Synthesis of novel tridentate pyrazole–bipyridine ligands for Co-complexes as redox-couples in dye-sensitized solar cells

Article abstract of DOI:10.1016/j.tet.2015.09.032

Novel pyrazole bipyridine ligands have been synthesized from 4,4′-substituted bipyridines through oxidation, chlorination and non-catalyzed C–N coupling of potassium pyrazolate with 6-halogen-4,4′-bipyridines in diglyme. These tridentate pyrazole–bipyridine ligands are of interest as components of new redox systems for dye-sensitized solar cells.

Full text of DOI:10.1016/j.tet.2015.09.032

Tetrahedron 71 (2015) 8551e8556
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of novel tridentate pyrazoleebipyridine ligands for
Co-complexes as redox-couples in dye-sensitized solar cells
,
Alexander G. Zavozin a, Nikolai V. Ignat’ev b, Michael Schulte b, Sergei G. Zlotin a
*
a N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., Moscow 119991, Russia
b Merck KGaA, PM-APR-FT, Frankfurter Strasse 250, D-64293 Darmstadt, Germany
a r t i c l e i n f o
a b s t r a c t
Novel pyrazole bipyridine ligands have been synthesized from 4,40-substituted bipyridines through ox-
idation, chlorination and non-catalyzed CeN coupling of potassium pyrazolate with 6-halogen-4,40-bi-
pyridines in diglyme. These tridentate pyrazoleebipyridine ligands are of interest as components of new
redox systems for dye-sensitized solar cells.
Article history:
Received 5 July 2015
Received in revised form 3 September 2015
Accepted 14 September 2015
Available online 15 September 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Pyrazoleebipyridine ligands
Dye-sensitized solar cells
1. Introduction
a
variety of anions such as [PF6]ꢀ,1,3 [(CF3SO2)2N]ꢀ,5 and
[B(CN)4]ꢀ.2,6,7 In particular, Co(II)/(III)-complexes with the tetra-
Modern dye-sensitized solar cells (DSSC) are multicomponent
systems that consist of a semiconductor anode (an oxide, typically
TiO2), dye-sensitizer, counter-electrode (cathode) and electrolyte
containing a redox couple, solvent and some additives. Although
DSSCs have already reached solar-to-electric power-conversion
efficiency (PCE) above 11% (under standard air mass 1.5 and solar
light intensity 1000 W/m2 at 298 K) they are still a factor of 2 below
that of Si solar cells.1 For further PCE improvement, all DSSC com-
ponents need optimization and, in particular the development of
adjusted redox couples. Electrolytes containing the Iꢀ/I3ꢀ redox
system are commonly used in DSSC as the hole conductor. However
the Iꢀ/Iꢀ3 redox couple suffers from a low redox potential that limits
the open-circuit potential to 0.7e0.8 V for this type of DSSC.2
Iodide-containing electrolytes may also cause corrosion of current
collectors made from Ag or Cu. These demand non-corrosive elec-
trolytes with the redox couple, which would be a better match for
the oxidation potential of the dye.
cyanoborate anion provide good DSSC performance.6,8
Recently, Merck KGaA (Darmstadt, Germany) has applied for the
patents claiming the preparation and use of Co-complexes with
[BH(CN)3]ꢀ, [BF(CN)3]ꢀ9,10 and [BF(C2F5)(CN)2]ꢀ11 anions as a redox
couple in DSSC. Heterocyclic ligands, which coordinate on the Co
cation, influence the redox properties12 and solubility of Co-
complexes in organic solvents. 2,20-Bipyridine (bpy) and 2,20:60,200-
terpyridine (terpy) derivatives are extensively studied as chelating
heterocyclic ligands.13 Inparticular, a series of homoleptic octahedral
cobalt (II) complexes with bidentate or tridentate azole-pyridine li-
gands (where azole is 1,2,4-triazole or substituted pyrazole) have
been recently prepared by non-catalyzed CeN coupling of azole with
fluoro-, chloro- or bromopyridine or bpy in DMSO in the presence of
potassium tert-butoxide as a base.12 Among them, pyrazole-bpy li-
gands are considered to be promising electrolyte components for
dye-sensitized solar cells. Furthermore, symmetrical tetradentate
6,60-di(pyrazol-1-yl)-4,40-dicarboxy and 4,40-diethoxycarbonyl-bpy
ligands have also been synthesized by a sophisticated multi-step
reaction sequence.14 Such kind of tetradentate ligands are of in-
terest in organometallic chemistry for building supramolecular
structures with a defined architecture.
Recently, several articles on the use of the Coþ2/Coþ3 redox
couple in DSSC have been published.1,3 The oxidation potential of
Coþ2-complexes and reduction potential of Coþ3-complexes were
demonstrated to depend on the counter-anion and on the nature of
ligands coordinated on the metal site. A variety of ligands have been
developed and studied with a view to stabilize the oxidation state
of Co(II) and Co(III).4 Co(II)/(III)-complexes are known to have
To the best of our knowledge, tridentate azole-bpy ligands
bearing electron-withdrawing substituents in the pyridine rings
capable of coordinating on the TiO2 layer have not been reported so
far. Herein we describe the first syntheses of pyrazol-1-yl-bpy de-
rivatives 1aed with carboxy, alkoxycarbonyl and aminocarbonyl
groups at positions 4 and 40 of the bpy structural fragment.
* Corresponding author. E-mail address: zlotin@ioc.ac.ru (S.G. Zlotin).
http://dx.doi.org/10.1016/j.tet.2015.09.032
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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A.G. Zavozin et al. / Tetrahedron 71 (2015) 8551e8556
2. Results and discussion
Compounds 4aed were selectively oxidized to the corre-
sponding mono-N-oxides 7aed with H2O2 in TFA (Scheme 3).
