Reactivity of thiosemicarbazides with redox active metal Ions: Controlled formation of coordination complexes versus heterocyclic compounds

Article abstract of DOI:10.1002/chem.200801446

The reactions of 1,1-dimethyl-4-phenylthiosemicarbazide (LH) with Cu ^II and Sn^IV. have been investigated. If THF or methanol is used as solvent with Cu^II, oxidative cyclisation and coupling are observed, yielding a 1,2,4-t

Full text of DOI:10.1002/chem.200801446

DOI: 10.1002/chem.200801446
Reactivity of Thiosemicarbazides with Redox Active Metal Ions: Controlled
Formation of Coordination Complexes versus Heterocyclic Compounds
Elena Lꢀpez-Torres*[a, b] and Jonathan R. Dilworth*[a]
Abstract: The reactions of 1,1-dimeth-
yl-4-phenylthiosemicarbazide (LH)
the counterion, depending on the reac-
tion conditions. By contrast, reaction of
LH with SnI4 in acetone yields a 1,3-
thiazolium salt, with IÀ as counterion.
Reaction with CuII salts or SnI4 in basic
media leads to the formation of metal
complexes containing two deprotonat-
ed thiosemicarbazide ligands. In the re-
action of CuCl2 in water in the pres-
ence of acid a complex containing two
neutral ligands is obtained. Reactions
with SnCl4 are not able to induce
ligand cyclisation, although a coordina-
tion compound with two neutral li-
gands was isolated from methanol.
with CuII and SnIV have been investi-
gated. If THF or methanol is used as
solvent with CuII, oxidative cyclisation
and coupling are observed, yielding a
1,2,4-thiadiazole or a 1,3,4-thiadiazoli-
um salt. SnI4 is also able to induce oxi-
dative coupling of two thiosemicarba-
zide ligands, yielding 1,2,4-thiadiazoli-
Keywords: complexation · hetero-
cycles · oxidation · structure eluci-
dation · thiosemicarbazides
À
um or 1,2,4-triazolium salts, with I3 as
Introduction
Complexes of thiosemicarbazide or thiosemicarbazone li-
gands with non-transition metals such as tin have not re-
ceived much attention and there are few reports in the liter-
ature, in spite of the potential applications of tin com-
pounds, for example as anticancer agents,[18–21] anti-inflam-
matory drugs,[22] PVC stabilisers[23] and pesticides.[24] The co-
ordination chemistry of tin in solution and in the solid state
is an attractive target for structural studies by means of
spectroscopic and diffraction techniques, with the advantage
of the detecting subtle changes in the coordination sphere of
the tin atom with great sensitivity by 119Sn NMR spectros
copy.[25]
The coordination chemistry of bis and mono thiosemicar-
bazones with redox active transition metal ions, such as Cu,
Fe and Sn can be extremely complex with a wide range of
products being formed depending on solvent, reaction con-
ditions and the metal ion used. We have investigated the co-
ordination chemistry of bis(thiosemicarbazone) ligands at
length in the context of the hypoxic selectivity of the copper
complexes.[26–29] We have found that the synthesis of both
the free ligands and the complexes is complicated by the in-
traligand formation of cyclic products arising from coupling
of the two thiosemicarbazone limbs.[30]
The coordination chemistry of copper with N,S-donor li-
gands has been widely studied. Within these N,S-donors thi-
osemicarbazides and thiosemicarbazones have received con-
siderable attention, as they have potential applications as
antiviral, antibacterial or anticancer chemotherapeutic
agents,[1–11] and recently the use of thiosemicarbazones as hy-
poxic selective delivery agents for radioactive copper has
created much interest.[12–16] Moreover, thiosemicarbazide
complexes have been used in crystal engineering, as they
have been shown to be useful bifunctional ligands in prepar-
ing hydrogen-bonded arrays containing metal centres.[17] In
addition to having N and S donor atoms the thiosemicarba-
zide ligands have two NH groups, which can form hydrogen
bonds.
[a] Dr. E. Lꢀpez-Torres, Prof. J. R. Dilworth
Chemistry Department, Inorganic Chemistry Laboratory
University of Oxford
South Parks Road, OX1 3QR, Oxford (UK)
Fax : (+44)1865-272690
E-mail: jon.dilworth@chem.ox.ac.uk
[b] Dr. E. Lꢀpez-Torres
For monothiosemicarbazones, interligand cyclisation
occurs on reaction with methanolic ferric chloride or cupric
perchlorate under reflux to yield heterocyclic compounds.[31]
The reaction is highly substituent dependent and for R2 =H,
1,3,4-thiadiazoles (Figure 1E) are formed whereas for R2 =
Departamento de Quꢁmica Inorgꢂnica
Universidad Autꢀnoma de Madrid
C/ FranciscoTomꢂs y Valiente 7, Cantoblanco 28049, Madrid (Spain)
Fax : (+44)91-4974844
E-mail: elena.lopez@uam.es
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Chem. Eur. J. 2009, 15, 3012 – 3023

FULL PAPER
of synthetic products with biological activities within the
central nervous system,[37] G-coupled receptors,[38] inflamma-
tion,[39] cardiovascular system[40] or antibiotic activity[41] and
1,2,4-triazoles are antimycotic,[42] Alzheimerꢄs disease retard-
ing[43] and anticancer drugs.[44]
A good deal work has been done on thiosemicarbazones
and their complexes, whereas the chemistry of thiosemicar-
bazides has been much less explored and few X-ray crystal
structures of thiosemicarbazide complexes have been report-
ed. This lack of investigation is particularly true for N(3)-
substituted compounds, although there are some reports on
Cu, Ni, Zn and Pt complexes.[45–48]
In this paper we report the reaction pathways for
PhNHCSNHNMe2 with copper and tin salts, and show that
the selection of the appropriate reaction conditions permits
control of the product formed. A range of new heterocyclic
derivatives are reported. Some of the Cu chemistry was de-
scribed in an earlier communication,[49] but herein we give
full structural details of the products and, additionally, de-
scribe reactions with SnIV compounds.
Results
Synthesis: The summary of the reaction conditions used to
determine the outcome of the reactions of LH with CuII or
SnIV are shown in Schemes 1 and 2. In the case of copper,
the use of a basic medium permits the isolation of the stable
complex [CuIIL2] 1. By contrast, if CuII chloride is used in
THF, ligand deprotonation does not occur and a redox pro-
cess between the ligand and the metal ion takes place to
Figure 1. Thiosemicarbazides A–F and 3, 5, 7 and 9.
Me 1,2,4-triazoline thiones (Figure 1F) are formed in good
yields. With copper(II) the reaction was concentration de-
pendent with uncharacterised copper thiosemicarbazone
complexes being formed at higher concentrations and the
thiadiazoles at concentrations <0.01m.[32,33] The solvent and
pH dependence of the reactions was not discussed, and any
metal complexes formed were not identified.
As a prelude to studying the reactivity of bis(thiosemicar-
bazides) with copper(II) in the context of exploring the
effect of removal of the imine conjugation on hypoxic selec-
tivity, we have here initially explored the chemistry of the
monothiosemicarbazide PhNHCSNHNMe2. We elected to
use a dialkylated terminal nitrogen to minimise complica-
tions due to NH loss by oxidation and to simplify the ligand
synthesis. By comparison with the chemistry of monothiose-
micarbazones we hoped to also assess the effect of having
additional sp3 hybridised nitrogen atoms present. We wished
to establish if these reactions give rise to defined copper
complexes or new heterocyclic compounds and if the reac-
tions could be controlled. To our knowledge the reactions of
such thiosemicarbazides with redox active metal ions, such
as Cu has not been previously reported. We have also in-
cluded tin for reasons discussed above.
yield the heterocyclic compounds [(C9H10N3S)2]ACTHNUGRTENUNG[CuCl4] 3
and [C18H22N6S] 5. The formation of 3 is induced by the re-
duction of Cu and the presence of CuII in compound 3 arises
from the aerial oxidation of the CuI cation. If LH is reacted
with CuCl2 in water in the presence of HCl, the ligands do
not deprotonate and there is no redox, leading to the forma-
tion of complex [CuII(LH)2Cl]Cl 2. This complex is unstable
in solution in the absence of HCl and, even in the solid state
slowly, decomposes to give 1. If the reaction of CuCl2 is car-
ried out in methanol a mixture of 2, 3 and 5 is isolated. If
complex 2 is treated with LiOH or Et3N, as bases, complex
1 is formed. This is not a reversible process, because if com-
plex 1 is reacted with HCl the major products formed are 3
and 5, although in the mass spectrum there is evidence of a
small amount of 2. In the case of CuI the reaction must be
done under a nitrogen atmosphere to avoid Cu oxidation,
and complex [CuI(LH)2]SCN 4 is obtained, which oxidises in
solution in the presence of air to yield heterocycle 5.
