Visible-Light-Mediated Photocatalytic Aerobic Dehydrogenation of N-heterocycles by Surface-Grafted TiO2 and 4-amino-TEMPO

Article abstract of DOI:10.1021/acscatal.9b03322

Herein, the visible-light-induced dehydrogenation of N-heterocycles such as tetrahydroquinolines, tetrahydroisoquinolines, and indolines in O₂-containing suspensions of a commercially available titanium dioxide photocatalyst yielding the corresponding heteroarenes is presented. 4-Amino-2,2,6,6-tetramethylpipiridinyloxyl (4-amino-TEMPO) was found to exhibit a beneficial role, as it increased the yield and improved the selectivity of the dehydrogenation reaction. Both the selectivity and the yield are further enhanced by grafting 0.1 wt % of Ni(II) ions onto the TiO₂ surface. It is proposed that the basic reactant adsorbs at Lewis acid sites present at the TiO₂ surface. The dehydrogenation reaction is initiated by visible-light excitation of the resulting surface complex and a subsequent single-electron transfer from the excited N-heterocycle via the conduction band of TiO₂ to O₂. Ni(II) ions possibly serve as an electron transfer bridge between the conduction band of TiO₂ and O₂, while the TEMPO derivative is assumed to act as a selective redox mediator involved in reactions of the generated reactive oxygen species.

Full text of DOI:10.1021/acscatal.9b03322

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Article
Visible-Light Mediated Photocatalytic Aerobic Dehydrogenation
of N-Heterocycles by Surface Grafted TiO2 and 4-Amino-TEMPO
Narmina O. Balayeva, Nan Zheng, Ralf Dillert, and Detlef W. Bahnemann
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b03322 • Publication Date (Web): 15 Oct 2019
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Visible-Light Mediated Photocatalytic Aerobic
Dehydrogenation of N-Heterocycles by Surface
Grafted TiO2 and 4-amino-TEMPO
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Narmina O. Balayeva a*, Nan Zheng b*, Ralf Dillert a,c, Detlef W. Bahnemann a,c,d*
a Institute of Technical Chemistry, Gottfried Wilhelm Leibniz University of Hannover, Callinstr.
5, D-30167 Hannover, Germany
b
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701
(USA)
c
Laboratory of Nano and Quantum Engineering, Gottfried Wilhelm Leibniz University of
Hannover, Schneiderberg 39, D 30167 Hannover, Germany
d Laboratory “Photoactive Nanocomposite Materials”, Saint-Petersburg State University,
Ulyanovskaya str. 1, Peterhof, 198504 Saint-Petersburg, Russia
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ABSTRACT:
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Herein, the visible-light-induced dehydrogenation of N-heterocycles such as
tetrahydroquinolines, tetrahydroisoquinolines, and indolines in O2-containing suspensions of a
commercially available titanium dioxide photocatalyst yielding the corresponding heteroarenes is
presented. 4-amino-2,2,6,6-tetramethylpipiridinyloxyl (4-amino-TEMPO) was found to exhibit a
beneficial role as it increased the yield and improved the selectivity of the dehydrogenation
reaction. Both the selectivity and the yield are further enhanced by grafting 0.1 wt% Ni(II) ions
onto the TiO2 surface. It is proposed that the basic reactant adsorbs at Lewis acid sites present at
the TiO2 surface. The dehydrogenation reaction is initiated by visible light excitation of the
resulting surface complex and a subsequent single electron transfer from the excited N-
heterocycle via the conduction band of TiO2 to O2. Ni(II) ions possibly serve as an electron
transfer bridge between the conduction band of TiO2 and O2, while the TEMPO derivative is
assumed to act as a selective redox mediator involved in reactions of the generated reactive
oxygen species.
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KEYWORDS: dehydrogenation, N-heterocyclic amines, surface complex, TiO2, visible light
INTRODUCTION:
N-heteroarenes are considered as a privileged structure in medicinal chemistry and material
science enabling requisite functionalities. Therefore, the development of innovative methods for
N-heteroarene synthesis as well as for the improvement of existing synthesis methods became an
essential topic in contemporary organic synthesis.1,2 Compared to the commonly used cross-
coupling strategy that relies on the availability of the pre-functionalized heteroarene precursors,
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dehydrogenation of N-heterocycles provides a complementary approach capable of introducing
substituents to the saturated N-heterocycle core. This feature overcomes constraints of the
precursor in the former approach and thus permits the synthesis of substituted N-heteroarenes
that are not accessible by the cross-coupling reaction.
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In general, the dehydrogenation of N-heterocyclic amines is classified into two subclasses:
acceptorless and acceptor assisted dehydrogenation, depending on whether a hydrogen atom
acceptor is used. Organometallic complexes composed of Ru, Ni, Co, or Ir have been extensively
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developed as homogenous catalysts for the acceptorless dehydrogenation of N-heterocycles,
however, the catalysts in these reaction systems are not recyclable. Therefore, alternative
carbon-supported metal catalysts8 such as hydroxyapatite-bound Pd 9 and Pt/C 10 have been used
to replace the organometallic complexes in the acceptorless dehydrogenation. Most recently, Pd-
doped hydrotalcite catalysts were used for the acceptorless dehydrogenation of both, primary and
secondary amines at 140°C in the p-xylene solvent.11 Similarly, an acceptorless dehydrogenative
aromatization of cyclic amines by Pd/LDH (layered double hydroxide) catalysts was also
reported.12 Nevertheless, most of the existing heterogeneous catalytic systems employed for the
acceptorless dehydrogenation involve noble metals or require relatively forcing reaction
conditions (e.g., temperatures >140 °C and/or long reaction times) thus restricting their
applicability on large scales.
