Convenient and Multistep Preparation of Oligopyridines Bearing Multiple Dansyl and Nitroxide Radicals

Article abstract of DOI:10.1055/s-2003-42083

A series of pyridine and bipyridine molecules combining dual fluorescent (dansyl) and magnetic (free radical) probes has been prepared by a linear multistep protocol from the corresponding monodansylated derivatives. The grafting of the flexible aliphatic radical is realized by the use of a chloromethylnitronyl nitroxide derivative under basic conditions and with KI as a mediator. The synthetic potential of 2-[(5-dimethylamino-1-naphthalenesulfonamide)methyl]-6-formylpyridine is assessed by the construction, in a first step, of an aliphatic nitroxide radical and subsequently of an additional aromatic radical. The synthetic methods reported herein provide a practical approach to the rational design of ligands bearing various kinds of functionalities such as chromogenic and spinlabeled fragments. A significant merit of this method is that it allows the introduction of the fluorescent substituent onto the pyridine or bipyridine framework at the beginning of the synthetic protocol.

Full text of DOI:10.1055/s-2003-42083

PAPER
2145
Convenient and Multistep Preparation of Oligopyridines Bearing Multiple
Dansyl and Nitroxide Radicals
O
ligopyridines B
a
earing
M
ul
y
tiple
D
ansyl
m
and Nitroxide Radic
o
als nd Ziessel,* Christophe Stroh
Laboratoire de Chimie Moléculaire, Associé au CNRS, Ecole de Chimie, Polymères Matériaux de Strasbourg (ECPM), 25 rue Becquerel,
67087 Strasbourg, Cedex 02, France
Fax +33(3)90242689; E-mail: ziessel@chimie.u-strasbg.fr
Received 26 May 2003; revised 2 July 2003
tected -amino acids,4 nitroxides,5 aminotroponimiate
Abstract: A series of pyridine and bipyridine molecules combining
rings,6 tripodal complexants,7 a variety of macrocyclic
dual fluorescent (dansyl) and magnetic (free radical) probes has
platforms such as calix[4]arenes,8 -cyclodextrin,9
been prepared by a linear multistep protocol from the corresponding
1,4,7,10-tetraazacyclododecane,10 and poly(propylene-
monodansylated derivatives. The grafting of the flexible aliphatic
radical is realized by the use of a chloromethylnitronyl nitroxide de- amine) dendrimers.11 Dansyl fragments are also very pop-
rivative under basic conditions and with KI as a mediator. The syn-
ular as auxiliaries for fluorescence switch in optical
sensors.12
thetic potential of 2-[(5-dimethylamino-1-naphthalenesulfon-
amide)methyl]-6-formylpyridine is assessed by the construction, in
Interest in nitroxide free radicals stems in part from their
use as spin-labeled probes13 but also as paramagnetic
building blocks for the assemblage of multidimensional
arrays, some of them exhibit very interesting cooperative
magnetic properties.14,15 Nevertheless, in comparison with
these separated field of research, the synthesis of hybrid
derivatives bearing dual dansyl and free radicals is less
extensive than one might expect. This shortcoming is due
largely to difficulties in synthesizing the prerequisite
starting materials. A notable advance was previously re-
ported by Hideg and co-workers, who have shown that the
dansylation of aniline substituted nitroxide radicals is fea-
sible.16 Depending on the structure of the molecule, mod-
ulation of the fluorescence of the dansyl reporter is
effective depending on the nature of the radical species
[nitronyl-nitroxide (NIT) versus an imino-nitroxide
(IM)].16
a first step, of an aliphatic nitroxide radical and subsequently of an
additional aromatic radical. The synthetic methods reported herein
provide a practical approach to the rational design of ligands bear-
ing various kinds of functionalities such as chromogenic and spin-
labeled fragments. A significant merit of this method is that it al-
lows the introduction of the fluorescent substituent onto the pyri-
dine or bipyridine framework at the beginning of the synthetic
protocol.
Key words: pyridine, bipyridine, dansyl, nitroxide radicals, ab-
sorption spectrum
The engineering of molecules bearing chelating centers,
fluorescent and paramagnetic probes offers a wealth of
possibilities for the construction of sophisticated scaffold-
ings with predesigned optical and magnetic properties.1
The realization of this potential required a detailed under-
standing of the chemistry and also of the intrinsic features
of the individual building blocks to allow prediction and
design of novel systems.2 To gain insight into the devel-
opment of new class of material and to integrate them in
new devices such as chemiosensors we have to embrace
different measurement techniques including UV-visible
absorption, EPR, photoluminescence, measurement of the
excited states of lifetime in a time resolved mode in dilute
solution and/or in solid-state films. The objectives to this
research program is to synthesize and characterize a novel
series of spin-labeled molecules bearing a singlet reporter
(dansyl fragment) and an electron-donor (radical moi-
eties) in order to tune the luminescence characteristics in
the presence of adventitious cations or other substrates.3
The investigation of their spectroscopic, electrochemical,
photophysical, structure-property relationship and optimi-
zation will be performed in a second step.
Since few years we have been interested in the synthesis
and properties of nitroxide radicals containing chelating
centers.17 For this purpose we have developed a synthetic
strategy based on the construction of molecules bearing
aldehyde as well as reactive halide functions in order to
involve them in palladium/copper-promoted cross cou-
pling reactions with terminal alkynes reagents.18 As we
were particularly interested in the behavior of these scaf-
folds in magneto-optical properties, we decided to inves-
tigate the synthesis of novel molecules bearing a stable
and very efficient organic fluorophore. As a model reac-
tion we first studied the conversion of 2-aminomethyl-6-
hydroxymethylpyridine (4) into the corresponding N-sub-
stituted dansylated derivative 5 as sketched in Scheme 1.
After some experimentation it became evident that this re-
action is regioselective affording the selective alkylation
of the amino fragment in 75%. The synthetic route to this
interesting derivative 5 employs straightforward reactions
that are easily accomplished on a large scale. The prepa-
ration of the starting material 419 was realized in three
steps from the commercially available 2,6-bis(hydroxy-
methyl)pyridine (1) as shown in Scheme 1.
Dansyl moieties have been successfully employed as
fluorogenic probes in several cases which include N-pro-
SYNTHESIS 2003, No. 14, pp 2145–2154
0
2.
1
0
.
2
0
0
3
Advanced online publication: 24.09.2003
DOI: 10.1055/s-2003-42083; Art ID: Z06903SS.pdf
© Georg Thieme Verlag Stuttgart · New York

2146
R. Ziessel, C. Stroh
PAPER
Br
Br
Br
N
+
(a)
(b)
HO
OH
N
+
N
N
(c)
1
HO
HO
N
N
N
N
Br -
2
3
(d) , (e)
H
H
O
N
N
HO
N
SO2
N
SO2
(f)
HO
NH2
(g)
N
6
5
4
N
N
Scheme 1 (a) HBr (37%), reflux; (b) aq NaOH 40%; (c) hexamethylenetetramine, CH2Cl2, reflux; (d) HCl (36%), EtOH, reflux; (e) 2 N aq
NaOH; (f) DANS–Cl (1 equiv), MeCN, Et3N, r.t.; (g) MnO2, CH2Cl2, r.t.
Figure 1 ORTEP view of compound 5.
The dansylated alcohol 5 crystallizes in the P-1 space
group and an ORTEP view is given in Figure 1. The bond
distances around the pyridine ring are in conformity keep-
ing with related X-ray molecular structures. It is of inter-
est to note that the sulfonamide fragment is located in an
anti position versus the pyridine ring (N3–C14–C13–N2
torsion angle = 171.0°). Furthermore, the hydroxymethyl
fragment adopt an eclipsed conformation versus one of
the hydrogen atom of the methylene bridge (N3–C18–
C19–O3 torsion angle = 67.8°). This interesting arrange-
ment of the atoms is auspicious for intermolecular hydro-
gen bonding in the solid state (vide infra). Additionally,
the nitrogen atom of the sulfonamide fragment is almost
planar, as evidenced by the fact that the sum of the angles
provided by all the substituents is 359.2°. Furthermore,
the plane formed by these fragments is quasi orthogonal to
the plane formed by the pyridine cycle (H01–N2–C13–
C14 torsion angle = 91.2°). As expected one of the sp3
sulfur–oxygen bond lies in a trans position versus the py-
ridine CN bond (C13–N2–S–O1 torsion angle = 162.4°).
Finally, it is of interest to note that the naphthyl group de-
viates slightly from the mean plane formed by the tertiary
amine (tilt angle ca. 110°). Close examination of the pack-
ing of these molecules in the solid state reveal two inter-
esting features. The packing is essentially governed by a
Figure 2 a) Intermolecular hydrogen bonding between molecules
hydrogen bonding network as well as by - stacking of
of 5: shortest distances 1.86 and 1.96 Å; b)
between neighboring molecules of 5, shortest distances 3.52 Å.
- stacking interaction
the naphthyl rings as shown in Figure 2. The shortest hy-
drogen bond is observed between the hydrogen of the al-
cohol of one molecule and the sulfonamide group of a
neighboring molecule (O3–H01 distance ca. 1.86 Å). Two
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Oligopyridines Bearing Multiple Dansyl and Nitroxide Radicals
2147
types of hydrogen bonds are evidenced by the X-ray mo- tween the electron rich aliphatic radical and the more elec-
lecular structure determination. Two molecules of 5 are tron demanding aromatic radical. A nice solution came
arranged in a head-to tail fashion to form a dimer out, when we discovered that protection of the aldehyde
(Figure 2a), in which a second hydrogen bond is observed function with an oxolane leading to compound 7 allowed
between the oxygen atom of the sulfonamide function and the smooth alkylation of the sulfonamide to provide the
the hydrogen atom of the primary alcohol (O1–H02 dis- desired derivative 8. This reaction required the presence
tance ca. 1.90 Å) forming an infinite chain of dimeric of catalytic amounts of KI favoring the in situ exchange of
units. Finally, a second type of stabilizing interaction is the halide and the presence of a base, which quenched the
due to a favorable – overlapping (average distance ca. nascent acid (Scheme 2). During this reaction, we found
3.52 Å) between two neighboring naphthyl subunits only traces of the alkylation of the pyridine fragment lead-
(Figure 2b).
ing, as expected, to polar derivatives. It is worth pointing
out that a single step was required to synthesize the target
bisradical 13. The use of the sulfate salt of 2,3-bis(hy-
droxyamino)-2,3-dimethylbutane favors the in situ depro-
tection of the aldehyde and the in situ condensation to the
intermediate five-membered ring. Such a simultaneous
and one-pot deprotection of the aldehyde and condensa-
tion step has been previously exploited with instable alde-
hydes.21 Phase-transfer oxidation is straightforward and
produced the bisradical 13 in acceptable yield
(Scheme 2).
Additional studies on the chemical reactivity of com-
pound 5 shows that the primary alcohol is readily oxidized
under mild conditions with MnO2 to the corresponding
formyl compound 6 in 75% (Scheme 1). This molecule is
of special interest because it has the potential for the con-
struction of two different kind of spin carries such as, one
radical on the formyl site (aromatic nitroxide) and a sec-
ond radical on the sulfonamide site (aliphatic nitroxide).
In the first case, condensation of 6 with 2,3-bis(hy-
droxyamino)-2,3-dimethylbutane afforded the intermedi-
ate dihydroxyimidazolidine 10 which by phase-transfer In order to check the generality of the regioselective alky-
oxidation with aqueous sodium periodate gave the deep lation reaction with chloromethylnitronyl nitroxide, we
blue radical 11 in fair yield (Scheme 2). The presence of attempted the reaction with derivative 5. It was soon es-
trace amounts of SeO220 during the condensation step al- tablished that, with KI the reaction is completely re-
lowed the intermediate formation of the monohydroxyim- giospecific and no pyridine or NMe2 alkylation was
idazolidine 9 which similarly provided after phase- observed (Scheme 4). This is probably due to the relative-
transfer oxidation the expected orange monoradical 12 in ly low pK value of the sulfonamide and the mild experi-
good yield. Direct alkylation of the remaining sulfona- mental conditions.22 However, the yield is significantly
mide function with chloromethylnitronyl nitroxide failed lower compared to the alkylation of derivative 7. In this
providing intractable mixture of compounds (Scheme 3). case the O-alkylation of the benzylic function could not be
This is probably due to electron-transfer processes be- excluded, despite the fact that the ether derivative could
Scheme 2 (a) HOCH2CH2OH, p-TsOH, benzene; (b) chloromethylnitronyl nitroxide, K2CO3, KI (10 mol%), MeCN, 60 °C; (c) 2,3-bis(hy-
droxyamino)-2,3-dimethylbutane sulfate salt, MeOH, r.t.; (d) 2,3-bis(hydroxyamino)-2,3-dimethylbutane, MeOH, r.t.; (e) 2,3-bis(hydroxyami-
no)-2,3-dimethylbutane, SeO2, r.t., MeOH; (f) NaIO4, CH2Cl2, H2O, r.t.
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R. Ziessel, C. Stroh
PAPER
Scheme 3 (a) chloromethylnitronyl nitroxide (1 equiv), K2CO3, KI (10 mol%), MeCN, 30–60 °C
O
O
N
N
Cl
N
N
H
O
HO
O
N
N
HO
SO2
N
N
SO2
(a)
5
14
N
N
Scheme 4 (a) chloromethylnitronyl nitroxide (1 equiv), K2CO3, KI (10 mol%), MeCN, 60 °C
not be properly isolated possibly due to its inherent insta- viously formulated for the preparation of compound 5.
bility.
The selective alkylation of the sulfonamide is effective
and the prior difficulties are circumvented by the absence
of the benzylic alcohol function. The dialkylation of de-
rivatives 16 and 22 is driven by the stoichiometry of start-
ing reagents.
