Transformations of 1-(2-Aminophenyl)propan-2-ol to 2-Methylindoline

Article abstract of DOI:10.1007/s10562-014-1474-3

The transformation reaction of 1-(2-aminophenyl)propan-2-ol was studied at 200 °C under argon pressure. A range of catalysts was applied including carbon, titania and zeolite supported Ru, Pd, Pt, Rh, and Ir, as well as metal free zeolites. The highest conversion was obtained with H-Beta-150 and H-Beta-25 and the highest selectivity to 2-methylindoline was achieved with 0.3 % Ir-H-Beta-150 and H-Beta-25. Although the selectivity to 2-methylindole was high for all catalysts, formation of the final product 2-methylindoline only took place over the most acidic catalysts.

Full text of DOI:10.1007/s10562-014-1474-3

Catal Lett
DOI 10.1007/s10562-014-1474-3
Transformations of 1-(2-Aminophenyl)propan-2-ol
to 2-Methylindoline
•
Heidi Bernas Yuliya S. Demidova Atte Aho Irina L. Simakova
•
•
•
•
•
•
•
Narendra Kumar Yosra Laribi Philippe Perrichon Reko Leino
Dmitry Yu. Murzin
Received: 21 November 2014 / Accepted: 29 December 2014
Ó Springer Science+Business Media New York 2015
Abstract The transformation reaction of 1-(2-amino-
phenyl)propan-2-ol was studied at 200 °C under argon
pressure. A range of catalysts was applied including car-
bon, titania and zeolite supported Ru, Pd, Pt, Rh, and Ir, as
well as metal free zeolites. The highest conversion was
obtained with H-Beta-150 and H-Beta-25 and the highest
selectivity to 2-methylindoline was achieved with 0.3 %
Ir–H-Beta-150 and H-Beta-25. Although the selectivity to
2-methylindole was high for all catalysts, formation of the
final product 2-methylindoline only took place over the
most acidic catalysts.
Graphical Abstract
Keywords Acidity ꢀ Alcohols ꢀ Amines ꢀ Zeolites
1 Introduction
Amines are intermediates and products of great importance
for chemical and life science applications. Secondary
amines can be synthesized through N-alkylation of primary
amines or through additions to imines, aziridines and car-
bonyls in the case of alkyl amines, as well as through
N-alkylation of primary aryl amines and through addition
to imines (reductive alkylation) in the case of aromatic
amines [1]. For secondary aromatic amines, the N-alkyl-
ation can be achieved starting from nonactivated aryl
amines using either alkyl halides or alcohols, or the
N-alkylation can be accomplished by metal-catalyzed
reactions or using protected aromatic amines [1]. Hydrogen
borrowing reaction with alcohols is an environmentally
friendly alternative for synthesis of secondary amines [2–
4], where the first step is the removal of hydrogen from the
alcohol by the catalyst to form an aldehyde, after which the
amine reacts with the aldehyde forming an imine and
water, and finally hydrogen is returned by the catalyst to
the imine resulting in an amine (Scheme 1).
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1474-3) contains supplementary
material, which is available to authorized users.
H. Bernas ꢀ A. Aho ꢀ N. Kumar ꢀ D. Yu. Murzin (&)
Laboratory of Industrial Chemistry and Reaction Engineering,
˚
Process Chemistry Centre, Abo Akademi University,
Biskopsgatan 8, 20500 Turku, Finland
e-mail: dmurzin@abo.fi
Y. S. Demidova ꢀ I. L. Simakova
Boreskov Institute of Catalysis, 630090 Novosibirsk, Russia
Y. S. Demidova ꢀ I. L. Simakova
Novosibirsk State University, 630090 Novosibirsk, Russia
Y. Laribi ꢀ P. Perrichon
Sanofi-Aventis Recherche & Developpement, Centre de
Recherche de Vitry-sur-Seine 13, quai Jules Guesde, BP 14,
94403 Vitry-sur-Seine, France
Hydrogen borrowing reactions have previously been
studied using homogeneous metal complexes [5–13],
although heterogeneous catalysts containing metals such as
R. Leino
Laboratory of Organic Chemistry, Abo Akademi University,
Biskopsgatan 8, 20500 Turku, Finland
˚
123

H. Bernas et al.
aqueous solution, dried overnight at 120 °C and reduced by
hydrogen at temperature ramp 2 °C/min up to 350 °C.
