Rhenium diazenide ternary complexes with dithiocarbamate ligands: Towards new rhenium radiopharmaceuticals

Article abstract of DOI:10.1039/b611403b

The reaction of the mono-diazenide core, [ReCl₂(NNC ₆H₄-4-OCH₃)(NCCH₃)(PPh ₃)₂], with four equivalents of the sodium or potassium salts of dithiocarbamate (dtc) ligands gives neutral complexes of the formula [Re(NNC₆H₄-4-OCH₃)(dtc)₂(PPh ₃)]. It is possible to use a wide range of dithiocarbamate ligands (S₂CNRR′) with a variety of R groups (R = R′ = methyl, phenyl or ethyl; R = methyl, R′ = phenyl and R = R′ = morpholino). Substitution reactions with dtc ligands on the mono-diazenide derived from 2-hydrazinopyridine, [ReCl₂(NNC₅H₄N)(PPh ₃)₂, give the analogous complexes, [Re(NNC ₆H₅N)(dtc)₂(PPh₃)]. The new complexes have been characterised by a combination of NMR spectroscopy, mass spectrometry and X-ray crystallography. Cyclic voltammetry measurements in dimethyl formamide show that the rhenium diazenido-dtc complexes undergo a quasi-reversible oxidation tentatively assigned to a Re^III/Re ^IV oxidation. Since the parent complex, [ReCl₂(NNC ₆H₄-4-R)(NCCH₃)(PPh₃)₂] can be prepared directly from perrhenate and readily derivatised with dtc ligands these complexes have potential relevance to the development of new therapeutic rhenium radiopharmaceuticals. This journal is The Royal Society of Chemistry.

Full text of DOI:10.1039/b611403b

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www.rsc.org/dalton | Dalton Transactions
Rhenium diazenide ternary complexes with dithiocarbamate ligands: towards
new rhenium radiopharmaceuticals
Andrew R. Cowley,a Jonathan R. Dilworth,*b Paul S. Donnellyc,d and Susan J. Rossb
Received 10th August 2006, Accepted 9th October 2006
First published as an Advance Article on the web 31st October 2006
DOI: 10.1039/b611403b
The reaction of the mono-diazenide core, [ReCl2(NNC6H4-4-OCH3)(NCCH3)(PPh3)2], with four
equivalents of the sodium or potassium salts of dithiocarbamate (dtc) ligands gives neutral complexes
of the formula [Re(NNC6H4-4-OCH3)(dtc)2(PPh3)]. It is possible to use a wide range of dithiocarbamate
ligands (S2CNRRꢀ) with a variety of R groups (R = Rꢀ = methyl, phenyl or ethyl; R = methyl,
Rꢀ = phenyl and R = Rꢀ = morpholino). Substitution reactions with dtc ligands on the
mono-diazenide derived from 2-hydrazinopyridine, [ReCl2(NNC5H4N)(PPh3)2, give the analogous
complexes, [Re(NNC6H5N)(dtc)2(PPh3)]. The new complexes have been characterised by a combination
of NMR spectroscopy, mass spectrometry and X-ray crystallography. Cyclic voltammetry
measurements in dimethyl formamide show that the rhenium diazenido-dtc complexes undergo a
quasi-reversible oxidation tentatively assigned to a ReIII/ReIV oxidation. Since the parent complex,
[ReCl2(NNC6H4-4-R)(NCCH3)(PPh3)2] can be prepared directly from perrhenate and readily
derivatised with dtc ligands these complexes have potential relevance to the development of new
therapeutic rhenium radiopharmaceuticals.
a high oxidation state precursor, [TcO4]−, with the appropriate
Introduction
hydrazine with reduction of the metal, oxidation of the hydrazine
There is currently considerable interest in the development of new
to diazenide and formation of a metal–nitrogen multiple bond.
radiotherapeutic cancer agents based on rhenium. There are two
b-emitting isotopes of Re, 186Re and 188Re, which have suitable
The metal–nitrogen multiple bond is sufficiently stable for in vivo
imaging applications. HYNIC can occupy one or two coordination
nuclear properties for therapeutic applications. 188Re is readily
sites so further co-ligands are required to occupy the other sites
available from a generator by decay of 188W and is obtained as
on the five- or six-coordinate metal atom. A well developed
a very dilute solution of [ReO4]−.1,2 This can provide a useful
technetium system which is undergoing clinical trials utilizes
source of sterilising b radiation if it can be targeted in vivo.3 Such
targeting can be achieved by the incorporation of the metal atom
a HYNIC derivatized cyclic peptide to form a metal–nitrogen
multiple bond with the metal. The remaining coordination sites
in a coordination complex using a bifunctional ligand. Ideally the
are occupied by a combination of tricine and a water soluble
ligand must form a highly stable complex and possess a point
phosphine to give a ternary system. The coordinative flexibility
of further functionalisation that can allow the attachment of
of prochiral tricine combined with the ability of pyridylhydrazine-
biologically active molecules to provide specificity and selectivity
derived ligands to act as either a monodentate or bidentate ligand
in vivo.4
results in there being a large array of potential isomeric forms.9
Similar systems have been investigated with rhenium as its
coordination chemistry is superficially similar to technetium,
although rhenium is more kinetically inert than technetium and,
significantly, it is much harder to reduce [ReO4]− than [TcO4]−.1
The coordination chemistry of the HYNIC system is shown by the
reaction of [ReO4]− with 2-hydrazinopyridine which gives systems
in which two pyridylhydrazine-derived units are coordinated to the
rhenium.12–15 X-Ray structural characterisation of the compounds
formed revealed a complex coordination chemistry due to the
ability of the pyridylhydrazine-derived ligands to coordinate as
either monodentate or bidentate ligands and the existence of
protic equilibria.15 This results in radiolabelled protein conjugates
made using this system consisting of mixtures of complexes
which have proved difficult to characterise fully. We have recently
reported the reaction of arylhydrazines directly with perrhenate in
acetonitrile to give a high yield of a mono-aryl diazenide complex,
which has the potential to provide access to a new core for the
development of radiotherapeutic agents based on rhenium.16 We
The use of functionalised diazenide (NNAr, Ar = aryl or
2-pyridyl) ligands for the targeting of radiopharmaceuticals
based on technetium is well established,5,6 particularly for the
HYNIC system (where HYNIC = N-oxysuccinimidylhydrazino-
nicotinamide) which uses the substituted pyridyl group as the
bifunctional ligand.7–11 The activated ester can be used to attach
a variety of biologically active targeting molecules whilst the
hydrazine fragment is used to form a metal–nitrogen multiple
bond with Tc. The synthetic approach involves the reaction of
aChemical Crystallography, University of Oxford, 12 Mansfield Road,
Oxford, U. K. OX1 3TA
bChemistry Research Laboratory, University of Oxford, 12 Mansfield Road,
Oxford, U. K. OX1 3TA. E-mail: jon.dilworth@chem.ox.ac.uk; Fax: 01865-
272690; Tel: 01865-285151
cSchool of Chemistry, University of Melbourne, Victoria, 3010, Australia.
E-mail: pauld@unimelb.edu.au
dBio21 Molecular Science and Biotechnology Institute, University of Mel-
bourne, Victoria, 3010, Australia
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now report that the mono-aryl diazenide core undergoes high yield
substitution reactions with substituted dithiocarbamate ligands
(dtc) to form stable, well defined ternary complexes, of the type
[Re(NNAr)(dtc)2(PPh3)].
