Suzuki reactions with stable organic radicals - Synthesis of biphenyls substituted with nitronyl-nitroxide radicals

Article abstract of DOI:10.1002/ejoc.200500116

The synthesis of biphenyls substituted with nitronyl-nitroxide organic radicals is described. To investigate the Suzuki-type cross-coupling reaction conditions in the presence of the radical, a model compound 1 was prepared. The successful coupling was extended to cyano-functionalized, biphenylic, paramagnetic molecules. Both the ortho- and meta-iodophenyl-nitronyl-nitroxide radicals were used to synthesize radicals 2 and 3. The characterizations of the spin-labelled molecules obtained by this synthetic strategy include two X-ray crystal structures and magnetic measurements. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500116

FULL PAPER
Suzuki Reactions with Stable Organic Radicals – Synthesis of Biphenyls
Substituted with Nitronyl-Nitroxide Radicals
Christophe Stroh,[a] Marcel Mayor,*[a,b] and Carsten von Hänisch[a]
Keywords: C–C Coupling / Radicals / Magnetic properties / Nitronyl nitroxide
The synthesis of biphenyls substituted with nitronyl-ni-
troxide organic radicals is described. To investigate the Su-
zuki-type cross-coupling reaction conditions in the presence
of the radical, a model compound 1 was prepared. The suc-
cessful coupling was extended to cyano-functionalized, bi-
phenylic, paramagnetic molecules. Both the ortho- and meta-
iodophenyl-nitronyl-nitroxide radicals were used to synthe-
size radicals 2 and 3. The characterizations of the spin-lab-
elled molecules obtained by this synthetic strategy include
two X-ray crystal structures and magnetic measurements.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
paramagnetic subunits turned out to be of particular im-
portance to tune the properties. Also, the intermolecular
interaction of monoradicals in the solid state depends on
both the spatial arrangement of the radical subunits and
the molecular structure bearing these units.[12] To control
both key features by rational design, the synthesis of rigid
molecular structures as scaffolds for functional building
blocks is an elegant approach which has already been used
in different research areas like light harvesting sys-
tems[13a–13e] and molecular electronics.[14a–14d] Many rigid
organic scaffolds consisting of linked aromatic subunits, like
shape persistent macrocycles, have been reported.[15a–15d]
The most prominent examples are acetylene- and directly-
linked aromatic π systems, both synthetically based on me-
tal-catalyzed coupling reactions like the Sonogashira reac-
tion[16] and the Suzuki reaction,[17] respectively. While Sono-
gashira reactions have already been applied to arrange
stable radicals within a molecular framework,[18a–18d] to the
best of our knowledge, Suzuki reactions with organic radi-
cals have not yet been reported, even though biphenyl-
based structures have been investigated.[19a–19d] The combi-
nation of a Suzuki-type cross-coupling reaction and ni-
tronyl-nitroxide radical building blocks enables the synthe-
sis of spin-labelled oligophenylenes and may also lead to
larger organic scaffolds containing paramagnetic subunits.
Here we report the first protocol for a Suzuki-type cross-
coupling reaction in the presence of a nitronyl-nitroxide
radical.
Introduction
Stable organic radicals are intensively investigated due to
particular features induced by the presence of an unpaired
electron. The electronic properties of a large number of
spin-labels and spin-probes have been studied in various en-
vironments,[1a–1e] and the magnetic features of various radi-
cals have been explored, giving rise to the fascinating field
of molecular magnetism.[2a–2d] Major advances involving
the magnetic properties of molecules have been made with
model compounds based on Ullman’s nitronyl-nitroxide
radicals[3a–3b] since the discovery of the first purely organic
magnet.[4]
To study the intramolecular coupling between the spins
of radicals, conjugated organic oligo- and polyradicals have
been synthesized.[5a–5e] Nitronyl-nitroxide diradicals and tri-
radicals gave valuable results,[6a–6d] and the spin density dis-
tribution in such systems has been mapped.[7] Well suited
for the preparation of multidimensional scaffolds, these rad-
icals have been used as building blocks of linear, 2-D, 3-D
or cyclic structures.[8a–8f] Moreover, tailor-made molecules
combining stable organic radicals with other functional
subunits allow the investigation of the interaction between
an unpaired electron spin and other electrons of different
sources. For example, redox-active groups have been com-
bined with radicals,[9a–9b] and organic radicals bearing chro-
mophores were prepared as magneto-optical systems[10a–10d]
and to study switching effects.[11] However, in all these oli-
goradical investigations the spatial arrangement of the radi-
