Heterogeneous photocatalysis of azides: Extending nitrene photochemistry to longer wavelengths

Article abstract of DOI:10.1039/d0cc04118a

The photodecomposition of azides to generate nitrenes usually requires wavelengths in the <300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.

Full text of DOI:10.1039/d0cc04118a

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DOI: 10.1039/D0CC04118A
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Heterogeneous photocatalysis of azides: extending nitrenes
photochemistry to longer wavelengths
Ignacio D. Lemira,b, Juan Argüellob, Anabel E. Lanterna*a, Juan C. Scaiano*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The photodecomposition of azides to generate nitrenes usually The reduction of azides to amines is a valuable synthetic
requires wavelengths in the <300 nm region. Here we show this approach due to the azide’s ease of preparation and good
reaction can be readily performed in the UVA region (368 nm) when stability (room temperature and air) and their important role as
2
catalyzed by Pd-decorated TiO2. In aqueous media the reaction protecting groups.1, This process is frequently performed
leads to amines, with water acting as H source; however, in non- under reductive conditions using high H2 pressures3-5 or hydride
6,
7
9
protic and non-nucleophilic media – such as acetonitrile – nitrenes sources
that leave organic debris behind.8, The direct
recombine to yield azo compounds, while azirine-mediated trap- photolysis of aromatic azides could also yield the formation of
ping occurs in the presence of nucleophiles. The heterogeneous amines by promoting the extrusion of nitrogen and generation
process facilitates catalyst separation while showing great of nitrenes;10, 11 however, this well-known process is usually
chemoselectivity and high yields.
carried out under extreme irradiation conditions (<300 nm).
Recent contributions12, 13 have explored the use of visible light,
although using non-green solvents and harsh H sources. The use
of copper-based catalysts was also explored, taking advantage
of the well-known interaction between Cu and azide groups.3, 6,
In this work, we demonstrate that the conversion of azides to
nitrenes can be performed at long wavelengths (UVA) when Pd-
decorated-TiO2 (Pd@TiO2) is the catalyst, leading to formation
of azo compounds, azirine mediated trapping, and reduction to
amines, all easily controlled by experimental parameters.
Aqueous media leads to water as the sole H source for the
reduction of azides into anilines using Pd-decorated TiO2 as
photocatalyst. The reaction is carried out under mild conditions
– water solvent, room temperature, inert atmosphere, UVA
14
Palladium species are also known as promoters for N2
extrusion from azides.15 We have previously shown that the use
of metal-decorated TiO2 as photocatalyst can facilitate transfer
17
hydrogenation reactions using the solvent as H source.16,
Particularly, it has been suggested that Pd–H species are prone
to be generated in materials such as Pd-decorated TiO2
(Pd@TiO2) under illumination.16 These species can act as
reductive sites for suitable acceptors on the Pd surface.
irradiation, heterogeneous catalyst
–
with great
chemoselectivity and high yields. These mild reductive
conditions usually lead to better selectivity and facilitate the
reaction workup, as the catalyst can be easily separated by
centrifugation or filtration, whereas oxidised solvent debris can
be eliminated during solvent removal. In addition, the use of
longer UV irradiation (UVA) minimises photodegradation of
products, a common issue from photochemistry performed
under UVB or UVC irradiation.
Additionally, Pd@TiO2 has shown great efficiency as
a
heterogeneous photocatalyst, capable of retaining catalytic
activity upon several reusability cycles under different
conditions. 18
Here, we used our previously reported Pd@TiO2
16, 19
(see
details in SI) to reduce different organic azides in water under
mild conditions obtaining yields up to 98%. A series of control
reactions (Table S1) were carried out to help us understand the
system. As previously noted, the presence of Pd is critical to
ensure optimal charge carrier transportation, and the
concomitant delay of the TiO2 electron-hole recombination.20
Not surprisingly, the reaction does not work when the catalyst
is replaced by bare TiO2. The reaction can proceed under UVA
irradiation (368 nm LED) but no products are detected when
visible light (465 nm LED) is used instead. This suggests that
excitation of TiO2 is required for the reaction to proceed. The
a. Department of Chemistry and Biomolecular Science and Centre for Advanced
Materials Research (CAMaR), University of Ottawa, 10 Marie Curie, Ottawa, ON
K1N 6N5, Canada.
b. INFIQC-CONICET-UNC, Departamento de Química Orgánica, Facultad de
Ciencias Químicas, Universidad Nacion-al de Córdoba, Ciudad Universitaria,
X5000HUA Córdoba, Argentina.