The use of dithiocarbamate as a co-ligand avoids the isomeric
complexity of tricine systems. These complexes have been charac-
terised by X-ray crystallography, NMR, mass spectroscopy and
HPLC. The complexes offer potential for the development of well
defined ternary systems suitable for the development of rhenium
based therapeutic agents.
The reaction of 2-hydrazinopyridine hydrochloride with
[ReO4]− in methanol allows the isolation of [ReCl3(N
=
15
=
NC5H4NH)(HN NC5H4N)] in high yields (Scheme 2). The
structure contains two ligands which originate from the 2-
hydrazinopyridine, one acting as a bidentate ligand, coordinating
through the pyridine nitrogen atom and a diazene a-nitrogen.
The other coordinates as a monodentate ligand with the pyridine
nitrogen atom protonated. The reaction of this compound with
triphenylphosphine in ethanol in the presence of base results in the
=
=
formation of [ReCl2(PPh3)(N NC5H4N)(HN C5H4N)]. We have
found that the reaction of 2-hydrazinopyridine dihydrochloride
with perrhenate in acetonitrile also results in the formation of
Results and discussion
=
=
[ReCl3(N NC5H4NH)(HN NC5H4N)], which precipitates from
the reaction mixture, but the yield of the reaction in acetonitrile is
significantly lower than that reported in methanol.15 The filtrate of
the acetonitrile reaction mixture is dark red and addition of triph-
enylphosphine to this mixture followed by heating at reflux for 4 h
allows the isolation of [Re(NNC5H4N)Cl2(PPh3)2] (B) (Scheme 2).
The same compound has been reported as the product of the
reaction of 2-hydrazinopyridine with [ReOCl3(PPh3)2].18 When
additional conc. HCl is present, the majority of the solid formed
is not [Re(NNC5H4N)Cl2(PPh3)2] but the known compound
[ReNCl2(PPh3)2], which was identified by X-ray crystallography.19
The mono-diazenide complex A can be readily and rapidly
substituted with a variety of ligands to form kinetically inert
species whilst maintaining the mono-diazenide core. The use of
co-ligands to complement a particular metal core is particularly
attractive in the development of radiopharmaceuticals as it
can allow subtle control of factors such as complex stability,
lipophilicity, charge and ultimately biodistribution.
We recently reported that the reaction of [NH4][ReO4] or
[nBu4N][ReO4] with substituted phenylhydrazines (NH2NHC6H4-
4-R; where R = OCH3, Cl, or CO2CH3) in acetonitrile in the
presence of aqueous acid results in the rapid formation of a red
solution.16 The electrospray mass spectra of the reaction mixture
when R = OCH3 show that several different rhenium diazenide
species are present but by far the biggest peak (in negative ion
mode, with appropriate isotope distribution) corresponds to the
mono-diazenide species [ReCl4(NNC6H4-4-OCH3)]− at m/z =
462. Addition of triphenylphosphine results in the formation of a
single species by HPLC and a red air-stable solid, [ReCl2(NNC6H4-
4-OCH3)(NCH3)(PPh3)2] (A) (Scheme 1), in isolated yields of
about 70%. It appears that the triphenylphosphine may sta-
bilise the diazenide core and drive the reaction to completion.
Similar observations have been made from other species with
metal–nitrogen multiple bonds.17 Interestingly, these compounds
are not accessible from the reaction of the well known rhe-
nium precursor, [ReOCl3(PPh3)2], with arylhydrazines in aceto-
nitrile.
The reaction of the mono-diazenide ‘core’ compound, A, with
approximately 4 equivalents of the sodium or potassium salts of
dithiocarbamate ligands in methanol allows the ready isolation
of the neutral complexes [Re(NNC6H4-4-R)(dtc)2(PPh3)] as red-
brown solids in high yields (Scheme 1).
It is possible to use a wide variety of dithiocarbamate ligands,
(S2CNRRꢀ, where R = Me and Rꢀ = Me or Ph, R = Rꢀ = Ph or Et
and finally where RRꢀ = morpholino (C4H8NO)) and in each case
the product of the substitution is [Re(NNC6H4-4-R)(dtc)2(PPh3)]
(Fig. 1). The electrospray mass spectra of the complexes all show
peaks corresponding to the [M + H+].
Crystals suitable for single crystal X-ray studies were grown of
the compounds resulting from the reaction of mono-diazenide 1
with sodium dimethyl dithiocarbamate and sodium methyl phenyl
Scheme 1 The synthesis of 1–5.
Scheme 2 The reaction of perrhenate with 2-hydrazinopyrdine dihydrochloride and triphenylphosphine.
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Fig. 1 Rhenium diazenide ternary complexes with dithiocarbamate ligands, complexes 1–10.
dithiocarbamate (Table 1). Representations of the structures are
shown in Fig. 2.
are shown in Fig. 3. A comparison of critical bond lengths and
angles relating to the diazenido ligand is shown in Table 2.
CCDC reference numbers 617262–617267. For crystallographic
data in CIF or other electronic format see DOI: 10.1039/b611403b
The site trans to the diazenide ligand is occupied by a sulfur atom
from one of the dithiocarbamate ligands, with the single phosphine
ligand occupying one of the sites cis to the diazenide ligand. The
Re–N–N system is essentially linear (Re1–N1–N2 = 176.6(3)◦)
and the Re–N1 and N1–N2 bond distances are characteristically
short, consistent with the monodentate diazenide ligand acting as
a “type A” monoanionic 3 electron donor.21 Further evidence of
the rhenium–nitrogen multiple bonding is provided by the trans-
lengthening effect of the –NNC6H4-4-OCH3 group; the Re–S bond
Solution NMR
All of the rhenium(III) (d4) complexes mentioned here are diamag-
netic and as such give informative 1H, 31P and 13C NMR spectra at
room temperature in CDCl3 solution, which have been assigned by
use of COSY, TOCSY, HMQC, HMBC and DEPT-135 sequences
as appropriate.
1
For [Re(NNC6H4OMe)(Me2dtc)2(PPh3)], the H NMR spec-
trum shows a clear AAꢀBBꢀ roofed pair of doublets at 6.80
and 6.69 ppm and a singlet at 3.73 ppm corresponding to the
para-disubstituted phenyl protons and the methoxy protons of
the diazenide ligand respectively. In the 13C spectrum, the two
protonated phenyl carbons, with signals at 120.79 and 113.82 ppm,
are shown by a HMBC correlation experiment to be linked to
signals at 156.17 and 128.51 ppm (quaternary carbons) and the
methoxy resonance at 55.5 ppm (Fig. 4).
˚
trans to the diazenide is at least 0.051 A longer than the other
Re–S bond lengths. The structures are similar with the rhenium
in a distorted octahedral environment and the two dithiocar-
bamate ligands acting as bidentate ligands, which are disposed
cis to each other. The mono-diazenide complex derived from 2-
2
hydrazinopyridine (B) and [ReCl2(g -NNCOPh)(PPh3)2] undergo
similar substitutions with sodium salts of dithiocarbamate ligands
to give compounds 6–10 (Fig. 1). Representations of the X-ray
crystal structures of [Re(NNPy)(Me2dtc)2(PPh3)] (6), [Re(NNPy)-
(Morphdtc)2(PPh3)] (7) and [Re(NNCOPh)(Me2dtc)2(PPh3)] (10)
Identification of the carbon ortho to the methoxy-substituted
site on the phenyl ring allows the proton doublets to be identified
unequivocally, with the proton ortho to the methoxy group at
6.69 ppm (consistent with its electron-donating substituent) and
Fig. 2 ORTEP20 representations of 1 (left) and 3 (right), showing thermal ellipsoids at the 50% probability level.