On the other hand, for the acceptor assisted dehydrogenation, various chemical oxidants such
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as 2,3-dichloro-5,6-dicyano-l,4-benzoquinone13, chloranil14, and selenium have been used in
stoichiometric amounts as the respective hydrogen acceptor. Conversely to these harsh methods,
considerable endeavors have been laid on the oxidative dehydrogenation of N-heterocycles based
15,16
on homogeneous catalysts such as copper
or oxyvanadium-based systems17 in air or O2
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environment. The heterogeneous counterpart has also been studied noticeably, with quite diverse
catalysts such as transition metal or metal oxide nanoparticles on graphene or activated carbon,
18–21 gold nanoclusters22, etc. having been reported to promote the dehydrogenation reactions.
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Unlike the approaches mentioned above, visible-light-harvesting photocatalytic
dehydrogenation reactions can be successfully performed under considerable milder reaction
conditions. Nevertheless, the true potential of photo-induced dehydrogenation catalysis is still
rather unexplored compared to the metal-catalyzed thermal dehydrogenation processes. For
example, the visible light-mediated oxidative dehydrogenation of N-heterocycles at ambient
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temperature using Ru(bpy)3Cl2·6H2O
and a dual catalyst system employing the Fukuzumi
acridinium salt with Pd(BF4)2 as photocatalysts have recently been reported.24 Later, rose
Bengal has been used to replace organometallic complexes for the dehydrogenation of N-
heteroarenes.25 The dehydrogenation of N-heterocycles under oxygen free inert condition and at
room temperature was also studied employing Ru(bpy)3Cl2·6H2O as visible-light active
photosensitizer coupled with Co(dmgH)2PyCl as co-catalyst.26 Regardless of the improved
reaction conditions, the recyclability and the cost-efficiency are still remaining as main issues
because of the employed organometallic complexes.
Therefore, herein a visible light-mediated dehydrogenation method for N-heterocycles using a
heterogeneous recyclable and economical photocatalyst is presented for the first time (Scheme
1.). For this purpose, TiO2 was used as the main photocatalyst. TiO2 is one of the most active and
also widely used heterogeneous photocatalysts due to some outstanding features such as stability,
non-toxicity, as well as cost-efficiency, abundancy, and reusability. Furthermore,
photocatalytically active TiO2 is commercially available in both, high quality and sufficient
quantity. Although TiO2 has been extensively exploited as photocatalyst for energy and
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environmental applications, its use in organic synthesis remains rather unexplored particularly
compared to homogeneous photocatalysts such as ruthenium and iridium complexes or organic
dyes.27 On the other hand, due to its large bandgap energy (Eg(rutile)=3.0 eV, Eg(anatase)=3.2 eV),
titania can only be excited by UV light, which usually results in poor chemoselectivity. To
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address the intrinsic limitations of TiO2 and develop a visible-light active photocatalytic system,
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numerous new strategies have been considered and employed.
It was found that upon
adsorption of tertiary amines on the surface of TiO2, a visible-light-harvesting surface complex is
formed due to Lewis acid-base interactions resulting in a red-shift of the absorption spectrum by
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about 10 nm.
Such approach avoids the formation of holes in the valence band of the
semiconductor that often provoke overoxidation in TiO2-catalyzed photochemistry. Thus, instead
of excitation of an electron from the valence band to the conduction band in TiO2, the adsorbed
amine injects an electron to the conduction band, which in turn donates this electron to O2,
yielding the superoxide radical anion. Previously, a similar approach has also been utilized to
develop a Diels–Alder reaction of indoles with electron-rich dienes in which indole-TiO2 surface
complexes are formed and identified as being responsible for visible light absorption.34,35
Moreover, the visible-light mediated oxidation of primary and secondary amines into the
corresponding imines employing surface complexes of different organic molecules such as
phenol36, catechol37, N-hydroxyphthalimide38, and salicylic acid39 on TiO2 in the presence of
TEMPO derivatives has been reported.
In the present work, transition metal nanoparticles or ions have been grafted onto the TiO2
surface to further improve the photocatalytic activity of TiO2 for the dehydrogenation of N-
heterocycles. Most likely these grafted metal ions on the surface of the TiO2 photocatalyst serve
as electron shuttles thus transferring the excited electrons to O2 and hence retarding their fast
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decay.40 Additionally, cooperative catalysts have been designed merging the TiO2 photocatalyst
with different derivatives of TEMPO to improve the overall chemoselectivity of the system. We
thus developed a selective photocatalytic aerobic dehydrogenation method for N-heterocycles
(tetrahydroquinolines, tetrahydroisoquinolines, indolines, and others) by employing surface
grafted, commercially available UV-100 (TiO2) photocatalyst and 4-amino-TEMPO upon visible
light illumination.
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It was found that Lewis acid surface sides on TiO2 enable the surface complexation between the
base sides of N-heterocycles acting as photosensitizers which are excited by visible light to
initiate a single electron transfer from the N-heterocycle via the conduction band of TiO2 to O2.
The resulting superoxide radical is likely involved in the dehydrogenation of the amine radical
cation to yield the N-heteroarenes. The critical role of 4-amino-TEMPO for improving the
selectivity and the reaction yield over 90% by creating an oxidizing surface saturated with H2O2
(byproduct) is discussed. Both, the selectivity and the reaction yield are further enhanced by
grafting 0.1 wt% Ni(II) ion onto TiO2 in which the nickel ions serve as electron transfer bridges
between the conduction band of TiO2 and adsorbed molecular oxygen. A plausible reaction
mechanism is proposed and discussed.
EXPERIMENTAL SECTION
Synthesis of the photocatalysts:
Commercial TiO2 (Hombikat UV-100 from Venator with 100% anatase crystal phase and ~ 320
m2/g specific surface area) has been used as the photocatalyst (materials section is presented in
the Supporting Information, SI). The grafting of Fe(III), Cu(II), Ni(II), Co(II), or Nb(V)
nanoclusters on the surface of UV-100 was performed by following a simple impregnation
28,40,41
method that has been reported before.