cal subunits and the molecular structures connecting these
Results and Discussion
[a] Institut for Nanotechnology, Forschungszentrum Karlsruhe
GmbH,
To investigate the compatibility of the nitronyl-nitroxide
radical structure with the conditions of a Suzuki cross-
coupling reaction, the model compounds 1–3 have been
chosen as synthetic targets (Scheme 1). All three structures
Postfach 3640, 76021 Karlsruhe, Germany
Fax: +49-7247-82-5685
E-mail: marcel.mayor@int.fzk.de
[b] Department of Chemistry, University of Basel,
St. Johanns-Rring 19, 4056 Basel, Switzerland
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DOI: 10.1002/ejoc.200500116
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consist of a nitronyl-nitroxide radical subunit linked to a yield of the alternative reaction pathway over the three steps
biphenyl core. Our synthetic strategy is to form the radical is in the same domain as the synthesis based on the classical
subunit first and subsequently assemble the biphenyl back- Ullman reaction. Considering the yield of 91% for the syn-
bone by a Suzuki coupling. To profit from the possibility thesis of biphenyl-2-carboxaldehyde 5, the overall yield for
offered by this alternative strategy, compounds 2 and 3 with 1 by the classical reaction pathway drops to 25%. Hence,
a cyano group at the peripheral ring as additional function- concerning the overall yield, both strategies are comparable,
ality have been synthesized. The cyano group is of particu- at least for the selected target compound. The loss in yield
lar interest because of its coordination features toward no- during the Suzuki reaction is most likely due to decomposi-
ble metal surfaces. Hence, compounds 2 and 3 enable the tion of the nitronyl-nitroxide radical subunit at higher tem-
decoration of metallic substrates with stable organic radi- perature. Both the temperature and the duration of the re-
cals. Not only is the electronic interaction with the underly- action may be reduced by careful choice of the catalyst and
ing surface of particular interest, but also the investigation the solvent, which might lead to further increase in the yield
of a spin probe at the end of a fixed molecular rod on a for the synthetic strategy; however, the focus of this work
single-molecule level.
was to demonstrate the feasibility of the synthetic concept
and to isolate and characterize the desired target com-
pounds in excellent purity for subsequent applications in
nanoscale physical devices and experiments.
Scheme 1. Molecular structures of the ortho-nitronyl-nitroxide
compounds 1 and 2 and of the meta-nitronyl-nitroxide compound
3.
From a synthetic point of view, we further show that a
halogen in the ortho position of a phenyl-nitronyl-nitroxide
can be substituted, a finding that increases the feasible
structural variety of the family of paramagnetic molecules.
The synthesis of radical 1 is displayed in Scheme 2. The
iodophenyl-nitronyl-nitroxide 4 and phenylboronic acid re-
act with each other in the presence of catalytic Pd(PPh3)4
and excess K2CO3 (aq.) in a toluene/MeOH (1:1) solvent
mixture at 80 °C. Despite very similar Rf values and colors
of both the starting compound 4 and the product 1, silica
gel chromatography allowed us to isolate 1 as a pink solid
in 43% yield. To compare synthetic strategies and to further
corroborate the structure of 1, it was also synthesized by the
classical synthetic strategy described by Ullman. A multiple
Scheme 2. Two synthetic strategies for the synthesis of the biphenyl-
nitronyl-nitroxide conjugated radical 1. New pathway: a) phenylbo-
ronic acid, Pd(PPh3)4, Na2CO3 (aq.), Tol/MeOH, 1:1, 80 °C, 2 h,
43%. Classical pathway: b) DHA, MeOH, room temperature, 4 d,
73%. c) NaIO4, CH2Cl2/H2O, 1 h, 37 %.
To corroborate the structure of 1, single crystals suitable
condensation of N,NЈ-dihydroxy-2,3-diamino-2,3-dimethyl- for X-ray analysis were grown by slow diffusion of hexane
butane (DHA)[20] with the aldehyde-functionalized biphenyl into a solution of 1 in CH2Cl2. The solid-state structure of
5 in MeOH gave the intermediate compound 6. Oxidation 1 is discussed below and displayed in Figure 2.
with NaIO4 in a biphasic mixture gave the desired product
To investigate the versatility of this alternative strategy,
1. For this two-step reaction sequence, an overall yield of both starting compounds have been varied. As displayed in
27% was obtained after purification by column chromatog- Scheme 3, 4-cyanophenylboronic-acid was used instead of
raphy. The isolated compound 1 synthesized by both strate- phenylboronic acid to synthesize 2 and 3. For the synthesis
gies displayed identical characterization data and proper- of 3, 3-iodophenyl-nitronyl-nitroxide 9 was synthesized in
ties. The 43% yield of this alternative strategy is rather a comparable reaction sequence as described above for 4.
