The complex [ReO{HNN(CH3)CS2CH3}2]Cl, a suitable precursor for the preparation of bis(dithiocarbamato)nitridorhenium(V) species

Article abstract of DOI:10.1016/S0022-328X(98)00988-7

The rhenium intermediate [ReO{HNN(CH₃)CS₂CH₃}₂]Cl 1 reacts in acetone with N,N-disubstituated dithiocarbamate salts R₂R₁NCS₂X (R₁=R₂=Me, Et, C₆H₅ or R₁R₂=[-CH₂-]₅, X=Na or Li) to provide a good yield of a characteristic nitrido compound: bisdialkyl(-diaryl)dithiocarbamatonitridorhenium(V), ReN(S₂CNR₁R₂)₂. The new preparation of the key species 1 in water is also reported. It allows an original one-pot synthesis of bis(diethyldithiocarbamato)nitridorhenium (V) complex ReN(S₂CNEt₂)₂.

Full text of DOI:10.1016/S0022-328X(98)00988-7

Journal of Organometallic Chemistry 575 (1999) 145–148
The complex [ReO{HNN(CH3)CS2CH3}2]Cl, a suitable precursor for
the preparation of bis(dithiocarbamato)nitridorhenium(V) species
Florian Demaimay, Alain Roucoux *, Nicolas Noiret, Henri Patin
Laboratoire de Chimie Organique et des Substances Naturelles, CNRS ESA 6052-Ecole Nationale Supe´rieure de Chimie de Rennes,
A6enue du Ge´ne´ral Leclerc, 35700 Rennes, France
Received 23 April 1998; received in revised form 4 September 1998
Abstract
The rhenium intermediate [ReO{HNN(CH3)CS2CH3}2]Cl 1 reacts in acetone with N,N-disubstituated dithiocarbamate salts
R2R1NCS2X (R1=R2=Me, Et, C6H5 or R1R2=[–CH2–]5, X=Na or Li) to provide a good yield of a characteristic nitrido
compound: bisdialkyl(-diaryl)dithiocarbamatonitridorhenium(V), ReN(S2CNR1R2)2. The new preparation of the key species 1 in
water is also reported. It allows an original one-pot synthesis of bis(diethyldithiocarbamato)nitridorhenium (V) complex
ReN(S2CNEt2)2. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: Nitrido-rhenium; Dithiocarbamate; N-methyl-S-methyldithiocarbazate; Aqueous chemistry; One-pot synthesis
1. Introduction
Recent attempts have been focused on the transfor-
mation of the oxorhenium core (ReVꢁO) into nitrido
complexes bearing thiosemicarbazides in hydrochloric
acid medium but mechanistic approaches are still neces-
sary to elucidate the N–N bond cleavage step [20,21].
In this paper, we describe the use of the oxo-species
[ReO(HNN(CH3)CS2CH3)2]Cl 1 for the formation of
characterized bis(dithiocarbamato)nitridorhenium (V)
complexes ReN(S2CNR1R2)2. We report also the origi-
nal preparation of the key intermediate 1 in water and
the one-pot synthesis of the bis(diethyldithiocarbam-
ato)nitridorhenium compound ReN(S2CNEt2)2.
Knowledge and development of the chemistry of new
neutral rhenium complexes are of crucial importance
for the design and the easy synthesis of future therapeu-
tic radiopharmaceuticals using Re-186/188 [1–6].
Rhenium complexes in the oxidation state +V with
ligands such as bulky thiols [7], diphosphines [8], o-
aminophenyldiphenylphosphine [9] benzamidinates and
dithiophosphinates [10,11] have been studied, and the
chemistry of the ReꢀN core has been widely developed.
Several complexes of rhenium V containing dithiocar-
bamate ligands have been reported [12–14] and have
shown at microscopic level a myocardial uptake simi-
larly to analogous compounds prepared with the
isostructural radioelement 99mTc [15–17].
Traditionally, at macroscopic level, neutral dithiocar-
bamate complexes of rhenium V are obtained by substi-
tution reaction in organic medium of the previously
prepared nitridorhenium precursor ReNCl2(PPh3)2
[18,19].
* Corresponding author. Tel.: +33-2-99871338; fax: +33-
299871332; e-mail: alain.roucoux@ensc-rennes.fr.
Scheme 1.
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(98)00988-7