The Rh/TiO2, Ru/TiO2, and Pd/TiO2 catalysts were
prepared by incipient wetness impregnation technique. The
nominal metal loading was 2 wt%. An aqueous solutions of
RhCl3ꢀnH2O (40 %, Sigma Aldrich), RuCl3ꢀnH2O
(40.49 %, Johnson Matthey), and PdCl2 (59.2 %, Reachim,
Russia) were used as metal precursors and TiO2 (Sachtle-
ben Chemie GmbH, 100 % anatase phase) was used as the
support. The rhodium and ruthenium metal precursors
dissolved in distilled H2O, as well as palladium chloride
dissolved in HCl were then added dropwise to the support.
The solid was dried at room temperature overnight,
reduced in hydrogen at 350 °C (1 °C/min) for Ru and Rh,
and at 300 °C (1 °C/min) in case of Pd precursors.
Synthesis of Ir–H-Beta-150-IE (SiO2/Al2O3 molar ratio
150) zeolite catalyst was carried out by ion-exchange
method and Ir–H-Beta-150-IMP by evaporation-impreg-
nation in a rotavapour using aqueous solution of iridium
chloride. NH4-Beta-150 zeolite obtained from Zeolyst
International was transformed to H-Beta-150 by step cal-
cination procedure in a muffle oven. Ir modified H-Beta-
150 zeolite catalyst was dried at 100 °C in an oven and
calcined at 400 °C. Ru-MCM-41 mesoporous catalyst was
prepared using in situ method by direct addition of aqueous
ruthenium (III) chloride in the gel solution of MCM-41
mesoporous material. The detail description for the syn-
thesis of Ru-MCM-41 mesoporous catalysts is given in
Ref. [28].
R
NHR'
NR'
R
R
OH
O
Cat
Cat-H2
H2NR'
- H2O
R
Scheme 1 General scheme for hydrogen borrowing reactions
ruthenium [14–16], gold [17–19], silver [20], nickel [21],
palladium [22], platinum [23], platinum–tin [24] and cop-
per [25] have also been used. In this work, the dehy-
drogenation-cyclization and hydrogen borrowing of 1-(2-
aminophenyl)propan-2-ol to 2-methylindole and 2-methy-
lindoline was investigated. Both products are known to be
used as intermediates for synthesizing pharmaceuticals,
and can be applied also for synthesis of dyes, pigments and
optical brighteners. The hydrogen borrowing of 1-(2-ami-
nophenyl)propan-2-ol, not reported previously in the lit-
erature, was carried out in an autoclave under argon
pressure at 200 °C using a range of supported noble metal
catalysts and zeolites without any metal. Heterogeneous
catalysts have not been used previously for cyclization of
1-(2-aminophenyl)propan-2-ol to 2-methylindole (the
dehydrogenation-cyclization reaction), which has been
reported previously using iridium complexes under oxida-
tive conditions [26], not directly relevant for hydrogen
borrowing methodology.
The H-Beta-25 zeolite catalyst was modified with plat-
inum using aqueous solution of hexachloroplatinic acid
(Merck). The modification of H-Beta-25 catalyst with Pt
was carried out using evaporation impregnation method in
a rotator evaporator for 24 h. The catalyst was recovered
after the completion of synthesis, dried at 100 °C and
calcined in a muffle oven at 400 °C.
NH4-Beta-25 and NH4-Beta-300 zeolites (SiO2/Al2O3
molar ratio 25 and 300 respectively) were obtained from
Zeolyst International and were transformed to proton forms
by step calcinations at 450 °C in a muffle oven.
2 Experimental
2.1 Catalysts
Commercial catalysts from Degussa, 5 % Ru/C (H105 XB/
W 5 %), 10 % Pd/C (E101 NE/W 10 %), 5 % Rh/C (G106
B/W 5 %), 5 % Pt/C (F105 N/W 5 %) were used.
Mesoporous graphite-like carbon material of the Sibunit
family was used as a support material to prepare Ir/Sibunit.
