Ionic-liquid salt-mediated synthesis of 4′-(pyridyl)-terpyridines

Article abstract of DOI:10.1080/00397910903046838

One-pot reactions to produce isomeric 4′-(pyridyl) 2,2′:6′,2"-terpyridine under moderate conditions are described using imidazolium-based ionic liquid and quaternary ammonium-based molten salts as solvent media. The use of eutectic molten salts as a reaction media proved effective in sequential aldol and Michael addition reactions, leading to substituted terpyridines. The desired product was obtained in reasonable yield via a simple, one-pot reaction.

Full text of DOI:10.1080/00397910903046838

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Ionic-Liquid Salt-Mediated Synthesis of
4′-(Pyridyl)-terpyridines
Sumit V. Jadhav a , Pravin G. Ingole a & Hari C. Bajaj a
a Discipline of Inorganic Materials and Catalysis, Central Salt and
Marine Chemicals Research Institute, Council of Scientific and
Industrial Research, Bhavnagar, Gujarat, India
Published online: 12 Mar 2010.
To cite this article: Sumit V. Jadhav , Pravin G. Ingole & Hari C. Bajaj (2010) Ionic-Liquid Salt-
Mediated Synthesis of 4′-(Pyridyl)-terpyridines, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:8, 1142-1148, DOI:
10.1080/00397910903046838
To link to this article: http://dx.doi.org/10.1080/00397910903046838
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Synthetic Communications1, 40: 1142–1148, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903046838
IONIC-LIQUID SALT-MEDIATED SYNTHESIS OF
40-(PYRIDYL)-TERPYRIDINES
Sumit V. Jadhav, Pravin G. Ingole, and Hari C. Bajaj
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine
Chemicals Research Institute, Council of Scientific and Industrial Research,
Bhavnagar, Gujarat, India
One-pot reactions to produce isomeric 40-(pyridyl) 2,20:60,200-terpyridine under moderate
conditions are described using imidazolium-based ionic liquid and quaternary ammonium-
based molten salts as solvent media. The use of eutectic molten salts as a reaction media
proved effective in sequential aldol and Michael addition reactions, leading to substituted
terpyridines. The desired product was obtained in reasonable yield via a simple, one-pot
reaction.
Keywords: Green chemistry; ionic liquid; quaternary ammonium salts; terpyridines
INTRODUCTION
Over the past couple of years, the oligopyridines and in particular 2,20:60,200-
terpyridines (TPY) have been the subject of intensive investigation in the area of
supramolecular chemistry. Organic moieties bearing TPY subunits are extremely
versatile building blocks for the construction of libraries of metallo-supramolecular
assemblies as a consequence of their favorable geometry, which leads to coordi-
nation with various metal ions.[1,2] The enormous interest in this class of compounds
has been driven by their strong metal-to-ligand charge-transfer transitions, facile
electron-transfer properties, and sufficiently extendable 3MLCT (metal-to-ligand
charge transfer) excited states.[3] In recent times, TPYs have drawn wide attention
because of their potential applications in photochemistry for the design of lumi-
nescent devices or as sensitizers for light-to-electricity conversion[4] and dye-
sensitized solar cells,[5] in catalysis,[6] in nanoscience,[7,8] and in biochemistry.[9–11]
For the diverse range of applications, easy access to differently functionalized
TPY on a large scale and good yields are prerequisites. Conventional approaches to
TPY synthesis involves either coupling reactions of pyridine subunits,[12,13] conden-
sation reactions,[14,15] or pyrolysis[16]; however, these methods suffer several dis-
advantages such as multistep procedure, long reaction time, poor yield, and use of
Received February 1, 2009.
Address correspondence to Hari C. Bajaj, Discipline of Inorganic Materials and Catalysis, Central
Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research, G. B. Marg,
Bhavnagar 364002, Gujarat, India. E-mail: hcbajaj@csmcri.org
1142

