Intermolecular interactions of punicin derivatives

Article abstract of DOI:10.1016/j.tet.2010.06.079

The 2- and 4-methyl derivates of punicin [N-(2′,5′- dihydroxyphenyl)-pyridinium chloride] were subjected to Knoevenagel reactions. Starting materials as well as reaction products were examined with respect to homo and hetero-intermolecular interactions. It was found that N-(2′,5′-dihydroxyphenyl)-2-methylpyridinium chloride forms a stable 2:1 complex to hydroquinone. Decomplexation can be accomplished by anion exchange to tetraphenylborate, or by competing complexation with p-benzoquinone. Results of three single crystal X-ray analyses as well as NMR titrations and dilution experiments are presented.

Full text of DOI:10.1016/j.tet.2010.06.079

Tetrahedron 66 (2010) 7149e7154
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Intermolecular interactions of punicin derivatives
,
Marcel Albrecht a, Mimoza Gjikaj b, Andreas Schmidt a
*
a Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany
b Clausthal University of Technology, Institute of Inorganic Chemistry, Paul-Ernst-Strasse 4, D-38678 Clausthal-Zellerfeld, Germany
a r t i c l e i n f o
a b s t r a c t
The 2- and 4-methyl derivates of punicin [N-(20,50-dihydroxyphenyl)-pyridinium chloride] were subjected
to Knoevenagel reactions. Starting materials as well as reaction products were examined with respect to
homo and hetero-intermolecular interactions. It was found that N-(20,50-dihydroxyphenyl)-2-methylpyr-
idinium chloride forms a stable 2:1 complex to hydroquinone. Decomplexation can be accomplished by
anion exchange totetraphenylborate, or bycompeting complexationwith p-benzoquinone. Results of three
single crystal X-ray analyses as well as NMR titrations and dilution experiments are presented.
Ó 2010 Elsevier Ltd. All rights reserved.
Article history:
Received 29 April 2010
Received in revised form 25 June 2010
Accepted 28 June 2010
Available online 7 July 2010
Keywords:
Pyridinium-phenolate
NMR titration
p-Complex
Quinhydrone
1. Introduction
the class of cross-conjugated mesomeric betaines (CCMB). Deproto-
nation of these betaines by the addition of bases yields the red
Punicin 1 is a yellow alkaloid from the leaves of Punica granatum
L.,1 which possesses an astonishing variety of properties (Scheme 1).
In aqueous solution, it forms an orange-colored mixture of two tau-
tomeric heterocyclic mesomeric betaines, which differ in their type of
conjugation.2 Thus, betaine 2A belongs to the class of conjugated
mesomeric betaines3 (CMB), whereas its tautomer 2B is a member of
monoanionicspecies3. Hydroxide-inducedpericyclicringcleavageof
3 yields 4, which is reddish-black in color. These processes are re-
versible on addition of acids.4
Pyridinium substituted quinones obviously are only stable when
they are substituted with additional olate groups,5 amines,6 chlo-
rine,7 or DMAP.8 We found that substitution of punicin by the
electron-donating group propenolate (D in 5), give stable, in-
tensively dark blue colored species 6 on oxidation.9 These can be
used in organic synthesis as oxidizing agents. 3-Substituted pyri-
dines as partial structures result in the formation of atropisomers of
5 and 69 (Scheme 2).
OH
O
OH
N
N
N
-H
+H
O
OH
OH
2B
2A
1
R
R
O
O
OH
OH
-H
N
D
N
D
+H
oxidation
O
O
O
N
OH
O
O
5
6
N
+H
-H2O
H
Scheme 2. Quinones of substituted punicins.
4
3
Moreover, punicin and its derivatives form persistent radical
cations, such as 7 and radical anions, such as 8 depending on the
reaction conditions and the methods of stabilization. Accordingly,
punicin as well as its derivatives are redoxactive compounds. As an
example, punicin attached to a polymer backbone stabilizes the
radical cation species 7.
Scheme 1. The alkaloid punicin.
* Corresponding author. Fax: þ49 5323/72 2858; e-mail address: schmidt@ioc.
tu-clausthal.de (A. Schmidt).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.079

7150
M. Albrecht et al. / Tetrahedron 66 (2010) 7149e7154
R1
Radical anions such as 8 can be used in reversible photocatalytic
1.
electron-transfer reactions employing a sensitizer and a sacrificial
donor such as EDTA. Under these conditions, oxygen is converted
into hydroxide and H2O2. The radicals were characterized by ESR
and solid-state ENDOR spectroscopy (Scheme 3).10 These results
were used to prepare new photoresponsive materials.11
Cl
Cl
R1
R2
O
OH
OH
N
OH
OH
OH
OH
N
AcOH
2. HCl
N
2
R2
Me
O
: R1 = H, R2 = Me
: R1 = Me, R2 = H
10aC
9
10a
OH
O
10b
N
N
Scheme 5.
O
OH
2B
2A
Cl
CHO
red.
oxid.
