Rigid nitronyl-nitroxide-labelled anchoring molecules: Syntheses, structural and magnetic investigations

Article abstract of DOI:10.1016/j.tetlet.2004.10.140

Two reaction pathways have been used for the synthesis of new paramagnetic conjugated molecules bearing a nitrogen-based anchoring group. Both compounds are obtained in good yields and spin concentrations. The syntheses of two rigid organic molecular rods bearing a nitronyl-nitroxide radical and a terminal nitrogen-based functionality like a pyridine or a cyano group are reported. Both new paramagnetic molecules are fully characterized, including crystal structure analysis. Furthermore their magnetic behaviours in the crystalline state are investigated and their spin concentration corroborate their excellent purity. While the pyridine functionalized rod is synthesized by converting the corresponding benzaldehyde to the phenyl-nitronyl-nitroxide radical, the synthesis of the cyano functionalized rod demonstrates the accessibility of highly sophisticated spin-labelled molecules via cross-coupling reaction with a meta-iodo-phenyl-nitronyl-nitroxide moiety.

Full text of DOI:10.1016/j.tetlet.2004.10.140

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9623–9626
Rigid nitronyl-nitroxide-labelled anchoring molecules:
syntheses, structural and magnetic investigations
Christophe Stroh, Marcel Mayor* and Carsten von Ha¨nisch
Forschungszentrum Karlsruhe GmbH, Institut fu¨r Nanotechnologie, Postfach 3640, 76021 Karlsruhe, Germany
Received 27 August 2004; revised 22 October 2004; accepted 26 October 2004
Available online 11 November 2004
Abstract—The syntheses of two rigid organic molecular rods bearing a nitronyl-nitroxide radical and a terminal nitrogen-based
functionality like a pyridine or a cyano group are reported. Both new paramagnetic molecules are fully characterized, including crys-
tal structure analysis. Furthermore their magnetic behaviours in the crystalline state are investigated and their spin concentration
corroborate their excellent purity. While the pyridine functionalized rod is synthesized by converting the corresponding benzalde-
hyde to the phenyl-nitronyl-nitroxide radical, the synthesis of the cyano functionalized rod demonstrates the accessibility of highly
sophisticated spin-labelled molecules via cross-coupling reaction with a meta-iodo-phenyl-nitronyl-nitroxide moiety.
Ó 2004 Elsevier Ltd. All rights reserved.
The presence of unpaired electrons in organic molecules
is of great interest as the promising combination of the
virtually unlimited structural diversity of organic chem-
istry and the amazing physics of paramagnetic scaffolds.
Stable organic radicals have been used as spin-labels for
biological and medical applications.1 Paramagnetic mole-
cules have also been used in the field of molecular mag-
netism to investigate the interaction either between their
unpaired electrons2 or with other unpaired electrons of
the neighbouring radicals3 or paramagnetic metals.4
More recently, several groups focussed on the interac-
tion between an unpaired electron of a stable organic
radical and excited electrons. The combination of vari-
ous chromophores with radicals has been achieved for
that purpose.5
scribed in literature and their use for surface or nano-
particle coating are rare.7
Moreover, the interaction between an unpaired electron
of an organic radical and an electron flow is unprece-
dented to our knowledge. In fact, only few studies with
paramagnetic metal-containing molecules have been re-
ported like a paramagnetic metal complex connected be-
tween two gold electrodes, showing
a particular
behaviour due to the presence of an unpaired electron
spin.8
The synthesis of more and more sophisticated molecules
with specific properties or shapes will therefore be of
valuable interest to increase the knowledge about their
behaviours on different types of surfaces and the new
properties they could induce.
In the course for the investigation of the behaviour of
unpaired electrons in different environments, a challeng-
ing goal is the design of paramagnetic molecular rods
for the functionalization of surfaces. Together with the
observation of organic radicals on surfaces, the investi-
gation of their properties in two dimensions is fascinat-
ing. However, even if several conjugated systems bearing
radicals have been published,6 spin-labelled conjugated
organic anchoring molecules are not frequently de-
In this communication, we present the syntheses of the
two rigid rod p-conjugated paramagnetic molecules
combining a nitronyl-nitroxide moiety and a terminal
nitrogen donor atom as anchoring functionality. To
the best of our knowledge, elongated conjugated mole-
cules bearing a nitronyl-nitroxide spin-containing unit
together with an anchor group have not been reported.
The X-ray crystal structures and magnetic measure-
ments are shown for both compounds, pointing at the
efficiency of the applied reaction strategies. In particu-
lar, the efficient integration of an iodo-phenyl-nitronyl-
nitroxide as modular building block of a functionalized
Keywords: Stable radical; Rigid rod; Molecular magnet; Sonogashira
coupling reaction.
*
Corresponding author. Fax: +49 7247 82 5685; e-mail:
marcel.mayor@int.fzk.de
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.140

