Copper versus thioether-centered oxidation: Mechanistic insights into the non-innocent redox behavior of tripodal benzimidazolylaminothioether ligands

Article abstract of DOI:10.1002/chem.201203498

A series of Cu⁺ complexes with ligands that feature varying numbers of benzimidazole/thioether donors and methylene or ethylene linkers between the central nitrogen atom and the thioether sulfur atoms have been spectroscopically and electrochemically characterized. Cyclic voltammetry measurements indicated that the highest Cu²⁺/Cu⁺ redox potentials correspond to sulfur-rich coordination environments, with values decreasing as the thioether donors are replaced by nitrogen-donating benzimidazoles. Both Cu²⁺ and Cu⁺ complexes were studied by DFT. Their electronic properties were determined by analyzing their frontier orbitals, relative energies, and the contributions to the orbitals involved in redox processes, which revealed that the HOMOs of the more sulfur-rich copper complexes, particularly those with methylene linkers (-N-CH₂-S-), show significant aromatic thioether character. Thus, the theoretically predicted initial oxidation at the sulfur atom of the methylene-bridged ligands agrees with the experimentally determined oxidation waves in the voltammograms of the NS₃- and N₂S₂-type ligands as being ligand-based, as opposed to the copper-based processes of the ethylene-bridged Cu⁺ complexes. The electrochemical and theoretical results are consistent with our previously reported mechanistic proposal for Cu ²⁺-promoted oxidative C-S bond cleavage, which in this work resulted in the isolation and complete characterization (including by X-ray crystallography) of the decomposition products of two ligands employed, further supporting the novel reactivity pathway invoked. The combined results raise the possibility that the reactions of copper-thioether complexes in chemical and biochemical systems occur with redox participation of the sulfur atom. Copyright

Full text of DOI:10.1002/chem.201203498

FULL PAPER
DOI: 10.1002/chem.201203498
Copper Versus Thioether-Centered Oxidation: Mechanistic Insights into the
Non-Innocent Redox Behavior of Tripodal Benzimidazolylaminothioether
Ligands
Paulina R. Martꢀnez-Alanis,[a] Brenda N. Sꢁnchez Eguꢀa,[a] Vꢀctor M. Ugalde-Saldꢀvar,[b]
Ignacio Regla,[c] Patricia Demare,[c] Gabriel Aullꢂn,[d] and Ivan Castillo*[a]
Abstract: A series of Cu+ complexes
with ligands that feature varying num-
bers of benzimidazole/thioether donors
and methylene or ethylene linkers be-
tween the central nitrogen atom and
the thioether sulfur atoms have been
spectroscopically and electrochemically
volved in redox processes, which re-
vealed that the HOMOs of the more
sulfur-rich copper complexes, particu-
larly those with methylene linkers
processes of the ethylene-bridged Cu+
complexes. The electrochemical and
theoretical results are consistent with
our previously reported mechanistic
proposal for Cu2+-promoted oxidative
ꢀ ꢀ
ꢀ ꢀ
( N CH2 S ), show significant aro-
matic thioether character. Thus, the
theoretically predicted initial oxidation
at the sulfur atom of the methylene-
bridged ligands agrees with the experi-
mentally determined oxidation waves
in the voltammograms of the NS3- and
N2S2-type ligands as being ligand-
based, as opposed to the copper-based
ꢀ
C S bond cleavage, which in this work
resulted in the isolation and complete
characterization (including by X-ray
crystallography) of the decomposition
products of two ligands employed, fur-
ther supporting the novel reactivity
pathway invoked. The combined results
raise the possibility that the reactions
of copper–thioether complexes in
chemical and biochemical systems
occur with redox participation of the
sulfur atom.
characterized.
Cyclic
voltammetry
measurements indicated that the high-
est Cu2+/Cu+ redox potentials corre-
spond to sulfur-rich coordination envi-
ronments, with values decreasing as the
thioether donors are replaced by nitro-
gen-donating benzimidazoles. Both
Cu2+ and Cu+ complexes were studied
by DFT. Their electronic properties
were determined by analyzing their
frontier orbitals, relative energies, and
the contributions to the orbitals in-
Keywords: copper · density func-
tional calculations · electrochemis-
try · oxidation · reaction mecha-
nisms
Introduction
these sulfur-based donors.[2] For example, in addition to the
predominantly thiolate-based Cu+ metallochaperones, thio-
ethers from methionine have been identified in copper traf-
ficking.[1a,i] Perhaps more intriguingly, methionine residues
have also been identified in several types of copper mono-
oxygenases;[1e,f,i,3] these systems, along with the involvement
of a cysteine residue in the generation of the active site of
galactose oxidase,[4] have increased the interest in copper–
thioether systems. Reports on relevant inorganic model sys-
tems have established that copper centers in thioether-rich
coordination environments are characterized by high redox
potentials for the Cu2+/Cu+ couple. Among these, the ethyl-
ene-bridged tripodal NS3 ligands employed by Rorabacher
and co-workers have redox potentials of approximately
280 mV relative to the ferrocenium/ferrocene (Fc+/Fc) cou-
ple.[1c,5] In addition to the number of thioether donors, redox
properties can also be modulated by the size of the chelate
formed upon complexation of polydentate ligands; for ex-
ample, related tripodal ligands with N2S2 coordination envi-
ronments have half-wave potentials as high as 540 mV (vs.
Fc+/Fc) as a result of the six-membered chelates formed.[6]
Our research group recently reported the synthesis of
The presence of thioether ligands in bioinorganic systems,
particularly in the active sites of copper-containing metallo-
ACHTUNGTRENNUNG
enzymes,[1] has resulted in a growing number of reports on
[a] Dr. P. R. Martꢀnez-Alanis, B. N. Sꢁnchez Eguꢀa, Prof. I. Castillo
Instituto de Quꢀmica, Universidad Nacional Autꢂnoma de Mꢃxico
Circuito Exterior, CU, Mꢃxico DF, 04510 (Mꢃxico)
Fax : (+5255)5616-2217
E-mail: joseivan@unam.mx
[b] Prof. V. M. Ugalde-Saldꢀvar
Facultad de Quꢀmica, Divisiꢂn de Estudios de Posgrado
Universidad Nacional Autꢂnoma de Mꢃxico
Circuito Exterior, CU, Mꢃxico DF, 04510 (Mꢃxico)
[c] Prof. I. Regla, Dr. P. Demare
Facultad de Estudios Superiores – Zaragoza
Universidad Nacional Autꢂnoma de Mꢃxico
Batalla del 5 de Mayo y Fuerte de Loreto
Mꢃxico DF, 09230 (Mꢃxico)
[d] Dr. G. Aullꢂn
Departament de Quꢀmica Inorgꢄnica, Universitat de Barcelona
Martꢀ i Franquꢅs 1–11, 08028 Barcelona (Spain)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203498.
neutral tripodal aminotrithioethers NACTHNUTRGNEUNG
(CH2SAr)3 (L1 and
Chem. Eur. J. 2013, 19, 6067 – 6079
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6067

Results and Discussion
Synthesis and characterization
Ligands: The ligands were designed and prepared with a
view to accessing compounds with varying numbers of thio-
ether/benzimidazole donors in order to systematically study
the spectroscopic, structural, and electrochemical properties
of their copper complexes. Aminotrithioethers L1 and L1Bu
were prepared by the condensation of thiophenols with
hexaACHTNUGRTNEUNG
methylenetetramine (HMT), as described previously.[7]
Ligand L1’, the “long-arm” analogue of L1 that incorporates
an additional methylene linker between the amine and thio-
ether functionalities, was synthesized by nucleophilic attack
of the thiophenol on tris(2-bromoethyl)amine, as depicted in
Scheme 2. Introduction of one benzimidazole donor in L2
Scheme 2. Synthesis of L1’.
Scheme 1. Tripodal ligands studied in this work.
L1Bu in Scheme 1) as well as their reactivity towards Cu+
required the initial synthesis of 1-methyl-2-aminomethyl-
[7]
and Cu2+
.
The ligands are oxidized by Cu2+ ions, which
benzimidazole (B) from precursor A[9] starting from
ACHTUNGTRENNUNG
are in turn reduced to Cu+, which indicates that the methyl-
ene linker has an intrinsic reactivity that does not allow the
determination of half-wave potentials (E1/2). Nonetheless,
determination of the anodic peak potentials (Epa) of the
Cu+ complexes in acetonitrile solution revealed that they
have high redox potentials for the Cu2+/Cu+ couple, such
that ligand-based oxidation occurs before oxidation at the
copper center. To further investigate the redox properties of
methylene-bridged thioethers, we have synthesized related
sulfur-containing ligands that incorporate the biologically
relevant benzimidazole as mimics of the ubiquitous histidine
residues in the active sites of copper-containing metalloen-
zymes.[8] A combined experimental and theoretical study of
the effect of thioether ligands on the electrochemical prop-
erties of their copper complexes based on the systematic
variation of the number of sulfur (thioether) and nitrogen
(benzimidazole) donors was undertaken. The results ob-
tained, including the isolated and fully characterized oxida-
tive decomposition products of two of the ligands, allowed
us to postulate a mechanism for the reactions observed. The
new ligands considered in this work include the “short-arm”
bis- and monothioethers L2 and L3, the “long-arm” ana-
logues L2’ and L3’, and the previously reported tris(2-methyl-
benzimidazolyl)amine (L4) and its N-methylated analogue
L4’ (Scheme 1).
1-methyl-2-chloromethylbenzimidazole
(Scheme 3). Subsequent condensation with 2 equiv of para-
and
HMT
Scheme 3. Synthesis of L2.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
the condensation step, which would likely lead to intractable
products as a result of nucleophilic attack of the benzimid-
AHCTUNGTREGaNNUN zole nitrogen atom on formaldehyde. The long-arm ana-
logue L2’ was prepared by nucleophilic substitution of the
tert-butoxycarbonyl (Boc)-protected derivative 1-Boc-2-
chloromethylbenzimidazole by bis(2,4-dimethylphenylthio-
AHCTUNGTRENNUNG
ethyl)amine (C)[8,10] to provide the Boc-protected precursor
D (Scheme 4). Deprotection of the benzimidazolyl moiety
by acid treatment resulted in L2’ in an overall yield of 60%.