The preparation procedures and properties of Sibunit carbons
are described elsewhere [27]. Prior to use, the support was
washed to remove any impurities, first by boiling Sibunit with
distilled water to remove suspended coal dust, then washing
with HCl (2 M) under reflux for 4 h, and finally washed with
distilled water and dried at 120 °C. The iridium catalysts used
in the experiments were prepared using solutions of reagent
grade IrCl4ꢀnH2O in HCl (0.5 M) (Ir content 52.9 %, JSC
‘‘The Gulidov Krasnoyarsk non-ferrous metals plant’’) by
deposition–precipitation. To prepare the catalyst, the carbon
support was dispersed in water. An appropriate amount of an
aqueous solution of H2IrCl6 was added dropwise under
moderate stirring, followed by addition of Na2CO3 (1 M)
2.2 Experimental Procedure
The experiments were carried out in a 300 ml autoclave
(Parr instruments) under argon pressure (99.999 %, AGA).
Synthesis of 1-(2-aminophenyl)propan-2-ol was carried out
as described in the literature [26]. Toluene was purchased
from J.T. Baker (‘‘Baker analyzed’’). 2-Methylindole and
2-methylindoline were purchased from Sigma Aldrich
(98 % purity), Before the experiment, the catalyst was
reduced, in case of Ru, Pt, Rh, and Ir ex situ at 400 °C (for
1 h, heating rate 5 °C/min) in hydrogen, for 10 % Pd/C
in situ at 200 °C for 1 h and 2 % Pd/TiO2 in situ at 100 °C
123

Transformations of 1-(2-Aminophenyl)propan-2-ol to 2-Methylindoline
for 1 h under hydrogen. The ex situ reduced catalysts were
also pre-treated in situ at 100 °C for 30 min under hydro-
gen, after which the reactor was flushed with argon. The
reactor containing catalyst and 70 ml solvent was heated to
the reaction temperature under argon at 1,650 rpm. The
reactant and 50 ml solvent was degassed in the bubbling
unit for 5 min using argon and then added to the reactor.
The total pressure in the reactor were 12 bar. The reaction
time was set to zero and the experiment was started.
Samples were taken at different time intervals and
analyzed by a gas chromatograph (GC). The samples were
prepared for GC using 0.5 ml of the sample taken from the
reactor and to this 0.5 ml of an internal standard, consisting
of 0.02 M undecane in toluene, was added. An aliquot of
1 ll of the sample was injected with an autosampler to the
GC. The injector temperature was 220 °C and the split
ratio 50:1. A Supelco B-Dex-225 column was used with the
helium gas flow of 0.9 ml/min. The following temperature
program was applied: 130 °C for 60 min and 10 °C/min to
160 °C, where it maintained for 10 min. The flame ioni-
zation detector (FID) was kept at 300 °C.
calibration was based on the Si 2p peak at 103.3 eV. The
sensitivity factors used in the quantitative analysis for Si
2p, O 1s, Ir 4f7/2, and Ru 3d5/2 were 0.283, 0.711, 2.402 and
2.208 respectively.
The platinum content of H-Beta-25 was analyzed using
inductively coupled plasma atomic emission spectroscopy
(ICP-AES). Around 50 mg of the catalyst was dissolved
using 4 ml aqua regia and 2 ml of hydrofluoric acid in a
microwave oven. The dissolved sample was diluted to
100 ml with de-ionized water and further diluted to 1:5,
after which it was analyzed.
2.4 Thermodynamic Calculations
To estimate the reaction thermodynamic characteristics the
quantum chemical calculations were carried out by using
the molecular modeling program HyperChem 8.0. Initial
molecular geometry was optimized by semi-empirical PM3
method. Based on vibrational analysis and statistical ther-
modynamics, standard thermodynamic functions such as
enthalpy, entropy and heat capacity at different tempera-
tures were obtained.
2.3 Catalyst Characterization
To determine the metal particle size and dispersion, cata-
lysts were analyzed by CO pulse chemisorption (Autochem
2910, Micrometrics). In these experiments, 0.05–0.1 g of
the sample was placed into a quartz U-tube containing
silica wool, the tube was inserted to the system and the
sample was dried in a stream of helium gas at 50 °C for
30 min. Next, the sample was reduced at the same tem-
perature and time as in the reduction before the experiment
in hydrogen, using helium as a carrier gas, after which it
was flushed with helium (retained at the reduction tem-
perature) for 1 h, cooled to room temperature, placed on
water bath, and subsequently the CO pulses were intro-
duced (10 % CO in helium, helium as a carrier gas) until
the adsorption was complete. The dispersion was calcu-
lated from the amount of CO consumed, assuming the
metal:CO stoichiometry to be unity.