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the meta at 6.80 ppm. Four singlets corresponding to the four
methyl groups on the two dithiocarbamate ligands (A and B) are
present at 3.33 (A), 3.27 (A), 3.00 (B), 2.91 ppm (B): for each pair of
methyl signals, the related methyl carbons and the quaternary CS2
carbon for each ligand at 38.35, 39.43, and 225.11 ppm (A) and
38.07, 38.60 and 205.17 ppm (B). The consistent downfield shift
for ligand A suggests that this group of resonances may be due to
a less shielded site which could be caused by the trans effect of the
diazenide ligand and so this dithiocarbamate ligand is tentatively
assigned as having sulfur donor-atoms in the sites cis and trans
to the diazenide nitrogen. The PPh3 ligand shows multiplets in
the proton NMR at 7.52–7.40 ppm (ortho) and at 7.28–7.20 ppm
(meta and para), and singlets in the carbon spectrum at 135.71,
134.07, 129.08 and 127.41 ppm (quaternary, ortho, para and meta
respectively), with a singlet in 31P NMR at 14.33 ppm.
The related pyridyl-diazenido compound [Re(NNPy)-
(Me2dtc)2(PPh3)] has many similarities in its NMR behaviour.
The most prominent difference is the resonances due to the pyridyl
ring in the 1H spectrum. These were assigned on the basis of their
coupling constants by looking at the large 7.0 and 8.0 Hz values
characteristic of coupling between the site para to the pyridyl
nitrogen and one next to it in a substituted pyridine aromatic
system.22 This placed the resonance at 6.81 ppm ortho to the
diazenide, the carbon para to the pyridyl nitrogen (with couplings
at both 7.0 and 8.0 Hz) at 7.33 ppm, the one meta to the pyridyl N
at 6.64 ppm and the last signal ortho to the pyridyl N at 8.19 ppm,
with a coupling of 5.0 Hz to its meta neighbour also typical of
such an interaction in a substituted pyridyl ring.
Signals from the triphenylphosphine ligand are shifted down-
field (meta; 7.54–7.49 ppm 1H) and upfield (ortho and para; 7.26–
7.19 ppm 1H), suggesting a subtle difference in the electronic
nature of the complex as a whole, with the para-substituted
phenyl-diazenido ligand relatively more electron-donating than
the pyridyl-diazenido ligand. The 31P singlet is shifted downfield
to 14.61 ppm. This effect is also seen in the dithiocarbamate
resonances: for the methyl signals for the cis, trans-ligand A, one
signal is almost unchanged at 3.32 ppm (a difference of 0.01 ppm),
but the other is moved upfield to 3.27 ppm, a difference of 0.1 ppm.
For the symmetrically bound cis, cis-ligand B both methyl signals
are shifted upfield by a similar amount to 2.94 and 2.83 ppm
(differences of 0.06 and 0.08 ppm, respectively).
Certain features are common to many of these compounds:
phosphorus–carbon coupling causes the signals due to PPh3
to appear as doublets in 13C NMR, with an increase in the
coupling constant on coordination for the quaternary carbon
(typically 47 Hz (c.f. 20 Hz in free PPh3). This is presumed
to be due to the back-bonding of the phosphine ligand, which
reduces shielding on the quaternary carbon. Anomalously, no P–
C coupling is observed for [Re(NNAr)(Me2dtc)2(PPh3)] (although
it is observed for [Re(NNPy)(Me2dtc)2(PPh3)]), suggesting that
this may be due to a coincidentally negative or zero value
coupling constant. 31P NMR shows a singlet at 14.3–16.7 ppm
(phenyldiazenido compounds with the anomalous exception of
2, dP −5.17 ppm), 14.2–15.6 ppm (pyridyldiazenido compounds)
or 14.2 ppm (benzoyldiazenido compound 10), although on close
inspection a slight “double” nature to this peak can be observed
for compounds 2–5 and 6–9 due to the fluxional nature of these
structures in solution. The solution fluxionality was resolved
for 1, for which the 1H NMR spectrum of this complex in
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Fig. 3 ORTEP representations of 6 (left), 7 (centre) and 10 (right). Thermal ellipsoids are at the 20% probability level.
Table 2 Selected lengths and angles for the new rhenium diazenido complexes
Re–N–N/◦
˚
˚
Complex
M–N/A
N–N/A
Category A linear, uninegative, 3e donor
[Re(NNC6H4OMe)(Me2dtc)2(PPh3)] (1)
[Re(NNC6H4OMe)(PhMedtc)2(PPh3)] (3)
[Re(NNPy)(Me2dtc)2(PPh3)] (6)
[Re(NNPy)(Morphdtc)2(PPh3)] (7)
[Re(NNCOPh)(Me2dtc)2(PPh3)] (10)
1.7–1.8
1.2–1.3
161–173
176.6(3)
177.6(3)
176.6(4)
178.7(4)
175.7(6)
1.773(3)
1.762(4)
1.747(5)
1.753(5)
1.734(7)
1.248(5)
1.261(5)
1.277(7)
1.244(7)
1.279(9)
Entries in italics relate to the categories of hydrazine-derived ligands proposed by Hirsch-Kuchma et al.21
Fig. 5 1H NMR spectra for 3, showing methyl protons at (a) 323 K,
(b) ambient temperature and (c) 213 K.
Fig. 4 1H–13C HMBC spectrum of 1 showing long-range coupling
between (1) NNAr aromatic protons, (2) OCH3, (3) dtc A CH3 and (4)
dtc B CH3 and (a) dtc B CS2, (b) NNAr ipso carbon, (c) and (d) dtc A and
B methyl carbon atoms and (e) dtc A CS2 (folded†).
simplified. This behaviour is consistent with a mechanism of
C–N bond rotation,23–28 with the steric bulk of the phosphine
ligand and the phenyl N-substituent forming a kinetic barrier to
free rotation of the C–N bond of the cis, trans-dithiocarbamate
ligand. However, a mechanism involving change to a monodentate
coordination mode and then return to a bidentate mode cannot
be ruled out. Variable temperature studies did not improve the
spectra for compounds with symmetrical dithiocarbamate ligands
relative to those at room temperature.