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Copper Versus Thioether-Centered Oxidation
FULL PAPER
Figure 1. Mercury diagram of the cation [CuL1’]+ at the 50% probability
ꢀ
level. The disordered PF6 anion and hydrogen atoms have been omitted
ꢀ
ꢀ
for clarity. Selected bond lengths [ꢇ]: Cu S1 2.319(1), Cu S2 2.288(1),
ꢀ
ꢀ
ꢀ
ꢀ
Cu S3 2.246(1), Cu N1 2.217(4); selected bond angles [8]: S1 Cu S2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
100.29(4), S1 Cu S3 133.81(5), S2 Cu S3 125.77(5), S1 Cu N1
ꢀ
ꢀ
ꢀ
ꢀ
83.07(9), S2 Cu N1 91.09(9), S3 Cu N1 92.04(9).
Scheme 4. Procedure for the synthesis of compound L2’.
angles reflect the distortion, varying from 100.29(4) to
The other ligands considered in this work are bis(benz-
133.81(5)8. These parameters are comparable to average
imidazolyl)aminothioether L3 and its long-arm derivative
bond lengths of 2.26 ꢇ for Cu S and 2.17 ꢇ for Cu N, and
ꢀ
ꢀ
L3’, the previously reported tris(benzimidazolyl)amine L4
and its copper complexes,[11] and its methylated analogue
L4’. Attempts to obtain L3 by different approaches were un-
successful; these included the reaction of bis(1-methyl-2-
methylbenzimidazolyl)amine with one equivalent of parafor-
maldehyde and 2,4-dimethylthiophenol as well as the reac-
tion with S-chloromethyl-2,4-dimethylphenylthioether. Com-
pound L3 was nonetheless included in the theoretical studies
for comparison purposes. The preparation of L3’ has previ-
ously been reported.[8] All the ligands were completely char-
acterized (see the Experimental Section).
average bond angles of 120 and 918 for S Cu S and
ꢀ
ꢀ
ꢀ
ꢀ
S Cu N, respectively, for the analogous (tris(methylthio-
ethyl)amine)–Cu+ complex with S-methyl substituents.[5a]
Complex [CuL2]ClO4 (2) was obtained as a colorless solid,
although the reaction between L2 and [Cu
(CH3CN)4]ClO4
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
appears to be affected by the formation of insoluble prod-
ucts, which had to be eliminated by filtration to obtain ana-
lytically pure samples of 2, thus resulting in a low yield. Fi-
nally, complex [CuL2’]ClO4 (2’) was obtained in moderate
yield as colorless microcrystals. Both 2 and 2’ are oxidized
1
by chloroform, but their H and 13C NMR spectra in CD3CN
are consistent with equivalent thioether arms in both cases.
The resonances in the H NMR spectrum of complex 2 are
1
Cu+ complexes: Complexes were prepared and character-
ized under an inert atmosphere by mixing equimolar
broader than those of ligand L2, and are shifted slightly
downfield due to the inductive effect of the Cu+ ion; the ar-
omatic protons shift by 0.03 to 0.14 ppm, whereas the meth-
ylene linker between the thioether and the tertiary amine is
shifted downfield by 0.30 ppm. In the case of complex 2’,
amounts of [CuACHTUNGTRENNUNG
(CH3CN)4]ClO4 and the ligands L1’, L2, and
L2’ in acetonitrile; the corresponding cuprous complexes
with ligands L1, L1Bu, and L3’ have been examined previous-
ly.[7,12] All the new complexes were characterized by spectro-
scopic techniques. Complex [CuL1’]ClO4 (1’) was obtained in
1
the resonances in the H NMR spectrum are also broader
1
a yield of 54% as a tan-colored solid. Its H and 13C NMR
than those of the corresponding ligand L2’, with downfield
shifts of 0.02 to 0.06 ppm for the aromatic protons and
0.08 ppm for the protons of the ethylene linker between the
thioether group and the tertiary amine. The larger shift of
the resonance of the methylene linker observed for the
short-arm ligand in complex 2 indicates that the effect of
the proximity of the Cu+ ion is more pronounced than for
the long-arm analogue 2’.
spectra in CDCl3 are characterized by equivalent signals for
the thioether arms with two singlets corresponding to
methyl groups at d=2.26 and 2.38 ppm, whereas the linker
methylene groups give rise to
a broad resonance at
d=3.03 ppm. Single crystals suitable for X-ray diffractome-
try were obtained with hexafluorophosphate as the counter
ion by slow evaporation of an acetonitrile solution; the
solid-state structure of [CuL1’]PF6 is presented in Figure 1.
The Cu+ center is in a trigonal-pyramidal environment de-
fined by the three thioether donors in the basal positions;
Interaction of Cu2+ with methylene-bridged ligands L2 and
L3: We have previously reported the oxidation of the meth-
ylene-bridged ligands L1 and L1Bu upon interaction with
ꢀ
the average Cu S distance is 2.28 ꢇ and the central amine
as the axial donor has a Cu N1 distance of 2.217(4) ꢇ. The
Cu2+ salts.[7] Likewise, the reaction of Cu
ACHTNGUTERNU(NG ClO4)2·6H2O with
ꢀ
ligand arms adopt a propeller-type arrangement with virtual
C3v symmetry, as previously reported for a related com-
plex.[5a] The triangular disposition of the thioethers is rather
distorted because the distances vary from 2.319(1) ꢇ for
L2 results in ligand oxidation with concomitant reduction of
1
Cu2+ to Cu+. Analysis of the H NMR spectra obtained in
the presence of 0.5, 1.0, 1.5, and 2.0 equivalents of Cu2+ al-
lowed the identification of the oxidation products 2,4-
ꢀ
ꢀ
ꢀ
ꢀ
Cu S1 to 2.246(1) ꢇ for Cu S3; the corresponding S Cu S
dimethACTHNGUTERNNyUG lthiophenol, the corresponding disulfide, and
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6069

I. Castillo et al.
bis(2,4-dimethylphenylthio)methane (see Figure S1 in the
Supporting Information), based on a comparison with the
spectra of authentic samples.[7] FAB-MS analysis of the final
reaction products confirmed the presence of the disulfide
coordinated to Cu+ (see Figure S2). By analogy with the ob-
servations for the Cu2+/L1 and L1Bu systems[7a] as well as for
the related compound bis(2,4-dimethylphenylthio)meth-
which by an analogous sequence, culminates in the hetero-
AHCTUNGTREGUNbNN icyclic compound M. In addition to the MS and NMR
spectroscopic evidence for the presence of ArSH, ArSSAr,
and ArSCH2SAr, the oxidation of L2 by Cu2+ yielded crys-
tals of the diperchlorate salt of M suitable for X-ray diffrac-
tion, as shown in Figure 2a. The two benzimidazole frag-
ments adopt a nearly parallel orientation, likely due to p–p
stacking interactions, defined by a distance of 3.23 ꢇ be-
tween the five-membered ring centroids and of 4.10 ꢇ be-
tween the six-membered rings. Intermolecular stacking in-
teractions extend along the crystallographic c axis, as depict-
ed in Figure 2b, with the five-membered aromatic ring from
one molecule aligned with the six-membered ring of an ad-
jacent molecule at a distance of 3.63 ꢇ.
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
proposed in which the formation of the sulfur-based radical
cation is accompanied by reduction to Cu+. Subsequent het-
ꢀ
erolytic cleavage of the C S bond results in a thiyl radical
ArS· and the iminium species E (Scheme 5). Intermediate E
can then be attacked by another molecule of L2 to generate
G, which, after loss of the carbosulfonium cation ArS=
Attempts to obtain L3 were unsuccessful, although analy-
+
1
CH2
,
may be oxidized by the radical-cation species
sis of the reaction products by H NMR spectroscopy indi-
[ArSCH2SAr]·+ (from the combination of ArS· and ArS=
cated that it may be formed in small amounts. This observa-
tion was made during the condensation of bis(1-methyl-2-
methylbenzimidazolyl)amine (Q) with one equivalent of
paraformaldehyde and 2,4-dimethylthiophenol. Efforts to
isolate L3 present in the condensation reaction mixture led
to bis[di(1-methyl-2-methylbenzimidazolyl)amino]methane
(R in Scheme 6). Compound R
+
ꢀ
CH2 in Scheme 5). Further C S bond rupture would lead
to the iminium species J with subsequent intramolecular
attack by a benzimidazole nitrogen atom leading to the
seven-member heterocyclic species L. Addition of another
equivalent of Cu2+ generates a new radical-cation species,
was characterized by 1H NMR
spectroscopy in the reaction
mixture and, ultimately, in the
solid state as the corresponding
Cu2+–perchlorate complex (see
below).
The
addition
of
Cu-
AHCTUNGTRENN(GNU ClO4)2·6H2O to the condensa-
tion reaction mixture in an at-
tempt to trap the small amount
of L3 formed as the Cu2+ com-
plex resulted instead in the for-
mation of [Cu(R)]ACHTNUTRGNEUNG(ClO4)2, as
evidenced by EPR spectroscopy
and X-ray crystallography. The
former technique gave rise to
an axial spectrum in CH2Cl2
solution with a perpendicular
region consistent with coupling
to six I=1 nuclei, four benzimi-
dazoles, and two amine nitro-
gen donors, resulting in a 13-
line signal centered at g=2.045
(J=13.5 G; see Figure S3 in the
Supporting Information). In the
solid state, however, the com-
plex has
a highly distorted
square-pyramidal coordination
geometry with the basal posi-
tions defined by the four benz-
AHCTUNGTERGiNNUN midazolyl groups and one of
the aliphatic amines at the axial
position, as shown in Figure 3.
Scheme 5. Mechanism proposed for the oxidation of L2 by Cu2+
.
The average Cu N distance to
ꢀ
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Copper Versus Thioether-Centered Oxidation
FULL PAPER
Figure 2. a) Mercury diagram of bicycloACTHNUTRGENN[UG 1,4,4]undecane-bisACHUTNGTREN(NUNG 2,3-(1-methyl-
benzimidazolyl))diammonium dication (M) at the 50% probability level.
