,[11] Fe,[12] and Os[13] complexes, the still indis-
pensable use of cocatalysts such as bases and stabilizing
agents and limitations for catalyst recycling are factors that
need improvement. Meanwhile, other syntheses with metal-
free protocols require harsh reaction conditions to achieve rea-
sonable yields of products.[14]
gation, easy and safe disposal, safe storage, long lifetimes, in-
creased eco-friendliness, regenerability, and reusability. In the
past few years, heterogeneous catalysts such as Pd/MgO[15] or
Fe2O3,[8] Ag/Mo or Ag/Al2O3,[16] Au/TiO2,[9] and copper–alumi-
num hydrotalcite[17] were developed for the N-alkylation of
amines. However, most of them required harsh reaction condi-
tions.
Zr-based metal–organic frameworks (MOFs; UiO66-NH2) have
a large specific surface area and pore size as well as good
chemical resistance to water and organic solvents, which result
in desirable properties for catalytic applications.[18] These new,
highly stable materials, after the adequate postsynthetic modi-
fication, can act as heterogeneous catalysts that combine the
properties of soluble organometallic complexes with those of
the MOF as a support. We have described that Rh- and Ir-Zr-
based MOFs can be used as multifunctional catalysts for one-
pot and cascade reactions.[19] Herein, we show that it is possi-
ble to develop an environmentally friendly synthetic method
for the N-alkylation of amines with alcohols by using a bifunc-
tional Ir-Zr-MOF and working under mild reaction conditions.
Heterogeneous catalysts have some advantages over homo-
geneous catalysts, such as low cost, tolerance to a wide range
of temperatures and pressures, easy and inexpensive removal
from the reaction mixture through simple filtration or centrifu-
Results and Discussion
An Ir-Zr-MOF catalyst was prepared by using the method de-
scribed previously (Scheme 1).[19] The starting material was
[18a–20]
UiO66-NH2
because the presence of NH2 groups in the
linker (2-aminoterephthalic acid) enables the functionalization
of the material and generation of an Ir complex attached to
UiO66-NH2. In addition, UiO66-NH2 possesses Lewis acid sites
(Zr), which gives rise to a bifunctional catalyst that combines
acidity and metallic sites. As described earlier,[19] the 13C NMR
(see Figures S1 and S2 in the Supporting Information) and FTIR
(see Figures S3 and S4 in the Supporting Information) spectra
of the resulting samples are dominated by the bands assigned
to the parent groups and by the skeletal modes of MOFs (i.e.,
bands in the FTIR spectra at 1600–1585, 1500–1430, and
700 cmÀ1). The functional groups obtained from the postsyn-
thetic modification of the starting UiO66-NH2 material can be
[a] A. M. Rasero-Almansa, Prof. M. Iglesias
Inst. Ciencia de Materiales de Madrid, CSIC
C/Sor Juana Inꢀs de la Cruz, n8 3, 28049 Madrid (Spain)
Fax: (+34)913720623
E-mail: marta.iglesias@icmm.csic.es
[b] Prof. A. Corma
Inst. Tecnologꢁa Quꢁmica, UPV-CSIC
Avda. los Naranjos, s/n, 46022 Valencia (Spain)
E-mail: acorma@itq.upv.es
[c] Prof. F. Sꢂnchez
Inst. Quꢁmica Orgꢀnica General, CSIC
C/Juan de la Cierva, n8 3, 28006 Madrid (Spain)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402101.
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X-ray photoelectron spectros-
copy (XPS) analysis was per-
formed on Zr-[LIr]-MOF. The
sample was kept in vacuum
overnight before XPS measure-
ments. The spectrum was cali-
brated with respect to the C1s
peak. The survey scan XPS spec-
trum of the Zr-[LIr]-MOF samples
(see Figure S12 in the Support-
ing Information) confirms the
presence of Ir in addition to the
UiO66 framework elements (Zr,
C, N). The XPS spectrum shows
N1s (399.1 eV) and C1s signals,
and the latter comprises sp2
carbon (284.6 eV) and sp3 carbon
neighboring oxygen (287.9 eV).
The XPS core level for Ir (the Ir4f
region) shows peaks at 64.8 and
62.1 eV (assigned to Ir4f7/2 and Ir4f5/2), which indicates the Ird+
oxidation state in the samples.[21]
Scheme 1. Preparation of Ir-Zr-MOF.
observed in the full spectral range, which is the intensity pro-
portional to the level of conversion, particularly the band at
760 cmÀ1, which is assigned to the CÀC vibrational mode in ar-
omatic compounds and which does not overlap with other vi-
brational modes. The stability of the modified UiO66-NH2-
MOFs was examined by using thermogravimetric analysis
(Figure 1). The modified samples show thermal stabilities com-
parable with those of UiO66-NH2 with decomposition tempera-
Figure 2. SEM images of a) UiO66-NH2-L and b) UiO66-NH2-[LIr]BF4.
Figure 1. XRD patterns of UiO66-NH2, UiO66-NH2-L, and UiO-66NH2-[LIr]BF4.
tures near 3508C in air (see Figure S7 in the Supporting Infor-
mation). The results of N2 adsorption further confirm the stabil-
ity of the porous structure after the formation of the Ir com-
plex attached to the framework (see Figure S8 in the Support-
ing Information).
The SEM images show that no textural changes in the mate-
rials occurred after the postsynthetic treatment. In any case,
the observed Ir sites were homogeneously dispersed in the
samples (Figure 2). The TEM image (Figure 3) does not confirm
the presence of Ir nanoparticles.
Figure 3. TEM image of UiO66-NH2-[LIr]BF4.
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Catalyst screening for the alkylation of amines with alcohols
Table 1. N-Alkylation of amines with alcohols[a] with Ir-Zr-MOF-supported
catalysts.[a]
Reaction with auxiliary H2
We have shown that supported Au, Pt, Ni, and Ru nanoparti-
cles can be used to perform the chemoselective amination of
ketones and aldehydes with nitroarenes.[22] In
a recent
Catalyst
H2 pressure
[bar][b]
R
R’
Yield[%] (h)[c]
paper,[19a] we have reported on the use of the Ir-MOF catalyst
for the atom economic synthesis of mono-N-alkyl amines
through the reductive amination of aldehydes with nitroarenes
in the presence of H2. The process involves firstly a chemoselec-
tive reduction of the nitro compound to the corresponding
amine with H2 in the presence of the carbonyl substrate on
the Ir site. Then, the condensation between the aromatic
amine and the carbonyl group would occur on the acid sites
of the catalyst (MOF support) (Scheme 2). Finally, the hydroge-
nation of the resulting imine with the Ir complexes would give
the secondary amine.
1
2
3
4
5
6
7
8
9
[LIrCl] (3 mol%)
[LIrCl] (3 mol%)
1
4
4
6
6
6
6
4
4
4
4
Ph
Ph
Ph
Cy
Ph
Cy
Ph
Ph
Ph
Bn
Bn
Et
100 (6)
99 (20)
100 (20)
70 (20)
100 (24)
85 (24)
5 (24)
100 (10)
100 (4)
100 (23)
70 (4)
iPr
iPr
iPr
2-Bu
2-Bu
Et
Et
Et
iPr
iPr
Zr-[LIrCl] (0.4 mol%)
Zr-[LIrCl] (0.4 mol%)
Zr-[LIr]+ (0.25 mol%)
Zr-[LIr]+ (0.25 mol%)
blank
[LIr]+ (0.2 mol%)
Zr-[LIr]+ (0.2 mol%)
[LIr]+ (0.2 mol%)
Zr-[LIr]+ (0.2 mol%)
10
11
[a] Reaction conditions: Autoclave Engineers reactor, 1 mmol of amine
substrate, 40 mL of alcohol, T=808C; [b] 1 bar=100 kPa; [c] Yields are
based on amine substrates.
After identifying the potential of Zr-[LIr]BF4 as a catalyst, we
investigated the scope and limitations of this transformation.
Various primary or secondary alcohols could be coupled with
aniline, which gave monoalkylated amines in high yields. Al-
though primary alcohols react to produce the corresponding
amines in a few hours, secondary alcohols proved to be less re-
active and longer reaction times were required.
For the N-alkylation of aniline with ethanol (Table 1, entries
1, 8, and 9), the supported Ir-Zr-MOF catalyst was superior to
the corresponding soluble Ir complex, which indicates that the
Ir complex moiety in the heterogeneous catalyst is crucial and
the support material Zr-MOF also plays an important role in
promoting the reaction. This effect can be related to the Lewis
acidity of the Zr cluster, which promotes the imine formation
and introduces an additional benefit from the point of view of
increasing H2 concentration and/or stabilizing the reaction
transition state, as reported previously.[23]
Scheme 2. One-pot synthesis of secondary amines catalyzed by Ir-Zr-MOF in
the presence of H2. R1 =H, 4-I, 4-Br, 4-OCH3; R2 =Ph, OCH3Ph, C6H13.