CDCl3 at room temperature shows broadened signals for methyl
and aromatic protons. Variable temperature NMR studies were
undertaken to show that the six broad methyl signals (i.e. four due
to dimethyldithiocarbamate ligands and two due to the methoxy
substituent on the aryldiazenido ligand) observed at ambient
temperature (approximately 293 K) coalesce into three signals at
323 K and are resolved into 12 sharp singlets at 213 K (Fig. 5).
Unfortunately the aromatic protons are not completely resolved
at 213 K and the freezing point of the solvent prohibits further
investigation, but the aromatic region is nevertheless greatly
Cyclic voltammetry
An initial study of the electrochemistry of 1, 6 and 10 was carried
out using cyclic voltammetry to establish the location of key redox
processes. Representative voltammograms for the three complexes
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Table 3 Electrochemistry of mono-diazenido complexes
Complex
E
1/2/V
iPa/iPc
Peak separation/mVa
[Re(NNC6H4OMe)(Me2dtc)2(PPh3)] (1)
−0.13
−0.12
+0.08
0.69
0.94
0.59
98
100
83
[Re(NNPy)(Me2dtc)2(PPh3)] (6)
[Re(NNCOPh)(Me2dtc)2(PPh3)] (10)
a Under the same conditions, the ferrocene/ferrocenium couple has a peak separation of 100 mV.
with a scan rate of 100 mV s−1 are shown in Fig. 6. All three
complexes show quasi-reversible processes in the range −0.13 to +
0.08 V versus the standard calomel electrode, which is interesting
as the [ReCl2(NNC6H4OMe)(NCMe)(PPh3)2] starting material
shows a fully reversible process at 0.56 V; for its p-chlorophenyl
analogue this occurs at 0.60 V.16 The shift in the redox process
to a more accessible potential, which is tentatively assigned as a
Re3+/Re4+ couple, indicates that the dithiocarbamate ligands may
act to stabilise the rhenium(IV) oxidation state. For the less soluble
benzoyldiazenido complex, 10, the shift of the redox couple to a
slightly more positive potential is attributed to the inductive effect
of the benzoyl group in comparison to the aromatic substituents
of 1 and 6 (Table 3).
are no known rhenium or technetium complexes exhibiting a
“bent” (type B) diazenido ligand (such that the chelating diazenido
ligands have been taken as an approximation of their likely
structural properties). Møller and Jørgensen have shown that
for the “linear” diazenido complex [ReCl2(NNPh)(PPhMe2)3],
the third HOMO includes the p-bond between the diazenido
ligand and the [ReCl2(PPhMe2)3]+ fragment and the Nb lone pair,
while the antibonding orbital is the LUMO.29 This is in sharp
contrast to the “bent” diazenido complex [RhCl(NNPh)(PPh3)3]+
(for which the p* orbital is the HOMO) and similar frontier
orbitals are found for rhenium complexes with other types of
bent organohydrazine-derived ligands.21 It is tempting to infer
from this that the diazenido complexes for which the Re–N–N
bond angle most closely approaches 180◦ are those which could
be most stable and, if this is so, the new family of dithiocarbamate
complexes, for which Re–N–N is 175.7–178.7◦, is of considerable
interest. However it has been found that there is very little change
in M–N bond overlap population with M–N–N bond angle over
the range of interest.29 It must be remembered that it is simplistic to
assume bond lengths and angles correlate with bond strengths and
complex stability and that they may be influenced by extraneous
factors such as crystal packing.
We have shown that the parent [ReCl2(MeCN)(NNAr)(PPh3)2]
complexes, readily available from perrhenate, can be derivatised
with dithiocarbamate ligands in a straightforward manner to give
complexes of the type [Re(NNAr)(dtc)2(PPh3)]. The use of dithio-
carbamate as a co-ligand avoids the isomeric complexity of tricine
systems that have been investigated in the past. In addition, dithio-
carbamate ligands can be prepared with a range of substituents
which might allow some control of biodistribution. A recent report
demonstrated that the [ReCl2(MeCN)(NNAr)(PPh3)2] can also be
derivatised with a crown ether-containing dithiocarbamate ligand
and a PNP-type bisphosphine (PNP) to give complexes of the
type [Re(NNAr)(dtc)(PNP)]+.30 These examples demonstrate the
potential of arylhydrazine bifunctional chelates for use in rhenium
radiopharmaceutical preparations.
Fig. 6 Cyclic voltammograms of 1, 6 and 10 in DMF (scan rate
100 mV s−1).
Conclusions
One of the overarching themes of the present work is to add
to the present body of knowledge about rhenium and its reac-
tions with organohydrazines. This is of interest not only from
the standpoint of developing aryldiazenido-linkers for rhenium
radiopharmaceuticals, but also for comparison with the known
behaviour of the HYNIC linker system with technetium and the
apparent failure of the same technology with rhenium. This could
be due to the more extreme conditions needed to overcome the
kinetic inertia of rhenium relative to technetium, which could
in some way prove damaging to the linker, or it could be that
the potentially supportive chelating interaction of the pyridyl
nitrogen with the metal ion is more beneficial to technetium
than it is to rhenium. In this context it is interesting that all
of the new rhenium-diazenido complexes prepared are “linear”
(type A)21 (including those pyridyl- and benzoyldiazenido ligands
which could potentially adopt a chelating mode) and that there
Experimental
Syntheses were carried out under a nitrogen atmosphere using
standard Schlenk techniques except where otherwise stated. When
working under nitrogen, methanol was dried with magnesium
turnings and a catalytic amount of iodine under a nitrogen
atmosphere and distilled before use. Other solvents, in particular
acetonitrile, were used as received and degassed before use. Cyclic
voltammetry measurements were carried out in degassed DMF
˚
dried over 3 A molecular sieves.
[ReCl2(NNC6H4OMe)(NCMe)(PPh3)2] (A) was made accord-
ing to the published procedure.16 Unless otherwise specified, other
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reagents were purchased from standard commercial suppliers
and were used as received. NMR samples were run on either a
Varian Mercury 300 (1H: 300.0 MHz, 31P: 121.5 MHz, 13C: 75.5
MHz) or a Varian Unityplus (1H: 500.0 MHz, 31P: 202.5 MHz,
13C: 126.0 MHz. NMR data was processed with Varian Solaris
software on Sun Microsystems workstations. All NMR spectra
were recorded at room temperature unless otherwise stated. 31P
NMR was referenced externally with H3PO4 taken as 0.0 ppm,
and for 1H and 13C NMR residual solvent peaks were used
as an internal reference (relative to tetramethylsilane). All 13C
and 31P NMR peaks are singlets unless otherwise specified. IR
spectra were recorded on a Perkin–Elmer Paragon 1000 FT-
IR spectrometer controlled by a personal computer running
Grams Analyst software in Microsoft Windows. Samples were
prepared as KBr discs. Data was subsequently processed with
Perkin–Elmer Spectrum for Windows software. Elemental anal-
yses were performed by the in-house elemental analysis service
at the Inorganic Chemistry Laboratory, University of Oxford,
on a Elementar Analysensysteme GmbH vario EL machine by
oxidative combustion (C, H, N, S, Cl) or with ICP-OES (Na) on a
Thermo Jarrell Ash Atom Scan 16. ES-MS samples were run on a
Micromass LCT ToF mass spectrometer and samples for positive
ion mode were treated with formic acid to encourage ionisation.
X-Ray crystal structures were determined on an Enraf-Nonius
KappaCCD diffractometer (graphite-monochromated Mo Ka
225.1 (CS2, dtcA), 205.2 (CS2, dtcB), 156.2 (Ar–H, ipso, NNAr,
ipso to methoxy), 135.7 (PPh, ipso), 134.1 (PPh, ortho), 129.1 (PPh,
para), 128.5 (Ar–H, ipso, NNAr, ipso to diazenide), 127.4 (PPh,
meta), 120.8 (NNAr), 113.8 (NNAr), 55.5 (OMe), 39.4 (Me, dtcA),
38.6 (Me, dtcB), 38.4 (Me, dtcA), 38.1 (Me, dtcB); m/z = 824.9
(100%) = [M + H+], 603.7 (5%) = [M–PPh3 + K+], 562.6 (70%) =
[M–PPh3 + H+]. E1/2 = −0.13 V, iPa/iPc = 0.69, peak separation =
98 mV.
