Copper(II) and Sodium(I) Complexes based on 3,7-Diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-oxide: Synthesis, Characterization, and Catalytic Activity

Article abstract of DOI:10.1002/asia.201800799

The reaction of 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) with metal salts of Cu^II or Na^I/Ni^II under mild conditions led to the oxidized phosphane derivative 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-oxide (DAPTA=O) and to the first examples of metal complexes based on the DAPTA=O ligand, that is, [Cu^II(μ-CH₃COO)₂(κO-DAPTA=O)]₂ (1) and [Na(1κOO′;2κO-DAPTA=O)(MeOH)]₂(BPh₄)₂ (2). The catalytic activity of 1 was tested in the Henry reaction and for the aerobic 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated oxidation of benzyl alcohol. Compound 1 was also evaluated as a model system for the catechol oxidase enzyme by using 3,5-di-tert-butylcatechol as the substrate. The kinetic data fitted the Michaelis–Menten equation and enabled the obtainment of a rate constant for the catalytic reaction; this rate constant is among the highest obtained for this substrate with the use of dinuclear Cu^II complexes. DFT calculations discarded a bridging mode binding type of the substrate and suggested a mixed-valence Cu^II/Cu^I complex intermediate, in which the spin electron density is mostly concentrated at one of the Cu atoms and at the organic ligand.

Full text of DOI:10.1002/asia.201800799

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Cu(II) and Na(I) complexes based on 3,7-Diacetyl-1,3,7-triaza-5-
phosphabicyclo[3.3.1]nonane-5-Oxide (DAPTA=O): synthesis,
characterization and catalytic activity
Authors: Maria de Fátima C. Guedes da Silva, Abdallah G. Mahmoud,
Ewelina I. Śliwa, Piotr Smoleński, Maxim L. Kuznetsov, and
Armando J. L. Pombeiro
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To be cited as: Chem. Asian J. 10.1002/asia.201800799
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10.1002/asia.201800799
Chemistry - An Asian Journal
Cu(II) and Na(I) complexes based on 3,7-Diacetyl-1,3,7-triaza-5-
phosphabicyclo[3.3.1]nonane-5-Oxide (DAPTA=O): synthesis,
characterization and catalytic activity
Abdallah G. Mahmoud,[a],[b] M. Fátima C. Guedes da Silva,*[a] Ewelina I. Śliwa, [c] Piotr
Smoleꢀski,*[c] Maxim L. Kuznetsov [a] and Armando J. L. Pombeiro [a]
[a]
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av.
Rovisco Pais, 1049-001 Lisboa, Portugal. E-mail: fatima.guedes@tecnico.ulisboa.pt
[b]
Department of Chemistry, Faculty of Science, Helwan University, Ain Helwan, 11795
Cairo, Egypt.
[c] Faculty of Chemistry, University of Wrocław, Ul. F. Joliot-Curie 14, 50-383 Wrocław,
Poland. Email: piotr.smolenski@chem.uni.wroc.pl
Key words: Catalysis, Catechol oxidase, Copper, DAPTA=O, Water soluble phosphanes
Abstract:
Reactions of 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) with metal
salts of Cu(II) or Na(I)/Ni(II) under mild conditions lead to the oxidized phosphane
derivative 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-oxide (DAPTA=O) and
to the first examples of metal complexes based on the DAPTA=O ligand, [CuII(-
CH3COO)2(O-DAPTA=O)]2 (1) and [Na(1OO’;2O-DAPTA=O)(MeOH)]2(BPh4)2 (2).
The catalytic activity of 1 was tested for Henry reaction, as well as for the aerobic TEMPO-
mediated oxidation of benzyl alcohol. Compound 1 has also been evaluated as a model
system for the catechol oxidase enzyme using 3,5-di-tert-butyl-catechol (3,5-dtbc) as the
substrate. The kinetic data fitted the Michaelis-Menten equation and enabled obtaining a rate
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constant for the catalytic reaction which are among the highest obtained for this substrate
using dinuclear Cu(II) complexes. DFT calculations discard a bridging mode binding type of
this substrate and propose a mixed-valence Cu(II)/Cu(I) complex intermediate where the spin
electron density is mostly concentrated at one of the Cu atoms and at the organic ligand.
Introduction
The interest of 1,3,5-triaza-7-phosphaadamantane (PTA) and its derivatives in transition
metal coordination chemistry is dramatically increasing due to the high solubility, stability in
water and far-reaching catalytic, medicinal and photoluminescent applications of the obtained
compounds.[1–3] The first example of a PTA-Cu(II) complex was reported by Tu et al. where
the metal is coordinated by a PTA-based cluster ligand.[4] Thereafter, coordination polymers
based on PTA with mixed-valence Cu(I)/Cu(II) were published.[5,6] The reported examples of
Cu complexes based on PTA-type ligands are mainly of Cu(I), even when Cu(II) salts were
used as starting materials, due to the tendency of PTA ligands to stabilize the lower metal
oxidation state.[7–10]
Among the large family of open-cage PTA derivatives,[2,11] 3,7-diacetyl-1,3,7-triaza-5-
phosphabicyclo[3.3.1]nonane (DAPTA) is a relevant one (figure 1)[12,13] and its binding
capacity has been intensively studied for Cu, Ru, Rh, Pd, Pt and Au transition metals to
produce complexes used mainly for biological applications[14–17] and, to a lesser extent, for
catalysis.[18–21] The DAPTA ligand usually exhibits the P-coordination mode to the metal
center,[13–16,21–24] and recently the N-coordination mode was also reported.[18] Although
DAPTA has two coordination sites from the acetyl oxygens, the O-coordination mode for
DAPTA has not been reported yet.
Figure 1. PTA and DAPTA
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The oxidized derivatives of PTA and DAPTA, 1,3,5-triaza-7-phosphaadamantane-7-oxide
(PTA=O) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane 5-oxide (DAPTA=O)
were synthesized for the first time in 1977 by Siele,[12] the former upon oxidation of PTA and
the latter by acetylation of PTA=O with acetic anhydride (scheme 1). Several examples are
known where PTA=O binds a metal cation in the O-,[25,26] N-,[25,27] ON-,[25] ONN-,[28] NNN-[29]
or ONNN- modes,[28,30] achieving either discrete metallic units or polymeric compounds. In a
number of cases,[25,27] different types of coordination modes were obtained in the same
molecule. For DAPTA=O, however, and despite being known for quite a long time and its
structure had already been established,[12] its coordination properties have not yet been
studied.