Electronic Supplementary Information (ESI) available: Details of synthesis and MS
and NMR spectroscopy, photo-catalytic reduction, reusability tests, absorption
spectra. See DOI: 10.1039/x0xx00000x
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absorption spectra of the azide reagents show they can only available hydrogen atoms or other organic materials that can
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absorb light at shorter wavelengths, below the emission region populate the Pd surface. The discussion tDhOatI: f1o0l.1lo0w39s/Dc0eCnCtr0e4s11o8nA
of the LED used for excitation (Figure S1). This shows that the selected examples from the scope of the reaction that is
aromatic amines are not obtained by direct photolysis of presented later in this contribution.
aromatic azides, but rather through a UVA light-assisted
hydrogenation of azide on Pd@TiO2 (Scheme 1). We have
previously shown that Pd decoration can extend the absorption
profile of TiO2 into the visible region, but that the photocatalytic
activity of the material can change greatly depending on the
21
irradiation wavelength used. Here we propose that Pd can
also facilitate N2 extrusion under longer UV light irradiation
through azide 휋-Pd interactions (Scheme 2); whilst, on the other
side of the oxidation cycle, water can donate an electron to the
photogenerated hole, generating reactive oxygen species (e.g.,
HO•)22 and acting as
H
source (H+). Noteworthy, the
Scheme 2. Proposed 흅-Pd interactions-assisted mechanism for the photocatalytic
formation of anilines via nitrene intermediate.
heterogeneous nature of the process was confirmed by leaching
experiments, where the reaction is unable to proceed once the
heterogeneous catalyst is filtered out of the solution (Figure 1,
left). Additionally, the catalyst can be reused several times
without loss of photocatalytic activity (Figure 1, right).
Using water as solvent, the presence of hydrides on the Pd
surface – following band gap excitation of the titania support
and electron migration to the PdNP – readily leads to the
reduction of the nitrene to the corresponding amine. A
comparison of phenyl azide (92% yield) with octyl azide (28%
yield) serves to illustrate the importance of 흅 interactions as
part of the process that brings the substrate to the catalytically
active sites. When the reaction is carried out in D2O, the
deuterated product is detected by NMR, 24 supporting water as
H/D source (Figures S2-S3). When the solvent is acetonitrile, the
surface generation of nitrene seems to occur just as efficiently
as in water, but hydride formation on the Pd surface (or the
release of hydride) seems to be far less efficient, and surface
nitrenes dimerize yielding azobenzene (68 % isolated yield) as
the only detectable product, as indicated in Scheme 3 below,
where square brackets designate surface processes.
Furthermore, we wondered whether amine formation in water
could be mediated by the azo compound. To this effect we
subjected azobenzene to the aqueous illumination protocol
used for the azide, and found the corresponding hydrazine as
the only product, while no aniline was detected; thus,
confirming that azobenzene is not in the reaction path leading
to aniline.
Scheme 1. Photochemistry of azides: formation of nitrene intermediates.
Figure 1. Left: Leaching test: reaction kinetics followed in the presence of catalyst (black)
or removing the catalyst after 1 h (blue). Right: reusability of the catalyst is assessed after
separation and reuse of catalyst (black) or without separation by subsequent additions
of the reagent (red). The double stars (**) indicate only 6 out of 8 mg of catalyst were
recovered and reused for these reactions.
Based on the control reactions carried shown in table S1, we
propose the mechanism of amine formation upon UVA Scheme 3. Proposed mechanisms for the reaction of nitrenes in water versus acetonitrile
(AcN) solvents. [ ] represent surface processes. Catalyst not shown for simplicity.
excitation in aqueous media shown in Scheme 2. Since both Pd
and UV light (excitation of TiO2) are necessary for the reaction
In the case of nitrenes in solution, singlets and triplets show
distinct characteristic behaviour.11 We note that in the schemes
and in the discussion above we have not mentioned multiplicity;
we assume that in the presence of the palladium surface ST
interconversion will be fast and perhaps these species are
largely indistinguishable when located on the metal surface.
Additionally, given the geometric opportunity, surface nitrenes
can undergo intramolecular processes, as indicated in the
carbazole formation (Scheme 4A), taking place in water with
to occur, we believe the excited electrons in the conduction
band of TiO2 can be trapped by PdNPs to reduce H+ and form
hydride species on the Pd surface (Pd-H). Concomitantly, azides
can undergo N2 extrusion (plausibly assisted by 흅-Pd
interactions in the cases of aromatic azides) to produce nitrenes
that can be stabilized on the Pd surface in a manner similar to
the documented interaction of nitrogen centred species with
PdNP23 and Pd complexes.15 At this point, with N2 gone, the fate
of the nitrenes will be determined by their interactions with
2 | J. Name., 2012, 00, 1-3
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29
>75% isolated yield. Further, the reaction shows typical products in the synthesis of nitriles from azides, and can be
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30
aziridine chemistry (Scheme 4B). It is unclear at this point favoured after tuning reaction conditionsD.OI:F1u0r.1t0h3e9r/,Du0CnCd0e4r1t1h8Ae
whether aziridines are in equilibrium with surface nitrenes, or same reaction conditions lower yields of aliphatic amines are
whether the reaction is driven by the addition of X-H. In any expected as can be seen in the case of octyl amine (28% isolated
event, there is literature precedent for equilibration between yield, entry 19).