The perchlorate anions and hydrogen atoms have been omitted for clari-
ty. b) p-stacking along the crystallographic c axis. Selected bond lengths
ꢀ
ꢀ
ꢀ
ꢀ
[ꢇ]: N1 C2 1.323(7), N1 C8 1.390(6), C2 N3 1.336(6), N3 C9 1.413(5),
Figure 3. Mercury diagram of [Cu(R)]ACHTNUTRGNEUNG(ClO4)2 at the 50% probability
level. The perchlorate anions, molecules of acetonitrile, and hydrogen
ꢀ
ꢀ
ꢀ
C10 N11 1.462(7), N11 C12 1.456(6), N11 C14 1.427(7); selected bond
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
angles [8]: C2 N1 C8 108.2(4), N1 C2 N3 110.5(4), N1 C2 C10
125.8(4), N3 C2 C10 123.5(4), C2 N3 C9 107.5(4), C2 N3 C14
125.9(4), C9 N3 C14 126.6(4), C2 C10 N11 112.9(4), C10 N11 C12
115.1(5), C10 N11 C14 117.0(4), C12 N11 C14 115.3(5).
ꢀ
atoms have been omitted for clarity. Selected bond lengths [ꢇ]: Cu1 N1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2.006(4), Cu N11 2.006(5), Cu1 N21 2.016(5), Cu1 N31 1.971(5), Cu1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
N43 2.393(4); selected bond angles [8]: N1 Cu1 N11 91.8(2), N1 Cu1
N21 176.8(2), N1 Cu1 N31 86.5(2), N1 Cu1 N43 100.7(2), N11 Cu1
N21 89.9(2), N11 Cu1 N31 164.1(2), N11 Cu1 N43 76.6(2), N21 Cu1
N31 92.6(2), N21 Cu1 N43 77.0(2), N31 Cu1 N43 119.3(2), N41 C42
N43 112.7(4).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
EPR spectrum. Analysis of the
oxidation products of the lig-
AHCTUNGTERNNUNG ,
ands L1, L1Bu, and L2 by Cu2+
as well as the inability to isolate
L3, suggests that the reactivity
may be attributed to the rela-
tive stability of the iminium cat-
ions obtained as a result of het-
ꢀ
erolytic C S bond cleavage of
the initially formed sulfur-cen-
tered radical cations. Taking
this into account, it is expected
that lengthening of the linker
arm to an ethylene fragment
(L1’, L2’, and L3’) may prevent
Cu2+ oxidation, thus precluding
Scheme 6. Synthesis of R from bis(1-methyl-2-methylbenzimidazolyl)amine (Q).
ꢀ
the benzimidazole ligands is 2.00 ꢇ, whereas the Cu1 N43
distance to the amine donor is considerably longer at
2.393(4) ꢇ; the nonbonded Cu1···N41 distance to the other
the formation of ArS· and the subsequent formation of the
+
stable iminium species R2N=CH2
.
ꢀ
ꢀ
tertiary amine is 2.810(3) ꢇ. All the NBz Cu NBz bond
angles involving the benzimidazole ligands are consistent
with a square coordination geometry around Cu2+, with
average values of 90.188 for those in cis positions and of
Synthesis of Cu2+ complexes with ethylene-bridged ligands:
In the case of L1’, attempts to prepare cupric complexes with
a
variety of Cu2+ salts, including CuCl2·4H2O, Cu-
AHCUTNTGERG(NNUN ClO4)2·6H2O, and CuSO4·6H2O, in MeOH, EtOH, and ace-
tonitrile resulted in the recovery of L1’ and the correspond-
ing cupric starting material or its reduction to Cu+ (presum-
ably with concomitant solvent oxidation). The cupric com-
plex of the long-arm ligand L2’ was synthesized by mixing
equimolar amounts of CuCl2·4H2O and the ligand in metha-
nolic solution. The complex [CuL2’Cl2] (2a’) was initially
characterized by IR spectroscopy, which showed ligand-de-
rived bands at 1747, 1475, and 1447 cmꢀ1. In addition, EPR
spectroscopy at 77 K revealed the presence of a signal that
appears to be isotropic with g=2.105. The corresponding
ꢀ
170.458 for the trans nitrogen donors. In contrast, the NBz
ꢀ
Cu NAx angles of the benzimidazole nitrogen donors to the
axial amine vary from 76.6(6) to 119.3(2)8, thereby revealing
the “tilt“ of the axial ligand towards N11 and N21 that re-
sults in the high degree of distortion from an ideal square-
based pyramid. The different coordination environments in
the solid state and in CH2Cl2 may be attributed to dynamic
behavior in solution, which enables the Cu2+ ion to rapidly
alternate between the two tertiary amine ligands or to coor-
dinate weakly to both of them, resulting in the observed
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I. Castillo et al.
cupric complex incorporating L3’, namely [CuL3’Cl]ClO4,[8]
Cu2+, as described in the reactivity studies in which ligand-
based oxidation occurs readily in the presence of the cupric
ion. In contrast, in the long-arm analogues Ln’, copper-cen-
tered oxidation occurs in the complexes [CuLn’]+ at an
anodic peak potential that is close to 500 mV less than the
value of the first oxidation potential of the ligand.
and a dicopper complex featuring the tris(benzimidazolyl)-
ACHTUNGTRENNUNG
amine ligand L4’, have previously been reported.[13]
Electrochemical studies
To understand the electrochemical effect of the coordination
of the mixed thioether/benzimidazole ligands to Cu+ and
All the electrochemical data are summarized in Table 1
with the ligand-based anodic peak potentials labeled succes-
sively starting from signal Iap as the lowest value. If the sig-
the observed reactivity of the short-arm ligands with Cu2+
,
we performed cyclic voltammetry studies on all the available
ligands and their complexes. Measurements were performed
at a concentration of 1 mm in acetonitrile solution at a rate
of 100 mVsꢀ1 and the data are referenced to the ferroceni-
um/ferrocene (Fc+/Fc) redox couple. All the ligands display
several oxidation waves, in some cases at relatively low po-
tentials, which made it necessary to unambiguously assign
each of the ligand-based oxidative processes (see Figures S4
and S5 in the Supporting Information). Analysis of the
cyclic voltammograms of the long-arm complexes [CuL1’]+
and [CuL2’]+ (and the previously reported [CuL3’]+)[8] re-
Table 1. Anodic peak potentials (Eap) for [CuLn]+ complexes in CH3CN.
Compound
Eap [mV]
IIap
Cu2+/Cu+
Iap
IIIap
IVap
Vap
A
844[a]
220
530
730
650
558
670
208
1080
980
1040
895
908
841
1330
1160
1420
1110
1236
1003
1500
–
1611
1543
1802
1155
–
E
1840
1960
1790
–
+
A
]
924[b]
761
AHCTUNGTRENNUNG
G
180
A
ꢀ60[c]
1870
[a] From ref. [7a]. [b] From ref. [7b]. [c] From ref. [8].
vealed quasi-reversible behavior for [CuL1’]2+
(anodic and cathodic peak separation DEp =EapꢀEcp =
220 mV) and reversible behavior for the [CuL2’]2+ [CuL2’]+
and [CuL3’]2+ [CuL3’]+ couples (DEp =100 and 110 mV, re-
spectively, see Figure 4).
/ACTHNGUTERNNUG
[CuL1’]+
/
A
nals of the corresponding Iap signals for the short- and long-
arm ligands (L1 vs. L1’, and L2 vs. L2’) are compared, it is evi-
dent that the first oxidation potential is approximately
115 mV lower for the short-arm analogues. This would place
the value of the Iap signal for the hypothetical L3 at around
93 mV, which means that it is susceptible to oxidation and
thus provides a viable explanation for the difficulty in isolat-
ing it. The observed species bis[di(2-methylbenzimidazolyl)-
/ACHTUNGTRENNUNG
AHCTUNGTREGaNNUN mino]methane (R) is formed instead as the most stable
product.
Theoretical studies
To evaluate the thermodynamic feasibility of the oxidation
of Cu+ complexes, we carried out density functional studies
on the [CuLn]+ and solvated [CuLn(NCMe)]+ complexes
ACHTUNGRTENNUGN
that may form in acetonitrile solution with the two families
of ligands Ln and Ln’ shown in Scheme 1. The coordination
of MeCN is energetically favorable in all cases, with values
between ꢀ4 and ꢀ24 kcalmolꢀ1 determined (Table 2), in
agreement with the high occurrence of tetrahedral Cu+
complexes.[14] The association of acetonitrile with the labile
Figure 4. Cyclic voltammograms for L2’ and its CuI complex. Iap–IVap cor-
respond to ligand-centered processes. The signal marked (fl) has been as-
signed to the reversible Cu2+/Cu+ redox couple. Inset: Enlargement of
the voltammogram; the mark (*) corresponds to a small excess of non-
coordinated Cu+ ions.
Table 2. Theoretical evaluation of changes in energy upon the coordina-
tion of acetonitrile to the Cu+ and Cu2+ complexes in solution.
DEcoord [kcalmolꢀ1
]
Cu+
Cu2+
For the short-arm ligand L2 (along with the previously re-
ported L1 and L1Bu),[7] determination of the redox processes
revealed that the oxidation of the ligands in the complex
occurs approximately 200 mV below the anodic peak poten-
tial (Eap) for the oxidation of the corresponding Cu+ com-
plexes (see Figure S6 in the Supporting Information). This
result is consistent with the oxidation of L2 (L1 and L1Bu) by
L1
ꢀ17.5
ꢀ18.3
ꢀ14.7
ꢀ8.4
n.a.
n.a.
ꢀ14.9
ꢀ22.9
ꢀ16.3
ꢀ23.6
L1Bu
L2
L3
L4
ꢀ5.4
L1’
ꢀ4.9
n.a.=not available
6072
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ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 6067 – 6079

Copper Versus Thioether-Centered Oxidation
FULL PAPER
Table 3. Main structural parameters for the optimized structures of Cu+
acterized Cu+–thioether complexes that contain the favored
five-membered chelate rings,[16] although longer than those
determined for [CuL1]PF6, likely due to the predicted pres-
ence of the additional acetonitrile ligand in solution.
complexes [CuL ACHTUNGTRENNUNG
n(NCMe)]+.