Reaction with SnI4 in basic medium yields, as in the case
of copper(II), a complex with two deprotonated ligands
[SnL2I2] 8. In methanol, depending on the addition order
and therefore on the relative concentrations of complexes
during the reaction, the selective synthesis of the positively
charged heterocyles [C18H23N6S]I3 6 and [C18H23N6]I3 7, by
the condensation of two LH molecules with elimination of
one sulfur atom in the case of 6 and two sulfur atoms in the
Thiadiazoles can be prepared by oxidative reactions of
thioureas and the known types are summarised in Figure 1.
Thiadiazoles are of considerable interest as they have potent
biological activities. For example 1,3,4-thiadiazoles can act
as antituberculitic,[34] antimycotic[35] and analgesic agents.[36]
1,2,4-thiadiazoles are fundamental constituents of a number
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E. Lꢀpez-Torres and J. R. Dilworth
Scheme 1. Reactions with copper salts.
Scheme 2. Reactions with SnI4.
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Reactivity of Thiosemicarbazides with Redox Active Metal Ions
FULL PAPER
À
formation of 7, is possible. In THF, the addition order is not
important and a mixture of 6 and 7 is always obtained. Re-
action in acetone yields the charged heterocycle
[C12H16N3S]I 9, via addition of the acetone to LH. SnCl4
does not induce ligand condensation and cyclisation and in
methanol gives complex [Sn(LH)2Cl2]Cl2 10. The presence
of both tin and iodide is therefore necessary to induce het-
erocycle formation. The appearance of the triodide anion in
6 and 7 confirms that iodide is oxidised to iodine in the
course of the reaction. We were not able to determine the
fate of the tin.
position with respect to C(1) N(1). The ligand core formed
by N(3), C(1), S(1), N(1) and N(2) is essentially planar, with
a mean deviation of 0.0275 ꢅ for N(1) from their least-
squares plane. The aromatic ring forms a dihedral angle of
75.518 with this plane. Formation of complexes, in which the
ligand acts as a NS chelate, takes place via one 1808 rotation
À
about C(1) N(1). The molecules form dimers through hy-
drogen bonds between one of the NH groups and the sulfur
atom [N(1)-H(1)···S(1)#1 3.3891(19) ꢅ; #1 Àx+2, Ày+1,
Àz+2].
Depending on the solvent used for recrystallisation, two
different polymorphs of complex 1 can be isolated: Complex
1a belongs to the monoclinic system and is recrystallised
from methanol and complex 1b is triclinic and is obtained
from diethyl ether. Both complexes (Figures 3 and 4) show
the CuII ion to be four-coordinate, bound to two deprotonat-
ed ligands in a N2S2 trans square-planar arrangement. The
complexes are centrosymmetric with the inversion point lo-
cated at the copper ion. Bond distances and angles in both
polymorphs are quite similar. A detailed description of the
monoclinic polymorph structure was previously reported.[49]
The main difference is the disposition of H(1) with respect
to the sulfur atom: in 1a they are located on the same side,
but in 1b they are in a trans disposition. Another difference
is the angle between the phenyl rings with the CuN2S2
plane: In complex 1a it is 32.978, whereas in the 1b form it
is 77.158. Within the complexes both phenyl rings are paral-
lel. In 1b the ligand is more planar than in 1a with a maxi-
mum deviation from the least-square plane of 0.014 ꢅ for
N(3). Although the ligand is deprotonated, there is not a
great deal of electronic delocalisation and the bond distan-
ces are closer to the ones expected for a single or double
bond. There is a great difference in the intermolecular inter-
actions of the two polymorphs. The position of the phenyl
rings in complex 1a does not allow the formation of hydro-
gen bonds, and although the ring distances are short
The heterocycles 5, 6 and 7 have a common structural
motif as shown in Schemes 1 and 2 indicating that their for-
mation involves the combination of two molecules of the
thiosesemicarbazide. However, they differ in the degree of
protonation and the nature of the atom X. Without further
investigation the factors determining the dimerisation and
ring closures are not at this stage clear. The trans geometry
observed for the complexes however suggests that the di-
merisation reaction does not occur on the metal. Heterocy-
cle formation requires the thiosemicarbazide to be protonat-
ed and the observed reduction of the metal or iodide implies
that oxidation of the protonated ligand to a diazenium spe-
cies occurs and this then reacts to give the observed prod-
ucts. Whatever the detailed mechanism might be we have
shown that by control of the reaction solvent and metal ion
we have demonstrated several new heterocyclic compounds
can be made reproducibly and in high yield.
X-ray crystallography: Crystallographic data for the com-
pounds are summarised in Table 1 and Table 2. The struc-
ture determination of LH shows (Figure 2) that in the solid
state the thiosemicarbazide exists in the thione form, sup-
À
ported by the presence of hydrazinic hydrogens and a C S
distance of 1.6813(18) ꢅ, which is much shorter than a
À
single C S bond and in which N(1) and N(3) are in a cis dis-
Table 1. Crystal data and structure refinement for LH, 1a, 1b, 2·3H2O and 3.
LH
1a
1b
2·3H2O
3
formula
Mr
C9H13N3S
195.28
C18H24CuN6S2Cu
452.11
C18H24CuN6S2Cu
452.11
C18H32N6SCuCl2O3
579.08
C18H20N6S2CuCl4
589.89
crystal system
space group
a [ꢅ]
b [ꢅ]
c [ꢅ]
monoclinic
P21/n
7.9674(5)
8.9890(9)
15.3692(16)
90
99.730(2)
90
1084.89(17)
4
monoclinic
P21/c
11.8923(4)
5.5608(2)
15.7983(5)
90
99.3695(14)
90
1030.81(6)
2
triclinic
P1
triclinic
P1
triclinic
P1
¯
¯
¯
5.9929(2)
7.8571(3)
11.2144(5)
79.8466(16)
88.0032(16)
86.3491(17)
518.58(3)
1
11.9663(2)
14.4251(2)
15.8806(2)
75.9094(6)
82.2199(6)
88.9297(5)
2633.99(7)
4
7.3900(2)
9.9448(2)
16.1842(3)
80.9969(10)
88.6086(10)
85.1073(9)
1170.40(5)
2
a [8]
b [8]
g [8]
V [ꢅ3]
Z
1c [MgmÀ3
]
1.196
1.457
1.448
1.460
1.647
m [mmÀ1
(000)
GOF on F2
reflns. collected
independent reflns., R
]
0.259
416
1.038
10478
2375, 0.0344
0.0399, 0.1001
À0.203, 0.251
1.277
470
1.0768
10012
2578, 0.040
0.0324, 0.0379
À0.36, 0.49
1.270
235
1.1104
7582
2336, 0.042
0.0318, 0.0349
À0.41, 0.39
1.221
1192
1.0957
40052
11902, 0.039
0.0444, 0.0515
À0.67, 0.98
1.588
598
1.0827
17872
5319, 0.039
0.0310, 0.0357
À0.51, 0.47
F
G
G
G
final R1 and wR2 [I>2s(I)]
residual density (min,max) [eꢅÀ3
]
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E. Lꢀpez-Torres and J. R. Dilworth
Table 2. Crystal data and structure refinement for 5, 6.toluene, 7 and 9.
bonds form infinite chains run-
ning parallel to the vector (À1,
0, 1), leading a 1D polymeric
structure. The differences in H-
bonding and structure observed
are attributable to the different
solvents used for recrystallisa-
tion, the use of methanol, as ex-
pected, disfavours H-bond for-
mation.
The asymmetric unit of com-
plex 2 contains two crystallo-
graphically-distinct molecules
of [Cu(LH)2Cl]À, two chlorides
and six molecules of water. The
two cations are geometrically
very similar and are related by
a non-crystallographic rotation
of the reciprocal vector (À1, 1,
1) (this is the axis about which
5
6·toluene
7
9
formula
Mr
C18H22N6S
354.48
C21.5H27N6SI3
782.27
C18H23N6I3
704.12
monoclinic
P21/n
14.2699(6)
9.4409(4)
18.6145(8)
90
112.099(2)
90
2323.53(17)
4
2.013
4.051
1328
C12H16N3SI
361.25
orthorhombic
Pbca
12.8851(8)
10.5632(7)
20.9109(15)
90
crystal system
space group
a [ꢅ]
b [ꢅ]
c [ꢅ]
monoclinic
P21/n
9.9219(2)
9.1243(2)
20.9556(6)
90
100.6344(12)
90
1864.54(8)
4
triclinic
P1
¯
8.8537(2)
10.0648(2)
16.5935(4)
99.4681(9)
93.4241(9)
107.0865(9)
1384.96(5)
2
a [8]
b [8]
90
90
g [8]
V [ꢅ3]
Z
2846.1(3)
8
1.691
2.381
1432
1.059
54708
3532, 0.0583
0.0195, 0.0389
À0.503, 0.448
1c [MgmÀ3
]
1.263
0.187
1.876
3.481
m [mmÀ1
]
F
(000)
752
1.0824
746
1.1010
GOF on F2
1.087
29067
5747, 0.0446
0.0265, 0.0552
À0.842, 1.060
reflns. collected
22563
21500
independent reflns, R
final R1 and wR2 [I>2s(I)]
residual density (min,max) [eꢅÀ3
(int)
4230, 0.047
0.0365, 0.0434
À0.18, 0.18
6279, 0.039
0.0305, 0.0331
À0.94, 0.99
]
Figure 2. Representation of molecular structure of LH. Thermal ellip-
soids at 40% probability. Selected bond distances (ꢅ) and angles (8):
S(1)ÀC(1) 1.6813(18), N(3)ÀC(1) 1.330(2), C(1)ÀN(1) 1.330(2),
N(1)ÀN(2) 1.399(2); N(1)-C(1)-N(3) 116.24(16) N(1)-C(1)-N(3)
116.24(16), N(3)-C(1)-S(1) 123.47(14), C(1)-N(1)-N(2) 120.81(17).
Figure 4. Representation of the molecular structure of 1b. Thermal ellip-
soids at 50% probability. Selected bond distances (ꢅ) and angles (8):
Cu(1)ÀS(1) 2.2250(6), Cu(1)ÀN(2) 2.067(2), S(1)ÀC(1) 1.743(3),
C(1)ÀN(1) 1.293(3), C(1)ÀN(3), 1.367(3), N(1)ÀN(2) 1.451(3); S(1)-
Cu(1)-S
ACHUTGTNREN(NUG 1 A) 179.99, S(1)-Cu(1)-N(2) 85.95(6), S(1)-Cu(1)-NACHTUNGTRENNUNG(2 A)
94.05(6), N(2)-Cu(1)-NCATHNUGTRNEN(UG 2 A) 179.99.
Figure 3. Representation of the molecular structure of 1a. Thermal ellip-
soids at 50% probability. Selected bond distances (ꢅ) and angles (8):
Cu(1)ÀS(1) 2.2419(6), Cu(1)ÀN(2) 2.0526(18), S(1)ÀC(1) 1.753(2),
C(1)ÀN(1) 1.284(3), C(1)ÀN(3), 1.381(3), N(1)ÀN(2) 1.454(2); S(1)-
the crystal is twinned, see the Experimental Section) and a
non-crystallographic translation. The geometry of the cat-
ions does not closely approximate to two-fold rotational
symmetry. The copper atom is in a square-based pyramid ar-
rangement (Figure 5) with t=0.02 (t=0 for sbp and t=1
for tbp).[50] The coordinated N and S atoms are approxi-
mately coplanar, with the Cu atoms displaced from their
best plane by 0.28 ꢅ towards the coordinated Cl. However,
the CuCl axes are not perpendicular to the N2S2 plane, but
are instead canted by 6.88 towards one of the chelate rings.
Cu(1)-S
ACHTUNGTRENNUNG(1 A) 179.99, S(1)-Cu(1)-N(2) 85.41(5), S(1)-Cu(1)-NACHTUNGTERN(NUGN 2 A)
94.59(5), N(2)-Cu(1)-NACHTUNGTRENNUNG(2 A) 179.99.
enough, the angles between centroids prevents p–p stacking.
In complex 1b the NH group forms a hydrogen bond to the
À
imine-like
N
of
a
neighbouring molecule [N(3)
H(1)···N(1)#1 2.964(3) ꢅ; #1 Àx, 2Ày, Àz]. The hydrogen
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Reactivity of Thiosemicarbazides with Redox Active Metal Ions
FULL PAPER
Figure 5. Representation of the molecular structure of 2·3H2O. Thermal
ellipsoids at 50% probability. Only one of the molecules and one chloride
ion in the asymmetric unit are shown. The water molecules have been
omitted for clarity. Selected bond distances (ꢅ) and angles (8):
Cu(1)ÀS(1) 2.2674(12), Cu(1)ÀN(2) 2.073(4), Cu(1)ÀS(2) 2.2951(12),
Cu(1)ÀN(5) 2.072(4), Cu(1)ÀCl(1) 2.6411(14), S(1)ÀC(1) 1.709(5),
C(1)ÀN(1) 1.324(6), C(1)ÀN(3), 1.334(6), N(1)ÀN(2) 1.434(5),
S(2)ÀC(10) 1.707(5), C(10)ÀN(4) 1.338(6), C(10)ÀN(6), 1.333(6),
N(4)ÀN(5) 1.429(5); S(1)-Cu(1)-S(2) 164.20(5), S(1)-Cu(1)-N(2)
86.46(11), S(1)-Cu(1)-N(5) 91.68(11), N(2)-Cu(1)-N(5) 165.89(14), Cl(1)-
Cu(1)-S(1) 102.32(5), Cl(1)-Cu(1)-N(2) 102.27(12), Cl(1)-Cu(1)-S(2)
93.23(4).
Figure 6. Representation of the molecular structure of 3. Thermal ellip-
soids at 50% probability. Selected bond distances (ꢅ) and angles (8):
N(3)ÀC(1) 1.339(3), C(1)ÀN(1) 1.313(3), N(1)ÀN(2) 1.376(3),
N(2)ÀC(8) 1.296(3), C(8)ÀS(1) 1.694(3), S(1)ÀC(1) 1.759(2),
C(10)ÀN(6) 1.341(3), C(10)ÀN(4) 1.317(3), N(4)ÀN(5) 1.374(3),
N(5)ÀC(17) 1.303(3), C(17)ÀS(2) 1.688(3), S(2)ÀC(10) 1.760(2); C(2)-
N(3)-C(1) 128.9(2), N(3)-C(1)-N(1) 126.2(2), N(3)-C(1)-S(1) 119.48(17),
C(1)-N(1)-N(2) 108.13(19), N(1)-N(2)-C(8) 118.0(2), N(2)-C(8)-S(1)
111.64(18), S(1)-C(1)-N(1) 114.36(18), C(11)-N(6)-C(10) 128.8(2), N(6)-
C(10)-N(4) 126.4(2), N(6)-C(10)-S(2) 119.32(17), C(10)-N(4)-N(5)
108.28(19), N(4)-N(5)-C(17) 117.6(2), N(5)-C(17)-S(2) 111.97(18), S(2)-
C(10)-N(4) 114.25(17).
This may be the reason why the [N(2)-N(1)-C(1)-S(1)] che-
late ring is almost flat whereas [N(5)-N(4)-C(10)-S(2)] is ap-
preciably buckled, as bond distances and angles in both
rings are similar. Although the ligand is not deprotonated
there is more electronic delocalization than in complex 1, as
methyl group. The asymmetric unit contains two independ-
ent molecules of the cation and a single molecule of the
anion, none of which have any crystallographic symmetry.
The four-coordinate geometry index t4 is 0.33, so the
À
À
evidenced by the average C(1) N(1) and C(1) S(1) bond
distances, 1.331 and 1.708 (1.284 and 1.753 for complex 1),
which are intermediate between single and double bonds,
2À
CuCl4 ion presents a strongly distorted square-planar ge-
ometry, as t4 =1 for tetrahedral and 0 for square-planar.[54]
In addition, all the Cu-Cl distances are different. The cations
are both linked to the anion by N-H···Cl hydrogen bonds
[N(3)-H(2)···Cl(1) 3.378(2) ꢅ, N(6)-H(4)···Cl(6) 3.266(2) ꢅ].
The hydrogen-bonded assembly has an approximately two-
fold axis of rotation. Bond distances and angles in both het-
erocyclic rings are not identical but are very similar. The
À
whereas in complex 1 the C N bond distance correlates well
À
with a double bond and the C S bond is close to the value
À
expected for a single bond (ca 1.82 ꢅ). The Cu Cl bond
lengths are quite long [2.6411(14) and 2.6248(13) ꢅ], al-
though they are in the range of other complexes with a
chlorido ligand in the apex of a square-based pyramid.[51–53]
The phenyl rings are perpendicular to the ligand chain, the
angles being 74.26 and 83.758. All of the NH groups partici-
pate in hydrogen bonding, with both the free and coordinat-
ed Cl atoms acting as acceptors together with the solvent.