Electron-withdrawing C(O)R-groups in compounds 4aed did not
hinder the oxidation reaction, and compounds 7aed were obtained
in 84e93% yields and did not require further purification owing to
high purity. It is worth noting that oxidation of 4,40-bis(diethyla-
minocarbonyl)-6,60-dimethyl-bpy with m-CPBA in CHCl3 pro-
ceeded much less selectively, and resulted in a mixture of the
corresponding mono- (30%) and di-N-oxides (49%).19 6-Chloro-4,40-
disubstituted bpy 8aed were prepared in 54e91% yields by re-
We attempted two synthetic approaches to prepare target pyr-
azol-1-yl-bpy-4,40-dicarboxylic acid derivatives 1aed (Scheme 1).
The first was based on the conversion of commercially available
(Acros) 4,40-dimethyl-bpy 2 to 4,40-dimethyl-6-(1H-pyrazol-1-yl)-
bpy 3 followed by oxidation of the methyl groups in compound 3.
The second approach included initial oxidation of the methyl
groups in 2, to be followed by coupling of functionalized bpy de-
rivative 4 with the pyrazolate unit.
Scheme 1. Retro-syntheses of pyrazol-1-yl-bpy derivatives 1aed sourced from commercially available 4,40-dimethyl-bpy 2.
In exploring the first reaction pathway, we found that 4,40-di-
methyl-bpy 2 could be quantitatively oxidized to bpy-N-oxide 5 by
a modified literature procedure,15aef using a H2O2/TFA oxidizing
system instead of m-CPBA in CHCl3. Compound 5 was converted to
the corresponding 6-chloro derivative 6 by refluxing in POCl3
(Scheme 2).16 CeN coupling of chloro-derivate 6 with potassium
pyrazolate in diglyme at 130 ꢁC resulted in the formation of 4,40-
dimethyl-6-(1H-pyrazol-1-yl)-bpy 3. Unfortunately, our attempts
to oxidize the methyl groups in compound 3 to carboxy groups with
K2Cr2O7 in H2SO4 failed. The reaction mixture heating at 70 ꢁC for
3 h (typical conditions for oxidation with K2Cr2O7/H2SO4) afforded
a complex mixture of products that contained neither starting
compound 3 nor dicarboxylic acid 1a. Varying the reaction condi-
tions did not bring about any improvement.
ductive chlorination of N-oxides 7aed with an excess of POCl3
under reflux. This reaction proceeded much faster (ꢂ2.5 h vs 9 h)
than chlorination of compound 5 bearing electron-donating methyl
groups in the pyridine ring (Scheme 2). Alternatively, chloro-
derivate 8a was synthesized by oxidation of 6-chloro-4,40-di-
methyl-bpy 6 with K2Cr2O7 in H2SO4 (Scheme 3), though the yield
of compound 8a was lower in this case (49% vs 69%).
Desired 4,40-dicarboxy-6-(1H-pyrazol-1-yl)-bpy ligand 1a was
prepared in a moderate yield (34%) by non-catalyzed CeN coupling
of 6-chloro-bpy 8a with potassium pyrazolate under harsh condi-
tions (130 ꢁC, 20 h) in diglyme. Compounds 8c and 8d reacted with
potassium pyrazolate under milder conditions (90 ꢁC,1 h) to give 1c
and 1d in 52% and 64% yields, correspondingly (Scheme 3). Apart
from coupling products 1c and 1d, acid 4a was detected in the re-
Scheme 2. Synthesis of 4,40-dimethyl-6-(1H-pyrazol-1-yl)-bpy 3 from 2.
Therefore we changed our strategy. First, we oxidized starting
compound 2 to known dicarboxylic acid 4a by the action of K2Cr2O7
in H2SO4.17 Compound 4a smoothly reacted with CH2N2 in
a CHCl3eEt2O solvent mixture to afford corresponding diester 4b in
85% yield. Compound 4a also appeared convertible to diamides 4c
and 4d, which were prepared in 56% and 70% yield, respectively, by
means of a modified protocol.18 The new procedure includes in situ
generation of acid chloride from 4a by the action of SOCl2 followed
by its reaction with corresponding secondary amines.
action mixture as a by-product (10e15%). The formation of side
product 4a can be explained by a concurrent nucleophilic sub-
stitution of the amino moiety of the C(O)R group in 8c and 8d by
pyrazolate anions. The hydrolysis of the pyrazolocarbonyl CeN
bond in this intermediate during the aqueous workup leads to 4a.
Our attempts to apply the CeN coupling procedure to the syn-
thesis of base-sensitive di-ester 1b from chloride 8b and potassium
pyrazolate failed. Only di-carboxylic acid 8a contaminated with
unidentified by-products was isolated from the reaction mixture in

A.G. Zavozin et al. / Tetrahedron 71 (2015) 8551e8556
8553
Scheme 3. Synthesis of pyrazol-1-yl-bpy-4,40-dicarboxylic acid derivatives 1aed.
this case. Therefore, compound 1b was prepared in 65% yield by
treatment of corresponding di-acid 1a with diazomethane.
applied as a dry carrier; interface temperature was set at 180 ꢁC.
Melting points were measured on a Boetius heating table. The
solvents were pre-purified. The research-grade reagents were used
as supplied by Merck (Darmstadt, Germany) and Acros. Caution!
Diazomethane is toxic and explosive. The preparation must be
carried out in a good hood with an adequate shield.