OH
red.
O
oxid.
OH
N
+
10a
piperidine
(cat.)
dispropor-
tionation
N
N
OH
OH
O
11
(31 %)
8
7
Scheme 6.
Scheme 3. Radicals from punicin.
The 4-methylpyridinium derivative 10b reacted with benzal-
dehyde in the presence of catalytic amounts of piperidine to give
the trans-1-(20,50-dihydroxyphenyl)-4-styrylpyridinium salt 12.
Likewise, isonicotinaldehyde and picolinaldehyde reacted to afford
the 4-(2-(pyridinyl)vinyl)pyridinium salts 13a,b (Scheme 7).
During the last decades much attention has also been devoted to
the synthesis and characterisation of charge-transfer complexes
(CT) of pyridinium salts with different molecules, such as iodide,12
tetrafluoroborate,13 and aromatic organic donors.14 Especially su-
pramolecular cyclophane systems based on bispyridinium salts
with crown ether structures have been widely explored, as these
complexes are interesting building blocks for the preparation of
molecular switches or complexation reagents.15 Resulting from
their remarkable optical and electrochemical properties CT com-
plexes have found applications as photoinitiators16 for polymeri-
sation reactions, fluorescent dyes,17 and molecular nanoparticles.18
These properties prompted us to examine intermolecular in-
Cl
CHO
OH
OH
N
piperidine
(cat.)
12 (47 %)
teractions of punicin which possesses
p-donor and p-acceptor
properties in different parts of the molecule (Scheme 4). We ex-
amined complexes in the solid state as well as in solution by X-ray
single crystal analyses and by NMR titrations, respectively.
10b
Cl
CHO
Z
Y
Z
OH
Y
N
π
π
-acceptor
-donor
piperidine
(cat.)
OH
13a
OH
: Y = CH, Z = N (21 %)
13b: Y = N, Z = CH (48 %)
N
R
HO
Scheme 7.
Scheme 4. Complexing partial structures of punicin derivatives.
The punicin derivatives 11e13 were obtained after chromato-
graphic work-up and subsequent precipitation from a methanolic
solution as yellow to light red solids. In all compounds, the trans
configuration of the double bond was proved by a coupling con-
stant of 16e17 Hz in the 1H NMR spectra, and the results of X-ray
analyses (vide infra). On deprotonation with bases, all punicin
derivatives 10e13 form intensively red to dark brown colored
mesomeric betaines similar to 2A/B shown in Scheme 1. Charac-
teristically, 1H NMR resonance frequencies of starting material
10b, which is the best soluble compound of the series, taken in
DMSO-d6 shift by 0.1 ppm (pyridinium protons) and 0.4 ppm
(protons of the hydroquinone) upfield on deprotonation. Similar
values were obtained for compound 12. All other betaines are
sparsely soluble and could therefore neither be purified nor
characterized completely.
2. Results and discussion
2.1. Syntheses of model compounds
It is known that p-benzoquinone reacts with pyridines in acidic
medium to punicin derivatives.19 We chose 2-methylpyridine and
4-methylpyridine as reaction partners, because they allow Knoe-
venagel reactions to larger
p-conjugated systems. Thus, 10a and
10b were prepared in 57% and 79% yield, respectively. As a matter of
fact, compound 10a was isolated as a complex (10aC) of two mol-
ecules of the pyridinium salt and one molecule of hydroquinone.
Knoevenagel reaction of punicin derivative 10aC with benzal-
dehyde resulted in the formation of the styrylpyridinium com-
pound 11 in moderate yield (Scheme 6).

M. Albrecht et al. / Tetrahedron 66 (2010) 7149e7154
7151
2.2. Intermolecular interactions
We started our studies with a single crystal X-ray analysis of
compound 12. Single crystals were obtained by slow evaporation of
a solution of 12 in diluted HCl. The compound crystallized with one
molecule of water of crystallization. Hydrogen bonds are formed
between both hydroxyl groups of the hydroquinone and the chloride
ion and the waterofcrystallization(not shownforclarity)withangles
of 155.9ꢀ and 171.8ꢀ, respectively. Additional information concerning
hydrogen-bond distances and angles is presented in Table 1. Vertical
interactions with a distance of 3.902 Å between the hydroquinone
rings of each molecule can be observed. This value is larger than the
van-der-Waals distance (3.4 Å). The dihedral angles C2eN1eC7eC12
and C5eN1eC7eC8 were determined to be ꢁ52.771(18)ꢀ and
ꢁ53.343(18)ꢀ, respectively (crystallographic numbering). The torsion
angle between the pyridine and the benzene ring connected by the
double bond is 13.192ꢀ (Fig. 1).
Table 1
Hydrogen-bond distances (Å) and angles (ꢀ) for C15H15ClNO3 (10aC) and
C19H18ClNO3 (12)
DeH/A
15H15ClNO3
O(8)eH(8) /Cl
DeH
H/A
D/A
DeH/A
C
Figure 2. Sandwich-type arrangement of 10aC.