moderate or even poor. However, the reaction pathway is of Commercial 3-iodobenzaldehyde was converted by conden-
particular interest for target compounds bearing functional sation with DHA to 1,3-dihydroxy-2-(3-iodophenyl)-
groups that are not sensitive under the conditions of the 4,4,5,5-tetramethylimidazolidine 8 in 94% yield. Oxidation
classical Ullman reaction, like aldehydes. To compare the with NaIO4 gave 9 in a 96% yield. For the synthesis of both
overall yields, the synthetic steps (Scheme 3) leading to 2- compounds 2 and 3, a similar Suzuki coupling protocol as
iodophenyl-nitronyl-nitroxide 4 have to be considered also. described above for 1 has been applied. The reactions were
Starting with commercial 2-iodobenzaldehyde, 1,3-dihy- monitored by thin-layer chromatography (TLC) and were
droxy-2-(2-iodophenyl)-4,4,5,5-tetramethylimidazolidine
7
quenched with excess cold water after 2 to 2.5 h at 80 °C.
was obtained by a multiple condensation with DHA in 88% The desired compounds were isolated by flash chromatog-
yield. Subsequent oxidation of 7 with NaIO4 in a biphasic raphy as a pink solid in 40% yield for 2 and as violet micro-
mixture afforded 4 with a yield of 68%. The 26% overall crystals in 44% yield for 3.
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Suzuki Reactions with Stable Organic Radicals
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Scheme 3. Synthesis of the substituted phenyl-nitronyl-nitroxide conjugated radicals 2 and 3 and their precursors 4, 7, 8 and 9. a) DHA,
MeOH, room temperature, 3–5 d, 88% for 7 and 94% for 8. b) NaIO4, CH2Cl2/H2O, 2 h, 68 % for 4 and 96% for 9. c) Cyanophenylboronic
acid, Pd(PPh3)4, Na2CO3 (aq.), Tol/MeOH, 1:1, 80 °C, 2–2.5 h, 40% for 2 and 44% for 3.
The structure of 3 was also confirmed by X-ray analysis. in the ortho position. This results in an increased steric re-
Single crystals suitable for X-ray analysis were prepared by pulsion which twists these two delocalized electronic sub-
slow diffusion of hexane into a solution of 3 in CH2Cl2.
units out of the plane of the central phenyl ring. The tor-
In addition to the X-ray structures of 1 and 3, radicals 1– sion angle between the nitronyl-nitroxide unit and the cen-
3 prepared by the Suzuki-type cross-coupling reaction were tral phenyl ring is increased, and the π systems are sepa-
characterized by MALDI-TOF spectrometry, FT-IR and rated. In contrast, the meta-substitution pattern of com-
UV/Vis spectroscopy, and elemental analysis. Furthermore, pound 3 puts both subunits at a considerably larger dis-
the purity of the samples was investigated by SQUID tech- tance, and as a consequence, the arrangement of the central
niques.
benzene ring and the nitronyl-nitroxide structure is flat,
The MALDI-TOF spectra of all three compounds 1–3 which results in a chromophore delocalized over both sys-
are very comparable and typical for structures bearing ni- tems. This interpretation is further supported by the solid-
tronyl-nitroxide radical subunits. An intense signal for the state structures of 1 and 3.
ionized molecule is followed by the signal arising from the
In the solid-state structure of 1, the nitronyl-nitroxide
molecule having lost one oxygen atom. A third intense sig- moiety shows bond lengths as typically found for such radi-
nal, arising from the loss of both oxygen atoms, is also ob- cals (NO = 1.29 Å, CN = 1.35 Å) (Figure 2). However, the
served for all three compounds.
mean plane of the radical makes a larger dihedral angle
The IR spectra of all three compounds display compar- with the plane of the adjacent phenyl ring than generally
able features, again pointing at the presence of the nitronyl- observed (ca. 69.9°). As already mentioned above, this is
nitroxide substructure. All three samples display the charac- due to the steric hindrance of the ortho substituent. Inter-
teristic νNO vibration band at 1367 cm–1 for 1, 1369 cm–1 estingly, the dihedral angle between the phenyl rings is 46.3°
for 2, and 1363 cm–1 for 3. In addition, compounds 2 and and is affected less by the radical subunit in the ortho posi-
3 display the characteristic νCϵN vibration band at tion. Although the structural proximity of the radical oxy-
2226 cm–1 of the cyano group.