3. Conclusions
Unknown tridentate pyrazole-bpy heterocycles bearing carboxy,
ethoxycarbonyl and carbamino groups in the pyridine ring have
been synthesized from commercially available 4,40-dimethyl-2,20-
bipyridine in 4e5 steps using simple and reproducible oxidation,
chlorination and non-catalyzed CeN coupling reactions. The pro-
posed synthetic protocol is easily scalable and convenient for the
preparation of multi-gram quantities of tridentate pyrazole-bpy
ligands having carboxylic acid moieties that enable the co-
ordination on the TiO2 site. The new ligands can be used to stabilize
metal cations in the high oxidation state, which are of interest as
redox couples for potential applications in dye-sensitized solar
cells.
4.2. Synthesis of starting compounds 4
4.2.1. Dimethyl 2,20-bipyridine-4,40-dicarboxylate (4b). An ether
solution (30 mL) of CH2N2 prepared from N-methyl-N-nitrosourea
(2.18 g, 21.2 mmol) and 50% aqueous KOH (10 mL) was added
dropwise to stirred suspension of 2,20-bipyridine-4,40-dicarboxylic
acid 4a (1.00 g, 4.10 mmol) in CHCl3 (80 mL) at ambient tempera-
ture. Upon the evolution of nitrogen, the reaction mixture was fil-
tered from minor solid impurities and the solvents were removed
under reduced pressure (10 Torr) at 20 ꢁS. The residue was washed
with n-hexane (30 mL) and filtered off to afford 4b as light beige
powder. Yield 0.94 g (85%), mp 215 ꢁS (lit.20 mp 214 ꢁC); Rf 0.61
(Silica gel, CH2Cl2/MeOH (19:1)). The 1H NMR spectrum corre-
sponds to reported data.17b
4. Experimental
4.1. General
The IR spectra (KBr pellets) were recorded on a Bruker IFS 113v
spectrometer. Chromatography was performed on a column filled
with Silicagel 0.035e0.070 mm, 60 A (Acros) or with Aluminium
4.2.2. 4,40-Bis(diethylaminocarbonyl)-2,20-bipyridine
(4c). 2,20-
Bipyridine-4,40-dicarbonyl dichloride [prepared from 2,20-bipyr-
idine-4,40-dicarboxylic acid 4a (0.98 g, 4.0 mmol) and SOCl2 (20 mL)
under reflux for 20e24 h17,21] was dissolved in anhydrous THF
(15.0 mL). Then solution of diethylamine (5.0 mL, 48.3 mmol) in
THF (4.0 mL) was added at 0e5 ꢁC over 10 min and the reaction
mixture was stirred at ambient temperature for 1 h. All volatile
materials were removed under reduced pressure (10 Torr) and the
remaining brown oil was purified by column chromatography
(Al2O3; eluent CHCl3) to afford a mixture (w2.0 g) of 4c and
diethylamine hydrochloride (according to 1H NMR data). This
mixture was rinsed with cold water (2ꢃ2.0 mL), filtered and dried
in air affording 4c as light beige crystals (0.80 g, 56%), mp
118e120 ꢁS; nmax 2976, 1634, 1594, 1546, 1477, 1452, 1434, 1387,
1356, 1311, 1291, 1219, 1092, 1072, 855, 788, 717, 610 cmꢀ1; Rf 0.43
(Al2O3; eluent CHCl3); dH (CDCl3), 8.72 (2H, d, J 4.6 Hz), 8.40 (2H, s),
7.28 (2H, d, J 4.6 Hz), 3.57 (4H, q, J 6.7 Hz), 3.26 (4H, q, J 6.7 Hz), 1.26
oxide (neutral, Brockmann I, 50e200
mm, 60A). The reaction
progress was by TLC monitored on ‘Merck Silica gel 60 F254’ or
‘Merck Aluminium Oxide 60 F254 neutral’ plates; visualization by I2
or UV. The NMR spectra were recorded on a Bruker AM 300 (1H
300.13; 13C 75.47 MHz) spectrometer. The chemical shifts are re-
ported in parts per million relative to tetramethylsilane. The high
resolution mass spectra (HRMS) were measured on a Bruker
micrOTOF II Electrospray Ionization (ESI) mass spectrometer. The
measurements were done either in the positive ion mode (interface
capillary voltage: 4500 V) or in the negative ion mode (3200 V); the
mass range from m/z 50 to m/z 3000 Da; external or internal cali-
bration was done with Electrospray Calibrant Solution (Fluka). A
syringe was used to inject a solution of the examined compound in
acetonitrile, methanol or water (flowrate 3 mL/min). Nitrogen was

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A.G. Zavozin et al. / Tetrahedron 71 (2015) 8551e8556
(6H, t, J 6.7 Hz),1.13 (6H, t, J 6.7 Hz); 1H NMR was in accordance with
the reported data.18 dC (CDCl3): 168.7 (CO), 155.9, 149.7, 145.9, 121.0,
118.2, 43.3, 39.4, 14.2, 12.9. HRMS: MHþ, found 355.2122,
CHCl3/MeOH (19:1)); dH (CDCl3): 8.95 (1H, s), 8.75 (1H, d, J 4.9 Hz),
8.23e8.32 (2H, m), 7.26e7.38 (2H, m), 3.21e3.60 (8H, m), 1.10e1.30
(12H, m); dC (CDCl3): 168.4 (CO),167.3 (CO),149.9,149.1,146.4,145.1,
140.8, 133.9, 125.9, 123.8, 122.4, 122.0, 43.5, 39.6, 14.2, 12.9; HRMS:
MHþ, found 371.2066, C20H27N4O3þ calcd 371.2078; MNaþ, found
393.1889; C20H26N4O3Naþ calcd 393.1897.