0.771
0.749
2.328
2.377
3.082
3.108
165.9
165.6
O(14)eH(14) /Cl
The p-stacking properties of 10a and hydroquinone in solution
C
19H18ClNO3
were also examined. The comparison between the chemical shifts
of probe protons provides a qualitative measure of the strengths of
binding between the components of the complex. As expected, the
1H NMR signals of the pyridinium protons of the complex
[2$10aþhydroquinone] are the most affected. They shift to lower
field on dilution of the complex in D2O, whereas the resonance
frequencies of the hydroquinone partial structure of the punicin
remain virtually unchanged (Table 2).
O(11)eH(11) /Cl
O(1)eH(1) /Cl
O(8)eH(8) /O(1)
0.955
0.831
0.884
2.184
2.309
1.725
3.079
3.104
2.603
155.9
160.4
171.8
Table 2
Dilution experiment of the complex [2 10aþhydroquinone]
HO
N
Cl
OH
Me
OH
HO
OH
1
2
3
N
Cl
4
Me
HO
Figure 1. Molecular drawing of 12.
Concentration of complex [2$10aþhydroquinone]
d
1-H
d
2-H d 3-H d 4-H
Next, we turned our attention to complex formation with hy-
droquinone. As already mentioned, compound 10a formed a stable
-complex 10aC (cf. Scheme 5) consisting of 2 equiv of the salt 10a
Saturated solution
150 mmol/L
100 mmol/L
50 mmol/L
8.47 7.84 8.41 7.92
8.48 7.85 8.42 7.92
8.54 7.87 8.44 7.95
8.58 7.89 8.46 7.97
8.63 7.91 8.47 8.00
p
and 1 equivof hydroquinone. This complexcan be recrystallized. We
were able to obtain suitable crystals for a single crystal X-ray anal-
ysis. The molecular drawings are shown in Figure 2. The punicin
derivative adopts a non-planar conformation with dihedral angles
C2eN1eC7eC12 of ꢁ90.371(10)ꢀ and C6eN1eC7eC8 of ꢁ85.055
(10)ꢀ. The molecular drawing shows a sandwich-type arrangement
of the two pyridinium moieties and the hydroquinone, which is lo-
cated at distances of 3.601 Å and 3.621 Å to the pyridinium rings,
respectively. The pyridinium and hydroquinone ring adopt an angle
of 13.499(47)ꢀ to each other. The hydroquinone moieties of each
punicin derivative stack to another hydroquinone ring of a neigh-
boring molecule. Hydrogen bonds are found between the chloride
ion and the hydroxy group at the 8-position of the hydroquinone
moiety of the punicin and the added hydroquinone (Table 1).
5 mmol/L
In solution, Coulomb interactionsbetween the positivelycharged
pyridinium ring, its counterion, and the complexing hydroquinone
as shown in Scheme 8 play an important role. In this case, the shape
of the counterion has a direct influence of complex formation ca-
pabilities. As a matter of fact, anion exchange of the chloride to the
sterically more demanding tetraphenylborate yields the pure salt
10c without the presence of any complexing hydroquinone.
Decomplexation of[2$10aþhydroquinone] canalso be performed by
addition of an excess of p-benzoquinone to an aqueous solution of
complex 10aC. On addition, a black solid spontaneously precipitated,
which can be identified by NMR spectroscopy as quinhydrone.

7152
M. Albrecht et al. / Tetrahedron 66 (2010) 7149e7154
HO
HO
N
2 Cl
N
Cl
Cl
N
H
OH
OH
OH
OH
Me
OH
Me
HClaq
N
13b
O
HCl
13c
HO
OH
HO
OH
1
1
2
2
3
Scheme 9. Formation of a stable salt 13c.
N
3
N
Cl
4
4
Me
Me
HO
HO
10a
[2
+ hydroquinone]
+NaBPh4
-NaCl
-hydroquinone
+ p-benzoquinone
- quinhydrone
OH
OH
OH
Cl
N
N
BPh4
Me
Me
OH
10a
10c
Scheme 8. Quinhydrone formation by addition of p-benzoquinone and anion ex-
change by NaBPh4. Both methods result in decomplexation.
Extraction with dichloromethane to remove the remaining p-ben-
zoquinone and evaporation of the aqueous phase resulted in com-
pound 10a in pure form. No change of the resonance frequencies can
be observed by addition of p-benzoquinone to the purified punicin
Figure 3. Molecular drawing of 13c.
crystallizes with one molecule of water. A hydrogen bond is ob-
served between the hydroxyl group of the hydroquinone moiety at
the 8-position (crystallographic numbering) and the water of
crystallization with an angle of 167.2ꢀ. Furthermore, a bridged
hydrogen bond connection is formed between the other hydroxyl
group (11-position), the chloride anion and the protonated ni-
trogen of the pyridinium ring with angles of 175.5ꢀ and 171.8ꢀ,
respectively. Details are given in Table 4. The dihedral angles
C2eN1eC7eC12 and C5eN1eC7eC8 were determined to be
ꢁ60.204(21)ꢀ and ꢁ59.223(21)ꢀ, respectively. The torsion angle
between the pyridine and the protonated pyridine ring connected
by the double bond has a value of 51.659ꢀ. In contrast to com-
pound 12, in 13c homo vertical interactions are formed between
the hydroquinone moiety and the pyridinium ring of an adjacent
molecule. The distances are 4.273 and 3.863 Å, respectively.
derivative 10a, so that interactions between the
p-accepting qui-
none and the -donating hydroquinone partial structure of punicin
p
can be excluded under these conditions.