[a]
[a]
[a]
Ligand Cu···NL
Donor Geometry[b]
ꢀ
Cu S
ꢀ
Cu NBz
ꢀ
Cu NA
L1
L2
L3
L4
L1’
L2’
L3’
L4
3.12
3.10
2.57
2.74
2.51
2.73
2.89
2.83
2.46 (ꢈ3)
2.49 (ꢈ2) 2.07
3.78
–
2.52 (ꢈ3)
2.52 (ꢈ2) 2.09
2.61
–
–
2.01
2.01
NS3
N2S2
N4
TET
TET
TET
TET
TBP
TET
TET
TET
The short-arm benzimidazolylamino-dithioether complex
2.07 (ꢈ2) 1.99
2.16 (ꢈ3) 2.06
–
[CuL
sulfur atoms having a Cu S distance of 2.49 ꢇ (0.03 ꢇ
2(NCMe)]+ has a tetracoordinated Cu+ ion with two
ACHTUNGTRENNUNG
N4
ꢀ
2.17
2.12
N2S3
N2S2
N3S
N4
1(NCMe)]+), one benz-
longer than the distance in [CuL ACHTNUGRTENNUGN
2.10 (ꢈ2) 2.07
2.16 (ꢈ3) 2.06
ꢀ
imidazole nitrogen with a Cu NBz distance of 2.07 ꢇ, and
ꢀ
one acetonitrile molecule at Cu NA 2.01 ꢇ in a pseudotetra-
[a] NL, NBz, and NA denote the coordinated nitrogen atom of the tripodal
ligand, benzimidazole, and acetonitrile, respectively. [b] Geometries
around the copper ions (TET=tetrahedral, TBP=trigonal bipyramid)
were deduced by continuous shape measures of the coordination polyhe-
dra.
ꢀ
ꢀ
hedral environment (TET) with a S Cu S angle of 1158.
Analogously, we have assigned a pseudotetrahedral coordi-
nation to the Cu+ ion in its long-arm congener [CuL2’-
AHCTUNGTRENNUNG
(NCMe)]+, with the two sulfur atoms at a distance of
2.52 ꢇ, 0.03 ꢇ longer than the corresponding short-arm ana-
ACTHNUTRGNEUNG
logue but identical to that in [CuL1’(NCMe)]+. Both the
ꢀ
cuprous centers was not evidenced by ESI-MS, which can be
attributed to fast ligand-exchange processes.
Cu NBz distance of 2.09 ꢇ to the benzimidazole and the
ꢀ
Cu NA distance of 2.12 ꢇ to the molecule of acetonitrile
are longer than those in [CuL
tributed to the contribution of the tertiary amine as a weak
fifth donor atom (Cu NL, 2.73 ꢇ), although continuous
A
Initial Cu+ complexes: The molecular geometries of [CuLn]+
ꢀ
and the solvated [CuL
and their main geometrical parameters are shown in
Table 3. In the [CuL
1(NCMe)]+ and [CuL1Bu(NCMe)]+ com-
N
shape measures suggest a very distorted geometry around
the copper center. It is evident that the complex with the
long-arm ligand is more flexible due to the longer ethylene
arm, which allows the weak coordination of the tertiary
amine to copper.
The optimized structures of complexes [CuL
and [CuL3’(NCMe)]+ are characterized by a pseudotetrahe-
dral coordination environment. As in the case of the benz-
A
ACHTUNGTRENNUNG
plexes, the cuprous ion is tetracoordinated by the three
sulfur atoms of the ligand and one acetonitrile molecule, de-
fining a pseudotetrahedral environment (TET). The initial
optimization was probed with the hypothetical tris(phenyl-
3(NCMe)]+
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
the 2,4-dimethylphenyl derivative L1, which revealed that
the sulfur atoms are largely pyramidalized (312–3158).[15] In
AHCTUNGTREGiNNUN midazolylamino-dithioether described above, the coordina-
ꢀ
both cases, the aromatic rings have an angle w for NL···Cu
NA of about 56–608 (Scheme 7). Important changes are ob-
tion of the short-arm ligand L3 to the Cu+ center is highly
restricted, thereby resulting in a nonbonding Cu···S distance
of 3.78 ꢇ (sum of the van der Waals radii, 3.20 ꢇ). In con-
ACTHNUTRGNEUNG
trast, in the long-arm complex [CuL3’(NCMe)]+, chelation
by the thioether sulfur and the tertiary amine nitrogen
atoms gives rise to five-membered rings with a calculated
ꢀ
Cu S distance of 2.61 ꢇ. As a general observation, the coor-
dination of the tertiary amine nitrogen atoms in the short-
arm ligands to the Cu+ centers are geometrically restricted
because their coordination would lead to highly strained
four-membered rings. Finally, the complexes formed be-
tween tris(benzimidazolyl)amino ligands L4 or L4’ and Cu+
favor the tetrahedral geometry with identical distances of
Scheme 7. Definition of the
copper.
w angle in arylthioether complexes of
served when tBu substituents are present at the 2-position
of the aromatic rings due to increased steric hindrance, as
corroborated by single molecular models. A closer analysis
ꢀ
ꢀ
2.16 and 2.06 ꢇ for Cu NBz and Cu NA, respectively. In
both cases, the axial Cu···NL distances are long enough
(about 26%) to consider that the nitrogen atoms of the
1Bu(NCMe)]+ reflects this
of the optimized structure of [CuL ACTHUNGRTENNGUN
steric repulsion in a variety of structural parameters: 1) the
angle w increases to 848, 2) the sulfur atoms lose pyramidali-
ty with the sum of the angles reaching a value of 3238,
polyACTHGNUTERNNUdG entate ligands interact only weakly with the copper
centers. Note that the Cu···NL distance in [CuL4(NCMe)]+
ACTHNUTRGNEUNG
is similar to that found in the [CuL2’(NCMe)]+ complex
ꢀ
3) the Cu NL distance is approximately 0.02 ꢇ longer than
(Table 3).
the corresponding phenyl or 2,4-dimethylphenyl analogues,
and 4) the tricoordinated copper ions in [CuL1Bu
]
have
Oxidized complexes: For the short-arm family of ligands, the
experimental data acquired thus far has only allowed us to
speculate the molecular geometries of the oxidized species.
+
ꢀ
ꢀ
smaller S Cu S angles. The long-arm trithioether complex
ACHTUNGTRENNUNG
[CuL1’(NCMe)]+ has a distorted trigonal-bipyramid (TBP)
geometry around the cuprous ion, with the Cu+ bound to all
When the metal ion was computationally oxidized to Cu2+
,
ꢀ
sulfur atoms with an average Cu S distance of 2.52 ꢇ.
These distances are consistent with crystallographically char-
the optimization process showed instability of the tetracoor-
dinated structures, with less than 15% of the unpaired elec-
Chem. Eur. J. 2013, 19, 6067 – 6079
ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6073

I. Castillo et al.
tron density remaining at the metal center. Because the
analysis of this molecular geometry suggests the decoordina-
tion of one thioether group, the full optimization of tricoor-
dation, whereas the negative charge on five atoms, namely
CAr, decreases, as expected for an oxidized species. Finally,
the spin density shows that the oxidized arylthioether frag-
ment contains more than 84% of the unpaired electron,
which indicates that oxidation occurs in the uncoordinated
aromatic ring, whereas the copper has less than 1% of the
unpaired spin density (see Table S1 in the Supporting Infor-
mation). These computational results are consistent with the
oxidation process observed for the short-arm ligands upon
interaction with Cu2+, which results in the formation of M
and R via the proposed sulfur-based radical-cation inter-
mediates outlined in Schemes 5 and 6.
dinated [CuL ACHTUNGTRENNUNG
n(NCMe)]2+ complexes was carried out and
the results indicate that such unbound thioether species are
the final oxidation products (Scheme 8). However, these tri-
The optimized structures were validated by comparing the
bonding parameters obtained with those in related structur-
ACTHNUTRGNEUNG
ally characterized complexes. [CuL3’(NCMe)]2+ can be com-
pared with the previously reported [CuL3’Cl]ClO4,[8] in
which the acetonitrile ligand is replaced by a coordinated
ꢀ
ꢀ
ꢀ
chloride. The calculated Cu NL, Cu NBz, and Cu S distan-
ces of 2.39, 2.00, and 2.59 ꢇ compare reasonably well with
the experimentally determined values of 2.13, 1.95, and
2.75 ꢇ. Moreover, the coordination geometry was correctly
predicted to be square pyramidal (SPY in Table 4). With
Scheme 8. Proposed oxidative reactivity of [CuLn]+ complexes in acetoni-
trile.
coordinated complexes are unstable in the case of the re-
Table 4. Main structural parameters for the optimized structures of Cu2+
n(NCMe)]+ and tetracoordinated struc-
duced species [CuL ACHTUNGRTENNUGN
n(NCMe)]2+
complexes [CuL CAHTUNGRTENNUGN .
tures were obtained upon reoptimization.
[a]
[a]
[a]
ꢀ
ꢀ
ꢀ
Ligand Cu···NL
Cu S
Cu NBz
Cu NA
Donor Geom-
etry[b]
ꢀ
The CS S bond lengths in the oxidized ligand arm depict-
ed in Scheme 8 are somewhat shorter in [CuL
n(NCMe)]2+
L2
L3
L4
L1’
L2’
L3’
L4’
3.52
2.13
2.14
2.09
2.13
2.39
2.15
2.41, 3.86 2.00
2.88
1.98
N2S
N4S
N5
TRI
TBP
TBP
TBP
TBP
SPY
TBP
than those in the tricoordinated reduced species, that is,
2.01 (ꢈ2) 2.04
2.10 (ꢈ 3) 2.04
those found in the [CuLn]+ and [CuLn(NCMe)]+ complexes
AHCTUNGTRENNUNG
–
2.54 (ꢈ3)
2.53 (ꢈ2) 2.10
2.59
–
–
2.01
2.03
N2S3
N3S2
N4S
N5
(1.73 vs. 1.80 ꢇ, respectively). This structural change is ac-
companied by an increase in the bond angles around the
sulfur atoms of more than 28. Thus, the aromatic ring ap-
pears to have some degree of asymmetric delocalization,
which suggests an aromatic description compatible with the
resonance form shown in Scheme 9 with some CS=S double-
2.00 (ꢈ2) 2.15
2.11 (ꢈ3) 2.03
[a] NL, NBz, and NA denote the coordinated nitrogen atom of the tripodal
ligand, benzimidazole, and acetonitrile, respectively. [b] Geometries
around the copper centers (TRI=trigonal, TBP=trigonal bipyramid,
SPY=square pyramid) were deduced by continuous shape measures of
the coordination polyhedra.
