2.1 Hydrazonyl Halides
15
Ph
Cl
N
NH
Br
Ph
N
N
Br
R
Me
F
NO 2
pK a
9.64
9.42
~8
Ph
Cl
N
N
Br
Ph
N
NH
Br
+/- H
+
+/- Cl
-
+/- Cl
-
R
R
R
R
-H
+
Scheme 2.3 The pKa of the hydrazonyl halide can be influenced by substituent
MeO 2 C
Cl
N
NH
MeO 2 C
MeO 2 C
N
NH
MeO 2 C
Ag
+
AgCl (s)
MeO 2 C
N
N
MeO 2 C
CO 3
2HCO 3
-
Scheme 2.4 The use of silver salts in the generation of NIs
Numerous examples exist in the literature documenting the successful application
of both organic and inorganic bases within this reaction manifold. For example,
inorganic bases have shown to be competent in the generation of NIs in aqueous
media, as evidenced in the first reported example of NI cycloaddition under such
conditions (Scheme 2.5) [11].
The presence of a halide counter-ion itself in the reaction milieu can also have a
significant impact upon the reactivity of the NI. Recent examples in the literature have
shown that when generating NIs through irreversible means (Sect. 2.4), performing
the reaction in PBS buffer can lower the reactivity, by trapping some of the dipole as
the corresponding hydrazonyl chloride (Scheme 2.6). This is accomplished by the
presence of the chloride anion within the buffer [12].