As the former functionalization of compounds 5 and 7
gave satisfactory results, we were encouraged to extend
this reaction to additional mono- or didansylated pyridine
or bipyridine frameworks (Scheme 5). Here the highly lu-
minescent molecules 16, 19 and 22 were prepared in ex- Preliminary studies on the chemical stability, of these
cellent yield from the corresponding mono- and molecules in dilute solution, is provided by EPR studies
diaminomethyl derivatives under similar conditions pre- (Figure 4). As a matter of fact such studies have been only
Scheme 5 (a) DANS-Cl (2 equiv) for 15 and 21 and (1 equiv) with 18, MeCN, Et3N, r.t.; (b) chloromethylnitronyl nitroxide (2 equiv) for 16
and 22 and (1 equiv) with 19, K2CO3, KI (10 mol%), MeCN, 60 °C
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PAPER
Oligopyridines Bearing Multiple Dansyl and Nitroxide Radicals
2149
scarcely performed.23 We checked by EPR that the ther-
mal stability of monoradicals 11 and 12 is excellent in po-
lar and apolar solvents at 10–5 M. No loss of the signal
intensity and the shape of the spectra were found when di-
lute solutions were allowed to stand in the dark or in sun-
light over 60 hours. The stability of these hybrid
molecules is as good as the one found for classical nitrox-
ide radicals previously prepared in our laboratory
(Figure 3).
Figure 3 Structures of some known classical nitroxide radicals
A–C.
However, the steady state irradiation with more powerful
light sources (e.g. 100 W, Olympus Xe lamp without cut-
off filter) shows major modification of the EPR spectrum
over irradiation time. The typical five lines spectrum char-
acteristic of the nitronyl nitroxide radical 11 (g = 2.0066)
is progressively transformed into a seven line spectrum
characteristic of an imino nitroxide radical (Figure 4a). It
is surmised that during the irradiation selective deoxygen-
ation of the radical 11 to the radical 12 is achieved. It is
interesting to note that at the early stage of the photolysis
process a transient species is observed. In order to check
that this species is due to the presence of the pendent dan-
syl fragment or pyridine ring, the photolysis of derivatives
A, B, C (Figure 3) was undertaken in different solvents
(Figure 4b). During the photolysis of compounds A and B
no transient species was observed in three different sol-
vents. However, it appears clearly that a very similar in-
termediate species is present during photolysis of the
pyridine based derivative C.
Figure 4 a) Evolution of the EPR spectrum of derivative 11 as a
function of irradiation time, in CH2Cl2 at 10–5 M. Top trace: before ir-
radiation, and successive irradiation of 10 min slots. Bottom trace: af-
ter 30 min irradiation. b) Irradiation of compound C at 10–5 M for 15
min a) in CH2Cl2; b) acetone; c) MeOH.
absorption bands to transitions localized on the ancillary
pyridine or bipyridine - * transitions in the UV at ap-
proximately 250 to 280 nm,26 to the dansyl singlet state
transitions in the near UV around 340 nm27 and n
*
transition of the nitroxide radical around 550 nm
(Figure 5b).28,29 As expected the latter transition is absent
in the spectrum of related diamagnetic species
(Figure 5a). Finally, it appears that no significant modifi-
cation of the absorption spectrum of the diamagnetic and
paramagnetic derivatives was observed in dilute solution
when the samples are stored in the absence of direct light
over at least two days.
This observation excludes a major contribution of the dan-
syl fragment but strengthened the fact that the pyridine
moiety plays a major role during the photochemical event.
In this case also it appears that the photoconversion of the
nitronyl nitroxide to the imino nitroxide species is very ef-
fective and does not depend on the nature and polarity of
the solvent. At the present stage of our investigations the
nature of this transient species is not known but might re-
sult from the stabilization (or trapping) of a very reactive
radical by the pyridine ring possibly in the form of a pyri-
dine N-oxide radical. Photolysis experiments at cryogenic
temperature would provide some useful information
about the chemical nature of this very reactive intermedi-
ate. Previous studies on the direct and photosensitized
photochemistry of stable free radicals in aprotic solvent
have revealed similar deoxygenation processes but in-
volving the reactivity of the aliphatic side chain.24,25
Taken as a whole, the results presented here provide a ra-
tional approach for the synthesis of hybrid molecules
bearing dansyl and free radical subunits. All reactions are
effective under mild and well controlled reaction condi-
tions and cleanly gives the desired molecules. Symmetri-
cally substituted ligands were prepared in two steps from
the corresponding
aminomethyl starting materials.
Asymmetrically substituted pyridines were synthesized in
three and five steps from the hydroxymethyl compound
leading respectively to molecules with one and two free
radicals. This finding expands the synthetic scope of dan-
sylated molecules carrying free radicals and makes readi-
ly accessible a class of previously rare ligands. The
Figure 5 illustrates the absorption spectra of dansylated
pyridine and bipyridine ligands and their nitronyl nitrox-
ide counterparts. Comparison with the spectra of the indi-
vidual fragments allows assignment of the various
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2150
R. Ziessel, C. Stroh
PAPER
ture was cooled down to 0 °C and neutralized (pH 6.9) with aq 40%
NaOH. H2O (200 mL) was added and the white precipitate was ex-
tracted with CH2Cl2 (5 × 100 mL). The combined organic layers
were evaporated to dryness and the solid was purified by flash chro-
matography (silica gel) using CH2Cl2 as eluent to separate first the
dibromo adduct (11%), followed by elution with Et2O providing the
desired product 2; yield: 2.8 g (39%).
IR (KBr): 3213, 3054, 2975, 2840, 1593, 1568, 1456, 1348, 1218,
1201, 1148, 1090, 1064, 1000, 800, 755, 736, 636, 616, 569, 506
cm–1.
1H NMR (CDCl3): = 7.66 (t, 1 H, 3J = 7.6 Hz, H-4), 7.30 (d, 1 H,
3
3J = 7.6 Hz, H-3), 7.19 (d, 1 H, J = 8.0 Hz, H-5), 4.72 (d, 2 H,
3J = 4.4 Hz, CH2O), 4.50 (s, 2 H, CH2Br), 4.26 (br, 1 H, OH).
13C{1H} NMR (CDCl3): = 159.2, 155.8, 137.8, 122.1, 119.9, 64.0
(CH2O), 33.5 (CH2Br).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 268 (4900), 229 nm (4300).
Anal. Calcd for C7H8BrNO (202.05): C, 41.61; H, 3.99; N, 6.93.
Found: C, 41.45; H, 3.89; N, 6.79.
2-[(Hexamethylenetetrammonium)methyl]-6-hydroxymeth-
ylpyridine Bromide (3)
2-Bromomethyl-6-hydroxymethylpyridine (2; 0.5 g, 2.47 mmol)
and hexamethylenetetramine (0.42 g, 2.96 mmol) in CH2Cl2 (20
mL) were refluxed for 4 h. The white precipitate was filtered and
washed with Et2O (3 × 50 mL) to afford 0.840 g (98%) of 3.
