Heterogeneous mesoporous manganese oxide catalyst for aerobic and additive-free oxidative aromatization of N-heterocycles

Article abstract of DOI:10.1039/c6cc09095h

Herein, we report a heterogeneous, aerobic, additive-free and environmentally benign catalytic protocol for oxidative aromatization of saturated nitrogen-heterocycles using a mesoporous manganese oxide material. The aromatized products can be separated by easy filtration and the catalyst is reusable for at least four cycles. Mechanistic investigation provides evidence for radical intermediates, a multi-electron redox cycle between Mn centers, and an oxygen exchange mechanism.

Full text of DOI:10.1039/c6cc09095h

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Heterogeneous mesoporous manganese oxide
catalyst for aerobic and additive-free oxidative
aromatization of N-heterocycles†
Cite this:DOI: 10.1039/c6cc09095h
Received 14th November 2016,
Accepted 25th January 2017
Kankana Mullick, Sourav Biswas,‡ Alfredo M. Angeles-Boza* and Steven L. Suib*
DOI: 10.1039/c6cc09095h
rsc.li/chemcomm
Herein, we report a heterogeneous, aerobic, additive-free and
environmentally benign catalytic protocol for oxidative aromatization
of saturated nitrogen-heterocycles using a mesoporous manganese
oxide material. The aromatized products can be separated by easy
filtration and the catalyst is reusable for at least four cycles.
Mechanistic investigation provides evidence for radical inter-
mediates, a multi-electron redox cycle between Mn centers, and
an oxygen exchange mechanism.
Nitrogen-containing heterocyclic aromatic compounds are common
intermediates in pharmaceutical and biologically relevant
molecules.1–4 The typical procedure to access heteroarenes
involves dehydrogenation reactions from the corresponding
saturated heterocycles. In the acceptorless dehydrogenation
reaction, Fe-, Ru- and Ir-based catalysts have been used
(Scheme 1A).5–10 More recently, metal-free boron based catalysts
have been reported to catalyze this reaction.11 An alternative
procedure utilizes catalytic oxidative dehydrogenation of saturated
nitrogen heterocycles under oxygen atmosphere (Scheme 1B).
Several homogeneous catalysts have been successfully employed
for the oxidative dehydrogenation route.12–16 From an environmental
perspective, heterogeneous catalysts are preferred due to the facile
product separation and the prospects of catalyst reusability. Some
Scheme 1 Various routes to synthesize N-heterocyclic aromatic compounds.
existing heterogeneous catalysts for oxidative aromatization of broad substrate scope and excellent reusability.25 Additionally,
N-heterocycles are Rh-, Pd-, and Pt-based catalysts, Pd3Pb, Au nano- Stahl and co-workers have used cobalt oxide supported nitrogen
particles, and Ru supported on different metal oxide supports.17–24 doped graphene catalysts for oxidative aromatization at low
Notably, most of the systems are based on less abundant precious temperatures.26 Despite their good catalytic performance, these
metals and display narrow substrate scope.
systems require either difficult catalyst preparation methods or
Beller and co-workers have reported an efficient hetero- use of high oxygen pressure and additives. Therefore, a simple,
geneous iron–nitrogen doped graphene core–shell catalyst with efficient heterogeneous catalytic system for oxidative aromati-
zation of N-heterocycles under aerobic, atmospheric conditions
is highly desirable.
Department of Chemistry, University of Connecticut, 55 North Eagleville Rd., Storrs,