[Re(NN(C6H4OMe)(Et2dtc)2(PPh3)] (2). This compound was
synthesised following the method used for1, with reaction solution
evaporated to dryness. Yield (crude solid) 44% (0.04 g, 0.05 mmol).
Brown needle-like crystals suitable for elemental analysis were
grown by layering CH2Cl2 with pentane. (Found C, 46.25; N, 6.14;
H, 4.99%. C33H42N4OPReS4 requires C, 46.25; N, 6.54; H, 4.94%);
mmax/cm−1 = (CN) 1558, (N N) 1493, (COMe)124, (Ar, para-
=
disubst.) 830, (mono-subst. Ph) 746 and 695; dH (CDCl3) 7.49–
7.44 (6H, m, PPh3 ortho), 7.32–7.17 (9H, m, PPh3 meta and para),
6.86 (2H, d, JHH = 9.0 Hz, AAꢀ part of an AAꢀBBꢀ spin system,
para-disubst. ring, NNAr), 6.63 (2H, d, JHH = 9.0 Hz, BBꢀ part
of an AAꢀBBꢀ spin system, para-disubst. ring, NNAr), 3.73 (3H, s,
o/l, OMe), 3.94–3.08 (8H, m, broad, o/l, CH2, dtc), 1.41–0.84
(12H, m, CH3, dtc); dP (CDCl3) −5.17; dC (CDCl3) 161.6 (NNAr,
ipso), 134.6–134.3 (m, PPh3), 134.1–133.9 (m), 132.8–132.1 (m,
PPh3, ipso), 129.7–129.3 (m, Ph), 129.0–128.9 (m), 128.8–128.6
(m), 128.0–127.8 (m, PPh3), 121.1–120.2 (m, NNAr), 114.3–114.1
(m, NNAr), 55.9–55.7 (OMe), 45.3–41.7 (m, CH2), 15.7–12.5 (m,
CH3). NB: Despite several attempts and probably due to complex
fluxionality in solution, no CS2 peaks could be observed; m/z =
880 (35%) = [M]+, 618 (8%) = [M–PPh3]+.
˚
radiation, k = 0.71073 A) and processed using the DENZO-
SMN package,31 the direct-methods program SIR9232 and the
CRYSTALS program suite.33
Cyclic voltammetry experiments were carried out using a BAS
Electrochemical Analysis System equipped with BAS Epsilon
software (v.1.40.67NT). Sample solutions for cyclic voltammetry
were prepared by dissolving a crystalline sample of each complex
in degassed, dry DMF, using [NH4][BF4] at 0.02 mol dm−3 as
a supporting electrolyte and the ferrocene/ferrocenium redox
couple as an internal reference (+ 0.53 V vs. SCE). Data were
collected at room temperature using a platinum working electrode
and an Ag/Ag+ reference electrode.
[Re(NN(C6H4OMe)(PhMedtc)2(PPh3)] (3). This compound
was synthesised following the method used for 1: 3 is a brown solid
produced from [ReCl2(NNC6H4OMe)(NCMe)(PPh3)2] (0.10 g,
0.10 mmol) in 34% yield (0.03 g, 0.04 mmol). Brown crystals of
[Re(NNC6H4OMe)(PhMedtc)2(PPh3)] were grown by diffusion of
pentane into a CHCl3 solution. mmax/cm−1 = (CN) 1553.6, (N N)
=
1492.2, (PPh) 1435.0, (COMe) 1241.6, (Ar, para-disubst.) 828.0,
(mono-subst. Ph) 745.6 and 695.4; dH (CDCl3, 213 K) 7.50–7.16
(m, PPh3), 7.00–6.97 (d, aromatic), 6.93–6.80 (m, aromatic), 6.77–
6.62 (m, NNAr), 3.78, 3.76, 3.74 and 3.71 (all OMe), 3.65, 3.60,
3.56 (o/l) and 3.56 (o/l; all CH3, dtc A), 3.26, 3.20, 3.17, 3.16 (all
CH3, dtc B). NB: As there are four species present in solution no
integrals are quoted. Also, at 213 K the CH3 signals are completely
resolved but the aromatic signals are not; dP (CDCl3, 213 K) 16.76,
16.70, 16.58; dP (CDCl3, 293 K) 15.11, 14.93; dC (CDCl3, 213 K)
∼225.9 (CS2, dtc A), 205.5 (CS2, dtc B), 155.4 (NNAr, ipso(OMe)),
155.4–155.3 (m) and 155.3–155.2 (m; both aromatic), 142.2–142.0
(m) and 141.3 (s; both aromatic), 134.6–134.4 (m, aromatic),
134.2–134.0 (m, aromatic), 133.9–133.5 (m, aromatic), 129.5–
129.3 (m, aromatic), 129.1–128.9 (m, aromatic), 128.6–128.3 (m,
aromatic), 127.7–127.3 (m, aromatic), 126.5–126.4 (m, aromatic),
126.3–126.0 (m, aromatic), 120.4–120.3 (m) and 120.2–120.1 (m;
both NNAr), 113.4–113.1 (m, NNAr), 55.3–55.2 (m, OMe), 41.6–
41.3 (m, CH3, dtc), 41.0–40.7 (m, CH3, dtc), 40.2–39.9 (m, CH3,
dtc) [NB: signals marked ∼ are derived from HMBC only]; m/z =
948.3 (100%) = [M + H+], 687.1 (72%) = [M–PPh3 + H+].
Preparation of a family of compounds of the type
[Re(NNC6H4OMe)(RRꢀdtc)2(PPh3)]
[Re(NN(C6H4OMe)(Me2dtc)2(PPh3)] (1). Sodium dimethyl-
dithiocarbamate hydrate (0.09 g, ≤0.63 mmol) was dis-
solved in MeOH (10 ml) and heated at reflux tem-
perature with [Re(NNC6H4OMe)Cl2(NCMe)(PPh3)2] (0.10 g,
0.11 mmol) for 12 h, then allowed to cool. The brown
solid formed was collected by filtration and rinsed with
MeOH. Yield 74% (0.07 g, 0.08 mmol). Brown crystals of
[Re(NNC6H4OMe)(Me2dtc)2(PPh3)] were grown by diffusion of
Et2O into a CH2Cl2 solution. (Found: C, 42.32; N, 6.16; H, 3.76%.