In brief, metal salts with the appropriate ratio (0.1
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wt %) relative to titania were added into an aqueous TiO2 suspension and stirred at 90 °C for 1 h
to attain metal ion nanoclusters on the surface of TiO2. Subsequently, the suspension was rinsed
and centrifuged 3 times with copious amounts of deionized water. Afterward the precipitate was
dried at 110 °C for 24 h and milled into a fine powder. To prepare 0.1 wt % Pt, Rh, and Pd
photo-deposited TiO2 photocatalysts, a 50 mL single neck reactor was taken. The appropriate
amount of metal precursor salt was dissolved into 20 mL of methanol/deionized water mixture
(1:3 ratio), and 1 g of commercial TiO2 UV-100 was added into the system before closing the
reactor. The suspension was continuously stirred for 24 h under 1 mW/cm2 UV light irradiation.
Afterward, the suspension was centrifuged, and the powder was rinsed three times with 50 mL of
water. The obtained precipitant was dried at 110 °C for 24 h.
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To gain some insight into the structure of the as-prepared surface grafted TiO2 (namely
Ni(II)/TiO2), we used a series of characterization techniques including X-ray diffraction (XRD)
(SI Figure S2), transmission electron microscopy (TEM) (SI Figure S3), diffuse reflectance
spectroscopy (DRS) (SI Figure S4), FTIR spectroscopy, Brunauer–Emmett–Teller (BET), N2
adsorption-desorption isotherms (SI Figure S8), and electron-paramagnetic resonance
spectroscopy (EPR) (SI Figure S9). The content of Ni ions grafted onto TiO2 surface was
determined using ICP-OES measurement. Instrumental conditions and detailed characterization
techniques are presented in the SI.
Photocatalytic Reaction Procedure:
10 mg TiO2 or surface-modified TiO2 (0.03 mol·L-1) dispersed in 4 mL of an appropriate solvent
were filled in an oven dried 20 mL vial employed as the photoreactor. 4-amino-TEMPO or
different TEMPO derivatives (13.7 mg, 0.08 mmol, 20 mol% respective to the substrate) and 1, 2,
3, 4-tetrahydroquinoline (0.4 mmol) or other substrates were added to the suspension. The
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reaction mixture was sonicated for 5 min until the TiO2 catalyst was completely dispersed. After
tightly sealing the suspension, the reaction environment was purged with molecular oxygen for
about 20 min to displace any air present in the reactor. The reaction was carried out for 24 h
under visible light illumination (LED array with λmax=453 nm) with continuous stirring.
Afterward, the catalyst was separated from the reaction mixture by centrifuging. The product was
isolated employing flash column chromatography. In the case of optimization reactions, shown in
Table 1, benzyl alcohol (20.6 μL, 0.2 mmol, 50 mol %) was added to the solution as an internal
standard. 1, 2, 3, 4-Tetrahydroquinoline was chosen as the representative substrate to optimize
the reaction conditions.
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The corresponding calibration curves of the starting material (reactant) and the product were
obtained by GC-FID (gas chromatography - flame ionized detector). The yield and the rest of the
reactant were calculated with the calibration curves equation obtained by GC-FID. (For details
see Fig. S1(a) and S1(b) in the SI). In brief, the yield of the product (Y), the conversion of the
reactant (C), and the selectivity of the reaction (S) have been calculated employing the equations
np
(1)
(2)
푌 = n × 100
R
0
nR0 ― nR
퐶 =
× 100
= C × 100
is the amount of the product, is the starting amount of the reactant, and
nR0
Y
S
(3)
where
is the
np
nR
nR
0
remaining amount of the reactant.
The apparent quantum yield ( 푎푝푝) of product formation has been calculated to compare the
훷
photocatalytic activity of the established reaction conditions (Table 1). The apparent quantum
yield (
) was calculated with Φapp = rate of formation / photon flux.
훷푎푝푝
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The photon flux was calculated with
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퐼 ·퐴·휆
(4)
푝ℎ표푡표푛 푓푙푢푥 = 푁 ·ℎ·푐
퐴
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and the irradiance I= 4 mW/cm2, the irradiated area A= 4 cm2, and the wavelength λ=453 nm.
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NA, h, and c are the Avogadro constant, Planck number, and speed of light, respectively.
RESULTS AND DISCUSSION:
The absorption spectra of UV-100, UV-100 with 1,2,3,4-tetrahydroquinoline (1,2,3,4-THQ)
in CH3CN solvent has been measured to scrutinize the effect of N-heterocyclic amines on the
absorption spectrum of TiO2 and to determine the suitable wavelength of light source for the
dehydrogenation reactions (Figure 1). A solution of 1,2,3,4-THQ in CH3CN absorbs at
wavelengths lower than 350 nm while TiO2 in CH3CN absorbs at wavelengths lower than 380
nm. However, a significant red-shift about 60 nm is observed in the absorption spectra of TiO2
suspensions containing 1,2,3,4-THQ which is clear evidence for the formation of a visible light-
responsive surface-complex. In comparison, no red-shift is observed in the presence of non-
semiconducting SiO2 with a high surface area, and the absorption edge observed at about 350 nm
and weak absorption edge up to 450 nm corresponds to 1,2,3,4-tetrahydoquinoline. These results
strongly suggested that the surface complex is formed due to the Lewis acid (TiO2)/base
(tetrahydroquinolines) interaction. To support this data, an ATR-FTIR spectroscopy
measurement was performed, and the band at around 1600 cm-1 and 3400 cm-1 corresponding to a
free amine group vanished upon the addition of TiO2 (UV-100). This ATR-FTIR data was
another clear evidence of the surface-complex formation (Figure 2).