Scheme 1. Synthesis of PTA=O and DAPTA=O
Nitroaldol (Henry) reaction constitutes an important C-C bond formation reaction,
accomplished by coupling nitroalkanes with carbonyl (aldehydes or ketones) compounds to
produce the corresponding β-nitro alcohols (scheme 2).[31,32] These are products of great
synthetic utility in view of their possible conversion into other valuable intermediates,
including the reduction of the nitro group to produce β-amino alcohols,[33] oxidation to yield
α-nitro ketones,[34] or dehydration to afford nitroalkenes.[35] The nitroaldol reaction can be
promoted (or catalyzed) by Lewis acidic metal complexes to activate the carbonyl group, by
bases to facilitate the deprotonation of nitroalkane, or both.[36–41]
Scheme 2. Catalytic Nitroaldol (Henry) reaction (general pictogram)
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The aerobic oxidation of benzylic alcohols catalyzed by transition metal salts or complexes
and in the presence of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical is an
interesting process that has been intensively studied through the last two decades, as the
produced benzylic aldehydes are versatile intermediates for syntheses of other fine
chemicals.[42,43]
Several copper- and other transition metal-based complexes, which effectively catalyze this
reaction under different conditions, have been studied by our group.[44–47]
Among the metalloenzymes that perform the oxidation of organic compounds by activating
molecular dioxygen is catechol oxidase, a type III metalloprotein that contains copper at the
active center. Such enzyme has the ability to catalyze the oxidation of ortho-phenols to the
appropriate ortho-quinones by molecular oxygen.[48–50] The catecholase activity of various
mono- and dicopper compounds, as well as copper clusters with different structural
topologies, has been widely explored.[49–60]
In this work we aimed to pursue our interests on the coordination chemistry of PTA and
derivatives,[5–10,14,26,28,61–64] chaining the aforementioned lines towards: i) the synthesis and
characterization of hydrosoluble transition metal complexes containing DAPTA or
DAPTA=O, the coordination chemistry of which is virtually unexplored; ii) the
understanding of the experimental conditions for the DAPTA oxidation to DAPTA=O; iii)
the study of the catalytic properties of the obtained copper(II) complex, [CuII(-
CH3COO)2(O-DAPTA=O)]2 (1), towards nitroaldol (Henry) reaction and alcohols oxidation
in water as reaction medium, as well as, iv) the study of the biomimetic behaviour of this
copper complex towards catechol oxidation.
Results and Discussion
Synthesis and characterization of complexes 1 and 2
The DAPTA=O ligand has been formed spontaneously by a one-pot simple reaction of
DAPTA with metal salts in air under mild conditions (scheme 3). The dinuclear air-stable
Cu(II) complex [Cu(-CH3COO)2(O-DAPTA=O)]2 (1) was obtained by reaction of Cu(II)
acetate monohydrate with DAPTA under air and at room temperature (route1, scheme 3) and
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stemmed from oxidation of DAPTA, presumably with concomitant reduction of Cu(II)
resulting in the O-bound DAPTA=O Cu(II) complex 1. This complex exhibits a high
solubility in water, dimethyl sulfoxide, methanol, ethanol, acetonitrile and dichloromethane,
whereas it is not soluble in diethyl ether and hexane.
The addition of Na(BPh4) to a methanolic solution of DAPTA in air at room temperature and
in the presence of nickel acetate hexahydrate led to the formation of the dinuclear sodium
complex [Na(-1OO’;2O-DAPTA=O)(MeOH)]2(BPh4)2 (2) as a white air-stable solid
(route 2, scheme 3). The reaction also involved the oxidation of DAPTA and the presence of
a Ni(II) salt proved to be essential for the formation of 2. Complex 2 exhibits a high solubility
in water, dimethyl sulfoxide and methanol, but it is not soluble in other common solvents.
Scheme 3. Synthetic procedures for DAPTA=O metal complexes
1
Compounds 1 and 2 were characterized by elemental analysis, ESI(+)-MS, FT-IR, H and
31P{1H} NMR spectroscopies and single-crystal X-ray diffraction analysis. The IR spectra of
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the complexes exhibit ν(P=O) at 1153 (1) and 1163 (2) cm-1, as well as ν(C=O) at 1627 (1)
and 1631 (2) cm-1, which are close to the typical values of free phosphane oxide [ν(P=O) at
1
1190 cm-1 and ν(C=O) at 1615].[12] Despite the paramagnetism of 1, its H and 31P NMR
1
spectra showed the signals corresponding to DAPTA=O fragments, although with the H
signals slightly broadened. The observation of NMR resonances in paramagnetic compounds
have been reported and attributed to the ligands remote locations from the paramagnetic
metal ions.[4–6] The 1H NMR spectra of 1 and 2 display similar resonances for the acyl methyl
groups and methylene protons compared to the free DAPTA.[22] For both compounds, the
1
sole acyl methyl resonances in the H NMR spectra indicates their equivalent environment.
The splitting patterns assigned to the methylene NCH2N and PCH2N protons (3.5-5.8 ppm)
are indicative of their diastereotopicity, also revealing the coupling of all PCH2N protons to
31
the phosphorus nucleus.[22] The sharp singlets at  2.95 (1) or 3.10 (2) in the P{1H} NMR
spectra are slightly downfield from the resonance of free DAPTA=O (2.20 ppm).[13]
Adventitious water seems to play a crucial role for DAPTA oxidation and the formation of
compounds 1 and 2, since they could not be obtained using dry solvents and under strict inert
conditions, despite the presence of some water in the metal salts. They could be formed,
however, by performing the reactions in undried degassed solvents, using Schlenck
techniques and under N2 atmosphere.
The role of water in such an oxidation process has already been reported by Frost et al.,[25] for
related systems where DAPTA is oxidized to DAPTA=O + 2H+. In our case, this oxidation
process is presumably combined with the reduction of Cu(II) (route1, scheme 3) or Ni(II)
(route 2, scheme 3). To prove the role of water in the DAPTA oxidation process, the
synthesis of 1 was undertaken under inert N2 atmosphere, using freshly dried solvents and
18
18O-labeled water (H2 O) in the reaction medium (see experimental part). The obtained
material was analysed using ESI(+)-MS, and the spectrum reveals a set of fragments
attributable to DAPTA=O18 (see experimental part and figure S1).
X-ray diffraction analysis. Compounds 1 and 2 crystallize in the triclinic space group and
are both dimeric with their asymmetric units containing only half of the molecules, viz. a
Cu(II) cation O-bound by two acetate and one DAPTA=O ligands in 1, and a Na(I) cation O-
bound by a chelating DAPTA=O and a methanol molecule in 2, the latter also containing a
tetraphenylborate counter-ion. The second halves of the molecules are generated by
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symmetry (figure 2) and give rise to ring-type neutral (in 1) or cationic (in 2) dinuclear units.
While in 1 the metal cations are gathered by means of four bridging chelate acetate anions, in
2 the metal cations are connected solely via the oxidized phosphane moiety which, overall,
acts as a three O-donor ligand. Thus, the copper atoms in 1 assume perfect all-O square
pyramidal geometries (5 = 0.00)[65] and the sodium atoms in 2 display distorted all-O
tetrahedral ones (4 = 0.77).[66] In 1 the metals are involved in just one type of metallacycle,
an 8-membered C2Cu2O4 ring, but the sodium cations in 2 are engaged in 14-, 16- and 18-
membered metallacycles of the type CxNyNa2O4P2 (x = 4 or 6; y = 2 or 4). In both structures
the metals, the P and the Ophosphane atoms lie in the same plane. In 1 no other atoms can be
included in such plane, while in 2 it also contains the amine N1 and the methylene C1 atoms.