gen and H atoms of the external phenyl ring may suggest
Considerable differences in the UV/Vis spectra of the an intramolecular H bond, the distance of 3.17 Å [O(1)···
three radicals can be detected by the bare eye. While the H–C(15)] is too large for such an interaction.
two ortho nitronyl-nitroxide functionalized biphenyls 1 and
Close examination of the crystal packing shows an anti-
2 are pink, the meta nitronyl-nitroxide functionalized bi- parallel stacked arrangement of two neighboring radicals
phenyl 3 is violet. In the UV/Vis spectra the longest wave- with a shortest distance above the van der Waals distance
length absorption of 3 is considerably bathochromically
shifted (Ϸ25 nm) relative to 1 and 2 (Figure 1). In the two
latter compounds, the nitronyl-nitroxide subunit and the pe-
ripheral phenyl ring are connected at the central phenyl ring
Figure 2. ORTEP view of the molecular structure of radical 1. Se-
lected bond lengths [pm] and bond angles [°]: O(1)–N(1) 128.8(2),
N(2)–O(2) 128.6(2), N(2)–C(1) 134.7(2), N(1)–C(1) 135.2(2), C(8)–
C(1) 148.5(2), N(2)–C(1)–C(8)–C(13) 71.5, N(1)–C(1)–C(8)–C(9)
68.3, C(8)–C(13)–C(14)–C(15) 46.7, C(12)–C(13)–C(14)–C(19)
46.0.
Figure 1. UV/Vis spectra of the three radicals in CH2Cl2 solution
at 293 K and concentrations of 9.15×10–4, 2.60×10–4 and
3.05×10–4  for 1, 2, and 3, respectively.
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C. Stroh, M. Mayor, C. von Hänisch
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of 3.72 Å between the O1 atoms (N–O···OЈ–NЈ = 180.0°,
O···OЈ–NЈ = 97.2°, C–N–O···OЈ = 88.2°); π stacking be-
tween the aromatic subunits is not observed.
The crystal structure of compound 3 contains two inde-
pendent molecules, which are displayed individually in Fig-
ure 3a,b. Both show NO and CN bond lengths characteris-
tic of such radicals (ca. 1.29–1.30 and 1.36 Å, respectively).
However, one radical (Figure 3b) makes a dihedral mean
angle of 21.6° with its adjacent phenyl ring, while this mean
angle is only 13.7° in the second molecule (Figure 3a).
Furthermore, the dihedral mean angle between the two
phenyl rings is also larger in the first molecule than in the
second (ca. 25.9° and 19.5°, respectively).
The packing of radical 3 is considerably different from
the one found for 1. π-Stacking of antiparallel molecules
predominates, and the distances between the phenyl rings
are nearly 3.5 Å. Interestingly, the distances between the ni-
trogen atom of the cyano group and the oxygen atoms of
the radicals are between 3.36 and 3.90 Å. The formation
of this crystal packing is probably based on dipole-dipole
interactions between these polar molecules. Within these
stackings, one out of two radicals shows a short contact
with a neighboring radical (O(3)···O(3Ј) = 3.58 Å) (Fig-
ure 3c).
The purity of compounds 1–3 is documented by their
accurate elemental analysis. However, the nitronyl-nitroxide
subunit as a stable organic radical allows us to confirm the
purity of the sample by investigating the spin concentration
Figure 3. a) and b) ORTEP view of the two molecular structures
of radical 3. Selected bond lengths [pm] and bond angles [°]: N(2)–
O(1) 129.2(3), N(3)–O(2) 129.5(3), C(14)–N(3) 136.1(4), C(14)–
N(2) 136.4(4), C(12)–C(14) 147.4(4), C(5)–C(8) 150.3(4), C(1)–C(2)
145.6(5), C(1)–N(1) 115.8(4), N(3)–C(14)–C(12)–C(13) 14.6, N(2)–
C(14)–C(12)–C(11) 12.9, C(13)–C(8)–C(5)–C(6) 19.3, C(9)–C(8)–
C(5)–C(4) 19.6 and N(5)–O(3) 129.7(3), N(6)–O(4) 129.8(3), C(34)–
N(5) 136.2(4), C(34)–N(6) 136.4(4), C(30)–C(34) 146.0(5), C(25)–
C(28) 150.8(4), C(21)–C(22) 145.7(5), C(21)–N(4) 116.9(4), N(5)–
C(34)–C(30)–C(29) 21.1, N(6)–C(34)–C(30)–C(31) 22.2, C(29)–
C(28)–C(25)–C(24) 26.0, C(33)–C(28)–C(25)–C(26) 25.8. c) Pack-
ing of radical 3 showing the isolated pairs.