As Ir complexes have shown to be active for performing the
N-alkylation of amines with alcohols, we used the Ir-Zr-MOF
catalyst for such a type of reaction because large pores of
UiO66-NH2 (2.69 nm) would allow free diffusion of reactants
and products and thus the use of UiO66-NH2 is an efficient
way to heterogenize the Ir complex. Thus, the N-alkylation of
amines was performed in 2-propanol (1 bar H2 pressure;
1 bar=100 kPa) with the neutral [LIrCl] complex as a homoge-
neous catalyst and good conversion and selectivities were ob-
tained (Table 1, entries 1 and 2). In contrast, the catalytic evalu-
ation of Ir-MOF catalysts was performed by mixing them with
nitrobenzene in 2-propanol in an Autoclave Engineers reactor
(100 mL) at 808C under 4–6 bar H2 pressure. Thus, the N-alkyla-
tion of the amine with the alcohol occurs, and with the use of
the heterogeneous Zr-[LIrCl] (0.4 mol%) complex as a catalyst,
high conversion and selectivity were obtained, which were
higher than those obtained with the homogeneous catalyst.
The activity of the homogeneous catalyst could be increased
significantly with the substitution of the chloride ligand by
a less coordinating counterion such as [BF4]À. With the use of
this anion, activity was also higher for the Zr-[IrL]BF4 catalyst,
which was again similar to the activity of the homogeneous
catalyst. The temperature could be lowered to 508C; however,
longer reaction time was needed to obtain high conversion.
Reaction in the absence of H2
Of all the catalysts examined before, Zr-[LIr]BF4 demonstrated
the best catalytic performance, and therefore, we decided to
use this system for the N-alkylation of amines in the absence
of H2 by using a H2 borrowing mechanism (Scheme 3).[15,24,25]
The reaction was conducted with 0.2 mol% Zr-[LIr]BF4
(based on Ir), and the scope of N-alkylation was explored with
different combinations of substrates (primary, such as 1-hexyla-
mine; reactive cyclic secondary amines, such as piperidine; and
Scheme 3. N-alkylation of amines with alcohols in the absence of H2 and
base.
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The accepted mechanism for
the alkylation of amines with al-
cohols in the absence of H2 in-
volves three steps: alcohol dehy-
drogenation, reaction of the re-
sulting carbonyl with the amine
to form the imine, and hydroge-
nation of the imine with the hy-
dride complex formed in the
first step (Scheme 3). In the reac-
tion of alcohols with amines, we
could not detect the intermedi-
ate imine product. This result in-
dicates that either the hydroge-
nation of the imine formed in an
external cycle is fast or that the
entire catalytic cyclic occurs with
all the intermediates attached to
the catalysts; in our case sup-
ported by the presence of an
hemilabile amino group in the
ligand,[26] the intermediate alde-
hyde remains coordinated to the
Ir complex and reacts with the
amine to give the hemiaminal
group, which is also attached to
the catalyst; dehydration to the
imine and reduction to the prod-
uct amine would also occur
without breaking the coordina-
tion to the catalyst, as has been
proposed by Yamaguchi et al.[27]
and Madsen et al.[28]
Table 2. N-Alkylation of amines with alcohols catalyzed by Zr-[LIr]BF4.
Entry
Alcohol
Amine
T
t
[h]
Yield
[%][a]
TOF
[b]
[8C]
[hÀ1
940
22
]
1
2
80[c]
2
100
100
80[c]
24
3
4
80[c]
2
2
100
100
450
570
80[c]
5
6
80[c]
120[d]
6
2
10
100
–
202
7
8
80[d]
120[d]
6
10
100
–
980
0.5
9
10
11
180[d]
125[e]
150[e]
24
2
2.5
10
42
90
–
105
180
12
150[e]
2
0
–
[a] Products were characterized by NMR, mass spectra, and yields of isolated products are based on amine sub-
strates; [b] TOF=turnover frequency; mmolsubstrate mmolcatalystÀ1 hÀ1. [c] Autoclave Engineers reactor, 0.20 mol%
catalyst (based on Ir), 1 mmol of amine substrate, 40 mL of alcohol; [d] Glass microreactor (Supelco),
0.20 mol% catalyst (based on Ir), 1 mmol of amine substrate, 2 mL of alcohol; [e] Microwave reactor.