IR (KBr): 3347, 2972, 2941, 2894, 1591, 1571, 1464, 1436, 1303,
1269, 1254, 1237, 1200, 1111, 1046, 1005, 991, 934, 825, 812, 785,
652, 571, 501 cm–1.
Figure 5 a) Normalized absorption spectrum in CH2Cl2 solution of
a series of mono- and didansylated compounds; b) normalized ab-
sorption spectrum in CH2Cl2 solution of a series of radicals bearing a
single dansyl fragment.
2-Aminomethyl-6-hydroxymethylpyridine (4)
A mixtutre of 3 (0.796 g, 0.435 mmol), HCl (37%, 4.4 mL) and
EtOH (20 mL) was heated at 100 °C. After 17 h, the clear solution
was cooled down to r.t., then Et2O (150 mL) was added and the re-
sulting white precipitate was filtered off. The solid was dissolved in
H2O (4 mL) and the solution was basified with 6 N aq NaOH to
pH 14. The product was extracted with CH2Cl2 (4 × 100 mL). After
drying (MgSO4), the solvent was evaporated to give 4; yield:
0.307 g (97%).
demonstrated ability of these molecules to be robust in di-
lute solutions and in the solid state augurs well for imme-
diate and long term advances in the field of sensors.
The 200.1 (1H) and 50.3 MHz (13C) NMR spectra were recorded at
r.t. on a Bruker AC 200 spectrometer in CDCl3 Residual CHCl3 in
CDCl3 ( H = 7.26 and C = 77.3) were used as internal standards. In
order to avoid acidic traces, the deuterated solvent was passed
through a cartouche of basic alumina. FT-IR spectra were recorded
as KBr pellets on a Nicolet 210 spectrometer. High Resolution Mass
Spectral Analysis (HRMS) were performed using a Mariner ESI-
Tof instrument from Applied Bio-System/Perking Elmer. Fast-
atom bombardement (FAB, positive mode) mass spectra were re-
corded with a ZAB-HF-VB-analytical apparatus in m-nitrobenzyl
alcohol (m-NBA) as matrix. Chromatographic purification was con-
ducted using 0.063–0.200 mm silica gel or aluminum oxide 90
(Merck). TLC was performed on silica gel or aluminum oxide plates
(Merck) coated with fluorescent indicator. All mixtures of solvents
are given in v/v ratio.
2,6-Bis(aminomethyl)pyridinium trichloride (15),30 6-aminometh-
yl-2,2 -bipyridine (18),31 6,6 -aminomethyl-2,2 -bipyridine (21),32
chloromethylnitronyl nitroxide,33 and 2,3-bis(hydroxyamino)-2,3-
dimethylbutane34 were prepared according to literature procedures.
CH2Cl2 was distilled from CaH2. Et3N was dried over KOH prior to
distillation. MeCN was filtered over aluminum oxide (Merck, Act
III) and distilled over P2O5. Dansyl chloride, MnO2, NaIO4 were
used as purchased.
IR (KBr) = 3365, 2977, 1597, 1577, 1459, 1382, 1319, 1049, 616
cm–1.
3
1H NMR (CDCl3): = 7.64 (t, 1 H, J = 7.6 Hz), 7.18 (d, 1 H,
3J = 7.6 Hz), 7.10 (d, 1 H, 3J = 7.6 Hz), 4.74 (s, 2 H, CH2O), 3.98 (s,
2 H, CH2N), 2.26 (br, OH, NH2, H2O).
MALDI-TOF: m/z (%) = 139.1 ([M + H]+, 100%).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 272 nm (4400).
2-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-6-hy-
droxymethylpyridine (5)
To a solution of 4 (0.260 g, 1.88 mmol) and dansyl chloride (0.507
g, 1.88 mmol) in anhyd
MeCN (10 mL) was added slowly anhyd Et3N (1 mL). The yellow
precipitate disappeared instantaneously, to yield a yellow-greenish
solution. After stirring for 64 h at r.t., the reaction mixture was evap-
orated to dryness. The residual oil was dissolved in CH2Cl2 (50 mL)
and vigourously washed with H2O (3 × 25 mL). The organic phase
was dried (MgSO4) and evaporated to dryness. The remaining oil
was purified by flash chromatography (silica gel, eluent: CH2Cl2
with a gradient of 1% MeOH) to afford 5 (0.526 g, 75%).
IR (KBr): 3433, 3147, 2962, 2924, 2876, 2838, 1588, 1573, 1456,
1420, 1398, 1384, 1324 (SO2N), 1262, 1231, 1158 (SO2N), 1140,
1121, 1092, 1047, 1017, 961, 851, 784 cm–1.
2-Bromomethyl-6-hydroxymethylpyridine (2)
A mixture of 2,6-bis(hydroxymethyl)pyridine (1; 5 g, 35.9 mmol)
and HBr (37%, 50 mL) was refluxed for 1 h. The crude yellow mix-
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Oligopyridines Bearing Multiple Dansyl and Nitroxide Radicals
2151
1H NMR (CDCl3): = 8.42 (d, 1 H, J = 8.4 Hz), 8.29 (d, 1 H,
3J = 8.4 Hz), 8.19 (dd, 1 H, 3J = 7.4 Hz, 4J = 1.0 Hz), 7.55–7.33 (m,
3 H), 7.13 (d, 1 H, 3J = 7.2 Hz), 6.91 (d, 1 H, 3J = 7.6 Hz), 6.84 (d,
UV-Vis (CH2Cl2), , ( , M–1cm–1) = 270 (3500), 347 nm (1500).
Anal. Calcd for C21H23N3O4S (413.49): C, 61.00; H, 5.61; N, 10.16.
Found: C, 60.79; H, 5.43; N, 9.93.
3
3
1 H, J = 7.6 Hz), 6.25 (t, 1 H, J = 5.6 Hz, NH), 4.44 (s, 2 H,
3
CH2OH), 4.19 (d, 2 H, J = 5.2 Hz, CH2NH), 3.41 (br, 1 H, OH),
2-{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-3-
oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]methyl}-6-
(1,3-dioxolan-2-yl)pyridine (8)
2.84 (s, 6 H, CH3).
13C{1H} NMR (CDCl3): = 158.9, 154.2, 152.0, 137.1, 134.7,
130.4, 129.8, 129.7, 129.6, 128.4, 123.2, 120.5, 119.2, 118.9, 115.2,
64.1, 47.8, 45.5.
FAB+ (m-NBA): m/z (%): 372.2 ([M + H]+, 100), 123.2 ([M –
DANS + H], 20).
