A new efficient approach to 3-methylindole: Vapor-phase synthesis from aniline and glycerol over Cu-based catalyst

Article abstract of DOI:10.1016/j.catcom.2010.08.011

A novel efficient method for vapor-phase synthesis of 3-methylindole from aniline and glycerol has been developed over Cu-based catalysts. The catalysts were characterized by BET, XRD, H₂-TPR and NH₃-TPD techniques. The results indicated that Cu/SiO₂-Al₂O ₃ catalyst exhibited high activity. The yield of 3-methylindole could be up to 40% when the Cu loading was 5.41 wt% and the reaction temperature was 240 °C. Moreover, the catalyst could be reused without obvious loss of the yield even after reaction time of 46 h. Copper-based catalyst with good dispersion and large amount of weak acid sites was favorable for producing 3-methylindole. A possible reaction pathway for the catalytic synthesis of 3-methylindole was proposed.

Full text of DOI:10.1016/j.catcom.2010.08.011

Catalysis Communications 12 (2010) 147–150
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
A new efficient approach to 3-methylindole: Vapor-phase synthesis from aniline and
glycerol over Cu-based catalyst
⁎
Wei Sun, Dong-Yan Liu, Hai-Yan Zhu, Lei Shi , Qi Sun
Institute of Chemistry for Functionalized Materials, Liaoning Normal University, Dalian 116029, Liaoning, P. R. China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 May 2010
Received in revised form 20 July 2010
Accepted 9 August 2010
Available online 19 August 2010
A novel efficient method for vapor-phase synthesis of 3-methylindole from aniline and glycerol has been
developed over Cu-based catalysts. The catalysts were characterized by BET, XRD, H2-TPR and NH3-TPD
techniques. The results indicated that Cu/SiO2-Al2O3 catalyst exhibited high activity. The yield of 3-methylindole
could be up to 40% when the Cu loading was 5.41 wt% and the reaction temperature was 240 °C. Moreover, the
catalyst could be reused without obvious loss of the yield even after reaction time of 46 h. Copper-based catalyst
with good dispersion and large amount of weak acid sites was favorable for producing 3-methylindole. A possible
reaction pathway for the catalytic synthesis of 3-methylindole was proposed.
Keywords:
Cu-based catalysts
3-Methylindole
Aniline
© 2010 Elsevier B.V. All rights reserved.
Glycerol
Weak acid sites
Dispersion
1. Introduction
synthesis of 3-methylindole from aniline and 1,2-propanediol, a yield of
35% was obtained [13]. However, the Ag/SiO2 catalyst showed poor
For several years, indole and its derivatives are widely used in
medicine, agriculture and industry [1–3]. 3-Methylindole, an important
nitrogen-containing heterocyclic chemical, has received considerable
attention owing to its potential application as perfume and synthesizing
herbicides, antidiuretic, stimulant antihypertensive, muscular relaxant,
respiratory inhibitor and heart stimulant medicaments, etc. [4,5].
To date, many synthetic routes have been developed for the
synthesis of indoles (Scheme 1). Among them, liquid-phase method is
often considered conventional because it can give the product in a good
yield. However, many starting materials are expensive and some
catalysts preparations are complicated as well as its stringent
environmental concern on the reactions, which limited the further
development of indole and its derivatives [6–8]. Hence, the develop-
ment of vapor-phase synthesis is of general interest. Although many
vapor-phase syntheses of indoles are reported [9,10], only a few reports
are available about the vapor-phase synthesis of 3-methylindole.
One synthesis from indole and methanol (molar ratio of indole/
methanol was 1:6) took place over CeHY zeolite catalyst with 30%
yield of 3-methylindole, in which, however, expensive reagent of indole
and large amount of toxic methanol were used [11]. Recently, ZrO2/SiO2
catalyst was used in the synthesis of alkylindoles, just a yield of 12% was
obtained for 3-methylindole from aniline and 1,2-propanediol [12]. Our
research found that Ag/SiO2 was an active catalyst for the vapor-phase
stability and was deactivated rapidly with time on stream. Thus, the
development of an efficient approach for the vapor-phase synthesis of
3-methylindole is an important research target.