To support these mechanistic
approach, we performed the re-
action of aniline (1.0 mmol) with
alcohols). Excess amount of the alcohol was used not only as
a reactant but also as a solvent. Various amines reacted with
different alcohols in the presence of Zr-[IrL]BF4 and afforded
moderate to excellent yields of the corresponding N-alkylated
products (Table 2). The reaction of 1-hexylamine and piperidine
with ethanol gives the desired product in high yields (Table 2,
entries 1 and 3), whereas the reaction with an aliphatic secon-
dary alcohols such as 2-butanol occurs only with 1-hexylamine
(Table 2, entry 2). The reaction with tertiary tert-butanol does
not occur.
benzaldehyde (1.0 mmol) in benzylic alcohol in the presence of
catalytic amounts of Zr-[LIr]BF4 at 1008C for 1 h and obtained
N-benzylaniline quantitatively [Eq. (1)] (see Figure S12). More-
over, the reduction of benzylideneaniline (1.0 mmol) in the
presence of catalytic amounts of Zr-[LIr]BF4, with 2-propanol as
a sacrificial alcohol to form the iridium hydride intermediate,
resulted in the formation of traces of N-benzylaniline [Eq. (2)],
whereas the preformed imine is reacted exactly under the
same reaction conditions with 4 bar H2 pressure (see Fig-
ure S12 in the Supporting Information). This result suggests
that the uncoordinated imine could not undergo transfer hy-
drogenation with the present catalytic system. Thus, the fact
that the imine was never detected makes us favor a reaction
mechanism using the MOF catalyst in which the entire catalytic
cycle occurs with all the intermediates attached to the cata-
lyst.[27,28]
The reaction of piperidine or hexylamine with benzyl alcohol
occurs at 1208C in high yields (Table 2, entries 6 and 8); how-
ever, the reaction with aniline was unsuccessful even at higher
temperature (1808C) (entry 9), and the application of micro-
wave heating was necessary to achieve results comparable
with those achieved using thermal heating for other substrates
(entries 10 and 11). The reaction did not proceed in the ab-
sence of a catalyst or with UiO66-NH2-L (before forming the Ir
complex), which suggests that the reaction proceeds through
the direct involvement of Ir.
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Catalyst leaching and recycling
An experiment was performed to check whether the metal or
the metal complex leaching occurs during the reaction and
whether the leached species are totally or partially responsible
for the catalyst activity. Then, the reaction of hexylamine with
ethanol was stopped by hot filtration of the catalyst at 30% of
the amine formation. No further reaction occurred if the filtrate
was used to continue the reaction (Figure 4). This result indi-
Figure 5. Powder XRD patterns of Zr-[LIr]+-Fresh and Zr-[LIr]+-Recovered.
Figure 6. SEM images for a) Fresh UiO-66-NH2-[LIr]BF4 and b) UiO-66-NH2-
[LIr]BF4 recovered from the reaction
Figure 7. TEM images of a) fresh UiO66-NH2-[LIr]BF4 and b) recovered UiO66-
NH2-[LIr]BF4.
first four cycles, which remains stable or decays much more
slowly after four cycles. The used catalyst has also been stud-
ied by using FTIR spectroscopy, and the presence of new
bands related to amino groups indicates that some of the re-
action products can remain adsorbed on the catalyst and this
may affect the loss of activity observed, especially in the initial
cycles.
Figure 4. Results of the a) recycling experiment and b) hot filtration test.
cates that the catalytic process is heterogeneous. Furthermore,
the inductively coupled plasma analysis of the filtrate confirms
that the Ir content was below the detection limit (<0.10 ppm).
The used catalyst was also analyzed by using XRD, SEM, and
TEM, and the results are presented in Figures 5–7, which indi-
cate that the catalyst remains structurally stable during the cat-
alytic process.
Conclusions
We have found that the Ir-Zr-based metal–organic framework
is a highly efficient catalyst for producing higher amines from
amines and alcohols. Notably, this system readily catalyzes the
From the point of view of their reusability, the results pre-
sented in Figure 4 indicate a decrease in activity during the
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plasma atomic emission spectroscopy. Calcd (%): Ir 2.99; found: Ir
2.7.
N-alkylation of aliphatic alcohols. Notable advantages offered
by this method are broad substrate scope, high atom economy
(only water is a byproduct), reusability of the catalyst, environ-
mentally benign, higher yields of the desired products, and
a simple workup procedure, which makes it an attractive and
useful methodology for organic synthesis. The use of recycled
UiO66-NH2-[LIr]BF4 for N-alkylation reactions with different sub-
strates also produces the desired products in high yields. The
fact that the integrity and bifunctionality of both the Ir com-
plex and the Zr metal–organic framework support are main-
tained in consecutive runs meets the objective set to combine
the properties of a homogeneous and a heterogeneous cata-
lyst system into those of one sustainable hybrid catalyst
system.
Characterization
All the samples were characterized systematically by applying vari-
ous analytical and spectroscopic techniques; details can be found
in the Supporting Information.