A mixture of 7 (0.200 g, 0.484 mmol), K2CO3 (0.337 g, 2.420
mmol), KI (0.008 g, 10 mol%) and chloromethylnitronyl nitroxide
(0.120 g, 0.580 mmol) in MeCN (20 mL) was heated at 60 °C in the
dark for 2 h. Then the reaction was quenched with H2O (20 mL) and
extracted with CH2Cl2 (2 × 100 mL). The combined organic layers
were dried (MgSO4) and evaporated to dryness; yield: 78%. An an-
alyticaly pure sample 8 (0.220 g) was obtained by chromatography
(Al2O3, eluent: CH2Cl2 with a gradient of 1% MeOH).
UV-Vis (CH2Cl2): , ( , M–1cm–1) = 270 (5900), 343 nm (3100).
Anal. Calcd for C19H21N3O3S (371.46): C, 61.44; H, 5.70; N, 11.31.
Found: C, 61.21; H, 5.51; N, 11.01.
IR (KBr): 3520, 290, 1617, 1586, 1563, 1457, 1402, 1355 (NO),
1324 (SO2N), 1146 (SO2N), 1098, 824 cm–1.
2-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-6-
formylpyridine (6)
ESI-TOF: m/z (%) = 605.3 ([M + Na]+, 10), 568.3 ([M – O + 2 H +
To a solution of 5 (0.297 g, 0.80 mmol) in CH2Cl2 (50 mL) was add-
ed MnO2 (2.12 g, 30 equiv). The suspension was stirred for 45 h.
After filtration over Celite, the solvent was evaporated and the prod-
uct was purified by flash chromatography (silica gel, eluent: CH2Cl2
with a gradient of 1% MeOH) to give the desired product 6 (0.209
g); yield: 71%.
e–], 100), 552.3 ([M – 2 O + 2 H + e–], 10).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 545 (900), 330 (16500), 270 nm
(10200).
Anal. Calcd for C29H36N5O6S (582.69): C, 59.78; H, 6.23; N, 12.02.
Found: C, 59.44; H, 5.98; N, 11.81.
IR (KBr): 3256, 1697 (C=O), 1588, 1445, 1339, 1320 (SO2N), 1162
(SO2N), 1146, 1091, 1069, 856, 789 cm–1.
1H NMR (CDCl3): = 9.57 (s, 1 H, CHO), 8.34 (t, 2 H, 3J = 8.4 Hz),
8.18 (d, 1 H, 3J = 7.2 Hz), 7.58–7.50 (m, 3 H), 7.39 (t, 1 H, 3J = 7.8
Hz), 7.13–7.08 (m, 2 H), 6.13 (t, 1 H, 3J = 5.4 Hz, NH), 4.32 (d, 2
H, 3J = 6.0 Hz, CH2), 2.82 (s, 6 H, CH3).
13C{1H} NMR (CDCl3): = 192.6, 155.6, 152.0, 151.6, 137.2,
134.6, 130.5, 129.7, 129.6, 128.4, 125.7, 123.1, 120.0, 119.0, 115.5,
47.6, 45.4.
2-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-6-(1-
oxyl-3-oxide-4,4,5,5-tetramethylimidazolin-2-yl)pyridine (11)
Compound 6 (0.105 g, 0.284 mmol), and 2,3-bis(hydroxyamino)-
2,3-dimethylbutane (0.130 g, 0.877 mmol) were dissolved in
MeOH (10 mL). After stirring for 5 h at r.t. and in the dark, the so-
lution was evaporated to dryness. The residual solid was oxidized
with NaIO4 (0.090 g, 0.421 mmol) in a biphasic mixture of H2O–
CH2Cl2 (200 mL, 1:1) for 1 h. The product was extracted with
CH2Cl2 and the organic phase was dried (MgSO4) and evaporated.
The pure radical 11 (0.051 g) was obtained by chromatography
(Al2O3, eluent: CH2Cl2 with a gradient of 0.2% MeOH); yield: 36%.
IR (KBr): 3429, 2928, 1612, 1588, 1573, 1454, 1396, 1367 (NO),
1325 (SO2N), 1144 (SO2N), 1074, 791 cm–1.
FAB+ (m-NBA): m/z (%): 370.5 ([M + H]+, 100), 121.5 ([M –
DANS], 30).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 269 (3100), 345 nm (1200).
Anal. Calcd for C19H19N3O3S (369.44): C, 61.77, H, 5.18, N, 11.37.
Found: C, 61.41, H, 4.78, N, 10.91.
MS (ES+): m/z = 497.2 [M + H]+, 482.3 [M – O + 2H], 466.3 [M –
2O + 2H].
UV-Vis (CH2Cl2),
(9550), 294 (7200), 270 nm (11160).
,
(M–1cm–1) = 580 (300), 370 (13900), 355
2-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-6-
(1,3-dioxolan-2-yl)pyridine (7)
A mixture of 6 (0.200 g, 0.540 mmol), ethylene glycol (5 mL) and
p-toluenesulfonic acid (0.005 g) in benzene (20 mL) was refluxed
in a Dean–Stark apparatus overnight. The solvent was evaporated
under vacuum and brine was added, and the aqueous phase was ex-
tracted with CH2Cl2 (5 × 50 mL). The combined organic phases
were dried (Na2SO4) and the solvent was removed under vacuum.
The protected aldehyde was purified by chromatography (silica gel,
flash chromatography, eluent: CH2Cl2 with a gradient of 1%
MeOH) to give 7; yield: 0.213 g (95%).
Anal. Calcd for C25H30N5O4S (496.60): C, 60.46; H, 6.09; N, 14.10.
Found: C, 60,19; H, 5.84; N, 13.75.
2-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-6-(1-
oxyl-4,4,5,5-tetramethylimidazolin-2-yl)pyridine (12)
Compound 6 (0.114 g, 0.309 mmol), 2,3-bis(hydroxyamino)-2,3-
dimethylbutane (0.130 g, 0.877 mmol) were dissolved in MeOH (20
mL). After stirring for 9 h at r.t. and in the dark, the solution was
evaporated. The solid was oxidized with NaIO4 (0.090 g, 0.421
mmol) in a biphasic mixture of H2O–CH2Cl2 (200 mL, 1:1) for 45
min. The product was extracted with CH2Cl2 and the organic phases
were dried (MgSO4) and evaporated. The radical 12 (0.015 g) was
obtained after chromatography (Al2O3, eluent: CH2Cl2 with a gradi-
ent of 0.2% MeOH); yield: 10%.
IR (KBr): 3256, 3000, 2880, 1590, 1450, 1336, 1322 (SO2N), 1165
(SO2N), 1146, 1075, 865 cm–1.
1H NMR (CDCl3): = 8.3 (t, 2 H, 3J = 8.3 Hz), 8.22 (d, 1 H, 3J = 7.1
Hz), 7.58–7.52 (m, 3 H), 7.40 (t, 1 H, 3J = 7.8 Hz), 7.15–7.10 (m, 2
H), 6.15 (t, 1 H, 3J = 5.3 Hz, NH), 5.76 (s, 1 H, OCHO), 4.32 (d, 2
H, 3J = 6.0 Hz, CH2), 3.99 (s, 4 H, OCH2CH2O, 4 H), 2.82 (s, 6 H,
CH3).
