S. Anbu et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
5
(Hpic) and 2-pyrazinecarboxylic acid (Hpca), or bases such as pyr-
4. Experimental
idine, 3,5-dimethyl-1H-pyrazole, pyridazine, piperidine and trieth-
ylamine were tested, since they have been reported [54–61] to act
as promoters in peroxidative oxidations of cyclic, linear and
branched saturated hydrocarbons and alcohols (primary and sec-
ondary ones). The heteroaromatic N-based acids, Hpic and Hpca,
demonstrated an inhibitory effect on the reaction, and e.g. the
4.1. Materials and measurements
4.1.1. Catechol oxidation
4.1.1.1. Absorption spectroscopy. The catecholase like activity of the
complex described herein has been evaluated under air at 25 °C by
reaction with three different substrates (catechol (S1), 3,
5-ditertiarybutylcatechol (S2) and 3-nitrocatechol (S3)). Initially,
pH-dependent studies were carried out to determine the pH value
at which catecholase-like activity reached a maximum. The influ-
ence of the pH on the reaction rate for oxidation of catechol (S1,
S2 and S3) catalyzed by complex R-Cu2+ was determined over
the pH range of 5.0–9.5 at 25 °C. To a quartz cell were added
presence of 200 lM of acid (Hpic and Hpca) ((n(acid)/(n(catalyst
R-Cu2+)) = 20) results in an important yield drop (5% and 6%,
Fig. 4, entries 2 and 3, respectively) compared to the reaction car-
ried out under the same conditions (10 lM of catalyst, 80 °C, MW,
1 h) but in the absence of any additive (30%, Fig. 4, entry 1). A sim-
ilar inhibitory effect was observed for other Cu(II) systems [59,60].
In contrast, heteroaromatic N-based base additives have a ben-
eficial effect on the acetophenone product yield. In fact, the use of
5
195
l
L of a methanolic complex solution ([R-Cu2+] = 1.0 Â 10À3 M),
200 lM of a
N-based base (n(base)/(n(catalyst R-Cu2+)) = 20)
l
L of buffer [MES (pH 5.0–6.5) or HEPES (pH 7.0–9.5)], and
results normally in a significant yield increase. The most efficient
systems contain pyridine, 3,5-dimethyl-1H-pyrazole or pyridazine
leading to the yields of 82%, 69% and 73%, respectively (Fig. 4,
entries 4, 5 and 6, respectively). The systems containing triethyl-
amine and piperidine are much less active. However, the use of
K2CO3 (1 M solution), a N-free base, results in a high increase of
the conversion of the alcohol to the ketone (72%, entry 9, Fig. 4),
comparable to those obtained for pyridazine or 3,5-dimethyl-1H-
pyrazole. The role of basic additives, which facilitate the deproto-
nation of the alcohol, was already observed in other cases [62–69].
The effect of the presence of 2,2,6,6-tetramethylpiperidyl-1-oxyl
(TEMPO), a nitroxyl radical that is a known [62–68,70–72] pro-
moter in oxidation catalysis of alcohols, was also evaluated. In
accord, a significant yield increase was observed for the 1-phenyl-
ethanol oxidation catalyzed by R-Cu2+, from 30% in the absence of
TEMPO to 55% in its presence (Fig. 4, entries 1 and 10, respectively).