C
C
20H27N4Oþ2
20H26N4O2Naþ calcd 377.1948.
calcd
355.2129.
MNaþ,
found
377.1936.
4.2.3. 4,40-Bis(piperidin-1-ylcarbonyl)-2,20-bipyridine
(4d). Piperidine (3.2 mL, 32.0 mmol) solution in THF (4.0 mL) was
added to stirred 2,20-bipyridine-4,40-dicarbonyl dichloride
(4.0 mmol) solution in THF (15.0 mL) at 0e5 ꢁC during 10 min. The
reaction mixture was stirred at ambient temperature for 2 h. All
volatile materials were removed under reduced pressure (10 Torr).
Water (20 mL) was added to the residue, the precipitate was filtered
off, successively washed with water (3ꢃ5 mL) and hexane
(2ꢃ5 mL), and purified by flash chromatography (Al2O3, eluent
CHCl3) affording 4d as light beige crystals (1.06 g, 70%), mp
209e210 ꢁS (EtOAc/MeOH); nmax 2943, 2865, 1635, 1592, 1544,
1472, 1443, 1350, 1288, 1259, 1114, 1024, 891, 866, 762, 638 cmꢀ1; Rf
0.51 (Al2O3, eluent CHCl3/MeOH (19:1)); dH (CDCl3): 8.72 (2H, d, J
4.0 Hz), 8.40 (2H, s), 7.31 (2H, d, J 4.0 Hz), 3.68e3.78 (4H, m),
3.28e3.38 (4H, m), 1.48e1.80 (12H, m); dC (CDCl3): 167.6 (CO),
155.9, 149.7, 145.3, 121.4, 118.5, 48.5, 43.0, 26.5, 25.5, 24.4; HRMS:
MHþ, found 379.2120, C22H27N4O2þ calcd 379.2129. MNaþ, found
401.1941, C22H26N4O2Naþ calcd 401.1948.
4.3.5. 4,40-Bis(piperidin-1-ylcarbonyl)-2,20-bipyridine,
N-oxide
(7d). Colorless crystals, yield 5.20 g (88%), mp 163e165 ꢁC (hexane/
EtOAc); nmax 2941, 2856, 1632, 1553, 1473, 1442, 1358, 1285, 1259,
1115, 1029, 850, 639 cmꢀ1; Rf 0.39 (Al2O3, eluent CHCl3/MeOH
(19:1)); dH (CDCl3): 8.92 (1H, s), 8.74 (1H, d, J 4.6 Hz), 8.24e8.30 (2H,
m), 7.37 (1H, d, J 4.6 Hz), 7.32 (1H, d, J 5.2 Hz), 3.32e3.74 (8H, m),
1.50e1.75 (12H, m); dC (CDCl3): 167.2 (CO), 166.2 (CO), 150.0, 149.1,
146.3, 144.4, 140.8, 133.1, 126.3, 124.2, 122.7, 122.4, 48.7, 43.1, 26.4,
25.5, 24.4, 24.4; HRMS: MHþ, found 395.2077, C22H27N4Oþ3 calcd
395.2078; MNaþ, found 417.1903, C22H26N4O3Naþ calcd 417.1897.
4.4. General procedure for the synthesis of 6-chloro-4,40-di-R-
bipy 6 and 8aed
4,40-Di-R-2,20-bipyridine, N-oxide 5 or 7aed (10.0 mmol) was
slowly added to stirred POCl3 (10.0 equiv) at 0 ꢁC and the reaction
mixture was refluxed for 1e2 h (in case of 5 d for 9 h). Excess POCl3
was removed under reduced pressure (10 Torr) and ice-cooled
water (50 mL) was added to the residue. Precipitated 8a was fil-
tered, washed with water (3ꢃ5 mL, and dried in air to give pure
compound 8a. For isolation of 6 and 8bed, pH of the aqueous
suspension was adjusted to 6e7 with 5 M NaOH and the products
were extracted with CH2Cl2 (3ꢃ30 mL). The combined organic
extracts were dried over anhydrous Na2SO4 and evaporated under
reduced pressure (10 Torr). The remaining crude compound 6 and
8d were purified by column chromatography on Silica gel (eluent:
n-hexane/EtOAc (4:1)) and on Al2O3 (eluent: n-hexane/CHCl3
(1:1)), respectively. Analytically pure samples of compounds 8b and
8c were obtained by rinsing the oily residue with n-hexane or
diethyl ether, respectively.
4.3. General procedure for the synthesis of 4,40-di-R-bipy-N-
oxides 5 and 7aed
30% Aqueous H2O2 (2.25 mL, 22.0 mmol) was slowly added to
a solution (suspension in the case of 4a) of 4,40-di-R-2,20-bipyridine
2 or 4aed (15.0 mmol) in TFA (10.0 mL). The reaction mixture was
stirred at ambient temperature for 2e4 h (TLC monitoring) and
diluted with water (60 mL). The precipitated 7a was filtered off,
washed successively with water and acetone, dried in air and used
in subsequent reactions without further purification. For isolation
of 5 and 7bed, pH of the aqueous solution was carefully adjusted to
7 with 5 M aqueous NaOH and the products were extracted with
CHCl3 (3ꢃ20 mL). The combined extracts were dried over anhy-
drous MgSO4 and evaporated under reduced pressure (10 Torr). The
residue was washed with n-hexane (5 mL) affording analytically
pure samples of 5 and 7bed.
