2.4 Tetrazoles
23
From this report, photolysis of 2,5-diaryl tetrazoles quickly gathered momentum
as a popular approach to NI generation in both bioorthogonal and materials chemistry
(discussed further in Chap. 4) [12, 45]. The method was particularly attractive within
these fields due to the traceless, user-activated method of NI formation in which no
exogenous reagents were required.
One particularly active area of research was the development of novel tetrazoles
with increased values of λ max . When considering 2,5-diphenyl tetrazole, the prerequisite of a UV-B light source undoubtedly hindered the applications of the reaction,
due to the likelihood of causing cellular damage through reactivity with DNA [46].
Some of the first reports to address this issue focussed on altering the substituents
of both termini of the NI. The use of heteroatomic substituents on either aromatic
ring were shown to generate a “push-pull” system of electron flow, which raised the
wavelength into the lower energy UV-A range, while still forming the NI (Table 2.2,
entry 2) [47].
Subsequent efforts in this area were dedicated to extending the conjugation of
the π-electron system within the tetrazole, in order to increase the λ max . Tetrazoles
substituted by naphthalenes, thiophenes and pyrenes were all found to furnish the
relevant NI upon exposure to UV-A light [48–50]. In the cases of both the thiophene
and pyrene derivates, NI formation was observed at wavelengths of over 400 nm,
well into the visible region of the spectrum (Table 2.2, entries 4 and 5).
Other alterations to the reaction manifold demonstrated that further extension of
the operational wavelength could still be made. The use of two-photon excitation as
a means of tetrazole photolysis enabled the generation of a naphthalene-based NI
using a 700 nm laser (Table 2.2, entry 6) [51]. Another report exemplified the utility
of up-converting nanoparticles (UCNPs) in tetrazole photolysis. Yttrium, tantalum,
and ytterbium nanoparticles were found to facilitate NI formation from 5-phenyl,
2-pyrenyl tetrazoles using 974 nm light, successfully bringing the light required for
the photolysis of tetrazoles into the near infra-red region for the first time (Table 2.2,
entry 7) [52].
One additional advantage of the availability of numerous tetrazole species that
generate NIs at different wavelengths of light is the potential for their application in
“λ-orthogonal” chemistry, whereby two photolabile moieties may be selectively activated in the presence of one another using two different wavelengths of light [53, 54].
This technique can even be applied to two different tetrazole species (Scheme 2.15)
[55].
In comparison to the other methods of NI generation presented thus far, there
was surprising lack of mechanistic discussion into the photolysis of tetrazoles in the
years following the discovery of the reaction. Fifteen years after Huisgen’s initial
report, Padwa documented the quantum yields (QYs) of a number of diaryl tetrazoles,
making the proposal that the photodecomposition of the species originated from a
forbidden n-π* transition to the first excited singlet state [56].
Further measurements of the QYs of the tetrazoles followed [57]. In comparison
to other photochemical reactions, the QYs were generally good, indicating an efficient photolytic procedure. In one such report, it was found that very little about the
substrate was able to influence this QY. Solvent polarity, concentration, and even the
23
From this report, photolysis of 2,5-diaryl tetrazoles quickly gathered momentum
as a popular approach to NI generation in both bioorthogonal and materials chemistry
(discussed further in Chap. 4) [12, 45]. The method was particularly attractive within
these fields due to the traceless, user-activated method of NI formation in which no
exogenous reagents were required.
One particularly active area of research was the development of novel tetrazoles
with increased values of λ max . When considering 2,5-diphenyl tetrazole, the prerequisite of a UV-B light source undoubtedly hindered the applications of the reaction,
due to the likelihood of causing cellular damage through reactivity with DNA [46].
Some of the first reports to address this issue focussed on altering the substituents
of both termini of the NI. The use of heteroatomic substituents on either aromatic
ring were shown to generate a “push-pull” system of electron flow, which raised the
wavelength into the lower energy UV-A range, while still forming the NI (Table 2.2,
entry 2) [47].
Subsequent efforts in this area were dedicated to extending the conjugation of
the π-electron system within the tetrazole, in order to increase the λ max . Tetrazoles
substituted by naphthalenes, thiophenes and pyrenes were all found to furnish the
relevant NI upon exposure to UV-A light [48–50]. In the cases of both the thiophene
and pyrene derivates, NI formation was observed at wavelengths of over 400 nm,
well into the visible region of the spectrum (Table 2.2, entries 4 and 5).
Other alterations to the reaction manifold demonstrated that further extension of
the operational wavelength could still be made. The use of two-photon excitation as
a means of tetrazole photolysis enabled the generation of a naphthalene-based NI
using a 700 nm laser (Table 2.2, entry 6) [51]. Another report exemplified the utility
of up-converting nanoparticles (UCNPs) in tetrazole photolysis. Yttrium, tantalum,
and ytterbium nanoparticles were found to facilitate NI formation from 5-phenyl,
2-pyrenyl tetrazoles using 974 nm light, successfully bringing the light required for
the photolysis of tetrazoles into the near infra-red region for the first time (Table 2.2,
entry 7) [52].
One additional advantage of the availability of numerous tetrazole species that
generate NIs at different wavelengths of light is the potential for their application in
“λ-orthogonal” chemistry, whereby two photolabile moieties may be selectively activated in the presence of one another using two different wavelengths of light [53, 54].
This technique can even be applied to two different tetrazole species (Scheme 2.15)
[55].
In comparison to the other methods of NI generation presented thus far, there
was surprising lack of mechanistic discussion into the photolysis of tetrazoles in the
years following the discovery of the reaction. Fifteen years after Huisgen’s initial
report, Padwa documented the quantum yields (QYs) of a number of diaryl tetrazoles,
making the proposal that the photodecomposition of the species originated from a
forbidden n-π* transition to the first excited singlet state [56].
Further measurements of the QYs of the tetrazoles followed [57]. In comparison
to other photochemical reactions, the QYs were generally good, indicating an efficient photolytic procedure. In one such report, it was found that very little about the
substrate was able to influence this QY. Solvent polarity, concentration, and even the