4(NCMe)]2+, several Cu2+ complexes have
regard to [CuL CAHTUNGRTENNGUN
been reported, all of which have a trigonal-bipyramidal co-
ordination geometry (TBP) defined by L4 and a molecule of
H2O.[17] The distances from the cupric ion to the nitrogen
atoms of the ligand, calculated to be 2.14 and 2.10 ꢇ for
Scheme 9. Charge delocalization in an oxidized ligand “arm”.
ꢀ
ꢀ
bond character and consistent with the distribution of
Cu NL and Cu NBz, respectively, are reasonable compared
with the experimentally determined values of 2.10 and
2.04 ꢇ (average). Likewise, for the methylated version
ꢀ
ꢀ
CS CAr and CAr CAr bond lengths. In contrast, the unoxi-
ꢀ
dized phenyl rings present C C bond lengths similar to
ACTHNGUTERNNUG
[CuL4’(NCMe)]2+, the Cu N distances of 2.15 and 2.11 ꢇ
ꢀ
those expected for a fully delocalized ring.
ꢀ
ꢀ
Further computational evidence for the importance of the
(aryl)C=S resonant form comes from the calculated atomic
charges (from a natural population analysis) by comparing
calculated for Cu NL and Cu NBz, respectively, are compa-
rable to the reported values of 2.07 and 2.07 ꢇ (average) for
the dimeric, benzotriazolate-bridged Cu2+ complex descri-
bed as possessing a distorted trigonal-bipyramidal geome-
try.[14] It can be inferred that the long-arm ligands increase
the coordination number to five for the cupric cation,
whereas the geometric constraints imposed by the short-arm
ligands result in lower coordination numbers as well as
n(NCMe)]2+ with
those of the oxidized aromatic ring in [CuL ACTHUNGRTENNUGN
those of the reduced tricoordinated analogues. The sulfur
atom, for example, loses more electron density upon oxida-
tion of [CuL
on the other hand, remains practically unaltered upon oxi-
ACHTUNGTRENNUNG
n(NCMe)]2+ (about 0.4 electrons). The CS atom,
6074
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ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 6067 – 6079

Copper Versus Thioether-Centered Oxidation
FULL PAPER
highly distorted geometries such as the trigonal-bipyramidal
n(NCMe)]2+
coordination environment calculated for [CuL CAHTUNGRTENNUGN ,
ꢀ
which has a long Cu S distance of 2.88 ꢇ.
The redox potentials for the [CuL
G
/
G
ACHTUNGTRENNUNG
(NCMe)]+ couples can be evaluated by simulating the oxi-
dation process in acetonitrile solution. The results in Table 5
Table 5. Redox potentials referenced to the Fc+/Fc couple. The values
correspond to those calculated for oxidation at copper, the coordinated
ligand, and the experimentally determined potentials.
E [mV]
Calculated
Experimental
[CuL
(NCMe)]2+
[CuL
(NCMe)]+
Cu2+/Cu+
Cu+L0/Cu+L+
N
G
/
L1
L2
L3
L4
L1’
L2’
L3’
L4’
n.a.
n.a.
200
880
820
n.a.
n.a.
900
720
540
n.a.
844[a]
761
n.a.
ꢀ170
ꢀ213[b]
390
220
210
180
Figure 5. Energy diagram of the occupied frontier molecular orbitals of
ꢀ50
ꢀ60
n(NCMe)]+ complexes.
the short-arm [CuL ACHTUNGRTENNUGN
ꢀ200
ꢀ148[c]
[a] From ref. [7a]. [b] From ref. [11b], corrected for comparison with the
value of the Fc+/Fc redox couple. [c] From ref. [19], corrected for com-
parison with the value of the Fc+/Fc redox couple, determined in dimeth-
of the aromatic rings (Figure 5). In contrast, the long-arm
lig
ands L1’–L3’ give rise to Cu+ complexes that undergo oxi-
ACHTUNGTRENNUNG
ylformamide.[19] n.a.=not available.
AHCTUNGTRENNUNG
dation at the metal ion. Accordingly, the HOMO level for
these complexes correspond to metal-based d-type orbitals
(see Figure S7 in the Supporting Information). In the case of
the complex with L3, an arylthioether-derived molecular or-
bital at an energy level that is comparable to the copper-
based t2-type orbitals is expected for the optimized pseudo-
tetrahedral environment, as graphically depicted in Figure 5.
The experimental data described in the electrochemical sec-
tion for the series of ligands place the first anodic peak po-
tential of the proposed ligand L3 at around 93 mV, which
makes it susceptible to oxidation; this is supported by the
redox potential of 200 mV calculated for the Cu2+/Cu+
show that the half-wave potential calculated for the 2,4-di-
methylphenyl-substituted short-arm ligand L1 coordinated to
Cu+ is 880 mV, and it increases to 1220 mV when a tBu sub-
stituent is introduced at the 2-position in L1Bu (all values are
given relative to the Fc+/Fc couple). This variation must be
associated with the reorganization energy required as a
result of steric factors arising from the bulkier tert-butyl
2(NCMe)]+ is character-
group. Similarly, the complex [CuL ACTHUNGRTENNGUN
ized by a ligand-centered oxidation process in acetonitrile
solution giving rise to the species that formally corresponds
to [Cu(L2)+
N
couple in the hypothetical complex [CuL ACTHNGUTERNNUG
3(NCMe)]+ (entry 3
ior was not predicted by the calculations on the short-arm
in Table 5), which would result in ligand oxidation upon in-
complexes [CuL
A
ACHTUNGTRENNUNG
teraction with Cu2+. The marked difference between the
the redox potentials corresponding to the Cu2+/Cu+ couple
were calculated to be 200 and ꢀ170 mV, respectively. In this
context, the calculated redox potentials reported in Table 5
have a discrepancy of 60 mV or less with respect to the ex-
perimental values presented in Table 1 and pertinent refer-
aryl
Figure 6, which shows isodensity contours of the orbitals
corresponding to the optimized complexes [CuL
2(NCMe)]+
and [CuL2’(NCMe)]+.
ACHTUNGTRENtNGNU hioether- and copper-based HOMOs is exemplified in
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACTHNUTRGNEUNG
ences (with the sole exception of [CuL1’(NCMe)]+, which
shows a difference of 170 mV), which reveals that this com-
putational method is suitable for modeling these types of
complexes and obtaining reliable redox potentials.[6b,18]
Ligand- versus metal-centered redox processes can be ra-
tionalized on the basis of the relative energies calculated for
the frontier molecular orbitals of the complexes and, specifi-
cally, for the highest-occupied molecular orbital (HOMO),
which presumably loses an electron upon oxidation. The
Cu+ complexes of the sulfur-rich ligands L1, L1Bu, and L2
have HOMO orbitals with a major contribution from the
thioether groups, including the sulfur atom and the p system
Figure 6. Arylthioether- and copper-based HOMOs of a) the short-arm
[CuL
2(NCMe)]+ and b) the long-arm [CuL2’(NCMe)]+, respectively.
N
ACHTUNGTRENNUNG
Chem. Eur. J. 2013, 19, 6067 – 6079
ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6075

I. Castillo et al.
JEOL Eclipse 300 spectrometer in CDCl3 with tetramethylsilane as an in-
ternal standard or in CD3CN referenced relative to the residual solvent
protons at 300 (1H) or 75 MHz (13C). Mass spectra were recorded on a
JEOL JMS-SX-102A mass spectrometer at an accelerating voltage of
10 kV with a nitrobenzyl alcohol matrix and xenon atoms at 6 keV
(FAB+), a JEOL JMS-AX505HA spectrometer (electron ionization), or
a Bruker Daltonics Esquire 6000 spectrometer with an ion trap (electro-
spray). Elemental analyses were performed at the microanalytical facility
of the Unidad de Servicios de Apoyo a la Investigaciꢂn, Facultad de Quꢀ-
mica. Cyclic voltammetry measurements were performed under N2 in an-
hydrous acetonitrile with an EG&G PAR model 263A potentiostat–gal-
vanostat with a glassy carbon working electrode and a platinum wire aux-
iliary electrode. Potentials were recorded relative to a pseudo-reference
Conclusion
The electronic properties of two series of benzimidazole/
thioACHTUNGTRENNUNGether–copper complexes derived from the so-called
short- and long-arm ligands Ln and Ln’ have been examined
by experimental (cyclic voltammetry) and theoretical studies
(DFT calculations). The observed reactivity of the methyl-
ene-bridged short-arm ligands towards Cu2+ can be ex-
plained in terms of the ease of oxidation of the arylthioether
moiety, which results in the formation of the relatively
stable iminium cations as well as aryl disulfides. The feasibil-
ity of this process is reflected in the ligand-centered oxida-
tion potentials observed for the sulfur-rich, short-arm lig-
electrode of AgBr(s)/AgACHTUNTRGEN(NUG wire) immersed in a 0.1m Bu4NBr acetonitrile
solution. All voltammograms were recorded starting from the current
null potential (Ei =0) and were scanned in both directions, positive and
ands L1, L1Bu, and L2, which are lower than those of the Cu+
ions coordinated to the same ligands. DFT calculations have
.
negative, at a scan rate of 0.100 V sꢀ1. In agreement with IUPAC conven-
tion, the voltammogram of the ferrocinium]/ferrocene (Fc+/Fc) system
was recorded to establish the values of half-wave potentials (E1/2) from
the expression E1/2 =(Eap+Ecp)/2. To obtain the normalized current for
each complex, the measured current was divided by the exact molar con-
centration of the electroactive species. EPR spectra were recorded at
room temperature or at 77 K in quartz tubes with a JEOL JES-TE300
spectrometer operating at the X-band frequency (9.4 GHz) at 100 KHz
field modulation with a cylindrical cavity (TE011 mode). The static mag-
netic field was measured externally with a JEOL ES-FC5 precision gauss-
meter. Spectral acquisition, manipulations, and simulations were per-
formed by using the ESPRIT-382, v1.916 program.
n(NCMe)]+ complexes are
shown that tetracoordinated [CuL ACTHUNGRTENNGUN
formed in acetonitrile solution from [CuLn]+ with the short-
arm ligands, whereas the long-arm ligands give rise to both
tetra- and pentacoordinated [CuL
estingly, our theoretical studies predict the oxidation of
[CuL
n(NCMe)]+ to [CuLn(NCMe)]2+ or, more formally,
[Cu(Ln)+(NCMe)]+, with charge localized at one of the
arylthio
ether sites in the case of L1, L1Bu, and L2, in excellent
n’(NCMe)]+ species. Inter-
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
agreement with the experimental observations. For these
complexes, one of the thioether donors dissociates from the
copper ions and the localized unpaired electron in this func-
tional group as a radical cation favors a cascade reaction, as
also observed experimentally, resulting in the formation of
the isolated and fully characterized compounds M and R.