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Inspiring from this evidence, we conducted the optimization reactions using 1,2,3,4-THQ as
the model substrate, under blue light illumination (λ=453 nm) over UV-100 and 1 atm O2 in
CH3CN (Table 1, entry 1) for 24 h. The completely dehydrogenated quinoline was formed with
a yield of 35%. However, the selectivity was found to be rather poor. Addition of 4-amino-
TEMPO (Table 1, entry 2) or TEMPO (Table 1, entry 3) almost doubled the selectivity, yielding
quinoline in 79% yield. While, TEMPO was found to be stable during illumination, 4-amino-
TEMPO was degrading gradually and after 24 h of illumination no peak associated to 4-amino-
TEMPO was observed in the GC-FID chromatogram. Control studies showed that both, the
photocatalyst UV-100 (Table 1, entry 5) and light (Table 1, entry 6) was essential for the
dehydrogenation. O2 was found to be also critical for the reaction as no reaction occurred in an
inert (argon) atmosphere with UV-100 or Ni/UV-100 as the photocatalyst (see SI Table S1,
entry 5 and 6). A LED lamp emitting at a wavelength of 453 nm was found to be optimal light
source. Employing a 505 nm LED lamp resulted in a significant decrease of the reaction yield
(see SI Table S1, entry 7 and 8). Replacement of UV-100 by P25 (commercial TiO2 from
Evonik Degussa, with ~50 m2/g surface area, 20% rutile and 80% anatase) significantly reduced
the yield and the conversion (Table 1, entry 4). On the other hand, control reactions with
different metal oxides such as Al2O3, WO3, ZnO, and SiO2 gave negligible yields (See SI Table
S2, entries 1-4). This is in agreement with the absorption spectroscopy results of 1,2,3,4-THQ
and SiO2 mixture evincing that this oxide is not capable of catalyzing the dehydrogenation
reaction due to non-occurring surface complexation (SI, Table S2. entry 4). Solvent studies
revealed that CH3CN and i-PrOH are suitable dispersants, where i-PrOH shows slightly better
activity for the visible light-mediated dehydrogenation of tetrahydroquinoline in the presence of
a heterogeneous photocatalyst (SI Table S1, entries 1-4). To further improve the selectivity and
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the yield, we investigated various metal ions grafted and noble metal photodeposited UV-100 as
the photocatalyst. Metal ion grafted UV-100 (Cu2+, Ni2+, Co2+, Fe3+, Nb5+) consistently show
improved selectivity and yield in comparison with bare UV-100 (Table 1, entries 7-11). On the
other hand, UV-100 samples with 0.1 wt% photodeposited noble metal (Pd, Ru, and Rh) shows
significantly lower conversion of the probe compound (60%, 49%, and 30%, respectively) than
UV-100 even though the selectivity remained high (97%, 100%, and 88%) (Table 1, entries 12-
14). The specific surface area of UV-100 and surface grafted TiO2 with nickel ions was
measured to be 320 m2/g and 318 m2/g, respectively while showing similar nitrogen
physisorption isotherms (SI Figure S8). No peaks corresponding to metallic nickel or nickel
oxide were observed on X-ray diffractograms (SI, Figure S2) while TEM micrographs show a
highly porous morphology with a particle size of 3-5 nm (SI, Figure S3).
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The time-dependent experiments were performed with the optimized reaction condition using i-
PrOH as a solvent and UV-100 in the presence or the absence of 4-amino TEMPO, and 0.1 wt%
Ni(II) grafted UV-100 in the presence of 4-amino-TEMPO as photocatalysts under visible light
illumination. The formations of the yield and the selectivity of the dehydrogenation reaction of
1,2,3,4-THQ in the presence of three different photocatalysts within 24 hours with 3 hours time
interval have been calculated from GC-FID data ( Equation 1 and 3) and are shown in Figure 3.
As becomes obvious from Figure 3 (a), large amounts of quinoline are produced in the presence
of Ni (II)-grafted UV-100 and 4-amino TEMPO. Significantly lower amounts of product were
obtained in the presence as well as in the absence of 4-amino-TEMPO. Accordingly, the yields
at a point in time during illumination calculated from the data given in Figure 3 (a) were found
to decrease in the order Ni(II)/UV-100 + 4-amino-TEMPO > UV-100 + 4-amino-TEMPO > UV-
100 (Figure 3b). The results reveal that 4-amino-TEMPO significantly improves the reaction
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selectivity. Concomitantly, the selectivity was observed to be ~10 % higher when Ni(II)-grafted
UV-100 is used instead of suspension containing bare UV-100.
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Using the improved photocatalyst, 0.1 wt% Ni(II) ion-grafted TiO2, we compared TEMPO and
three other TEMPO derivatives in the dehydrogenation reaction, establishing 4-amino-TEMPO
as the optimal redox mediator for improving selectivity (Table 1, entries 15-18).
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The range of substrates was investigated under the optimized reaction conditions inspired by
the high photocatalyst activity of 0.1 wt% Ni/UV-100 and 20 mol% 4-amino-TEMPO in i-PrOH
and an O2 atmosphere (1 atm) at room temperature (Table 2). 1,2,3,4-THQs bearing a methoxy
(2b), methyl (2c and 2f), chloride (2e), or both a methyl and carboxyl group (2g) gave good to
excellent yields of quinolines. However, 1,2,3,4-THQs having a nitro or a hydroxy group at C-7
failed to dehydrogenate. The inactivity of the former substrate was probably due to difficult
oxidation of the aniline moiety caused by the strongly electron-withdrawing nitro group.