The Cu–Oacetate bond distances in 1 (table 1) are close to each other and shorter than the Cu–
Ophosphane [avg. 1.964(3) and 2.182(2) Å, respectively]; in 2 the Na–Ophosphane is the shortest
metal–O length [2.207(3) Å] followed by the Na–Omethanol bond [2.274(3) Å], the Na–Oacetyl
being the longest [2.285(3) and 2.329(3) Å]. The P–Ophosphane distances are of 1.490(3) Å in 1
and of 1.473(2)Å in 2. The metalmetal intramolecular distances adopt values of 2.612 (1)
and 6.996 Å (2), but the minimum intermolecular ones assume values of 7.515 and 7.216 Å
(in 1 and 2, respectively).
The BPh4 anion in 2 appears to play an important role in the stabilization of the structure in
view of the short C(or O)–H interactions concerning DAPTA=O (or methanol) ligand as
donor, which range from 2.49 to 2.96 Å. In addition, the observed intermolecular contacts
between the sodium cations and the C12, C13 and C14 aromatic carbons of the BPh4 anion,
with minimum distance of 3.182 Å pertaining to C13, may account for the distortion of the
tetrahedral environment in dimer 2.
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Figure 2. The molecular structures of 1 (top) and 2 (bottom) with partial atom labelling schemes. The
BPh4 counter-ions of 2 are omitted for clarity. Symmetry operations to generate the i equivalent
atoms: 1-x,-y,1-z (1) and 2-x,2-y,1-z (2).
Table 1. Selected bond distances (Å) and angles (º) for 1 and 2 [a]
1
2
1.969(3)
1.956(3)
1.964(3)
1.965(3)
2.182(2)
1.490(3)
2.6117(9)
128.66(14)
90.36(11)
96.76(10)
2.207(3)
2.285(3)
O1Cu1
O2Cu1i
O1Na1i
O2Na1
2.329(3)
O3Cu1
O4Cu1i
O3Na1
2.274(3)
O4Na1
1.473(2)
O5Cu1
O1P1
110.84(13)
103.49(10)
140.04(12)
101.20(11)
105.84(12)
O5P1
O1Na1O4i
O1Na1O2i
O4Na1O2
O1Na1O3i
O4Na1O3
Cu1Cu1i
P1O5Cu1
O3Cu1O1
O3Cu1O5
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94.22(10)
86.36(9)
O1Cu1O5
O2Na1O3
[a] See figure 2 legend for the symmetry codes
Catalytic activity of complex 1
Nitroaldol (Henry) reaction. Under mild conditions and in air, complex 1 was tested as
homogeneous catalyst for nitroaldol coupling of benzaldehyde with nitromethane and
nitroethane (see above and scheme 2) in aqueous medium. The optimization of the reaction
conditions was attained by exploring some experimental variables such as reaction time and
temperature.
Table 2 displays the results of the reaction of benzaldehyde with nitromethane to give 1-
phenyl-2-nitroethanol. By using 5 mol% of the catalyst, at 75 oC, the product yield increased
with time up to 94 % after 60 h (table 2, entries 1-9 and figure 3). No significant increase in
the yield was observed by extending the reaction time to 72 h. Using ethanol (another protic
solvent) gave higher yields than when using water for the same period of time (table 2,
o
entries 10 and 12: 97 against 87 %, both at 60 C). A 1:1 mixture of ethanol and water gave
an yield (96 %) identical to that when using ethanol alone (table 2, entry 11). It was also
observed that in water as the sole solvent, the conversion increased with the increase of
temperature up to 91% after 48 h (table 2, compare entries 8, 12, 13 and 14). In the presence
of a base (triethylamine), in water and for 24 h at room temperature, the conversion was
quantitative (table 2, entry 15). In the absence of 1 but in the presence of any of several
Cu(II) salts, only 12 to 38 % of conversion was achieved after 24 h at 75 ºC (table 2, entries
16-19).
Table 2. Henry reaction of nitromethane with benzaldehyde using complex 1 as catalyst [a]
Entry
Catalyst
Time
(h)
2
4
6
T (oC)
Solvent
Yield [b] TON [c]
(%)
1
2
3
4
75
75
75
75
Water
Water
Water
Water
7
1
1
1
1
2
3
4
8
15
21
38
8
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5
6
7
8
9
12
24
36
48
60
48
48
48
48
48
24
24
24
24
24
75
75
75
75
75
60
60
60
23
50
23
75
75
75
75
Water
Water
Water
Water
Water
45
1
1
1
1
1
1
1
1
9
69
87
91
94
97
96
87
72
87
>99
12
38
18
26
14
18
18
19
20
19
18
15
18
20
2
10
11
12
13
14
15 [d]
16
17
18
Ethanol
Water:Ethanol (1:1)
Water
Water
Water
Water
Water
Water
Water
Water
1
1
1
CuSO4.5H2O
Cu(OAc)2.H2O
CuCl2.2H2O
Cu(NO3)2.2.5H2O
8
4
5
19
[a]
Reaction conditions: benzaldehyde (0.5 mmol), 5 mol% of catalyst, 3 equiv of nitromethane (1.5
mmol), 2 mL of solvent. [b] Determined by 1H NMR analysis of the crude products (see Experimental
part and figure S2). [c] Number of moles of the product (1-phenyl-2-nitroethanol) per mol of catalyst.
[d] In the presence of 5 mol% triethylamine.
Figure 3. Variation of the product yield with time in the reaction between benzaldehyde and
nitromethane catalysed by 1.
The nitroaldol catalyzed reaction was also performed using nitroethane instead of
nitromethane, affording the anti and the syn diastereoisomeric forms of 1-phenyl-2-
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o
nitropropanol (table 3). In aqueous medium, using catalytic amounts of 1 at 75 C, a
maximum yield of 88 % is achieved in 60 h with a higher selectivity towards the syn isomer
(table 3, entries 1-5).
As indicated above, using a catalytic amount of a base (5 mol% of triethylamine) led to an
improvement in the reaction yield (87 %) in a shorter time and at room temperature (table 3,
entry 6), although in this case with a decrease in selectivity.
The catalytic study of complex 1 for nitroaldol reaction was extended to various para-
substituted aromatic aldehydes (table 4). With both nitroalkanes, the corresponding β-
nitroalcohols were obtained with yields ranging from 51 % to 97 %, with higher selectivity
towards the syn isomer when nitroethane was used. The results indicate that an aromatic
aldehyde bearing an electron-withdrawing group (nitro, bromo or chloro, table 4, entries 7-
12) exhibits a higher reactivity than those with electron-donating substituents (methoxy or
methyl, table 4, entries 1-4), which is due to the higher electrophilicity of the aldehyde group
in the first case.