Figure 4. SQUID measurements from 300–2 K for the three radi-
cals prepared by the new pathway; a) ortho-substituted compounds
1 (diamonds) and 2 (squares); b) meta-substituted compound 3
(circles).
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SQUID magnetometer operating at a field strength of 0.5 T. The
data were corrected for the magnetization of the sample holder
contribution, and diamagnetism of the molecules was estimated
from Pascal’s constants.[21]
of the compounds by SQUID measurements. Magnetic
measurements were recorded on a SQUID susceptometer
for all radicals on polycrystalline samples from 2–300 K.
The corresponding magnetic behaviors versus temperature
are reported in Figure 4a,b. At high temperature, the χ·T
versus T curves for all compounds are located near the ex-
pected value for one isolated S = 1/2 spin. The χ·T products
are 0.347, 0.353 and 0.373 emu·K·mol–1 at 300 K for 1, 2,
and 3 respectively. These values are consistent with an excel-
lent spin concentration and high purity of the samples. By
lowering the temperature, a decrease in the χ·T products is
observed for the three compounds at very low temperature,
revealing the presence of very weak intermolecular antifer-
romagnetic interactions. Despite a small difference in the
behavior of the meta-substituted derivative 3, which shows
a more rapid decrease in the χ·T product than in the ortho-
substituted radicals (Figure 4b), an interpretation of the
origin of the change in the magnetic behaviors would be
misleading in view of the complicated crystal packing of
the molecules.[12] Mean-field correction parameters θ of
–0.9, –1.6 and –3.3 K are obtained for 1, 2 and 3, respec-
Biphenyl-2-carboxaldehyde (5): Compound 5 was obtained as a
white solid (91%) from 2-iodobenzaldehyde and phenylboronic
acid by a standard procedure using Pd(PPh3)4 and Na2CO3 (aq.)
in DMF and after purification by chromatography on SiO2 (hex-
4
ane/Et2O, 9:1).[22] 1H NMR (CDCl3): δ = 10.01 (d, J = 0.9 Hz, 1
3
4
3
H, CHO), 8.05 (dd, J = 7.5, J = 1.2 Hz, 1 H, Ar), 7.7 (dt, J =
4
7.5, J = 1.2 Hz, 1 H, Ar), 7.55–7.39 (m, 7 H, Ar) ppm.
General Procedure for the Synthesis of Dihydroxyimidazolidine In-
termediates: The corresponding iodobenzaldehyde (gram scale) and
N,NЈ-dihydroxy-2,3-diamino-2,3-dimethyl-butane (ca. 1.5 equiv.) in
MeOH (30 mL) were stirred at room temperature in the dark for 3
to 5 d. The solution volume was reduced by half, and the white
precipitate was filtered and washed with MeOH, to give the title
compound.
Compound 7: White solid. Isolated yield: 88%. Rf = 0.41 (SiO2,
CH2Cl2/2%MeOH). M.p.: 196–199 °C (dec.). 1H NMR [(CD3)2-
3
3
SO]: δ = 7.79 (d, J = 7.8 Hz, 1 H, Ar), 7.63 (d, J = 7.8 Hz, 1 H,
3
3
Ar), 7.60 (s, 2 H, OH), 7.39 (t, J = 7.5 Hz, 1 H, Ar), 7.02 (t, J =
tively, by fitting the 1/χ = f(T) curves with the Curie–Weiss 7.8 Hz, 1 H, Ar), 4.94 (s, 1 H), 1.07 (s, 12 H, Me) ppm. 13C{1H}
NMR [(CD3)2SO]: δ = 143.7, 139.3, 131.7, 130.4, 128.6, 103.3, 92.6,
law over the complete temperature range.
67.1, 24.9, 18.6 ppm. IR (KBr): ν = 3247, 2985, 2926, 1465, 1450,
˜
1376, 1363, 1262, 1210, 1153, 1144, 1019, 1010, 917, 865, 752 cm–1.
MALDI-TOF (1,8,9-anthracenetriol): m/z (%) 362.7 [M]+ (100),
346.7 [M – OH + H]+ (12), 328.7 [M – 2OH]+ (12). C13H19IN2O2
(362.21): calcd. C 43.11, H 5.29, N 7.73; found C 43.13, H 5.29, N
7.75.