Whereas the inertness of the hydroxylated compound is probable owning to a competitive
complex formation on the TiO2 surface via the hydroxyl group. To test this hypothesis, the OH
group was protected as TBDMS (tert-butyldimethylsilyl) ether and then subjected to the standard
conditions. The desired quinoline 2d was isolated in 83% yield. 1,2,3,4-Tetrahydroisoquinolines
reacted quite differently from other N-heterocycles as they easily afford the partial
dehydrogenation product under the reaction conditions optimized for the dehydrogenation of
tetrahydroquinolines. The unsubstituted tetrahydroisoquinoline gave a mixture of the completely
dehydrogenated product 2h and the partially dehydrogenated product 2h* in 42% yield and 52%
yield, respectively. Raising the reaction temperature to 47 °C improved the conversion to the
completely dehydrogenated product, and the fully aromatized product 2i was obtained in 75%
yield. However, when the methyl substituent of 1-methyl-1,2,3,4-tetrahydroisoquinoline is
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replaced by a larger group such as phenyl, the partially dehydrogenated product 2k* was found
to be the major product 54% yield with only 33% of the completely dehydrogenated product 2k
even when the temperature is raised to 47°C. Interestingly, 6,7-dimethoxy-1,2,3,4-
tetrahydroisoquinoline only yields the completely dehydrogenated product 2j in 81% yield at
room temperature. The enhanced reactivity of this compound is presumably due to the presence
of the two electron-donating methoxy groups.
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The developed method was also applied to the dehydrogenation of indoline and 2-
methylindoline under the optimized reaction condition with slight changes. Thus, the O2 amount
in air was found to be sufficient to mediate the dehydrogenation of unsubstituted indoline to
indole 2n in 84% yield. Significant decomposition of the reactant was observed when the
reaction was performed in an O2 atmosphere (1 atm) thus revealing that indoline is more reactive
than the 1,2,3,4-tetrahydroquinolines. On the other hand, 2-methyl-substituted indoline was
shown to be less reactive and more tolerant towards O2 than unsubstituted indoline. An O2
pressure of 1 atm was required to produce 2-methylindole 2o in good yield (76%). 1,2,3,4-
tetrahydroquinoxaline, which was also exhibited good reactivity, yielded quinoxaline 2l in 83%
yield using 1 atm O2. Similar to indolines and quinolines, dehydrogenation of 2-phenyl-2-
imidazoline to 2-phenylimidazole 2m was achieved with an excellent reaction efficiency (93%)
under optimized reaction condition.
Since the leaching of the impregnated active metal ion sites during the reaction, phase
transformation, and agglomeration of nanoparticles is ubiquitous in heterogeneous
photocatalysis, we examined the reusability of 0.1 wt% Ni/TiO2 by performing four consecutive
experimental runs (See SI for details on the recycling procedure). Conversion of the probe
compound, as well as the yield of the product and the selectivity of product formation, was found
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to be stable even after 4 cycles (Figure 4). The surface area of the photocatalyst decreased from
318 m2/g to 217 m2/g after the 2nd cycle of the reaction but remained relatively constant after the
3rd and 4th cycles (210 and 206 m2/g, respectively). However, the surface area was restored from
206 m2/g after the 4th cycle to 313 m2/g by dispersing the used photocatalyst in 20 mL deionized
water and illuminating with a 500 W solar simulator lamp for 2 hours at ambient temperature.
The photocatalyst’s color also turned from pale yellow to pure white during illumination and the
surface-cleaned catalyst displayed high reactivity (91% yield) and selectivity (93%) in the 5th
cycle (Figure 4). N2 adsorption-desorption isotherm studies show that although the catalyst’s
mesoporosity decreases after the 4th cycle, the selectivity does not decrease drastically.
Additionally, cleaning the catalyst’s surface by illumination led to recovering the pore size that
showed adsorption-desorption isotherm similar to non-used 0.1 wt% Ni/TiO2 (SI Figure S8).
XRD and ICP-OES measurements did not reveal poisoning and leaching of the
photocatalyst, respectively. XRD patterns for bare TiO2, 0.1 wt% Ni/UV-100 before the 1st cycle
and after the 4th cycle displayed the typical crystal structure of the anatase phase without
showing the peaks corresponding to the nickel ion (SI Figure S2). Moreover, the ICP-OES
measurement showed that the content of nickel ions before and after the reaction did not change
drastically (before and after 4th cycle of reaction the content of nickel was 0.08 wt% with respect
to TiO2; see SI for sample preparation for the ICP-OES measurement).
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ATR-FTIR spectroscopy measurements were conducted to detect functional groups of organic
compounds adsorbed on the catalyst’s surface after the dehydrogenation reaction. Characteristic
bands at 2950 cm-1, 2370 cm-1, and 1640 cm-1, which were assigned to the stretching of C-H, C-
O and O-H groups of i-PrOH, respectively, as well as the broad band at 3400 cm-1, which
corresponds to the OH stretching of surface-adsorbed water molecules, were observed in all
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spectra (Figure 5). The intensity of this broad band at 3400 cm-1, was observed to start to
decrease after the 3rd cycle. The decline of the intensity of the OH stretching band was
rationalized by a gradual accumulation of organic compounds at the catalyst’s surface that results
in a displacement of the surface-adsorbed water by organic compounds. On the other hand, the
band at 1681cm-1, which was attributed to the C=N stretching, was observed only after the 3rd
cycle and disappeared after the catalyst was subjected to surface cleaning by solar light
illumination. Characteristic peaks of aromatic rings in the range of 1561 cm-1 (C=C), 1429 cm-1
(C-C), and 1276 cm-1 (Ar-N), were detected only in the used 0.1 wt% Ni/TiO2. This observation
was expected as those peaks were assigned to the imine products that were bound to the Lewis
acidic TiO2 surface.42 Based on the obtained results we propose a tentative mechanism for the
dehydrogenation reaction of tetrahydroquinolines as illustrated in Scheme 2.