The computational methodology described herein allows the
reproduction of redox potentials to within 10 mV of experi-
mentally determined values, thereby providing a valuable
tool for assessing the redox properties of complexes for
which cyclic voltammetry may not be readily applied, in-
X-ray crystallography: Single crystals were mounted on
a Bruker
SMART diffractometer equipped with an Apex CCD area detector.
Frames were collected by w scans and integrated with the Bruker SAINT
software package by using the appropriate unit cell. The structures were
solved by using SHELXS-97 and refined by full-matrix least-squares on
F2 with SHELXL-97. Weighted R factors, Rw, and all goodness-of-fit indi-
cators, S, are based on F2. The observed criterion of I>2s(I) was used
only to calculate the R factors. All non-hydrogen atoms were refined
with anisotropic thermal parameters in the final cycles of refinement. Hy-
drogen atoms were placed in idealized positions, with isotropic thermal
parameters assigned values of Uiso 1.2 times the thermal parameters of
the parent non-hydrogen atom. Selected crystallographic data are pre-
sented in Table 6.
cluding [CuL
ACHTUNGTRENNUNGthioethers can be considered as redox non-innocent ligands
ACHTUNGTRENNUNG
3(NCMe)]+ in this work. Finally, the aryl-
CCDC 902988, 902989, and 902990 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.a-
c.uk/data_request/cif.
in the methylene-linked derivatives,[12] and thus the range of
known sulfur-containing redox-active arylthiolates has been
extended to arylthioethers.[20] This kind of behavior has
been suggested for methionine donors in the active site of
copper monooxygenases,[21] which raises the need for a com-
prehensive study of the generality of the redox involvement
of thioether ligands in chemical and biochemical systems.
Computational details: Unrestricted calculations were carried out by
using the Gaussian 03 package.[23] The hybrid density functional method
known as B3LYP was applied.[24] Effective core potentials (ECP) were
used to represent the innermost electrons of the transition-metal atoms
and the valence double-z quality basis set LANL2DZ associated with the
pseudopotentials.[25] The basis set used for the light elements sulfur,
carbon, nitrogen, and hydrogen was 6-31G*.[26] Solvent effects were
taken into account through PCM calculations (acetonitrile, e=36.64)[27]
by using the geometries optimized for the gas phase (single-point calcula-
tions). Redox potentials were estimated from these solvent calculations
by using as reference a value of 5.08 V for the absolute standard hydro-
gen electrode (SHE) in acetonitrile.[28]
Experimental Section
Materials and methods: Air-sensitive compounds were manipulated
under an atmosphere of dinitrogen in a glove-box or under vacuum by
using Schlenk techniques. Solvents were dried by standard methods and
Structural analysis: Continuous shape measures were calculated with the
SHAPE program.[29] It provides quantitative information on how much
the coordination environment deviates from an ideal polyhedron and
helps us to assign the coordination sphere around the metal.[30]
distilled under N2 prior to use. Cu
(CH3CN)4]PF6, and Bu4NPF6 were used as received from commercial
suppliers (Warning! Metal perchlorates are potentially explosive and
ACHTUNGNERT(UNNG ClO4)2·6H2O, CuCl2·2H2O, [Cu-
ACHTUNGTRENNUNG
Ligand synthesis
(2,4-Me2C6H3SCH2CH2)3N (L1’): K2CO3 (2.15 g, 15.5 mmol) was added to
a solution of tris(2-bromoethyl)amine (1.50 g, 4.40 mmol) in anhydrous
THF (15 mL), and after stirring for 30 min in a Schlenk flask, the vola-
tiles were evaporated under vacuum. The mixture was redissolved in an-
hydrous acetonitrile (25 mL) and 2,4-dimethylbenzenethiol (1.84 g,
13.3 mmol) was added dropwise under N2. The reaction mixture was
[22]
should be handled with extreme care). [CuACHTUNRTGNE(UNG CH3CN)4]ClO4 and the lig-
ACHTUNGTRENNUNG
ands L1, L1Bu, and L3’ were prepared according to literature proce-
dures.[7,8] Melting points were determined on an Electrothermal Mel-
Temp apparatus and are uncorrected. IR spectra were recorded with a
Bruker Tensor 27 spectrophotometer in the 4000–400 cmꢀ1 region as
chloroform solutions or KBr disks. NMR spectra were recorded on a
6076
www.chemeurj.org
ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 6067 – 6079

Copper Versus Thioether-Centered Oxidation
Table 6. Selected crystallographic data.
FULL PAPER
20 mL) followed by drying with Na2SO4, filtration, and concen-
tration afforded 1-methyl-2-aminomethylbenzimidazole (B) as
a colorless solid. Yield: 142 mg (88%); 1H NMR (300 MHz,
CDCl3, 208C, TMS): d=6.87 (d, J=7.9 Hz, 1H; Ar), 6.78 (d,
J=7.9 Hz, 1H; Ar), 6.63 (m, 1H; Ar), 6.54 (m, 1H; Ar), 3.42
(s, 2H; CH2), 2.95 (s, 2H; NH2), 2.75 ppm (s, 3H; CH3); IR
(KBr): n˜ =3457, 3387, 3093, 3032, 2977, 2899, 2839, 2677, 2591,
2103, 1634, 1610, 1533, 1512, 1466, 1324, 1168, 11141, 1032,
788, 765, 562, 515, 490 cmꢀ1; MS (EI, CHCl3): m/z: 161 [B]+,
146 [BꢀMe]+.
Compound
G
M·CH3CN
[Cu(R)]ACTHNUGTRENNU(G ClO4)2·0.25
H2O·3CH3CN
empirical formula
Mr
C30H39CuNS3F6P
718.31
C23H26Cl2N7O8
599.41
C43H47.5Cl2CuN13O8.25
1012.88
100(2)
triclinic
¯
P1
0.08ꢈ0.18ꢈ0.21
13.477(3)
14.109(3)
14.144(3)
67.595(4)
66.396(4)
88.954(4)
2249.5(9)
2
T [K]
298(2)
100(2)
crystal system
space group
crystal size [mm]
a [ꢇ]
b [ꢇ]
c [ꢇ]
triclinic
P1
monoclinic
I2/a
¯
0.08ꢈ0.16ꢈ0.36
11.413(1)
11.933(1)
13.312(1)
76.881(1)
83.292(1)
65.653(1)
1608.1(2)
2
0.12ꢈ0.18ꢈ0.42
9.819(3)
18.253(5)
14.131(5)
90
90.169(3)
90
2532.6(13)
4
(2,4-Me2C6H3SCH2)2(1-Me-2-CH2C7H4N2)N (L2): Precursor B
(668 mg,
4.10 mmol),
2,4-dimethylthiophenol
(1.14 g,
8.28 mmol), and paraformaldehyde (248 mg, 8.28 mmol) were
placed in a 100 mL round-bottomed flask containing 4 ꢇ mo-
lecular sieves (500 mg) dissolved in toluene (30 mL). The mix-
ture was stirred for 7 h at 908C, filtered, the flask was washed
with CH2Cl2 (3ꢈ10 mL), the washings filtered, and finally the
filtrate was concentrated under reduced pressure until a turbid
solution was obtained. Cooling to ꢀ258C resulted in a color-
less solid that was washed with cold hexanes and recrystallized
from acetonitrile to afford bis(2,4-dimethylphenylthiomethyl)-
1-methylbenzimidazol-2-ylmethylamine (L2). Yield: 650 mg
(35%); m.p. 83–848C; 1H NMR (300 MHz, CDCl3, 208C,
TMS): d=7.69 (m, 2H; Ar), 7.25 (m, 2H; Ar), 7.11 (d, J=
7.6 Hz, 3H; Ar), 6.86 (s, 2H; Ar), 6.68 (d, J=7.9 Hz, 2H; Ar),
4.39 (s, 4H; CH2), 3.95 (s, 2H; CH2), 3.19 (s, 3H; CH3), 2.29 (s,
6H; CH3), 2.23 ppm (s, 6H; CH3); 13C{1H} NMR (75 MHz,
CDCl3, 208C, TMS): d=150.21 (Ar), 142.16 (Ar), 139.55 (Ar),
137.11 (Ar), 136.23 (Ar), 132.39 (Ar), 131.24 (Ar), 131.00 (Ar),
127.25 (Ar), 122.61 (Ar), 121.98 (Ar), 119.75 (Ar), 109.12 (Ar),
59.05 (CH2), 49.82 (CH2), 29.42 (CH3), 21.04 (CH3), 20.71 ppm
(CH3); IR (KBr): n˜ =3428, 3053, 3009, 2971, 2939, 2914, 2874,
2838, 1885, 1607, 1510, 1476, 1440, 1404, 1354, 1330, 1268,
a [8]
b [8]
g [8]
V [ꢇ3]
Z
m
G
]
0.981
0.321
0.674
q range
hkl range
1.91–25.36
ꢀ13ꢁhꢁ13
ꢀ14ꢁkꢁ14
ꢀ15ꢁlꢁ16
1.483
1.82–25.35
ꢀ11ꢁhꢁ11
ꢀ21ꢁkꢁ21
ꢀ16ꢁlꢁ17
1.572
1.67–25.41
ꢀ16ꢁhꢁ16
ꢀ17ꢁkꢁ16
ꢀ16ꢁlꢁ17
1.495
672
8245
8245
0.0702
1calcd [kgmꢀ3
]
refined parameters
total reflections
unique reflections
R1 [I>2s(I)]
wR2
440
17853
5874
0.0494
262
8235
2269
0.0753
0.1143
0.1765
0.1370
1.028
goodness of fit
0.9770
1.053
heated at reflux for 18 h and cooled to room temperature to evaporate
all volatiles under reduced pressure. The oily residue was extracted with
CH2Cl2 (2ꢈ20 mL), dried with Na2SO4, filtered, and the solvent evapo-
rated. The crude product was purified by column chromatography on
silica gel with hexanes/ethyl acetate (99:1 to 97:3) as eluent to afford
tris[2-(2,4-dimethylphenylthio)ethyl]amine (L1’) as a colorless oil. Yield:
0.67 g (30%); 1H NMR (300 MHz, CDCl3, 208C, TMS): d=7.14 (d, J=
7.8 Hz, 3H; Ar), 6.97 (s, 3H; Ar), 6.91 (d, J=7.8 Hz, 3H; Ar), 2.84 (m,
6H; CH2), 2.70 (m, 6H; CH2), 2.32 (s, 9H; CH3), 2.26 ppm (s, 9H; CH3);
13C{1H} NMR (75 MHz, CDCl3, 208C, TMS): d=137.11 (Ar), 134.90
(Ar), 130.51 (Ar), 130.11 (Ar), 128.10 (Ar), 126.15 (Ar), 52.27 (CH2),
30.33 (CH2), 19.87 (CH3), 19.43 ppm (CH3); IR (CHCl3): n˜ =3090, 3059,
3004, 2947, 2925, 2826, 2735, 1602, 1478, 1458, 1440, 1378, 1352, 1297,
1238, 1163, 1125, 1090, 1052, 1010, 961, 927, 886, 833, 806, 743, 641 cmꢀ1
;
MS (FAB, CHCl3): m/z: 324 [L2ꢀSC6H3Me2]+; elemental analysis calcd
(%) for C27H31N3S2: C 70.24, H 6.77, N 9.10; found: C 70.12, H 6.69, N
8.97.