C31H34N4OPReS4·CH2Cl2 requires C, 42.28; N, 6.16; H, 3.99%);
mmax/cm−1 (CN) 1557, (N N) 1493, (PPh) 1433, (COMe) 1245,
=
(para-disubst. ring) 824, (mono-subst. Ph) 742 and 693; dH (CDCl3)
7.52–7.40 (6H, m, PPh3 ortho), 7.28–7.20 (9H, m, PPh3 meta and
para), 6.80 (2H, d, JHH = 9.0 Hz, AAꢀ part of an AAꢀBBꢀ spin
system, para-disubst. Ar–H), 6.69 (2H, d, JHH = 9.0 Hz, BBꢀ part
of an AAꢀBBꢀ spin system, para-disubst. Ar–H), 3.73 (3H, s, OMe),
3.33 (3H, s, Me, dtcA), 3.27 (3H, s, Me, dtcA), 3.00 (3H, s, Me,
dtcB), 2.91 (3H, s, Me, dtcB); dP(CDCl3) 14.33 (s); dC(CDCl3)
[Re(NNC6H4OMe)(Ph2dtc)2(PPh3)] (4). This compound was
synthesised following the method used for 1: the product is a bright
This journal is
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Dalton Trans., 2007, 73–82 | 79
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red solid obtained from [ReCl2(NNC6H4OMe)(NCMe)(PPh3)2]
with pyridylhydrazine dihydrochloride (1.38 g, 7.58 mmol). The
reaction mixture was cooled to room temperature and filtered to
remove dark brown [ReCl3(NNPy)(HNNPy)], which was rinsed
with MeOH and dried. The filtrate was transferred to another
flask containing PPh3 (2.07 g, 7.89 mmol). After heating at reflux
for 4 h, the reaction mixture was allowed to cool and the dark
red crystalline precipitate formed was recovered by filtration and
washed with MeOH and pentane. [ReCl3(NNPy)(HNNPy)]: Yield
12% (0.04 g, 0.07 mmol). [ReCl2(NNPy)(PPh3)2] (B): yield 34%
(0.27 g, 0.30 mmol). Dark red crystals were grown by layering a
frozen solution of the complex in DMF with CH2Cl2 and allowing
slow mixing as they warmed to room temperature.
(0.10 g, 0.10 mmol) in 18% yield (0.02 g, 0.02 mmol). mmax/cm−1
=
=
(CN) 1561, (N N) 1492, (PPh) 1434, (COMe) 1240, (Ar, para-
disubst.) 827, (mono-subst. Ph) 754 and 692; dH (CDCl3) 7.46–7.42
(4.6 H, m, phenyl, dtc), 7.41–7.35 (10H, m, o/l, phenyl dtc and
PPh), 7.32–7.19 (16.5 H, m, o/l, phenyl dtc and PPh), 7.02–6.99
(3.9 H, m, phenyl, dtc), 6.79 (2H, dt, JHH = 2.0 and 9.0 Hz, AAꢀ
part of an AAꢀBBꢀ spin system, para-disubst. ring, NNAr), 6.68
(2H, dt, JHH = 2.0 and 9.0 Hz, BBꢀ part of an AAꢀBBꢀ spin system,
para-disubst. ring, NNAr), 3.74 (3H, s, OMe); dP (CDCl3) 15.53
(s); dC (CDCl3) 229.0 (CS2, dtc), 208.0 (CS2, dtc), 156.2 (NNAr,
ipso to OMe), 142.4 (Ph, dtc), 135.8 (d, JPC = 46.0 Hz, PPh, ipso),
134.1 (d, JPC = 10.5 Hz, PPh, ortho), 129.8 (Ph, dtc), 129.4 (Ph,
dtc), 129.1 (PPh, para), 128.7 (NNAr, ipso to NN), 128.5 (Ph,
dtc), 128.4 (Ph, dtc), 128.0 (Ph, dtc), 127.8 (d, JPC = 29.5 Hz,
PPh, meta), 127.6 (Ph, dtc), 127.4 (Ph, dtc), 126.9 (Ph, dtc), 121.0
(NNAr, ortho to OMe), 113.8 (NNAr, ortho to NN), 55.5 (OMe);
m/z = 1071.81 (60%) = [M]+.
Attempted synthesis of [ReCl2(NNPy)(PPh3)2] from
[ReCl3(NNPy)(HNNPy)]
[ReCl3(NNPy)(HNNPy)] (0.15 g, 0.34 mmol) was heated at reflux
temperature in acetonitrile (15 ml, degassed) with PPh3 (0.6 g,
2.28 mmol) for 4.5 h, which gave a reddish-brown solution and
metallic dark brown solid. The solid was recovered by filtration,
[Re(NN(C6H4OMe)(Morphdtc)2(PPh3)] (5). This compound
was synthesised following the method used for 1: product is a
brown solid formed from [ReCl2(NNC6H4OMe)(NCMe)(PPh3)2]
(0.10 g, 0.10 mmol) in 73% yield (0.07 g, 0.08 mmol). Crystals of 6
suitable for elemental analysis were obtained by layering a solution
of the complex in CH2Cl2 with Et2O. (Found C, 45.81; N, 6.13;
H, 4.04%. C35H38N4O3PReS4 requires C, 46.25; N 6.17; H, 4.22%);
1
washed with Et2O and dried. Yield 82% (0.12 g, 0.28 mmol). H
NMR (300 MHz, DMSO-d6): d 8.79 (1H, d, JHH = 5.5 Hz, pyridyl),
8.43 (1H, d, JHH = 5.5 Hz, pyridyl), 8.29 (1H, t, JHH = 7.5 Hz,
pyridyl), 7.99 (1H, t, overlapping, JHH = 5.5 Hz, pyridyl), 7.91
(1H, d, JHH = 8.5 Hz, pyridyl), 7.70 (1H, d, JHH = 8.5 Hz, pyridyl),
7.21 (1H, d, JHH = 6.5 Hz, pyridyl), 6.87 (1H, t, JHH = 6.5 Hz,
pyridyl), 6.87 (1H, t, JHH = 6.5 Hz, pyridyl).9
mmax/cm−1 = (CN) 1559, (N N) 1492, (C–O–C) 1235, (Ar, para-
=
disubst.) 830, (mono-subst. Ph) 746 and 695; dH (CDCl3) 7.46–7.37
(6H, m, PPh3 ortho), 7.27–7.21 (9H, m, PPh3 meta and para), 6.80
(2H, d, JHH = 9.0 Hz, AAꢀ part of an AAꢀBBꢀ spin system, NNAr),
6.71 (2H, d, JHH = 9.0 Hz, BBꢀ part of an AAꢀBBꢀ spin system,
NNAr), 4.15–4.02 (2H, m, CH2, dtc), 3.89–3.69 (2.1H, m, o/l,
CH2, dtc), 3.75 (5.9H, s, o/l, OMe), 3.69–3.23 (8H, m, br, CH2,
dtc); dP (CDCl3) 15.10 (s); dC (CDCl3) 226.0 (CS2, dtc), 204.9 (CS2,
dtc), 156.4 (NNAr, ipso to OMe), 135.4 (d, JPC = 46.5 Hz, PPh3,
ipso), 134.0 (d, JPC = 7.0 Hz, PPh3, ortho), 129.2 (PPh3, para), 128.4
(NNAr, ipso to diazenide), 127.6 (d, JPC = 6.5 Hz, PPh3, meta),
120.9 (NNAr), 113.8 (NNAr), 66.0 (CH2O, dtc), 65.7 (CH2O, dtc),
55.5 (OMe), 47.4 (CH2N, dtc), 46.0 (CH2N, dtc), 45.7 (CH2N, dtc),
45.1 (CH2N, dtc); m/z = 908 (100%) = [M]+;
Synthesis and characterisation of a family of complexes of formula
[Re(NNPy)(dtc)2(PPh3)] (6–9)
These reactions were carried out using the same methodology as
that used for the synthesis of compounds 1–5; deviations from this
method are specified where appropriate.