Glycerol is not only cheap and abundant, but also known as a
green feedstock for the production of various chemicals [14–17], such
as 1,3-propanediol, succinate, xylitol, propionate, etc. [18–20]. In this
paper, we report a new vapor-phase approach to 3-methylindole, in
which glycerol was employed as one of the reactants. A series of
materials were tested to find out an efficient catalyst for the reaction.
Active component loading, reaction temperature and the stability of
catalyst were investigated. BET, XRD, H2-TPR and NH3-TPD techniques
were used to reveal the relationship between the structure of Cu-based
catalysts and their catalytic performances.
2. Experimental
2.1. Preparation of catalysts
The catalysts were prepared by incipient wetness impregnation
using SiO2, γ-Al2O3 or SiO2-Al2O3 as support. After impregnating
support (20−40 mesh) with appropriate amount of nitrate aqueous
solution for 15 h at room temperature, the sample was dried at 120 °C
for 4 h, and then calcined at 500 °C for 4 h to obtain the catalyst
precursor. Prior to activity test, the catalyst precursor (3 mL) was in
situ reduced in a mixture gas composed of N2 (30 mL/min) and H2
(30 mL/min) at 250 °C for 2 h, then heated or cooled to reaction
temperature in 0.5 h and kept at the temperature for another 0.5 h.
⁎
Corresponding author. Tel.: +86 411 84258329.
E-mail address: shilei515@dl.cn (L. Shi).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.08.011

148
W. Sun et al. / Catalysis Communications 12 (2010) 147–150
CH3
Table 1
H2C OH
HC OH
H2C OH
The activity and selectivity of the catalysts.
Cat.
3H2O
Catalyst
Glycerol
conversion (%)
3-Methylindole
yield (%)
3-Methylindole
selectivity (%)
N
NH2
H
SiO2
γ-Al2O3
SiO2-Al2O3
FeO/SiO2
85
100
100
82
0
13
15
1
0.0
13.0
15.0
1.2
Scheme 1. Synthesis of 3-methylindole from aniline and glycerol.
CoO/SiO2
83
1
1.2
Ni/SiO2
Ag/SiO2
Cu/SiO2
100
100
100
94
0
5
12
6
4
0.0
5.0
12.0
6.4
4.2
2.2. Catalytic activity testing
FeO/r-Al2O3
CoO/r-Al2O3
Ni/r-Al2O3
Ag/r-Al2O3
Cu/r-Al2O3
FeO/SiO2-Al2O3
CoO/SiO2-Al2O3
Ni/SiO2-Al2O3
Ag/SiO2-Al2O3
Cu/SiO2-Al2O3
The catalytic reactions were carried out in a fix-bed continuous
flow glass reactor with inside diameter of 12 mm under atmospheric
pressure. The mixture of reactants (molar ratio of aniline/glycer-
ol=3:1, SV=1700 h−1, LHSV=0.4 h−1) was pumped through the
preheater where they were vaporized and then entered into the
reactor with flowing H2 (10 mL/min), steam (12 mL/h) and N2
(58 mL/min). The quantitative analysis of the reactants and products
was carried out on the SP-6890A gas chromatograph equipped with
an SE-54 capillary column. 1-Hexyl alcohol was used as an internal
standard. 3-Methylindole selectivity was calculated based on
glycerol conversion and 3-methylindole yield.
96
100
100
100
100
100
100
100
100
1
1.0
12
18
9
9
5
12.0
18.0
9.0
9.0
5.0
17
38
17.0
38.0
Reaction conditions: 240 °C, aniline/glycerol=3:1 molar ratio, SV=1700 h− 1
,
LHSV=0.4 h−1, H2 =10 mL/min, steam=12 mL/h, N2 =58 mL/min. Catalyst loading:
3.67 wt%. The results were taken at the fourth hour.
The side products were analyzed on a gas chromatograph with a
mass spectrometer (Shimadzu GCMS-QP2010) using a DB-5 capillary
column and a gas chromatograph connected to a hydrogen flame
ionization detector (FID-GC, SP-6800A) using OV-17 column.
3. Results and discussion
3.1. Performances of various catalysts in the synthesis of 3-methylindole
2.3. Regeneration of catalyst
For the synthesis of 3-methylindole from aniline and glycerol, the
activity and selectivity over various catalysts are presented in Table 1.