9624
C. Stroh et al. / Tetrahedron Letters 45 (2004) 9623–9626
molecular structure is here demonstrated for the first
time by a cross-coupling reaction.
both radicals show the molecular peak and fragmenta-
tions corresponding to the loss of both oxygen atoms
of the nitronyl-nitroxides. The characteristic mNO vibra-
tion band can be seen on the IR spectra (1364cmÀ1 for 1
and 2). As expected, the mC„C or mC„N vibration bands
are also observed (1: 2210cmÀ1, 2: 2226cmÀ1). On the
UV–vis spectra, the absorption band corresponding to
the characteristic n!p* of aryl-nitronyl-nitroxide
(586nm for 1 and for 2) corroborates also the character-
ization of the two coloured molecules.
The different terminal anchor groups of 1 and 2 required
two synthetic strategies.
(a) The synthetic strategy for radical 1 follows the clas-
sical Ullman synthesis. First the backbone of the rigid
rod structure is assembled. Containing an aldehyde
function as placeholder, this intermediate is subse-
quently transformed in two steps to the nitronyl-nitrox-
ide radical as displayed in Scheme 1.9 In more details,
the aldehyde 3 has been obtained by a Sonogashira-type
coupling reaction with the commercially available
hydrochloride salt of the bromo-pyridine and the 3-
ethynyl-benzaldehyde10 in a THF/i-Pr2NH mixture at
rt in 47–52% yield. A multiple condensation with the
N,N0-dihydroxy-2,3-diamino-2,3-dimethyl-butane 411 in
MeOH gave the bis-N-hydroxyl amine 5 in 62% yield.12
This intermediate product was oxidized by NaIO4 in a
CH2Cl2/H2Obiphasic mixture to give the desired blue
nitronyl-nitroxide 1 in 84% yield.13
X-ray crystal structures of both compounds were deter-
mined on single crystals obtained by slow evaporation
of a CH2Cl2–hexane mixture.17 Both compounds cryst-
allize monoclinic in the space group P21/c. The ORTEP
views of both molecules are shown in Figures 1a and 2a,
respectively.
The nitronyl-nitroxides have characteristic bond lengths
of such radicals having an unpaired electron equally
shared between two equivalent NOgroups
˚
(dNO = 1.27–1.28A). The dihedral angle between the
mean planes of the radical and the adjacent phenyl ring
is also typical of such molecules (28.8° for 1, 29.9° for 2).
Interestingly, the p system of the anchoring fragment
formed by the two aromatic rings and the triple bond
is highly conjugated as shown by the low dihedral angle
between the rings (13.6° for 1 and 2.3° for 2).
(b) An unlike synthetic strategy has been developed for
radical 2. The backbone of the rigid rod is assembled in
the final step by a Sonogashira–Hagihara type cross-
coupling reaction of molecular units, one of them bear-
ing already the nitronyl-nitroxide radical (Scheme 2).
To the best of our knowledge, this is the first synthesis
with
a
meta-iodo-phenyl-nitronyl-nitroxide showing
In both crystal structures, the packing shows p-stacking
between the terminal aromatic ring with the anchor
group and the benzene ring bearing the radical. The dis-
tances between the atoms of these aromatic systems are
the excellent spin concentration of the product. Such a
reaction step has been documented for the synthesis of
substituted pyridine derivatives or phenyl analogues
without additional substituents.14 Using the similar
NEt3/pyridine solvent mixture reported for couplings
with aryl-nitronyl-nitroxides at rt,15 the blue target rad-
ical was obtained with 59% yield and with excellent spin
concentration (vide infra).16
˚
in the range of 3.3–3.5A. Finally, two radicals are dis-
posed in a head-to-tail manner with a relatively large
intermolecular distance between the Oatom of one rad-
ical and the central C atom of the neighbouring radical
˚
˚
(4.30A for 1 and 4.21A for 2).
These two desired radicals are stable violet solids as
shown by the relatively high melting points. The prod-
ucts were characterized by MALDI-TOF, UV–vis, IR
spectroscopy, elemental analysis and single crystal X-
ray structure analysis. The MALDI-TOF spectra of
Magnetic measurements were done with a SQUID sus-
ceptometer for both radicals on poly-crystalline samples
from 2 to 300K. The corresponding magnetic behav-
iours versus temperature are reported, respectively, in
Figures 1b and 2b.
Scheme 1. Reagents and conditions: (i) 4, MeOH, 7d, rt; (ii) NaIO4, CH2Cl2, H2O, 1h, rt.
Scheme 2. Reagents and conditions: (i) PdCl2 (PPh3)2 10mol%, CuI 5mol%, NEt3/Py 1/4, 1.5h, rt.