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The 1,2,3,4-THQs binds to the surface of UV-100 to form a surface complex, which absorbs
visible light to become excited. Subsequently, the excited tetrahydroquinoline injects an electron
into the conduction band of the semiconductor UV-100. After being temporarily stored on the
surface grafted Ni ion, the photogenerated electron reduces O2 yielding the superoxide radical
anion. This radical anion abstracts two protons and one electron from the tetrahydroquinoline
radical cation thus forming the C=N bond. This sequence of reaction steps is repeated with the
partially dehydrogenated product as the reactant to complete the aromatization to the quinoline.
The grafted Ni ion (E°(Ni2+/Ni0)= -0.26V vs. NHE) 43 likely plays the role of an electron shuttle
which not only hinders the fast decay of the photogenerated electrons but also promotes the
reduction of O2 by conduction band electrons, thus enhancing the overall photo-activity of UV-
100. However, noble metal co-catalysts demonstrate relatively low reaction yield which can be
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explained by their electron scavenging capacity that retards the reaction momentum, eventually
causing low activity.
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In situ EPR measurements were performed with powders of 0.1 wt% Ni/UV-100 and bare TiO2
(UV-100) at 77 K in an argon atmosphere to examine the impact of the grafted Ni ion on the
electron shuttle process (Figure 6). In the dark, both samples showed characteristic peaks with g
values of g1=2.027, g2=2.009 and g3=2.005 (Signals D) which has been assigned to Ti4+-O2ˉ•
species.44 Upon UV-vis illumination, peaks at g1=2.018, g2=2.014 and g3=2.005 (Signals A) were
generated which have been proposed to correspond to the trapped holes, i.e., Ti4+-O˙¯-Ti4+-OH¯
radicals at the surface sites of TiO2. 45,46 Additionally, signals gǁ=1.96 and g﬩=1.990 (Signals B)
are formed during irradiation. These signals are indicating the presence of Ti3+ which are formed
by trapping of photogenerated electrons.47 The intensity of the signals B of the Ni/UV-100
photocatalyst is drastically decreased in comparison with bare TiO2 (Figure 6 (a)). This
observation is consistent with a previous report 48, which proved that the grafted Ni(II) ions
located on the surface and surface defects of TiO2, reduce the amount of Ti3+ species by trapping
photogenerated electrons. The broad weak signal at around g = 2.06 (Signal C) observed in both
bare TiO2 and 0.1 wt% Ni/UV-100 corresponds to the surface-adsorbed O2 molecules, which act
as an electron acceptors. 49
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The presence of a redox mediator such as TEMPO and 4-amino-TEMPO in the photocatalyst
suspension was found to have only a small impact on the conversion of the reactant but it
significantly increased the yield and selectivity of the desired reaction product (Table 1, entry 1-
3). The substantial effect shown by 4-amino-TEMPO prompted us to investigate its role in the
dehydrogenation reaction. To the best of our knowledge, TEMPO has been reported only by
Zhao50 and Chen51 as a cocatalyst in TiO2-catalyzed photochemistry. Somewhat related to this
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method, Lei reported the use of TEMPO as an organo-electrocatalyst in electrochemical
dehydrogenation of N-heterocycles in N2 atmosphere where TEMPO was proposed to be directly
responsible for the oxidation of N-heterocycles and subsequent dehydrogenation.52 However, we
observed that 4-amino-TEMPO plays a different role in this method. Our hypothesis is built
upon a noticeable phenomenon we observed during the screen studies. Without any redox
mediator namely 4-amino-TEMPO in the suspension (Table 1, entry 1) the initially light yellow
suspension became dark brown during the light-induced reaction in addition to the accompanied
low selectivity and yield. In contrast, in the presence of 4-amino-TEMPO, the reaction color
maintained light yellow throughout the reaction. We attribute the low conversion and selectivity
and the color change observed in the absence of 4-amino-TEMPO to the formation of H2O2/TiO2
surface complexes (See SI Figure S7), which saturate the TiO2 surface and prevent the formation
of the N-heterocycle-TiO2 surface complex necessary for an efficient electron transfer from the
excited organic moiety to the conduction band of the semiconducting TiO2. TEMPO and its
derivatives are known to be stable radicals and bear one-electron reversible oxidation to form
oxoammonium salts (TEMPO+).53 These compounds have been investigated as redox mediators
for electrochemically oxidizing primary and secondary alcohols.54,55 Sen and his group have
introduced the oxidation of hydrogen peroxide molecules over 4-hydroxy TEMPO.56 Lately, it
has been reported the electrocatalytic anodic oxidation of H2O2 by nitroxyl radicals and revealed
that among the TEMPO series, 4-amino-TEMPO shows the highest catalytic efficiency due to
the strong electron-withdrawing effect of an amino substituent.57 This evidence is in agreement
with our observation. Taking into account of developed insights over nitroxyl radicals, we have
anticipated the ongoing reaction pathways in our system. (Eqs. (5)-(8)).
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H2O2 + TiIV
Ti IV – OOH (surf.) + H+
(5)
(6)
(surf.)
NH2
NH2
-•
+
O2
O2
+
N
O
N
O
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NH2
NH2
TiIV
Ti IV – OOH (surf.)
+
+ OOH•
+
(7)
(8)
(surf.)
N
O
N
O
-• + H+
OOH•
O2
Thus, the generation of hydrogen peroxide molecules as a byproduct during the dehydrogenation
process of N-heterocycles initiates the formation of a surface complex with titania (Eq. (5). Since
4-amino-TEMPO shows weak absorption at the visible light region of 470 nm (SI Figure S6) we
expected the oxidation of TEMPO to the TEMPO+ and one-electron reduction of an oxygen
molecule to the superoxide radical anion (Eq. (6)). On the other hand, in contrast to TEMPO,
TEMPO+ is not paramagnetic. Therefore, to support this suggestion, EPR experiments with 4-
amino-TEMPO in the presence and in the absence of visible light (λ= 453 nm) illumination in an
oxygen atmosphere have been performed. The results show that the intensity of the EPR signals
belonging to 4-amino-TEMPO slightly decreases upon illumination which is suggesting that the
cation 4-amino-TEMPO+ is formed upon visible light illumination (SI Figure S10). Hence, the
generated oxoammonium cation leads to the decomposition of the surface titanium (IV)
hydrogen peroxide complex and subsequent generation of a superoxide radical (Eqs. (7)-(8)).