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Table 3. Henry reaction of nitroethane with benzaldehyde using complex 1 as catalyst [a]
Entry Time (h) T (oC)
Yield [b]
(%)
37
Selectivity [b]
(anti : syn)
28 : 72
TON [c]
1
2
12
24
36
48
60
24
75
75
75
75
75
23
7
48
66
83
88
23 : 77
27 : 73
30 : 70
29 : 71
10
13
17
18
18
3
4
5
6 [d]
87
49 : 51
[a]
Reaction conditions: benzaldehyde (0.5 mmol), 5 mol% of catalyst, 3 equiv of nitroethane (1.5
mmol), 2 mL of solvent. [b] Determined by 1H NMR analysis of crude products (see Experimental part
and figure S3). Number of moles of product (1-phenyl-2-nitropropanol) per mol of catalyst.
[c]
[d]
In
the presence of 5 mol% triethylamine.
Table 4. Henry reaction of nitroalkanes with various aldehydes using complex 1 as catalyst [a]
Yield [b]
(%)
51
Selectivity [b]
(anti : syn)
Entry
X
MeO
Me
H
R
TON [c]
10
10
16
16
18
16
20
18
19
18
18
17
1
2
3
4
5
6
7
8
9
H
Me
H
Me
H
Me
H
Me
H
-
51
81
80
91
83
97
91
95
32 : 68
-
33 : 67
-
30 : 70
-
NO2
Br
42 : 58
-
29 : 71
-
10
11
12
Me
H
Me
88
92
84
Cl
36 : 64
[a]
All reactions were performed at 75oC for 48 h in air, using 0.5 mmol of aldehyde with 5 mol% of
catalyst and 3 equiv. of nitroalkane (1.5 mmol) in 2 mL of water. [b] Determined by 1H NMR analysis
of crude products (see Experimental part and figure S4). [c] Number of moles of the produced β-nitro
alcohol, per mol of catalyst.
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Since complex 1 has a metal-acetate type structure, the mechanism of the reaction is expected
to be similar to that reported by Evans et al. for related catalytic systems,[67] where the Lewis
acidic copper(II) centers of 1, bearing moderately basic charged acetate ligands, would
facilitate the nitroalkane deprotonation as a prelude to the aldol addition step. It would also
activate the aldehyde moiety towards nucleophilic attack by the nitronate species
R(NO2)CH.[36]
In comparison to the few examples found in literature for catalytic nitroaldol reaction in
aqueous medium using catalysts based on different transition metals (table S1), the yields
observed in this work are found to be comparable or even better in some cases, taking into
consideration the reaction conditions such as temperature, amount of catalyst and reaction
time.[36,37,68–73]
Aerobic oxidation of benzyl alcohol. Compound 1 was also tested as catalyst for the aerobic
oxidation of benzyl alcohol mediated by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl
radical) in aqueous medium to give benzaldehyde (table 5). Performing this reaction for 6 h at
room temperature using 5 mol% of 1 and TEMPO, gave only 16 % yield on benzaldehyde
(Table 5, entry 1). Increasing the temperature to 80 oC rose the yield up to 41 % in 6 h (table
5, entry 2), and an extension of the reaction time, keeping this latter temperature, led to a
significant improvement of the yield (78 % after 21 h and 89 % after 48 h: table 5, entries 3
and 4). In agreement with what has already been reported,[44–47] the presence of a base
(K2CO3) and of TEMPO are crucial for the reaction to proceed (table 5, entries 5 and 6).
The catalysis mechanism is expected to be similar to the one previously proposed for a
Cu(II)-TEMPO-air radical catalytic system.[74,75] The TEMPO radical and base-assisted
deprotonated alcohol (RCH2O–) coordinate to the Cu(II) center which simultaneously
activates these species. Hydrogen abstraction of the alcoholate α-carbon by TEMPO occurs,
the resulting O-ligated RCHO radical being stabilized by H-bond. The following
intramolecular electron transfer from the bound radical to the Cu(II) center produces the
aldehyde (RCHO), TEMPO-H and a Cu(I) species which is thereafter TEMPO-mediated
reoxidized to Cu(II).
Table 5. Aerobic oxidation of benzyl alcohol to benzaldehyde using complex 1 as catalyst [a]
Page 13 of 33
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Chemistry - An Asian Journal
Entry Time (h)
Temp. (oC)
Yield[b]
(%)
16
TON [c]
1
2
6
6
23(RT)
80
3
8
41
3
4
21
48
6
6
6
80
80
80
80
78
89
14
<1
16
18
3
-
-
5 [d]
6 [e]
7 [f]
80
<1
[a]
All reactions were performed in open air using 0.5 mmol of benzyl alcohol, 5 mol% of catalyst 1
and 5 mol% of TEMPO in 2 mL of 0.1 M K2CO3 aqueous solution. [b] Calculated using GC analyses.
[c]
[d]
[e]
Number of moles of the product benzaldehyde, per mol of catalyst. In water without K2CO3.
Without TEMPO. [f] Without the metal catalyst.
Catecholase activity. The catalytic activity of compound 1 was also investigated in the
oxidation of 3,5-di-tert-butyl-catechol (3,5-dtbc) to the corresponding diketone 3,5-di-tert-
butyl-quinone (3,5-dtbq) under aerobic conditions as a model reaction (scheme 4). This
substrate has been broadly used because of the low redox potential for the quinone-catechol
couple (easy oxidation to the corresponding quinone) and of the bulky substituents which
inhibit degradation of the substrate for at least 6 h.[76]
tBu
tBu
Cat 1, MeOH
air
tBu
HO
tBu
O
OH
O
Scheme 4. Schematic representation of the oxidation of 3,5-dtbc to 3,5-dtbq
The product is stable and the UV-Vis spectrum in methanol shows an intense band at 390 nm
with  = 1518 M-1cm-1 (see figure S5). The absorption at 390 nm was measured as a function
of time over the first 5 min. In figure 4 it is observed the growth of the quinone band during
the reaction.
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Figure 4. Increase of quinone band at 390 nm after addition of compound 1 (6.57 × 105 M) to a
solution of 3,5-dtbc (1.35 × 102 M) in methanol at 25 °C
To determine the rate dependence on the substrate concentration, a solution of compound 1
was treated with different concentrations of 3,5-dtbc. The kinetic study was carried out using
the initial slope method. The rates of the reactions for different substrate concentrations was
fitted to the Michaelis-Menten equation (figure 5). On the basis of the obtained data, a rate
constant (kcat) of 50.8 min-1 was obtained, the maximum rate (Vmax) achieved was of 3.34 ×
103 ± 3.55 × 105 M min−1 and a Michaelis constant (KM) of 1.14 × 104 ± 9.21 × 106 M (R2
= 0.93566), therefore leading to a catalytic efficiency (kcat/KM) of 4.46 × 105 M1min1.
