We have investigated the possibility of Hofmann rear-
rangement under different reaction conditions using 2-phe-
nylacetamide 2 as a model substrate and Oxone as the
oxidant. First, we found that no reaction occurred between
amide 2 and Oxone in the absence of iodobenzene even after
several days. Addition of iodobenzene to the reaction mixture
resulted in the formation of benzylamine 3, which was
isolated as hydrochloride salt 3•HCl after treatment with HCl
using the purification procedure previously described by
Loudon.3a The mixture of CH3CN-H2O (1:1, v/v) was found
to be the best solvent system for this reaction. The optimized
reaction affording benzylamine hydrochloride 3•HCl in 95%
yield required at least 1 equiv of iodobenzene and 2 equiv
of Oxone (Scheme 2). The use of smaller amounts of
Scheme 1
.
Generation of Active Iodine(III) Species 1 from
Iodobenzene and Oxone
1).1s,6a Further study of this reaction (Scheme 1) has led us
to the development of a convenient experimental procedure
for the preparation of [bis(trifluoroacetoxy)iodo]perflu-
oroalkanes and [bis(trifluoroacetoxy)iodo]arenes by oxidation
of organic iodides using Oxone and trifluoroacetic acid.6b
Moreover, based on this process (Scheme 1), we were able
to develop a metalloporphyrin/iodine(III)-cocatalyzed oxy-
genation of aromatic hydrocarbons by Oxone in the presence
of 5-20 mol % of iodobenzene and 5 mol % of a water-
soluble iron(III)-porphyrin complex.6c
Scheme 2. Formation of Benzylamines by Hofmann
Rearrangement of Carboxamides using Oxone
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iodobenzene led to an incomplete conversion, and unfortu-
nately, we were not able to realize the catalytic variant of
this reaction. Under similar conditions, the reaction of
2-phenylbutyramide 4 afforded 1-phenylpropylamine 5 in
85% isolated yield (Scheme 2).
GC-MS studies have shown that various alkyl- and
benzylamines can be obtained from the corresponding
carboxamides (e.g., amides 6a-k shown in Table 1) using
this procedure. This procedure (Scheme 2), however, has only
limited practical value because of the laborious protocol for
isolation of amines or their hydrochloride salts from the
reaction mixture. Therefore, we decided to apply our protocol
to the preparation of carbamates, which are stable solids or
nonvolatile liquids that can be easily isolated from the
reaction mixture by extraction with ethyl acetate. In order
to obtain methyl carbamates 7 as isolable products under
our optimized reaction conditions, we investigated Hofmann
rearrangement of carboxamides 6 in methanol; the results
are summarized in Table 1.
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