204 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 204±205$
Oxidative Iodination of Aromatic Amides Using
Sodium Perborate or Hydrogen Peroxide with
Sodium Tungstate$
Philipp Beinker, James R. Hanson,* Nadja Meindl and
Inmaculada C. Rodriguez Medina
School of Chemistry, Physics and Environmental Science, University of Sussex, Brighton,
Sussex BN1 9QJ, UK
Hydrogen peroxide or sodium perborate in the presence of a sodium tungstate catalyst are shown to be cheap oxidants
for the iodination of aromatic amides using potassium iodide as the source of the iodine.
Recently there has been some interest in developing novel
methods for the bromination of aromatic compounds based
on the catalytic oxidation of the bromide ion to an
electrophilic species.1 Aromatic iodination2 using iodine also
requires an oxidant although the reactive electrophile may
be an acetylhypiodite or some similar oxyiodo species rather
than the simple iodonium ion.3,4 A variety of reagents have
been used2 in the oxidative iodination of aromatic
compounds using both elemental iodine and the iodide ion.
Recent examples of oxidants include lead tetraacetate5 and
mercuric oxide.6 We have shown that both hydrogen
peroxide and sodium perborate, in the presence of sodium
bromination whilst the iodination is a direct electrophilic
aromatic substitution. The iodination of N-acetyl-2-anisidine
gave a 1:3 mixture of 4- and 5-iodo-N-acetyl-2-anisidine in
90% yield using hydrogen peroxide as the oxidant. The
1
ratio of the products was established by H NMR using an
NOE eect from the NHCOMe and OMe signals to identify
the relevant aromatic signals [N-acetyl-4-iodo-2-methoxyani-
line, dH (DMSO) 7.24 and 7.76 (each 1 H, d, J 8.6 Hz), 7.31
(1 H, s); N-acetyl-5-iodo-2-methoxyaniline, dH (DMSO)
6.86 and 7.37 (each 1 H, d, J 8.5 Hz), 8.31 (1 H, s)]. The
iodination of the nitroacetanilides with sodium perborate
was accompanied by hydrolysis of the N-acetyl group to
form the amine. The iodination was faster with the hydro-
gen peroxide and hydrolysis did not occur.
In conclusion we have shown that the iodination of
aromatic amides can be achieved using potassium iodide
as the source of the iodine and a cheap oxidant such as
hydrogen peroxide or sodium perborate with sodium
tungstate as the catalyst.
tungstate as
a catalyst, are eective systems for the
oxidation of the bromide ion in the bromination of aromatic
amides7 and phenyl ethers.8 Here we describe the
application of these oxidants with the iodide ion to the
iodination of aromatic amides.
The iodination of
a limited number of aromatic
compounds using peroxyacetic acid and iodine has been
reported previously.3,9 The uncatalysed iodination of aniline
using hydrogen peroxide has also been described
previously.10 Sodium perborate in glacial acetic acid has
been used11 as a reagent for the oxidation of aromatic iodo
compounds to iodoso derivatives and hence there was the
possibility of over-oxidation of the iodo derivatives formed
in the substitution reaction. Sodium perborate will also
oxidize aromatic amines to azobenzenes and nitroarenes.
Potassium iodide was oxidized with either sodium
perborate or hydrogen peroxide in the presence of sodium
tungstate catalyst in glacial acetic acid solution. The
iodinations were then carried out in glacial acetic acid in the
presence of some sulfuric acid. The latter has been found
previously2 to facilitate aromatic iodination. The results of
the iodination of a representative range of aromatic amides
are given in Table 1. The products were identi®ed by their
mp and 1H NMR spectra. In general the reactions using
hydrogen peroxide as the oxidant proceeded in better yield
to give the mono-iodo compound without further oxidation.
The iodination of 2,6-dimethylacetanilide, unlike the
bromination which gives the 4-substituent, gave 2,6-
dimethyl-3-iodoacetanilide. The substitution pattern was
clear from the 1H NMR spectrum which showed two
Experimental
General Experimental Details.ÐMelting points are uncorrected.
1H NMR spectra were recorded in [2H6]DMSO at 300 MHz.
Iodination Using Sodium Perborate.ÐSodium perborate (3 g) was
dissolved in a mixture of glacial acetic acid (15 cm3) and acetic
anhydride (10 cm3). A solution of potassium iodide (1.4 g) and
sodium tungstate (300 mg) in water (10 cm3) was added together
with conc. sulfuric acid (5 cm3). The substrate (7.5 mmol) in glacial
acetic acid (10 cm3) was added and the solution was warmed to
50 8C over 1 h. The mixture was poured into water (100 cm3) and
the excess iodine was destroyed with sodium thiosulfate and the
solution was neutralized with sodium hydroxide. The product was
®ltered and recrystallized from ethanol. The products (see Table 1)
were identi®ed by their 1H NMR spectra and melting point data.
Occasionally it was necessary to extract the product with
chloroform in this last step. The extract was then washed with
water, dried over sodium sulfate and the solvent evaporated to give
the product.
Iodination Using Hydrogen Peroxide.ÐHydrogen peroxide (30%,
3 cm3) was dissolved in glacial acetic acid (20 cm3), cooled in ice
and treated with conc. sulfuric acid (1 cm3). A solution of potassium
iodide (1.6 g) and sodium tungstate (300 mg) in water (10 cm3) was
added. After 15 min a solution of the substrate (10 mmol) in glacial
acetic acid (10 cm3) was added and the mixture was warmed to
50 8C for 1 h. The mixture was poured into water (100 cm3) and the
excess iodine was destroyed with sodium sul®te. The solution was
neutralized with sodium hydroxide and the iodo derivative ®ltered
and recrystallized. The products (see Table 1) were identi®ed by
their 1H NMR spectra and mp data.
aromatic doublets (dH 6.80 and 7.67,
J 8.1 Hz). The
abnormal aromatic substitution of 2,6-dimethylacetanilide
has been noted previously12 and rationalized13 in terms of
the steric inhibition of resonance. The dierence between
the bromination and iodination may re¯ect a dierence in
mechanism. Thus the oxidative bromination might be
proceeding through an Orton mechanism involving prior N-
2,3-Dimethyl-4-iodoacetanilide. Mp 158 8C (Found: C, 41.7; H,
4.2; N, 4.7. C10H12NOI requires C, 41.5; H, 4.2; N, 4.8%) dH
(DMSO) 2.02, 2.14, 2.38 (each 3 H, s), 6.92 and 7.62 (each 1 H, d,
J 8.5 Hz), 9.43 (1 H, s, NH).
*To receive any correspondence.
2,6-Dimethyl-3-iodoacetanilide. Mp 190 8C (Found: C, 41.4; H,
4.2; N, 4.7. C10H12NOI requires C, 41.5; H, 4.2; N, 4.8%) dH
(DMSO) 2.15, 2.20, 2.35 (each 3 H, s), 6.98 and 7.79 (each 1 H, d,
J 8.2 Hz), 9.95 (1 H, s, NH).
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 (see J. Chem. Research (S), 1997, Issue 1); there is
therefore no corresponding material in J. Chem. Research (M).
Beinker, Philipp