3 Results and Discussion
3.1 Thermodynamics
Thermodynamic calculations made for the overall hydrogen
borrowing reaction neglected the temperature effect on the
enthalpy and entropy for hydrogen and water. The enthalpy
was zero for hydrogen and -241.84 kJ/mol for water and
the entropy was 130.52 J/mol K for hydrogen and 188.74
J/mol K for water. The enthalpy for a compound at tem-
perature T was calculated in the following way
DHT ¼ Df H0 þ ðT ꢁ T0Þ ꢀ ðcp;T ꢁ cp;0
where cp is heat capacity.
Þ
ð1Þ
The thermodynamic properties for the reactant and pro-
ducts at 298 K are given in Table S1 (Supporting informa-
tion). Table S2, S3 and S4 (Supporting information) give
the thermodynamic properties as a function of temperature
for 1-(2-aminophenyl)propan-2-ol, 2-methylindole, and
2-methylindoline respectively. Gibbs free energy calculated
for the hydrogen borrowing reaction and presented in Table
S5 (Supporting information) is clearly negative (ca.–90
kJ/mol) increasing its value with temperature.
X-ray fluorescence (XRF) technique was used in this
work to determine the metal loading (ARL with Rh anode)
for the TiO2 supported catalysts. As synthesized Ir–H-Beta-
150 zeolite and Ru-MCM-41 mesoporous catalysts were
characterized using X-ray powder diffraction for determi-
nation of phase purity and nitrogen adsorption for mea-
surement of surface area.
A Perkin-Elmer PHI 5400 spectrometer with a mono-
chromatized Al Ka X-ray source operated at 14 kV and
300 W was used in the XPS analysis of zeolite supported
metal catalysts. The pass energy of the analyzer was
17.9 eV and the energy step 0.1 eV. The binding energy
3.2 Catalyst Characterization
According to XRF analysis Ru-MCM-41 contains 3.3 wt%
of ruthenium, Ir–H-Beta-150-IE 0.3 wt% of iridium, and
123

H. Bernas et al.
Ir–H-Beta-150-IMP 0.5 wt% of iridium. The results for Pt–
H-Beta-25 were not reliable since the platinum and alu-
minum peaks overlapped. The ICP-OES gave 4.5 % of
platinum for Pt–H-Beta-25.
should follow the reaction sequence presented in
Scheme 2.
Since no ketone was observed among the products the
first step, e.g. the one giving 2-methylindole, involves in
fact dehydrogenation and cyclization, as well as the for-
mation of water, and can be further denoted as dehy-
drogenation-cyclization reaction. In the second step the
intermediate 2-methylindole is hydrogenated by hydrogen
that has been ‘‘borrowed’’ by the catalyst giving
2-methylindoline. Besides the main compounds N-propyl-
benzene amine was also formed in small amounts.
Various metal catalysts on carbon and titania support
were tested in order to see which metal would be active in
the hydrogen borrowing reaction. Because only dehy-
drogenation-cyclization reaction took place, metals sup-
ported on Beta zeolite and MCM-41 were also tested. It
turned out that these catalysts were active and Beta zeolite
per se with varied acidity was used to elucidate behaviour
of metal free catalysts.
X-ray powder diffraction patterns of Ru-MCM-41 mes-
oporous catalyst exhibited presence of RuO2 and MCM-41
phase. Direct introduction of Ru to MCM-41 did not
influence the parent structure of the mesoporous materials
[27]. Ir–H-Beta-150 catalyst exhibited patterns similar to
that of pristine H-Beta-150 zeolite catalyst, indicating the
integrity of Beta zeolite structure after IrCl3 modification.
The catalysts were characterized by CO chemisorption
to determine the metal dispersion and metal particle size,
and the results are given in Table 1.