Catalytic measurements
Method a
The N-alkylation reaction was performed in an Autoclave Engineers
reactor (100 mL). The amines were added to the catalyst suspen-
sion (0.2 mmol of Ir) in the alcohol (40 mL). The reactor was her-
metically sealed, pressurized with H2 (4 bar), and heated under
continuous stirring. Small liquid aliquots (ꢀ100 mL) were taken.
The progress of the reaction was monitored by using GC–MS. The
reaction mixture was filtered, and the solvent was removed under
reduced pressure to give the crude product.
Experimental Section
Reagents and materials
Starting materials were purchased and used without further purifi-
cation from commercial suppliers (Sigma–Aldrich and Alfa Aesar).
Dried, distilled, and deoxygenated solvents were used. All the
chemicals were used as-received. Postsynthetic modification reac-
tions were performed by using standard Schlenk techniques.
Method b
Synthesis of Ir-Zr-MOF
The N-alkylation reaction was performed in a glass microreactor
(2.0 mL, Supelco Analytical) equipped with a magnetic bar and
sensors for both temperature and pressure control. The amine
(1 mmol) was added to the catalyst suspension (19.2 mg,
0.002 mmol of Ir) in the alcohol (1 mL). The reactor was hermetical-
ly sealed and heated at 80–1208C under continuous stirring. Small
liquid aliquots (ꢀ10 mL) were taken. The progress of the reaction
was monitored by using GC–MS. After disappearance of the amine,
the reaction mixture was cooled to RT. The catalyst was removed
by filtration and rinsed with ethyl acetate; the removal of the sol-
vent in vacuum yielded a crude residue. All the products were
identified on the basis of NMR and mass spectral data.
The synthesis of UiO66-NH2, a Zr-based MOF, was performed by
using a method similar to that described elsewhere.[17a]
Synthesis of Zr-L-MOF, [Zr6O4(OH)4(BDC-NH2)6ÀxLx] (L=6-((dii-
sopropylamino)methyl)picolinaldehyde)
UiO66-NH2 (1.5 g, 1.6 mmol) was dispersed in CH2Cl2 (15 mL). To
this slurry, a solution of an aldehyde (375.0 mg, 1.7 mmol) in
CH2Cl2 (5 mL) was added dropwise at RT, and the mixture was
stirred for additional 6 h. The sample was collected by centrifuga-
tion, washed twice with CH2Cl2, and dried in air at 708C. Elemental
analysis was performed on samples outgassed under vacuum
(1008C, 12 h).
Elemental analysis calcd (%) for Zr6O4(OH)4(BDC-NH2)5.7(BDC-L)0.3
(corresponding to ꢀ5% amine functionalization): C 34.35, H 2.19,
N 5.09; found: C 34.45, H 2.64, N 5.07; 13C NMR (400 MHz, CP-MAS):
d=17.8 (CH3iPr), 45.8 (CHiPr), 50.6 (CH2), 116.1, 123.0, 132.1, 138.5,
151.4, 162.8 (imine C=N), 171.2 ppm (COO).
Recycling of Zr-[LIr]BF4-MOF
After the completion of the reaction, the catalyst was recovered
through the separation of solid Ir-MOF from the liquid by extensive
centrifugation. The recovered catalyst was washed thrice with
CH2Cl2 and then with ether, and finally the catalyst was dried at
1008C for 12 h and reused. The Zr-[LIr]BF4-MOF catalyst showed
consistent activity for five cycles.
Synthesis of Zr-[LIr]BF4-MOF, [Zr6O4(OH)4(BDC-NH2)6Àx
([LIr]BF4)x]
-
AgBF4 (8.7 mg, 0.044 mmol) was added to a solution of [IrCl(cod)]2
(cod=1,5-cyclooctadiene; 15 mg, 0.022 mmol) in THF (10 mL) at
RT, and the mixture was stirred for 1 h. Then, AgCl was filtered and
the solution containing [Ir(cod)]BF4 was added to a suspension of
UiO66-NH2-L (100 mg) in THF (10 mL). The mixture was stirred for
10 h; the solid was collected by centrifugation, washed twice with
THF, and dried in air at 708C. Elemental analysis was performed on
samples outgassed under vacuum (1008C, 4 h).
Hot filtration test of Zr-[LIr]BF4-MOF
A mixture of Zr-[LIr]BF4 (2.4 mg, 0.0002 mmol of Ir), the amine
(2.2 mL, 0.02 mmol), and the alcohol (1.0 mL) was placed in
a closed glass reactor (2.0 mL,Supelco) and stirred vigorously at
808C for 30 min. The conversion was approximately 30%. Then,
the solid catalyst was quickly separated after filtration of the reac-
tant mixtures. And the liquid was kept at 808C under vigorous stir-
ring for 2 h. The conversion was 32%. The conversion in the blank
thermal reaction without any catalyst at 808C was approximately
2%.