IR (KBr): 3434, 2925, 2853, 1588, 1574, 1451, 1384 (NO), 1326
(SO2N), 1161 (SO2N), 1145, 1073, 791 cm–1.
FAB+ (m-NBA): m/z (%) = 481.2 ([M + H]+, 100), 232.4 ([M –
DANS], 20.
UV-Vis (CH2Cl2): , ( , M–1cm–1) = 420 (700), 368 (12900), 360
(9500), 294 (8000), 268 nm (12000).
13C{1H} NMR (CDCl3): = 158.6, 154.0, 152.4, 138.5, 133.9,
131.5, 130.5, 130.2, 129.3, 124.7, 123.5, 121.4, 120.2, 116.3, 113.9,
73.8, 47.4, 46.7.
FAB+ (m-NBA): m/z (%): 414.1 ([M + H]+, 100), 167.3 ([M –
DANS + H]+, 30).
Anal. Calcd for C25H30N5O3S (480.60): C, 62.48; H, 6.29; N, 14.57.
Found: C, 62.23; H, 5.91; N, 14.29.
Synthesis 2003, No. 14, 2145–2154 © Thieme Stuttgart · New York

2152
R. Ziessel, C. Stroh
PAPER
2-{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-3-
oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]methyl}-6-
(1-oxyl-3-oxide-4,4,5,5-tetramethylimidazolin-2-yl)pyridine
(13)
FAB+ (m-NBA): m/z (%) = 604.5 ([M + H]+, 100), 355.3 ([M –
DANS], 25).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 229 (13300), 256 (13900), 344
nm (3900).
Compound 8 (0.200 g, 0.343 mmol), 2,3-bis(hydroxyamino)-2,3-
dimethylbutane sulfate salt (0.127 g, 0.514 mmol) were dissolved in
MeOH (10 mL). After stirring for 5 h at r.t. and in the dark, the so-
lution was evaporated to dryness. The residual solid was oxidized
with NaIO4 (0.075 g, 0.350 mmol) in a biphasic mixture of H2O–
CH2Cl2 (200 mL, 1:1) for 1 h. The product was extracted with
CH2Cl2 and the organic phase was dried (MgSO4) and evaporated.
The pure radical 13 (0.174 g) was obtained by chromatography
(Al2O3, eluent: CH2Cl2 with a gradient of 0.2% MeOH); yield: 76%.
Anal. Calcd for C31H33N5O4S2 (603.76): C, 61.67; H, 5.51; N,
11.60. Found: C, 61.40; H, 5.49; N, 11.41.
2,6-{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-
3-oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]meth-
yl}pyridine (17)
A mixture of 16 (0.200 g, 0.331 mmol), K2CO3 (0.150 g, 1.076
mmol), KI (0.0055 g, 10 mol%) and chloromethylnitronyl nitroxide
(0.150 g, 0.728 mmol) in MeCN (50 mL) was heated at 50 °C in the
dark for 3 h. The reaction was quenched with H2O (50 mL) and the
organic phase was extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were dried (MgSO4) and evaporated to dry-
ness; yield: 79%. An analyticaly pure sample 17 (0.246 g) was
obtained by chromatography (Al2O3, eluent: CH2Cl2 with a gradient
of 5% MeOH).
IR (KBr): 3450, 2930, 1615, 1584, 1570, 1453, 1398, 1370 (NO),
1323 (SO2N), 1141 (SO2N), 1075, 802 cm–1.
ESI-TOF: m/z (%) = 688.2 ([M + Na]+, 30), 666.2 ([M + H], 100),
635.3 ([M – 2 O + 2 H + e–], 10), 385.3 ([M – 2 O – DANS], <10).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 585 (1100), 375 (16500), 355
(10500), 330 (17000), 296 (10200), 270 nm (14000).
IR (KBr): 3298, 2939, 2857, 1585, 1456, 1436, 1412, 1324 (SO2N),
1162 (SO2N), 1146, 1093, 1070, 790, 775 cm–1.
FAB+ (m-NBA): m/z (%) = 942.1 ([M + H]+, 100), 926.1 ([M – O +
H], 70), 678.2 ([M – O – DANS], 30), 414.2 ([M – 2 DANS – 2 O],
<10).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 545 (1200), 345 (5600), 260
(17600), 248 (20200), 230 nm (21000).
Anal. Calcd for C33H43N7O6S (665.80): C, 59.53; H, 6.51; N, 14.73.
Found: C, 59.27; H, 6.31; N, 14.40.
2-{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-3-
oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]methyl}-6-
(hydroxymethyl)pyridine (14)
Compound 5 (0.099 g, 0.269 mmol), K2CO3 (0.075 g, 0.538 mmol),
KI (0.0045 g, 10 mol%) and chloromethylnitronyl nitroxide (0.061
g, 0.296 mmol) were dissolved in MeCN (20 mL) and heated at
60 °C in the dark for 2 h. Then, the reaction was quenched with H2O
(20 mL) and extracted with CH2Cl2 (2 × 100 mL). The organic layer
was dried (MgSO4) and evaporated to dryness; yield: 28%. An ana-
lytically pure sample 14 (0.041 g) was obtained by chromatography
(Al2O3, eluent: CH2Cl2 with a gradient of 1% MeOH).
Anal. Calcd for C47H59N9O8S2 (942.16): C, 59.92; H, 6.31; N,
13.38. Found: C, 59.6; H, 5.99; N, 13.12.
6-[(5-Dimethylamino-1-naphthalenesulfonamide)methyl]-2,2 -
bipyridine (19)
To a solution of 18 (0.937 g, 0.59 mmol) and dansyl chloride (0.159
g, 0.59 mmol) in distilled MeCN (10 mL) was added anhyd Et3N (1
mL) in portions and the mixture was stirred at r.t. for 40 h. H2O (75
mL) was added and the mixture was acidified with 10% aq HCl to
pH 1 and extracted with Et2O (3 × 75 mL). The aqueous phase was
basified with aq KOH to pH 8 and extracted with CH2Cl2 (3 × 100
mL). The combined organic layers were dried (MgSO4), evaporated
to dryness, and the crude solid was purified by flash chromatogra-
phy (silica gel, eluent: CH2Cl2 with a gradient of 1% MeOH) to give
the desired product 19; yield: 0.206 g (83%).
IR (KBr): 3293, 2936, 2852, 1573, 1453, 1432, 1415, 1323 (SO2N),
1160 (SO2N), 1143, 1091, 1065, 789, 771 cm–1.
ESI-TOF: m/z (%) = 563.3 ([M + Na]+, 10), 526.3 ([M – O + 2 H +
e–], 100), 510.3 ([M – 2 O+ 2 H + e–], 10).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 540 (800), 328 (15200), 269 nm
(9600).
Anal. Calcd for C27H34N5O5S (540.66): C, 59.98; H, 6.34; N, 12.95.
Found: C, 59.65; H, 6.21; N, 12.75.