4.4.1. 6-Chloro-4,40-dimethyl-2,20-bipyridine (6). Colorless crystals,
yield 1.31 g (60%), mp 100 ꢁC; Rf 0.44 (Silica gel, eluent n-hexane/
EtOAc (4:1)); dH (CDCl3): 8.51 (1H, d, J 4.9 Hz), 8.23 (1H, s), 8.17 (1H,
s), 7.11e7.18 (2H, m), 2.44 (3H, s, CH3), 2.42 (3H, s, CH3). 1H NMR was
consistent with reported data.16
4.3.1. 4,40-Dimethyl-2,20-bipyridine, N-oxide (5). Colorless crystals,
yield 2.94 g (98%), mp 94e95 ꢁC (lit.15c mp 83e84 ꢁC); Rf (Silica gel,
eluent CHCl3/MeOH (19:1)) 0.55. The 1H NMR spectra was consis-
tent with reported data.15c
4.4.2. 6-Chloro-4,40-dicarboxy-2,20-bipyridine (8a). Colorless pow-
der, yield 1.92 g (69%), mp >300 ꢁC; nmax 3071, 2922, 2852, 2562,
1705, 1593, 1553, 1480, 1447, 1410, 1363, 1299, 1234, 1169, 1144, 905,
4.3.2. 4,40-Dicarboxy-2,20-bipyridine, N-oxide (7a). Colorless solid,
yield 3.51 g (90%), mp >300 ꢁC; nmax 3120, 2446, 1914, 1729, 1555,
772, 676 cmꢀ1
; dH (DMSO-d6): 8.92 (1H, d, J 4.9 Hz), 8.75 (1H, s),
8.68 (1H, s), 7.90e7.96 (2H, m); dC (DMSO-d6): 165.8 (CO), 164.6
(CO), 156.1, 153.9, 150.9, 150.8, 142.9, 139.6, 124.0, 123.4,119.6, 118.4;
HRMS: MHþ, found 279.0169, C12H8ClN2O4þ calcd 279.0167; MNaþ,
found 300.9983; C12H7ClN2O4Naþ calcd 300.9987.
1465, 1368, 1310, 1281, 1217, 1197, 912, 837, 772, 669, 651 cmꢀ1
; dH
(DMSO-d6): 9.27 (1H, s), 8.98 (1H, d, J 4.7 Hz), 8.66 (1H, s), 8.50 (1H,
d, J 6.7 Hz), 7.97 (1H, d, J 4.5 Hz), 7.90 (1H, d, J 4.7 Hz); dC (DMSO-d6):
165.9 (CO), 164.7 (CO), 150.5, 149.6, 145.5, 141.4, 138.6, 127.6, 126.8,
125.8, 123.8, 123.7; HRMS: MHþ, found 261.0501. C12H9N2Oþ5 calcd
261.0506; MHꢀ, found 259.0356; C12H7N2Oꢀ5 , calcd 259.0360.
4.4.3. Dimethyl
6-chloro-2,20-bipyridine-4,40-dicarboxylate
(8b). Colorless crystals, yield 2.79 g (91%), mp 172 ꢁC; nmax 3091,
2960, 1735, 1592, 1554, 1414, 1361, 1294, 1269, 1253, 1131, 966, 855,
763, 694 cmꢀ1; Rf 0.48 (Silica gel, eluent n-hexane/EtOAc (4:1)); 1H
NMR was consistent with reported data;15f dC (CDCl3): 165.7 (CO),
164.5 (CO), 156.5, 155.2, 152.0, 150.2, 141.4, 138.7, 124.3, 123.8, 120.7,
119.3, 53.0, 52.9. HRMS: MHþ, found 307.0479, C14H11ClN2Oþ4 calcd
307.0480; MNaþ, found 329.0299, C14H10ClN2O4Naþ calcd
329.0300.
4.3.3. 4,40-Bis(methoxycarbonyl)-2,20-bipyridine,
N-oxide
(7b). Colorless crystals, yield 3.63 g (84%), mp 195 ꢁC [lit.15f nd];
nmax 3132, 2955, 1731, 1565, 1461, 1428, 1362, 1297, 1274, 1244, 1222,
1199, 1112, 962, 768, 689, 664 cmꢀ1; Rf 0.44 (Silica gel, eluent
CH2Cl2/MeOH (19:1)); dH (CDCl3) 9.34 (1H, s), 8.91 (1H, d, J 6.0 Hz),
8.79 (1H, d, J 1.8 Hz), 8.34 (1H, d, J 6.7 Hz), 7.95e7.88 (2H, m), 4.00
(3H, s), 3.98 (3H, s). 1H NMR was consistent with reported data.15f
4.4.4. 4,40-Bis(diethylaminocarbonyl)-6-chloro-2,20-bipyridine
(8c). Beige powder, yield 2.14 g (55%), mp 129e130 ꢁC; nmax 3066,
2978, 1634, 1591, 1537, 1482, 1463, 1441, 1361, 1295, 1280, 1220,
4.3.4. 4,40-Bis(diethylaminocarbonyl)-2,20-bipyridine,
(7c). Light yellow oil, yield 5.16 g (93%); Rf 0.52 (Al2O3, eluent
N-oxide

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8555
1155, 1072, 843, 622 cmꢀ1; Rf 0.80 (Al2O3, eluent CHCl3/MeOH
(19:1)); dH (CDCl3): 8.70 (1H, d, J 4.1 Hz), 8.40 (1H, s), 8.32 (1H, s),
7.32 (2H, s), 3.58 (4H, m), 3.25 (4H, m), 1.21e1.29 (6H, m), 1.10e1.16
(6H, m); dC (CDCl3): 168.4 (CO), 167.2 (CO), 156.2, 154.3, 151.4, 149.5,
148.6,146.2,121.6, 121.5, 118.6, 116.8, 43.3, 39.5, 39.4,14.2,14.1, 12.8;
HRMS: MHþ, found 389.1736, C20H26ClN4O2þ calcd 389.1739; MNaþ,
found 411.1552, C20H25ClN4O2Naþ calcd 411.1558.
calcd 421.2347; MNaþ, found 443.2160; C23H28N6O2Naþ calcd
443.2166.