When Fe, Co or Ni was employed as active component respectively,
glycerol conversion of 82–100% was obtained, but the selectivity of
3-methylindole was low (less than 10%). Based on the GC-MS analysis,
the main side products were N-methylaniline, N-ethylaniline
and indole, etc. Over the silver-based catalysts, the selectivity of
3-methylindole reached 5–17%. It is clearly observed that Cu-based
catalysts afforded 3-methylindole in higher yields than those obtained
over other catalysts. Besides, SiO2-Al2O3 support seemed to be favorable
for the desired transformation. Compared with the catalysts of
SiO2 or γ-Al2O3 supported, SiO2-Al2O3 supported catalysts
showed higher activity and selectivity. Among all the examined
catalysts, Cu/SiO2-Al2O3 exhibited the highest catalytic activity,
which the yield of 3-methylindole reached 38%.
Table 2 exhibits the yields of 3-methylindole over Cu/SiO2-Al2O3
catalyst with different Cu loadings. It can be seen that the yield
of 3-methylindole increased with the increase of Cu loading
from 1.87 to 5.41 wt%. When the Cu loading was 1.87 wt%, the
yield of 3-methylindole was only 33%. When the Cu loading was
5.41 wt%, the desired product could attain a yield as high as
40%. A further increase in Cu loading again, however, the yield of
3-methylindole decreased. 5.41 wt% of the Cu loading was the best
choice for Cu/SiO2-Al2O3 catalyst to produce 3-methylindole.
The inactivated catalyst was regenerated in the flow of O2
(3 mL/min) and N2 (57 mL/min) from ambient to 500 °C at a
linearly programmed rate of 5 °C/min and kept at the temperature
for 4 h. Prior to activity test, the catalyst was in situ reduced and
the process was the same as the reduction step of catalyst
preparation in 2.1.
2.4. Characterization of catalysts
BET surface areas of Cu-based catalysts were measured by an
AUTOSORB-1MP apparatus using ultra pure nitrogen as the analysis
gas. Before each measurement, the sample was outgassed overnight at
200 °C under 10−3 torr. The pore-size distribution curves were
obtained from the analysis of the desorption portion of the isotherms
using the BJH (Barrett–Joyner–Halenda) method.
X-ray diffraction (XRD) patterns were recorded by using a D8
Advance diffraction meter with Cu Kα source at radiation rate 0.5°/min
in the 2θ range of 30–80°. The voltage and current were 40 kV and
40 mA, respectively.
The temperature programmed reduction (H2-TPR) experiments
were performed in a quartz reactor with inside diameter of 6 mm and
length of 350 mm. The sample (100 mg) was pretreated in a flow of
ultra pure nitrogen gas of 50 mL/min at 100 °C for 1 h to remove water
and other contaminants. TPR profiles were obtained by heating the
samples under a 10% H2/Ar flow (50 mL/min) from 50 to 450 °C at a
linearly programmed rate of 10 °C/min. The hydrogen consumption
was recorded with a thermal conductivity detector.
The temperature programmed desorption of ammonia (NH3-TPD)
experiments were carried out in a quartz reactor used as in H2-TPR
experiment. 150 mg of the sample was firstly pretreated at 500 °C for
1 h in a flow of ultra pure helium gas (50 mL/min) to remove water
from the catalyst. In the following steps, the sample was saturated
with ammonia gas at 100 °C for 1 h and subsequently flushed with He
(50 mL/min) at 100 °C for 3 h to remove the physisorbed ammonia.
Hereinto, the heating rate for the TPD measurements was 10 °C/min
and the temperature range was from ambient to 700 °C.
Table 2
Effect of Cu loading on the activity and selectivity of Cu/SiO2-Al2O3 catalyst.
Cu loading
(wt%)
Glycerol
conversion (%)
3-Methylindole
yield (%)
3-Methylindole
selectivity (%)
1.87
3.67
5.41
7.08
8.70
100
100
100
100
100
33
38
40
37
34
33.0
38.0
40.0
37.0
34.0
Reaction conditions: 240 °C, aniline/glycerol=3:1 molar ratio, SV=1700 h− 1
,
LHSV=0.4 h−1, H2 =10 mL/min, steam=12 mL/h, N2 =58 mL/min. The results were
taken at the fourth hour.