5 % Rh/C and 5 % Pt/C had the smallest metal particle
size. 3.3 % Ru-MCM-41 had the largest metal particles,
followed by 5 % Ru/C, 10 % Pd/C and 0.5 % Ir–H-Beta-
150-IMP, 1 % Ir/Sibunit and finally by 0.3 % Ir–H-Beta-
150-IE and 4.5 % Pt–H-Beta-25.
TiO2 supported catalysts were characterized using XRF
and TEM. XRF confirmed that the catalyst loading was 2
wt%. The aim was to determine the metal particle size
using TEM, but as seen from the micrographs on Fig.
S1–S3 (Supporting information), it was difficult to see
the metal particles contour while the presence of metal on
the catalyst was definitely confirmed by EDX.
The results from the experiments using carbon and meso-
porous carbonSibunit supported catalysts are shown in Fig. 1.
As can be seen from Fig. 1 10 % Pd/C gave the highest
conversion in 4 h, followed by 5 % Pt/C, 5 % Ru/C, 5 % Rh/
C, and 1 % Ir/Sibunit (Fig. 1a). Selectivity to 2-methylin-
dole was almost 100 % (Fig. 1b) while 2-methylindoline
was completely absent. Figure 2 displays the results for
titania supported catalysts. The highest conversion was
obtained for 2 % Rh/TiO2, followed by 2 % Pd/TiO2, and
2 % Ru/TiO2 (Fig. 2a). The selectivity to 2-methylindole
was above 80 % (Fig. 2b) while selectivity to 2-methylind-
oline was equal to zero.
3.3 Catalytic Activity
If transformations of 1-(2-aminophenyl)propan-2-ol are in
line with the hydrogen borrowing reaction path then they
Table 1 Characterization of
the catalysts
Catalyst
Dispersion (%)
Metal particle size (nm)
5 % Ru/C
13
36
46
16
18
23
15
21
7
10
3
5 % Pt/C
5 % Rh/C
2
10 % Pd/C
7
1 % Ir/Sibunit
6
0.3 % Ir–H-Beta-150-IE
0.5 % Ir–H-Beta-150-IMP
4.5 % Pt–H-Beta-25
3.3 % Ru-MCM-41
5
7
5
18
Scheme 2 Reaction scheme for the hydrogen borrowing of 1-(2-aminophenyl)propan-2-ol
123

Transformations of 1-(2-Aminophenyl)propan-2-ol to 2-Methylindoline
Fig. 1 Transformations of 1-(2-aminophenyl)propan-2-ol: filled
square = 5 % Ru/C, Degussa H105 XB/W 5 %, filled trian-
gle = 10 % Pd/C, Degussa E101 NE/W 10 %, filled diamond = 5 %
Pt/C, Degussa F105 N/W 5 %, open square = 5 % Rh/C, Degussa
G106 B/W 5 %, open triangle = 1 % Ir/Sibunit, a conversion versus
time and b selectivity to 2-methylindole versus conversion. Reaction
conditions: 0.02 M in 120 ml toluene, 0.5 g catalyst, 200 °C, 12 bar
total pressure (argon), 1,650 rpm
Fig. 2 Transformations of 1-(2-aminophenyl)propan-2-ol: filled
square = 2 % Pd/TiO2, filled triangle = 2 % Ru/TiO2, filled
diamond = 2 % Rh/TiO2, a conversion versus time and b selectivity
to 2-methylindole versus conversion. Reaction conditions: 0.02 M in
120 ml toluene, 0.5 g catalyst, 200 °C, 12 bar total pressure (argon),
1,650 rpm
The results for metal catalysts supported on zeolites and
mesoporous materials are presented in Fig. 3. The highest
conversion was obtained for 4.5 % Pt–H-Beta-25, followed
by 0.5 % Ir–H-Beta-150-IMP, 0.3 % Ir–H-Beta-150-IE,
and 3.3 % Ru-MCM-41 (Fig. 3a). The highest selectivity
to 2-methylindoline was obtained with 0.3 % Ir–H-Beta-
150-IE, followed by 0.5 % Ir–H-Beta-150-IMP, 3.3 %
Ru-MCM-41, and 4.5 % Pt–H-Beta-25 (Fig. 3b). The
selectivity decreased with conversion whereas the selectivity
to 2-methylindole increased with conversion (Fig. 3c).