Conclusions
An alternative reaction pathway based on a Suzuki-type
cross-coupling reaction in the presence of a nitronyl-ni-
troxide radical has been used for the first time. The signifi-
Compound 8: White solid. Isolated yield: 94%. Rf = 0.38 (SiO2,
cance of the synthetic strategy in the preparation of new CH2Cl2/2%MeOH). M.p.: 158 °C (dec.). 1H NMR [(CD3)2SO]: δ
= 7.84 (m, 1 H, Ar + 2 H, OH), 7.63 (m, 1 H, Ar), 7.46 (m, 1 H,
Ar), 7.14 (t, 3J = 7.8 Hz, 1 H, Ar), 4.45 (s, 1 H), 1.07 (s, 6 H, Me),
1.03 (s, 6 H, Me) ppm. 13C{1H} NMR [(CD3)2SO]: δ = 144.8,
136.8, 135.9, 129.9, 128.1, 94.3, 89.6, 66.2, 24.4, 17.2 ppm. IR
functionalized paramagnetic molecules is demonstrated by
the synthesis of three biphenylic structures containing a ni-
tronyl-nitroxide subunit. These new compounds were fully
characterized, two of them by X-ray crystal structures, and
magnetic SQUID investigations corroborate their identity
and purity by excellent spin concentrations.
The synthesis of various paramagnetic structures de-
signed for physical experiments and investigations, like
compounds containing surface anchor groups and para-
magnetic molecular wires, will be further investigated in our
research group. Moreover, the assembly of macromolecules
containing several paramagnetic subunits may come within
reach using this new strategy.
(KBr): ν = 3217, 2913, 1593, 1569, 1430, 1379, 1368, 1267, 1215,
˜
1142, 1105, 995, 918, 899, 881, 816, 775, 690, 663, 507 cm–1.
MALDI-TOF (1,8,9-anthracenetriol): m/z (%) 362.7 [M]+ (100),
344.7 [M – H2O]+ (10), 328.7 [M – 2OH]+ (22). C13H19IN2O2
(362.21): calcd. C 43.11, H 5.29, N 7.73; found C 43.22, H 5.25, N
7.91.
General Procedure for the Synthesis of Nitronyl-nitroxides: The cor-
responding 1,3-dihydroxy-2-(iodophenyl)-4,4,5,5-tetramethylimida-
zolidine (1 to 2 g) in CH2Cl2 (1 to 2 L) and NaIO4 (ca. 2 equiv.) in
H2O (1.0 L) were vigorously stirred for 2 h in the dark at room
temperature. The organic layer was separated, washed with H2O,
and dried with MgSO4. The solvent was evaporated, and the crude
solid was purified by chromatography (SiO2, CH2Cl2 to CH2Cl2/
1–2% MeOH). The radical was recrystallized twice from CH2Cl2/
hexane to give the pure compound.
Experimental Section
General Remarks: 2-Iodobenzaldehyde and 3-iodobenzaldehyde
were purchased from Aldrich. N,NЈ-Dihydroxy-2,3-diamino-2,3-di-
methyl-butane was synthesized by following a reported method.[20]
All cross-coupling reactions were carried out under oxygen-free
conditions. Characterizations were performed with the following
instruments: melting points−Büchi B 540 (open capillaries, uncor-
rected values); UV/Vis−Varian Cary 500 Scan spectrophotometer;
IR−Perkin–Elmer Spectrum GX FT-IR system; MALDI-
TOF−PerSeptive Biosystems Voyager–DEPRO; elemental
analyses−CE Instruments Flash EA 1112 series. Magnetic suscep-
tibilities were measured on polycrystalline materials for 1 and 3 and
on a powder for 2 with a Quantum Design MPMS superconducting
Radical 4: Pink solid. Isolated yield: 68%. Rf = 0.26 (SiO2, CH2Cl2/
2%MeOH). M.p.: 165–167 °C. UV/Vis (CH2Cl2): λmax (ε, –1 cm–1)
= 546 (790), 329 (7310), 232 (11790) nm. IR (KBr): ν = 2987, 1457,
˜
1404, 1368, 1220, 1164, 1138, 1022, 753, 667, 539 cm–1. MALDI-
TOF (1,8,9-anthracenetriol): m/z %) 360.6 [M + H]+ (100), 344.7
[M – O + H]+ (95), 328.7 [M – 2O + H]+ (25). C13H16IN2O2
(359.18): calcd. C 43.47, H 4.49, N 7.80; found C 43.40, H 4.32, N
7.74.