[Re(NNPy)(Me2dtc)2(PPh3)] (6).
Method 1. The compound was synthesised from a mixture
of [Re(NNPy)Cl2(NCMe)(PPh3)2] and [ReNCl3(PPh3)2] (product
of [nBu4N][ReO4] and pyridylhydrazine dihydrochloride with
additional HCl, see above, total mass 0.71 g). The product
was formed as dark brown crystals in a suspension of orange
solid (thought to be unreacted [ReNCl2(PPh3)2] impurity), which
was pipetted off with the solvent. Crystals suitable for X-ray
structural determination and elemental analysis were obtained
by recrystallisation from a minimum amount of boiling methanol.
NMR and ES-MS were also carried out on this sample.
Reaction of pyridylhydrazine dihydrochloride with perrhenate and
triphenylphosphine (preparation of B).
Method 1. [nBu4N][ReO4] (0.46 g, 0.93 mmol) was dissolved in
acetonitrile (15 ml, degasssed) and heated at reflux temperature for
30 min with pyridylhydrazine dihydrochloride (0.71 g, 3.90 mmol)
and conc. HCl (0.3 ml, approx. 32%). The red-brown reaction mix-
ture was cooled to room temperature and filtered to remove a fawn
solid, presumed to be excess ligand. The filtrate was transferred to
another flask containing PPh3 (1.04 g, 3.97 mmol). After heating
at reflux for 2 h, the reaction mixture was allowed to cool. The
orange precipitate formed was recovered by filtration and washed
with iPrOH (2 × 5 ml) and pentane (2 × 5 ml). 0.45 g of the mixed
[ReNCl3(PPh3)2] and [ReCl2(NNPy)(PPh3)2] (B) was recovered.
Orange crystals were obtained by slow evaporation of a CH2Cl2
solution. The crystal structure was found to be [ReNCl2(PPh3)2]
(identical to that published by Doedens and Ibers).19 dP (DMSO-
d6) 26.64 ([ReNCl3(PPh3)2]), −6.85 ([ReCl2(NNPy)(PPh3)2]).
Method 2. [nBu4N][ReO4] (0.92 g, 1.87 mmol) was dissolved
in acetonitrile (15 ml, degassed) and heated at reflux for 30 min
Method 2. The compound was synthesised from pure dark red
[Re(NNPy)Cl2(PPh3)2]. The product was obtained as a brown
amorphous precipitate and its identity confirmed with ES-MS and
NMR. Yield 68% (0.05 g, 0.09 mmol) (Found C, 43.69; N, 8.49;
H, 4.26%. C29H31N5PReS4 requires C, 43.81; N, 8.81; H, 3.93%).
mmax/cm−1 = (CN and N N, overlapping) 1529, (2-subst. pyridyl,
=
ring str.) 1452, (PPh) 1434, (2-subst. pyridyl, ring str.) 1416, (NC2,
2-subst. pyridyl, ring str.) 1145, (pyridyl C–H deformation) 772,
(mono-subst. Ph) 745 and 693; dH (CDCl3) 8.19 (1H, ddd, JHH
=
0.5, 2.0 and 5.0 Hz, pyridyl, ortho to pyridyl N), 7.54–7.49 (6H,
m, PPh3, meta), 7.33 (1H, ddd, JHH = 2.0, 7.0 and 8.0 Hz, pyridyl,
meta to NN), 7.26–7.19 (9H, m, PPh3 ortho and para), 6.81 (1H,
dt, JHH = 1.0 and 8.0 Hz, pyridyl, ortho to NN), 6.64 (1H, ddd,
JHH = 1.0, 5.0 and 7.0 Hz, pyridyl, meta to pyridyl N), 3.32 (3H, s,
80 | Dalton Trans., 2007, 73–82
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Me, dtcA), 3.27 (3H, s, Me, dtcA), 2.94 (3H, s, Me, dtcB), 2.83
(3H, s, Me, dtcB); dP (CDCl3) 14.61 (s); dC (CDCl3) 225.7 (CS2,
dtcA), 205.0 (CS2, dtcB), 151.6 (pyridyl, ipso), 148.4 (pyridyl),
[Re(NNPy)(Ph2dtc)2(PPh3)] (9). This compound was synthe-
sised following the method used for 1: the product is a tomato-red
solid obtained in 69% yield (0.08 g, 0.07 mmol) from [ReCl2(g -
2
136.5 (pyridyl), 134.7 (d, JPC = 47.5 Hz, PPh, ipso), 134.3 (d, JPC
=
NNPy)(PPh3)2] (0.09 g, 0.10 mmol). Crystals suitable for elemental
analysis were grown by layering methanol on a dichloromethane
solution of the complex. (Found C, 56.13; N, 6.79; H, 3.75%.
9.5 Hz, PPh, ortho), 129.2 (d, JPC = 2.0 Hz, PPh, para), 127.3
(d, JPC = 10.0 Hz, PPh, meta), 117.6 (pyridyl), 114.8 (pyridyl),
39.6 (Me, dtc), 38.8 (Me, dtc), 38.5 (Me, dtc), 38.1 (Me, dtc);
m/z = 796.2 (100%) = [M + H+], 534.1 (95%) = [M–PPh3]+.
E1/2 = −0.12 V, iPa/iPc = 0.94, peak separation = 100 mV.
C49H39N5PReS4 requires C, 56.41; N, 6.71; H, 3.77%); mmax/cm−1
=
=
1517 (CN), 1490 (N N), 1450 (2-subst. pyridyl, ring str.), 1434
(PPh, weak), 1416 (2-subst. pyridyl, ring str.), 1142 (NC2/2-subst.
pyridyl, ring str.), 776 (pyridyl C–H deformation), 745, 697 and
691 (Ar, mono-subst.); dH (CDCl3) 8.12– 8.10 (1H, m, pyridyl),
7.48–7.43 (12H, m, phenyl), 7.41–7.36 (4.2H, m, phenyl), 7.34–
7.20 (approx. 12.9H, m, o/l solvent, pyridyl (1H) and phenyl),
7.00–6.97 (4H, m, phenyl), 6.82–6.79 (1H, m, pyridyl), 6.62–6.59
(1H, m, pyridyl); dP (CDCl3) 15.34 (s); dC (CDCl3) 229.2 (CS2),
208.6 (CS2), 151.4 and 151.4 (o/l, pyridyl), 148.4 (pyridyl), 142.3
(Ph), 142.0 (Ph), 136.5 (pyridyl), 134.8 (d, JPC = 46.5 Hz, PPh3),
134.3–134.2 (m, o/l, phenyl, dtc and PPh3), 129.3 (d, JPC = 18.0 Hz,
PPh3), 129.1 (Ph), 128.1 (Ph), 128.1 (Ph), 127.9 (Ph), 127.8–127.5
(m, o/l, Ph), 127.5 (Ph), 117.7 (pyridyl), 114.8 (pyridyl); m/z =
1044.6 (100%) = [M + H+], 782.5 (1%) = [M–PPh3]H+.
[Re(NNPy)(Morphdtc)2(PPh3)] (7). This compound was syn-
thesised following the method used for 1, from [ReCl2(g -
2
NNPy)(PPh3)2] (0.09 g, 0.10 mmol). Yield 86% (0.07 g, 0.09 mmol).