Elemental analysis calcd (%) for Zr6O4(OH)4(BDC-NH2)5.7([LIr]BF4)0.3: C
33.65, H 2.25, N 4.80; found: C 32.92, H 2.56, N 4.54. The amount
of Ir in the final solid was determined by using inductively coupled
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[9] L. He, X. B. Lou, J. Ni, Y. M. Liu, Y. Cao, H. Y. He, K. N. Fan, Chem. Eur. J.
2010, 16, 13965–13969.
Acknowledgements
[10] R. G. Rice, E. J. Kohn, J. Am. Chem. Soc. 1955, 77, 4052–4054.
[11] a) A. Martꢁnez-Asencio, D. J. Ramon, M. Yus, Tetrahedron Lett. 2010, 51,
325–327; b) A. Martꢁnez-Asencio, D. J. Ramon, M. Yus, Tetrahedron 2011,
67, 3140–3149.
[12] Y. Zhao, S. W. Foo, S. Saito, Angew. Chem. Int. Ed. 2011, 50, 3006–3009;
Angew. Chem. 2011, 123, 3062–3065.
We acknowledge financial support from the Ministerio de Econo-
mꢁa y Competitividad (Spain) (project no. MAT2011-29020-C02-
02), Consolider Program-Ingenio 2010 (project no. CSD-0050-
MULTICAT), and Severo Ochoa program. A.M.R.-A. thanks Minis-
terio de Economꢁa y Competitividad for FPI program.
[13] M. A. Esteruelas, N. Honczek, M. Olivan, E. OÇate, M. Valencia, Organo-
metallics 2011, 30, 2468–2471.
[14] a) G. Guillena, D. J. Ramon, M. Yus, Chem. Rev. 2010, 110, 1611–1641;
b) Y. Horikawa, Y. Uchino, T. Sato, Chem. Lett. 2003, 32, 232–233; c) Y.
Sprinzak, J. Am. Chem. Soc. 1956, 78, 3207–3208; d) N. Iranpoor, H. Fir-
ouzabadi, N. Nowrouzi, D. Khalili, Tetrahedron 2009, 65, 3893–3899;
e) Y. Du, S. Oishi, S. Saito, Chem. Eur. J. 2011, 17, 12262–12267.
[15] A. Corma, T. Ródenas, M. J. Sabater, Chem. Eur. J. 2010, 16, 254–260.
[16] a) X.-J. Cui, Y. Zhang, F. Shi, Y.-Q. Deng, Chem. Eur. J. 2011, 17, 1021–
1028; b) H. Liu, G.-K. Chuah, S. Jaenicke, J. Catal. 2012, 292, 130–137.
[17] a) P. R. Likhar, R. Arundhathi, M. L. Kantam, P. S. Prathima, Eur. J. Org.
Chem. 2009, 5383–5389; b) F. Shi, M. K. Tse, X. Cui, D. Gcrdes, D. Micha-
lik, T. Y. Deng, M. Beller, Angew. Chem. Int. Ed. 2009, 48, 5912–5915;
Angew. Chem. 2009, 121, 6026–6029.
Keywords: bifunctional catalyst · heterogeneous catalyst ·
iridium · N-alkylation · Zr-based MOF
[1] a) A. Seayad, M. Ahmed, H. Klein, R. Jachstell, T. Gross, M. Beller, Science
2002, 297, 1676–1678; b) B. R. Brown in The Organic Chemistry of Ali-
phatic Nitrogen Compounds, Cambridge University, Cambridge, 2004;
c) A. A. NfflÇez Magro, G. R. Eastham, D. J. Cole-Hamilton, Chem.
Commun. 2007, 3154–3156; d) R. N. Salvatore, C. H. Yoon, K. W. Jung,
Tetrahedron 2001, 57, 7785–7811; e) S. Arif, Surfactant Science Series:
Detergency of Special Surfactants, Vol. 98 (Ed.: F. Friedli), Marcel Dekker,
New York, 2001, pp. 71–115.
[18] a) A. Schaate, P. Roy, A. Godt, J. Lippke, F. Waltz, M. Wiebcke, P. Behrens,
Chem. Eur. J. 2011, 17, 6643–6651; b) M. Kandiah, M. H. Nilsen, S. Usse-
glio, S. Jakobsen, U. Olsbye, M. Tilset, Ch. Larabi, E. A. Quadrelli, F.
Bonino, K. P. Lillerud, Chem. Mater. 2010, 22, 6632–6640; c) W. Morris,
Ch. J. Doonan, O. M. Yaghi, Inorg. Chem. 2011, 50, 6853–6855; d) F. Ver-
moortele, R. Ameloot, A. Vimont, Ch. Serre, D. De Vos, Chem. Commun.
