Nitrosation of m-xylene, anisole, 4-nitrophenyl phenyl ether and
toluene in trifluoroacetic acid or in acetic–sulfuric acid mixtures
under nitric oxide
John H. Atherton,a Roy B. Moodie,*,b Darren R. Nobleb and Brian O’Sullivanb
a
ZENECA Huddersfield Works, Huddersfield, UK HD2 1FF
b Department of Chemistry, The University of Exeter, Exeter, UK EX4 4QD
N itrosation in trifluoroacetic acid or in acetic–sulfuric acid
mixtures is regioselective and accompanying non-selective
nitrous acid catalysed nitration can be avoided by purging
with nitric oxide.
Studies of electrophilic aromatic nitrosation in which the prod-
ucts have been clearly characterised are remarkably few.1 Aro-
matic substrates strongly activated to electrophilic substitution
appear to be necessary and products are often unstable under
the conditions used.
Nitrosoaryl ethers, formed by the nitrosation of aryl ethers in
aqueous acid, are rapidly converted to nitrosophenols.2,3 With
alkylbenzenes, nitration rather than nitrosation is often the
observed reaction; m-xylene in 65% sulfuric acid or 91% tri-
fluoroacetic acid gives a mixture of nitro-m-xylenes in a reaction
in which nitroso-m-xylenes were detected as intermediates.4 The
most successful method reported for aromatic nitrosation has
used nitrosonium tetrafluoroborate in acetonitrile,5 but the
reagent is expensive and the reaction is slow, m-xylene for
instance giving 4-nitroso-m-xylene in 85% yield after 24 h.
Nitrosation is much more regioselective than nitration, both
with ethers and with alkyl benzenes,5 and in view of the ease of
oxidation of the nitroso product to the corresponding nitro
compound, offers an attractive method for regioselective nitra-
tion, i.e. nitrosation followed by oxidation. For this purpose
accompanying nitrous acid catalysed nitration, a totally differ-
ent and less selective reaction in which a mixture of nitro-
isomers are formed by the combination of the aromatic radical
cation with nitrogen dioxide6 must be minimised. The use of an
inert atmosphere5,7 is helpful in preventing NO2 production by
the aerial oxidation of nitrous acid.8 However nitrogen dioxide
Fig. 1 Concentrations of m-xylene (), 4-nitroso-m-xylene (᭡) and 4-
can still be formed reversibly by dinitrogen trioxide homolysis
and the aromatic radical cation (RCϩ) can be formed, also
reversibly, by electron transfer from aromatic to nitrosonium
ion. We report the novel use of nitric oxide as a purging gas to
prevent oxidative decomposition of nitrous acid and to reduce
through equilibria (1) and (2) the concentrations of both
nitro-m-xylene (᭹) as they vary with time in (a) 91% aqueous trifluoro-
acetic acid and (b) 100% trifluoroacetic acid containing 0.37 mol dmϪ3
trifluoroacetic anhydride. Solutions were flushed with NO throughout
and contained 0.48 mol dmϪ3 NIII, added by injection of oxygen into
the inlet NO gas stream prior to addition of m-xylene.
through a septum. Purging with nitric oxide or nitrogen was
continued during the experiment and samples of reaction solu-
tion were removed at intervals for analysis by gas chrom-
atography. Fig. 1 shows representative time profiles. Results are
summarised in Table 1.
N2O3
NO2 ϩ NO
RCϩ ϩ NO
(1)
(2)
AR ϩ NOϩ
partners of the non-regioselective product-forming step of
nitrous acid catalysed nitration.
Reaction of m-xylene with NIII in 91% trifluoroacetic acid is
reported 4 to give 4- and 2-nitro-m-xylenes in 5:1 proportion.
Our results show that regioselectivity is greatly improved by
purging with N2 and still more by using NO. Substitution at the
2-position is eliminated. The yield of the product, in these cir-
cumstances 4-nitroso-m-xylene, goes through a maximum [Fig.
1(a)], its further reaction giving in part 4-nitro-m-xylene and in
part unidentified products. A range of acetic–sulfuric mixtures
were also investigated as solvents. The results were similar;
those for the optimum mixtures are reported (Table 1).
The reaction solutions (trifluoroacetic acid or acetic–
sulfuric acid mixtures) were flushed first with nitrogen and
then with nitric oxide. Initially NIII was introduced as solid
sodium nitrite, but subsequently and more conveniently by
injection of oxygen gas into a bulb in the inlet tube for nitric
oxide. Tests of diluted samples showed that this procedure gave
a reaction solution containing 3–4 moles of NIII per mole of
oxygen injected. The NIII is present as an equilibrium mixture1,9
of HNO2, N2O3, N2O3Hϩ and NOϩ in as yet unknown propor-
tions, though we have evidence10 that in 100% trifluoroacetic
acid under our conditions NOϩ predominates. The aromatic,
mixed with a GC reference compound, was added by injection
Using 100% trifluoroacetic acid with sufficient added tri-
fluoroacetic anhydride to react with the water formed in the
production of NOϩ, leads to near quantitative production of
4-nitroso-m-xylene. The reaction is somewhat slower, but there
J. Chem. Soc., Perkin Trans. 2, 1997
663