Radical 9: Violet solid. Isolated yield: 96%. Rf = 0.55 (SiO2,
CH2Cl2/2%MeOH). M.p.: 156–160 °C. UV/Vis (CH2Cl2): λmax (ε,
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C. Stroh, M. Mayor, C. von Hänisch
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
–1 cm–1) = 588 (440), 368 (15360), 272 (11820), 229 (17160) nm.
Radical 3: Violet solid. Isolated yield: 44%. Rf = 0.43 (SiO2,
CH2Cl2/6%MeCN). M.p.: 135–136 °C. UV/Vis (CH2Cl2): λmax (ε,
IR (KBr): ν = 2981, 1553, 1477, 1445, 1415, 1371, 1360, 1294, 1209,
˜
1164, 1130, 791, 684, 673, 543, 455 cm–1. MALDI-TOF (1,8,9-an-
thracenetriol): m/z (%) 360.6 [M + H]+ (37), 344.6 [M – O + H]+
(100), 328.7 [M – 2O + H]+ (22). C13H16IN2O2 (359.18): calcd. C
43.47, H 4.49, N 7.80; found C 43.18, H 4.45, N 7.51.

–1 cm–1) 587 (460), 367 (11700), 271 (35790), 228 (11780) nm. IR
(KBr): ν = 3439, 2988, 2226, 1608, 1452, 1422, 1405, 1386, 1363,
˜
1308, 1278, 1214, 1167, 1135, 838, 793, 682, 539 cm–1. MALDI-
TOF (1,8,9-anthracenetriol): m/z (%) 335.9 [M + H]+ (80), 319.9
[M – O + H]+ (100), 303.9 [M – 2O + H]+ (20). C20H20N3O2
(334.39): calcd. C 71.84, H 6.03, N 12.57; found C 71.81, H 5.66,
N 12.26.
Synthesis of 1 by the Classical Pathway: Aldehyde 5 (70.5 mg,
0.39 mmol) and N,NЈ-dihydroxy-2,3-diamino-2,3-dimethyl-butane
(2 equiv.) in MeOH (3 mL) were stirred at room temperature in the
dark for 4 d. The white precipitate was filtered and washed with
MeOH to give 88.6 mg of the intermediate 6.
Crystal Data and Structure Refinement for 1 and 3: Data were col-
lected at 200 K on a STOE-IPDS2 diffractometer with graphite-
monochromated Mo-Kα radiation (λ = 0.71073 Å). The structures
were solved by direct methods and refined by full-matrix least-
squares analysis.
1
Compound 6: White solid. Isolated yield: 73%. H NMR [(CD3)2-
SO]: δ = 7.77–7.74 (m, 1 H), 7.50–7.30 (m, 9 H), 7.16–7.13 (m, 1
H), 4.84 (s, 1 H), 1.09 (s, 6 H, Me), 0.91 (s, 6 H, Me) ppm. 13C{1H}
NMR [(CD3)2SO]: δ = 143.8, 141.6, 139.5, 131.2, 130.9, 130.1,
128.4, 127.8, 127.6, 127.5, 85.4, 66.8, 25.2, 18.4 ppm. C19H24N2O2
(312.41): calcd. C 73.05, H 7.74, N 8.97; found C 72.83, H 7.84, N
8.93.
1: [C19H21N2O2]; M = 309.38, monoclinic, space group P21/c, a =
14.048(3) Å, b = 6.1625(12) Å, c = 19.408(4) Å, β = 98.95(3)°, V =
1659.7(6) Å3, Z = 4, Dc = 1.238 g/cm3, µ = 0.081 mm–1. 5207 reflec-
tions measured, 2461 independent reflections, (Rint = 0.0458), 1861
independent reflections with Fo Ͼ 4σ(Fo). 208 parameters (O, N,
C refined anisotropically, H atoms calculated at ideal positions),
R1 = 0.0400, wR2 = 0.1133 (all data), residual electron density:
0.148 eÅ3.
Compound 6 (61.6 mg, 0.20 mmol) in CH2Cl2 (100 mL) and NaIO4
(ca. 2 equiv.) in H2O (100 mL) were vigorously stirred for 1 h in
the dark at room temperature. The organic layer was separated,
washed with H2O, and dried with MgSO4. The solvent was evapo-
rated, and the crude solid was purified by chromatography (SiO2,
CH2Cl2 to CH2Cl2/1% MeCN) to give 37 mg of the target radical
1.