SYNTHESIS OF TPY IN IONIC LIQUID
1143
volatile organic compounds (VOCs) and toxic reagents. As a consequence, for the
stringent and growing environmental regulations, it is desirable to develop environ-
mentally cautious synthetic methods with minimal toxics, a foremost requirement of
green chemistry.[17] To date, polyethylene glycol (PEG)-mediated synthesis of TPY
via 1,5-diketone intermediate, reported by Smith et al.[18] is the most prominent
approach to synthesis of the target compound, both in the context of generality
and simplicity of the procedure. As we find in the literature, the various molten-salt
systems were successfully investigated as solvent media.[19,20] To the best of our
knowledge, synthesis of TPY in such solvent media has rarely been reported.
Herein, we have reported facile and clean synthesis of a series of isomeric
40-(pyridyl)-terpyridines 1–6 from appropriate precursors using imidazolium-based
ionic liquid (IL) as well as quaternary ammonium sulfates as reaction media.
EXPERIMENTAL
Materials
Isomeric pyridine carboxyaldehydes, acetyl pyridines, and imidazolium-based
ILs were purchased from Sigma-Aldrich (USA). Quaternary ammonium salts were
synthesized from n-propyl amine and di-ethylenetriamine, obtained from Spectro-
chem Fine Chemicals, Ltd. (India). Other common solvents and reagents were
obtained from S.D. Fine Chemicals, Ltd. (India). All chemicals were used as received
without further purification.
General
1H and 13C NMR spectra were recorded on a Bruker AX500 spectrometer
using CDCl3 as solvent and tetramethylsilane as an internal reference. Gas chroma-
tography–mass spectrometry (GC-MS) analyses were performed on a Shimadzu
QP-2010 spectrometer. Elemental analyses were done on a Perkin-Elmer 2400
CHNS=O analyzer.
Synthesis of Quaternary Ammonium Salts
Quaternary ammonium salts were synthesized by the procedure reported
elsewhere.[21] Sulfuric acid (0.1 mol) was added to 0.1 mol corresponding amine taken
in 50 ml chloroform in a 100-ml round-bottom flask under vigorous stirring. The
temperature was kept at 0 ꢀC. After the reaction, chloroform was removed using a
rotary evaporator. The crystalline solids obtained were further dried by evaporation
under high vacuum at 60 ꢀC.
Synthesis of 40-(Pyridyl)-terpyridines
In a typical reaction, 2-acetylpyridine (2.42 g, 20 mmol), was added to a suspen-
sion of 1-butyl-3-methylimidazolium tetrafluoroborate (10 cm3) crushed with sodium
hydroxide (0.8 g, 20 mmol) in a 100-ml round-bottom flask, and the mixture was
stirred for 10 min under ice. 2-Pyridine carboxyaldehyde (1.07 g, 10 mmol) was then

1144
S. V. JADHAV, P. G. INGOLE, AND H. C. BAJAJ
added, and the suspension was kept at 0 ꢀC for 2 h, with frequent manual stirring.
During this time, the reaction mixture turned wine red. After 2 h, ammonium acetate
(10 g, excess) was added, and the mixture was refluxed at 110 ꢀC for 2 h to yield a
dark-brown semi-crystalline precipitate. Cold water was then added to facilitate
the precipitation of product. Precipitate of 1 was isolated by filtration using a suction
filter pump, washed with 20 ml ꢁ 2 methanol–water mixture (1:5), and recrystallized
1
in chloroform (method 1). The product formed was characterized by H and 13C
NMR spectroscopy. Light yellow solid; yield 1.62 g (52%).
In the case of quaternary ammonium salts, a single-step process was adapted
(method 2) in which all the reagents were added simultaneously along with quatern-
ary ammonium salts (4 g) instead of 1-butyl-3-methylimidazolium tetrafluoroborate.
Although quaternary ammonium salts are solid at ambient temperature, upon mix-
ing with ammonium acetate, a sticky eutectic mixture is formed, which promotes the
reaction much faster. All other reagents were added in the same stoichiometric quan-
tity as in method 1, and the resulting mixture was directly refluxed at 140 ꢀC for 4 h;
further workup was the same as in method 1.
RESULTS AND DISCUSSION
Incorporation of pyridyl functionalities into the 40-position of the 2,
20:60,200-terpyridine in two steps as well as a single reaction step is demonstrated.
Treatment of 2-acetylpyridine and 2-pyridine carboxyaldehyde (2:l ratio) with
ammonium acetate in imidazolium-based IL as reaction medium afforded the target
product 1 in good yield in a two-step reaction (Scheme 1), whereas the eutectic
mixture of quaternary ammonium salts with ammonium acetate yields the title com-
pounds in a single step. The reaction is believed to proceed through a 1,5-diketone
[21]
intermediate
that can be readily converted into product 1. Both the methods to
synthesize TPY in the molten salts are simple and easy to use. These solvent systems
are becoming benign and are alternative reaction media in synthetic chemistry.
Scheme 1. Synthesis of TPY using molten salts as solvent media.