146
F. Demaimay et al. / Journal of Organometallic Chemistry 575 (1999) 145–148
Scheme 2.
2. Synthesis of bis(dithiocarbamato)nitridorhenium (V)
dichlorobistriphenylphosphine
nitridorhenium
(V)
ReNCl2(PPh3)2, is limited by the poor solubility of the
starting complex in organic solvents. An easy and
cheap access to nitridorhenium V species must start
with the commercially available potassium perrhenate
KReO4 which is water soluble. We have shown that the
cationic complex [ReO(HNN(CH3)CS2CH3)2]Cl 1 ob-
tained by Marchi et al. in an organic medium can be
easily and rapidly synthetized in water. In this context,
we have developed a new route for the formation of
dithiocarbamate-complex in water and shown the feasi-
bility of a one-pot synthesis.
Since a reduction step must occur, we tried several
reagents including triphenylphosphine sodium meta-
trisulfonate (TPPTS–Na) which have proved useful in
other circumstances [15]. Finally, best results were ob-
tained with stannous chloride and the N-methyl-S-
methyldithiocarbazate (H2NN(CH3)CS2CH3: 3) as the
nitrido donating group [23–25] proved to be the most
convenient in comparison to S-methyldithiocarbazate
(H2NNHCS2CH3) or succinic dihydrazide (H2NNHC-
OCH2CH2CONHNH2).
Recently, Marchi et al. reported the synthesis of the
complex [ReO(HNN(CH3)CS2CH3)2]Cl 1 (Scheme 1)
starting from ReOCl3(PPh3)2 and the transformation
into the chloro–nitrido compounds ReNCl2(PPh3)2
2
when 1 is treated with an excess of hydrochloric acid
and triphenylphosphine [22]. Here, we describe a route
for the synthesis of bis(dithiocarbamato)nitridorhenium
complexes
isostructural
to
99mTcN
radiopharmaceuticals.
On a macroscopic scale, the oxo species 1 reacts in
acetone with an excess of sodium or lithium dithiocar-
bamate salt R2R1NCS2− (R1=R2=Me, Et, C6H5 or
R1R2=[–CH2–]5)
to
form
nitrido
species
ReN(S2CNR1R2)2 (Scheme 2). A suitable excess of
dithiocarbamate salts (four equivalents with respect to
1) is required to give an efficient reaction. The mixture
is heated at reflux for five hours. A yellow precipitate is
formed which can be recrystallized from a mixture of
acetone/CH2Cl2 to afford crystals of bisdialkyl(-di-
aryl)dithiocarbamatonitridorhenium (Table 1) with a
satisfactory isolated yield (30–55%). All complexes
have been characterized by spectroscopic and elemental
analysis.
The formation of nitrido compounds of rhenium is
the result of the cleavage of the hydrazinic group N–N
of 1 by the presence of an excess of ligand. Very poor
yields are obtained if the reaction is carried out in
stoichiometric amounts and we confirm the easy trans-
formation of the oxo-rhenium core into nitrido-rhe-
nium core. In contradiction with the formation of the
known chloro-complex 2, we have observed that the
presence of HCl is not required [22]. It seems that the
oxo core [ReꢁO]3+ was sufficiently reactive to promote
the cleavage of the hydrazine N–N moiety by succesive
protonation with the concomitant triple bond ReꢀN
formation. We think that the proton of the hydrazinic
group HNN(CH3)– is the potential source for the
protonation of the oxo group in a concerted process.
Further studies towards the mechanism are in progress
in our laboratory.
All reactions proceed in the same flask in water
solution containing citric acid. This complexing reagent
brings several advantages: (i) a favorable pH value for
the reduction in Re (V), (ii) a convenient efficiency to
the complexation of tin derivatives in solution, (iii) a
probable participation in the temporary stabilization of
the nitrido–rhenium core in the solution before the
displacement by 3.
This one-pot synthesis occurs via successive reactions
in water solution: formation after 15 min at 100°C of a
yellow solution containing the rhenium intermediate
complex
1 then the addition of an excess of
(CH3CH2)2NCS2–Na at neutral pH (i.e. pH 7) to give
the required complex (Scheme 3).
Table 1
Synthesis of [ReN(S2CNR1R2)2] from [ReO(HNN(Me)C(S)SMe)2]Cl
R1R2NCS2X
R1
ReN(R1R2NCS2)
Rdt (%)
R2
X
Me
Et
C6H5
[–CH2–]5
Me
Et
C6H5
Na
Na
Li
37
31
40
55
3. Original one-pot synthesis of bis(diethyldithio-
carbamato)nitridorhenium (V) in water
Na
The main strategy, using exchange reaction from