Similarly to these observations, the resonance frequencies of
the a- und b-protons of the pyridinium ring of 10b (50 mmol/L
solution in D2O) shift upfield on addition of hydroquinone due to
complex formation under these conditions. Our results are shown
in Table 3.
Table 3
NMR titration of 10b with hydroquinone
OH
HO
Table 4
OH
Hydrogen-bond distances (Å) and angles (ꢀ) for C18H18Cl2N2O3 (13c)
1
2
N
Me
DeH/A
18H18Cl2N2O3
DeH
H/A
D/A
DeH/A
2´
1´
C
HO
O(11)eH(11) /Cl(1)
N(16)eH(16) /Cl(1)
O(8)eH(8) /O(1)
0.821
0.946
0.862
2.255
2.080
1.777
3.074
3.019
2.625
175.5
171.8
167.2
Ratio 10b:Hydroquinone
d
1-H
d 2-H
1:2
1:1
1:0.5
1:0.25
1:0.1
1:0
8.55
8.60
8.63
8.64
8.64
8.64
7.85
7.88
7.90
7.90
7.91
7.91
Complex formation between 13c and hydroquinone can also
be observed in solution. NMR measurements of different ratios of
13c (25 mmol/L in D2O) and hydroquinone were performed. The
results are shown in Table 5. Similar to the starting material 10b,
all protons of the two corresponding pyridine moieties shift
upfield due to vertical interactions. The maximum change of the
resonance frequencies can be observed for the two protons of the
double bond, which appear in the same spectroscopic region.
This indicates that the strongest binding interactions of 13c with
hydroquinone are localized in this part of the molecule. Similar
results were also obtained for a protonated form of 13a.
To gain more information about the
p-complexes of the
Knoevenagel products, compound 13b was converted to its dica-
tonic salt 13c by addition of concentrated hydrochloric acid to
a suspension of 13b. Precipitation resulted in the formation of the
protonated punicin derivative 13c in 55% yield, which has an in-
creased solubility in protic solvents, such as methanol and water
(Scheme 9).
In summary, we present homo- as well hetero-intermolecular
interactions of punicin derivatives, which supplement the broad
variety of properties of this class of compounds. These results
Single crystals of this salt were obtained by slow evaporation of
a diluted hydrochloric acid solution of 13c (Fig. 3). The compound

M. Albrecht et al. / Tetrahedron 66 (2010) 7149e7154
7153
Table 5
Further details on the crystal structure investigations may be
obtained from Cambridge Crystallographic Data Centre CCDC, 12
Union Road, Cambridge CB2 1EZ, fax (þ44) 1223 336 033, e-mail
(deposit@ccdc.cam.ac.uk) on quoting the depository numbers
CCDC-768706 for compound C15H15ClNO3, CCDC-768707 for
compound C19H18ClNO3, and CCDC-774496 for compound
C18H18Cl2N2O3.
NMR titration of 13c with hydroquinone
OH
2Cl
HO
1´ 2´
3
4
OH
5
.
N
N
H
6
1
2
HO
3.2.1. N-(20,50-Dihydroxyphenyl)-2-methylpyridinium chloride 10a
and its complex with hydroquinone. A solution of p-benzoquinone
(5.4 g, 50 mmol) in 35 mL of concd acetic acid was treated with
2-methylpyridine (4.9 mL, 50 mmol). The mixture was then
stirred for 24 h at rt, the resulting precipitate was filtered off,
dissolved in water, and precipitated again by addition of concd
HCl. By this way a complex of two molecules of 10a and one
molecule of hydroquinone is formed. Yield: 3.31 g (57%) of a pale
Ratio 13c:Hydroquinone
d
1-H
d
2-H
d
3-H
d
4-H
d
5-H
d
6-H
d C]C
1:2
1:1
1:0.5
1:0.25
1:0
8.83
8.86
8.87
8.88
8.89
8.24
8.27
8.28
8.29
8.30
8.25
8.28
8.29
8.30
8.31
8.48
8.50
8.50
8.51
8.51
7.90
7.91
7.92
7.92
7.93
8.67
8.69
8.69
8.70
8.70
7.77
7.82
7.84
7.85
7.87
brownish solid; mp 203e206 ꢀC. 1H NMR (DMSO-d6):
d
¼10.30 (s,
could stimulate the design of larger supramolecular architectures,
which take advantage of the complexing properties of punicin
derivatives.
