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

150 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
H
Me N
O
N Me
R
Ref. R = H (a) 151 ,
R = CH 3 (b) 152
+
O −
Ref. 152
PO(OEt)2
−
+
+
N
O− Ref. 153
Fig. 2.4 (continued)
− O
CH N P(O)(OEt)2
PPN 5, Ref. 148a
HO
+
O −
+
N PO(OEt)2
4-HOPPN, Ref. 148b
H
hydrochloride gave α-(4’-[2.2]paracyclophanyl) nitrones (151). From diethylphosphonoacetaldehyde
was obtained diethylphosphonomethylnitrone (152). The
reaction of cyclobutanone with N -methylhydroxylamine leads to N -methylcyclobutylideneamine-N
-oxide, which undergoes spontaneous dimerization. Therefore,
N -methylcyclobutylideneamine-N -oxide was used in situ in a 1,3-cycloaddition
reaction with active dipolarophiles (153) (Fig. 2.4).
For the synthesis of α-aryl-N -methylnitrones a silica gel-NaOH catalytic system
has been used. The reaction proceeds without solvents and in good yields,
irrespective of the electron-donor or electron-acceptor nature of the substituents
in benzaldehyde. Under similar reaction conditions ketones do not undergo the
reaction; therefore, it makes it possible to carry out selective syntheses in cases
where the system contains both aldehyde and ketone groups (154).
Z - ConÞguration is typical of the majority of α-aryl(hetaryl)-N -alkylaldonitrones.
The isolation of E-isomers in the condensation of aromatic aldehydes
with N -β-phenylethylhydroxylamine has been described (155). The synthesis of
α, N -diarylnitrones gives best results if acidic catalysis is employed (156), or
when clay is used as a catalyst (157). SigniÞcant reduction of reaction time and
increase in the yields of nitrones can be achieved if microwave irradiation is used
(158, 159). On the basis of polymeric arylaldehydes, the synthesis of polymeric
α,N -diarylnitrones has been described (160).
Condensation of N -substituted hydroxylamines with aldehydes and ketones is
widely used in the synthesis of various spin traps and biologically active nitrones
(Fig. 2.5) (161–186).
Molecular sieves are often used in condensation reactions. Thus, using 3 ûA
molecular sieves at room temperature, the condensation of alkylaldehydes with