Page 15 of 33
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Figure 5. Michaelis-Menten plot for the oxidation of 3,5-dtbc (concentration range: 6.73 × 105 – 1.35
× 102 M) catalyzed with complex 1 (6.57 × 105 M) in methanol at 25 °C.
The obtained value for the kinetic parameter is significantly higher than those reported for
other dinuclear Cu(II) compounds containing acetate ligands,[51,52,59,60] as well as for other
copper(II) compounds.[76–78] However, our kcat value is much lower than that found, e.g. for
the cationic compound [Cu2(H2L)(OH)(H2O)(NO3)](NO3)3 (L = 2,6-bis(N-ethylpiperazine-
iminomethyl)-4-methyl-phenolato), for which kcat was 540 min1,[79] but the catalytic
efficiency of this catalyst is shorter (2.35×105 M1min1) than that observed for 1 (see above).
It has been suggested that the geometry around the copper ions and the electronic features of
the complex determine its catecholase-like activity, with square-planar complexes commonly
being the most active ones.[60] In the case of 1 the change of bidentate to monodentate
coordination of two acetate bridging ligands can allow the coordination of 3,5-debc in the
usually proposed bridging mode between the two Cu(II) ions. The rate of this catalytic
reaction has been tentatively related, among other parameters, with the Cu···Cu separation in
Page 16 of 33
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Chemistry - An Asian Journal
the catalyst molecule: the larger this distance, the lower the reaction rate since the bridging of
the substrate between the metals is consequently hampered.[53] In this respect, the distance of
2.612 Å between the two metals in 1 is much shorter than that of ca. 2.9 Å considered as
appropriate for a copper catalyst mimicking catechol oxidase.[60] Contrary to what was found
for other dicopper-based catalysts where rigid frameworks are usually met together with good
electron donor bridging ligands such as phenoxide,[60] the two metals in 1 are hold solely by
acetate anions, with DAPTA=O eventually playing a stabilizing role of both the oxidized and
reduced states of copper.
In line with what has been proposed,[60,80] the 3,5-dtbc oxidation can involve (scheme 5) a
transient semiquinone radical and the Cu(II)-to-Cu(I) reduction of the metal centers; the
presence of dioxygen, would lead to the regeneration of the dicopper(II) catalyst 1.
Scheme 5. Proposed general mechanism of 3,5-dtbc oxidation catalyzed by complex 1 (the
DAPTA=O ligands were omitted for clarity).
Theoretical studies. With the aim to support the proposed catalytic cycle, theoretical DFT
calculations of the crucial steps of the catechol oxidation catalysed by the model complex
[Cu(-CH3COO)2(OPH3)]2 (1’) in triplet spin state have been carried out. Since the
Page 17 of 33
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coordination spheres of the copper atoms in the catalyst molecule are saturated, the ligation
of catechol to the metal center(s) requires the formation of a free coordination site. This may
occur upon protonation of one acetate ligand in 1’ by catechol to give intermediate 3
followed by the elimination of acetic acid leading to complex 4 (scheme 6). However, the
energy of the proton transfer from catechol to the acetate ligand is very high (43.6 kcal/mol),
and this pathway may be ruled out.
+
PH
O
+
3
H P
3
HO
OH
H P
H P HO
3
O
3
O
O
–
O
O
O
HO
O
O
O
O
O
Cu
O
O
Cu
Cu
Cu
O
Cu

Cu
O
O
–
O
–CH COOH
HO
–
O
3
O
O
O
O
O
O
O
O
O
O
PH
PH
3
3
(41.8)
4
(43.6)
3
(0.0)
1'
HO
H
O
HO
HO
O
O
O
H P
3
•
PH
O
O
–
3
O
H P
O
3
O
H
H P
3
HO OH
O
H P
3
O
O
O
Cu
H P
3
O
O
Cu
O
O
TS1
(9.0)
O
O
O
Cu
3
Cu
O
O
O
TS3
O
Cu
Cu
O
O
O
O
Cu
Cu
Cu
O
O
(16.5)
O
O
Cu
•
O
–CH COOH
3
O
O
HO
O
O
O
O
O
O
O
O
O
PH
O
3
O
O
PH
O
PH
O
PH
3
3
O
3
3
6a(8.9)
3
(9.1)
7(10.0)
5
(7.6)
9
(20.2)
10
+
O
O
HO
PH
3
O
H P
3
PH
3
H P
3
O
O
O
O
II
TS2
(21.1)
Cu – Cu
H P
3
O
O
O
O
O
1
O
I
H P
O
O
–
O
TS3
3
Cu – Cu
O
Cu
Cu
O
O
Cu
O
Cu
O
O
O
(27.7)
H
O
Cu
OH
O
O
Cu
Cu
O
O
–CH COOH
Cu
O
H
3
O
O
OH
O
O
O
O
O
O
PH
O
O
3
PH
OH
O
3
6b(9.7)
(22.6)
8
1
9(24.5)
1
10 (12.5)
Scheme 6. Mechanisms of the catechol oxidation catalyzed by the model complex 1’. The
Gibbs free energies in methanol solution are indicated in kcal/mol relative to 1’ + catechol.
The most favorable mechanism is boxed.
Another possibility is decoordination of an acetate ligand from one of the copper atoms to
give complex 5. This process requires only 9.1 kcal/mol (in terms of Gs). The ligation of
catechol to 5 is almost energetically neutral (Gs = –0.2 kcal/mol) and results in the
formation of complex 6. For the latter, two isomers with different positions of the catechol
ligand were found, 6a and 6b (scheme 6), but with similar energies. The proton transfer from
the catechol ligand to an acetate ligand in 6a or 6b leads to the hydrocatecholate
Cu(II)/Cu(II) complexes 7 or 8, respectively. The H-transfer in 6a occurs via transition state
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TS1 with very low activation energy of 0.1 kcal/mol. The H-transfer in 6b via TS2 requires a
much higher barrier of 11.4 kcal/mol and, therefore, this pathway may be excluded from the
following consideration.
Gibbs free energies of both TS1 and TS2 are slightly lower than the energies of the reaction
products 7 and 8, respectively. This may be explained by the fact that the equilibrium
geometries of all calculated species correspond to minima on the enthalpy (0 K) surface
rather than on the Gibbs free energy surface. Indeed, in terms of the enthalpy at 0 K, the
energies of both transition states are higher than the energies of the corresponding products
(table S2).
3
The monodentate acetic acid in 7 may be easily eliminated affording 9 (Gs = –2.3
3
kcal/mol). In structure 9, the hydrocatecholate ligand is coordinated to only one of the Cu
atoms, and thus a bridging bidentate type of the hydrocatecholate ligand was not found.