F. Demaimay et al. / Journal of Organometallic Chemistry 575 (1999) 145–148
147
Scheme 3.
The nitrido complex is purified by column chro-
5.1. Synthesis of bis(N-methyl-S-methyldithiocarbaz-
ato)oxorhenium (V) chloride [ReO(HNN(Me)C(S)-
SMe)2]Cl
matography over silica gel eluated with diethylether.
The yield of the isolated product is 41% based on
KReO4. The success of this method is based on the
reaction conditions which optimize the formation of the
intermediate and allow a one-pot synthesis with the
appropriate stabilizing ligands. We have isolated the
intermediate compound by extraction into CH2Cl2 and
purification by column chromatography to confirm the
structure (see Section 5) and we have verified that the
same product [ReN(S2CNEt2)2] is obtained in organic
medium with the route described in Scheme 2.
(a) A total of 30 mg (104 mmol) of potassium per-
rhenate in 5 cm3 water was added in a solution of 60
mg (266 mmol) stannous chloride dihydrate, 2.5 g (13
mmol) of citric acid and 100 mg (819 mmol) of 3 in 95
cm3 of water. After 15 min at 100°C, the solution
turned yellow. The organic products were extracted
from the yellow aqueous solution by chloroform (3×
20 cm3). The combined extracts were concentrated and
the orange residue was chromatographed on silica gel,
using acetone as an eluant. The last orange fraction was
concentrated to yield pure compound (19 mg, 35%).
m.p.=180–190°C (dec.) (CH2Cl2/hexane). C6H14-
ClN4OS4Re: calc.: C, 14.18; H, 2.78; N, 11.03. Found:
C, 13.94; H, 2.78; N, 10.68. 1H-NMR (CD2Cl2): 2.89 (s,
6H, SCH3); 4.14 (s, 6H, NCH3); 13.07 (s, 2H, NH).
13C{1H}-NMR (CD2Cl2): 18.47 (SCH3); 44.20 (NCH3);
167.90 (CS2). I.R. w(cm−1) 1600 [l(N–H)]; 1230 (CꢁS);
395 (Re–S).
The intermediate complex 1 which is obtained in
water shows an efficient ability to form nitrido com-
plexes with an excess of ligand. Recently, we have
observed also the same process in the preparation of
the
neutral
radiopharmaceuticals
[
188ReN{Et(EtO)NCS2}2] or [188ReN{CH3(CH2)8CS2}2]
for leucocyte labelling [26,27].
4. Conclusion
(b) An alternative procedure [22] is as follows: to a
suspension of trichlorobis(triphenylphosphino)oxorhen-
ium (V) (0.14 g, 0.18 mmol) in a mixture of CH2Cl2/
C6H6 (1:1, 50 cm3), N-methyl-S-methyldithiocarbazate
3 (0.054 g, 0.4 mmol) dissolved in the minimum volume
of CH2Cl2 was added . The reaction mixture was
refluxed with stirring for 30 min, producing an orange
precipitate on partial evaporation of the solvent. The
solution was cooled to room temperature and the pre-
cipitate was filtered off, and dried with diethylether.
The product was crystallized in CH2Cl2/hexane (60 mg,
66%).
We have reported the feasibility of a one-pot synthe-
sis in water of bis(dithiocarbamato)nitridorhenium
complexes. In a first step, an intermediate species
[ReO{HNN(CH3)CS2CH3}2]Cl is obtained which reacts
with a dithiocarbamate salt to give easily nitrido–rhe-
nium complexes with efficient yield. New macroscopic
reactions using the key intermediate with other ligands
such as thioamide [R1C(ꢁS)NHR2] which were tested
with the analogous technetium-99m at microscopic level
for white blood cells labelling [28], are underway.
5. Experimental
5.2. Synthesis of [ReN(S2CNR1R2)2] from
[ReO(HNN(Me)C(S)SMe)2]Cl
NMR spectra were recorded on a Bruker ARX 400,
MS spectra on a Finnigan Mat-Incos 500 EX, IR
spectra on a Nicolet 205 and elemental analysis on a
Carlo Erba 1106 (ENSCR). All manipulations were
carried out in an atmosphere of nitrogen using conven-
tional Schlenk-type apparatus. Distilled water was de-
Typical procedure: to a solution of bis(N-methyl-S-
methyldithiocarbazato)oxorhenium (V) chloride (100
mg, 0.20 mmol) in acetone (50 cm3) the desired dithio-
carbamate (0.80 mmol) dissolved in the minimum vol-
ume of acetone was added. The solution was refluxed
with stirring for 5 h under a stream of nitrogen. The
solution gradually became yellow–brown and was con-
centrated to a lower volume under reduced pressure.
gassed
prior
to
use.
The
compounds
N-methyl-S-methyldithiocarbazate 3 [23] and dithiocar-
bamate sodium salts [15] were synthesized as described
previously.

