Table 2 Amavadine catalysed peroxidative bromination and hydroxylation
other substrates and to other amavadine models and related
complexes. In particular, we have also observed catalytic
activity towards the above reactions for various vanadium( )
complexes with other polydentate ligands with N,3O-donor
atom sets such as triethanolaminate, e.g. [VO{N(CH2CH2O)3}]
b (see Tables 1 and 2), aminocarboxylates, etc.
of benzenea
V
Turnover number (TON)
V complex
H2O2+V HNO3+V BrC6H5
PhOH
To the best of our knowledge, this study provides the first
examples of vanadium catalysts for the peroxidative halogen-
ation of alkanes, at room temperature. It might be expected that
natural amavadine showed similar properties, i.e. the possibility
to act as a haloperoxidase or a peroxidase, catalysing the
peroxidative halogenation, hydroxylation and/or oxygenation
of organic substrates, but we note that, since for the halogen-
ation reactions the pH was very low, the results cannot be
directly extrapolated to biological conditions. Curiously, the
vanadium-dependent haloperoxidases, which probably devel-
oped later, since vanadium is in the oxidation state 5+, catalyse
halogenation reactions at pH 5–6 to give products that appear to
have defensive roles. On the basis of electrochemical studies3
we have suggested that amavadine, which, as stated, is a simple
complex, not an enzyme, may act as a kind of primitive
peroxidase (towards thiols) or as a catalase (if substrates other
than H2O2 are not present), behaving also as a protective agent
against external microbial pathogens or host body damage.
Halogenation of alkanes and aromatics which, as shown in this
work, occur in the laboratory at room temperature but very low
pH for the particular substrates studied, is unlikely to occur in
vivo with the substrates studied but may eventually be viable in
less extreme (even physiological) pH conditions for other more
favourable substrates.
Bromination:
Ca[V(HIDPA)2]
Ca[V(HIDA)2]
175
175
175
175
5050
3610
5050
3610
9
10
11
9
—
—
—
—
[VO{N(CH2CH2O)3}]
Hydroxylation:
Ca[V(HIDPA)2]
Ca[V(HIDA)2]
[VO{N(CH2CH2O)3}]
a See footnotes to Table 1.
440
440
440
72
72
72
—
—
—
6
16
8
activity. Hence, e.g. TON ca. 10–15 for the molar ratios
H2O2+V = 175 and HNO3+V = 3610.
No activity was found for the free (hydroxyimino)di-
carboxylic acids H3·HIDPA or H3·HIDA and the active species
has the metal in the 5+ oxidation state (the starting blue VIV
complexes are oxidized by H2O2 to the corresponding red VV
forms, as observed by the immediate colour change of the
reaction solution on addition of the peroxide). The presence of
vanadium in the 5+ oxidation state has also been demonstrated
in the vanadium-dependent bromoperoxidases and the forma-
tion of peroxo–vanadium complexes as active intermediate
species has been proposed.1a,b In our system, the hydroxy-
imine(12) groups, h -(O–N1), of the HIDPA32 or HIDA32
2
This work has been partially supported by the Fundação para
a Ciência e a Tecnologia and the PRAXIS XXI programme,
Portugal.
ligands that bind to the metal are isoelectronic with per-
oxide(22) and therefore the oxidized complexes relate to
bis(peroxo)-vanadium( ) species. Nevertheless, the presence of
V
H2O2 is required for the detection of activity and the vanadium-
promoted Br2 oxidation by H2O2 (to HOBr or a derivative
thereof) occurs in the aqueous phase and the halogenation of the
organic substrate in the organic phase (NCMe). The vanadium
complexes are soluble in both solvents and the peroxidative
halogenation occurs smoothly even without addition of a phase-
transfer agent.
Apart from behaving as catalysts for the halo-functionaliza-
tion of alkanes and aromatics, as shown above, synthetic
amavadine and its model can also catalyse, at room temperature,
the hydroxylation (reactions 2) and/or oxo-functionalization of
these types of substrates. The reactions occur in homogeneous
conditions (single-phase system), by treatment of an acetonitrile
solution of the vanadium complex, in the presence of H2O2 and
HNO3, with the substrate (Tables 1 and 2).
Notes and references
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J. J. R. Fraústo da Silva and R. J. P. Williams, Clarendon Press, Oxford,
1993.
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Silva, J. J. R. Fraústo da Silva, M. C. T. A. Vaz and L. Vilas-Boas,
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RH + H2O2 æAæmaævadæineÆROH + H2O
(2)
The system does not require so high an acidic medium as for
bromination, and the activity towards oxygenation of cyclohex-
ane to cyclohexanol and cyclohexanone, which is already
detected without added acid (overall TON = 4, 6 h reaction
time), reaches a maximum (overall TON ca. 50 in the
[V(HIDA)2]22 system) for an acid+vanadium molar ratio of ca.
140 (for H2O2+V = 440). The alcohol is always the main
product, but the ketone also forms. The selectivity is dependent
on the experimental conditions, in particular the amounts of
H2O2 and HNO3, and e.g. for the above conditions, the obtained
cyclohexanol/cyclohexanone molar ratio is 5.3, whereas a value
of 9.2 is reached for HNO3+V = 72 (also for H2O2+V = 440).
The selective oxidation to the alcohol, although less ex-
tensive, occurs for benzene (that forms exclusively phenol,
TON = 16 or 6 for the corresponding [V(HIDA)2]22 or
[V(HIDPA)2]22 systems), whereas mesitylene (1,3,5-trime-
thylbenzene) is oxidized to the aldehyde (3,5-dimethylbenzal-
dehyde) (TON = 13 or 7, respectively) rather than to the
alcohol.
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Attempts to characterize active intermediate vanadium
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1846
Chem. Commun., 2000, 1845–1846