2H, OH), 9.70 (s, 2H, OH), 8.97 (dd, J¼6.2, 1.1 Hz, 2H), 8.65 (dddþs,
J¼7.9, 6.2, 1.1 Hz, 2Hþ2H), 8.22 (d, J¼7.5 Hz, 2H), 8.06 (m, 2H),
7.08 (m, 2H), 6.97 (m, 4H), 6.55 (s, 4H), 2.51 (s, 6H, methyleH)
ppm; 13C NMR (DMSO-d6):
d
¼156.4, 150.4, 149.7, 146.7, 146.6,
3. Experimental
3.1. General
142.9, 129.2, 128.1, 125.5, 119.3, 118.0, 115.6, 112.4, 19.9 ppm; IR
(KBr): 3166, 1629, 1524, 1514, 1453, 1337, 1267, 1199, 852, 776,
649, 629 cmꢁ1
.
Decomplexation was achieved by addition of 4 equiv of p-
benzoquinone (216 mg, 2 mmol) to an aqueous solution of com-
plex 10a (292 mg, 0.5 mmol). The mixture was stirred for 15 h at rt
and the resulting solid was filtered off. The filtrate was extracted
with five portions (50 mL) dichloromethane and the resulting
aqueous phase was evaporated under reduced pressure to give the
product as an orange colored waxy solid. Yield: 204 mg (86%). 1H
The 1H and 13C NMR spectra were recorded on Bruker ARX-400
and DPX-200 spectrometers and were taken in DMSO-d6 and D2O
at 200 and 400 MHz at 20 ꢀC. As an internal standard the solvent
signals of DMSO-d6 at 2.50 ppm and D2O at 4.72 ppm were used.
The chemical shifts are reported in parts per million. Multiplicities
are described by using the following abbreviations: s¼singlet,
d¼doublet, t¼triplet, m¼multiplet, br¼broad.
NMR (DMSO-d6):
d
¼10.35 (s, 1H, OH), 9.73 (s, 1H, OH), 8.97 (dd,
J¼6.2, 1.1 Hz, 2H), 8.65 (ddd, J¼7.9, J¼6.2, 1.1 Hz, 1H), 8.22 (d,
J¼7.9 Hz, 1H), 8.06 (m, 1H), 7.10 (m, 1H), 6.98 (m, 2H), 2.51 (s, 3H,
methyleH) ppm.
3.2. X-ray diffraction analysis
Suitable single crystals of the title compounds were selected
under a polarization microscope and mounted in a glass capillary
(d¼0.3 mm). The crystal structures were determined by X-ray dif-
fraction analysis using graphite monochromated Mo Ka radiation
(0.71073 Å) [T¼223(2) K], whereas the scattering intensities were
collected with a single crystal diffractometer (STOE IPDS II). The
crystal structures were solved by Direct Methods using SHELXS-97
and refined using alternating cycles of least squares refinements
against F2 (SHELXL-97). All non-H atoms were located in Difference
Fourier maps and were refined with anisotropic displacement pa-
rameters. The H positions were determined by a final Difference
Fourier Synthesis.
3.2.2. N-(20,50-Dihydroxyphenyl)-4-methylpyridinium chloride 10b.
A solution of p-benzoquinone (5.4 g, 50 mmol) in 35 mL of concd
acetic acid was treated with 4-methylpyridine (4.86 mL, 50 mmol).
The mixture was stirred for 24 h at rt, then concd hydrochloric acid
was added. The resulting solid was filtered off and washed sub-
sequently with chloroform and ethyl acetate. Yield: 9.34 g (79%) of
a pale brownish solid; dec 247e248 ꢀC. 1H NMR (DMSO-d6):
d
¼10.19 (br s, 2H, OHeH), 8.99 (d, J¼6.7 Hz, 2H), 8.08 (d, J¼6.7 Hz,
2H), 7.13 (m, 1H), 6.99 (m, 2H), 2.69 (s, 3H, methyleH) ppm; 13C
NMR (DMSO-d6):
d
¼160.2, 150.3, 145.2, 142.7, 129.6, 128.1, 119.1,
118.0, 112.5, 21.7 ppm; IR (KBr): 3170, 1637, 1518, 1459, 1401, 1351,
1323, 1216, 827, 792, 652, 477 cmꢁ1. All spectroscopic data are in
agreement with literature values.4
C15H15ClNO3 (10aC) crystallized in the monoclinic space group
C2/c (no. 15), lattice parameters a¼13.035(2) Å, b¼15.153(2) Å,
c¼13.979(2) Å,
b
¼91.07(1)ꢀ, V¼2760.5(7) Å3, Z¼8, dcalc.