SYNTHESIS OF TPY IN IONIC LIQUID
1145
Table 1. Yields and elemental analysis of synthesized 40-(pyridyl)-terpyridines
Elemental analysis
experimentally found (%)b
Yield (%)a
Salt 1
Compound
Ring I
Rings II, III
IL 1
Salt 2
C
H
N
1
2
3
4
5
6
2-Pyridyl
3-Pyridyl
4-Pyridyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
2-Pyridyl
2-Pyridyl
2-Pyridyl
3-Pyridyl
3-Pyridyl
3-Pyridyl
52
42
46
41
46
45
48
35
38
40
40
38
49
35
36
40
44
42
77.1
77.7
77.6
77.5
77.3
77.6
4.4
4.6
4.7
4.3
4.6
4.1
17.9
18.3
18.3
18.1
18.3
17.9
aIL 1, 1-butyl 3-methyl imidazolium tetrafluoroborate; salt 1, di-ethylenetriamine sulfate; salt 2,
n-propylamine sulfate.
bTheoretically calculated elemental analysis results are C ¼ 77.4%, H ¼ 4.55%, and N ¼ 18.05%.
Eutectic molten salts have many fascinating properties, including no measur-
able vapor pressure (hence cannot emit VOCs), nonflammability, high polarity,
and solubility for a wide range of materials including inorganic, organic, and
even polymeric materials. Molten salts (ILs) can be broadly categorized as
imidazolium-based and quaternary ammonium salts.
To optimize the reaction temperature in method 2, the reaction of 2-
acetylpyridine, 2-pyridine-carboxyaldehyde, and ammonium acetate with NaOH
was carried out at temperatures ranging from 100 to 140 ꢀC in increments of
10 ꢀC. The better yields were obtained at 140 ꢀC and remain unaffected when tem-
perature was further increased to 160 ꢀC. Under these optimized reaction conditions
(140 ꢀC), we have synthesized a series of six isomeric 40-(pyridyl)-terpyridines 1–6 in
acceptable purity and yields using method 1 with imidazolium-based IL and method
2 with quaternary ammonium salts (Table 1). Being hydrophilic, salts can be
removed easily from the product by extensive washing with water. The product 1
in purified form can easily be collected by filtration instead of tedious column
chromatography, which reduces the VOCs.
Although cleaner reaction conditions leading to good yields and purity are
observed in imidazolium-based solvents via method 1, the high cost remains a main
hurdle to employing these ecofriendly solvents on a pilot scale. There is a need for
alternative reaction media that can satisfy expectations regarding yield and purity
of the compounds. In present work, we have synthesized and used two quaternary
ammonium salts (n-propylamine sulfate and di-ethylenetriamine sulfate) as nontoxic
and nonvolatile reaction media, which are emerging as ideal candidates in a variety
of synthetic organic transformation because of their ease of preparation and in parti-
cular low cost. They gave comparable yield of the products with already existing
methods[21] (i.e., in PEG, about 44–55%).
1
The compounds are characterized by H and 13C NMR spectroscopy.
Spectral Data
Compound 1. Yellow powder, dH (500 MHz, CDCl3) 9.09 (s, 2H, Ar), 8.80
(m, 1H, Ar), 8.74 (m, 2H, Ar), 8.66 (d, 2H, Ar), 8.10 (d, 1H, Ar), 7.87 (dt, 2H,