The water molecules also have additional short non-bonded
contacts, presumably also indicative of hydrogen bonding,
although as their H atoms could not be located, these are
ambiguous. The NH···Cl bonds link the cations and anions
to form a centrosymmetric assembly containing four of each
species. The hydrogen bonding involving water cross-links
these to form a 3D network. The Cl anions are positioned
between the cations and the distance to the Cu atoms of
more than 7 ꢅ rules out any bonding interaction.
À
À
À
À
N(2) C(8), N(5) C(17), N(1) C(1) and N(4) C(10) bond
distances correspond to double bonds, whereas the remain-
À
À
À
ing C N, the N N and the C S bond distances are close to
the value expected for single bonds. The thiadiazolium rings
AHCTUNGTRENNUNG
are virtually planar with mean deviations from their least-
squares planes of 0.0058 ꢅ for N(2) and 0.0081 ꢅ for S(2)
and they are coplanar with the phenyl groups.
The crystal structure of the 1,2,4-thiadiazole ligand 5 is
made up of discrete molecules of [C18H22N6S] (Figure 7).
The heterocyclic ligand consists of a C2N2S ring, with four
À
À
pendant substituents [N N(Me)2, Ph, N Ph, N(Me)2]. The
five-member ring can be considered planar, with a maxi-
mum deviation of 0.0537 ꢅ for C(10) from the least-squares
plane The bond distances in the ring are closer to the values
expected for single bonds, which indicates a weak electronic
delocalization. The C=N bond lengths in the exocyclic imino
groups are almost identical. The torsion angles about the
The crystal structure of compound 3 was previously re-
ported[49] and consists of a copper(II) salt containing one
[CuCl4]2À anion and two positively charged 3-methyl-1,3,4-
thiadiazolium cations (Figure 6), which are formed by the
oxidation and cyclisation of the thiosemicarbazide, via the
formation of a bond between sulfur and a deprotonated
À
two C=N bonds indicate that C(1) N(2) is slightly more
À
twisted than C(10) N(6). The rotation angle of the phenyl
Chem. Eur. J. 2009, 15, 3012 – 3023
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3017

E. Lꢀpez-Torres and J. R. Dilworth
difference between both heterocycles is that 6 exhibits a
greater electronic delocalization, with bond distances inter-
mediate between single and double bonds and therefore, the
thiadiazole ring is more planar than in 5, with a mean devia-
tion of 0.0142 for N(3) from the least-squares plane. Al-
though in 5 both exocyclic C=N bonds are almost identical,
in 6 they are quite different, being the one corresponding to
the protonated nitrogen the largest and is significantly
longer than in 5 [1.330(6) vs. 1.272(2) respectively]. Another
difference is the disposition of the phenyl rings, whereas in 5
they are virtually perpendicular to each other, probably due
to steric factors, the proton present in 6 causes the dihedral
angle between the aromatic rings to be 28.228. The angles
between the phenyls and the thiadiazole ring are 67.47 and
Figure 7. Representation of the molecular structure of 5. Thermal ellip-
soids at 40% probability. Selected bond distances (ꢅ) and angles (8):
N(2)ÀC(1) 1.276(2), C(1)ÀN(1) 1.379(2), N(3)ÀN(2) 1.4700(18),
C(1)ÀS(1) 1.7438(16), S(1)ÀN(4) 1.8013(14), C(10)ÀN(6) 1.272(2),
C(10)ÀN(4) 1.398(2), N(4)ÀN(5) 1.4067(19), N(1)ÀC(10) 1.401(2); N(3)-
N(2)-C(1) 104.28(13), N(2)-C(1)-S(1) 121.56(13), C(1)-S(1)-N(4)
88.83(7), S(1)-N(4)-C(10) 112.62(11), N(4)-C(10)-N(1) 109.77(13), C(10)-
N(1)-C(1) 115.78(13), N(2)-C(1)-S(1) 121.56(13), C(10)-N(6)-C(11)
123.13(14), C(10)-N(4)-N(5) 115.10(13), S(1)-N(4)-N(5) 117.97(10), N(4)-
C(10)-N(6) 130.05(15), N(1)-C(10)-N(6) 120.17(14), N(1)-C(1)-N(2)
126.23(15).
À
À
62.428 for C(2) C(7) and C(11) C(16) respectively.
The crystal structure of the 1,2,4-triazolium salt
7
À
(Figure 9) consists of discrete units of [C18H23N6] with I3 as
counterion. The C2N3 ring is planar with a maximum devia-
tion from their least-squares plane of 0.0375 ꢅ for N(5), the
ring attached to N(6) (74.218), close to being perpendicular
to the thiadiazol ring. This suggests little conjugation be-
tween the lone-pair electrons of the N(1) atom and the p
electrons of the phenyl ring. The other aromatic ring also
has a large rotation angle (68.188), and the dihedral angle
between both aromatic rings is 75.748.
The 1,2,4-thiadiazolium salt 6 (Figure 8) shows the same
atom disposition as 5, but in this compound N(6) is proton-
À
ated and there is an I3 molecule as counterion. The main
Figure 9. Representation of the molecular structure of 7. Thermal ellip-
soids at 50% probability. The counterion has been omitted for clarity. Se-
lected bond distances (ꢅ) and angles (8): N(1)ÀC(1) 1.392(4), C(1)ÀN(2)
1.257(4), N(2)ÀN(3) 1.407(4), C(1)ÀN(5) 1.502(4), N(5)ÀN(4) 1.457(4),
C(10)ÀN(6) 1.342(4), C(10)ÀN(4) 1.307(4), N(1)ÀC(10) 1.403(4); N(3)-
N(2)-C(1) 123.0(3), N(2)-C(1)-N(5) 116.0(3), C(1)-N(5)-N(4) 107.6(2),
N(5)-N(4)-C(10) 104.8(3), N(4)-C(10)-N(1), 115.4(3), C(10)-N(1)-C(1)
107.6(3), C(10)-N(6)-C(11) 125.8(3), C(17)-N(5)-N(4) 108.8(3), C(18)-
N(5)-N(4) 108.2(3), N(4)-C(10)-N(6) 123.2(3), N(1)-C(10)-N(6) 121.4(3),
N(1)-C(1)-N(2) 139.8(3).
positively charged nitrogen atom. There are two double
bonds, one endo and one exocyclic. In spite of the positive
charge and the double bonds, the triazolium ring does not
show electronic delocalization, the bond distances corre-
sponding to double or single bonds. The dihedral angle be-
tween the aromatic rings is 46.178, and the angles between
the rings and the heterocycle are 52.71 and 24.608 for the
phenyls attached to N(1) and N(2) respectively.
The 1,3-thiazolium salt 9 is made up of [C12H16N3S] units
(Figure 10) with IÀ as counterion. This C3NS heterocycle is
the most planar, with a mean deviation of 0.0094 ꢅ for N(1)
from the least-squares plane. As occurred in 7, there is one
endo and one exocyclic double bond, but to difference with
that, in this molecule there is electronic delocalization, the
bond distances being intermediate between single and
Figure 8. Representation of the molecular structure of 6. Thermal ellip-
soids at 50% probability. The counterion has been omitted for clarity. Se-
lected bond distances (ꢅ) and angles (8): N(1)ÀC(1) 1.276(6), C(1)ÀN(3)
1.393(6), N(1)ÀN(2) 1.464(5), C(1)ÀS(1) 1.733(4), S(1)ÀN(4) 1.783(4),
C(10)ÀN(6) 1.330(6), C(10)ÀN(4) 1.341(6), N(4)ÀN(5) 1.408(5),
N(3)ÀC(10) 1.364(6); N(2)-N(1)-C(1) 102.3(3), N(1)-C(1)-S(1) 119.1(3),
C(1)-S(1)-N(4) 85.87(19), S(1)-N(4)-C(10) 115.2(3), N(4)-C(10)-N(3)
112.1(4), C(10)-N(3)-C(1) 112.2(4), N(3)-C(1)-S(1) 114.6(3), C(10)-N(6)-
C(11) 130.0(4), C(10)-N(4)-N(5) 118.3(4), S(1)-N(4)-N(5) 126.3(3), N(4)-
C(10)-N(6) 120.2(4), N(3)-C(10)-N(6) 127.7(4), N(1)-C(1)-N(3) 126.3(4).