¼
1.409 g cmꢁ3, F(000)¼1224 using 2444 independent reflections
3.2.3. trans-N-(20,50-Dihydroxyphenyl)-2-styrylpyridinium chloride
11. A solution of the complex of (20,50-dihydroxyphenyl)-2-meth-
ylpyridinium chloride 10a with hydroquinone (672 mg, 2.3 mmol
of the salt) in 30 mL of anhyd methanol was treated with benzal-
dehyde (0.25 mg, 2.5 mmol) and 10 drops of piperidine. The mix-
ture was then heated at reflux temperature for 13 h. The solvent
was then distilled off in vacuo and the residue was chromato-
graphed (chloroform/MeOH¼7:1). The resulting solid was dis-
solved in methanol and precipitated by the addition of chloroform.
Yield: 235 mg (31%) of a yellow solid; dec 202 ꢀC (DSC). 1H NMR
and 241 parameters. R1¼0.0421, wR2¼0.0924 [I>2
s(I)], goodness of
fit on F2¼1.055, residual electron density¼0.213 and ꢁ0.272 e Åꢁ3
.
C19H18ClNO3 (12) crystallized in the monoclinic space group
P21/c (no. 14), lattice parameters a¼9.474(2) Å, b¼14.172(2) Å,
c¼12.908(2) Å,
b
¼90.22(1)ꢀ, V¼1733.1(5) Å3, Z¼4, dcalc.
¼
1.318 g cmꢁ3, F(000)¼720 using 3065 independent reflections
and 290 parameters. R1¼0.0670, wR2¼0.0906 [I>2
s(I)], good-
ness of fit on F2¼1.127, residual electron density¼0.188 and
ꢁ0.198 e Åꢁ3
.
C18H18Cl2N2O3 (13c) crystallized in the monoclinic space group
P21/n (no. 14), lattice parameters a¼14.262(3) Å, b¼8.021(1) Å,
(200 MHz, DMSO-d6):
d
¼10.32 (br s, 1H, OHeH), 9.81 (br s, 1H,
OHeH), 8.95 (d, J¼5.6 Hz, 1H), 8.73 (m, 2H), 8.12 (d, J¼16.3 Hz, 1H),
c¼16.610(1) Å,
b
¼106.81(1)ꢀ, V¼1819.0(5) Å3, Z¼4, dcalc.
¼
8.03 (m,1H), 7.44 (m, 5H), 7.08 (m, 3H), 6.74 (d, J¼16.3 Hz,1H) ppm;
1.392 g cmꢁ3, F(000)¼792 using 3203 independent reflections and
13C NMR (50 MHz, DMSO-d6):
d
¼152.5, 150.4, 146.5, 145.8, 143.5,
299 parameters. R1¼0.0440, wR2¼0.0903[I>2
s(I)], goodness offiton
142.7, 134.5, 130.9, 129.3, 127.9, 127.5, 125.4, 124.7, 119.7, 118.0, 117.2,
113.1 ppm; IR (KBr): 3029, 1615, 1561, 1528, 1499, 1447, 1354, 1268,
F2¼1.061, residual electron density¼0.266 and ꢁ0.221 e Åꢁ3
.

7154
M. Albrecht et al. / Tetrahedron 66 (2010) 7149e7154
1206, 1127, 974, 836, 798, 775, 685 cmꢁ1. HRESIMS: calcd for
C19H16NOþ2 : 290.1180. Found: 290.1173.
solid; dec: 221 ꢀC (DSC). 1H NMR (200 MHz, DMSO-d6):
d
¼10.51 (br
s, 1H, OHeH), 9.80 (br s, 1H, OHeH), 9.08 (d, J¼6.5 Hz, 2H), 8.71 (d,
J¼3.6 Hz,1H), 8.47 (d, J¼6.5 Hz, 2H), 8.20 (d, J¼16.0 Hz,1H), 7.95 (m,
2H), 7.73 (d, J¼7.6 Hz, 1H), 7.45 (t, J¼5.5 Hz, 1H), 7.15 (d, J¼8.8 Hz,
1H), 7.07 (d, J¼2.5 Hz, 1H), 6.98 (dd, J¼8.8 Hz, J¼2.5 Hz, 1H) ppm;
3.2.4. trans-N-(20,50-Dihydroxyphenyl)-4-styrylpyridinium chloride
12. A solution of N-(20,50-dihydroxyphenyl)-4-methylpyridinium
chloride 10b (237 mg, 1 mmol) in 10 mL of anhyd methanol was
treated with benzaldehyde (0.11 mL, 1.1 mmol) and three drops of
piperidine. The mixture was then heated at reflux temperature for
24 h. After evaporation of the solvent in vacuo, the residue was
chromatographed (silica gel; chloroform/MeOH¼8:1). Recry-
stallization from chloroform/MeOH gave an orange-colored solid.