The reaction performed at 90 °C and in the presence of TEMPO
achieved 81% product yield (Fig. 4, entry 11). The TEMPO promoted
reaction conceivably involves its coordination, as well as of the
alcohol substrate, followed by Cu-centered oxidative dehydrogena-
tion of the alcohol upon H-abstraction [26–29,71–75]. Our group
reported some efficient systems involving alkoxy-1,3,5-triazapent-
adienate Cu(II) complexes [69], bis- and tris-pyridyl amino and
imino thioether Cu complexes [52] for the MW-assisted oxidation
of secondary alcohols to the corresponding ketones. The above cat-
alytic systems lead to comparable yields and/or TONs to those of
this work. A highly efficient system involving self-assembled dicop-
per(II) diethanolaminate cores toward (i) the aerobic aqueous med-
ium oxidation of benzyl alcohols, mediated by TEMPO radical, and
(ii) the solvent-free oxidation of secondary alcohols to ketones by
ButOOH under microwave (MW) irradiation was also reported
[30]. Recently, a cage-like silsesquioxane based-dicopper(II) com-
plex has been described with a high catalytic activity in the oxida-
tion reactions of benzene and alcohols with peroxides in
acetonitrile [76]. Quantitative amount of acetophenone was pro-
duced in the oxidation of 1-phenylethanol with ButOOH, after 4 h
at 50 °C, in the presence of the copper(II) silsesquioxane
2500
l
L of air-saturated methanol. The reaction was initiated with
the addition of 300 lL of a methanolic substrate solution ([sub-
strate] = 3.00 Â 10À3 M) and monitored for 15 min. The absorption
at kmax = 410 nm (e
= 1900 MÀ1 cmÀ1), characteristic of the formed
corresponding quinone, was measured as a function of time on a
Perkin-Elmer LAMBDA 750 UV–Vis spectrophotometer. To take
into account the spontaneous oxidation of the substrate, correction
was carried out using a reference cell under identical conditions
but without the addition of the catalyst. The initial rate was
obtained from the slope of the absorbance versus time plot over
the first 15 min of the reaction. The Michaelis–Menten model
was applied and the kinetic parameters were obtained from
nonlinear square fits using the program Origin 8.0.
4.1.1.2. 1H NMR spectroscopy. 3,5-Di-tert-butyl catechol (43 mg,
0.192 mmol) dissolved in methanol (2 mL) was added to metha-
nol/HEPES buffer (pH 8.2) solution of R-Cu2+ (2.5 mg, 0.002 mmol)
(3 mL) (100:1 ratio of substrate and catalyst). The mixture was stir-
red for 1 h, and the solvent was removed under reduced pressure.
The residue was extracted with CH2Cl2 (3 Â 10 mL). The organic
fractions were combined, filtered through Celite, and dried over
Na2SO4. The solvent was removed under reduced pressure, and
the residue (36 mg), as analyzed by 1H NMR spectroscopy in CDCl3
is a mixture of the product 3,5-dtbq (54%) and the substrate 3,5-
dtbc (46%). Yield of 3,5-dtbq relative to the starting 3,5-dtbc = 46%.
1H NMR (CDCl3, 300 MHz) d (ppm): 3,5-dtbc: 6.92 (CH aromatic, s,
1H), 6.78(CH aromatic, s, 1H), 5.48 (OH, s, 1H), 4.90 (OH, s, 1H),
1.44 (CH aliphatic, s, 9H) and 1.29 (CH aliphatic, s, 9H); 3,5-dtbq:
6.91 (CH aromatic, s, 1H), 6.77 (CH aromatic, s, 1H), 1.27 (CH
aliphatic, s, 9H) and 1.22 (CH aliphatic, s, 9H).
4.1.2. Alcohol oxidation
Oxidation reactions of the alcohols were carried out in sealed
cylindric Pyrex tubes under focused microwave irradiation as fol-
lows: the alcohol (5 mmol), catalysts R and R-Cu2+ (1–100
lmol)
and a 70% aqueous solution of ButOOH (10 mmol) were introduced
in the tube. This was then placed in the microwave reactor and the
system was left under stirring and under irradiation (10 W) for
[(PhSiO1.5)10(CuO)2(NaO0.5)2(EtOH)4] compound [76].
0.25–6 h at 80 °C. After cooling to room temperature, 300 lL of
3. Conclusions
benzaldehyde (internal standard) and 5 mL of CH3CN (to extract
the substrate and the organic products from the reaction mixture)
were added. The obtained mixture was stirred during 10 min and
then a sample (1 lL) was taken from the organic phase and
analyzed by GC using the internal standard method.
We have designed a new benzoyl hydrazone based dimeric cop-
per(II) complex R-Cu2+ which displays an efficient catecholase like
activity in slightly basic medium. This system also provides an
experimental evidence that the proximity of the CuII centers plays
an important role in the two electron aerobic oxidation of the
model substrates catechol, 3,5-ditertiarybutyl catechol and 3-nit-
rocatechol. In addition, the Cu(II) complex shows a good catalytic
activity in an important alcohol oxidation with an organoperoxide
reaction under added solvent free conditions.
Acknowledgements
S.A. is grateful to the Foundation for Science and Technology
(FCT), Portugal for the award of postdoctoral fellowship (Ref: