A library of peralkylated bis-guanidine ligands for use in biomimetic coordination chemistry

Article abstract of DOI:10.1002/ejoc.200500340

A series of bis-guanidine ligands designed for use in biomimetic coordination chemistry has been extended to a library matrix combining unprecedented substitutional flexibility within the guanidyl residues with a wide range of aliphatic and aromatic space

Full text of DOI:10.1002/ejoc.200500340

FULL PAPER
A Library of Peralkylated Bis-guanidine Ligands for Use in Biomimetic
Coordination Chemistry
Sonja Herres-Pawlis,[a] Adam Neuba,[a] Oliver Seewald,[a] Tarimala Seshadri,[a]
Hans Egold,[a] Ulrich Flörke,[a] and Gerald Henkel*[a]
Dedicated to Professor Bernt Krebs
Keywords: Nitrogen donor ligands / Guanidine ligands / Ligand design
A series of bis-guanidine ligands designed for use in biomi-
metic coordination chemistry has been extended to a library
matrix combining unprecedented substitutional flexibility
within the guanidyl residues with a wide range of aliphatic
and aromatic spacers connecting these functionalities. The
underlying protocol can be used with predefined ureas as
well as secondary amines to build up these units by reaction
with phosgene if the ureas are otherwise unavailable. In the
latter case, the resulting urea intermediates do not have to
be isolated as the reaction proceeds further with additional
phosgene to yield a chloroformamidinium chloride which is
transformed into the bis-guanidine functionality by subse-
quent reaction with a suitable primary diamine in the pres-
ence of triethylamine as an auxiliary base. This concept has
been used to synthesise and characterise more then two
dozen different bis-guanidines based on 12 discrete monogu-
anidine units and seven different spacers. These spacers
have been chosen such that the most important phenotypes
have been dealt with and which range from rigid to more
flexible scaffolds. In addition to spacers with no metal-bind-
ing capabilities, other species containing further donor func-
tions such as N-methyldiphenyleneamine or pyridine-2,6-
diyl have also been used. The substitution patterns of the
guanidine residues can be classified into acyclic and cyclic
types. Among the cyclic types, one subset is characterised by
five- or six-membered heterocycles containing both the
amino nitrogen atoms and another one by individual N-het-
erocyclic systems for each amino nitrogen. Structurally char-
acterised examples are 2-{2-[2-(tetramethylguanidino)-
ethoxy]ethoxy}-1-(tetramethylguanidino)ethane (TMG2doo)
in its diprotonated form and 2,2Ј-bis[2N-(1,1Ј,3,3Ј-tetra-
methylguanidine)]diphenyleneamine (TMG2PA) as well
as N1,N3-bis(dimorpholinomethylene)propane-1,3-diamine
(DMorphG2p) as free bases. For the permethylated bis-
guanidine derivatives, the barrier to rotation around the
(C=N)guanidine bond has been determined by means of tem-
perature-dependent EXSY 1H NMR spectroscopy to range
between 54 and 79 kJmol–1 depending on the type of spacer.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
of the metal ion and consequently merely represent coun-
terions.[5,6] Whilst the application of negatively charged gu-
anidinates has become more widespread in coordination
chemistry, the use of neutral guanidines has not, to date,
received similar attention.[1] Bailey et al. have investigated
the behaviour of monodentate guanidine ligands,[7] whereas
Coles and co-workers introduced bicyclic guanidine systems
into coordination chemistry.[2] These systems are mostly not
peralkylated, but meanwhile, peralkylated phosphorus-[8] or
silicon-bridged[9] bis-guanidine systems have been devel-
oped. Pruszynski[10] Pohl[11] and Sundermeyer[12] and their
co-workers have investigated peralkylated guanidine sys-
tems with organic bridges. Furthermore, Kuhn et al.[13] have
developed imidazoline-based systems that belong to the bis-
guanidine class of ligand.
Guanidines are emerging as a potentially useful class of
ligand owing to their versatile coordination chemistry. Neu-
tral guanidines [(R2N)2C=NR], guanidinates(1–) [(RN)2-
CNR2]– and guanidinates(2–) [(RN)2C=NR]2– are capable
of exhibiting a variety of coordination modes and a range
of donor properties and thus are compatible with a remark-
ably wide range of metal-ion requirements from all parts
of the periodic table.[1–4] Furthermore, numerous complexes
have been reported in which guanidinium cations are pres-
ent but these are not located within the coordination sphere
[a] Fakultät für Naturwissenschaften, Department Chemie, Uni-
versität Paderborn,
Warburger Strasse 100, 33098 Paderborn, Germany
Fax: +49-5251-603423
In guanidine complexes, coordination occurs almost ex-
clusively through the donation of the lone-pair electrons of
E-mail: biohenkel@uni-paderborn.de
Eur. J. Org. Chem. 2005, 4879–4890
DOI: 10.1002/ejoc.200500340
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4879

G. Henkel et al.
FULL PAPER
the Nimine atom to the appropriate acceptor orbitals of the
metal. Such ligands have been successfully used in the stabi-
lisation of different coordination geometries, including lin-
ear,[7,14] trigonal-planar,[2a,c,11] tetrahedral[2c,7,11] and trigo-
nal-bipyramidal[15] species.
Results and Discussion
Ligand Synthesis
The ligands were synthesised following a general pro-
cedure that allows the condensation of almost every ali-
phatic urea with almost every primary amine to form a gua-
nidine compound. This condensation reaction proceeds by
the transformation of the urea component into its corre-
sponding chloroformamidinium chloride, which is some-
times referred to as a Vilsmeier salt.[17e,18]
Conventional chloroformamidinium chlorides can be ob-
tained in good yields by the reaction of specific peralkylated
ureas with phosgene in toluene or acetonitrile.[18] The bio-
mimetic approach requires spatially demanding substituents
on the guanidine moieties because sterically hindered sys-
tems are expected to control the access of substrates to the
oxygen atoms in the corresponding copper–dioxygen com-
plexes. Therefore, a straightforward synthetic protocol
starting with bulky secondary amines has been developed
(Scheme 1).
In our search for bifunctional nitrogen donor ligands
able to stabilise unusually high metal oxidation states, we
became interested in peralkylated guanidyl-type systems.
Bis(tetramethylguanidino)propylene (btmgp) was synthe-
sised as the first member of a series of bifunctional peral-
kylated guanidine ligands designed for use in biomimetic
coordination chemistry.[11,14–20] A great advantage of guani-
dine ligands lies in their stability towards fragmentation re-
actions. We have shown that btmgp-containing copper–di-
oxygen complexes react only with the peripheral substitu-
ents with conservation of the guanidine scaffold[20] in con-
trast to other systems in which dealkylation reactions are
observed.[21] Attempts to modify the guanidine moieties re-
sulted in the successful preparation of bis(dimethylpropyl-
eneguanidino)propylene (DMPG2p), bis(dipiperidylguani-
dino)propylene (DPipG2p)[17] and bis(dimethylethylenegu-
anidino)propylene (DMEG2p).[14] We have recently shown
that copper(i) complexes containing these ligands are able
to react with molecular oxygen under formation of a het-
erocyclic Cu2O2 core at low temperatures.[14,15,20]
By suitable modification of the guanidine substitution
patterns in such complexes, our intention was to redirect
their hydroxylation potential from the ligand to external
substrates such as 2,4-di-tert-butylphenol or methylated
aniline derivatives. As the ligands are bidentate, the reaction
centre should be easily accessible by external substrates and
well suited to substrate pre-coordination. In addition, the
oxygen atom is protected against too fast a reaction with
these substrates by the spatially demanding guanidine moie-
ties resulting in enhanced oxidation selectivities. At this
stage, efficient use of this potential is restricted owing to
a lack of accessible ligands demonstrating that a synthetic
protocol that supports our objectives has to be developed.
For this purpose, we have developed a modular approach
to bis-guanidine compounds that provides a library of bio-
mimetic ligands. This library contains compounds with
complete flexibility in the spacers connecting the guanidine
functionalities as well as in the substitution patterns of the
guanidine moieties. Modification of the spacer allows the
denticity, the bite angle and the coordination geometry to
be varied, whereas modification of the guanidine moieties
allows us to influence directly the σ-donating and π-ac-
cepting properties of the Nimine atom.[14]
Scheme 1. Generation of the chloroformamidinium chlorides.
In order to increase the steric demand of the guanidine
moieties and thus the oxygen-shielding effect in their com-
plexes, we have prepared a series of chloroformamidinium
chlorides from secondary amines containing the required
bulky substituents. By this method, the transformation of
almost every aliphatic secondary amine into the corre-
sponding chloroformamidinium chloride should be pos-
sible. In this paper, we report the synthesis and the charac-
terisation of 25 bis-guanidine ligands for the first time and
describe a new concept in guanidine ligand design.
Scheme 2. Reaction between the chloroformamidinium chloride
and the diamine.
4880
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890

Peralkylated Bis-guanidine Ligands for Use in Biomimetic Coordination Chemistry
FULL PAPER
This one-pot synthesis involves the reaction of two equiv- amine as an auxiliary base leads to the bis-hydrochloride of
alents of a secondary amine with two equivalents of phos- the ligand. The by-product NEt3·HCl was separated by
gene in acetonitrile. In the first reaction step, the alkyl-sub- adding 1 equiv. of NaOH per guanidine functionality and
stituted urea is formed and triethylamine acts as an auxil- removing the resulting NEt3 and the solvent under reduced
iary base by capturing the released HCl (Scheme 1). In the pressure. The hydrochloride was not isolated but deproton-
second step, a further equivalent of phosgene transforms ated by using the two-phase system of MeCN/50% aqueous
this urea into the chloroformamidinium chloride. KOH in order to obtain the pure free base which needs no
Reaction of the mixture containing the chloroformamidin- further purification (Scheme 2).
ium chloride with a diamine in the presence of triethyl-
Table 1 gives an overview of the chloroformamidinium
chlorides prepared in this work. By using these chloro-
formamidinium chlorides, the guanidine moieties shown in
Figure 1 could be synthesised, where Gx denotes the guani-
dine moiety derived from the chloroformamidinium chlo-
ride Vx and RS indicates the connection with the spacer.
The spacers shown in Figure 2 have been used as con-
stituents of the bis-guanidine ligands for several reasons:
the propane-1,3-diyl (p) spacer is a typical aliphatic spacer
with a suitable “bite” for 3d metal coordination,[11,14,16,20]
the flexible 3,6-dioxaoctane-1,8-diyl (doo) spacer offers
more donor functions for metal coordination, whereas the
cyclohexane-1,3-diyl (ch) system is more rigid. The aro-
matic systems diphenyleneamine (PA), N-methyldiphenyl-
eneamine (MePA) and pyridine-2,6-diyl (py) offer a further
N-donor function whilst the m-xylene-α,αЈ-diyl (mX) unit
has a great “bite” and more flexibility than the other spa-
cers.
Table 1. Overview of the chloroformamidinium chlorides R1R2N–
CCl2–NR3R4.[a]
Substituents R1–R4
Chloroformamidinium
chloride
R1, R2, R3, R4: Me
*
*
V1[b]
V2[c]
V3[d]
V4[b]
V5[b]
V6[d]
V7[e]
R1, R2, R3, R4: Et
R1, R2, R3, R4: iPr
R1, R4: Me; R2–R3: –(CH2)2–
R1, R4: Me; R2–R3: –(CH2)3–
R1, R4: nPr; R2–R3: –(CH2)3–
R1–R2, R3–R4: –(CH2)5–
*
*
*
*
R1–R2, R3–R4: –CH(Me)(CH2)3CH(Me)–
R1–R2, R3–R4: –C(Me)2(CH2)3C(Me)2–
R1–R2, R3–R4: –CHNCHCH–
R1–R2, R3–R4: –(CH2)2O(CH2)2–
R1–R2, R3–R4: –(CH2)2S(CH2)2–
V8[d]
V9[d]
V10[d]
V11[d]
V12[d]
*
[a] Reactions starting from the urea are marked with an asterisk.
[b] Ref.[12,14] [c] Ref.[17e] [d] This work. [e] Ref.[18]
Figure 2. Spacer units of the bis-guanidine ligands (G indicates the
position of the attached guanidine moiety).
Figure 1. Guanidine portions of the bis-guanidine ligands.
Eur. J. Org. Chem. 2005, 4879–4890
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4881

G. Henkel et al.
FULL PAPER
Table 2. Overview of the synthesised ligands.
Guanidine moieties
Spacers
PA
p
doo
ch
MePA
mX
py
TMG (G1)
TMG2p[a]
(L1–1)
TMG2doo
(L1–2)
TMG2ch
(L1–3)
TMG2PA
(L1–4)
TMG2MePA
TMG2mX
(L1–6)
TMG2py
(L1–7)
(L1–5)
TEG (G2)
TEG2p
TEG2mX
TEG2py
(L2–1)
(L2–6)
(L2–7)
TiPG (G3)
TiPG2p
(L3–1)
DMEG (G4)
DMPG (G5)
DPPG (G6)
DMEG2p[b]
(L4–1)
DMEG2doo
(L4–2)
DMPG2doo
DMEG2ch
(L4–3)
DMEG2mX
(L4–6)
DMPG2mX
DMEG2py
(L4–7)
DMPG2py
DMPG2p[c]
(L5–1)
DMPG2MePA
(L5–2)
(L5–5)
(L5–6)
(L5–7)
DPPG2p
(L6–1)
DPipG (G7)
DPipG2p[c]
(L7–1)
B(DMPip)G (G8)
B(TMPip)G (G9)
DImG (G10)
DMorphG (G11)
DSMorphG (G12)
B(DMPip)G2p
(L8–1)
B(TMPip)G2p
(L9–1)
DImG2p
(L10–1)
DMorphG2p (L11–1)
DMorphG2doo
(L11–2)
DSMorphG2p (L12–1)
[a] Known in the literature as btmgp, see ref.[11,14,16,20] [b] Ref.[14] [c] Ref.[14,17a,17b]
The modular approach, which is illustrated in Figure 3, of the acetonitrile solution. The results of the structure
allows systematic tuning of the properties of polyguanidine analyses are shown in Figures 4, 5 and 6, while selected
ligands. By combining the different spacers and guanidine bond lengths and angles are collected in Table 3, and pa-
moieties, a library of bis-guanidine ligands could be built rameters relating to data collection and refinement are
up (Table 2).
listed in Table 6.
Table 3. Selected bond lengths and angles of the molecules in
crystals of L1–4, L11–1 and of the ligand cation in crystals of
[H2L1–2]I2·Et2O (average values).
L1–4
L11–1
[H2L1–2]I2·Et2O
Bond lengths [Å]
N=C
1.282
1.365
1.273
1.402
1.349
1.336
Cimine–Namine
Bond angles [°]
Namine–C–Namine
113.6
112.0
120.1
Crystals of L1–4 contain two crystallographically inde-
pendent but otherwise identical molecules. One of them (A)
is shown in Figure 4. The structural features of this aro-
Figure 3. Schematic representation of the variable modules in the
bis-guanidine ligands.
matic guanidine ligand (N=C, 1.281 Å; Cimine–Namine
,
1.365 Å; Nimine–Carom, 1.402 Å) are comparable to those re-
ported for TMGN (N=C, 1.282 Å; Cimine–Namine, 1.384 Å;
Nimine–Carom, 1.399 Å).[12c] The trigonal-planar environ-
Crystal Structures
In order to discuss the structural features of this diverse ment of the nitrogen atom that connects the two phenyl
series of ligands, we chose three crystal structures for a rings is remarkable. The corresponding N–C bonds are
closer look: the structure of L1–4 exhibits properties typical drastically shortened to 1.400 Å which indicates delocali-
of aromatic bis-guanidine ligands whereas L11–1 is a typi- sation of the free amine electron-pair into the phenyl π sys-
cal aliphatic bis-guanidine ligand. Compound [H2L1–2] tem. The phenyl rings are twisted against each other by an
I2·Et2O contains a typical diprotonated bis-guanidine li- angle of 36.7°. The angles between the CN3-guanidine
gand.
plane and the Cimine–Namine–(Calkyl)2-planes within the gua-
Single crystals of [H2L1–2]I2·Et2O were grown by slow nidine moieties have a mean value of 31.9° (individual val-
diffusion of diethyl ether into an acetonitrile solution. Sin- ues range from 22.2 to 38.6°). Furthermore, the N–H group
gle crystals of L1–4 were obtained by slow crystallisation forms a bifurcated hydrogen bridge to the imine nitrogen
at –25 °C whereas L11–1 crystallised by slow evaporation atoms (av. 2.235 Å, corrected for N–H, 1.080 Å).
4882
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890

Peralkylated Bis-guanidine Ligands for Use in Biomimetic Coordination Chemistry
FULL PAPER
graphic inversion centre (Figure 6). The bond lengths are
typical of a protonated guanidine (C=NH+, 1.349(3) Å;
Cimine–Namine av., 1.336 Å; these compare with C=NH+,
1.334 Å and Cimine–Namine, 1.341 Å for [H2btmgp]2+).[11a]
The bond lengths in the guanidine centre are equal. There-
fore, the conjugation is enhanced although the dihedral
angles are diminished only to a small extent (on average
30.8°; individual values range from 29.8 to 31.8°). The io-
dide ions are stabilised by N–H···I hydrogen bonds with
H···I distances of 2.768 Å.
Figure 4. Molecular structure of compound L1–4 (N: random dots;
H···N hydrogen bonds: dashed line).
The molecular structure of L11–1 is depicted in Figure 5.
The molecule lies on a crystallographic two-fold axis that
runs through the centre of the spacer. The geometric pa-
rameters of this ligand (N=C, 1.272 Å; Cimine–Namine
,
1.402 Å) are in good agreement with those of the aliphatic
guanidine ligand DPipG2p (L7–1) (N=C, 1.276 Å; Cimine
–
Namine, 1.399 Å). The guanidine moieties are planar as ex-
pected.[17a] The angles between the CN3 guanidine plane
and the Cimine–Namine–(Calkyl)2 planes are larger (on average
36.0°; individual values range from 29.0 to 42.9°) than those
of L1–4 as steric hindrance forces the NR2 units to twist
around the Cimine–Namine axis.
Figure 6. Molecular structure of [H2L1–2]2+ in crystals of [H2L1–
2]I2·Et2O (N: random dots; O: regular dot pattern; I: cross-hatched;
H···I and H···N hydrogen bonds: dashed lines).
NMR Spectroscopy
The chemical shifts of the dimethylamino groups of the
ligands containing the tetramethylguanidine moiety are
listed in Table 4. The 1H and 13C NMR spectra of the gua-
nidine ligands with aliphatic spacers exhibit two separate
signals for the methyl groups. On heating, these two signals
approach each other and coincide on reaching the coalesc-
ence temperature. Compared with the aliphatic systems de-
scribed above, the aromatic systems exhibit only one signal
for the methyl groups at room temperature. This signal
splits into two resonances of equal intensity if the tempera-
ture is lowered.
This behaviour is caused by a syn–anti exchange typical
of guanidines which has been discussed for selected TMG
systems by Kessler and Leibfritz.[22a] In the case of penta-
substituted guanidines, rotation around the C–NR2 single
Figure 5. Molecular structure of compound L11–1 (N: random
dots; O: regular dot pattern).
The N=C double bonds of this ligand are clearly local- bonds as well as syn–anti isomerisation can take place (Fig-
ised in contrast to the diprotonated form of L1–2 in which ure 7). Rotation around a C–NR2 single bond is too rapid
the double bond is delocalised over the guanidine centre. on the NMR timescale to result in individual resonances
Compound [H2L1–2]I2·Et2O comprises the diprotonated even at low temperatures. This is not the case with the syn–
form of TMG2doo, two iodine anions and a diethyl ether anti exchange which can principally be caused by rotation
molecule. The centroid of the cation lies on a crystallo- around the C=N bond or by inversion.[22a]
Eur. J. Org. Chem. 2005, 4879–4890
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4883

G. Henkel et al.
FULL PAPER
Table 4. NMR spectroscopic shifts of the NMe2 groups at 298 K.
δ [ppm]
1H
13C
btmgp (L1–1)
2.56, 2.65
2.94, 3.02
2.51, 2.60
2.95, 3.09
2.42, 2.49
2.68
38.6, 39.4[a]
40.1, 40.5[a]
38.6, 39.5
40.0, 40.4
39.1, 39.6
38.6
H2btmgpCl2 (H2L1–1Cl2)
TMG2doo (L1–2)
H2TMG2dooI2 (H2L1–2I2)
TMG2ch (L1–3)
TMG2PA (L1–4)
TMG2MePA (L1–5)
TMG2mX (L1–6)
TMG2py (L1–7)
TMGN
2.58
2.65
39.9
38.7
2.73
39.9
2.65[b]
39.4[b]
H2TMGN(PF6)2
2.95[b]
41.6[b]
[a] Ref.[11a] [b] Ref.[12c]
Figure 8. Eyring plot (293–318 K) for syn–anti exchange in
TMG2doo (L1–2).
Figure 7. Rotation around the C=N double bond in tetramethyl-
guanidino molecules.
The coalescence behaviour of selected guanidine ligands
was investigated by EXSY 1H NMR spectroscopy. The kin-
etic data were determined from the resulting Eyring plots
(Figures 8 and 9 and Table 5).
Table 5 clearly shows that aromatic tetramethylguani-
dines have lower activation barriers for the syn–anti ex-
change than aliphatic ones. Our findings are thus in accord-
ance with data for related systems reported in the litera-
ture.[12c,22a] In aromatic systems like TMG2PA and TMGN,
the C=N bond is weakened as a result of conjugation with
Figure 9. Eyring plot (213–233 K) for syn–anti exchange in
TMG2PA (L1–4).
the adjacent aromatic system resulting in lower energy bar- case of btmgp and TMG2doo, an inversion mechanism ap-
riers. In contrast, in aliphatic systems like btmgp, pears to be unlikely owing to the restrictions introduced by
TMG2doo or [Bz2TMG]+, which lack these effects, the free the second guanidyl function attached to the same linker.
enthalpies of activation have to be considerably higher. The This means that rotation takes place that is facilitated if we
free enthalpies of activation of btmgp and TMG2doo are in go from smaller to larger alkyl chains. With this in mind
good agreement with the values reported for simple alkyl- and taking the data for comparable monoguanidine mole-
substituted guanidines like pentamethylguanidine (TMG- cules into account, which are nearly identical,[22a] a unique
CH3) and tetramethyl-ethyl- or tetramethyl-propyl-guani- rotational mechanism for all these systems can be pos-
dine (TMG-C2H5 and TMG-C3H7, respectively). In the tulated.
Table 5. Coalescence parameters of syn–anti isomerisation.
Solvent
Tc [K]
ΔH‡ [kJmol–1]
ΔS‡ [Jmol–1 K–1]
ΔG0‡ [kJmol–1]
btmgp (L1–1)
TMG2doo (L1–2)
TMG2PA (L1–4)
TMG2MePA (L1–5)
TMG2py (L1–7)
TMGN
[D6]DMSO
[D6]DMSO
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CDCl3/CS2
CDCl3
375
348
267
242
92.4 1.5
77.0 0.8
41.5 2.3
46.2 0.8
21.8 0.3
–40.9 2.7
78.6 1.7
70.5 0.9
53.7 3.0
[a]
–
–
[a]
229
253[b]
238[c]
276[d]
346[c]
338[c]
326[c]
53.4[b]
48.3[b]
50.7[c]
61.1[d]
78.2[c]
76.2[c]
73.2[c]
TMGPh
[Bz2TMG]+
TMG-CH3
TMG-C2H5
TMG-C3H7
CDCl3
CDCl3
CDCl3
[a] Temperature range limited by solvent (Tmin = 183 K). [b] Ref.[12c] [c] Ref.[22a] [d] Ref.[22b]
4884 © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890

Peralkylated Bis-guanidine Ligands for Use in Biomimetic Coordination Chemistry
FULL PAPER
niques. Solvents were purified according to literature procedures
and stored under nitrogen. Triethylamine and 1,3-diaminopropane
were used as purchased from Fluka. The chloroformamidinium
chlorides V1, V2, V4, V5 and V7 were prepared according to litera-
ture procedures.[12,14,17e,18]
The inductive effect of homoaromatic neighbourhoods
can be enhanced by using a more electron-rich system like
pyridine, as has been observed for TMG2py (Tc = 229 K).
The aromatic ligand TMG2MePA exhibits coalescence of
the methyl singlets at 242 K. A similar value was found for
TMGPh (Tc = 238 K)[22a] whereas the methyl signal of the
TMG2PA molecule splits into two components below
267 K. This temperature is remarkably high in comparison
with those reported for other aromatic systems like TMGN
(253 K).[12c] Additionally, TMG2PA has a negative acti-
vation entropy for the rotation around the C=N bond indi-
cating that hydrogen bonds participate in the exchange
mechanism (Figure 4). It is assumed that the bifurcated hy-
drogen bond between the amino hydrogen atom and the
two guanidine nitrogen atoms stabilises the conformation
observed in the crystal resulting in a raised activation bar-
rier of rotation and thus in a higher coalescence tempera-
ture.
Physical Measurements: Spectra were recorded with the following
spectrometers: NMR: Bruker AMX 300 and Avance 500. The
NMR signals were referenced to residual solvents measured relative
to TMS. IR: Nicolet P510. UV: Perkin-Elmer Lambda 45. MS (EI,
70 eV): Saturn 2. Elemental analyses: Perkin-Elmer analysator
Model 2400.
Crystal Structure Determinations: Data were collected with a
Bruker AXS SMART APEX CCD diffractometer, Mo-Kα radia-
tion with graphite monochromator at T = 120(2) K, absorption
corrections by multiscans (SADABS[23]); structures were solved by
direct methods[23] and subsequent Fourier difference maps. Full-
[23]
matrix least-squares refinement on F²
with all but hydrogen
atoms refined anisotropically; hydrogen atoms were located from
difference Fourier maps and refined at idealized positions assuming
“riding” modes and U(H) = 1.2Uiso(C) or 1.5Uiso(C-methyl). Perti-
nent crystal and refinement data are given in Table 6.
Conclusions
CCDC-237479 (for L1–4), CCDC-275934 (for L11–1) and CCDC-
275935 (for [H2L1–2]I2·Et2O) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
The assembly of bis-guanidine molecules starting from
secondary amines and phosgene for use in biomimetic coor-
dination chemistry, especially in the field of copper-con-
trolled oxygen activation, has provided a set of bifunctional
N-donor ligands. Each member of this series is expected
to redefine the redox capabilities of its corresponding CuI
complexes towards molecular oxygen in a specific fashion
depending on the spatial demands of the guanidine func-
tionalities as well as on the conformational freedom pos-
sible within the steric limits allowed by the spacer fragments
connecting these units.
In contrast to established literature procedures, our
method to arrive at bis-guanidine molecules is not depend-
ent on predefined peralkylated urea precursors as we start
from secondary amines as simple building blocks and thus
define the urea intermediates by simply choosing suitably
substituted starting materials. The synthetic protocol has
been optimised to obtain overall yields in the range of 65–
95%. This modular approach allows universal modification
of the aliphatic guanidine substitution pattern as well as of
the spacers with respect to rigidity, extension of the back-
bone and additional donor functions.
The bis-guanidine molecules described here are currently
used as ligands with CuI with the aim being to activate mol-
ecular oxygen for the selective catalytic oxidation of organic
substrates. The possibility of controlling oxidation selectiv-
ity by peripheral modifications is a particularly attractive
feature of this ligand design. In general, such a matrix of
bis-guanidine ligands can also be screened for their ability
to stabilise complexes of other transition metals in un-
usually high oxidation states.
1
EXSY H NMR Measurements: Variable-temperature EXSY spec-
tra of compounds L1–1, L1–2 and L1–4 were recorded with the
pulse program noesygpph from Bruker’s pulse program library. The
mixing time τm was optimised according to literature procedures[22c]
and amounted to 200 ms. As the observed exchange process of the
methyl groups is a simple two-side case with equal populations and
uncoupled spins the exchange rate constant has been calculated[22c]
from the integrals of the diagonal- and cross-peaks: k = (τm–1)ln[(r
+ 1)/(r – 1)], where r = (ID1 + ID2)/(IC1 + IC2) and ID1, ID2 are the
integrals of the diagonal-peaks and IC1, IC2 are the integrals of the
cross-peaks.
Preparation of Compounds: CAUTION! Phosgene is a severe toxic
agent that can cause pulmonary embolism and in the case of heavy
exposure may be lethal. Use only in a well-ventilated fume hood.
N,N,NЈ,NЈ-Tetraisopropylchloroformamidinium Chloride (V3): In a
Schlenk flask fitted with a condenser cooled to –40 °C, phosgene
was passed through a solution of diisopropylamine (0.2 mol, 20.2 g,
14.5 mL) and NEt3 (0.2 mol, 20.2 g, 27.9 mL) in dry MeCN
(200 mL) at 0 °C (attention: highly exothermic) for 15 min. The
urea was formed immediately, but the solution could not be stirred
owing to its high viscosity. After 30 min, the reaction mixture was
allowed to warm to room temperature and was stirred again. Then
the mixture was heated at 40 °C for 40 h. After the mixture had
cooled to room temperature, the solvent was evaporated under re-
duced pressure in order to obtain the product with NEt3·HCl as a
by-product as a colourless wax; yield about 80% (22.6 g).
N,NЈ-Dipropyl-N,NЈ-propyleneurea: Based on
a literature pro-
cedure,[19] N,NЈ-trimethyleneurea (Fluka, 0.05 mol, 5 g) in freshly
distilled dioxane (200 mL) was treated with NaH (0.11 mol, 2.64 g).
The reaction mixture was refluxed for 16 h and then cooled to
room temperature. After the addition of propyl iodide (0.2 mol,
34.0 g, 59.2 mL), the reaction mixture was refluxed for another 16 h
and filtered to remove precipitated NaI. After evaporation of the
solvent, vacuum distillation of the residual oil yielded the product
as a yellow oil in a yield of about 60% (5.5 g). 1H NMR (500 MHz,
Experimental Section
Materials and Methods: All manipulations were performed under
nitrogen (99,996%) dried with P4O10 granulate using Schlenk tech-
Eur. J. Org. Chem. 2005, 4879–4890
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4885

G. Henkel et al.
FULL PAPER
Table 6. Crystallographic data for L1–4, L11–1 and [H2L1–2]I2·Et2O.
L1–4
L11–1
[H2L1–2]I2·Et2O
Empirical formula
Mr
C22H33N7
395.5
C21H38N6O4
438.6
C20H48I2N6O3
674.4
Crystal size [mm]
0.30×0.15×0.12
monoclinic
P21/n
18.577(4)
13.218(3)
20.144(4)
113.24(3)
4545(2)
8
0.40×0.38×0.28
monoclinic
C2/c
16.4003(11)
8.2314(4)
16.6413(9)
92.310(2)
2244.7(2)
4
0.30×0.28×0.06
monoclinic
P21/n
8.1966(4)
14.0360(7)
12.3715(6)
93.983(1)
1419.9(1)
2
Crystal system
Space group
a [Å]
b [Å]
c [Å]
β [°]
V [ų]
Z
[gcm–³]
1.156
1.298
1.578
calcd.
F(000)
Θ range [°]
Reflections collected
Reflections unique
Variables
1712
1.3–28.3
24735
10255
539
952
2.4–28.2
13601
2771
145
680
2.2–28.3
12043
3515
153
R1 [I Ͼ 2σ(I)]
wR2 (all data)
Min/max ΔF [eÅ–³]
0.055
0.119
–0.19/0.17
0.038
0.107
–0.18/0.34
0.027
0.074
–0.40/1.19
CDCl3, 25 °C): δ = 0.83 (t, 6 H, CH3), 1.50 (m, 4 H, CH2), 1.89 a solution of 1,1Ј-carbonyl-diimidazole (Fluka, 154 mmol, 25 g) in
(m, 2 H, CH2), 3.23 (m, 8 H, CH2) ppm. 13C NMR (125 MHz,
dry MeCN (300 mL) for 15 min. The reaction mixture was stirred
CDCl3, 25 °C): δ = 11.2 (CH3), 21.0 (CH2), 22.5 (CH2), 45.7 (CH2), for 2 h at room temperature and for another 30 h at 40 °C. The
49.7 (CH2), 155.9 (Cquat) ppm.
mixture was then cooled to room temperature and the excess phos-
gene and MeCN were evaporated under reduced pressure. The yel-
low residue was dried in vacuo; yield: 80% (26.7 g).
N,NЈ-Dipropyl-N,NЈ-propylenechloroformamidinium Chloride (V6):
In a Schlenk flask fitted with a condenser cooled to –30 °C, phos-
gene was passed at 0 °C through a solution of N,NЈ-dipropyl-N,NЈ-
propyleneurea (90 mmol, 16.6 g) in dry toluene (150 mL) for
20 min. The reaction mixture was stirred for 2 h at room tempera-
ture and for another 80 h at 40 °C. Afterwards the mixture was
cooled to room temperature and the toluene was decanted. The
residual orange oil was washed with dry diethyl ether and dried in
vacuo; yield: 80% (17.2 g).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 0.86 (t, 6 H, CH3), 1.65
(m, 4 H, CH2), 2.19 (m, 2 H, CH2), 3.62 (t, 4 H, CH2), 3.87 (t, 4
H, CH2) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 10.8
(CH3), 19.6 (CH2), 20.7 (CH2), 49.5 (CH2), 57.7 (CH2), 151.1
(Cquat) ppm.
Chloroformamidinium Chloride V11: In a Schlenk flask fitted with
a condenser cooled to –40 °C, phosgene was passed through a solu-
tion of morpholine (0.2 mol, 17.4 g, 17.5 mL) and NEt3 (0.2 mol,
20.2 g, 27.9 mL) in dry MeCN (250 mL) at 0 °C (attention: highly
exothermic) for 15 min. The urea was formed immediately, but the
solution could not be stirred owing to its high viscosity. After
30 min, the reaction mixture was allowed to warm to room tem-
perature and it was then stirred again. The mixture was heated at
40 °C for 50 h. The mixture was then cooled to room temperature
and the solvent was evaporated under reduced pressure in order to
obtain the product as a yellow oil in a yield of about 70% (17.9 g)
together with NEt3·HCl as a by-product.
Chloroformamidinium Chloride V12: In a Schlenk flask fitted with
a condenser cooled to –40 °C, phosgene was passed through a solu-
tion of thiomorpholine (0.049 mol, 5 g) and NEt3 (0.097 mol, 9.7 g,
13.4 mL) in dry MeCN (150 mL) at 0 °C for 15 min. After 30 min,
the reaction mixture was allowed to warm to room temperature
and heated at 40 °C for 50 h. The mixture was then cooled to room
temperature and the solvent was evaporated under reduced pres-
sure in order to obtain the product as a yellow powder in a yield
of about 45% (3.2 g) as well as NEt3·HCl.
Chloroformamidinium Chloride V8: In a Schlenk flask fitted with a
condenser cooled to –30 °C, phosgene was passed through a solu-
tion of cis-2,6-dimethylpiperidine (0.1 mol, 11.3 g, 9.3 mL) and
NEt3 (0.1 mol, 10.1 g, 14.0 mL) in dry MeCN (200 mL) at 0 °C for
15 min. After 30 min, the reaction mixture was allowed to warm to
room temperature and heated at 40 °C for 36 h. The mixture was
then cooled to room temperature and the solvent was evaporated
under reduced pressure in order to obtain the product as a colour-
less powder in a yield of about 65% (9.9 g) as well as NEt3·HCl.
General Synthesis of Bis-guanidine Ligands from Chloroformamidin-
ium Chlorides V1, V2, V4–V7 and V10: A solution of the chloro-
formamidinium chloride (40 mmol) in dry MeCN (60 mL) was
added dropwise under vigorous stirring to an ice-cooled solution
of a diamine (20 mmol) and triethylamine (5.57 mL, 4.04 g,
40 mmol) in dry MeCN (30 mL). After 3 h at reflux, a solution of
NaOH (1.6 g, 40 mmol) in water was added. The solvent and NEt3
were then evaporated under vacuum. In order to deprotonate the
bis-hydrochloride, 50 wt.-% KOH (aq,, 25 mL) was added and the
free base was extracted into the MeCN phase (3×25 mL). The or-
ganic phase was dried with Na2SO4 over charcoal. After filtration
through Celite®, the solvent was evaporated under reduced pres-
sure.
Chloroformamidinium Chloride V9: In a Schlenk flask fitted with a
condenser cooled to –30 °C, phosgene was passed through a solu-
tion of 2,2,6,6-tetramethylpiperidine (0.1 mol, 14.1 g, 11.7 mL) and
NEt3 (0.1 mol, 10.1 g, 14.0 mL) in dry MeCN (200 mL) at 0 °C for
15 min. After 30 min, the reaction mixture was allowed to warm to
room temperature and then heated at 40 °C for 50 h. The mixture
was then cooled to room temperature and the solvent was evapo-
rated under reduced pressure in order to obtain the product as
yellow powder in a yield of about 57% (10.3 g) as well as
NEt3·HCl.
Chloroformamidinium Chloride V10: In a Schlenk flask fitted with
a condenser cooled to –30 °C, phosgene was passed at 0 °C through
4886
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890

Peralkylated Bis-guanidine Ligands for Use in Biomimetic Coordination Chemistry
FULL PAPER
General Synthesis of Bis-guanidine Ligands from Chloroformamidin-
ium Chlorides V3, V8, V9, V11, V12: The reaction mixture contain-
ing the chloroformamidinium chloride (40 mmol) in dry MeCN
(60 mL) was added dropwise under vigorous stirring to an ice-co-
oled solution of a diamine (20 mmol) and triethylamine (5.57 mL,
4.04 g, 40 mmol) in dry MeCN (30 mL). After 3 h at reflux, a solu-
tion of NaOH (4.8 g, 120 mmol) in water was added. The solvent
and NEt3 were then evaporated under vacuum. In order to depro-
tonate the bis-hydrochloride, 50 wt.-% KOH (aq. 25 mL) was added
and the free base was extracted into the MeCN phase (3×25 mL).
The organic phase was dried with Na2SO4 over charcoal. After
filtration through Celite®, the solvent was evaporated under re-
duced pressure.
C16H34N6: C 61.88, H 11.04, N 27.08; found C 61.72, H 11.38, N
26.90.
Bis[2-(1,1,3,3-tetramethylguanidino)phenyl]amine, TMG2PA (L1–4):
Off-white powder, after recrystallisation colourless needles, yield:
1
81% (6.4 g), m.p. = 128 °C. H NMR (300 MHz, CDCl3, 25 °C): δ
3
4
= 2.68 (s, 24 H, CH3), 6.53 (dd, J = 7.72, J = 1.5 Hz, 2 H), 6.71
3
4
3
4
(dt, J = 7.60, J = 1.5 Hz, 2 H), 6.82 (dt, J = 7.70, J = 1.5 Hz,
2 H), 6.95 (s, 1 H, N–H), 7.37 (dd, 3J = 7.70, 4J = 1.6 Hz, 2
1
H) ppm. H NMR (300 MHz, CD3CN, 25 °C): δ = 2.64 (s, 24 H,
CH3), 6.44 (dd, J = 7.6, J = 1.3 Hz, 2 H), 6.67 (dt, J = 7.60, J
= 1.3 Hz, 2 H), 6.77 (dt, J = 7.60, J = 1.3 Hz, 2 H), 7.24 (s, 1 H,
N–H), 7.30 (dd, 3J = 7.60, 4J = 1.3 Hz, 2 H) ppm. 13C NMR
(75 MHz, CD3CN, 25 °C): δ = 38.6 (CH3), 112.8, 116.9, 119.9,
3
4
3
4
3
4
120.0, 135.5, 140.4, 159.4 (Cgua) ppm. IR (KBr): ν = 3302 (w) (N–
˜
1-(1,1,3,3-Tetramethylguanidino)-2-{2-[2-(1,1,3,3-tetramethylguani-
dino)ethoxy]ethoxy}ethane, TMG2doo (L1–2): Colourless oil, yield:
96% (6.6 g). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 2.51 (s, 12
H, CH3), 2.60 (s, 12 H, CH3), 3.19 (t, 3J = 6.9 Hz, 4 H, CH2), 3.44
(t, 3J = 6.9 Hz, 4 H, CH2), 3.51 (s, 4 H, CH2) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 38.6 (CH3), 39.5 (CH3), 49.4 (CH2),
70.2 (CH2), 73.3 (CH2), 160.8 (Cgua) ppm. IR (film between NaCl
H), 3062 (w), 3033 (w), 2993 (w), 2941 (m), 2916 (m), 2873 (m),
2841 (m), 2808 (w), 2789 (w), 1597 (vs) (C=N), 1591 (vs) (C=N),
1570 (vs) (C=N), 1565 (vs) (C=N), 1512 (vs) (C=N), 1508 (vs)
(C=N), 1483 (s), 1437 (m), 1419 (s), 1379 (vs), 1338 (m), 1265 (m),
1230 (m), 1215 (m), 1140 (s), 1111 (m), 1062 (w), 1051 (w), 1034
(w), 1020 (s), 922 (w), 911 (w), 852 (w), 777 (m), 731 (s), 710 (w),
654 (w), 619 (w), 552 (w) cm–1. UV/Vis {CH2Cl2, λmax (ε/m–1 cm–1):
242 (13900), 323 nm (10100). EI-MS [CH2Cl2]: m/z (%) = 350 (100)
[M – 45]+, 305 (10) [M – 90]+, 58 (18) [CH2NMe2]+. Elemental
analysis (M = 395.3 gmol–1): calcd. for C22H33N7: C 66.80, H, 8.41,
N 24.79; found C 66.45, H 8.74, N 24.40.
plates): ν = 2995 (w), 2868 (vs), 2800 (w), 1619 (vs) (C=N), 1496
˜
(m) (C=N), 1452 (m) (C=N), 1367 (vs), 1299 (w), 1236 (m), 1137
(s) (C–O–C), 1064 (m) (C–O–C), 991 (w) cm–1. EI-MS: m/z (%) =
344.4 (1) [M]+, 300 (5) [M – NMe2]+, 230 (2) [M – (NMe2)2CN]+,
186 (7) [M
– – NMe2,
(NMe2)2CN(CH2)2O]+, 173 (8) [M
NC(NMe2)2]+, 141 (71) [M – (NMe2)2CN(CH2)2O]+, 129 (44) [M –
{NMe2NCH3CN(CH2)2O(CH2)2}]+, 114 (6) [M – (NMe2)2CN-
(CH2)2O(CH2)2]+, 100 (17) [M – (NMe2)2CN(CH2)2O(CH2)2-
N]+, 85 (100) [M – (NMe2)2CN(CH2)2O(CH2)2N, CH3]+, 71 (17)
[M – (NMe2)2CN(CH2)2O(CH2)2, NMe2]+. Elemental analysis (M
= 344.3 gmol–1): calcd. for C16H36N6O2: C 55.77, H 10.54, N 24.40;
found C 55.54, H 10.89, N 24.15.
Methylbis[2-(1,1,3,3-tetramethylguanidino)phenyl]amine,
TMG2-
MePA (L1–5): Dark red-violet powder, yield: 76% (6.2 g), m.p. =
95 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.58 (s, 24 H, CH3),
3.38 (s, 3 H, N–CH3), 6.45 (m, 2 H), 6.75–6.85 (m, 6 H) ppm. 13C
NMR (75 MHz, CD3CN, 25 °C): δ = 39.9 (gua-CH3), 68.3 (CH3),
115.6, 117.8, 120.7, 122.8, 130.6, 131.6, 159.2 (Cgua) ppm. IR
(KBr): ν = 3180 (vw), 2941 (w), 2870 (w), 2793 (w), 1626 (vs)
˜
(C=N), 1552 (vs) (C=N), 1504 (m), 1473 (m), 1458 (m), 1438 (m),
1414 (m), 1402 (m), 1308 (m), 1254 (w), 1227 (w), 1165 (m), 1127
(vs), 1065 (m), 1036 (m), 906 (w), 877 (w), 849 (w), 762 (m), 747
(m), 619 (m), 503 (w) cm–1. UV/Vis (CH2Cl2) λmax (ε/m–1 cm–1): 260
(12900), 322 (4300), 517 nm (450). EI-MS [CH2Cl2]: m/z (%) = 409
(100) [M]+, 364 (70) [M – 45]+, 319 (52) [M – 90]+, 58 (75)
[H2TMG2doo]I2·Et2O ([H2L1–2]I2·Et2O): Compound L1–2
(688 mg, 2 mmol) was dissolved in THF (10 mL) and added to a
suspension of ammonium iodide (576 mg, 4 mmol) in THF
(10 mL). The reaction mixture was refluxed for 2 h and the solvent
removed under reduced pressure. The resulting precipitate was dis-
solved in acetonitrile (15 mL) and filtered. Diethyl ether was added
to the colourless filtrate by vapour diffusion to form [H2L1–2]-
I2·Et2O as colourless needles; yield: 90% (1.08 g).
[CH2NMe2]+, 44 (33) [NMe2]+. Elemental analysis (M
=
409.3 gmol–1): calcd. for C23H35N7: C 67.45, H 8.61, N 21.94;
found C 67.84, H 8.88, N 21.85.
1H NMR (500 MHz, CD3CN, 25 °C): δ = 2.95 (s, 12 H, CH3), 3.09
α,αЈ-Bis(1,1,3,3-tetramethylguanidino)-m-xylene, TMG2mX (L1–6):
Colourless oil, yield: 96% (6.4 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 2.65 (s, 24 H, CH3), 4.40 (s, 4 H, CH2), 7.13 (m, 3 H,
CH), 7.28 (s, 1 H, CH) ppm. 13C NMR (125 MHz, CDCl3, 25 °C):
δ = 38.7 (CH3), 52.9 (CH2), 124.4 (CH), 125.7 (CH), 127.4 (CH),
3
(s, 12 H, CH3), 3.37 (t, J = 5.2 Hz, 4 H, CH2), 3.61 (s, 4 H, CH2),
3
3.78 (t, J = 5.2 Hz, 4 H, CH2), 8.8 (v br.s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 40.0 (CH3), 40.4 (CH3), 45.3 (CH2),
69.4 (CH2), 70.4 (CH2), 162.2 (Cgua) ppm. IR (KBr): ν = 3456 (m),
˜
3178 (m), 2943 (w), 2858 (w), 1620 (vs) (C=N), 1584 (vs) (C=N),
1462 (m), 1450 (m), 1404 (s), 1315 (w), 1173 (w), 1135 (m), 1115
(m), 1092 (m), 889 (w) cm–1. Elemental analysis (M = 600.1 gmol–1,
after drying in vacuo): calcd. for C16H38N6O2I2: C 31.99, H 6.38,
N 14.00; found C 32.19, H 6.23, N 13.93.
143.0 (Cquat), 160.1 (Cgua) ppm. IR (film between NaCl plates): ν
˜
= 2996 (w), 2925 (m), 2884 (m), 2796 (w), 1554 (vs) (C=N), 1457
(m), 1423 (m), 1390 (s), 1346 (w), 1238 (w), 1155 (m), 1108 (w),
1062 (w), 1031 (w) cm–1. EI-MS: m/z (%) = 332.4 (42) [M]+, 279
(11), 234 (12) [M – C(NMe2)2 + 2H]+, 213 (28), 175 (18), 149 (42),
116 (31), 105 (68) [CH2–Ph–CH2 + 1]+, 91 (13) [C7H7]+, 85 (82),
72 (80), 57 (59). Elemental analysis (M = 332.3 gmol–1): calcd. for
C18H32N6: C 65.01, H 9.71, N 25.29; found C 64.92, H 10.06, N
25.02.
1,3-Bis(1,1,3,3-tetramethylguanidino)cyclohexane, TMG2ch (L1–3):
Colourless oil, yield: 95% (5.9 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.0–1.6 (m, 8 H, CH2 from ring), 2.42 (s, 12 H, CH3),
2.49 (s, 12 H, CH3), 3.44 (m, 2 H, CH) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 20.0 (CH2), 32.6 (CH2), 33.7 (CH2), 39.1 (CH3), 2,6-Bis(1,1,3,3-tetramethylguanidino)pyridine, TMG2py (L1–7):
39.6 (CH3), 50.7 (CH), 159.2 (Cgua) ppm. IR (film between NaCl
plates): ν = 2993 (m), 2925 (m), 2856 (m), 1618 (vs) (C=N), 1496
Colourless waxy solid, yield: 93% (5.7 g). 1H NMR (500 MHz,
CDCl3, 25 °C): δ = 2.73 (s, 24 H, CH3), 6.30 (d, 3J = 7.48 Hz, 2
˜
3
(vs) (C=N), 1450 (s), 1402 (m), 1363 (m), 1236 (m), 1126 (s), 1056 H), 7.37 (t, J = 7.48 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3,
(w), 1012 (w) cm–1. EI-MS: m/z (%) = 310.3 (49) [M]+, 267 (11) 25 °C): δ = 39.9 (CH3), 107.7 (CH), 138.4 (CH), 158.0 (Cquat), 161.4
[M – N(CH3)2 + H]+, 212 (5), 195 (50), 151 (75), 100 (52), 85 (55),
(Cgua) ppm. IR (KBr): ν = 3062 (m), 2993 (m), 2937 (s), 2871 (s),
˜
71 (100), 57 (22). Elemental analysis (M = 310.3 gmol–1): calcd. for
1604 s (C=N), 1552 (vs) (C=N), 1539 (vs) (C=N), 1411 (vs), 1389
Eur. J. Org. Chem. 2005, 4879–4890
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4887

G. Henkel et al.
FULL PAPER
(vs), 1225 (s), 1213 (s), 1132 (vs), 1058 (m), 1022 (s), 1003 (m), 912 (5), 230 (90) [(iPr2N)2C=NH2 + 2H]+, 215 (19), 175 (9), 149 (11),
(m), 812 (s), 739 (m), 614 (w), 555 (w), 514 (w), 441 (w) cm–1. EI-
114 (20) [(iPr2N)2CH2]+, 112 (18) [(iPr2N)2C]+, 86 (100) [iPr–N–
CH–CH3 + H]+, 41 (76). Elemental analysis (M = 494.5 gmol–1):
MS: m/z (%) = 305.3 (81) [M]+, 290 (9) [M – CH3]+, 261 (11) [M –
NMe2]+, 245 (15), 202 (48), 189 (22), 161 (12), 132 (31), 116 (49) calcd. for C29H62N6: C 70.37, H 12.64, N 16.99; found C 70.16, H
[H2N=CN2(CH3)4]+, 85 (50), 72(100). Elemental analysis (M =
305.3 gmol–1): calcd. for C15H27N7: C 58.97, H 8.91, N 32.11;
found C 58.72, H 9.16, N 32.02.
12.90, N 16.95.
1-(1,3-Dimethylimidazolidin-2-ylideneamino)-2-{2-[2-(1,3-dimethyl-
imidazolidin-2-ylideneamino)ethoxy]ethoxy}ethane,
DMEG2doo
1,3-Bis(1,1,3,3-tetraethylguanidino)propane,
TEG2p
(L2–1):
(L4–2): Colourless oil, yield: 98% (6.6 g). 1H NMR (500 MHz,
CDCl3, 25 °C): δ = 2.77 (s, 6 H, CH3), 2.79 (s, 6 H, CH3), 3.15 (s,
Colourless oil, yield: 97% (7.4 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.00 (s, 24 H, CH3), 1.78 (m, 2 H, CH2), 3.00 (q, 8 H, 8 H, CH2), 3.59 (br., 8 H, CH2), 3.66 (s, 4 H, CH2) ppm. 13C NMR
CH2), 3.12 (q, 8 H, CH2), 3.14 (t, 4 H, CH2) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 12.9 (CH3), 13.6 (CH3), 35.9 (CH2), 49.4 (CH2), 70.5 (CH2), 73.7 (CH2), 157.9 (Cgua) ppm. IR (film
41.3 (CH2CH3), 42.5 (CH2CH3), 48.7 (CH2), 158.0 (Cgua) ppm. IR between NaCl plates): ν = 2915 (w), 2858 (m), 1666 (vs) (C=N),
(125 MHz, CDCl3, 25 °C): δ = 31.5 (CH3), 36.3 (CH3), 47.4 (CH2),
˜
(film between NaCl plates): ν = 2966 (m), 2929 (m), 2870 (m), 1610 1617 (vs) (C=N), 1483 (m), 1441 (m), 1383 (m), 1302 (w), 1122 (s)
˜
(vs) (C=N), 1454 (w), 1400 (m), 1375 (m), 1336 (w), 1300 (w), 1261 (C–O–C), 1023 (m) cm–1. EI-MS: m/z (%) = 340.2 (1) [M]+, 325 (1)
(s), 1219 (w), 1134 (w) cm–1. EI-MS: m/z (%) = 382.4 (73) [M]+,
[M – CH3]+, 184 (4), 140 (9) [CH2CH2N=CN2(CH3)2C2H4]+, 126
353(19) [M – Et]+, 310 (5) [M – NEt2]+, 228 (12) [M – C(NEt2)2]+, (100) [CH2N=CN2(CH3)2C2H4]+, 112 (8), 85 (3). Elemental analy-
205 (62), 198 (57), 142 (51), 113 (100) [CH2N=C(NEt2)2]+, 85 (42), sis (M = 340.3 gmol–1): calcd. for C16H32N6O2: C 56.43, H 9.48,
72 (41) [NEt2]+. Elemental analysis (M = 382.4 gmol–1): calcd. for
C21H46N6: C 65.90, H 12.12, N 21.97; found C 65.61, H 12.37, N
22.02.
N 24.69; found C 56.21, H 9.76, N 24.81.
N1,N3-Bis(1,3-dimethylimidazolidin-2-ylidene)cyclohexane-1,3-di-
amine, DMEG2ch (L4–3): Colourless powder, yield: 93% (5.7 g).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 1.16–1.72 (m, 8 H, CH2
from ring), 2.71 (s, 12 H, CH3), 3.05 (m, 8 H, CH2), 4.05 (m, 2 H,
CH) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 20.0 (CH2),
25.6 (CH2), 35.7 (CH2), 45.1 (CH2), 49.0 (CH3), 53.2 (CH), 155.8
α,αЈ-Bis(1,1,3,3-tetraethylguanidino)-m-xylene, TEG2mX (L2–6):
Colourless oil, yield: 95% (8.4 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.07 (s, 24 H, CH3), 3.10 (q, 8 H, CH2), 3.22 (q, 8 H,
CH2), 4.36 (s, 4 H, CH2), 7.22 (m, 3 H, CH), 7.29 (s, 1 H, CH) ppm.
13C NMR (125 MHz, CDCl3, 25 °C): δ = 13.4 (CH3), 41.4 (benzyl-
(Cgua) ppm. IR (KBr): ν =: 2933 (s), 2852 (s), 1660 (vs) (C=N),
˜
CH2), 42.7 (CH2), 124.9 (CH), 126.5 (CH), 127.6 (CH), 143.3 1637 (vs) (C=N), 1477 (m), 1442 (m), 1410 (m), 1379 (s), 1259 (s),
(Cquat), 159.1 (Cgua) ppm. IR (film between NaCl plates): ν = 2968 1226 (s), 1142 (w), 1119 (w), 1095 (w), 1065 (w), 1032 (s), 991 (m),
˜
(m), 2929 (m), 2870 (m), 1604 (vs) (C=N), 1450 (m), 1403 (m), 1375 953 (s), 908 (m), 877 (m), 850 (m), 766 (w), 719 (m), 669 (w), 642
(m), 1338 (w), 1302 (w), 1261 (s), 1203 (w), 1132 (w), 1068 (w) cm–1.
EI-MS: m/z (%) = 444.4(70) [M]+, 372 (22) [M – NEt2]+, 275 (75)
[M – HN=C(NEt2)2]+, 172 (39) [H2N=C(NEt2)2]+, 119 (31), 105
(75) [CH2–Ph–CH2 + 1]+, 91 (11) [C7H7]+, 72 (100) [NEt2]+. Ele-
mental analysis (M = 444.4 gmol–1): calcd. for C26H48N6: C 70.21,
H 10.89, N 18.91; found C 70.06, H 11.20, N 18.74.
(m), 580 (m), 538 (w), 503 (w) cm–1. EI-MS: m/z (%) = 306.2 (11)
[M]+, 263 (19) [M – NMe2 + H]+, 193 (100) [M – N=CN2(C2H4)
Me2–H]+, 152 (35), 114 (32) [H2N=CN2(C2H4)Me2]+, 98 (29), 70
(23), 55 (15). Elemental analysis (M = 306.2 gmol–1): calcd. for
C16H30N6: C 62.69, H 9.87, N 27.43; found C 62.41, H 10.03, N
27.56.
2,6-Bis(1,1,3,3-tetraethylguanidino)pyridine,
TEG2py
(L2–7):
N1,N3-Bis(1,3-dimethylimidazolidin-2-ylidene)-m-xylylene-α,αЈ-di-
amine, DMEG2mX (L4–6): Colourless oil, yield: 96% (6.3 g). 1H
Colourless oil, yield: 95% (7.9 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.06 (m, 24 H, NCH2CH3), 3.07 (m, 16 H, NCH2CH3), NMR (500 MHz, CDCl3, 25 °C): δ = 2.78 (s, 12 H, CH3), 3.18 (t,
3
3
6.22 (d, J = 7 Hz, 8 Hz, 2 H), 7.22 (t, J = 7 Hz, 8 Hz, 1 H) ppm.
8 H, CH2), 4.67 (s, 4 H, CH2), 7.24 (m, 3 H, CH), 7.39 (s, 1 H,
13C NMR (125 MHz, CDCl3, 25 °C): δ = 12.82 (CH3), 42.66 (CH2), CH) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 31.5 (CH3),
104.99 (CH), 138.48 (CH), 157.90 (Cquat), 159.37 (Cgua) ppm. IR
(film between NaCl plates): ν = 3064 (vw), 2970 (s), 2931 (m), 2871
45.06 (CH2), 49.54 (CH2), 50.89 (CH2), 124.4 (CH), 125.4 (CH),
127.7 (CH), 143.2 (Cquat), 157.7 (Cgua) ppm. IR (film between NaCl
˜
(m), 1556 (vs) (C=N)Gua, 1531 (vs) (C=N)Gua, 1483 (m), 1446 (vs), plates): ν = 2935 (m), 2843 (m), 1655 (vs) (C=N), 1483 (m), 1437
˜
1417 (vs) (C=N)Pyridine, 1377 (s), 1356 (m), 1269 (vs), 1198 (m), (m), 1384 (m), 1350 (w), 1269 (s), 1230 (w), 1199 (w), 1065
1136 (vs), 1057 (vs) cm–1. EI-MS: m/z (%) =417 (8) [M]+, 388 (2)
(w) cm–1. EI-MS: m/z (%) = 328.3 (19) [M]+, 313.2 (8) [M –
[M – Et]+, 345 (1) [M – NEt2]+, 274 (3) [M – 2 NEt2 + H]+, 263 CH3]+, 232.2 (78), 215 (26), 126 (56) [CH2N=C(CH3)2C2H4]+, 114
(52) [M – C(NEt2)2 + 2H]+, 191 (49) [M – C(NEt2)2 – NEt2
+
(100) [H2N=CN2(CH3)2C2H4]+, 112 (60) [N3C5H10]+, 106 (81), 91.1
2H]+, 172 (58) [H2N=C(NEt2)2]+, 163 (52) [M – C(NEt2)2 – NEt2 – (40) [C7H7]+. Elemental analysis (M = 328.3 gmol–1): calcd. for
Et + 3 H]+, 100 (70) [H2N=C(NEt2) – NEt2]+, 72 (100) [NEt2]+, C18H28N6: C 65.81, H 8.60, N 25.60; found C 65.61, H 8.97, N
29 (61) [Et]+. Elemental analysis (M = 417.4 gmol–1): calcd. for
C23H43N7: C 66.13, H 10.38, N 23.49; found C 65.81, H 10.55, N
23.64.
25.42.
N2,N6-Bis(1,3-dimethylimidazolidin-2-ylidene)pyridine-2,6-diamine,
DMEG2py (L4–7): Colourless waxy solid, yield: 92% (5.5 g). 1H
NMR (500 MHz, CDCl3, 25 °C): δ = 2.65 (s, 12 H, CH3), 3.30 (s,
8 H, CH2), 6.23 (d, 3J = 7.7 Hz, 2 H), 7.23 (t, 3J = 7.7 Hz, 1
1,3-Bis(1,1,3,3-tetraisopropylguanidino)propane, TiPG2p (L3–1):
Off-white powder, yield: 81% (8.0 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.23 (d, 24 H, CH3), 1.46 (d, 24 H, CH3), 1.59 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 34.9 (CH3), 48.2
H, CH2), 3.31 (t, 4 H, CH2), 3.40 (m, 4 H, CH), 3.82 (m, 4 H, (CH2), 108.2 (CH), 138.6 (CH), 157.8 (Cquat), 160.9 (Cgua) ppm. IR
CH) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 19.2 (CH3), (KBr): ν = 3161 (w), 3064 (w), 2919 (m), 2852 (m), 1616 (vs)
˜
21.4 (CH3), 31.6 (CH2), 36.7 (CH2), 45.2 (CH), 47.4 (CH), 157.7
(Cgua) ppm. IR (KBr): ν = 2972 (s), 2845 (m), 2774 (m), 2721 (m),
(C=N), 1569 (s) (C=N), 1541 (vs) (C=N), 1429 (s), 1281 (s), 1236
(m), 1193 (w), 1144 (w), 1038 (m), 955 (m), 808 (m), 702 (w), 669
˜
1699 (s), 1622 (vs) (C=N), 1525 (vs), 1473 (s), 1451 (m), 1405 (m), (w), 582 (w) cm–1. EI-MS: m/z (%) = 301.2 (89) [M]+, 300 (100)
1309 (m), 1153 (m), 765 (w) cm–1. EI-MS: m/z (%): = 494.4 (0.1)
[M – H]+, 245 (9), 205 (39) [M – CN2(CH3)2C2H4 + 2H]+, 204 (58)
[M]+, 459 (1) [M – Me]+, 429 (5), 401 (1), 355 (8), 314 (13), 281 [M – CN2(CH3)2C2H4 + H]+, 189 (9), 132 (7), 114 (11), 98 (8)
4888
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890

Peralkylated Bis-guanidine Ligands for Use in Biomimetic Coordination Chemistry
FULL PAPER
[N=CN2(CH3)2C2H4]+, 70 (29). Elemental analysis (M = (28), 112 (25) [N=CN2(CH3)2C3H6]+, 109 (19), 70 (11). Elemental
301.2 g mol–1): calcd. for C15H23N7: C 59.76, H 7.70, N 32.54;
found C 59.49, H 7.91, N 32.60.
analysis (M = 329.2 gmol–1): calcd. for C17H27N7: C 61.96, H 8.27,
N 29.77; found C 61.65, H 8.42, N 29.93.
2-(2-{2-[Tetrahydro-1,3-dimethylpyrimidin-2(1H)-ylideneamino]-
ethoxy}ethoxy)-N-[tetrahydro-1,3-dimethylpyrimidin-2(1H)-ylidene-
amino]ethanamine, DMPG2doo (L5–2): Colourless oil, yield: 93%
(6.8 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.58 (m, 4 H,
N1,N3-Bis[tetrahydro-1,3-dipropylpyrimidin-2(1H)-ylidene]propane-
1,3-diamine, DPPG2p (L6–1): Yellowish oil, yield: 89% (7.2 g). H
NMR (500 MHz, CDCl3, 25 °C): δ = 0.83 (t, 12 H, CH3), 1.44 (q,
1
2 H, CH2), 1.56 (m, 8 H, CH2), 1.91 (m, 4 H, CH2), 3.19 (m, 20
CH2), 1.88 (m, 8 H, CH2), 2.85 (s, 12 H, CH3), 3.20 (t, 4 H, CH2), H, CH2) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 11.6
3.54 (br., 8 H, CH2) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ (CH3), 21.3 (CH2), 22.7 (CH2), 46.1 (CH2), 49.9 (CH2), 53.7 (CH2),
= 21.6 (CH2), 38.4 (CH3), 39.1 (CH3), 48.1 (CH2), 49.6 (CH2), 70.5 158.0 (Cgua) ppm. IR (film between NaCl plates): ν = 2960 (s), 2931
˜
(CH2), 73.9 (CH2), 160.1 (Cgua) ppm. IR (film between NaCl
plates): ν = 2925 (w), 2865 (m), 1635 (vs) (C=N), 1620 (vs) (C=N),
(m), 2871 (m), 1633 (vs) (C=N), 1604 (vs) (C=N), 1500 (m), 1456
(m), 1363 (m), 1325 (w), 1296 (m), 1263 (w), 1207 (s), 1099
˜
1558 (m), 1541 (s), 1458 (m), 1386 (m), 1309 (w), 1261 (m), 1101 (m) cm–1. EI-MS: m/z (%) = 406.4 (9) [M]+, 391 (1) [M – Me]+, 363
(s) (C–O–C), 1045 (m) (C–O–C), 850 (w), 742 (w), 627 (s) cm–1.
(1) [M – Pr]+, 240 (10), 211 (15), 184 (28) [H2N=CN2Pr2C3H6]+,
155 (100), 113 (38), 70 (32), 98.1 (29), 70.0 (23), 55.1 (14.5). Ele-
EI-MS: m/z (%) = 368.4 (1) [M]+, 266 (21), 205 (8), 152 (9), 173
(8) [M – NMe2, NC{N(CH3)2}2]+, 141 (65) [M – {N(CH3)2}2- mental analysis (M = 406.4 gmol–1): calcd. for C23H46N6: C 67.92,
CN(CH2)2O]+, 128 (100) [H2N=CN2(CH3)2C3H6]+, 98 (34), 70 H 11.41, N 20.67; found C 67.61, H 11.67, N 20.72.
(48). Elemental analysis (M = 368.3 g mol– 1): calcd. for
N1,N3-Bis[bis(2,6-dimethylpiperidin-1-yl)methylene]propane-1,3-di-
C18H36N6O2: C 58.65, H 9.85, N 22.81; found C 58.42, H 10.16,
N 22.73.
1
amine, B(DMPip)G2p (L8–1): Yellowish oil, yield: 76% (8.2 g). H
NMR (500 MHz, CDCl3, 25 °C): δ = 1.01 (d, 24 H, CH3), 1.53 (m,
N-Methyl-2,2Ј-bis[tetrahydro-1,3-dimethylpyrimidin-2(1H)-ylidene-
amino]diphenyleneamine, DMPG2MePA (L5–5): Dark red-violet
oil, yield: 68% (5.9 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ =
16 H, CH2), 1.61 (m, 2 H, CH2), 1.68 (m, 8 H, CH2), 2.58 (m, 8
H, CH), 2.70 (t, 4 H, CH2) ppm. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 21.5 (CH2), 23.0 (CH3), 24.9 (CH2-Pip), 33.9 (CH2-
6.95 (m, 4 H, CH), 6.7 (m, 4 H, CH), 2.9 (s, 15 H, CH3), 1.9 (m, Pip), 39.8 (CH2), 52.4 (CH), 157.0 (Cgua) ppm. IR (film between
8 H, CH2), 1.65 (m, 4 H, CH2) ppm. 13C NMR (125 MHz,
NaCl plates): ν =: 2958 (s), 2931 (s), 2871 (m), 1693 (vs) (C=N),
˜
CD3CN, 25 °C): δ = 21.1 (CH2), 38.0 (CH3), 48.6 (CH2), 69.1 (N– 1651 (vs) (C=N), 1643 (vs) (C=N), 1537 (s), 1479 (m), 1415 (m),
CH3), 115.2, 117.6, 122.1, 124.6, 136.5 (Cquat), 142.1(Cquat), 153.3 1373 (w), 1311 (m), 1275 (w), 1236 (w), 1159 (m) cm–1. EI-MS:
(Cgua) ppm. IR (KBr): ν = 3065 (w), 3025 (w), 2940 (m), 2869 (m), m/z (%) = 542 (0.01) [M]+, 430 (1) [M – Me2Pip]+, 292 (13) [M –
˜
2345 (w), 1621 (vs) (C=N), 1563 (vs) (C=N), 1546 (vs) (C=N), 1452 N=C(Me2Pip)2]+, 279 (14) [M – CH2N=C(Me2Pip)2 + H]+, 237 (9)
(s), 1417 (s), 1317 (s), 1120 (m), 1052 (m), 746 (s) cm–1. EI-MS
[(Me2Pip)2CH]+, 183 (22), 149 (48), 112 (43) [Me2Pip]+, 98 (100)
[CH2Cl2]: m/z (%) = 433.6 (1) [M]+, 419 (2) [M – 14]+, 323 (5), 285
[CH3CH(CH2)3CHCH3]+, 56 (39). Elemental analysis (M =
(3), 252 (100), 213 (98), 181 (33), 128 (30) [H2N=CN2(CH3)2- 542.5 gmol–1): calcd. for C33H62N6: C 72.99, H 11.52, N 15.49;
C3H6]+, 112 (29), 69 (48), 58 (69). Elemental analysis (M =
433.3 g mol–1): calcd. for C25H35N7: C 69.24, H 8.14, N 22.62;
found C 69.02, H 8.49, N 22.49.
found C 72.64, H 11.75, N 15.61.
N1,N3-Bis[bis(2,2,6,6-tetramethylpiperidin-1-yl)methylene]propane-
1,3-diamine, B(TMPip)G2p (L9–1): Yellow oil, yield: 72% (9.4 g).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 1.05 (s, 48 H, CH3), 1.18
(m, 2 H, CH2), 1.50 (m, 8 H, CH2), 3.17 (t, 16 H, CH2), 3.29 (t, 4
N1,N3-Bis[tetrahydro-1,3-dimethylpyrimidin-2(1H)-ylidene]-m-xylyl-
ene-α,αЈ-diamine, DMPG2mX (L5–6): Colourless oil, yield: 95%
(6.8 g). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 1.83 (q, 4 H, CH2), H, CH2) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 13.2
2.86 (s, 12 H, CH3), 3.07 (t, 8 H, CH2), 4.36 (s, 4 H, CH2), 7.21
(CH3), 13.9 (CH3), 16.3 (CH2), 35.0 (CH2), 40.4 (CH2), 41.1 (CH2),
42.2 (CH2), 56.7 (Cquat), 156.4 (Cgua) ppm. IR (film between NaCl
(m, 3 H, CH), 7.33 (s, 1 H, CH) ppm. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 20.5 (CH2), 39.0 (CH3), 48.3 (CH2), 51.57 (CH2), 124.9 plates): ν = 2970 (s), 2935 (m), 2733 (w), 1645 (vs) (C=N), 1531
˜
(CH), 126.5 (CH), 127.9 (CH), 142.6 (Cquat), 157.6 (Cgua) ppm. IR
(vs) (C=N), 1454 (m), 1379 (s), 1351 (m), 1271 (s), 1223 (m), 1182
(film between NaCl plates): ν = 2635 (m), 2843 (m), 1655 (vs)
(w) cm–1. EI-MS: m/z (%) = 654 (0.01) [M]+, 408 (2), 340 (4), 308
˜
(C=N), 1483 (m), 1437 (m), 1402 (w), 1385 (m), 1350 (w), 1269 (s), (8) [(Me4Pip)2C=NH2]+, 268 (6), 240 (13), 184 (21), 157 (28), 140
1231 (w), 1199 (w), 1065 (w) cm–1. EI-MS: m/z (%) = 356.3 (20)
(11) [Me4Pip]+, 126 (35) [Me4Pip-N]+, 109 (58), 84 (22) [(CH3)2-
C(CH2)3]+, 69 (37) [CH3C(CH2)3]+, 58 (100). Elemental analysis
[M]+, 229 (15), 178 (5), 149 (7), 128 (100) [H2N=CN2(CH3)2-
C3H6]+, 99 (22), 57 (23). Elemental analysis (M = 356.3 gmol–1): (M = 654.6 gmol–1): calcd. for C41H78N6: C 75.16, H 12.01, N
calcd. for C20H32N6: C 67.36, H 9.05, N 23.58; found C 67.12, H
9.41, N 23.47.
12.83; found C 74.91, H 12.37, N 12.72.
N1,N3-Bis[di(1H-imidazol-1-yl)methylene]propane-1,3-diamine,
DImG2p (L10–1): Yellow powder, yield: 58 % (4.2 g). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 1.92 (m, 2 H, CH2), 3.3 (m, 4 H,
=N–CH2-), 7.12 (s, 8 H, =N–CH=CH–N-), 7.71 (s, 4 H, -N–
N2,N6-Bis[tetrahydro-1,3-dimethylpyrimidin-2(1H)-ylidene]pyridine-
2,6-diamine, DMPG2py (L5–7): Colourless waxy solid, yield: 94%
(6.2 g). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 1.90 (m, 4 H,
CH2), 2.78 (s, 6 H, CH3), 2.84 (s, 6 H, CH3), 3.17 (m, 8 H, CH2), CH=N-) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 21.3
3
3
3
5.74 (d, J = 7.7 Hz, 1 H), 5.89 (d, J = 7.7 Hz, 1 H), 7.10 (t, J = (CH2), 40.0 (CH2), 121.9 (CH=CH), 135.1 (CH), 155.2 (Cgua) ppm.
7.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 22.2 IR (KBr): ν = 3122 (m), 3035 (m), 2935 (m), 2843 (m), 2698 (m),
˜
(CH2), 35.6 (CH3), 39.2 (CH3), 47.8 (CH2), 104.7 (CH), 138.5
2607 (m), 1791 (m), 1689 (s), 1652 (vs) (C=N), 1533 (vs) (C=N),
1482 (s), 1442 (vs), 1373 (m), 1324 (s), 1257 (s), 1222 (w), 1197 (w),
1141 (m), 1095 (s), 1064 (s), 1035 m) cm–1. EI-MS: m/z (%) = 362.3
(CH), 157.8 (Cquat), 161.9 (Cgua) ppm. IR (KBr): ν = 3010 (w),
˜
2902 (w), 2856 (w), 1624 (vs) (C=N), 1529 (vs), 1448 (s), 1413 (s),
1317 (s), 1252 (m), 1221 (m), 1157 (w), 1109 (w), 1059 (m), 802 (0.1) [M]+, 212 (10), 179 (21), 151 (22), 123 (35), 116 (24), 68,0
(w), 756 (w), 709 (w), 474 (w) cm–1. EI-MS: m/z (%) = 329.2 (62) (100) [C3H4N2]+. Elemental analysis (M = 362.2 gmol–1): calcd. for
[M]+, 314 (4) [M – CH3]+, 245 (33), 219 (100) [M – CN2(CH3)2- C17H18N10: C 56.33, H 5.01, N 38.66; found C 56.43, H 5.16, N
C3H6 + 2 H]+, 218 (48) [M – CN2(CH3)2C3H6 + H]+, 191 (9), 148 38.41.
Eur. J. Org. Chem. 2005, 4879–4890
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4889

G. Henkel et al.
FULL PAPER
N1,N3-Bis(dimorpholinomethylene)propane-1,3-diamine,
DMorphG2p (L11–1): White powder, after recrystallisation colour-
less needles, yield: 71 % (6.2 g). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 1.75 (q, 2 H, CH2), 3.02–3.38 (br., 18 H, CH2), 3.64–
6.76 (m, 14 H, CH2) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ
[1] P. J. Bailey, S. Pace, Coord. Chem. Rev. 2001, 214, 91–141.
[2] a) S. H. Oakley, D. B. Soria, M. P. Coles, P. B. Hitchcock, J.
Chem. Soc., Dalton Trans. 2004, 537–546; b) S. H. Oakley,
M. P. Coles, P. B. Hitchcock, Inorg. Chem. 2004, 43, 5168–5170;
c) S. H. Oakley, M. P. Coles, P. B. Hitchcock, Inorg. Chem.
2003, 42, 3154–3156.
= 25.58, 44.0, 47.2, 48.5, 157.3 (Cgua) ppm. IR (KBr): ν = 2967
˜
(m), 2898 (m), 2844 (m), 1633 (vs) (C=N), 1600 (vs) (C=N), 1436
(s), 1386 (m), 1357 (m), 1268 (vs), 1228 (m), 1114 (vs) (C–O–C),
1027 (m), 883 (s), 601 (m) cm–1. EI-MS: m/z (%) = 438.3 (6) [M]+,
408 (11) [M – CH2O]+, 393 (12) [M – CH3CH2O]+, 363 (21) [M –
2(CH2O)–(CH3CH2O)]+, 283 (13) [M – C3H6NC(Morph)]+, 254 (6)
[M – C6H6NC(Morph)-(CH2O)]+, 226 (14) [M – CH2NC-
(Morph)2]+, 196 (42) [M – C3H6NC(Morph)2]+, 171 (17) [M –
CNC3H6NC(Morph)2]+, 127 (61) [M – CNC3H6NC(Morph)2-
C3H6]+, 86 (37) [Morph]+. Elemental analysis (M = 438.3 gmol–1):
calcd. for C21H38N6O4: C 57.50, H 8.74, N 19.17; found C 57.31,
H 8.97, N 18.87.
[3] I. Georgieva, N. Mintcheva, N. Trendafilova, M. Mitewa, Vibr.
Spectr. 2001, 27, 153–164.
[4] R. Longhi, R. D. Drago, Inorg. Chem. 1965, 4, 11–14.
[5] C. N. Morimoto, E. C. Lingafelter, Acta Crystallogr., Sect B
1970, 26, 335–337.
[6] T. Kolev, T. Todorov, R. Petrova, Acta Crystallogr., Sect. E
2002, 58, o111–o113.
[7] P. J. Bailey, K. J. Grant, S. Pace, S. Parsons, L. J. Stewart, J.
Chem. Soc., Dalton Trans. 1997, 4263–4266.
[8] J. Münchenberg, A. K. Fischer, H. Thönnesen, P. G. Jones, R.
Schmutzler, J. Organomet. Chem. 1997, 529, 361–374.
[9] S. H. Oakley, M. P. Coles, P. B. Hitchcock, J. Chem. Soc., Dal-
ton Trans. 2004, 1113–1114.
2-{2-[2-(Dimorpholinomethyleneamino)ethoxy]ethoxy}-N-(di-
orpholinomethylene)ethanamine, DMorphG2doo (L11–2): White
powder, after recrystallisation colourless needles, yield: 65% (6.7 g).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 3.1–3.3 (br., 16 H, Morph-
CH2), 3.41 (t, 4 H, CH2, 3.61 (t, 4 H, CH2), 3.66 (s, 4 H, CH2),
3.69 (m, 16 H, Morph-CH2) ppm. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 47.2 (Morph-CH2), 48.3, 66.8 (Morph-CH2), 67.1, 70.5,
[10] P. Pruszynski, K. T. Leffek, B. Borecka, T. S. Cameron, Acta
Crystallogr., Sect. C 1992, 48, 1638–1641.
[11] a) S. Pohl, M. Harmjanz, J. Schneider, W. Saak, G. Henkel,
J. Chem. Soc., Dalton Trans. 2000, 3473–3479; b) S. Pohl, M.
Harmjanz, J. Schneider, W. Saak, G. Henkel, Inorg. Chim. Acta
2000, 311, 106–112.
[12] a) H. Wittmann, V. Raab, A. Schorm, J. Plackmeyer, J. Sun-
dermeyer, Eur. J. Inorg. Chem. 2001, 1937–1948; b) V. Raab, J.
Kipke, O. Burghaus, J. Sundermeyer, Inorg. Chem. 2001, 40,
6964–6971; c) V. Raab, J. Kipke, R. M. Gschwind, J. Sun-
dermeyer, Chem. Eur. J. 2002, 8, 1682–1693.
[13] N. Kuhn, M. Grathwohl, M. Steinmann, G. Henkel, Z. Natur-
forsch., Teil B 1998, 53, 997–1003.
[14] S. Herres-Pawlis, U. Flörke, G. Henkel, Eur. J. Inorg. Chem.
2005, 3815–3824.
[15] S. Herres-Pawlis, T. Seshadri, U. Flörke, G. Henkel, manuscript
in preparation.
[16] H. Wittmann, A. Schorm, J. Sundermeyer, Z. Anorg. Allg.
Chem. 2000, 626, 1583–1590.
163.8 (Cgua) ppm. IR (KBr): ν = 2972 (m), 2893 (s), 2856 (s), 1647
˜
m (C=N), 1621 (vs) (C=N), 1458 (m), 1413 (s), 1390 (s), 1360 (m),
1300 (m), 1265 (vs), 1228 (m), 1115 (vs) (C–O–C), 1070 (m), 1032
(s), 991 (w), 966 (w), 881 (s), 833 (w), 611 (w) cm–1. EI-MS: m/z
(%) = 512.6 (0.1) [M]+, 426 (4) [M – Morph]+, 314 (5) [M –
NC(Morph)2]+, 270 (19) [M – NC(Morph)2-(CH2)2O]+, 226 (18)
[M – NC(Morph)2 – 2(CH2)2O]+, 200 (22) [(Morph)2CNH2]+, 169
(52), 127 (100), 114 (69), 86 (37) [Morph]+, 70 (69) [Morph-O]+.
Elemental analysis (M = 512.3 gmol–1): calcd. for C24H44N6O6: C
56.21, H 8.66, N 16.40; found C 56.10, H 8.87, N 16.64.
[17] a) S. Herres, U. Flörke, G. Henkel, Acta Crystallogr., Sect. C
2004, 60, o358–o360; b) S. Herres, U. Flörke, G. Henkel, Acta
Crystallogr., Sect. C 2004, 60, m659–m660; c) T. Seshadri, U.
Flörke, G. Henkel, Acta Crystallogr., Sect. E 2004, 60, o401–
o402; d) S. Herres-Pawlis, U. Flörke, G. Henkel, Acta Crys-
tallogr., Sect. E 2005, 61, m79–m81; e) S. Herres-Pawlis, U.
Flörke, G. Henkel, Inorg. Chem. Commun. 2005, submitted.
[18] a) H. Eilingsfeld, M. Seefelder, H. Weidinger, Angew. Chem.
1960, 72, 836–845; b) H. Eilingsfeld, G. Neubauer, M. See-
felder, H. Weidinger, Chem. Ber. 1964, 97, 1232–1245; c) W.
Kantlehner, E. Haug, W. W. Mergen, P. Speh, T. Maier, J. J.
Kapassakalidis, H.-J. Bräuner, H. Hagen, Liebigs Ann. Chem.
1984, 1, 108–126.
N1,N3-Bis[bis(thiomorpholino)methylene]propane-1,3-diamine, DS-
MorphG2p (L12–1): Yellowish powder, yield: 66% (6.6 g). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 1.25 (q, 2 H, CH2), 2.65 (m, 16,
CH2), 3.2 (m, 16 H, CH2), 3.4 (t, 4 H, CH2) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 13.5 (CH2), 27.0 (SMorph-CH2),
42.3 (SMorph-CH2), 46.6 (CH2), 158.0 (Cgua) ppm. IR (KBr): ν =
˜
2969 (m), 2911 (m), 1733 (m), 1621 (vs) (C=N), 1533 (s), 1405 (s),
1374 (m), 1292 (m), 1251 (m), 1205 (m), 1170 (m) cm–1. EI-MS:
m/z (%) = 502.1 (23) [M]+, 487 (76), 469 (98) [M – S]+, 443 (45)
[M
– –
SEt]+, 400 (33) [M SMorph]+, 384 (34), 298 (9)
[M – 2SMorph]+, 196 (23) [M – 3SMorph]+, 143 (100) [HN=C–
SMorph]+, 102 (44) [SMorph]+, 87 (38), 69 (30). Elemental analysis
(M = 502.2 gmol–1): calcd. for C21H38N6S4: C 50.18, H 7.63, N
16.73; found C 50.02, H 7.41, N 16.45.
[19] C.-D. Li, S. L. Mella, A. C. Sartorelli, J. Med. Chem. 1981, 24,
1089–1092.
[20] S. Herres, A. J. Heuwing, U. Flörke, J. Schneider, G. Henkel,
Inorg. Chim. Acta 2005, 358, 1089–1096.
[21] E. A. Lewis, W. B. Tolman, Chem. Rev. 2004, 104, 1047–1076.
[22] a) H. Kessler, D. Leibfritz, Tetrahedron 1970, 26, 1805–1820;
b) A. V. Santoro, G. Mickevicius, J. Org. Chem. 1979, 44, 117–
120; c) C. L. Perrin, T. J. Dwyer, Chem. Rev. 1990, 90, 935–967.
[23] Bruker AXS Inc., Madison, Wisconsin, USA, 2002. SMART
(Ver. 5.62), SAINT (Ver. 6.02), SHELXTL (Ver. 6.10) and SA-
DABS (Version 2.03).
Acknowledgments
We gratefully acknowledge the financial support of the Fonds der
Chemischen Industrie (FCI), the Deutsche Forschungsgemein-
schaft and the Bundesministerium für Bildung und Forschung. S.
H.-P. thanks the FCI for granting a Fonds fellowship.
Received: May 11, 2005
Published Online: September 27, 2005
4890
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4879–4890