To test this hypothesis, we measured the concentration of H2O2 formed during the
dehydrogenation reaction in the absence (Table 1, entry 1) and the presence of 4-amino-TEMPO
(Table 1, entry 2). Indeed, the concentration of H2O2 is observed to be significantly higher in the
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absence of 4-amino-TEMPO (see SI Figure S11).25 The lower concentration of H2O2, which is a
strong oxidizing agent, observed in the presence of the 4-amino-TEMPO resulted in minimizing
possible side reactions, thus improving the selectivity of the desired reaction.
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Conclusions
In summary, a visible-light-mediated aerobic dehydrogenation method of N-heterocyclic amines
is developed using commercially available anatase TiO2, UV-100. By employing three-pronged
approach (visible light excitation of a N-heterocycle-TiO2 surface complex, Ni(II) ion-grafted
TiO2, and 4-amino-TEMPO for improving selectivity) we successfully achieved to activate the
UV-active TiO2 to be a highly selective visible light responsive photocatalyst. The conspicuous
studies regarding the N-heterocycle/TiO2 surface complex formation supported that organic
transformation over bare TiO2 upon visible light illumination is practicable. The essential role of
4-amino-TEMPO was improving reaction selectivity to prevent the saturation of the TiO2 surface
by H2O2 and also assist its degradation. The surface-grafted TiO2 with 0.1 wt% Ni(II) ion
improved the yield and the selectivity, most probably because the metal ion acts as an electron
transfer bridge, and reduction process occurs to produce superoxide radical anions. One of the
well-known issues that plague TiO2 as a successful photocatalyst in organic synthesis is non-
selective oxidation of organic reactants and products resulting in poor yields and selectivity. The
present approach employing TiO2 as the photocatalyst and 4-amino-TEMPO as a selective redox
mediator under mild reaction conditions effectively overcomes this existing issue for
synthesizing N-heterocyclic aromatic compounds. Importantly, the present method comprises
low-cost, environmentally friendly photocatalyst, and visible light. Moreover, the photocatalytic
system maintains its chemical stability presenting high selectivity and the reaction yield over
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recycles. The achieved results demonstrate that the method is remarkably applicable for the
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numerous substrate scopes.
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FIGURES
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Figure 1. Normalized extinction spectra for the bare TiO2 (UV-100), SiO2/1,2,3,4-
tetrahydroquinoline,
TiO2/1,2,3,4-tetrahydroquinoline,
and
1,2,3,4-tetrahydroquinoline.
Absorption spectroscopy measurements were performed at the same concentration of the catalyst
and substrate as appropriate to the organic reaction condition in a CH3CN solvent.
Figure 2. FTIR spectra of CH3CN solvent, 1,2,3,4-tetrahydroquinoline, and UV-100 (TiO2) /
1,2,3,4-tetrahydroquinoline suspension. The right figure shows magnification of the area
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between dashed lines in the left figure. All measurements were performed at the same
concentration of the catalyst and substrate as appropriate to the organic reaction condition.
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Figure 3. Amounts of products formed during 24 h of illumination (a) and time-dependent
change in the yield and selectivity (b). Reactions conditions: 10 mg photocatalysts (UV-100
or Ni (II)-grafted UV-100), LED lamp, λ=453nm, 4 mW/cm2, 1 atm O2, 0.4 mmol 1,2,3,4-
THQ, 0.08 mmol 4-amino-TEMPO, 4 mL i-PrOH.
Figure 4. Oxidative dehydrogenation of 1,2,3,4-tetrahydroquinoline: recycling of 0.1 wt%
Ni/TiO2. Reactions condition: 10 mg photocatalyst, 24 hours visible light illumination (LED
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lamp, λ=453nm, 4 mW/cm2), 1 atm O2, 0.4 mmol 1,2,3,4-THQ, 0.08 mmol 4-amino-TEMPO, 4
mL i-PrOH. The 5th cycling was performed after cleaning the catalyst by solar light illumination
for 2 h. Yields calculated according to the GC-FID calibration using benzyl alcohol as an internal
standard.
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Figure 5. ATR-FTIR spectra of the bare TiO2 (UV-100) (black line), 0.1 wt% Ni grafted TiO2 before
reaction (blue line), used 0.1 wt% Ni grafted TiO2 after 3 cycles of the reaction (red line), and used
0.1 wt% Ni grafted TiO2 after cleaning with 500W solar simulator light (green line)
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Figure 6. In situ EPR spectra at 77K of TiO2 (a) and 0.1 wt% Ni(II) ion-grafted TiO2 (b) in the
dark and under 1 min; 2 min; 3 min; and 5 min UV-vis light irradiation (Xe lamp, λ=300-
450nm). The spectra under light irradiation are obtained by subtracting the spectrum in the dark.
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SCHEMES
Previous works:
This work:
+ H2O2
R
R
0.1 wt% Ni/TiO2
N
N
R
+ H2O2
R
H
20 mol% 4-amino-TEMPO
N
N
H
blue LED
24h, r.t.
1) Ru(bpy)32+, visible light, O2, r.t.
2) Organo-photoredox, air, visible light, r.t.
 Non-toxic photocatalysts/solvent
 Low-cost
 Recyclable/reuse
 Noble metal free
Scheme 1. Oxidative dehydrogenation of N-heterocyclic amines into the corresponding imines.