In order to elucidate the role of metal, Beta zeolites per
se without any metal were tested (Fig. 4).
2-methylindoline obtained for H-Beta-25 was almost 70 %
(Fig. 4b) decreasing with conversion. Interestingly, the
selectivity to 2-methylindole increased with conversion
(Fig. 4c). The yield of 2-methylindoline went through a
maximum, withthehighestyieldof34 %obtainedforH-Beta-
25(Fig. 4d). Reddy etal. [29] used zeolites ZSM-5 with varied
acidity, H-Mordenite and H-Y in the cyclocondensation of
5-amino-1-pentanol to piperidine at 350 °C. The yield of
piperidine increased with increasingSi/Al ratio, meaning that a
less acidic zeolite gave higher yield to piperidine contrary to
the results in the present study. Since it was noticed that the
yield of 2-methylindoline passes through a maximum, dehy-
drogenation of 2-methylindoline to 2-methylindole over
H-Beta-25 under argon at 200 °C was also tested and as seen
from Fig. 5, the conversion was 91 % in 4 h.
The most acidic zeolite (H-Beta-25) together with the sec-
ond most acidic (H-Beta-150) demonstrated the highest con-
version (Fig. 4a). Thehighest selectivity to thedesiredproduct
123

H. Bernas et al.
Fig. 3 Transformations of 1-(2-aminophenyl)propan-2-ol: filled
square = 0.5 % Ir–H-Beta-150-IMP, filled triangle = 3.3 % Ru-
MCM-41, filled diamond = 0.3 % Ir–H-Beta-75-IE, open square =
2-methylindoline versus conversion, and c selectivity to 2-methylin-
dole versus conversion. Reaction conditions: 0.02 M in 120 ml
toluene, 0.5 g catalyst, 200 °C, 12 bar total pressure (argon),
1,650 rpm
Pt–H-Beta-25
a
conversion versus time,
b
selectivity to
The conversion in 4 h, the turnover frequency (TOF) at
1 h reaction time as well as the selectivity to 2-methylin-
dole and 2-methylindoline at 30 % conversion are pre-
sented in Table 2.
discussed addressing a feasibility to hydrogenate 2-meth-
ylindole to 2-methylindoline. In some recent publications
hydrogenation of 2-methylindole to 2-methylindoline has
been studied showing that addition of an acid is needed to
enhance the reaction rate [30, 31] of the hydrogenation
reaction.
Conversion was 100 % in 4 h for 0.5 % Ir–H-Beta-150-
IMP, 4.5 % Pt–H-Beta-25, H-Beta-25, and H-Beta-150.
The TOF was the highest for Beta zeolite supported iridium
catalysts, but since the reaction also takes place on only
support material, such comparison based on exposed site of
Ir is not a fair one. Selectivity to the desired product
2-methylindoline at 30 % conversion was the highest for
0.3 % Ir–H-Beta-150-IE followed by H-Beta-25. Acidic
support itself gave high yields of the desired product, while
the acidic support combined with the metal afforded even
higher yields.
Scheme 1 illustrates the concept of hydrogen borrowing
reactions for primary alcohols. For secondary alcohols this
scheme should be modified and account for formation of
ketones (Scheme 2). The reaction mechanism for the
hydrogen borrowing reaction under inert atmosphere in the
case of 1-(2-aminophenylpropan-2-ol should thus include:
(i) removal of hydrogen and formation of a ketone, (ii)
cyclization and removal of water to form an imine in the
liquid phase, (iii) protonation of imine and subsequent
hydrogenation forming an amine. Typically hydrogena-
tion–dehydrogenation steps require presence of metal sites,
while amination in principle can occur at least in the case
of aldehydes even without any catalyst [32]. As already
mentioned in the current work no formation of ketone was
observed by GC analysis. Moreover, dependence of
selectivity to 2-methylindole and 2-methylindoline on
Transformations of the starting substrate to methylin-
dole take place in the presence of all catalysts investigated,
while generation of 2-methylindoline proved to be more
challenging proceeding only with the acidic catalysts.