4.6.3. 4,40-Bis(piperidin-1-ylcarbonyl)-6-(1H-pyrazol-1-yl)-2,20-bi-
pyridine (1d). Colorless crystals, yield 1.62 g, (64%), mp 153e155 ꢁC
(hexane); nmax 2936, 2857, 1635, 1552, 1471, 1446, 1397, 1285, 1129,
1057, 952, 854, 755, 638 cmꢀ1; Rf 0.36 (Al2O3, eluent CHCl3/MeOH
(19:1)), dH (CDCl3): 8.70e8.82 (2H, m), 8.43 (1H, s), 8.33 (1H, s), 8.02
(1H, s), 7.77 (1H, s), 7.34 (1H, m), 6.51 (1H, s), 3.71e3.83 (4H, m),
3.30e3.42 (4H, m), 1.51e1.80 (8H, m), 1.23e1.32 (4H, m), dC (CDCl3):
167.5 (CO), 167.1 (CO), 155.1, 154.3, 151.4, 149.4, 148.4, 145.6, 142.5,
127.3, 121.5, 118.8, 116.3, 110.4, 108.1, 48.6, 43.0, 26.6, 26.5, 26.5,
26.5, 25.5, 24.4. HRMS: MHþ, found 445.2360, C25H29N6Oþ2 calcd
445.2347; MNaþ, found 467.2175, C25H28N6O2Naþ calcd 467.2166.
4.4.5. 4,40-Bis(piperidin-1-ylcarbonyl)-6-chloro-2,20-bipyridine
(8d). Colorless crystals, yield 2.23 g (54%), mp 195e196 ꢁC (Et2O);
nmax 2937, 2858, 1637, 1591, 1536, 1477, 1445, 1358, 1289, 1274, 1127,
854, 636 cmꢀ1; Rf 0.45 (Al2O3, eluent CHCl3/MeOH (19:1)); dH
(CDCl3): 8.70 (1H, d, J 4.5 Hz), 8.39 (1H, s), 8.33 (1H, s), 7.25e7.35
(2H, m), 3.68e3.78 (4H, m), 3.27e3.37 (4H, m), 1.51e1.76 (12H, m);
dC (CDCl3): 167.4 (CO), 166.2 (CO), 156.5, 154.5, 151.5, 149.8, 148.1,
145.5, 122.0, 121.9, 118.9, 117.1, 48.6, 43.1, 43.0, 26.5, 25.5, 24.4, 24.4;
HRMS: MHþ, found 413.1748, C22H26ClN4O2þ calcd 413.1739; MNaþ,
found 435.1558, C22H25ClN4O2Naþ calcd 435.1558.
4.7. Synthesis of 4,40-di-R-6-(1H-pyrazol-1-yl)-2,20-bipyr-
idines 1a and 1b
4.7.1. 4,40-Dicarboxy-6-(1H-pyrazol-1-yl)-2,20-bipyridine
(1a). 6-
4.5. Alternative methods for the synthesis of 6-chloro-4,40-
dicarboxy-bipy 8a
Chloro-4,40-dicarboxy-2,20-bipyridine 8a (0.45 g, 1.6 mmol) was
added to excess potassium pyrazolate [prepared from pyrazole
(0.28 g, 4.0 mmol) and potassium metal (0.32 g, 8.2 mmol) at 70 ꢁC
in anhydrous diglyme (15 mL)]. The reaction mixture was stirred at
130 ꢁC for 20 h, cooled to ambient temperature and diluted with
water (50 mL). The suspended solid material was filtered off, and
pH of filtrate was adjusted to 6 with 30% H2SO4 resulting in the
sedimentation. The precipitate was filtered off, washed with water
(2ꢃ10 mL) and dried in air affording 1a (0.17 g, 34%), mp >300 ꢁS;
nmax 3110, 2762, 2469, 1889, 1721, 1561, 1466, 1402, 1377, 1288, 1278,
Potassium bichromate (2.86 g, 9.72 mmol) was slowly added to
solution of 6-chloro-4,40-dimethyl-2,20-bipyridine
6
(0.6 g,
2.74 mmol) in H2SO4 (10 mL) at ꢂ40 ꢁC. The reaction mixture was
kept at ambient temperature overnight and poured onto ice. The
precipitate was filtered off, washed with water (3ꢃ5 mL) and dried
in air affording 8a (0.37 g, 49%). The product was identical to the
sample prepared by reductive chlorination of N-oxide 7a.