Scheme 2. A plausible mechanism of the ongoing reaction in the presence of 4-amino-TEMPO
and surface-grafted 0.1 wt% Ni/TiO2 photocatalyst.
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Table 1. Optimization of the reaction conditions a
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TiO2, co-catalyst
+H2O2
blue LED
453 nm, 1atm O2
N
N
H
1a
2a
9
훷퐴푝푝
Entry
Catalysts
Redox mediator
C
(%)
Y
S
(%) b
(%) c
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1d
2
3
UV-100
UV-100
UV-100
P25
-
81
98
86
24
3
n.d.
100
100
95
100
100
62
49
34
80
69
93
100
35
79
70
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3
n.d.
91
91
90
90
93
60
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30
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77
92(91g)
43
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81
42
100
n.d.
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91
95
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97
100
88
73
88
83
92
0.95·10-2
2.14·10-2
1.90·10-2
0.27·10-2
0.08·10-2
-
2.47·10-2
2.47·10-2
2.44·10-2
2.44·10-2
2.52·10-2
1.63·10-2
1.33·10-2
0.81·10-2
1.57·10-2
1.57·10-2
2.09·10-2
2.49·10-2
4-amino-TEMPO
TEMPO
4
-
5e
6d
7
-
4-amino-TEMPO
-
UV-100 (in dark)
Cu/UV-100
Ni/UV-100
Nb/UV-100
Fe/UV-100
Co/UV-100
Pd/UV-100
Ru/UV-100
Rh/UV-100
Ni/UV-100
Ni/UV-100
Ni/UV-100
Ni/UV-100
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
4-amino-TEMPO
TEMPO
8
9
10
11
12
13
14
15f
16f
17f
18f
4-hydroxy-TEMPO
4-oxo-TEMPO
4-amino-TEMPO
19
Ni/UV-100
-
93
57
61
1.54·10-2
a Reactions condition: 10 mg photocatalyst TiO2 (UV-100 or P25), 24 h visible light illumination
(LED lamp, λ=453nm, 4 mW/cm2), 1 atm O2, 0.4 mmol 1,2,3,4-THQ, 0.08 mmol TEMPO
derivatives, 4 mL CH3CN. b calculated according to the GC-FID calibration using benzyl alcohol
as an internal standard. c ratio of yield over conversion. d no TEMPO. e no TiO2. f i-PrOH instead
of CH3CN. g isolated yield.
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Table 2. Dehydrogenation of other derivatives of N-heterocyclic amines a
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Ni(II)/TiO2
Z
X
Z
X
( )
Y
( )
Y
n
n
R1
4-Amino TEMPO
i-PrOH, 1atm O2
blue LED 453 nm
R1
+ H2O2
R2
R2
1a-o
2a-o
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11
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21
22
23
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25
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X, Y, Z = N or C
n = 0 or 1
Yield (%)b
75
Yield (%)b
Substrates
NH
Substrates
N
Entry
Products
N
Entry
1
Products
9c
91
N
2a
H
2i
1i
1a
O
O
O
O
10d
11c
81
2
94
91
NH
N
N
N
O
O
H
1b
2b
1j
2j
33; 54*
N
3
4
N
NH
N
N
2c
H
1c
83
92
74
2k
1k
2k*
TBSO
N
TBSO
Cl
N
H
1d
1e
2d
H
N
N
12
83
Cl
5
6
N
N
H
N
N
H
2e
2f
2l
1l
N
N
13
93
84
N
N
N
N
H
H
H
1f
2m
1m
14e
N
7
8
93
N
H
N
N
H
HO
O
H
HO
O
2g
1n
2n
1g
42; 52*
76
15
N
N
NH
N
N
H
H
1o
2o
2h*
2h
1h
a
Reactions condition: 10 mg photocatalyst, 24 hours visible light illumination (LED lamp,
λ=453 nm, 4 mW/cm2), 1 atm O2, 0.4 mmol organic substrate, 0.08 mmol 4-amino-TEMPO, 4
b
c
d
mL i-PrOH, room temperature. The yields are those of the isolated products. 47 °C. 1:1
CH2Cl2: i-PrOH was used as the solvent. e Air was used. * Partial dehydrogenation yield.
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ASSOCIATED CONTENT
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Supporting information. A listing of the contents of each file supplied as SI should be included.
For instructions on what should be included in the SI as well as how to prepare this material for
publications, refer to the journal’s Instructions for Authors.
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The following files are available free of charge.
Materials and chemicals, results of the analytical methods (GC-FID, XRD, TEM, UV-vis, BET,
ICP-OES, EPR, ATR-FTIR, and FTIR), data of control reactions, catalyst recycling procedure,
detection of hydrogen peroxide, NMR characterization of compounds (PDF).
AUTHOR INFORMATION
Corresponding Author
*Narmina O. Balayeva; balayeva@iftc.uni-hannover.de
* Nan Zheng; nzheng@uark.edu
* Detlef W. Bahnemann; bahnemann@iftc.uni-hannover.de
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval
to the final version of the manuscript.
ACKNOWLEDGMENT
Narmina Balayeva gratefully acknowledges the financial support from Graduate Academy of
Leibniz University Hannover in the frame of “Research Stay Abroad Program” at the University
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of Arkansas, Chemistry and Biochemistry Department. The authors would like to thank M.Sc.
Barbara Nunes from Prof. D. Bahnemann group, Institute of Technical Chemistry at the Leibniz
University of Hannover for XRD and TEM measurement, and M.Sc. Malte Schäfer from Prof. P.
Behrens group, Institute of Inorganic Chemistry at the Leibniz University of Hannover for the
BET (physisorption isotherms) measurement. Institute of Geology for ICP-OES, Laboratorium
für Nano- und Quantenengineering (LNQE) for TEM and Institute of Inorganic Chemistry at the
Leibniz University of Hannover for ATR-FTIR and BET equipment are kindly acknowledged.
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