1146
S. V. JADHAV, P. G. INGOLE, AND H. C. BAJAJ
Ar), 7.85 (dt, 1H, Ar), 7.35 (m, 3H, Ar). dC (125 MHz, CDCl3) 156.21, 156.14,
155.05, 150.02, 149.19, 148.61, 136.90, 136.87, 123.86, 123.75, 121.33, 121.29,
118.61. GC-MS (EI): m=z (%) 310 (100) [M]þ.
Compound 2. Light brown solid, dH (500 MHz, CDCl3) 9.13 (dd, 1H, Ar),
8.73 (s, 2H, Ar), 8.70 (m, 2H, Ar), 8.66 (dd, 1H, Ar), 8.57 (m, 2H, Ar), 8.20 (m,
1H, Ar), 7.89 (dt, 2H, Ar), 7.48 (m, 1H, Ar), 7.37 (m, 2H, Ar). dC(125 MHz, CDCl3)
156.23, 155.85, 150.10, 149.19, 148.43, 147.22, 136.96, 134.69, 134.27, 124.06, 123.67,
121.39, 118.80. GC-MS (EI): m=z (%) 310 (100) [M]þ.
Compound 3. Mauve solid, dH (500 MHz, CDCl3) 8.89 (s, 2H, Ar), 8.84 (m,
2H, Ar), 8.75 (dd, 2H, Ar), 8.65 (d, 2H, Ar), 7.97 (dt, 2H, Ar), 7.53 (m, 2H, Ar), 7.41
(dd, 2H, Ar). dC (125 MHz, CDCl3) 156.41, 155.73, 150.57, 149.24, 149.22, 145.58,
137.01, 124.15, 121.72, 121.39, 118.67. GC-MS (EI): m=z (%) 310 (100) [M]þ.
Compound 4. White solid, dH (500 MHz, CDCl3) 9.56 (m, 2H, Ar), 8.82 (m,
1H, Ar), 8.72 (dd, 2H, Ar), 8.70 (dt, 2H, Ar), 8.57 (s, 2H, Ar), 7.97 (d, 1H, Ar), 7.90
(dt, 1H, Ar), 7.50 (dd, 2H, Ar), 7.44 (m, 1H, Ar). dC (125 MHz, CDCl3) 155.57,
154.42, 150.26, 150.19, 148.56, 148.49, 137.31, 134.59, 134.57, 124.23, 123.63,
121.10, 117.08. GC-MS (EI): m=z (%) 310 (100) [M]þ.
Compound 5. White powder, dH (500 MHz, CDCl3) 9.39 (m, 2H, Ar), 9.02
(m, 1H, Ar), 8.74 (dd, 1H, Ar), 8.72 (dd, 2H, Ar), 8.54 (dt, 2H, Ar), 8.08 (dt, 1H,
Ar), 7.96 (s, 2H, Ar), 7.52 (dd, 1H, Ar), 7.49 (dd, 2H, Ar). dC (125 MHz, CDCl3)
155.78, 150.54, 150.45, 148.40, 148.22, 147.46, 134.66, 134.61, 134.39, 134.33,
124.04, 123.73, 117.61. GC-MS (EI): m=z (%) 310 (100) [M]þ.
Compound 6. Light brown solid, dH (500 MHz, CDCl3) 9.48 (m, 2H, Ar),
8.87 (m, 2H, Ar), 8.73 (dd, 2H, Ar), 8.54 (dt, 2H, Ar), 7.97 (s, 2H, Ar), 7.67 (m,
2H, Ar), 7.52 (dd, 2H, Ar). dC (125 MHz, CDCl3) 155.92, 150.88, 150.57, 148.45,
148.42, 145.65, 134.57, 134.21, 123.73, 121.60, 117.42. GC-MS (EI): m=z (%) 310
(100) [M]þ.
CONCLUSION
A novel, convenient route for the introduction of pyridyl ring in the 40-position
of the terpyridine using nontoxic solvent systems has been established. Besides
([BMIM] [BF4]), some eutectic mixtures of quaternary ammonium molten salts were
employed, which were relatively cheap and easy to prepare. Yield of the products
comparable with already existing methods (i.e., in PEG about 44–55%: see
Ref. 21), accessible starting materials, and relative ease of workup are sufficient
advantages to open a new avenue in the synthesis of terpyridines using less
hazardous conditions.
ACKNOWLEDGMENTS
We gratefully acknowledge the Council of Scientific and Industrial Research,
New Delhi, India, for funding under the network project NWP-0010. We also thank
the Analytical Sciences Discipline of the institute for analysis facilities.

SYNTHESIS OF TPY IN IONIC LIQUID
1147
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