(2,4-Me2C6H3SCH2CH2)2NH (C): Bis(2-chloroethyl)amine hydrochloride
(2.00 g, 11.2 mmol) and K2CO3 (12.0 g, 86.9 mmol) were dissolved in an-
hydrous CH3CN (100 mL) in a 250 mL Schlenk flask under N2. Whilst
stirring, 2,4-dimethylthiophenol (4.00 g, 22.2 mmol) was added dropwise
and the mixture was heated at reflux for 7 h. After cooling, the solution
was filtered and concentrated under reduced pressure. The product was
purified by column chromatography on silica gel with CH2Cl2 as eluent
to afford bis(2,4-dimethylphenylthioethyl)amine (C) as a tan-colored oil.
Yield: 2.47 g (64%); 1H NMR (300 MHz, CDCl3, 208C, TMS): d=7.71
(d, J=7.7 Hz, 2H; Ar), 7.00 (m, 2H; Ar), 6.93 (d, J=7.9 Hz, 2H; Ar),
2.96 (m, 4H; CH2), 2.79 (m, 4H; CH2), 2.36 (s, 6H; CH3), 2.27 ppm (s,
6H; CH3); IR (KBr): n˜ =3346, 3005, 2977, 2922, 2860, 2731, 1747, 1695,
1602, 1542, 1477, 1452, 1393, 1363, 1351, 1319, 1295, 1261, 1213, 1153,
1168, 1102, 989, 951, 904, 859 cmꢀ1
; MS (FAB, CHCl3): m/z: 510
[L1’+H]+, 372 [L1’ꢀC6H3Me2]+, 358 [L1’ꢀCH2SC6H3Me2]+; elemental
analysis calcd (%) for C30H39NS3: C 70.67, H 7.71, N 2.75; found: C
70.81, H 7.99, N 3.19.
A
ACHTUNGTRENNUNG(C6H12N4)CH2C7H4N2]Cl (A): Hexamethylenetetramine (140 mg,
1089, 1057, 1016, 810, 766, 743 cmꢀ1
;
MS (EI, CHCl3): m/z: 208
[CꢀSC6H3Me2]+.
a
tomed flask. The mixture was stirred at 608C until an off-white solid
started to deposit after 2, 7, 14, and 24 h. After each of these intervals of
time, the solid was collected by filtration and the solution further heated
and stirred to obtain the precursor 1-methyl-2-(hexamethylenetetraami-
nomethyl)benzimidazolium chloride (A). Yield: 238 mg (74%); The com-
pound was partially characterized before proceeding with the next step.
1H NMR (300 MHz, CDCl3, 208C, TMS): d=7.67 (m, 1H; Ar), 7.50 (m,
1H; Ar), 7.41 (m, 2H; Ar), 4.78 (s, 10H; CH2), 4.38 (s, 2H; CH2),
3.82 ppm (s, 3H; CH3); IR (KBr): n˜ =3114, 3045, 2811, 2172, 2015, 1757,
(2,4-Me2C6H3SCH2CH2)2ACHTNUTRGNEUNG[1-tBuOC(O)-2-CH2C7H4N2]N (D): Precursor C
(345 mg, 1.00 mmol), KI (ca. 15 mg), K2CO3 (414 mg, 3.00 mmol), and 1-
tert-butoxycarbonyl-2-(chloromethyl)benzimidazole (266 mg, 1.00 mmol)
AHCTUNGTRENNUNG
were placed in an Erlenmeyer flask along with CH3CN (30 mL) under
N2. The mixture was stirred for 48 h and then filtered. The solids remain-
ing in the reaction flask were extracted with CH2Cl2 (3ꢈ10 mL) and the
combined organic phases were concentrated in a rotary evaporator until
a solid started to deposit. Further concentration and cooling resulted in
an off-white solid that was purified by column chromatography on silica
gel with hexanes/CH2Cl2 (1:1) as eluent to afford bis(2,4-dimethylphe-
nylthioethyl)(1-tert-butoxycarbonylbenzimidazol-2-ylmethyl)amine (D) as
a colorless solid. Yield: 210 mg (36%); 1H NMR (300 MHz, CDCl3,
208C, TMS): d=7.84 (m, 1H; Ar), 7.71 (m, 1H; Ar), 7.38 (m, 2H; Ar),
7.06 (m, 2H; Ar), 6.93 (s, 2H; Ar), 6.87 (m, 2H; Ar), 4.28 (s, 2H; CH2),
2.93 (s, 8H; CH2), 2.41 (s, 6H; CH3), 2.22 (s, 6H; CH3), 1.69 ppm (s, 9H;
1543, 1403, 1074, 689 cmꢀ1
[(C6H12N4)CH2]+.
;
MS (EI, CHCl3): m/z: 324 [A]+, 145
1-Me-2-NH2CH2C7H4N2 (B): Compound A (320 mg, 1.00 mmol) was dis-
solved in ethanol (7 mL) in an Erlenmeyer flask and concentrated HCl
(0.3 mL) was then added dropwise. After stirring for 24 h, H2O (4 mL)
was added and the pH of the mixture was raised to 11 by slowly adding
solid K2CO3 whilst stirring for 2 h. Extraction with ethyl acetate (3ꢈ
CACTHNURGTNEG(UN CH3)3); IR (KBr): n˜ =3397, 3059, 2923, 2834, 2733, 1618, 1534, 1476,
Chem. Eur. J. 2013, 19, 6067 – 6079
ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6077

I. Castillo et al.
1452, 1422, 1377, 1345, 1270, 1223, 1118, 1097, 1054, 1027, 870, 811, 746,
618, 543, 437 cmꢀ1; MS (FAB, CHCl3): m/z: 575 [D+H]+, 475 [Dꢀ(tert-
butoxycarbonyl)+H]+.
CH3), 2.20 ppm (s, 6H; CH3); 13C{1H} NMR (75 MHz, CD3CN, 208C,
CHD2CN): d=152.56 (Ar), 137.52 (Ar), 136.38 (Ar), 130.60 (Ar), 129.20
(Ar), 127.99 (Ar), 126.38 (Ar), 122.24 (Ar), 76.23 (CH2), 52.63 (CH2),
32.71 (CH2), 19.89 (CH3), 19.56 ppm (CH3); IR (KBr): n˜ =3305, 2978,
2921, 1601, 1476, 1449, 1382, 1280, 1233, 1087, 1047, 923, 873, 808, 750,
619, 541, 433 cmꢀ1; MS (ESI, CH3CN): m/z: 538 [CuL2’]+; elemental anal-
ysis calcd (%) for C28H33ClCuN3O4S2: C 52.65, H 5.21, N 6.58; found: C
52.89, H 5.56, N 6.28.
(2,4-Me2C6H3SCH2CH2)2(2-CH2C7H5N2)N (L2’): Compound D (617 mg,
1.15 mmol) was dissolved in acetone (15 mL) in an Erlenmeyer flask. A
3m HCl solution (0.42 mL, 1.20 mmol) was then added dropwise, the mix-
ture was stirred for 17 h, distilled H2O (20 mL) was added, and then the
acetone was evaporated under reduced pressure. Solid K2CO3 was added
until pH 11 and the mixture was extracted with ethyl acetate. After
drying with Na2SO4, the organic phase was concentrated and cooled to
ꢀ208C to obtain crystals of bis(2,4-dimethylphenylthioethyl)(benzimid-
[(2,4-Me2C6H3SCH2CH2)2(2-CH2C7H5N2)N]CuCl2 (2a’): A 25 mL Erlen-
meyer flask was charged with L2’ (100 mg, 0.21 mmol) and then
CuCl2·2H2O (62 mg, 0.36 mmol) and EtOH (5 mL) were added. The mix-
ture was stirred for 3 h and then concentrated under reduced pressure.