nitrenes and azirines (Scheme S2).11 When the reaction is In conclusion, we have demonstrated that the heterogeneous
performed in the presence of diisopropylamine (DIPA), the photocatalytic conversion of azides to nitrenes can be initiated
corresponding ortho-substituted product is obtained with UVA light when the azides interact with Pd@TiO2, leading
quantitatively. Moreover, when the azide incorporates a to surface-stabilized nitrenes; their fate depends on the reactive
carbonyl moiety the product can be readily explained by the opportunities present on the surface and determined by the
Curtius rearrangement (Scheme 5, table 1, entry 20) to produce solvent and potential presence of nucleophiles. Specifically,
only isocyanate, a typical product of nitrene rearrangement.25 reduction of organo-azides to amines can be achieved by using
Notably, no hydrogenation product (amide formation) is found, water as H source. A broad range of organo-azides can be
suggesting concerted Curtius rearrangement without formation reduced with excellent yields showing the reaction
of benzoyl nitrene intermediate. Additionally, the formation of chemoselectivity towards azides versus all terminal alkene,
aniline via hydrolysis was not detected, probably due to the nitro, carbonyl, and carboxylic groups. Furthermore, when the
neutrality conditions of the reaction (pH ~ neutral).
media is non-protic and non-nucleophilic, as is the case in
acetonitrile, the surface nitrenes undergo recombination to
produce the azo compound. In a nutshell, this strategy can be
used to replace the conventional photolysis of azides,
facilitating the chemistry of nitrenes at longer wavelengths, as
azides do not usually absorb in the UVA region.
Conflicts of interest
There are no conflicts to declare.
Acknowledgement
This work was supported by the Natural Sciences and
Engineering Research Council of Canada, the Canada
Foundation for Innovation, the Canada Research Chairs
Program and funding from Canada's International Development
Research Centre (IDRC). IDL is a grateful recipient of the
Emerging Leaders of the Americas Program (ELAP) scholarship.
Scheme 4. A- Formation of carbazole, B- Nucleophilic substitution of aziridines.
The reduction of aryl azides (Table 1) shows some dependence
on the electronic nature of the substituent group. Thus, aryl
azides substituted with electron-donating groups (EDG) in para
position show slightly higher reaction yields (80-97%)
comparing to those obtained with electron-withdrawing groups
(EWG) in the same position (50-80%), whereas –with the
exception of F– no reaction was detected for halogen
substituents, likely due to heavy atom effect (i.e., intersystem
crossing generating triplet states favoured in the presence of
heavy atoms). 26, 27 Notably, the reaction shows 100% selectivity
towards reduction of azide group versus ketone (entry 8),
carboxyl (entry 9), nitro (entry 10), and alkene groups (entry 13).
These results further support our proposed mechanism.
Particularly, the absence of cyclization in the alkene derivative
(entry 13) together with the lack of reactivity of halogenated
compounds do not support an electron transfer pathway,
where the iodine and bromine derivatives are expected to
undergo dehalogenation and chlorine derivates to form p-
chloroaniline.28 Additionally, biphenyl azides (entries 14-15) can
undergo intramolecular cyclization to furnish carbazole
products with high yields and selectivity. Moreover, the
reaction of benzyl azide yields the imine product with 100%
selectivity (entry 18). This species is often seen as one of the by-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Table 1. Scope of the photocatalytic reduction of azidesa
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Select, 2018, 3, 96-99.
7. J. G. Du, G. Xu, H. K. Lin, G. W. Wang, M. L. Tao and W. Q.
Zhang, Green Chem., 2016, 18, 2726-2735.
8. Y. P. Wu, B. Yang, J. Tian, S. B. Yu, H. Wang, D. W. Zhang, Y. Liu
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Entry
Substrate
Product
Yieldc
92%
66%
88%
97%
81%
56%
Conversionb
>99%
82%
1
2
3
4
5
6
91%
>99%
>99%
71%
10. D. E. Falvey and A. D. Gudmundsdottir, Nitrenes and nitrenium
ions, Wiley, Hoboken, New Jersey, 2013.