Connecticut 06269, USA. E-mail: alfredo.angeles-boza@uconn.edu,
steven.suib@uconn.edu
We have designed a series of mesoporous materials by an
inverse-micelle templated evaporation induced self-assembly
technique.27 Mesoporous manganese oxide materials prepared
by this method showed excellent performance in aerobic oxida-
tion of alcohols to aldehydes, amines to imines, anilines to azo
compounds, tandem oxidative reactions from alcohols, and
† Electronic supplementary information (ESI) available: Experimental details,
Tables S1–S4, Fig. S1–S12 and Schemes S1–S3 and spectral characterization of
typical products. See DOI: 10.1039/c6cc09095h
‡ Present address: Department of Chemistry, University of Wisconsin-Madison,
1101 University Avenue, Madison, Wisconsin 53706, USA.
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oxidative coupling of alkynes to diyne derivatives.28–32 These pluronic surfactant (P123) was used as the building block. The
manganese oxide materials have versatile structural forms with material was formed by aggregation of nanoparticles with intra-
high thermal stability. The manganese redox cycling and labile particle voids within the mesostructure. As indicated by the
lattice oxygen molecules have been shown to be determinant powder X-ray diffraction measurements (Fig. S1, ESI†) the mate-
factors in the catalytic performance of these novel materials. rial was amorphous at low calcination temperatures (o350 1C)
Herein, we present our effort to use mesoporous manganese and formed a crystalline bixbyite (Mn2O3) phase at higher
oxide materials for the aerobic dehydrogenation of saturated temperatures (4400 1C). The mesoporous structure of meso
N-heterocycles to their corresponding aromatic derivatives. MnOx was confirmed by nitrogen sorption studies (Fig. S2a,
Absence of precious metals and additives, use of air as the sole ESI†), where a type IV adsorption isotherms, followed by type I
oxidant, easy isolation of products, along with proper catalyst hysteresis loop were observed irrespective of calcination tempera-
reusability make our catalytic protocol an attractive choice for tures. The material possessed uniform mesoporous size distribu-
oxidative aromatization of N-heterocyclic compounds.
tions (Fig. S2b, ESI†) and an increment in pore size was observed
To examine the activity of the manganese oxide catalysts we with higher calcination temperature due to sintering of the
initially selected 1,2,3,4-tetrahydroquinoline as the test substrate. nanoparticles (Table S2, ESI†). The oxidation states of Mn (deter-
In a comparative study, 1,2,3,4-tetrahydroquinoline was reacted mined by X-ray photoelectron spectra [XPS]) was found to be 3+ at
with different phases of well-known manganese oxide materials for different calcination temperatures (Fig. S3, ESI†). The O 1s XPS
oxidation reactions. The mesoporous manganese oxide material (Fig. S4, ESI†) of meso MnOx-250 showed features typical of
(meso MnOx), prepared by an inverse micelle templated self- manganese oxide materials having multiple oxygen species.
assembly method,27 provided a 50% conversion with 499%
The high surface area and poor crystalline nature of the
selectivity to the target compound quinoline in aerobic conditions material are critical for achieving high efficiency. Highly accessible
(Table 1, entry 1). No improvement of activity was observed by surface area provides larger amounts of catalytically active sites,
introducing Cs promoter ions (Table 1, entry 2). Relatively higher whereas the poor crystalline nature of the material results in highly
conversions were achieved using two other active manganese oxide accessible and labile lattice oxygen. The performance of the meso
phases, octahedral molecular sieves (K-OMS-2) and amorphous MnOx material was investigated as a function of calcination
manganese oxide (AMO),33 however selectivity decreased signifi- temperatures, since calcination has a remarkable effect on
cantly due to formation of N-oxide by over oxidation (Table 1, the surface area and crystallinity of the material (Fig. S5, ESI†).
entries 3 and 4). Notably, a reaction with commercial nonporous The highest conversion (72%) was achieved when the material
Mn2O3 gave negligible conversion, similar to catalyst-free condi- was calcined to 350 1C (highest surface area, 226 m2 gÀ1 and
tions (Table 1, entries 5 and 6). The continual increase of perfor- amorphous in nature) and the conversion decreased signifi-
mance with catalyst loading (Table 1, entries 7–9) indicates that cantly when the material was heated to 450 1C (26%) due to
the system is not suffering from adsorption and mass transfer. The lowering of surface area (150 m2 gÀ1) and increasing crystallinity.
reaction was also surveyed with different solvents of varying
While investigating the role of oxidant, the reaction under
polarity. As revealed in Table S1 (ESI†), the reaction was facilitated pure molecular oxygen instead of air did not improve the
in the presence of polar solvents and N,N-dimethylformamide conversion but reduced the selectivity of quinoline due to
(DMF) emerged as the best solvent.