3018
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Chem. Eur. J. 2009, 15, 3012 – 3023

Reactivity of Thiosemicarbazides with Redox Active Metal Ions
FULL PAPER
Figure 10. Representation of the molecular structure of 9. Thermal ellip-
soids at 50% probability. The counterion has been omitted for clarity. Se-
lected bond distances (ꢅ) and angles (8): S(1)ÀC(1) 1.711(13),
N(3)ÀC(1) 1.330(17), C(1)ÀN(1) 1.344(16), N(1)ÀN(2) 1.400(15),
S(1)ÀC(11) 1.740(14), N(1)ÀC(10) 1.410(17), C(10)ÀC(11) 1.333(19),
C(10)ÀC(12) 1.487(19); N(1)-C(1)-N(3) 121.3(12), N(3)-C(1)-S(1)
127.5(10), C(1)-N(1)-N(2) 115.9(11), C(1)-S(1)-C(11) 90.5(7), S(1)-C(11)-
C(10) 112.6(10), C(11)-C(10)-N(1) 111.2(12), C(10)-N(1)-C(1) 114.6(11),
N(1)-C(1)-S(1) 111.1(10), C(10)-N(1)-N(2) 129.3(11), N(1)-C(10)-C(12)
121.4(12), C(11)-C(10)-C(12) 127.4(13).
Figure 11. Mass spectrum (FAB) of complex [Sn(L)2I2] 8.
double bonds. The dihedral angle between the five-mem-
bered ring and the phenyl group is 41.858.
Mass spectrometry and infrared spectroscopy: Electrospray
mass spectrum of the complex [CuL2] 1 shows a peak at
452.1 amu corresponding to the molecular ion. ESI of com-
plex
2 show a peak at 453.1 amu corresponding to
[Cu(LH)2]+, owing to the loss of the Cl from the cationic
part. The ESI of 4 shows a peak at 453.1 amu attributable to
[Cu(LH)2]+. The ESI spectrum of 1,2,4-thiadiazole 5 shows
the [M+H]+ ion at 355.2 amu. The rest of the heterocycles
show peaks corresponding to the cationic part as well as
other fragments, owing to the loss of some pendant groups
(see the Experimental Section). The FABMS spectrum of
the tin complex [SnL2I2] 8 shows peaks corresponding to
[M+H]+ and to the loss of L or I (Figure 11). Complex
[Sn(LH)2Cl2]Cl2 10 shows in the ESI spectrum one peak at-
tributable to the cationic part and two other peaks, owing to
the loss of one chloride or one ligand (Figure 12). The ex-
perimental isotopic patterns match the theoretical ones for
all the peaks.
The infrared spectrum of the free ligand shows bands cor-
responding to N-H stretching vibrations. This, together with
the absence of any band in the 2800–2600 cmÀ1 region corre-
sponding to the thiol tautomer, agrees with the imine-thione
form of the ligand observed in the X-ray structure. Owing to
electronic delocalization the IR spectra of the complexes
show both C=N and C=S stretching vibrations.
Figure 12. Mass spectrum (ESI) of complex [Sn(LH)2Cl2]Cl2 10.
With respect to the heterocycles all of them, except 5,
À
which does not have any N H group, show bands corre-
À
sponding to u
A
confirmed by the IR spectra, as well as the other functional
groups present in the compounds (see the Experimental
Section).
NMR spectroscopy: The 1H NMR spectrum of the ligand
LH shows a strong dependence of the position of the acidic
proton with the solvent. Although in [D6]DMSO it appears
at 9.69 ppm in CDCl3 it is shifted to 7.03 ppm and to
8.05 ppm in acetone. The proton corresponding to the other
À
amine group, NH Ph, is less sensitive to the solvent al-
though also suffers slight variations. Owing to the paramag-
1
netism of the CuII species, their H NMR spectra could not
1
be recorded. The H NMR in CDCl3 of the CuI complex 4
1
In complexes 1 and 8 there is a decrease in the number of
À
shows the expected ligand resonances. In the H NMR spec-
bands corresponding to u
N
trum of complex 8 the signal at 7.03 ppm corresponding to
one NH has disappeared, which confirms the ligand depro-
tonation. The 1H NMR spectrum of complex 10 in
[D6]DMSO corresponds to the free ligand, indicating de-
composition in this solvent. As this complex is not soluble in
protonation, whereas the number of bands in 2, 4 and 10
suggests that the ligand is neutral. The presence of thiocya-
nate in complex 4 is confirmed by the presence of a sharp
À ꢀ
and strong band at 2052 cmÀ1corresponding to u
ACTHNUTRGNE(NUG S C N).
Chem. Eur. J. 2009, 15, 3012 – 3023
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3019

E. Lꢀpez-Torres and J. R. Dilworth
CDCl3, the NMR studies were completed in [D6]acetone.
The spectrum shows two signals corresponding to two NH
groups slightly shifted with respect to the free ligand in the
same solvent, confirming that the ligand is neutral, as was
suggested by the IR. The H NMR spectra of the organic
molecules show all the peaks expected for the functional
groups present in the heterocycles.
compounds or metal complexes. Figure 1 summarises the
thiadiazoles (A to F) that have been previously reported by
the oxidation of thiosemicarbazones R1CH=NNR2CSNHR3
or thioureas RNHCSNHR. Also presented in the Figure for
comparison are the four new heterocycles prepared in this
work, the numbering following that used in the text. By
comparison with other known thiadiazoles and related com-
pounds these may well have interesting biological proper-
ties.
1
The 13C NMR spectrum of LH confirms that the thione
form is retained in solution. The 13C NMR spectrum of the
CuI complex 4 does not clearly indicate the coordination
mode of the ligand, because the position of the signals cor-
responding to the CS and NMe2 groups have not shifted
very much, relative to the free ligands, although all the
other data suggests that coordination has occurred. For the
tin complex 8 and 10, the 13C peak corresponding to the CS
group is shifted ca. 3 ppm upfield, and the peaks for the
methyl groups have moved ca. 3ppm downfield relative to
the free ligand. This suggests that the sulfur atoms and the
dimethylamine nitrogen are bonded to the metal in both
complexes. The spectra of the heterocyclic compounds show
signals consistent with the structures found in the solid state
(see the Experimental Section).
Reactions with copper salts: In basic solution simple com-
plexation of the thiosemicarbazide to copper occurs and the
identity of the new 2:1 complexes have been confirmed by
an X-ray crystal structure. In the absence of base the reac-
tions in methanol lead to complex mixtures, which we were
unable to separate. However, use of THF as solvent permit-
ted the reproducible isolation of two new heterocycles 3 and
5. It seems feasible that the less polar solvent THF may sta-
bilise the diazenium ion and permit more controlled chemis-
try to occur. We have not investigated the mechanism of
this reaction in any detail, but one possibility is that reduc-
tion of CuII to CuI and oxidation of the thiosemicarbazide
occurs to give a diazenium ion Me2N=NCSNHPh. These re-
actions require the presence of air and the actual oxidant
may, at least in part, be dioxygen. The nature of the hetero-
cycle formed will then depend on subsequent reactions of
the diazenium species. It is clear that the cyclisation reaction
to 3 involves one of the methyls of the dimethylamino
group reacting with sulfur, whereas formation of 5 requires
the coupling of two diazenium ions with elimination of HSÀ
or H2S, but we do not know the precise factors determining
which route is involved. We cannot at this stage exclude the
possibility of radical reactions in a situation in which one
electron redox processes (CuII/CuI) are involved.
The 119Sn chemical shift observed in complex 10,
À625.6 ppm, is indicative of SnIV in a hexa-coordinate envi-
ronment and it is in agreement with the chemical shift of
other complexes found in the literature.[55,56] This value falls
within the range of N2S2Cl2 coordination in which the pres-
ence of two chlorido ligands leads to a more negative value
of the chemical shift than the one found with S, N, O or C-
donor ligands, owing to their inductive effect and also to the
À
possibility of additional p-contribution to the Sn Cl bond,
which would shield the nucleus to a greater extent.[56] These
factors increase significantly when chlorido is changed for
iodido and the 119Sn NMR of complex 8 is À1844 ppm,
which correlates well with SnIV in a N2S2I2 environment.[57]
Taking all this data into account, the structures proposed
for complexes 4, 8 and 10, for which was not possible to
obtain crystals suitable for X-ray analysis, are those repre-
sented in Scheme 1 for complex 4, in Scheme 2 for complex
8 and in Figure 13 for complex 10.