2011, 47, 1521–1523; e) S. J. Garibay, S. M. Cohen, Chem. Commun.
2010, 46, 7700–7702.
[2] a) S. L. Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv. Synth. Catal.
2006, 348, 23–39; b) O. Navarro, N. Marion, J. Mei, S. P. Nolan, Chem.
Eur. J. 2006, 12, 5142–5148; c) K. Fujita, Z. Li, N. Ozeki, R. Yamaguchi,
Tetrahedron Lett. 2003, 44, 2687–2690.
[3] a) Ch. Gunanathan, D. Milstein, Science 2013, 341, 249; b) G. E. Dober-
einer, R. H. Crabtree, Chem. Rev. 2010, 110, 681–703; c) T. Suzuki, Chem.
Rev. 2011, 111, 1825–1845; d) J. Liu, X. F. Wu, J. A. Iggo, J. L. Xiao, Coord.
Chem. Rev. 2008, 252, 782–809.
[19] a) M. Pintado-Sierra, A. M. Rasero-Almansa, A. Corma, M. Iglesias, F.
Sꢀnchez, J. Catal. 2013, 299, 137–145; b) A. M. Rasero-Almansa, A.
Corma, M. Iglesias, F. Sꢀnchez, ChemCatChem 2013, 5, 3092–3100.
[20] a) J. H. Cavka, S. Jakobsen, U. Olsbye, N. Guillou, C. Lamberti, S. Bordiga,
K. P. Lillerud, J. Am. Chem. Soc. 2008, 130, 13850; b) M. Kim, S. M.
Cohen, CrystEngComm 2012, 14, 4096.
[21] a) C. Wagner, W. M. Riggs, L. E. Davis, J. F. Moulder, G. E. Muilenberg,
Handbook of X-ray Photoelectron Spectroscopy, Physical Electronic Divi-
sion, Vol. 55, PerkinElmer, E. Prairie, MN, 1979; b) C. Campos, C. Torres,
M. Oportus, M. A. PeÇa, J. L. G. Fierro, P. Reyes, Catal. Today 2013, 213,
93–100; c) U. Hintermair, S. W. Sheehan, A. R. Parent, D. H. Ess, D. T. Ri-
chens, P. H. Vaccaro, G. W. Brudvig, R. H. Crabtree, J. Am. Chem. Soc.
2013, 135, 10837–10851; d) P. lvarez, C. Blanco, R. MenØndez, ACS
Catal. 2013, 3, 1307–1317.
[22] a) L. L. Santos, P. Serna, A. Corma, Chem. Eur. J. 2009, 15, 8196; b) M. J.
Climent, A. Corma, S. Iborra, L. L. Santos, Chem. Eur. J. 2009, 15, 8834.
[23] a) B. Pugin, H. Lendert, F. Spindler, H. U. Blaser, Adv. Synth. Catal. 2002,
344, 974–979; b) C. Gonzꢀlez-Arellano, A. Corma, M. Iglesias, F. Sꢀnchez,
Adv. Synth. Catal. 2004, 346, 1316–1328.
[24] a) P. Rubio-MarquØs, A. Leyva-Perez, A. Corma, Chem. Commun. 2013,
49, 8160–8162; b) A. Corma, T. Ródenas, M. J. Sabater, J. Catal. 2011,
279, 319–327.
[4] a) T. Mizuta, S. Sakagushi, Y. J. Ishii, Org. Chem. 2005, 70, 2195–2199;
b) T. E. Müller, K. C. Hultzsch, M. Yus, F. Foubelo, M. Tada, Chem. Rev.
2008, 108, 3795–3892; c) T. C. Nugent, M. El-Shazly, Adv. Synth. Catal.
2010, 352, 753–819; d) K. Krüger, A. Tillack, M. Beller, ChemSusChem
2009, 2, 715–717; e) J. Ward, R. Wohlgemuth, Curr. Org. Chem. 2010,
14, 1914–1927; f) D. Crozet, M. Urrutigoity, P. Kalck, ChemCatChem
2011, 3, 1102–1118.
[5] a) K. Fujita, C. Asai, T. Yamaguchi, F. Hanasaka, R. Yamaguchi, Org. Lett.
2005, 7, 4017–4019; b) A. Pontes da Costa, M. Viciano, M. Sanaffl, S.