over-oxidation (Table S3, entries 1 and 2, ESI†). However,
The mesoporous manganese oxide materials were synthesized conversion was increased significantly under a pressurized
by an inverse micelle templated method, where a non-polar oxygen system using lower amounts of catalyst (Table S3,
entries 3 and 4, ESI†). This is due to the higher solubility of
oxygen in the solvent under high pressure. Therefore, after
Table
1
Comparison of catalysts for aromatization of 1,2,3,4-tetra-
extensive screening of all reaction parameters, we chose aerobic
conditions in DMF at 130 1C as the optimal reaction condition
for the meso MnOx-350 catalyst.
hydroquinolinea
Preventing deactivation of catalysts due to aggregation and
leaching of active metals in solution is a challenge for hetero-
geneous catalytic systems. To verify for leaching of active metals,
we performed a hot filtration (Fig. S6, ESI†). The catalyst was
removed from the reaction system after 3 h (at about 30%
conversion) and the filtrate was kept under the same reaction
conditions for the next 20 h. No further reaction was observed,
which confirmed the absence of active metals in the solution.
To check for reusability, the catalyst was retrieved from the
reaction mixture by centrifugation and washed with excess
DMF and ethanol. Prior to reuse, the catalyst was reactivated
at 250 1C for 30 min to remove any adsorbed substrates.
As observed in Fig. S7a (ESI†) the catalyst can be reused for at
least four times without any loss of activity and selectivity.
Entry Catalyst
Catalyst amount (mg) Conv.b (%) Selec.b (%)
1
2
3
4
5
6
7
8
9
Meso MnOx
Meso Cs/MnOx 25
K-OMS-2
AMO
C-Mn2O3
No
Meso MnOx
Meso MnOx
Meso MnOx
25
50
50
65
60
1
499
499
70
25
25
25
0
5
10
50
90
499
499
499
499
499
1
11
25
80
a
Reaction conditions: 1,2,3,4-tetrahydroquinoline (0.25 mmol), catalyst
b
(required amount), DMF (5 mL), 130 1C, air balloon, 5 h. Conversions
and selectivity were determined by GC-MS based on concentration of
1,2,3,4-tetrahydroquinoline.
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Table 2 Oxidative dehydrogenation of N-heterocycles by meso MnOxa
Additionally, the X-ray diffraction studies confirmed that the
amorphous nature of the catalyst was retained after multiple
reuse cycles (Fig. S7b, ESI†). Therefore, our catalyst is hetero-
geneous, stable, and reusable.
No. Substrate
1
Product
Conv.b (%) Sel.b (%) TONc
499
499
95
1.7
1.7
The kinetic aspects of the reaction were determined by
conducting a time-dependent study (Fig. S8, ESI†). Formation
of quinoline N-oxide was observed in trace amounts after 3 h.
A first order rate equation was derived with respect to 1,2,3,4-
tetrahydroquinoline with a rate constant of (2.9 Æ 0.1) Â
10À5 sÀ1 (Fig. S9, ESI†). A series of time-dependent experiments
were performed in the temperature range of 80–140 1C.
The apparent activation energy was estimated as 8.3 Æ
0.2 kcal molÀ1 using the Arrhenius equation (Fig. S10, ESI†).
The current methodology works well for a diverse library
of N-containing aromatic heterocycles. The products can be
isolated easily by filtration followed by solvent evaporation.