Reactions with tin salts: The situation is more complex here
due to the dependence on the anion. The fact that heterocy-
cle formation is observed for the more easily reduced SnI4
suggests that the metal centre is reduced to SnII whereas the
ligands are oxidised to diazenium cations as observed with
copper. However, the appearance of the triodide anion in 7
indicates that redox reactions involving iodide may also be
involved. Also the formation of 7 is favoured under condi-
tions in which the metal is in excess and suggests that the
tin plays a role in the removal of the second sulfur molecule
as a tin sulfide. The formation of 9 involves trapping of the
oxidised species with the acetone solvent rather than dimeri-
sation.
Comparison with thiosemicarbazones: The metal oxidation
of thiosemicarbazones leads exclusively to intraligand cycli-
sation reactions, owing to the availability of the imine
carbon as a site for nucleophilic attack by nitrogen or sulfur.
In the thiosemicarbazide studied here, the imine based cycli-
sation is not available and a more complex coupling of two
Figure 13. Proposed structure for complex [Sn(LH)2Cl2]Cl2 10.
Discussion
We have shown that control of the conditions in the reac-
tions of the thiosemicarbazide PhNHCSNHNMe2 with
copper or tin salts can give rise either to new heterocyclic
À
ligands occurs with N-S and N C bond formation. In this re-
spect there is, as expected, a closer analogy between the oxi-
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Reactivity of Thiosemicarbazides with Redox Active Metal Ions
FULL PAPER
In complex 2 an initial attempt to index the diffraction pattern suggested
a C-centred monoclinic cell, with a=18.66, b=32.03, c=18.80 ꢅ, b=
111.68. However, the data could not be processed successfully with this
cell. Further examination showed that the diffraction pattern could be
completely indexed by assuming it to be a two-component twin, with a
unit cell of 1/4 the volume. The two components are related by a 1808 ro-
tation about the reciprocal vector (À1, 1, 1). As a result of the (coinci-
dental) relationships between the cell parameters, half of the reflections
in the two patterns overlap almost exactly, whereas the other half are
quite distinct.
dative coupling of thiosemicarbazides and thioureas than
there is with the reactions of thiosemicarbazones.
Conclusion
This work has shown that the reactions of thiosemicarba-
zides with oxidising metal salts in THF or methanol under
neutral conditions, provides a valid and convenient route to
new potentially biologically active thiadiazole and related
heterocyclic compounds. Moreover, use higher pH leads to
the isolation of identifiable metal complexes.
CCDC 623527 (1a), 623528 (3) , 695040 (LH), 695041 (1b), 695042
(2·3H2O), 695043 (5), 695044 (6·toluene) 695045 (7), and 695046 (9) con-
tain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1,1-dimethyl-4-phenylthiosemicarbazide (LH): To a solution of phenyliso-
thiocyanate (2 mL, 16.72 mmol) in diethyl ether (25 mL) was added 1,1-
dimethylhydrazine (1.3 mL, 17.11 mmol). The solution was stirred at
room temperature for 15 min. Then the white solid was filtered off,
washed with diethyl ether and vacuum dried (3.19 g, 98%). 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS): d=9.69 (s, 1H; NH), 9.17 (s, 1H;
NH), 7.63–7.60 (d, 2H; o-Ph), 7.30–7.25 (t, 2H; m-Ph), 7.12–7.07 (t, 1H;
p-Ph), 2.52 (s, 6H; Me); 1H NMR (300 MHz, CDCl3, 258C, TMS): d=
9.13 (s, 1H; NH), 7.59–7.56 (d, 2H; o-Ph), 7.33–7.27 (t, 2H; m-Ph), 7.15–
7.11 (t, 1H; p-Ph), 7.03 (s, 1H; NH), 2.58 (s, 6H; Me); 1H NMR
(300 MHz, [D6]acetone, 258C, TMS): d=9.66 (s, 1H; NH), 8.05 (s, 1H;
NH), 7.80–7.76 (d, 2H; o-Ph), 7.33–7.28 (t, 2H; m-Ph), 7.12–7.09 (t, 1H;
p-Ph), 2.65 (s, 6H; Me) 13C NMR (300 MHz, [D6]DMSO, 258C, TMS):
d=177.3 (C=S), 139.71 (i-Ph), 128.2 (m-Ph), 124.8 (p-Ph), 124.7 (o-Ph),
46.4 (Me); IR (KBr): n˜ =3278 (s), 3147 (s) [u(NH)], 1612 (s) [d (NH)],
1589 (s) [d (NCS)], 856 (w) [u(CS]; MS (Probe FI): m/z (%): 195.1 (100)
[M]; elemental analysis calcd (%) for C9H13N3S: C 55.4, H 6.7; N 21.5, S
16.4; found: C 55.5, H 6.6, N 21.4, S 16.4.
Experimental Section
Materials and measurements: All reagents and solvents were obtained
from commercial sources (Sigma–Aldrich and Lancaster) and were used
as received. Elemental analyses were performed by the microanalysis
service of the department at the University of Oxford. NMR spectra
were recorded by using a Varian Mercury VX300 spectrometer (1H NMR
at 300 MHz and 13C{1H} NMR at 75.5 MHz) using the residual solvent
signal as an internal reference. 119Sn NMR spectra were recorded by
using a Bruker AMX 300 spectrophotometer with SnMe4 as internal ref-
erences. Mass spectra were recorded by using a Micromass LCT time-of-
flight mass spectrometer using positive ion electrospray (ESI+) or solid
probe field ionization (FI) techniques and fast atom bombardment
(FAB) mass spectra were recorded by using a VG Auto Spec instrument
using Cs as the fast atom and m-nitrobenzilalcohol (mNBA) as the
matrix.
Crystal structure determination: Crystals of 1, 2, 3, 5 and 6 were mounted
on a glass fibre using perfluoropolyether oil and cooled rapidly to 150 K
in a stream of cold N2 using an Oxford Cryosystems CRYOSTREAM
unit. Diffraction data were measured using by an Enraf–Nonius Kap-
paCCD diffractometer (graphite-monochromated MoKa radiation).
Measurements of crystals of LH, 7 and 9 were carried out by using a
Bruker SMART 6 K CCD area detector with a Rigaku Rotating Anode
(CuKa radiation). For complexes 1, 2, 3, 5 and 6 intensity data were pro-
cessed by using the DENZO-SMN package[58] and the structures were
solved using the direct-methods program SIR92,[59] which located all non-
hydrogen atoms. Subsequent full-matrix least-squares refinement was car-
ried out using the CRYSTALS program suite.[60] For LH, 7 and 9 the in-
tensity data frames were integrated by use of the SAINT[61] program,
which also applied corrections for Lorentz and polarisation effects and
the SHELXTL[62] software package, version 6.10, was used for space
group determination, structure solution and refinement and the struc-
tures were solved by direct methods using SHELXS-97,[63] completed
with difference Fourier syntheses and refined by full-matrix least-squares.
Coordinates and anisotropic thermal parameters of all non-hydrogen
atoms were refined. The NH hydrogen atoms were located in a differ-
ence Fourier map and their coordinates and isotropic thermal parameters
subsequently refined and the hydrogen thermal parameters restrained to
be similar to those of their parent N atoms. CH hydrogen atoms were
positioned geometrically after each cycle of refinement. For complex 2
the hydrogen atoms of the molecules of water could not be located in the
difference Fourier map, presumably as a result of disorder. They have
been omitted from the model (but included in calculations of the formula
weight etc). In compound 6 a difference Fourier map showed a number
of peaks of additional electron density, which were identified as the C
atoms of a molecule of toluene disordered over two sites related by a
crystallographic inversion. Their coordinates, anisotropic thermal param-
eters and site occupancies were refined, subject to restraint of the aro-
ACHUNTGRENN[UG CuL2] (1): A suspension of CuCAHTUNGTERN(NUGN OAc)2·H2O (0.103 g, 0.51 mmol) in
methanol (10 mL) was added over LH (0.200 g, 1.02 mmol) dissolved in
the same solvent (10 mL). The red mixture was stirred at room tempera-
ture for 1 hour. The red solid was filtered off, washed with methanol and
diethyl ether and vacuum dried (0.191 g, 82%). IR (KBr): n˜ =3178 (s)
[u(NH)], 1601 (w) [u(CN)], 1581 (s) cmÀ1 [d (NCS)], 814 (w) [u(CS)];
MS (ESI): m/z (%) 452.1 (100) ([M+H]+); elemental analysis calcd (%)
for C18H24N6S2Cu: C 47.8, H 5.4, N 18.6, S 14.2, Cu 14.1; found: C 47.3, H
5.3, N 18.6, S 14.2, Cu 14.1. Single crystals suitable for X-ray analysis of
1a were grown in methanol and of 1b in diethyl ether. The same com-
plex is obtained if two equivalents of LH are reacted with one of
CuCl2·2H2O or CuCAHTUNGRTEN(NGNU NO3)2·3H2O in the presence of lithium hydroxide or
triethylamine.