W. Sun et al. / Catalysis Communications 12 (2010) 147–150
149
Table 3
Table 4
Effect of the reaction temperature on the activity and selectivity of Cu/SiO2-Al2O3
catalyst.
The specific surface area and total pore volume of Cu-based catalysts.
Catalyst
Specific surface area (m2/g)
Total pore volume (mL/g)
Temperature
(°C)
Glycerol
conversion (%)
3-Methylindole
yield (%)
3-Methylindole
selectivity (%)
Cu/SiO2-Al2O3
Cu/γ-Al2O3
Cu/SiO2
308.4
332.5
381.3
0.6029
0.8807
0.9403
220
240
260
280
100
100
100
100
34
40
36
31
34.0
40.0
36.0
31.0
Reaction conditions: aniline/glycerol=3:1 molar ratio, SV=1700 h−1, LHSV=0.4 h−1
H2 =10 mL/min, steam=12 mL/h, N2 =58 mL/min. Copper loading: 5.41 wt%. The
results were taken at the fourth hour.
,
(111) and (200) reflections of crystalline copper, were observed on
Cu/SiO2 catalyst and no distinct copper diffraction peaks were found
on Cu/SiO2-Al2O3 or Cu/γ-Al2O3, suggested that copper existed in
bigger particles on the surface of SiO2 and presented in an amorphous
state on CuO/SiO2-Al2O3 or Cu/γ-Al2O3 [21]. This was ascribed to the
interactions between copper and the supports. For the Cu/SiO2
catalyst, in spite of its relatively large specific surface area, the
interaction between Cu and SiO2 was weak, as a result, it was easy for
the Cu particles to get together on the surface of SiO2, whereas, the
interaction between Cu and SiO2-Al2O3 or γ-Al2O3 was strong, which
resulted in the good dispersion of copper particles on the support of
SiO2-Al2O3 or γ-Al2O3. From the results of XRD and Table 1 it can be
deduced that bigger copper particles on Cu-based catalyst took
disadvantage of the synthesis of 3-methylindole.
The effect of reaction temperature was investigated over
Cu/SiO2-Al2O3 catalyst. As shown in Table 3 the yield of 3-
methylindole increased at first, then decreased as the tempera-
ture shifted from 220 to 280 °C. At 220 °C, a 34% yield of 3-
methylindole was obtained. To our delight, the target product
yield can be enhanced to 40% when increased the reaction
temperature to 240 °C. In the case of higher temperature such as
260 °C or 280 °C, the lower yield of 36% or 31% was obtained,
respectively. 240 °C was propitious temperature to the produc-
tion of 3-methylindole.
The stability of the Cu/SiO2-Al2O3 catalyst in the synthesis of
3-methylindole was examined under the reaction temperature of
240 °C and the Cu loading of 5.41 wt%. It can be seen in Fig. 1 that
although the yield of 3-methylindole dropped to about 30% after
reaction time of 10 h, the yield could be recovered when the catalyst
was regenerated in the flow of O2 (5%) and N2 (95%). The yield of
3-methylindole was up to 37% after the catalyst was reused successively
five times (nearly 46 h), indicating that the stability of theCu/SiO2-Al2O3
catalyst was good.
Cu (111)
Cu (200)
(3)
3.2. Catalyst characterization
Table 4 showed the specific surface areas and total pore volumes
for different Cu-based catalysts. It can be seen that the specific surface
area and total pore volume on Cu/SiO2-Al2O3 were all smaller than
those on Cu/γ-Al2O3 or Cu/SiO2. Considering the activities of Cu-based
catalysts it can be obtained that the specific surface area and total pore
volume were not the crucial factors for the vapor-phase synthesis of
3-methylindole.
(2)
(1)
30
40
50
2 (°)
60
70
80
The X-ray diffraction patterns of Cu-based catalysts are shown in
Fig. 2. Two big diffraction peaks at about 43.1° and 50.3°, assigned to
Fig. 2. XRD patterns of Cu/SiO2-Al2O3 (1), Cu/γ-Al2O3 (2) and Cu/SiO2 (3).