The following transformation of the hydrocatecholate into quinone may occur via two
possible routes. The first one includes a proton transfer from the hydrocatecholate ligand to
3
3
one of the acetates in 9 via TS3 and, after acetic acid elimination, leads to the triplet
3
complex 10. In this complex, spin electron density is mostly concentrated at one of the Cu
atoms and at the organic ligand (figure 6) indicating that this is a mixed valence Cu(II)/Cu(I)
complex and that the proton shift in 39 results in the intramolecular single-electron oxidation
of catechol to semiquinone by one of the metal centers. The second single-electron oxidation
3
of the semiquinolate ligand in 10 to the quinone product occurs upon spontaneous spin
1
conversion to the singlet closed shell Cu(I)/Cu(I) complex 10 with both acetic acid and
quinone molecules being in the second coordination sphere (Gs = 7.7 kcal/mol).
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Figure 6. Spin density distribution in 310.
The next pathways include the excitation of complex 39 into the singlet spin state followed by
1
1
the proton transfer via the singlet TS3 to yield the quinone complex 10. This pathway is
associated with the activation barrier of 27.7 kcal/mol that is too high for a reaction easily
occurring at room temperature.
The most plausible mechanism of the catechol oxidation can be described by the following
sequence of the reaction steps: 1’  5 (+ catechol)  6a  7  39 (–CH3COOH)  310 
110 (scheme 6). The calculated overall Gibbs free energy of activation for the catechol
3
oxidation is 16.5 kcal/mol, and TS3 is the rate limiting transition state. Such rather low
activation barrier correlates with the experimental data on the rapid conversion of 3,5-tdbc at
room temperature.
Conclusions
Two dinuclear hydrosoluble complexes of Cu(II) and Na(I) are reported, which constitute the
first examples of metal complexes containing DAPTA=O as ligands. The oxidized phosphane
ligand was prepared in a one-pot simple reaction of DAPTA in an undried solvent, in the
presence of a metal salt in air under mild conditions. Based on the results obtained by
deliberately using 18O-labeled water, the source of oxygen in the DAPTA=O ligand was
proved to be this solvent, adventitiously present in the reaction mixture. Of interest is that the
Na(I) complex 2 represents the first case of DAPTA core O-coordination ability through the
oxygen atoms of the acetyl groups.
The Cu(II) complex 1 was proved to be a moderately active catalyst not only for the Henry
reaction but also for the aerobic alcohol oxidation, using water as solvent. Moreover,
compound 1 has been successfully evaluated as a model for the catechol oxidase enzyme by
using 3,5-di-tert-butyl-catechol (3,5-dtbc) as substrate, showing one of the highest activities
(as measured by the catalytic rate constant kcat of 50.8 min1) and one of the highest catalytic
efficiencies (determined by the kcat/KM ratio of 4.46 × 105 M1min1), as compared to other
previously described dinuclear acetate-bridging copper(II) complexes.
Theoretical DFT calculations revealed that the most plausible mechanism of the catechol
oxidation into quinone catalysed by the diphosphinoxido tetraacetate dicopper(II) complex
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includes the decoordination of an acetate ligand from one of the Cu centers in the catalyst
molecule and ligation of the catechol molecule to the formed vacant coordination site, then
followed by proton transfer from the catechol to the monodentate acetate and elimination of
acetic acid; a second proton transfer from the hydrocatecholate ligand to an acetate ligand and
spin conversion of the formed product gives the final quinone and a Cu(I)/Cu(I) complex.
The proposed mechanism involves, therefore, a mixed valence Cu(II)/Cu(I) species and the
cooperation of the acetate ligand. Despite the dinuclear character of the catalyst, during the
oxidation process the catechol substrate appears to interact directly with only one of the metal
centers.
The study demonstrates for the first time that DAPTA=O can behave as a convenient ligand
under various viewpoints: i) it imparts water solubility to its complexes, allowing their use in
water, e.g. as catalysts; ii) it assists the metal center, Cu(II), to acquire suitable electronic
properties for Lewis acid and oxidation catalysis; iii) it conceivably provides stereochemical
protection of the metal center, assisting its stabilization along the reaction. Therefore, the
coordination chemistry of this still virtually unexplored ligand deserves to be further
explored, namely in fields of Lewis acid and redox catalysis in aqueous medium.
Experimental Section
Materials and Methods. Starting materials (copper acetate monohydrate, nickel acetate
hexahydrate, sodium tetraphenylborate, 3,5-di-tert-butylcatechol and 3,5-di-tert-
butylquinone) and solvents were obtained from commercial sources and used as received
without further purifications. DAPTA was synthesized by following an already published
procedure,[12,13] and all synthetic work was performed in air.
Carbon, hydrogen and nitrogen elemental analyses were carried out by the Microanalytical
services of the Instituto Superior Técnico. Fourier transform infrared (FTIR) spectra (4000–
1
31
400 cm-1) were recorded on a Bruker Vertex 70 instrument as KBr pellets. H and P NMR
spectra were measured at ambient temperature using Bruker Avance 300 or 400 MHz
1
spectrometers. All chemical shifts are quoted in δ (ppm). H NMR spectra were referenced
internally to residual protio-solvent resonance and are reported relative to tetramethylsilane;
31P chemical shifts were referenced using external 85% H3PO4. Electrospray mass spectra
were obtained with a Varian 500 MS LC Ion Trap Mass Spectrometer equipped with an
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electrospray (ESI) ion source. For electrospray ionization, the drying gas and flow rate were
optimized according to the particular sample with 35 p.s.i. nebulizer pressure. The
compounds were observed in the positive mode (capillary voltage = 80–105 V). Gas
chromatographic (GC) analyses were performed using a Fisons Instruments GC 8000 series
gas chromatograph with DB-624 (J&W) capillary column (FID detector) and the Jasco-
Borwin v.1.50 software. Catecholase activity studies were performed using an Agilent Cary
8454 UV-Visible Spectrophotometer with Agilent 89090A Peltier temperature controller and
magnetic stirrer controller, and 845x UV-Vis System.
Synthesis of [CuII(-CH3COO)2(O-DAPTA=O)]2 (1). A round bottom flask fitted with a
magnetic stirrer was charged with copper(II) acetate monohydrate (0.14 g, 0.7 mmol) and
DAPTA (0.17 g, 0.7 mmol) in 25 mL toluene and 10 mL ethanol. The obtained green
solution was stirred at room temperature for 8 hours then allowed to stand at ambient
temperature with the flask closed for 2 weeks to obtain cyan crystals of 1 suitable for X-ray
measurements. Yield, 31% (0.092 g, based on Cu).
