28
2 The Generation of Nitrile Imine Derivatives
pathway is dominant over the ISC pathway. As with the other properties discussed
above, charge recombination is inherent to individual molecules.
To summarise, the exact QY through which a 2-5-substituted tetrazole will generate the corresponding NI is non-trivial, and will require either empirical experimental
determination or advanced computational calculations on a case-by-case basis to elucidate whether NI formation is possible (Scheme 2.17). This is obviously a significant
disadvantage of using a novel 2,5-disubstituted tetrazole as an NI source in photolysis
experiments. Fortunately, cases whereby the corresponding NIs fail to form entirely
appear to be limited to only a handful of tetrazoles, containing nitro moieties and
dimethylamino functional groups [44, 58]. Many tetrazoles reported in the literature
have been shown to generate the relevant NI in good QYs.
2.5 Sydnones
Sydnones are mesoionic compounds that are typically represented as a cationic oxadiazole species with an exocyclic anionic oxygen atom [61]. Due to the zwitterionic
nature of sydnones, they have been known for some time to participate in 1,3-dipolar
cycloaddition reactions [62]. Cycloaddition of a sydnone species with a dipolarophile
will initially lead to a fused 5,5 ring system, which upon cycloreversion furnishes
CO 2 gas and the pyrazoline/pyrazole product (Scheme 2.18) [63].
While also applicable to the synthesis of pyrazoles and pyrazolines, thermal sydnone cycloadditions do not proceed through an NI intermediate. However, photolysis
of arylsydnone derivates activates an alternative mechanistic pathway by which the
sydnone expels CO 2 prior to any cycloaddition, generating the relevant NI in the
process [64]. This was first discovered by Piek in the late 1960s, however very little information was elucidated as the only products isolated in low yields were the
cycloadducts of the NI and the CO 2 gas expelled by the sydnone (Scheme 2.19) [65].
Within five years of this initial report, there was significant activity within the literature documenting attempts at understanding the mechanism of this decomposition
[66–75]. In addition to essentially corroborating that NIs are indeed formed through
the photolysis of sydnones, the debate centred on whether the NI was a primary or
secondary photoproduct. It was first proposed by Ohta that a diazirine species was
in fact the primary photoproduct of the reaction, which then further decomposed
to yield the NI (path A, Scheme 2.20) [69]. Meanwhile, Kato hypothesised that Naryl group migration could enable NI formation directly, without going through the
diazirine (path B, Scheme 2.20) [72].
A mechanistic study by Schmid and Heimgartner in 1978 later showed that when
generating diphenyl NI from 3,4-diphenyl sydnone, neither the C-Ph nor N-Ph bond
was broken at any point during this process [75]. This meant that photochemical NI
formation could not proceed through the proposed phenyl migration pathway, meaning that it is likely that diazirine formation represents the primary photoproduct of the
reaction (path A). However, it should be noted that some aspects of the mechanism
2 The Generation of Nitrile Imine Derivatives
pathway is dominant over the ISC pathway. As with the other properties discussed
above, charge recombination is inherent to individual molecules.
To summarise, the exact QY through which a 2-5-substituted tetrazole will generate the corresponding NI is non-trivial, and will require either empirical experimental
determination or advanced computational calculations on a case-by-case basis to elucidate whether NI formation is possible (Scheme 2.17). This is obviously a significant
disadvantage of using a novel 2,5-disubstituted tetrazole as an NI source in photolysis
experiments. Fortunately, cases whereby the corresponding NIs fail to form entirely
appear to be limited to only a handful of tetrazoles, containing nitro moieties and
dimethylamino functional groups [44, 58]. Many tetrazoles reported in the literature
have been shown to generate the relevant NI in good QYs.
2.5 Sydnones
Sydnones are mesoionic compounds that are typically represented as a cationic oxadiazole species with an exocyclic anionic oxygen atom [61]. Due to the zwitterionic
nature of sydnones, they have been known for some time to participate in 1,3-dipolar
cycloaddition reactions [62]. Cycloaddition of a sydnone species with a dipolarophile
will initially lead to a fused 5,5 ring system, which upon cycloreversion furnishes
CO 2 gas and the pyrazoline/pyrazole product (Scheme 2.18) [63].
While also applicable to the synthesis of pyrazoles and pyrazolines, thermal sydnone cycloadditions do not proceed through an NI intermediate. However, photolysis
of arylsydnone derivates activates an alternative mechanistic pathway by which the
sydnone expels CO 2 prior to any cycloaddition, generating the relevant NI in the
process [64]. This was first discovered by Piek in the late 1960s, however very little information was elucidated as the only products isolated in low yields were the
cycloadducts of the NI and the CO 2 gas expelled by the sydnone (Scheme 2.19) [65].
Within five years of this initial report, there was significant activity within the literature documenting attempts at understanding the mechanism of this decomposition
[66–75]. In addition to essentially corroborating that NIs are indeed formed through
the photolysis of sydnones, the debate centred on whether the NI was a primary or
secondary photoproduct. It was first proposed by Ohta that a diazirine species was
in fact the primary photoproduct of the reaction, which then further decomposed
to yield the NI (path A, Scheme 2.20) [69]. Meanwhile, Kato hypothesised that Naryl group migration could enable NI formation directly, without going through the
diazirine (path B, Scheme 2.20) [72].
A mechanistic study by Schmid and Heimgartner in 1978 later showed that when
generating diphenyl NI from 3,4-diphenyl sydnone, neither the C-Ph nor N-Ph bond
was broken at any point during this process [75]. This meant that photochemical NI
formation could not proceed through the proposed phenyl migration pathway, meaning that it is likely that diazirine formation represents the primary photoproduct of the
reaction (path A). However, it should be noted that some aspects of the mechanism