IR (KBr): 3292, 2939, 2831, 1581, 1456, 1431, 1407, 1324 (SO2N),
1162 (SO2N), 1144, 1091, 1072, 790, 775 cm–1.
2,6-Bis-[(5-dimethylamino-1-naphthalenesulfonamide)meth-
yl]pyridine (16)
3
1H NMR (CDCl3): = 8.58 (d, 1 H, J = 4.8 Hz), 8.36 (d, 2 H,
3
3
To a solution of 15 (0.683 g, 0.277 mmol) and dansyl chloride
(0.152 g, 0.563 mmol) in anhyd MeCN (10 mL) was added drop-
wise anhyd Et3N (3.5 mL). After keeping for 5 d at r.t., H2O (50 mL)
was added. The mixture was basified with 2 N aq NaOH to pH 9 and
extracted with CH2Cl2 (2 × 150 mL). The combined organic layers
were dried (MgSO4) and evaporated to dryness. The residual solid
was purified by flash chromatography (silica gel, eluent: CH2Cl2
with a gradient of 1% MeOH) to give, after recrystallisation from a
mixture of CH2Cl2–hexane, the desired compound 16; yield: 0.827
g (49%).
3J = 8.4 Hz), 8.22 (d, 1 H, J = 7.2 Hz), 8.05 (t, 2 H, J = 7.8 Hz),
4
7.72 (dt, 1 H, 3J = 7.6 Hz, J = 1.7 Hz), 7.50–7.34 (m, 3 H), 7.28–
7.22 (m, 1 H), 6.92 (t, 2 H, 3J = 7.8 Hz), 6.41 (t, 1 H, 3J = 5.4 Hz,
NH), 4.27 (d, 2 H, 3J = 5.2 Hz, CH2), 2.74 (s, 6 H, CH3).
13C{1H} NMR (CDCl3): = 155.2, 155.1, 153.9, 151.9, 149.1,
137.3, 136.8, 134.6, 130.4, 129.8, 129.6, 128.4, 123.9, 123.1, 121.7,
121.1, 119.6, 118.8, 115.1, 47.9, 45.3.
FAB+ (m-NBA): m/z (%) = 419.3 ([M + H]+, 100), 170.3 ([M –
DANS], 10).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 344 (3700), 288 (12900), 259
(17600), 246 (19600) 229 nm (19000).
IR (KBr): 3302, 2941, 2869, 1588, 1575, 1455, 1408, 1325 (SO2N),
1161 (SO2N), 1145, 1073, 1048, 791 cm–1.
3
1H NMR (CDCl3): = 8.40 (d, 1 H, J = 8.4 Hz), 8.15 (dd, 1 H,
Anal. Calcd for C23H22N4O2S + H2O (418.51 + 18.02): C, 63.28; H,
5.54; N, 12.83. Found: C, 63.32; H, 5.62; N, 12.89.
3J = 7.4 Hz, 4J = 1.0 Hz), 8.07 (d, 1 H, 3J = 8.4 Hz), 7.44–7.29 (m,
6 H), 7.08 (d, 2 H, 3J = 7.6 Hz), 6.81 (d, 2 H, 3J = 7.6 Hz), 6.46 (d,
3
3
6-{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-3-
oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]methyl}-
2,2 -bipyridine (20)
A mixture of 19 (0.050 g, 0.119 mmol), K2CO3 (0.058 g, 0.357
mmol), KI (0.002 g, 10 mol%), and chloromethylnitronyl nitroxide
2 H, J = 7.2 Hz), 5.61 (t, 2 H, J = 5.6 Hz, NH), 3.83 (d, 4 H,
3J = 5.6 Hz, CH2NH), 2.82 (s, 12 H, CH3).
13C{1H} NMR (CDCl3): = 154.2, 152.0, 136.4, 134.7, 130.4,
129.7, 129.5, 128.3, 123.2, 120.1, 118.6, 115.4, 47.5, 45.4.
Synthesis 2003, No. 14, 2145–2154 © Thieme Stuttgart · New York

PAPER
Oligopyridines Bearing Multiple Dansyl and Nitroxide Radicals
2153
(0.027 g, 0.139 mmol) in MeCN (20 mL) was heated at 60 °C in the
dark for 2.5 h. After 2 h, K2CO3 (0.050 g, 0.357 mmol) was added
and the suspension was heated at 60 °C for 2 additional h. The reac-
tion was quenched with H2O (20 mL) and extracted with CH2Cl2
(100 mL). The organic layer was dried (MgSO4) and evaporated to
dryness under vacuum; yield: 73%. An analytically pure sample
(0.051 g) was obtained by chromatography (Al2O3, eluent: CH2Cl2
with a gradient of 0.1% MeOH) and recrystallized from a mixture
CH2Cl2–hexane.
UV-Vis (CH2Cl2): ( , M–1cm–1) = 344 (3700), 288 (12900), 259
(17600), 246 (19600) 229 nm (19000).
Anal. Calcd for C52H62N10O8S2 (1019.24): C, 61.28; H, 6.13; N,
13.74. Found: C, 61.05; H, 5.91; N, 13.58.
References
(1) (a) Molecular Fluorescence, Principles and Applications;
Valeur, B., Ed.; Wiley-VCH: Weinheim Germany, 2002.
(b) Inorganic Materials; Bruce, D. M.; O’Hare, D., Eds.;
Wiley: Chichester, 1996. (c) Magnetism: Molecules to
Materials: Models and Experiments; Miller, J. S.; Drillon,
M., Eds.; Wiley-VCH: Weinheim Germany, 2001.
(2) Ziessel, R. Synthesis 1999, 1839.
(3) Lozinsky, E.; Martin, V. V.; Berezina, T. A.; Shames, A. I.;
Weis, A. L.; Likhtenshtein, G. I. J. Biochem. Biophys.
Methods 1999, 38, 29.
IR (KBr): 3296, 2931, 2856, 1582, 1453, 1433, 1415, 1324 (SO2N),
1162 (SO2N), 1148, 1089, 1068, 793, 775 cm–1.
ESI-TOF: m/z (%) = 610.2 ([M + Na]+, 100), 588.3 ([M + H], 80).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 540 (600), 327 (11500), 288
(12700), 270 nm (13000).
Anal. Calcd for C31H35N6O4S (587.24): C, 63.35; H, 6.00; N, 14.30.
Found: C, 63.27; H, 5.92; N, 13.99.
(4) Battistuzzi, G. G.; Grandi, G.; Menabue, L.; Pellacani, G. C.;
Sola, M. J. Chem. Soc., Dalton Trans. 1985, 2363.
(5) Blough, N. V.; Simpson, D. J. J. Am. Chem. Soc. 1988, 110,
1915.
(6) Fanz, K. J.; Singh, N.; Lippard, S. J. Angew. Chem. Int. Ed.
2000, 39, 2120.
(7) Prodi, L.; Bolletta, F.; Montalti, M.; Zaccheroni, N. Eur. J.