260
40
30
20
10
0
(3)
250
(2)
248
(1)
0
100
200
300
400
500
0
10
20
30
40
50
Temperature (°C)
Reaction time (h)
Fig. 1. The stability of Cu/SiO2-Al2O3 catalyst.
Fig. 3. H2-TPR profiles of CuO/SiO2-Al2O3 (1), CuO/γ-Al2O3 (2) and CuO/SiO2 (3).

150
W. Sun et al. / Catalysis Communications 12 (2010) 147–150
It is well known that acid sites facilitated the reactants of aniline
and glycerol to adsorb on the catalyst. However, it was unfavorable for
the synthesis of 3-methylindole if the acidity of the catalyst was
strong because 3-methylindole desorbed from the catalyst difficultly
and as a result, the further reaction of 3-methylindole happened easily
and the selectivity of the target product was low.
4. Reaction pathway
For the vapor-phase synthesis of 3-methylindole, a possible reaction
pathway over Cu-based catalyst was proposed (Fig. 5) [23–25], in which
2-hydroxypropylaldehyde (2-HPAL) might be formed from glycerol,
then 2-HPAL produced a Schiff's base (SB) by N-alkylation of aniline, SB
cyclized to 3-methylindole. Because 2-HPAL and SB was not detected by
GC-MS, it could be deduced that steps 2 and 3 were fast.
(1)
(2)
(3)
50
100
150
200
250
300
350
5. Conclusion
Temperature (°C)
A new efficient and convenient route was developed for the vapor-
phase synthesis of 3-methylindole from readily available reactants of
aniline and glycerol under mild conditions. Cu/SiO2-Al2O3 catalyst showed
high activity. A 40% yield of 3-methylindole was obtained when the Cu
loading was 5.41 wt% and the reaction temperature was 240 °C. Moreover,
the stability of Cu/SiO2-Al2O3 catalyst was good. The catalyst could be
reused without obvious loss of the yield even after reaction time of 46 h.
There existed the strong interaction between Cu and SiO2-Al2O3, which
promoted copper dispersed on the surface of the support commendably.
Copper-based catalyst with good dispersion and large amount of weak
acid sites was favorable for the synthesis of 3-methylindole because small
copper particles could provide large amount of active sites and weak acid
sites could facilitate the adsorption of reactants on the catalyst and the
desorption of 3-methylindole from the catalyst. A possible reaction
pathway for the catalytic synthesis of 3-methylindole was proposed.
Fig. 4. NH3-TPD profiles of Cu/SiO2-Al2O3 (1), Cu/γ-Al2O3 (2) and Cu/SiO2 (3).
The reducibility of supported CuO samples was investigated by
H2-TPR experiments and the profiles are given in Fig. 3. On the
sample of CuO/SiO2-Al2O3 or CuO/γ-Al2O3, more than two reduction
peaks were observed. Considering the results of XRD it can be
deduced that the big reduction peak at the relative lower
temperature was the dispersed CuO species and the small peaks
at relative higher temperature were attributed to the reduction of
very small amount of bulk CuO particles [22]. On the sample of
CuO/SiO2, only one reduction peak existed at about 260 °C, assigned
to the reduction of bulk CuO phase [21]. Moreover, the main
reduction peak on CuO/SiO2-Al2O3 or CuO/γ-Al2O3 shifted towards
the lower temperature compared with the reduction of CuO/SiO2,
suggested that the dispersed CuO particles were more easily
reduced than the bulk CuO ones.
NH3-TPD profiles can be used to illuminate the distribution and the
amount of acid sites of catalyst. From Fig. 4 it can be seen that three
desorption peaks existed on the Cu-based catalysts. The peak at lower
temperature (b150 °C) was assigned to the weak acid sites, while the
others at higher temperature (150–350 °C) were corresponded to the
middle-strong acid sites. The amount of weak acid sites on Cu/SiO2-Al2O3
was largest, followed by that on Cu/γ-Al2O3 and Cu/SiO2. Considering the
results in Table 1 it can be obtained that copper-based catalyst with large
amount of weak acid sites was favorable for the synthesis of 3-
methylindole.
Acknowledgements
The work was financially supported by the Education Department
of Liaoning Province, China (No. 2009A421).
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