FTIR (KBr, selected bands, in cm−1): ν(C-H) 2943, ν(P=O) 1153, ν(C=O) 1627. Elemental
analysis: calcd (%) for C26H44Cu2N6O14P2: C 36.58, H 5.19, N 9.84; found: C 35.86, H 4.80,
1
N 8.78. H NMR (400 MHz, DMSO, δ): 5.38 (d, J = 12 Hz, 2H, NCH2N), 4.97–5.07 (br m,
2H, NCH2N and 2H, PCH2N), 4.81 (d, J = 12 Hz, 2H, NCH2N), 4.60–4.71 (br m, 2H,
PCH2N), 4.37 (m, 2H, PCH2N), 3.90 (m, 2H, PCH2N), 3.72-3.81 (br m, 2H, NCH2N and 4H,
PCH2N), 2.09 (s, 12H, NC(O)CH3), 1.93 (br s, 12H, CuC(O)CH3). 31P{1H} NMR (400 MHz,
DMSO, δ): 2.95. ESI-MS+ in H2O (m/z assignment,
%
intensity): 449
([Cu(DAPTA=O)(CH3COO)2 + Na]+, 100), 246 ([DAPTA=O + H]+, 71), 367
([Cu(DAPTA=O)(CH3COO)]+, 36), 445 ([Cu(DAPTA=O)(CH3COO)2 + H2O + H]+, 30), 513
([2 DAPTA=O + Na]+, 23), 612 ([Cu(DAPTA=O)2(CH3COO)]+, 39).
18
Experiment with O-labeled water. The above procedure for complex 1 preparation was
18
repeated using freshly dried solvents in inert N2 atmosphere and additional 50 µl of H2 O.
The obtained cyan powder was isolated by filtration, washed with diethyl ether and dried in
vacuum.
ESI-MS+ in H2O (m/z assignment, % intensity): 248 ([DAPTA=O18 + H]+, 24), 288
([(DAPTA=O18 + H2O + Na]+, 100), 369 ([Cu(DAPTA=O18)(CH3COO)]+, 14), 469
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([Cu(DAPTA=O18)(CH3COO)2 + H2O + Na]+, 40), 517 ([2 DAPTA=O18 + Na]+, 15), 616
([Cu(DAPTA=O18)2(CH3COO)]+, 9).
Synthesis of [Na(1OO’;2O-DAPTA=O)(MeOH)]2(BPh4)2 (2). A round bottom flask
fitted with a magnetic stirrer was charged with DAPTA (0.23 g, 1 mmol), sodium
tetraphenylborate Na(BPh4) (0.34 g, 1 mmol) and nickel acetate hexahydrate
Ni(CH3COO)2.6H2O (0.29 g, 1 mmol) in 10 mL methanol. The obtained solution was stirred
o
overnight at room temperature, then by slow diffusion of diethyl ether vapor at 4 C, white
crystals of 2 suitable for X-ray measurements were obtained. Yield, 32% (0.2 g, based on
Na).
FTIR (KBr, selected bands, ν in cm−1): ν(P=O) 1163, ν(C=O) 1631. Elemental analysis calcd
1
(%) for C68H80B2N6Na2O8P2: C 65.92, H 6.51, N 6.78; found: C 64.78, H 5.62, N 6.61. H
NMR (400 MHz, DMSO, δ): 7.71 (m, 16H, ArH Ph-C2,6-H), 6.92 (dd, J1 = J2 = 8 Hz, 16 H,
ArH Ph-C3,5-H), 6.78 (dd, J1 = J2 = 8 Hz, 8 H, ArH Ph-C4-H), 5.59 (br s, 2H, HOCH3), 5.39
(d, J = 12 Hz, 2H, NCH2N), 4.97–5.08 (br m, 2H, NCH2N and 2H, PCH2N), 4.81 (d, J = 12
Hz, 2H, NCH2N), 4.43 (m, 2H, PCH2N), 4.37 (d, J = 16 Hz, 2H, PCH2N), 4.02 (m, 2H,
PCH2N), 3.90 (d, J = 16 Hz, 2H, NCH2N), 3.78 (d, J = 8 Hz, 4H, PCH2N), 3.16 (s, 6 H,
31
HOCH3), 2.11 (s, 12H, C(O)CH3). P{1H} NMR (400 MHz, DMSO, δ): 3.10. ESI-MS- in
MeOH (m/z assignment, % intensity): 319 ([(C6H5)4B]-, 100). ESI-MS+ in MeOH (m/z
assignment, % intensity): 365 ([C6H5)4B + 2Na]+, 100), 300 ([Na(DAPTA=O)(MeOH)]+, 13).
X-ray structure determinations. X-ray quality crystals of 1 and 2 were immersed in cryo-
oil, mounted in a Nylon loop and measured at ambient temperature. Intensity data were
collected using a Bruker AXS-KAPPA APEX II PHOTON 100 diffractometer with graphite
monochromated Mo-Kα (0.71069 Å) radiation. Data were collected using omega scans of
0.5° per frame and full sphere of data were obtained. Cell parameters were retrieved using
Bruker SMART[81] software and refined using Bruker SAINT[81] on all the observed
reflections. Absorption corrections were applied using the SADABS program.[82] The
structures were solved by direct methods using SIR97 package[83] and refined with SHELXL-
2014/7.[84] Calculations were performed using the WinGX System-Version 2014.1.[85] The
hydrogen atoms were included in the refinement using the riding-model approximation;
Uiso(H) were defined as 1.2Ueq of the parent carbon atoms for phenyl and methylene residues,
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and 1.5Ueq of the parent carbon atoms for methyl. The O-bound H-atom of the coordinated
methanol was found in the difference Fourier map, the isotropic thermal parameter was set at
1.5 times the average thermal parameter of the oxygen atom and the position restrained by
using the DFIX and DANG commands. Least square refinements with anisotropic thermal
motion parameters for all the non-hydrogen atoms were employed. Crystallographic data and
selected structural details for compounds 1 and 2 are listed in table 6.
Table 6. Crystal data and structure refinement details for complexes 1 and 2.