11. M. S. Platz, in Reactive Intermediate Chemistry, eds. M. Jones,
Jr., R. A. Moss, M. Platz and M. Jones, Wiley-Interscience, Hoboken,
N.J., 2004, ch. 11, pp. 501-560.
12. Y.-P. Wu, B. Yang, J. Tian, S.-B. Yu, H. Wang, D.-W. Zhang, Y. Liu
and Z.-T. Li, Chem. Commun., 2017, 53, 13367-13370.
13. Y.-P. Wu, M. Yan, Z.-Z. Gao, J.-L. Hou, H. Wang, D.-W. Zhang, J.
Zhang and Z.-T. Li, Chin. Chem. Lett., 2019, 30, 1383-1386.
14. B. Zelenay, M. Besora, Z. Monasterio, D. Ventura-Espinosa, A. J.
P. White, F. Maseras and S. Diez-Gonzalez, Cat. Sci. Tech., 2018, 8,
5763-5773.
7
8
9
--
0%
70%
(100%)
91%
84%
81%
(100%)
52%
(100%)
10
64%
11
12
13
14
79%
54%
80%
72%
15. Z. Zhang, Z. Li, B. Fu and Z. Zhang, Chem. Comm., 2015, 51,
16312-16315.
16. A. Elhage, A. E. Lanterna and J. C. Scaiano, ACS Catal., 2017, 7,
250-255.
17. B. Wang, K. Duke, J. C. Scaiano and A. E. Lanterna, J. Catal.,
2019, 379, 33-38.
18. A. Elhage, A. E. Lanterna and J. C. Scaiano, Chem. Sci., 2019, 10,
1419-1425.
98%
(100%)
>99%
>99%
75%
19. A. Hainer, N. Marina, S. Rincon, P. Costa, A. E. Lanterna and J. C.
Scaiano, J. Am. Chem. Soc., 2019, 141, 4531-4535.
20. A. S. Hainer, J. S. Hodgins, V. Sandre, M. Vallieres, A. E. Lanterna
and J. C. Scaiano, ACS Ener. Lett., 2018, 3, 542-545.
21. A. Elhage, A. E. Lanterna and J. C. Scaiano, ACS Sust. Chem. Eng.,
2018, 6, 1717-1722.
22. M. Jonsson, in Visible-Light-Active Photocatalysis:
Nanostructured Catalyst Design, Mechanisms, and Applications, ed.
S. Ghosh, Wiley-VCH, Weinhem, 2018.
23. S. Singha, M. Sahoo and K. M. Parida, Dalton Trans., 2011, 40,
7130-7132.
24. A. Gevorgyan, S. Mkrtchyan, T. Grigoryan and V. O. Iaroshenko,
ChemPlusChem, 2018, 83, 375-382.
25. A. K. Ghosh, A. Sarkar and M. Brindisi, Org. Biomol. Chem.,
2018, 16, 2006-2027.
26. D. V. Korchagin, A. V. Akimov, E. A. Yureva, S. M. Aldoshin and E.
Y. Misochko, Chem. Phys. Lett., 2016, 659, 234-236.
27. N. P. Gritsan, D. Tigelaar and M. S. Platz, J. Phys. Chem. A, 1999,
103, 4465-4469.
42%
15
82%
35%
48%
72%
--
16
17
18
19
20
79%
99%
>99%
31%
CH3(CH2)6CH2N3 CH3(CH2)6CH2NH2
28%
89%
>99%
[a] Reaction conditions: 0.2 mmol organic azide, 8 mg of Pd@TiO2, 2 ml of H2O, Ar
atmosphere, UVA irradiation (368 nm LED working at 0.06 W/cm2), 5 h.
Conversions were estimated by GC-MS. [c]Purification was performed by flash
column chromatography and the products characterized by MS, 1H and 13C NMR.
Values between brackets correspond to the selectivity towards reduction of azide
group.
[b]
28. Y. Y. Chen, A. S. Kamlet, J. B. Steinman and D. R. Liu, Nature
Chem., 2011, 3, 146-153.
29. J. L. He, K. Yamaguchi and N. Mizuno, J. Org. Chem., 2011, 76,
4606-4610.
30. L. Martinez-Sarti and S. Diez-Gonzalez, ChemCatChem, 2013, 5,
1722-1724.
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4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0CC04118A
TABLE OF CONTENT ENTRY
R
R
NH2
N3
20 examples
Up to 98% yield
Water as H source
Mild conditions
Easy separation
h

Pd
TiO2
Pd-decorated TiO2 can induce azide photochemistry under longer-than-usual irradiation wavelengths and
mild reaction conditions to furnish nitrene chemistry products.