C. Stroh et al. / Tetrahedron Letters 45 (2004) 9623–9626
9625
of the curvature is observed, revealing the presence of
an antiferromagnetic behaviour. A mean-field correc-
tion h parameter of À5.4K is obtained by fitting the
1/v = f(T) curve with a Curie–Weiss law above 10K.
A similar shape is observed for compound 2. At high
temperature, the vÆT product is near the expected value
for one isolated S = 1/2 spin (vÆT = 0.381emuKmolÀ1
)
and the curve is horizontal down to ca. 50K. This con-
firms again the high spin concentration and the purity of
the sample prepared by the cross-coupling reaction in
the presence of a radical. Here again, the curve decreases
by lowering further the temperature due to intermolecu-
lar antiferromagnetic interactions. The best fit with a
Curie–Weiss law gave a h parameter of À1.9K.
In summary, two different synthetic strategies allowed
the preparation of rigid and conjugated paramagnetic
anchor molecules with different end groups. While the
frequently used and well-known Ullman synthesis of
nitronyl-nitroxide radicals is well suited for the intro-
duction of various functional groups in good yields,
the modular nature of the Sonogashira–Hagihara
cross-coupling reaction is very promising for the assem-
bly of more complex nitronyl-nitroxide radicals bearing
molecular structures. Seeing that, the enlargement of the
tool kit of acetylene scaffolding with iodo-phenyl-nitron-
yl-nitroxide derivatives will further be promoted. Fur-
thermore, the interactions between radical-bearing
subunits on surfaces, their coupling with the surface
and structure–property correlations of the rigid rod
structure are currently in the focus of our investigations.
Figure 1. (a) ORTEP view of the molecular structure of 1. (b)
Magnetic behaviour of compound 1 versus temperature.
Acknowledgements
We thank the Networkproject MOLMEM German
Ministry of Education and Research (BMBF-FZK 13
N 8360) for financial support, A. Derory (IPCMS,
Strasbourg) for magnetic measurements and the Alexan-
der von Humboldt Foundation for a post-doctoral fellow-
ship to C.S.
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17. Crystal data and structure refinement for 1 and 2:
Data were collected at 200K on a STOE diffractometer
with graphite-monochromated MoKa radiation (k =
˚
0.71073A) using hÀ2h scans. The structures were solved
by direct methods and refined by full-matrix least-squares
analysis. 1, M = 334.39, monoclinic, space group P21/c,
˚
c = 11.164(2)A,
with
a = 14.289(3),
b = 12.149(2),
3
˚
b = 111.44(3)°, V = 1804.1(6)A , Z = 4, Dc = 1.231Mg/
m3, l = 0.081mmÀ1. Parameters (226) were refined using
2302 unique observed reflections [I > 1r(I)] to give
R1 = 0.0745 and wR2 = 0.1349 (all data). Compound 2,
M = 358.41, monoclinic, space group P1/c, with
b =
˚
c = 11.547(2)A,
a = 13.647(3),
b = 12.340(3),
3
3
˚
100.98(3)°, V = 1909.1(7)A , Z = 4, Dc = 1.247Mg/m ,
l = 0.082mmÀ1. Parameters (244) were refined using
2760 unique observed reflections [I > 1r(I)] to give R1 =
0.0589 and wR2 = 0.1081 (all data). Crystallographic data
(excluding structure factors) for the structures in this
paper have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication
numbers CCDC 249046 for 1 and CCDC 249047 for 2,
respectively. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(0) 1223 336033 or
e-mail: deposit@ccdc.cam.ac.uk.
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