[Cu(LH)2Cl]Cl (2): CuCl2·2H2O (0.043 g, 0.25 mmol) dissolved in H2O
(2 mL) was added over a suspension of LH (0.100 g, 0.51 mmol) in 4 mL
of the same solvent with two drops of HCl. The green mixture was stirred
at room temperature for 30 min then, the bright green solid was filtered
off, washed with water and vacuum dried (0.096 g, 65%). IR (KBr): n˜ =
3147 (s) [u(NH)], 1599 (m) [u(CN)], 1558 (s) [d (NCS)], 842 (w) cmÀ1
[u(CS)]; elemental analysis calcd (%) for C18H26N6S2CuCl2: C 41.2, H
5.0, N 16.0, S 12.2, Cl 13.5, Cu 12.1; found: C 41.3, H 5.2, N 16.4, S 12.0,
Cl 13.2, Cu 12.0; MS (ESI): m/z (%) 453.1 (100) [M]+. Slow evaporation
of a methanolic solution gave single crystals suitable for X-ray analysis.
3-methyl-5-(phenylamino)-1,3,4-thiadiazol-3-ium tetrachlorocuprate(II)
[C9H10N3S]2ACHTNUGRTENUNG[CuCl4] (3): Over a solution of LH (0.100 g, 0.51 mmol) in
THF (5 mL) was added a solution of CuCl2·2H2O (0.043 g, 0.25 mmol) in
the same solvent (5 mL). The green mixture was stirred at room tempera-
ture for 1 hour. The green solid was filtered off, washed with THF and di-
ethyl ether and vacuum dried (0.125 g, 83%). IR (KBr): n˜ =3232 (m),
3193 (m) [u(NH)], 1604 (m) [u(CN)], 1566 (s) [d (NCS)], 840 (w) cmÀ1
[u(CS)]; MS (ESI): m/z 192.1 (100) [C9H10N3S]+; elemental analysis calcd
(%) for C18H20N6S2CuCl4: C 36.6, H 3.4, N 14.2, S 10.8, Cl 24.1, Cu 10.8;
found: C 36.9, H 3.6, N 14.3, S 10.9, Cl 23.9, Cu 10.7. After one day in
the freezer green crystals suitable for X-ray analysis were obtained from
the mother liquor.
À
À
matic C C bond lengths to 1.38(2) ꢅ, the aliphatic C C bond length to
1.54(2) ꢅ and all C-C-C angles to 120(2)8. Similarity restraints were ap-
plied to the thermal parameters of directly-bonded atoms. A 3-term Che-
bychev polynomial weighting Scheme was applied for all the complexes.
Chem. Eur. J. 2009, 15, 3012 – 3023
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3021

E. Lꢀpez-Torres and J. R. Dilworth
[Cu(LH)2]SCN (4): CuSCN (0.063 g, 0.52 mmol) was added over a solu-
tion of LH (0.200 g, 1.02 mmol) in methanol (20 mL) under N2 atmos-
phere. The mixture was refluxed for 5 h. The solution was concentrated
under vacuum until a pale pink solid appeared, which was filtered off,
washed with methanol and diethyl ether and vacuum dried (0.206 g,
79%). 1H NMR (300 MHZ, [D6]DMSO, 258C, TMS): d=9.73 (s, 1H;
NH), 9.15 (s, 1H; NH), 7.60–7.56 (d, 2H; o-Ph), 7.30–7.25 (t, 2H; m-Ph),
7.12–7.07 (t, 1H; p-Ph), 2.51 (s, 3H; Me), 2.47 (s, 3H; Me). 13C NMR:
(300 MHz, CDCl3, 258C, TMS): d=176.96 (C=S), 137.26 (i-Ph), 128.95
(m-Ph), 125.93 (p-Ph), 123.56 (o-Ph); 47.22 (Me); IR (KBr): n˜ =3279 (s),
(s, 6H; Me); 13C NMR (300 MHz, CDCl3, 258C, TMS): d=157.1, 149.3
(C=N), 137.2, 131.7, 130.9, 130.7, 129.6, 129.4, 129.1, 123.0, (Ph), 57.5,
48.0 (Me); IR (KBr): n˜ =3383 (w) [u(NH)], 3041 (w) [u
2924, 2856, 2785 (w) [u(CHMe)], 1701 (m), 1623, 1595 (s) [u(CN)], 1545
(s), 1491 (m) [u(CCPh)], 1449 (m) [das(C-HMe)], 1354 [ds(C-HMe)], 750,
690 (s) cmÀ1 [doop(CHPh)]; MS (FAB): m/z (%): 323.2 (100) [M]+, 308.2
ACHTUGNTREN(UNNG CHPh)], 2958.3,
AHCTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(10) [MÀMe]+, 293.1 (2) [MÀ2Me]+, 279.1 (5) [MÀNMe2]+, 265.1 (2)
[MÀNMe2-Me]+, 251.1 (5) [MÀNMe2À2Me]+; elemental analysis calcd
(%) for C18H23N6I3: C 30.7, H 3.3, N 11.9, I 54.1; found: C 31.0, H 3.4, N
12.0, I 53.8.
3148 (s) [u(NH)], 2052 (s) [uACTHUNRGTNE(NUG S=C=N)], 1607 (m) [u(CN)], 1596 (s) [d
[Sn(L)2I2] (8): Over
a solution of LH (0.200 g, 1.02 mmol) and
(NCS)], 835 (m) cmÀ1 [u(CS)]; MS (ESI): m/z (%): 453.10 (100) [M]+; el-
emental analysis calcd (%) for C19H26N7S3Cu: C 44.6, H 5.1, N 19.2, S
18.7, Cu 12.4; found: C 44.2, H 5.2, N 19.6, S 19.0, Cu 12.2.
LiOH·H2O (0.042 g, 1.02 mmol) in methanol (10 mL) was added solid
SnI4 (0.321 g, 0.51 mmol) in small amounts. The yellow mixture was
stirred at room temperature for one hour. The solution is concentrated
until a yellow precipitate was formed, which is filtered off, washed with
diethyl ether and vacuum dried (0.187 g, 48%). 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=9.18 (s, 1H; NH), 7.62–7.65 (d, 2H; o-Ph), 7.39–
7.33 (t, 2H; m-Ph), 7.20–7.18 (t, 1H; p-Ph), 2.65 (s, 6H; Me); 13C NMR
(300 MHz, CDCl3, 258C, TMS): d=172.7 (C=S), 136.0 (i-Ph), 128.6 (m-
Ph), 125.8 (p-Ph) , 123.8 (o-Ph), 48.6 (Me); 119Sn NMR (300 MHz,
CDCl3, 258C, SnMe4): d=À1843.9;IR (KBr): n˜ =3146 (s) [u(NH)], 1596
(w) [u(CN)], 15421 (s) [d (NCS)], 819 (w) cmÀ1 [u(CS)]; MS (FAB): m/z
(%): 762.6 (25) [M+H]+, 634.8 (100) [MÀI]+, 567.6 (60) [MÀL]+; ele-
mental analysis calcd (%) for C18H24N6S2SnI2: C 28.4, H 3.2, N 11.0, S
8.4, I 33.4, Sn 15.6; found: C 28.6, H 3.5, N 10.9, S 8.5, I 33.8, Sn 15.9.