1259, 1245, 1201, 1044, 1012, 767, 676 cmꢀ1
; dH (DMSO-d6):
4.6. General procedure for the synthesis of 4,40-di-R-6-(1H-
pyrazol-1-yl)-2,20-bipyridines 3 and 1c,d from corresponding
6-chlorocompounds 6 and 8c,d
8.66e8.95 (4H, m), 8.33 (1H, s), 7.84e7.97 (2H, m), 6.66 (1H, s); dC
(DMSO-d6): 171.2 (CO), 170.5 (CO), 159.6, 159.1, 156.5, 155.7, 148.0,
147.8, 144.9, 132.5, 129.0, 124.9, 122.6, 117.1, 114.0; HRMS: MHþ,
found 311.0780,
C
15H11N4Oþ4 calcd 311.0775; MNaþ, found
6-Chloro-4,40-di-R-bipyridine 6 or 8c,d (5.7 mmol) was added to
potassium pyrazolate [prepared from pyrazole (1.00 g, 14.3 mmol)
and potassium metal (0.53 g, 13.6 mmol) at 70 ꢁC in anhydrous
diglyme (30 mL)]. The reaction mixture was stirred at 130 ꢁC for
20 h (for 6) or at 90 ꢁC for 1 h (for 8c,d). Then it was cooled to
ambient temperature and diluted with water (100 mL). The pre-
cipitate was filtered off, thoroughly washed with water (3ꢃ10 mL),
dried in air and re-crystallized from the mixture of appropriate
solvents to afford pure compound 3 or 1c,d.
333.0590, C15H10N4O4Naþ calcd 333.0594.
4.7.2. 4,40-Dimethoxycarbonyl-6-(1H-pyrazol-1-yl)-2,20-bipyridine
(1b). Ether solution (6 mL) of CH2N2 prepared from methylni-
trosourea (0.40 g, 3.80 mmol) and 50% aq solution of KOH (3 mL)
was added dropwise to stirred suspension of 4,40-dicarboxy-6-(1H-
pyrazol-1-yl)-2,20-bipyridine 1a (0.17 g, 0.55 mmol) in diethyl ether
(5 mL). Upon the evolution of nitrogen, the reaction mixture was
stirred additionally for 15 min, filtered from minor solid impurities
and evaporated under reduced pressure (10 Torr) at 20 ꢁS. The
residue was purified by column chromatography (Silica gel, eluent
n-hexane/EtOAc (3:1)) affording 1b (0.12 g, 65%), mp 188 ꢁS (n-
hexane/EtOAc); nmax 3129, 3095, 2958, 1733, 1561, 1466, 1434, 1403,
1352, 1299, 1286, 1253, 1125, 1052, 972, 950, 765, 691, 671 cmꢀ1; Rf
0.34 (Silica gel, eluent n-hexane/EtOAc (3:1)); dH (CDCl3): 8.93 (1H,
s), 8.86e8.88 (2H, m), 8.77 (1H, s), 8.59 (1H, s), 7.91 (1H, d, J 4.1 Hz),
7.81 (1H, s), 6.55 (1H, s), 4.04 (3H, s), 4.02 (3H, s); dC (CDCl3): 165.6
(CO), 165.0 (CO), 155.8, 155.0, 152.0, 150.2, 142.7, 141.6, 138.6, 127.4,
123.5, 120.5, 118.2, 112.7, 108.3, 52.9, 52.8; HRMS: MHþ, found
339.1086, C17H15N4Oþ4 calcd 339.1088; MNaþ, found 361.0902,
4.6.1. 4,40-Dimethyl-6-(1H-pyrazol-1-yl)-2,20-bipyridine
(4,40-
dmpbp) (3). Colorless crystals, yield 1.20 g (84%), mp 125e126 ꢁC
(EtOH/H2O); nmax 3157, 3105, 1612, 1595, 1571, 1557, 1522, 1465,
1398, 1198, 1055, 1040, 953, 855, 831, 785, 765, 684, 513 cmꢀ1; Rf
0.42 (Al2O3, eluent n-hexane/EtOAc (4:1)); dH (CDCl3): 8.73 (1H, s),
8.52 (1H, d, J 4.9 Hz), 8.24 (1H, s), 8.14 (1H, s), 7.84 (1H, s), 7.75 (1H,
s), 7.13 (1H, d, J 4.4 Hz), 6.49 (1H, s), 2.49 (3H, s, CH3), 2.45 (3H, s,
CH3); dC (CDCl3): 155.3, 154.5, 151.3, 151.2, 149.0, 148.1, 141.9, 127.2,
124.9, 122.1, 119.8, 112.9, 107.5, 21.4, 21.3; HRMS: MHþ, found:
251.1291,
C
C
15H15Nþ4 calcd: 251.1291; MNaþ, found: 273.1109,
15H14N4Naþ calcd: 273.1111.
C
17H14N4O4Naþ calcd 361.0907.
4.6.2. 4,40-Bis(diethylaminocarbonyl)-6-(1H-pyrazol-1-yl)-2,20-bi-
pyridine (1c). Colorless crystals, yield 1.24 g, (52%), mp 124e125 ꢁC
(n-hexane/EtOAc); nmax 2970, 1629, 1622, 1553, 1459, 1398, 1284,
1220, 1099, 1056, 955, 790, 758, 633 cmꢀ1; Rf 0.70 (Al2O3, eluent
CHCl3/MeOH (19:1)), dH (CDCl3): 8.71 (1H, d, J 4.6 Hz), 8.68 (1H, d, J
2.3 Hz), 8.40 (1H, s), 8.31 (1H, s), 7.99 (1H, s), 7.74 (1H, s), 7.30 (1H, d,
J 4.6 Hz), 6.48 (1H, s), 3.62e3.53 (4H, m), 3.31e3.21 (4H, m),
1.30e1.12 (12H, m), dC (CDCl3): 168.7 (CO), 168.2 (CO), 155.2, 154.6,
151.3, 149.7, 148.8, 145.8, 142.4, 127.1, 121.2, 118.1, 115.9, 109.9, 108.0,
43.2, 39.4, 14.3, 12.8, HRMS: MHþ, found 421.2343, C23H29N6Oþ2
Acknowledgements
This work was financially supported by Merck KGaA, Darmstadt,
Germany.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.09.032.