13C NMR (50 MHz, DMSO-d6):
d
¼153.0, 152.8, 150.4, 150.2, 146.0,
142.7, 140.5, 137.4, 129.7, 126.5, 125.3, 124.7, 124.3, 119.1, 118.1,
112.6 ppm; IR (KBr): 3115, 3058, 1619, 1509, 1457, 1330, 1198, 1031,
972, 829, 770, 657, 524 cmꢁ1. HRESIMS: calcd for C18H15N2Oþ2 :
291.1134. Found: 291.1135.
Yield: 154 mg (47%); dec 272e273 ꢀC. 1H NMR (DMSO-d6):
d
¼10.48
(br s, 1H, OHeH), 9.78 (br s, 1H, OHeH), 9.03 (d, J¼6.4 Hz, 2H), 8.35
(d, J¼6.4 Hz, 2H), 8.18 (d, J¼16.3 Hz, 1H), 7.80 (m, 2H), 7.50 (m, 3H),
7.66 (d, J¼16.3 Hz, 1H), 7.14 (d, J¼8.8 Hz, 1H), 7.07 (d, J¼2.6 Hz, 1H),
6.97 (dd, J¼8.8 Hz, J¼2.6 Hz, 1H) ppm; 13C NMR (DMSO-d6):
References and notes
1. Nawwar, M. A. M.; Hussein, S. A. M.; Merfort, I. Phytochemistry 1994, 37, 1175.
2. Schmidt, A.; Mordhorst, T.; Nieger, M. Nat. Prod. Res. 2005, 19, 541.
3. Ollis, W. D.; Stanforth, S. P.; Ramsden, C. A. Tetrahedron 1985, 41, 2239.
4. Schmidt, A.; Mordhorst, T. ARKIVOC 2003, XIV, 233.
5. (a) Bock, H.; Nick, S.; Seitz, W.; Naether, C.; Bats, J. W. Z. Naturforsch. B 1996,
51, 153; (b) Weiss, R.; Salomon, N. J.; Miess, G. E.; Roth, R. Angew. Chem. 1986,
98, 925; Angew. Chem., Int. Ed. 1986, 25, 917; (c) Koch, A. S.; Harbison, W. G.;
Hubbard, J. M.; de Kort, M.; Roe, B. A. J. Org. Chem. 1996, 61, 5959; (d) Yan-
chishin, V. A.; Karlivan, G. A.; Valter, R. E. Chem. Heterocycl. Comp. 1998, 34,
312; Khim. Geterotsikl. Soedin. 1998, 34, 346; (e) Matsunaga, Y.; McDowell, C.
A. Can. J. Chem. 1969, 38, 1167; (f) Jain, M. L.; Soni, R. P. J. Prakt. Chem. 1983,
325, 353.
6. Osman, A. M.; Hammam, A. S.; Salah, A. T. Indian J. Chem., Sect. B 1977, 15B, 1118.
7. Smith, R. E.; Davis, W. R. Anal. Chem. 1984, 56, 2345 and Ref. 5d.
8. Bock, H.; Nick, S.; Bats, J. W. Tetrahedron Lett. 1992, 33, 5941 and Ref. 5b.
9. Albrecht, M.; Schneider, O.; Schmidt, A. Org. Biomol. Chem. 2009, 7, 1445.
10. (a) Schmidt, A.; Mordhorst, T.; Fleischauer, H.; Jeschke, G. ARKIVOC 2005, X, 150;
(b) Schmidt, A.; Albrecht, M.; Mordhorst, T.; Topp, M.; Jeschke, G. J. Mater. Chem.
2007, 17, 2793.
d
¼153.6, 150.4, 145.7, 142.7, 141.8, 135.2, 130.6, 129.6, 129.1, 128.3,
123.5, 123.4, 119.0, 118.1, 112.6 ppm; IR (KBr): 3057, 1614, 1507,
1455, 1339, 1270, 1189, 1119, 973, 825, 794, 767, 692 cmꢁ1. HRE-
SIMS: [C19H16NOþ2 ] calcd 290.1180. Found: 290.1181.
3.2.5. trans-N-(20,50-Dihydroxyphenyl)-4-(2-(pyridin-4-yl)vinyl)pyr-
idinium chloride 13a. A solution of N-(20,50-dihydroxyphenyl)-4-
methylpyridinium chloride 10b (544 mg, 2.3 mmol) in 30 mL of
anhyd methanol was treated with pyridine-4-carbaldehyde (0.24 mL,
2.5 mmol) and five drops of piperidine. After heating at reflux tem-
perature for 15 h, the solvent was distilled off in vacuo and the
resulting residue was chromatographed (chloroform/MeOH¼7:1).
The resulting solid was dissolved in methanol and precipitated by
addition of chloroform. Yield: 160 mg (21%) of a red solid; dec 283 ꢀC
11. Albrecht, M.; Yulikov, M.; Kohn, T.; Jeschke, G.; Adams, J.; Schmidt, A. J. Mater.
Chem. 2010, 20, 3025.
12. (a) Tosato, M. L.; Settimj, G.; Cignitti, M. Bioelectrochem. Bioenerg. 1975, 2, 163;
(b) Pal, M.; Bagchi, S. Proc. Indian Acad. Sci. 1984, 93, 1331.