3: [C20H20N3O2]; M = 334.39, monoclinic, space group P21/n, a =
7.1496(14) Å, b = 15.405(3) Å, c = 32.682(7) Å, β = 92.89(3)°, V =
3595.0(12) Å3, Z = 8, Dc = 1.236 g/cm3, µ = 0.082 mm–1. 7420
reflections measured, 4540 independent reflections, (Rint = 0.0486),
2520 independent reflections with Fo Ͼ 4σ(Fo). 451 parameters (O,
N, C refined anisotropically, H atoms calculated at ideal positions),
R1 = 0.0513, wR2 = 0.1415 (all data), residual electron density:
0.320 eÅ3.
Radical 1 (Classical Pathway): Pink solid. Isolated yield: 37%. Rf
= 0.09 (SiO2, CH2Cl2/3%MeCN). UV/Vis (CH2Cl2): λmax = 563,
324, 307, 237 (sh), 227 nm. IR (KBr): ν = 3434, 2982, 2930, 1638,
1600, 1474, 1451, 1403, 1365, 1220, 1165, 1135, 1073, 759, 704,
538, 455 cm–1. MALDI-TOF (1,8,9-anthracenetriol): m/z (%) 310.8
[M + H]+ (35), 294.8 [M – O + H]+ (100), 278.8 [M – 2O + H]+
(23).
˜
CCDC-260852 (1) and 260853 (3) contain the supplementary crys-
tallographic 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.
General Procedure for the Suzuki-Type Cross-Coupling Reaction:
Iodophenyl-nitronyl-nitroxide (100 to 300 mg) and phenylboronic
acid or 4-cyanophenylboronic acid (ca. 1.5 equiv.) were dissolved
in toluene/MeOH 1:1 (10 m), and the solution was deoxygenated
by bubbling with Ar. Pd(PPh3)4 (5 mol-%) was added under Ar,
followed by a deoxygenated solution of Na2CO3 (ca. 7 equiv.) in
H2O (ca. 1.5 ). The mixture was heated at 80 °C for 2–2.5 h. H2O
(300 mL) was added, and the product was extracted with CH2Cl2
(500 mL). The organic phase was washed with H2O (100 mL), dried
with MgSO4, and the solvents were evaporated. The crude product
was purified by chromatography (SiO2, CH2Cl2/1–3%MeCN) to
give the pure product.
Acknowledgments
We thank the Networkproject MOLMEM German Ministry of
Education and Research (BMBF-FZK 13  8360) for financial sup-
port, the Alexander von Humboldt Foundation for a post-doctoral
fellowship to C.S. and Alain Derory (IPCMS – Strasbourg) for
magnetic measurements.
Radical 1: Pink solid. Isolated yield: 43%. Rf = 0.09 (SiO2, CH2Cl2/
3%MeCN). M.p.: 139–145 °C. UV/Vis (CH2Cl2): λmax (ε, –1 cm–1)
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M. C. Krishna, A. Russo, J. Yoo, S. English, J. B. Mitchell,
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A. Samouilov, P. Kuppusamy, J. L. Zweier, J. Magnet. Res.
2001, 148, 155–164; e) P. P. Borbat, A. J. Costa-Filho, K. A.
Earle, J. K. Moscicki, J. H. Freed, Science 2001, 291, 266–269.
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237 (13180), 226 (13590) nm. IR (KBr): ν = 3516, 3057, 2998, 2942,
˜
1631, 1481, 1472, 1449, 1441, 1403, 1389, 1367, 1218, 1168, 1137,
1010, 869, 850, 772, 765, 754, 705, 539, 459 cm–1. MALDI-TOF
(1,8,9-anthracenetriol): m/z (%) 310.9 [M + H]+ (80), 294.9 [M – O
+ H]+ (100), 278.9 [M – 2O + H]+ (35). C19H21N2O2 (309.38):
calcd. C 73.76, H 6.84, N 9.05; found C 73.81, H 6.46, N 8.98.
Radical 2: Pink solid. Isolated yield: 40%. Rf = 0.22 (SiO2, CH2Cl2/
6%MeCN). M.p.: 170–175 °C. UV/Vis (CH2Cl2): λmax (ε, –1 cm–1)
564 (720), 321 (6250), 250 (18070) nm. IR (KBr): ν = 3443, 2991,
˜
2226, 1608, 1476, 1448, 1403, 1369, 1217, 1170, 1135, 841, 760, 572
cm–1. MALDI-TOF (1,8,9-anthracenetriol): m/z (%) 335.8 [M + H]+
(75), 319.8 [M – O + H]+ (100), 303.8 [M – 2O + H]+ (25).
C20H20N3O2 (Mr = 334.39): calcd. C 71.84, H 6.03, N 12.57; found
C 71.56, H 6.16, N 12.44.
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3702
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 3697–3703

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