5-(2,2-dimethylhydrazono)-N,N-dimethyl-4-phenyl-3-(phenylimino)-1,2,4-
thiadiazolidin-2-amine [C18H22N6S] (5): Attempts to recrystallise complex
4 always lead to colourless crystals together with another yellow crystal-
line material. X-Ray crystallography of both compounds showed that the
yellow crystals were S8, whereas the colourless ones were a 1,2,4-thiadi-
ACHTUNGTRENNUNG
a
(2.5 mL) was added dropwise. The mixture was stirred at room tempera-
ture for 45 min. During this time a yellow precipitate corresponding to el-
emental sulfur was formed. The mixture was filtered off and the solution
was added dropwise over 20 mL of deionizated water containing five
drops of NH3 conc. and cooled in an ice bath. Immediately a white pre-
cipitated was formed, which was filtered off, washed with several portions
of water and vacuum dried (0.086 g, 95%). 1H NMR (300 MHz, CDCl3,
258C, TMS): d=7.48–7.39 (m, 6H; Ph), 7.14–7.094 (t, 2H; Ph), 6.84–6.79
(t, 2H; Ph), 2.5 (s, 6H; Me), 2.2 (s, 6H; Me). 13C NMR (300 MHz,
CDCl3, 258C, TMS): d=149,2 (C=N), 136.4, 129.0, 128.6, 128.0, 127.8,
N-(3-(dimethylamino)4-methylthiazol-2
A
benzenaminium
iodine [C12H16N3S][I] (9): Over a solution of LH (0.200 g, 1.02 mmol) in
acetone (5 mL) was added a suspension of SnI4 (0.321 g, 0.51 mmol) in
the same solvent (10 mL). The dark red solution was stirred at room tem-
perature for one hour. Slow evaporation of the mother liquor afforded
orange crystals suitable for X-ray analysis (0.326 g, 88%). 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=9.15 (s, 1H; NH), 7.54–7.52 (d, 2H;
o-Ph), 7.40–7.35 (t, 2H; m-Ph), 7.26–7.211 (d, 1H; p-Ph), 6.99 (s, 12H;
CH=C), 3.25 (s, 6H; NMe2), 2.70 (s, 3H; Me); 13C NMR (300 MHz,
CDCl3, 258C, TMS): d=146.0, 145.5 (=C-N, C=N), 132.0 (i-Ph), 130.5
(m-Ph), 129.3 (p-Ph), 123.5 (o-Ph), 101.9 (=C-S), 48.4 (NMe2), 16.1
120.9, 120.5 (Ph), 47.2 42.6 (Me); IR (KBr): n˜ =3063 (w) [u
2854, 2777, 2815 (w) [u(CHMe)], 1674 (m), 1612 (s) [u(CN)], 1589 (s) [d-
(NCS)], 1489 (m) [u(CCPh)], 1458 (m) [das(C-HMe)], 1388 (m) [ds(C-
Me)], 694 (m) cmÀ1 [doop
ACHTUGNTRNEN(UNG CHPh)], 2955,
ACHTUNGTRENNUNG
A
E
N
ACHTUNGTRENNUNG
H
ACHTUGNRTNE(NUNG CHPh)]; MS (ESI): m/z (%) 355.2 (10) [M+
H]+, 311.1 (100) [MÀNMe2]+; elemental analysis calcd (%) for
(Me); IR (KBr): 3281 (m) [u(NH)], 3061 (w) [u
[u(CHMe)], 1593 (s) [u(CN)], 1565 (s) [d(NCS)], 1494 (m) [u
1456 (m) [das(C-HMe)], 1375 (m) [ds -
(C-HMe)], 758, 703 (s) cmÀ1 [doop
ACHTUNGTRENNUNG
T
A
ACHTUNGTRENNUNG
C18H22N6S: C 61.0, H 6.1, N 24.0, S 9.1; found: C 61.2, H 6.2, N 23.7, S
9.0.
A
E
AHCTUNGTRENNUNG
(CHPh)]; MS (FAB): m/z (%) 234.1 (100) [M]+, 189.0 (25) [M>M->
N-2-(dimethylamino)-5-(2,2-dimethylhydrazono)-4-phenyl-1,2,4-thiadi-
ACHTUNGTRENNUNGazolidin-3-ylidene)benzenaminium triiodone [C18H23N6S][I3] (6): Over a
NMe2]+; elemental analysis calcd (%) for C12H16N3SI: C 39.9, H 4.5, N
11.6, S 8.9, I 35.1; found: C 39.6, H 4.4, N 11.8, S 8.7, I 35.6.
solution of SnI4 (0.321 g, 0.51 mmol) in methanol (10 mL) was dropped
very slowly a solution of LH (0.200 g, 1.02 mmol) in the same solvent
(10 mL). The orange solution was stirred at room temperature for one
hour. The solution is kept at À248C for two days and the yellow precipi-
tate (S8) formed is removed by filtration. Slow evaporation of the mother
liquor afforded brown crystals suitable for X-ray analysis (0.248 g, 66%).
1H NMR (300 MHz, CDCl3, 258C, TMS): d=9.23 (s, 1H; NH), 7.58–7.52
(t, 1H; Ph), 7.51–7.47 (d, 3H; Ph), 7.41–7.33 (m, 4H; Ph), 7.24–7.09 (m,
2H; Ph), 3.21 (s, 6H; C=N-NMe2), 2.70 (s, 6H; N-NMe2); 13C NMR
(300 MHz, CDCl3, 258C, TMS): d=166.9 (C=N+), 156.0 (C=N), 139.3,
132.1, 130.5, 129.2, 128.9, 124.9, 123.4, 122.7 (Ph), 47.4 (=N-NMe2), 45.7
[Sn(LH)2Cl2]Cl2 (10): SnCl4 (0.06 mL, 0.51 mmol) was added over a solu-
tion of LH (0.200 g, 1.02 mmol) in dried methanol (10 mL) under N2 at-
mosphere. The yellow solution was stirred at room temperature for 2 h.
The solution is concentrated until a yellow precipitate was formed, which
was filtered off, washed with methanol and diethyl ether and dried in
vacuum (0.250 g, 75%). 1H NMR (300 MHz, [D6]acetone, 258C, TMS):
d=9.75 (s, 1H; NH), 7.71 (s, 1H; NH), 7.49–7.40 (m, 5H; Ph), 3.31 (s,
6H; NMe2); 13C NMR (300 MHz, [D6]acetone, 258C): d=174.1 (C=S),
138.6 (i-Ph), 128.7 (m-Ph), 125.9 (p-Ph) , 123.4 (o-Ph), 49.8 (Me)119Sn
NMR (300 MHz, [D6]acetone, 258C, SnMe4): d=À625.6; IR (KBr): n˜ =
3315, 3234, 3120 (s) [u(NH)], 1570 (m) [u(CN)], 1518 (s) [d (NCS)], 833
(w) cmÀ1 [u(CS)]; MS (ESI): m/z (%): 578.9 (90) [Sn(LH)(L)Cl2]+, 542.9
(30) [Sn(L)2Cl]+, 383.9 (15) [Sn(L)Cl2]+; elemental analysis calcd (%)
for C18H24N6S2Cl2Sn: C 33.2, H 4.0, N 12.9, S 9.8, Cl 21.8, Sn 18.2; found:
C 33.5, H 4.2, N 12.7, S 9.5, Cl 21.4, Sn 18.7.
(N-NMe2); IR (KBr): n˜ =3209 (s) [u(NH)], 3051 (w) [u
2873 (w) [u(CHMe)], 1627 (m) [u(CN)], 1535 (s) [d(NCS)], 1443 (m) [das-
(C-HMe)], 1342 (m) [ds (CHPh)]; MS (FAB):
(C-HMe)], 696 (s) cmÀ1 [doop
ACHTUGNTRNEN(UNG CHPh)], 2939,
A
ACHTUNGTRENNUNG
A
E
ACHTUNGTRENNUNG
m/z (%): 355.1 (90) [M]+; elemental analysis calcd (%) for C18H23N6SI3:
C 29.3, H 3.1, N 11.4, S 4.3, I 51.7; found: C 29.7, H 3.2, N 11.6, S 4.7, I
51.7.
5-(2,2-dimethylhydrazono)-1,1-dimethyl-4-phenyl-3-(phenylamino)-4,5-di-
hydro-1H-1,2,4-triazol-1-ium triiodone [C18H23N6][I3] (7) Over a solution
of LH (0.200 g, 1.02 mmol) in methanol (10 mL) was dropped very slowly
a solution of SnI4 (0.321 g, 0.51 mmol) in the same solvent (10 mL). The
orange solution was stirred at room temperature for one hour. The solu-
tion is kept at À248C for two days and the yellow precipitate (S8) formed
is removed by filtration. Slow evaporation of the mother liquor afforded
dark red crystals suitable for X-ray analysis (0.263 g, 73%). 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=8.75 (s, 1H; NH), 7.60–7.54 (m, 4H;
Ph), 7.48–7.46 (d, 3H; Ph), 7.37–7.32 (t, 3H; Ph), 3.61 (s, 6H; Me), 2.08
Acknowledgements
E. Lꢀpez-Torres thanks Cꢆsar J. Pastor from “Servicio Interdepartamen-
tal de Investigaciꢀn” of the UAM for the crystal measurements and
DGICYT for financial support (Project CT2005–07788/BQU).
3022
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 3012 – 3023

Reactivity of Thiosemicarbazides with Redox Active Metal Ions
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Received: July 17, 2008
Published online: January 29, 2009
Chem. Eur. J. 2009, 15, 3012 – 3023
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3023