Crystals suitable for elemental analysis and X-ray structural
determinationwereobtained bylayeringafrozen dichloromethane
solution of 7 with methanol and allowing them to mix as they
warmed to room temperature. (Found C, 42.39; N, 7.22; H, 3.98%.
C33H35N5O2PReS4.CH2Cl2 requires C, 42.36; N, 7.26; H, 3.87%).
mmax/cm−1 = (CN) 1516, (N N) 1493, (2-subst. pyridyl, ring str.)
=
1455, (PPh) 1432, (2-subst. pyridyl, ring str.) 1412, (NC2, 2-subst.
pyridyl, ring str.) 1147, (pyridyl C–H deformation, weak) 775,
(mono-subst. Ph) 747 and 670; dH (CDCl3) 8.21 (1H, ddd, JHH
=
[Re(g1-NNCOPh)(Me2dtc)2(PPh3)] (10). This compound was
1.0, 2.0 and 5.0 Hz, pyridyl, ortho to pyridyl N), 7.54–7.42 (6H,
m, PPh3), 7.32 (1H, ddd, JHH = 2.0, 7.0 and 8.0 Hz pyridyl, meta
2
synthesised following the method used for 1, from [ReCl2(g -
NNCOPh)(PPh3)2] (0.10 g, 0.10 mmol). Within the first hour of
heating at reflux temperature, the reaction mixture changed from a
green suspension to a brown one. The dark brown solid formed was
recovered by filtration, washed with Et2O and dried under vacuum.
Yield 86% (0.07 g, 0.09 mmol). Crystals suitable for elemental
analysis and X-ray structural determination were obtained by
diffusion of Et2O into a CH2Cl2 solution of the complex. (Found
C, 45.28; N, 6.80; H, 4.03%. C31H32N4OPReS4 requires C, 45.29;
=
to N N), 7.28–7.20 (9H, m, PPh3), 6.68 (1H, o/l, dt, JHH = 1.0
=
and 8.0 Hz, pyridyl, ortho to N N, roofing to meta to pyridyl N),
6.66 (1H, o/l, ddd, JHH = 1.0, 5.0 and 7.0 Hz, pyridyl, meta to
=
pyridyl N, roofing to ortho to N N), 4.16–4.05 (2.2H, m, CH2-
fluxional) 3.88–3.69 (6.4H, m, CH2-fluxional), 3.68–3.43 (4.3H, m,
broad, CH2-fluxional), 3.43–3.30 (2.0H, m, broad, CH2-fluxional),
3.30–3.17 (1.2H, m, broad, CH2-fluxional); dP (CDCl3) 15.53 (s);
dC (CDCl3) 225.9 (CS2, dtcA), 205.1 (CS2, dtcB), 151.3 (pyridyl,
ipso), 148.4 (pyridyl, ortho to pyridyl N), 136.4 (pyridyl, meta
N, 6.82; H, 3.92%); mmax/cm−1 = (C O) 1625, (o/l, incl. CN) 1542–
=
=
1532, (N N) 1495, (PPh) 1434, 1234, (monosubst. Ph) 734 and
=
to N N), 134.3 (d, JPC = 47.5 Hz, PPh3, ipso), 134.3 (d, JPC
=
695; dH (CDCl3) 7.75 (2H, d, JHH = 7.5 Hz, benzoyl, ortho), 7.60–
7.52 (6H, m, PPh3, ortho), 7.36 (1H, t, JHH = 7.5 Hz, o/l, benzoyl,
para), 7.34–7.27 (9H, m, o/l, PPh3, meta and para), 7.26–7.17 (2H,
m, o/l, benzoyl, meta), 3.34 (3H, s, methyl, dtc), 3.30 (3H, s, methyl,
dtc), 2.89 (3H, s, methyl, dtc), 2.78 (3H, s, methyl, dtc); dP (CDCl3)
10.0 Hz, PPh3, ortho), 129.3 (d, JPC = 2.0 Hz, PPh3, para), 127.5
(d, JPC = 10.0 Hz, PPh3, meta), 118.0 (pyridyl, meta to pyridyl N),
=
114.7 (pyridyl, ortho to N N), 66.0 (CH2, dtc), 65.6 (CH2, dtc),
47.3 (CH2, dtc), 46.1 (CH2, dtc), 45.8 (CH2, dtc), 45.1 (CH2, dtc);
m/z = 880 (55%) = [M + H]+, 618 (8%) = [M–PPh3 + H]+.
=
14.24 (s); dC (CDCl3) 205.3 (CS2), 170.9 (C O), 135.2 (benzoyl,
ipso), 134.5 (d, JPC = 10.0 Hz, PPh3, ortho), 132.6 (d, JPC = 48.5 Hz,
PPh3, ipso), 131.1 (benzoyl, para), 129.43 (d, JPC = 2.0 Hz, PPh3,
[Re(NNPy)(PhMedtc)2(PPh3)](8). This compound was syn-
thesised following the method used for 1, using [ReCl2(g -
2
para), 128.1 (benzoyl, ortho), 127.5 (benzoyl, meta), 127.4 (d, JPC
=
NNPy)(PPh3)2] (0.09 g, 0.10 mmol). After refluxing overnight a
clear dark red solution was formed, which was evaporated to
dryness and extracted with pentane overnight, then filtered off,
rinsed with pentane and dried on the frit. This gave a brown solid
(mass 0.15 g). dH (CDCl3) 8.21–8.14 (1H, m, pyridyl), 7.73–7.68
(1H, m), 7.54–7.48 (4.2H, m, PPh3), 7.46–7.23 (25.6H, m, o/l
solvent, aromatic), 7.21–7.15 (6.2H, m, aromatic), 6.92 (0.8H, d,
br, J = 6.5 Hz, aromatic), 6.86 (0.8H, d, J = 6.5, br, o/l, aromatic),
6.84 (0.8H, d, J = 8.5 Hz, o/l, aromatic), 6.76 (0.8H, dd, J =
8.0 Hz, aromatic) 6.68 (1.1H, t, J = 7.5 Hz, aromatic), 6.66– 6.58
(1.1H, m, aromatic), 3.58 (1.5H, s, o/l, Me), 3.57 (1.5H, s, o/l,
Me), 3.24 (1.5H, s, o/l, Me), 3.19 (1.5H, s, o/l, Me) [NB: Based on
1H NMR integrals for CH3 peaks, the ratio of rotational isomers
at ambient temperature is approx. 1 :1 ]; dP (CDCl3) 15.63 (s)
and 15.40 (s) ppm (two rotational isomers); ES-MS (positive ion
mode): m/z = 920.5 (100%) = [M + H+], 658.3 (10%) = [M–PPh3
+ H+].
10.0 Hz, PPh3, meta), 39.6 (methyl, dtc), 38.9 (methyl, dtc), 38.7
(methyl, dtc), 38.1 (methyl, dtc); m/z = 823.0856 (25%) = [M +
H+] (C31H33N4OPS4Re requires 823.0833; difference 2.8 ppm).
E1/2 = +0.08 V, iPa/iPc = 0.59, peak separation = 83 mV.
Acknowledgements
The authors would like to thank Dr Nicholas H. Rees and Mr
Colin Sparrow for assistance with NMR and ES-MS respectively,
Hermann Starck GmbH for the gift of rhenium metal, and
the EPSRC, the Australian Research Council, the University of
Oxford and St. Catherine’s College for funding.
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