Chapter 2
The Generation of Nitrile Imine
Derivatives
Abstract Owing to the promiscuous reactivity profile of the nitrile imine, the species
is normally generated as an intermediate during the desired reaction. This requires
the selection of a precursor that is able to furnish the desired moiety when exposed
to appropriate conditions. This chapter discusses a library of different molecules that
have previously been employed as sources of nitrile imines. Of particular importance
within this field are the hydrazonyl halides and the 2,5-tetrazoles, which have risen to
prominence as the two most common methods of nitrile imine generation within the
literature. The methods employed in the liberation of the dipole are also explored,
with a broad scope of different reaction conditions available, including photolytic
generation via UV light.
Keywords Nitrile imine · 1,3-dipole · Hydrazonyl halide · Tetrazole · Photolysis
As discussed above, most forms of the NI moiety are unstable under standard conditions, and must be generated in situ by an appropriate precursor. The generation
of NI derivatives is possible through a range of chemical transformations, each with
their own advantages and disadvantages. Examples of each of these are provided in
the subsequent sections.
2.1 Hydrazonyl Halides
The most common NI precursor that can be found in the literature is the hydrazonyl
halide, or a derivative thereof [1]. The NI species are typically generated from this precursor through treatment with a base, as shown in Scheme 2.1, causing deprotonation
and subsequent elimination of the halide [2].
The generation of NIs from hydrazonyl chlorides was first noted in Huisgen’s
original 1959 report, as an alternative to the thermolysis of 2,5-disubstituted tetrazoles (Sect. 2.4.1) [3]. Treatment of diphenyl hydrazonyl chloride with triethylamine
in the presence of dicyclopentadiene yielded the expected pyrazoline in an 83% yield
(Scheme 2.2). The liberation of the NI in this manner was later shown to be a reversible
© Springer Nature Switzerland AG 2020
C. Jamieson and K. Livingstone, The Nitrile Imine 1,3-Dipole,
https://doi.org/10.1007/978-3-030-43481-6_2
13
The Generation of Nitrile Imine
Derivatives
Abstract Owing to the promiscuous reactivity profile of the nitrile imine, the species
is normally generated as an intermediate during the desired reaction. This requires
the selection of a precursor that is able to furnish the desired moiety when exposed
to appropriate conditions. This chapter discusses a library of different molecules that
have previously been employed as sources of nitrile imines. Of particular importance
within this field are the hydrazonyl halides and the 2,5-tetrazoles, which have risen to
prominence as the two most common methods of nitrile imine generation within the
literature. The methods employed in the liberation of the dipole are also explored,
with a broad scope of different reaction conditions available, including photolytic
generation via UV light.
Keywords Nitrile imine · 1,3-dipole · Hydrazonyl halide · Tetrazole · Photolysis
As discussed above, most forms of the NI moiety are unstable under standard conditions, and must be generated in situ by an appropriate precursor. The generation
of NI derivatives is possible through a range of chemical transformations, each with
their own advantages and disadvantages. Examples of each of these are provided in
the subsequent sections.
2.1 Hydrazonyl Halides
The most common NI precursor that can be found in the literature is the hydrazonyl
halide, or a derivative thereof [1]. The NI species are typically generated from this precursor through treatment with a base, as shown in Scheme 2.1, causing deprotonation
and subsequent elimination of the halide [2].
The generation of NIs from hydrazonyl chlorides was first noted in Huisgen’s
original 1959 report, as an alternative to the thermolysis of 2,5-disubstituted tetrazoles (Sect. 2.4.1) [3]. Treatment of diphenyl hydrazonyl chloride with triethylamine
in the presence of dicyclopentadiene yielded the expected pyrazoline in an 83% yield
(Scheme 2.2). The liberation of the NI in this manner was later shown to be a reversible
© Springer Nature Switzerland AG 2020
C. Jamieson and K. Livingstone, The Nitrile Imine 1,3-Dipole,
https://doi.org/10.1007/978-3-030-43481-6_2
13