Chem. Pap.
suspension was filtered and the solvent was removed in
vacuo. The residue was purified by column chromatogra-
phy (silica gel, ethyl acetate) to afford the desired product
Results and discussion
N-Benzylmethylamine was employed as a model com-
pound in the oxidation reaction using IBX and CDCl3 was
employed as the solvent for in situ investigation of the
oxidation. Although the reaction afforded interesting imine
products including N-benzylidenemethanamine and 1H-
isoindole in a 1:1 ratio upon IBX oxidation in DMSO
(Nicolaou et al. 2003, 2004), the present oxidation reaction
surprisingly only yielded benzaldehyde without any oxi-
dation by-products (Scheme 2). The amount of IBX used in
1
(43 mg, 93% yield). H NMR (400 MHz, 25 °C, CDCl3):
d = 10.18 (s, 1H), 9.14 (s, 1H), 8.90 (d, 1H, J = 4.0 Hz),
8.23 (d, 1H, J = 4.0 Hz), 7.55 (t, 1H, J = 4.0 Hz) ppm.
13C NMR (100 MHz, 25 °C, CDCl3): d = 190.78, 154.73,
152.07, 135.83, 131.4, 124.11 ppm. ESI–MS: M ? Na?,
found 130.1 (calc. 130.11).
N-(p-Methoxybenzyl)-N-methylamine
1
the oxidation reaction was optimized using the H NMR
A solution of amine (68 mg, 0.45 mmol) and IBX
(252 mg, 0.90 mmol) in 10 mL of CHCl3 was heated at
reflux with vigorous stirring for 6 h. The suspension was
filtered and the filtrate was washed in sequence with 10%
NaOH (5 mL 9 3), 1 M HCl (5 mL 9 3), and water. The
organic layer was dried with MgSO4 and concentrated in
vacuo to afford the desired product (57 mg, 91% yield). 1H
NMR (400 MHz, 25 °C, CDCl3): d = 9.89 (s, 1H), 7.85
(d, 2H, J = 8.0 Hz), 7.01 (d, 2H, J = 8.0 Hz), 3.90 (s, 3H)
ppm. 13C NMR (100 MHz, 25 °C, CDCl3): d = 190.89,
164.60, 132.01, 129.91, 114.31, 55.60 ppm. ESI–MS:
M ? Na?, found 159.1(calc. 159.15).
spectra recorded in CDCl3 (Fig. 1). The presence of 1
equiv. of oxidant produced about 60% conversion of the
amine compound in 12 h and prolonging the reaction time
did not afford any more aldehyde product. The yield was
improved upon the addition of more IBX. The product
yield increased by about 12% with the addition of
1.2 equiv. of IBX and kept on increasing to 83% upon
adding more oxidant (1.5 equiv. of IBX). Finally, complete
transformation from the amine to aldehyde was accom-
plished in the presence of 2 equiv. of IBX. The solvent
effect on the oxidation was investigated using various
solvents including ethyl acetate, THF, n-hexane, acetone,
and acetonitrile (Table 1). It was interesting to note that the
oxidation activity of IBX significantly depends on the
polarity of the solvent used. The benzaldehyde product was
provided with acceptable yields of 71 and 59% in ethyl
acetate and THF, respectively. However, there was only a
34% yield obtained in n-hexane and just trace aldehyde
was observed in the solvents, acetone, and acetonitrile. The
oxidation of N-benzylmethylamine in DMSO provided
55% conversion to the aldehyde, which could be attributed
to the good solubility of IBX in DMSO. The results indi-
cated that the IBX oxidation of N-benzylmethylamine
could benefit in solvents with moderate polarity (CHCl3,
ethyl acetate and THF), while the reactivity decreases in
highly polar solvents (acetone and acetonitrile) and non-
polar solvents (n-hexane).
N-(4-Chlorophenyl)-N-methylamine
A solution of amine (70 mg, 0.45 mmol) and IBX
(252 mg, 0.90 mmol) in 10 mL of CHCl3 was heated at
reflux with vigorous stirring for 4 h. The resulting sus-
pension was filtered and the filtrate was washed in
sequence with 10% NaOH (5 mL 9 3), 1 M HCl
(5 mL 9 3), and water. The organic layer was dried with
MgSO4 and removed in vacuo to afford the desired product
1
(60 mg, 94% yield). H NMR (400 MHz, 25 °C, CDCl3):
d = 9.98 (s, 1H), 7.82 (d, 2H, J = 8.0 Hz), 7.51 (d, 2H,
J = 8.0 Hz) ppm. 13C NMR (100 MHz, 25 °C, CDCl3):
d = 186.22, 136.29, 130.01, 126.24, 124.79 ppm. ESI–
MS: M ? H?, found 141.7 (calc. 141.57).
Nicolaou proposed that IBX oxidation of secondary
amines to yield the corresponding imine products goes
through an ionic mechanism on the basis of the formation
of an IBX-amine complex (Scheme 3, Step 1), which was
Screening for solvents
N-Benzylmethylamine (7 mg) and IBX (25 mg) in differ-
ent solvents including ethyl acetate, THF, n-hexane, ace-
tone, acetonitrile, and DMSO was heated at 60 °C with
vigorous stirring for 4 h. The resulting suspension was
filtered and the solvent removed in vacuo. The resulting
residue was dissolved into 0.6 mL of CDCl3 and the yield
1
identified using ESI–MS and H NMR spectroscopy, and
the by-product aldehydes were attributed to hydrolysis of
the imine (Nicolaou et al. 2003, 2004). Although no imine
intermediate was observed in the present case, even when
1
evaluated using H NMR spectroscopy.
N
H
IBX
O
CDCl3, 60 °C
Scheme 2 IBX oxidation of N-benzylmethylamine
123