Isolated yields of some of the aromatized products along with
their NMR spectra are provided (see ESI†). The presence of
electron donating substituents in the aromatic ring of 1,2,3,4-
tetrahydroquinoline did not alter the catalytic activity (entries 2
and 3, Table 2). The present protocol can be applicable to
functional groups containing electron lone pairs (–OMe), which
were found to partially deactivate the aforementioned boron-
based catalytic system due to coordination.11 The presence of the
electron withdrawing group –NO2 in the aromatic ring resulted
in moderate conversions (70%, entry 5, Table 2). These results
can be interpreted as a measure of the susceptibility of the
catalytic efficiency to substituent effects. Substitutions at position
2 of the saturated ring of 1,2,3,4-tetrahydroquinoline resulted in
lower conversion due to steric effects that retard the abstraction of
the a C–H hydrogen (entry 5, Table 2). Quinoxaline and indole
derivatives are representative structural motifs in biologically and
pharmaceutically relevant molecules.34 The oxidative dehydro-
2
3
499
499
93 (89) 1.7
4
5
6
70
80
499
1.4
1.5
1.7
499
499
499
7
499
499 (92) 1.7
499 (94) 1.7
8d
499
9
nd
0
0
0
a
Reaction conditions: substrate (0.25 mmol), meso MnOx (25 mg),
b
DMF (3 mL), 130 1C, 20 h, air balloon. Conversion and selectivity were
determined by GC-MS. Numbers in parenthesis refer to yields of
isolated products. Isolation was carried out in acetonitrile at 80 1C.
c
d
TON = moles of amines converted/moles of catalyst. 120 1C and 5 h.
nd = not determined.
genation method by meso MnOx could be an attractive synthetic products (corresponding alcohol and ketone) with negligible
route for preparation of quinoxaline and indole. As observed, conversion (Scheme S2, ESI†) indicating that direct C–C
a substituted 2-methylindoline and a saturated 1,2,3,4-tetra- dehydrogenation is unlikely to occur in the present reaction
hydroquinoxaline can be effectively aromatized with quantitative conditions. Therefore, the presence of nitrogen in the saturated
conversion (499%) and selectivity (entries 6 and 7, Table 2). The cyclic alkane moiety is necessary to begin the reaction by
excellent functional group tolerance of the present protocol was transferring an electron to the Mn center. The formed amine
exhibited by the oxidative aromatization of Hantzsch ester, radical species can then undergo a C–H dehydrogenation to
which yielded the desired aromatic product with quantitative form an imine (CQN) intermediate (Scheme 2). This is rein-
conversion (499%) and excellent selectivity (499%) at lower forced by the fact that, substrate lacking an a C–H proton
temperature and short reaction time (entry 8, Table 2). On the (1,2,3,4-tetrahydro-2,2,4,7-tetramethylquinoline, Scheme S3, ESI†)
other hand, N heterocycles lacking an adjacent ancillary benzene did not form any product. The final aromatized product is
ring did not produce any product (entry 9, Table 2).
Several control experiments were then performed to gain cyclic imine as reported by Jones and co-workers.5
mechanistic insights of the present catalytic protocol. In the The formation of the radical amine intermediate results in
probably formed by a second dehydrogenation from a tautomeric
report by Beller and co-workers, the reaction is initiated by the reduction of surface active Mn centers, which leads to
forming a radical intermediate by transfer of electron from release of labile lattice oxygen.29,32 Under catalytic turnover
1,2,3,4-tetrahydroquinoline to the catalyst. By introducing the conditions, the reduced Mn species can be re-oxidized by
radical scavenger 2,6-di-tert-butyl-4-methylphenol in the reac- dioxygen with production of H2O2, which can disproportionate
tion mixture, we trapped the radical intermediate formed after to water and O2 in the presence of manganese oxide.35 The aerobic
the electron transfer step (Scheme S1, ESI†). This result atmosphere is critical as loss of lattice oxygen should be replen-
suggested similar reaction pathways for our system and the ished by the aerial oxygen. This is consistent with the observation
catalyst reported by Beller and co-workers.25 A reaction of of lower catalytic efficiency under nitrogen atmosphere (18%
1,2,3,4-tetrahydronaphthalene only produced the oxidized conversion) compared to aerobic conditions (50% conversion).
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Scheme 2 Proposed mechanism of oxidative aromatization of 1,2,3,4-
tetrahydroquinoline.
A kinetic analysis under nitrogen atmosphere revealed a decrease
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lower temperature (80 1C) in acetonitrile with formation of
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involvement of labile lattice oxygen are important factors for
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AMAB acknowledges the financial support from the University of
Connecticut. SLS thanks support of the US Department of Energy,
Office of Basic Energy Sciences, Division of Chemical, Biological and
Geological Sciences under grant DE-FG02-86ER13622.A000.
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