148
F. Demaimay et al. / Journal of Organometallic Chemistry 575 (1999) 145–148
The reaction mixture was allowed to cool to room
temperature, producing a yellow precipitate. This was
filtered off and chromatographed on silica gel, using
CH2Cl2 as eluant, the yellow fraction was concentrated
to give crystals of the desired product which could be
recrystallized in acetone or acetone/CH2Cl2.
H]+ 185Re). IR (cm−1): 1523 (wCN); 1077 (wCS); 1010
(
(wReꢀN). C10H20N2S4Re: calc.: C, 24.20; H, 4.06; N, 8.5.
Found: C, 24.30; H, 4.00; N, 8.70%.
References
ReN(S2CNMe2)2: 1H-NMR (Me2SO-d6): 1.85 (t,
12H, J=7.1 Hz, CH3). 13C{1H}-NMR (Me2SO-d6):
15.34 (CH3); 231.08 (CS2). C6H12N3S4Re: Calc.: C,
16.36; H, 2.75; N, 9.54. Found: C, 16.1; H, 2.61; N,
9.4%. IR (cm−1): 1020 (wReꢀN).
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ReN(S2CN(C6H5)2)2: 1H-NMR (CDCl3): 7.46–7.39
(m, C6H5 10H,). 13C{1H}-NMR (CDCl3): 127.0, 129.2,
129.9 (3CH), 141.4 (Cq); 259.6 (CS2).). C26H20N3S4Re:
Calc.: C, 45.33; H, 2.93; N, 6.1. Found: C, 45.91; H,
2.88; N, 6.0%.
ReN(S2CN(–CH2–)5)2: m.p.=255–260°C (acetone).
C12H20N3S4Re: calc.: C, 27.68; H, 3.87; N, 8.07. Found:
1
C, 27.64; H, 3.84; N, 7.56%. H-NMR (CD2Cl2): 1.72–
1.77 (m, 6H, CH2); 3.85 and 3.95 (2m, 4H, NCH2).
13C{1H}-NMR (CD2Cl2): 24.0 (CH2); 25.8 (CH2); 49.4
(NCH2); 230.9 (CS2).
ReN(S2CNEt2)2: m.p.=245°C (dec). 1H-NMR
(Me2SO-d6): 3.83 (m, 4H); 3.69 (m, 4H); 1.28 (t, 12H).
13C{1H}-NMR (Me2SO-d6): 13.22 (CH3); 46.50 (CH2);
230.16 (CS2). MS (CI, NH3) m/z 498 (100) [M+H]+
(
187Re); 496 (42) [M+H]+
(wReꢀN).
(
185Re). IR (cm−1): 1010
5.3. One-pot synthesis of [ReN(S2CNEt2)2] in water
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A total of 30 mg (104 mmol) of potassium perrhenate
in 5 cm3 water was added to a solution containing 60
mg (266 mmol) of stannous chloride dihydrate, 2.5 g (13
mmol) of citric acid and 100 mg (819 mmol) of 3 in 95
cm3 of water. After 15 min at 100°C, the solution
turned yellow. The solution was neutralized with car-
bonate buffer (pH 10.3, 0.5 mol l−1) and 1 g (4.4
mmol) of DEDC–Na in 10 cm3 water was added. After
40 min at 60°C, the organic products were extracted by
chloroform (3×30 cm3), and the solution dried and
concentrated. The resulting mixture was chro-
matographed over silica gel using diethyl ether as elu-
ant. Concentration of the last yellow fractions gave a
yellow powder. m=20 mg (41 mmol, 41%). m.p.=
245°C (dec). 1H-NMR (400.13 MHz, DMSO-d6) l
(ppm): 1.10 (t, 12H, CH3); 3.70 (m, 4H, CH2–Ha); 3.82
(m, 4H, CH2–Hb). 13C-NMR (100.2 MHz, DMSO-d6)
l (ppm): 13.2 (CH3); 46.4 (CH2); 230.2 (CS2). MS (CI,
[26] F. Demaimay, L. Dazord, A. Roucoux, N. Noiret, H. Patin, A.
Moisan, Nucl. Med. Biol. 24 (1997) 701.
[27] F. Demaimay, L. Dazord, A. Roucoux, N. Noiret, H. Patin, A.
Moisan, Nucl. Med. Biol. (in press).
[28] F. Me´vellec, F. Demaimay, A. Roucoux, A. Moisan, N. Noiret,
H. Patin, J. Label. Compds. Radiopharm. (in press).
NH3) m/z 498 (100) [M+H]+
(
187Re); 496 (42) [M+
.