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

N
+
O −
•
+ ClO 2
N
O •
H
O Cl
O
Scheme 2.100
NITRONE REACTIONS 215
N
O •
O + HClO
the absence of nucleophiles leads to the corresponding hydroxamic acids. During
oxidation, the formation of acyl nitroxyl radicals was observed (Scheme 2.100).
The use of lead tetraacetate as an oxidant gives O-acetyl derivatives of the
corresponding hydroxamic acids (475, 476, 506).
2.6.3.2. Oxidative Alkoxylation of Nitrones to α-Alkoxy Nitrones and α-Alkoxy
Substituted Nitroxyl Radicals The Þrst direct experimental evidence of the
possibility to carry out radical cation nucleophilic addition to nitrones with the
formation of nitroxyl radicals has been cited in Section 2.4. Further, such a reaction
route was referred to as “inverted spin trapping”; this route is an alternative
to a “conventional spin trapping” (508–512). Realization of either mechanism
depends on the reaction conditions; namely, on the strength of both nucleophile
and oxidant. The use of strong oxidants in weak nucleophilic media tends to
favour the radical cation mechanism.
For the Þrst time, the possibility of carrying out preparative inverted spin trapping
was demonstrated by the oxidative methoxylation of heterocyclic nitrones
derived from 4H -imidazole-1,3-dioxide (219) (Scheme 2.79) (513, 514).
Owing to the existence of two centers for nucleophilic attack (at C2 and C5) in
radical cations (220) obtained from the oxidation of 4-H -imidazole-1,3-dioxides
(219), the formation of two products of methoxy group addition was observed,
namely NNR (221) and NR of 3-imidazoline-3-oxide (222). The ratio of the products
depends on the electronic nature of substitutes R 1 and R 2 . Both, the donor
character of R 1 and acceptor character of R 2 facilitate the formation of nitroxyl
radicals (222) with the yield of (221) increasing with the inverted effect of the
substituents. As was mentioned in Section 2.4, the results of preparative electrochemical
oxidative methoxylation of 4H -imidazole-1,3-dioxides are similar to
the results of chemical oxidation.
Oxidation of mono-N -oxides 4H -imidazole (223) and (224) with PbO2 in
methanol leads to the formation of stable α,α-dimethoxy-substituted nitroxyl radicals
(271) and methoxy substituted imino nitroxyl radicals (INR) (272)–(274)
(Scheme 2.101) (514).
Oxidation of oxazolidine derivatives (275) gives isomeric pairs (A) and (B)
of α-methoxy-substituted oxazolidine nitroxyl radicals (276a–d, f, g) andα,αdimethoxy-substituted
nitroxyl radical (276e) (Scheme 2.102) (515).
In addition to the oxidative alkoxylation of 4H -imidazole and oxazolidine
derivatives, the reaction was also used with other cyclic aldo-nitrones such as
DMPO, derivatives of 3-imidazoline-3-oxide (228–232) (506), and derivatives