The blue-green oil was triturated and washed with Et2O (2ꢈ10 mL) to
give 2a’. Yield: 176 mg (67%); m.p. 91–938C; IR (KBr): n˜ =3028, 2972,
2919, 2855, 1747, 1597, 1474, 1447, 1373, 1313, 1274, 1223, 1151, 1120,
1048, 922, 807, 748, 623, 543, 434 cmꢀ1; UV/Vis (THF): lmax (e)=588
(170), 423 (1040), 254 nm (17240 molꢀ1 dm3 cmꢀ1); MS (FAB, CH2Cl2):
m/z: 573 [CuClL2’]+, 538 [CuL2’]+; EPR (77 K, CH2Cl2): g=2.010; ele-
mental analysis calcd (%) for C28H35Cl2CuN3OS2: C 53.54, H 5.62, N
6.69; found: C 53.18, H 5.43, N 6.31.
ACHTUNGTRENNUNG
azol-2-ylmethyl)amine (L2’) 8C, TMS): d=7.52 (s, 2H; Ar), 7.23 (m, 2H;
Ar), 7.10 (d, J=7.8 Hz, 3H; Ar), 6.98 (s, 2H; Ar), 6.84 (d, J=7.8 Hz,
2H; Ar), 3.98 (s, 2H; CH2), 2.94 (m, 4H; CH2), 2.88 (s, 4H; CH3), 2.34
(s, 6H; CH3), 2.24 ppm (s, 6H; CH3); 13C{1H} NMR (75 MHz, CDCl3,
208C, TMS): d=152.15 (Ar), 138.31 (Ar), 136.56 (Ar), 131.27 (Ar), 130.
63 (Ar), 129.70 (Ar), 127.30 (Ar), 123.22 (Ar), 114.83 (Ar), 53.76 (CH2),
52.04 (CH2), 31.60 (CH2), 20.81 (CH3), 20.39 ppm (CH3); IR (KBr): n˜ =
3339, 3059, 2923, 2834, 2733, 1476, 1452, 1422, 1377, 1345, 1270, 1223,
1118, 1097, 1054, 1027, 870, 811, 746, 618, 543 cmꢀ1; MS (FAB, CHCl3):
m/z: 476 [L2’+H]+, 338 [L2’ꢀSC6H3Me2]+, 324 [L2’ꢀCH2SC6H3Me2]+; ele-
mental analysis calcd (%) for C28H33N3S2: C 70.69, H 6.99, N 8.83; found:
C 70.21, H 7.01, N 8.71.
{[(2-CH2C7H5N2)2N]2CH2}CuACTHUNRTGENN(UG ClO4)2 ([Cu(R)]CAHTUNTGERN(NUGN ClO4)2): A 25 mL Erlen-
meyer flask was charged with a mixture of bis(1-methylbenzimidazol-2-
ylmethyl)amine (Q; 110mg, 0.36 mmol), paraformaldehyde (1.1mg, 0.36
mmol), and 2,4-dimethylthiophenol (50mg, 0.36 mmol) with the intention
Synthesis of complexes
of synthesizing L3, assuming a quantitative yield of bis
ACHTUNGTRENNUNG
[(2,4-Me2C6H3SCH2CH2)3N]Cu
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
charged with L1’ (380 mg, 0.75 mmol) and then [Cu
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(244 mg, 0.75 mmol) and CH3CN (15 mL) were added. The mixture was
stirred for 2 h, the volatiles were evaporated under reduced pressure, and
the colorless solid obtained was washed with diethyl ether (15 mL) to
afford complex 1’. Yield: 300 mg (60%); m.p. 72–758C; 1H NMR
(300 MHz, CDCl3, 208C, TMS): d=6.99 (m, 3H; Ar), 3.03 (m, 4H;
CH2CH2), 2.38 (s, 3H; CH3), 2.26 ppm (s, 6H; CH3); 13C{1H} NMR
(75 MHz, CDCl3, 208C, TMS): d=138.44 (Ar), 137.04 (Ar), 132.66 (Ar),
132.50 (Ar), 128.29 (Ar), 127.00 (Ar), 125.28 (Ar), 50.89 (CH2), 35.50
(CH2), 21.09 (CH3), 20.76 ppm (CH3); IR (KBr): n˜ =2918, 2852, 1601,
1476, 1449, 1377, 1291, 1233, 1081, 1047, 924, 876, 809, 723, 621, 543,
437 cmꢀ1; MS (ESI, CH3CN): m/z: 572 [CuL1’]+; elemental analysis calcd
(%) for C30H39ClCuNO4S2: C 53.55, H 5.84, N 2.08; found: C 53.81, H
5.66, N 2.10.
and the mixture was stirred for 18 h. After filtration, slow evaporation of
the solution resulted in blue-green microcrystals that were washed with
cold diethyl ether to afford the complex [Cu(R)]ACTHNUTRGNE(UNG ClO4)2. Yield: 73 mg
(46%); m.p. 202–2068C; IR (KBr): n˜ =3544, 2946, 2843, 1611, 1506,
1455, 1321, 1294, 1208, 1160, 1077, 1013, 933, 839, 808, 749, 622, 568, 543,
516, 434 cmꢀ1; EPR (77 K, CH2Cl2): g? =2.045 (J=13.5 G), g|| =2.241
(A|| =170 G); elemental analysis calcd (%) for C37H46Cl2CuN10O12: C
46.42, H 4.84, N 14.63; found: C 46.17, H 4.67, N 14.18.
[(2,4-Me2C6H3SCH2)2(1-Me-2-CH2C7H4N2)N]Cu
Schlenk tube was charged with L2 (100 mg, 0.21 mmol) and then [Cu-
(CH3CN)4]ClO4 (68 mg, 0.21 mmol) and CH3CN (20 mL) were added.
ACHTUNGETRN(NGNU ClO4) (2): A 100 mL
Acknowledgements
ACHTUNGTRENNUNG
IC, PRMA, and BNSE thank CONACyT (Proyecto 151837, Becas 27252
and 254496) for financial support and Ivꢁn Monsalvo for assistance in the
preparation of 1-methyl-2-chloromethylbenzimidazole. Additional finan-
cial support was provided by the Spanish Direcciꢀn General de Investiga-
ciꢀn (DGI; grant CTQ2011-23862-C02-01/BQU) and the Departament
d’Universitats, Recerca i Societat de la Informaciꢀ (DURSI) of the Gener-
alitat de Catalunya (grant 2009SGR-1459). The computing resources at
the Centre de Supercomputaciꢀ de Catalunya (CESCA) were made avail-
able in part through a grant from the Fundaciꢀ Catalana per a la Recerca
(FCR) and the Universitat de Barcelona. We thank Rubꢃn A. Toscano
and Simꢂn Hernꢁndez-Ortega for crystallographic work, Virginia
Gꢂmez-Vidales for EPR, Erꢃndira Garcꢀa-Rꢀos and Carmen Mꢁrquez for
ESI-MS, Rocꢀo PatiÇo-Maya for IR, Luis Velasco for FAB-MS, and
Marꢀa de la Paz Orta and Alejandra NfflÇez for combustion analyses.
The mixture was stirred for 24 h, then filtered through a cannula and con-
centrated under reduced pressure until a turbid solution was obtained.
Cooling to ꢀ258C resulted in a colorless solid that was filtered and
washed with cold diethyl ether to afford complex 2. Yield: 31 mg (24%);
1H NMR (300 MHz, CD3CN, 208C, CHD2CN): d=7.60 (m, 2H; Ar),
7.39 (m, 2H; Ar), 7.10 (d, J=7.9 Hz, 3H; Ar), 6.91 (s, 2H; Ar), 6.71 (d,
J=7.9 Hz, 2H; Ar), 4.36 (s, 3H; CH3), 4.09 (s, 4H; CH2), 3.33 (s, 2H;
CH2), 2.30 (s, 3H; CH3), 1.95 ppm (s, 3H; CH3); 13C{1H} NMR (75 MHz,
CDCl3, 208C, CHD2CN): d=138.71 (Ar), 133.06 (Ar), 132.30 (Ar),
131.91 (Ar), 131.79 (Ar), 129.27 (Ar), 128.44 (Ar), 128.30 (Ar), 115.03
(Ar), 113.83 (Ar), 113.43(Ar), 113.05(Ar), 68.01 (CH2), 47.06 (CH2),
30.95 (NCH3), 21.06 (CH3), 20.84 ppm (CH3); MS (ESI, CH3CN): m/z:
523 [CuL2]+, 385 [CuL2ꢀSC6H3Me2]+; IR (KBr): n˜ =3465, 3435, 3002,
2965, 2917, 2862, 1475, 1439, 1092, 1049, 797, 621, 588, 434 cmꢀ1; elemen-
tal analysis calcd (%) for C27H31ClCuN3O4S2: C 51.91, H 5.00, N 6.73;
found: C 51.72, H 5.21, N 6.38.
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[(2,4-Me2C6H3SCH2CH2)2(2-CH2C7H5N2)N]Cu
Schlenk tube was charged with L2’ (100 mg, 0.21 mmol) and then [Cu-
(CH3CN)4]ClO4 (69 mg, 0.21 mmol) and CH3CN (15 mL) were added.
A
A
100 mL
ACHTUNGTRENNUNG
The mixture was stirred for 24 h, then filtered through a cannula, and
concentrated under reduced pressure until a turbid solution was ob-
tained. Cooling to ꢀ258C resulted in a colorless solid that was filtered
and washed with cold diethyl ether to afford complex 2’. Yield: 48 mg
(33%); 1H NMR (300 MHz, CD3CN, 208C, CHD2CN): d=11.41 (s, 1H;
NH), 7.66 (m, 2H; Ar), 7.17 (m, 4H; Ar), 6.95 (s, 2H; Ar), 6.75 (d, J=
7.8 Hz, 2H; Ar), 4.25 (s, 2H; CH2), 2.83 (m, 8H; CH2CH2), 2.34 (s, 6H;
6078
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Chem. Eur. J. 2013, 19, 6067 – 6079

Copper Versus Thioether-Centered Oxidation
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Received: October 1, 2012
Published online: March 11, 2013
Chem. Eur. J. 2013, 19, 6067 – 6079
ꢆ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6079