1
C26H44Cu2N6O14P2
853.69
2
C68H80B2N6Na2O8P2
1238.92
Empirical formula
Formula Weight
Crystal system
triclinic
triclinic
Space group
P –1
P -1
Temperature/K
296 (2)
293(2)
a/Å
b/Å
c/Å
8.5049(12)
10.0708(13)
11.0145(15)
96.825(5)
98.513(5)
108.285(4)
872.1(2)
10.968(8)
11.624(9)
13.403(9)
88.81(3)
71.89(3)
77.02(3)
1581(2)

/

V (Å3)
Z
1
1
Dcalc (g cm–3)
1.626
1.302
F000
(Mo K) (mm–1)
442
1.385
656
0.144
Rfls. collected/unique/observed
14577/ 3176/ 2191
0.0934
0.0433, 0.0779
22296/ 5842/ 3646
0.0687
0.0536, 0.1196
Rint
[a]
[b]
Final R1 , wR2 (I  2σ)
Goodness-of-fit on F2
0.983
[b]
0.955
[a]
R = ||Fo|–|Fc||/|Fo|; wR(F2) = [w(|Fo|2 – |Fc|2)2/w|Fo|4]½
Catalytic activity studies
Nitroaldol (Henry) reaction. In a typical experiment, the nitroalkane (1.5 mmol) was added
to a solution of complex 1 (0.025 mmol) in 2 mL water, and the mixture was stirred for 15
minutes. The aldehyde (0.5 mmol) was added and the solution stirred in air under conditions
and time intervals indicated in tables 2, 3 and 4. Then the mixture was diluted with 3 mL
water and extracted three times with 10 mL of diethyl ether. The combined extracts were
dried over anhydrous Na2SO4, and the mixture was then filtered off. After removal of diethyl
ether under vacuum, the residue was taken for analysis by 1H NMR spectroscopy, in CDCl3,
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in order to calculate the yield of obtained β-nitroalcohol, as no other products were detected
1
(figures S2-4). The usage of H NMR spectroscopy for the calculation of the obtained yields
of β-nitroalcohols has proved to be effective in several other cases.[36,38,40,68,86–88] A number of
1H NMR analyses were also performed in the presence of an internal standard (1,2-
dimethoxyethane) to verify the efficiency of the procedure, giving yields similar to those
obtained by the above method. The ratio between the anti and syn diastereoisomers of 1-
phenyl-2-nitropropanol, obtained in the nitroaldol catalytic reaction using nitroethane, was
1
also determined by H NMR spectroscopy, as the values of vicinal coupling constants
between the α-O–C–H and the α-N–C–H protons identify the isomers (J = 7–9 Hz for the
anti-isomer, and J = 3.2–4 for the syn-isomer).[89,90]
Aerobic benzyl alcohol oxidation in aqueous medium. In a typical experiment, to a round
bottom flask equipped with a condenser and a magnetic stirrer, benzyl alcohol (0.5 mmol)
was added to 2 mL of 0.1 M K2CO3 aqueous solution, followed by catalyst 1 (0.025 mmol)
and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 0.025 mmol). The obtained mixture was
vigorously stirred under conditions and time intervals indicated in table 5 and in air.
Eventually, the reaction mixture was neutralized with an appropriate amount of 1 M HCl and
extracted with ethyl acetate. The organic phase was then analyzed by gas chromatography
using cyclopentanone as internal standard.
Catecholase activity. The experiments were performed under aerobic conditions at constant
stirring and temperature of 25ºC (monitored with a contact thermometer dipped in the
solution). Measurements were performed using 1 cm path length quartz cuvette. In a typical
test, the 6.73 × 105 – 1.35 × 102 M fresh methanol solutions of 3,5-di-tert-butylcatechol
(3,5-dtbc) were treated with a 6.57 × 105 M methanol solution of compound 1 (1 – 205
equivalents). The absorbance was also measured at 390 nm (ε = 1518 M-1cm-1) as a function
of time, over the first 5 min immediately after the addition of catalyst. Control experiment
carried out under the same conditions but in the absence of copper(II) catalyst showed no
conversion of 3,5-dtbc to 3,5-dtbq.
Computational Details
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10.1002/asia.201800799
Chemistry - An Asian Journal
The full geometry optimization of all structures and transition states was carried out at the
DFT level of theory using the M06 functional[91] with the help of the Gaussian-09 program
package.[92] No symmetry operations were applied for any of the structures calculated. The
geometry optimization was carried out using a relativistic Stuttgart pseudopotential which
describes 10 core electrons and the appropriate contracted basis set (8s7p6d)/[6s5p3d] for the
copper atom[93] and the 6-31G* basis set for other atoms. Single-point calculations were then
performed on the basis of the equilibrium geometries found by using the 6-311+G** basis set
for nonmetal atoms. The Hessian matrix was calculated analytically for all optimized
structures to prove the location of correct minima (no imaginary frequencies) or saddle points
(only one imaginary frequency) and to estimate the thermodynamic parameters, the latter
being calculated at 25 °C. The nature of transition states was investigated by analysis of the
vectors associated with the imaginary frequency and by calculations of the intrinsic reaction
coordinates (IRC) by using the method developed by Gonzalez and Schlegel.[94–96]
The total energies corrected for solvent effects (Es) were estimated at the single-point
calculations on the basis of gas-phase geometries at the CPCM-M06/6-311+G**//gas-M06/6-
31G* level of theory using the polarizable continuum model in the CPCM version[97,98] with
methanol as the solvent. The dispersion, repulsion and cavitation terms were considered. The
entropic term in solutions (Ss) was calculated according to the procedure described by
Wertz[99] and Cooper and Ziegler[100] using equations (1)–(4):
S1 = RlnVsm,liq/Vm,gas
S2 = RlnV°m/Vsm,liq
(1)
(2)
°,s
liq
°,s
s
−(S +RlnV
/V
)
훼 = S
(3)
m,gas
gas
m,liq
°,s
s
(S +RlnV
/V
)
m,gas
gas
m,liq
Ss = Sg + Ssol = Sg + [S1 + (Sg + S1) + S2] =
Sg – 12.72 cal/mol•K – 0.32(Sg – 12.72 cal/mol•K) + 6.37 cal/mol•K
(4)
where Sg is the gas-phase entropy of the solute, ΔSsol is the solvation entropy, S°,sliq, S°,s
gas
and Vsm,liq are the standard entropies and molar volumes of the solvent in the liquid or gas
phases (127.2 and 239.9 J/mol•K and 40.46 mL/mol, respectively, for CH3OH), Vm,gas is the
molar volume of the ideal gas at 25 °C (24450 mL/mol), V°m is the molar volume of the
solution that corresponds to the standard conditions (1000 mL/mol). The enthalpies and
Page 26 of 33
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10.1002/asia.201800799
Chemistry - An Asian Journal
Gibbs free energies in solution (Hs and Gs, respectively) were estimated using expressions (5)
and (6)
Hs = Es(6-311+G**) + Hg(6-31G*) – Eg(6-311+G**)
Gs = Hs –TSs
(5)
(6)
where Es and Eg are the total energies in solution and the gas phase and Hg is the gas-phase
enthalpy calculated at the corresponding level.
Supporting information
CCDC 1576097 (for 1) and 1576098 (for 2) contain the supplementary crystallographic data
for this paper. This data can be obtained free of charge from The Cambridge Crystallographic
Data Center via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
This work has been partially supported by the Foundation for Science and Technology (FCT),
(UID/QUI/00100/2013), Portugal and NCN program (Grant No. 2012/07/B/ST/00885),
Poland. A. G. M. is thankful to the CATSUS doctoral program of FCT for his PhD fellowship
(SFRH/BD/106006/2014). The authors acknowledge the Portuguese NMR Network (IST-UL
Center) for access to the NMR facility and the IST Node of the Portuguese Network of Mass-
spectrometry for the ESI-MS measurements. Piotr Jakimowicz (Faculty of Biotechnology,
University of Wroclaw, Wroclaw, Poland) was acknowledged for his assistance in the
catechol oxidation studies.
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