Some traces of 2-methylindoline were obtained with 2 %
Ru/TiO2. If the overall reaction follows the hydrogen
borrowing path then experimental results should be
123

Transformations of 1-(2-Aminophenyl)propan-2-ol to 2-Methylindoline
Fig. 4 Transformations of 1-(2-aminophenyl)propan-2-ol: filled
square = H-Beta-25, filled diamond = H-Beta-150, filled trian-
gle = H-Beta-300, a conversion versus time, b selectivity to
2-methylindoline versus conversion, c selectivity to 2-methylindole
versus conversion, and d yield to 2-methylindoline versus time.
Reaction conditions: 0.02 M in 120 ml toluene, 0.5 g catalyst,
200 °C, 12 bar total pressure (argon), 1,650 rpm
the Gibbs energy for this reaction is the same as was cal-
culated for the overall hydrogen borrowing reaction.
Dehydration of various alcohols to olefins in the presence
of zeolites is well known [33, 34]. The main argument
against formation of an intermediate olefin, which in fact
was not observed experimentally, is that olefins are mainly
used for C-alkylation being typically not applied for
N-alkylation as well as O- and S-alkylation due to low
reactivity. At the same time even direct acid promoted
cyclodehydration of amino alcohols should not be ruled out
as demonstrated recently for similar homogeneous acid
catalyzed reactions [35, 36].
Fig. 5 Dehydrogenation of 2-methylindoline to 2-methylindole over
H-Beta-25. Reaction conditions: 0.02 M in 120 ml toluene, 0.5 g
catalyst, 200 °C, 12 bar total pressure (argon), 1,650 rpm
4 Conclusions
conversion as well an experimental evidence on 2-methy-
lindoline dehydrogenation to 2-methylindole (Fig. 5) are
not in line with Scheme 2, but rather fitted with an alter-
native reaction network presented in Scheme 3.
Transformations of 1-(2-aminophenyl)propan-2-ol to
2-methylindoline and 2-methylindole were studied using
carbon, titania and zeolite supported Ru, Pd, Pt, Rh, and Ir
as well as zeolites without any metal sites at 200 °C in
argon (12 bar total pressure). High yields of 2-methylin-
dole were obtained with the majority of tested catalysts,
It should be noted that transformation of 1-(2-amino-
phenyl)propan-2ol to 2-methylindoline through the path
presented in Scheme 3 is thermodynamically feasible as
123

H. Bernas et al.
Table 2 Results from catalyst screening
Catalyst
Conv. 4 h (%)
TOFa (h-1
)
Sel.b Methylindole (%)
Sel.b Methylindoline (%)
5 % Ru/C
81
17.2
25.7
9.9
20.4
69.6
–
96
99
93
98
100
91
95
81
19
69
91
80
31
68
56
0
5 % Pt/C
91
0
5 % Rh/C
67
0
10 % Pd/C
94
0
1 % Ir/Sibunit
2 % Ru/TiO2
2 % Rh/TiO2
2 % Pd/TiO2
0.3 % Ir–H-Beta-150-IE
0.5 % Ir–H-Beta-150-IMP
4.5 % Pt–H-Beta-25
3.3 % Ru-MCM-41
H-Beta-25
36
0
58
3
82
–
0
76
–
0
93
858.9
997.4
90.9
25.9
–
80
31
6
100
100
37
14
67
11
40
100
100
65
H-Beta-150
–
H-Beta-300
–
a
Moles of reactant reacted per mole of metal and hour
Selectivity at 30 % conversion
b
Scheme 3 Transformation of 1-(2-aminophenyl)propan-2-ol through dehydration-cyclization and dehydrogenation
6. Blank B, Madalska M, Kempe R (2008) Adv Synth Catal
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while acidic zeolite catalysts with or even without metal
can also result in formation of 2-methylindoline. Reaction
network was proposed which comprised dehydration–
cyclization and dehydrogenation steps.
˚
Acknowledgments This work is a part of activities at the Abo
Akademi Process Chemistry Centre (PCC), a Centre of Excellence
˚
financed by Abo Akademi University. Financial support from Euro-
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pean Union through the Seventh Framework Programme (Project
246095-2) is gratefully acknowledged. Mr. Markku Reunanen and Dr.
Annika Smeds are acknowledged for analysis by GC–MS.
14:11474–11479
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