Inorg. Chem. 1999, 455.
(8) Talanova, G. G.; Elkarim, N. S. A.; Talanov, V. S.; Bartsch,
R. A. Anal. Chem. 1999, 71, 3106.
(9) Tamura, M.; Ueno, A. Chem. Lett. 1998, 369.
(10) Aoki, S.; Kawatani, H.; Goto, T.; Kimura, E.; Shiro, M. J.
Am. Chem. Soc. 2001, 123, 1123.
(11) Vögtle, F.; Gestermann, S. N.; C, ; Ceroni, P.; Vicinelli, V.;
Balzani, V. J. Am. Chem. Soc. 2000, 122, 10398.
(12) Herbelin, S. E.; Blough, N. V. J. Phys. Chem. B 1998, 102,
8170.
(13) Synthetic Chemistry of Stable Nitroxides; Volodarsky, L. B.;
Reznikov, V. A.; Ovcharenko, V. I., Eds.; CRC Press: Boca
Raton Florida, 1994.
(14) Inoue, K.; Hayamizu, T.; Iwamura, H.; Hashizume, D.;
Ohashi, Y. J. Am. Chem. Soc. 1996, 118, 1803.
(15) Inoue, K.; Iwamura, H. J. Am. Chem. Soc. 1994, 116, 3173.
(16) Kalai, T.; Jekö, J.; Szabo, Z.; Parkanyi, L.; Hideg, K.
Synthesis 1997, 1049.
6,6 -Bis-[(5-dimethylamino-1-naphthalenesulfonamide)meth-
yl]-2,2 -bipyridine (22)
To a solution of 21 (0.178 g, 0.83 mmol) and dansyl chloride (0.448
g, 1.66 mmol) in distilled MeCN (20 mL) was added anhyd Et3N
(1.5 mL) in portions and the mixture was stirred at r.t. for 23 h. H2O
(50 mL) was added and the mixture was extracted with CH2Cl2
(3 × 100 mL). The combined organic layers were dried (MgSO4),
evaporated to dryness, and the crude solid was purified by flash
chromatography (silica gel, eluent: CH2Cl2 with a gradient of 1%
MeOH) to give the desired product 22 (0.380 g), after recrystallisa-
tion from a mixture of CH2Cl2–hexane; yield: 67%.
IR (KBr): 3301, 2943, 2835, 1580, 1458, 1432, 1325 (SO2N), 1162
(SO2N), 1146, 1098, 1078, 800 cm–1.
3
1H NMR (CDCl3): = 8.42–8.22 (m, 6 H), 7.85 (d, 2 H, J = 7.6
3
Hz), 7.58–7.35 (m, 6 H), 6.98 (d, 4 H, J = 7.6 Hz), 6.17 (t, 2 H,
3
3J = 5.2 Hz, NH), 4.26 (d, 4 H, J = 5.2 Hz, CH2), 2.77 (s, 12 H,
CH3).
13C{1H} NMR (CDCl3): = 154.2, 153.8, 152.0, 137.3, 134.4,
130.5, 129.7, 128.0, 123.1, 121.9, 119.7, 118.7, 115.0, 47.7, 45.4.
FAB+ (m-NBA): m/z (%) = 681.1 ([M + H]+, 100), 433.2.3 ([M –
DANS], 20), 185.2 ([M – 2 DANS], <5).
UV-Vis (CH2Cl2): ( , M–1cm–1) = 344 (7500), 291 (19300), 269
nm (23800).
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(b) Ulrich, G.; Stroh, C.; Ziessel, R. C. R. Acad. Sci. Paris
2001, 4, 113.
Anal Calcd for C36H36N6O4S2 (680.84): C, 63.51; H, 5.33; N, 12.34.
Found: C, 63.37; H, 5.12; N, 12.02.
(18) Ziessel, R.; El-ghayoury, Synthesis 2000, 2137.
(19) (a) Fornasier, R.; Milani, D.; Scrimin, P.; Tonellato, U. J.
Chem. Soc., Perkin Trans. 2 1986, 233. (b) Fornasier, R.;
Scrimimin, P.; Tecilla, P.; Tonellato, U. J. Am. Chem. Soc.
1989, 111, 224.
(20) Ulrich, G.; Ziessel, R. Tetrahedron Lett. 1994, 35, 1215.
(21) Stroh, C.; Turek, P.; Ziessel, R. Chem. Commun. 1998, 2337.
(22) Métivier, R.; Leray, I.; Valeur, B. Chem. Commun. 2003,
996.
(23) (a) Keana, J. F. W.; Baitis, F. Tetrahedron Lett. 1968, 365.
(b) Keana, J. F. W.; Dinerstein, R. J.; Baitis, F. J. Org. Chem.
1971, 36, 209.
(24) Ullman, E. F.; Call, L.; Tseng, S. S. J. Am. Chem. Soc. 1973,
95, 1677.
6,6 -{[5-Dimethylamino-1-naphthalenesulfonamide-N-(1-oxyl-
3-oxide-4,4,5,5-tetramethylimidazolin-2-methyl-2-yl)]methyl}-
2,2 -bipyridine (23)
Compound 22 (0.0937 g, 0.59 mmol) and dansyl chloride (0.159 g,
0.590 mmol) were dissolved in distilled MeCN (10 mL). Anhyd
Et3N (1 mL) was added and the mixture was stirred at r.t. for 40 h.
After this period, H2O (75 mL) was added. The mixture was acidi-
fied with 10% aq HCl to pH 1 and extracted with Et2O (3 × 75 mL).
The aqueous phase was basified with aq KOH to pH 8 and extracted
with CH2Cl2 (3 × 100 mL). The combined organic layers were dried
(MgSO4), evaporated to dryness, and the crude solid was purified by
flash chromatography (silica gel, eluent: CH2Cl2 with a gradient of
?% MeOH) to give the desired product 23 (0.206 g); yield: 83%.
(25) Call, L.; Ullman, E. F. Tetrahedron Lett. 1973, 961.
(26) De Armond, M. K.; Carlin, C. M. Coord. Chem. Rev. 1981,
36, 325.
(27) (a) Koike, T.; Watanabe, T.; Aoki, S.; Kimura, E.; Shiro, M.
J. Am. Chem. Soc. 1996, 118, 12696. (b) Hill, R. R.;
Richenburg, C. W.; Roberts, D. R. J. Photochem. Photobiol.
1969, 97, 109.
IR (KBr): 3292, 2939, 2831, 1581, 1456, 1431, 1407, 1324 (SO2N),
1162 (SO2N), 1144, 1091, 1072, 790, 775 cm–1.
FAB+ (m-NBA): m/z (%) = 1019.2 ([M + H]+, 100), 986.2 ([M – 2
O], 50), 738.4 ([M – 2 O – DANS], 30).
Synthesis 2003, No. 14, 2145–2154 © Thieme Stuttgart · New York

2154
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PAPER
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Synthesis 2003, No. 14, 2145–2154 © Thieme Stuttgart · New York