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A.G. Zavozin et al. / Tetrahedron 71 (2015) 8551e8556
11. Ignatyev, N.; Schulte, M.; Kawata, K.; Landmann, J.; Sprenger, J. A. P.; Finze, M.
References and notes
Patent Application filed, (Merck Patent GmbH, Darmstadt, Germany).
€
12. Shavaleev, N. M.; Kessler, F.; Gratzel, M.; Nazeeruddin, M. K. Inorg. Chim. Acta
1. Yum, J.-H.; Baranoff, E.; Kessler, F.; Moehl, T.; Ahmad, S.; Bessho, T.; Marchioro,
A.; Ghadiri, E.; Moser, J.-E.; Yi, C.; Nazeeruddin, Md. K.; Gratzel, M. Nat. Com-
mun. 2012, 3, 631.
2. Tsao, H. N.; Yi, C.; Moehl, T.; Yum, J.-H.; Zakeeruddin, S. M.; Nazeeruddin, M. K.;
Gratzel, M. ChemSusChem 2011, 4, 591e594.
3. Kim, H.-S.; Ko, S.-B.; Jang, I.-H.; Park, N.-G. Chem. Commun. 2011, 12637e12639.
4. Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements, Band 2, Part 26.
Cobalt, Rhodium, Iridium; Elsevier Science Ltd, 1997.
5. (a) Burschka, J.; Dualeh, A.; Kessler, F.; Baranoff, E.; Cevey-Ha, N.-L.; Yi, C.;
Nazeeruddin, M. K.; Gratzel, M. J. Am. Chem. Soc. 2011, 133, 18042e18045; (b)
Nockemann, P.; Pellens, M.; Hecke, K. V.; Meervelt, L. V.; Wouters, J.; Thijs, B.;
Vanecht, E.; Parac-Vogt, T. N.; Mehdi, N.; Schaltin, S.; Fransaer, J.; Zahn, S.;
Kirchner, B.; Binnemans, K. Chem.dEur. J. 2010, 16, 1849e1858.
6. Tsao, H. N.; Burschka, J.; Yi, C.; Kessler, F.; Nazeeruddin, M. K.; Gratzel, M. Energy
Environ. Sci. 2011, 4, 4921e4924.
7. Yella, A.; Lee, H.-W.; Tsao, H. N.; Yi, C.; Chadrian, A. K.; Nazeeruddin, M. K.; Diau,
E. W.-G.; Yeh, C.-Y.; Zakeeruddin, S. M.; Gratzel, M. Science 2011, 334, 629e634.
2013, 407, 261e268.
€
13. Downard, A. J.; Honey, G. E.; Steel, P. J. Inorg. Chem. 1991, 30, 3733e3737.
€
14. Klein, C.; Baranoff, E.; Gratzel, M.; Nazeeruddin, M. K. Tetrahedron Lett. 2011, 52,
584e587.
€
15. (a) Young, M. C.; Liew, E.; Ashby, J.; McCoy, K. E.; Hooley, R. J. Chem. Commun.
2013, 6331e6333; (b) Zalas, M.; Gierczyk, B.; Ceglowski, M.; Schroeder, G.
Chem. Pap. 2012, 66, 733e740; (c) Kodama, K.; Kobayashi, A.; Hirose, T. Tetra-
hedron Lett. 2013, 54, 5514e5517; (d) Siana, L. D.; Hamachi, I.; Meyer, T. J. J. Org.
Chem. 1989, 54, 1731e1735; (e) Patent: EP 1424336 A1, 2004; (f) Kim, J.-J.; Choi,
H.; Paek, S.; Kim, C.; Lim, K.; Ju, M.-J.; Kang, H. S.; Kang, M.-S.; Ko, J. Inorg. Chem.
2011, 50, 11340e11347.
€
16. Lilio, A. M.; Grice, K. A.; Kubiak, C. P. Eur. J. Inorg. Chem. 2013, 4016e4023.
17. (a) Wu, K.-L.; Li, C.-H.; Chi, Y.; Clifford, Y. N.; Cabau, L.; Palomares, E.; Cheng, Yi-
M.; Pan, H.-A.; Chou, P.-T. J. Am. Chem. Soc. 2012, 134, 7488e7496; (b) Muldoon,
J.; Ashcroft, A. E.; Wilson, A. Chem.dEur. J. 2010, 16, 100e103.
18. Aldridge, W. S., III; Hornstein, B. J.; Serron, S.; Dattelbaum, D. M.; Schoonover, J.
R.; Meyer, T. J. J. Org. Chem. 2006, 71, 5186e5190.
€
€
8. Nazeeruddin, M.; Graetzel, M.; Baranoff, E.; Kessler, F.; Yum, J.-H.; Yella, A.;
Tsao, H. N.; WO 2012/114315 (A1), Ecole Polytechnique Federale de Lausanne.
9. Ignatyev, N.; Schulte, M.; Kawata, K. WO 2014/082706 A1 (Merck Patent GmbH,
Darmstadt, Germany).
19. Harding, M. M.; Koert, U.; Lehn, J.-M.; Marquis-Regault, A.; Piguet, C.; Siegel, J.
Helv. Chim. Acta 1991, 74, 594e610.
20. Ohkanda, J.; Satoh, R.; Kato, N. Chem. Commun. 2009, 6949e6951.
21. Khatua, S.; Schmittel, M. Org. Lett. 2013, 15, 4422e4425.
10. Ignatyev, N.; Schulte, M.; Kawata, K.; Berhardt, E.; Berhardt-Pitchougina, V.;
Willner, H. WO 2014/082704 A1 (Merck Patent GmbH, Darmstadt, Germany).