Merino, J. Tejeda, E. Peris, B. Royo, Organometallics 2008, 27, 1305–
1309; c) D. Gnanamgari, E. L. O. Sauer, N. D. Schley, C. Butler, C. D. Incar-
vito, R. H. Crabtree, Organometallics 2009, 28, 321–325; d) D. Gnanam-
gari, C. H. Leung, N. D. Schley, S. T. Hilton, R. H. Crabtree, Org. Biomol.
Chem. 2008, 6, 4442–4445; e) L. J. Allen, R. H. Crabtree, Green Chem.
2010, 12, 1362–1364; f) A. P. da Costa, M. Sanaffl, E. Peris, B. Royo,
Dalton Trans. 2009, 6960–6966; g) B. Blank, M. Madalska, R. Kempe,
Adv. Synth. Catal. 2008, 350, 749–758; h) A. Prades, R. Corber, M. Poya-
tos, E. Peris, Chem. Eur. J. 2008, 14, 11474–11479; i) Y.-H. Chang, C.-F. Fu,
Y.-H. Liu, S.-M. Peng, J.-T. Chen, S.-T. Liu, Dalton Trans. 2009, 861–867;
j) B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. 2009, 15, 3790–3799; k) S.
Michlik, R. Kempe, Chem. Eur. J. 2010, 16, 13193–13198; l) D. Balcells, A.
Nova, E. Clot, D. Gnanamgari, R. H. Crabtree, O. Eisenstein, Organometal-
lics 2008, 27, 2529–2535.
[6] a) C. S. Cho, Organometallics 2003, 22, 3608–3610; b) D. Milstein, Top.
Catal. 2010, 53, 915–923; c) S. Musa, S. Fronton, L. Vaccaro, D. Gelman,
Organometallics 2013, 32, 3069–3073; d) R. Martꢁnez, D. J. Ramon, M.
Yus, Tetrahedron 2006, 62, 8982–8987; e) M. Viciano, M. Sanaffl, E. Peris,
Organometallics 2007, 26, 6050–6054; f) A. Prades, M. Viciano, M. San-
affl, E. Peris, Organometallics 2008, 27, 4254–4259; g) J. W. Kim, K. Ya-
maguchi, N. Mizuno, J. Catal. 2009, 263, 205–208; h) M. H. S. A. Hamid,
C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C. Maytum, A. J. A. Watson,
M. J. Williams, J. Am. Chem. Soc. 2009, 131, 1766–1774; i) M. Bertoli, A.
Choualeb, A. J. Lough, B. Moore, D. Spasyuk, D. G. Gusev, Organometal-
lics 2011, 30, 3479–3482.
[25] a) A. J. A. Watson, J. M. J. Williams, Science 2010, 329, 635–636; b) S.
Bähn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatCh-
em 2011, 3, 1853–1864.
[26] a) M. V. JimØnez, J. Fernꢀndez-Tornos, J. J. PØrez-Torrente, F. J. Modrego,
S. Winterle, C. Cunchillos, F. J. Lahoz, L. A. Oro, Organometallics 2011,
30, 5493–5508; b) C. del Pozo, A. Corma, M. Iglesias, F. Sꢀnchez, Green
Chem. 2011, 13, 2471–2481.
[27] K.-I. Fujita, Y. Enoki, R. Yamaguchi, Tetrahedron 2008, 64, 1943–1954.
[28] P. Fristrup, M. Tursky, R. Madsen, Org. Biomol. Chem. 2012, 10, 2569.
[7] R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit, N. Tongpenyai, J. Chem. Soc.
Chem. Commun. 1981, 611–612.
[8] a) Y. Zhang, X. Qi, X. Cui, F. Shi, Y. Deng, Tetrahedron Lett. 2011, 52,
1334–1338; b) Y. Xie, S. Liu, Y. Liu, Y. Wen, G.-J. Deng, Org. Lett. 2012,
14, 1692–1695.
Received: March 4, 2014
Revised: March 12, 2014
Published online on && &&, 0000
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 8
&
7
&
ÞÞ
These are not the final page numbers!

FULL PAPERS
A. M. Rasero-Almansa, A. Corma,*
M. Iglesias,* F. Sꢂnchez
&& – &&
Design of a Bifunctional Ir–Zr Based
Metal–Organic Framework
Heterogeneous Catalyst for the N-
Alkylation of Amines with Alcohols
Better be direct than elusive: The
direct N-alkylation of amines with alco-
hols is performed with an Ir-Zr-based
metal–organic framework multifunction-
al heterogeneous catalyst. This system
is efficient and environmentally benign
for the synthesis of various organic
amines in air in the absence of a base.
The catalyst is recovered and reused
without significant loss of activity, and
only water is produced as a byproduct.
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 8
&
8
&
ÞÞ
These are not the final page numbers!