(DSC). 1H NMR (200 MHz, DMSO-d6):
d
¼10.52 (br s, 1H, OHeH), 9.82
(br s,1H, OHeH), 9.12 (d, J¼6.7 Hz, 2H), 8.70 (d, J¼5.9 Hz, 2H), 8.42 (d,
J¼6.7 Hz, 2H), 8.15 (d, J¼16.4 Hz, 1H), 7.92 (d, J¼16.4 Hz, 1H), 7.72 (d,
J¼5.9 Hz, 2H), 7.15 (d, J¼8.8 Hz, 1H), 7.08 (d, J¼2.8 Hz, 1H), 6.98 (dd,
13. (a) Moody, G. J.; Owusu, R. K.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.;
Thomas, J. D. R.; Williams, D. J. Angew. Chem. 1987, 99, 939; Angew. Chem., Int.
Ed. 1987, 26, 890; (b) Zhu, D.; Kochi, J. K. Organometallics 1999, 18, 161.
14. (a) Verhoeven, J. W.; Dirkx, I. P.; de Boer, T. J. Tetrahedron 1969, 25, 3395; (b)
Shirai, M.; Koizumi, T.; Iguchi, Y.; Tanaka, M. Chem. Lett. 1975, 4, 915.
15. (a) Ashton, P. R.; Ballardini, R.; Balzani, V.; Credi, A.; Gandolfi, M. T.; Menzer, S.;
Pérez-García, L.; Prodi, L.; Stoddart, J. F.; Venturi, M.; White, A. J. P.; Williams, D.
J. J. Am. Chem. Soc. 1995, 117, 11171; (b) Odell, B.; Reddington, M. V.; Slawin, A.
M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D. J. Angew. Chem. 1988, 100, 1605;
Angew. Chem., Int. Ed. 1988, 27, 1547.
J¼8.8 Hz, J¼2.7 Hz,1H) ppm; 13C NMR (50 MHz, DMSO-d6):
¼152.6,
d
150.5, 150.4, 146.1, 142.7, 142.2, 138.7, 129.6, 127.7, 124.2, 121.9, 119.2,
118.1, 112.5 ppm; IR (KBr): 3122, 3054, 1625, 1606, 1509, 1454, 1341,
1284, 1202, 1068, 1014, 977, 838, 805, 654, 564, 533 cmꢁ1. HRESIMS:
Calcd for C18H15N2Oþ2 : 291.1134. Found: 291.1141.
ꢀ
16. Hizal, G.; Yagci, Y.; Schnabel, W. Polymer 1994, 35, 2428.
17. Li, Z.-X.; Xu, C.-H.; Sun, W.; Bai, Y.-C.; Zhang, C.; Fang, C.-J.; Yan, C.-H. New J.
3.2.6. trans-N-(20,50-Dihydroxyphenyl)-4-(2-(pyridin-2-yl)vinyl)pyr-
idinium chloride 13b. Pyridine-2-carbaldehyde (0.24 mL, 2.5 mmol)
and five drops of piperidine were added to a solution of N-(20,50-
dihydroxyphenyl)-4-methylpyridinium chloride 10b (544 mg,
2.3 mmol) in 30 mL of anhyd methanol. The mixture was then
heated at reflux temperature for 15 h. Then, the solvent was dis-
tilled off in vacuo und the residue was chromatographed (chloro-
form/MeOH¼7:1). The resulting solid was dissolved in methanol
and precipitated from chloroform. Yield: 360 mg (48%) of a yellow
Chem. 2009, 33, 853.
18. Wang, C.; Yin, S.; Chen, S.; Xu, H.; Wang, Z.; Zhang, X. Angew. Chem. 2008, 120,
9189; Angew. Chem., Int. Ed. 2008, 47, 9049.
19. (a) Zhang, S.-L.; Huang, Z.-S.; An, L.-K.; Bu, X.-Z.; Ma, L.; Li, Y.-M.; Chan, A. S.
C.; Gu, L.-Q. Org. Lett. 2004, 6, 4853; (b) Zhang, S.-L.; Huang, Z.-S.; Shen, Y.-D.;
Li, Y.-M.; Yao, J.-H.; Huang, M.; Chan, A. S. C.; Gu, L.-Q. Tetrahedron Lett. 2006,
47, 6757; (c) Zhang, S.-L.; Huang, Z.-S.; Li, Y.-M.; Chan, A. S. C.; Gu, L.-Q.
Tetrahedron 2008, 64, 4403; (d) Asper, S. P., Jr.; Sachs, B. A.; Laschever, E. F.
Proc. Soc. Exp. Biol. Med. 1951, 78, 824; (e) Barker, S. B.; Kiely, C. E., Jr.; Dirks,
H. B., Jr.; Klitgaard, H. M.; Wang, S. C.; Wawzonek, S. J. Pharmacol. Exp. Ther.
1950, 99, 202.