Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

STRUCTURE AND SPECTRA OF NITRONES 183
Δ
•
•
+ −
N O CH3 +
N O
TMIO TMINO
Scheme 2.71
compounds, such as imidazoles, benzimidazoles, benzimidazolones, oxazolones,
N -arylamidines, and quinoxalones (351).
A general synthetic method for acyclic α-alkoxynitrones (196) involves the
alkylation with trißates of hydroxamic acids (195) in neutral conditions (Scheme
2.69) (352). Similarly, the synthesis of cyclic methoxynitrone of pyrrolines (197)
has been carried out (353).
The presence in the heterocycle of additional basic centers or those open
to alkylation can lead to a change in reaction directions. It essentially limits
the application of this method in the formation of α-methoxy nitrones. In such
cases, it is reasonable to use diazomethane and, depending on the structure of
hydroxamic acid (198–201) the yields of α-methoxy nitrones (197), (202–204)
can rise from 17% up to 62% (Scheme 2.70) (353).
Recently, the use of ßash vacuum pyrolysis, at 420 ◦ C and at pressure less than
0.5 mm Hg has been described for the synthesis of isoindolyl nitrone 1,1,3-trimethylisoindole
N -oxide (TMINO) from isoindoline nitroxide 1,1,3,3-tetramethylisoindolin-2-yloxy
(TMIO), with yields up to 73% (Scheme 2.71) (354).
2.3. STRUCTURE AND SPECTRA OF NITRONES
2.3.1. Electronic Structure of Nitrones
The electronic structure of the nitrone group, except for the main A structure,
includes four canonical B–E structures. In the case of aromatic derivatives, it is
necessary to consider the conjugation with the benzene ring (structures F and G)
(Fig. 2.10) (355, 356).
Relative contribution of each of these structures differs signiÞcantly and is
determined by internal structural characteristics of the nitrones and by the inßuence
of external factors, such as changes in polarity of solvent, formation of
a hydrogen bond, and complexation and protonation. Changes in the electronic
structure of nitrones, effected by any of these factors, which are manifested
in the changes of physicochemical properties and spectral characteristics, can be
explained, qualitatively, by analyzing the relative contribution of A–G structures.
On the basis of a vector analysis of dipole moments of two series of nitrones
(355), a quantum-chemical computation of ab initio molecular orbitals of the
model nitrone CH2=N(H)O and its tautomers, and methyl derivatives (356), it
has been established that the bond in nitrones between C and N atoms is almost