Octafluoro-4,4′-bipyridine and its derivatives: Synthesis, molecular and crystal structure

Article abstract of DOI:10.1016/j.jfluchem.2009.11.022

The structure and chemical properties of perfluoro-4,4′-bipyridine have been studied. It was found that octafluoro-4,4′-bipyridine is a quite electron deficient system stable to the action of alkylating agents and sensitive to nucleophilic substitution of fluorine atoms. Depending on the reaction conditions and reagents used products could be obtained in which two and six fluorine atoms are substituted by nucleophiles. For all isolated compounds X-ray structure determination has been performed and the main peculiarities of the molecular and crystal structure of fluorine-containing bipyridines have been determined.

Full text of DOI:10.1016/j.jfluchem.2009.11.022

Journal of Fluorine Chemistry 131 (2010) 278–281
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Octafluoro-4,40-bipyridine and its derivatives: Synthesis, molecular and
crystal structure
*
Alexey V. Gutov , Eduard B. Rusanov, Alexey B. Ryabitskii, Alexander N. Chernega
Institute of Organic Chemistry NAS Ukraine, Murmanska st. 5, 02660 Kyiv -94, Ukraine
A R T I C L E I N F O
A B S T R A C T
The structure and chemical properties of perfluoro-4,40-bipyridine have been studied. It was found that
octafluoro-4,40-bipyridine is a quite electron deficient system stable to the action of alkylating agents
and sensitive to nucleophilic substitution of fluorine atoms. Depending on the reaction conditions and
reagents used products could be obtained in which two and six fluorine atoms are substituted by
nucleophiles. For all isolated compounds X-ray structure determination has been performed and the
main peculiarities of the molecular and crystal structure of fluorine-containing bipyridines have been
determined.
Article history:
Received 9 September 2009
Received in revised form 23 November 2009
Accepted 26 November 2009
Available online 5 December 2009
Keywords:
Perfluoro-4,40-bipyridine
Fluorine-containing bipyridines
X-ray structure determination
ß 2009 Elsevier B.V. All rights reserved.
1. Introduction
a pretty low yield of the product [11]. The most convenient method
of perfluorobipyridine synthesis is the reaction of perfluoropyr-
Bipyridine derivatives as convenient bidentate ligands [1–5] are
quite useful tectons in crystal engineering of new functional
materials. Moreover, among the bipyridine derivatives there are
many compounds of practical interest. For example, the viologens
(4,40-bipyridine tertiary salts) are unique photochromic materials
[3]. Nevertheless, there are no known fluorine-containing viologens,
whereas it is well-known that the properties of the fluorine-
substituted compounds usually are noticeably different from their
nonfluorinated analogues. It is common in pharmacology to
substitute hydrogen with fluorine in drugs with the aim to reinforce
and prolong their action. Moreover some compounds containing
polyfluoropyridine moiety possess high biological activity [6].
Chemistry of pentafluoropyridine, 4-bromo-2,3,5,6-tetrafluor-
opyridine and other analogues is well-established [7,8]. However,
the structure and the chemical properties of octafluorobipyridine
have not been studied yet, although the products of its reactions
are perspective for the design of small molecule scavengers [9],
novel electron acceptors [10], etc. Therefore, we have investigated
the structural peculiarities and chemical properties of octafluor-
obipyridine.
idine with hexaethyl triamidophosphite [12] (Scheme 1). To obtain
1 we have used this reaction with some important improvements
in the product isolation.
The DFT-calculations in B3LYP 6-31+G** basis set have
shown that the electronic density (NBO charge) on the nitrogen in
1 (ꢀ0.47 a.u.) is quitesimilar tothat forthe unsubstitutedbipyridine
(ꢀ0.45 a.u.). Therefore, one would expect that 1 would react with
common alkylating agents to form the fluorinated viologens.
Nevertheless, we have found that 1 remained unreacted under the
usual alkylation conditions (including heating) with dimethylsul-
phate, alkylhalogenides, triethyloxonium tetrafluoroborate and
even with ethyl-p-toluenesulphonate and methyl triflate at 100–
200 8C. Moreover 1 did not give an N-oxide with H2O2 in acetic
or trifluoroacetic acid and did not form salts with mineral acids
(HCl, H2SO4). Also we were unable to obtain complexes of 1 with
AgNO3, AgBr, NiCl2ꢁ6H2O, Ni(NO3)2ꢁ6H2O, CoCl2ꢁ6H2O, CoS2O6,
Cu(ClO4)2ꢁ6H2O, CuCl, CuCl2, Zn(NO3)2 and Zn(ClO4)2ꢁ6H2O using
different solvents and pH-values. Apparently the F-atoms have
substantial effect on the electronic structure of 1 that makes
N-atoms of 1 inert, though the results of DFT-calculations do not
show that.
At the same time it was shown that 1 is a very electron
deficient system sensitive to the nucleophilic attack (similar to
pentafluoropyridine [13]) and it reacts with excess of diethy-
lamine in boiling EtOH during 10 h and gives 2 as a main
product. The similar substitution of the two fluorine atoms in the
pyridine moiety was recently reported for the related
4-(perfluoroisopropyl)-2,3,5,6-tetrafluoropyridine in the reac-
tion with diethylamine [14].
2. Results and discussion
There are several methods of perfluorobipyridine (1) synthesis
but they all need expensive reagents and equipment, in addition to
* Corresponding author. Tel.: +380 044 499 46 46; fax: +380 044 573 26 43.
E-mail address: AVGutov@mail.ru (A.V. Gutov).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.11.022

A.V. Gutov et al. / Journal of Fluorine Chemistry 131 (2010) 278–281
279
Scheme 1. Synthesis of 1 and its reactions with the nucleophiles. (a) P(NEt2)3, Et2O;
(b) Et2NH, EtOH; and (c) PhSH, Na2CO3, EtOH.
Compound 1 reacts with thiophenol in boiling EtOH in the
presence of sodium carbonate for 8 h resulting in substitution of
six fluorine atoms and formation of 3.
Fig. 1. Two independent molecules in the crystal structure of 1.
X-ray investigation of 1 revealed that in the solid state there are
two crystallographically independent molecules A and B (Fig. 1)
with virtually identical bond lengths and angles (Table 1). The
inter-ring dihedral angles in the two independent molecules of 1
are noticeably different (53.08 in 1A and 64.78 in 1B) and are in a
good agreement with the results of ab initio quantum chemical
calculations of this molecule in the free state (Table 1) demon-
strating the flexibility of the fluorinated bipyridine core. In this
distribution was previously observed in the halogenated 2-
aminopyridines [20,21].
Two different-shape crystals of 3 were isolated and investigated
by X-ray diffraction and it was found that in this compound
molecules can adopt at least two conformations in the solid state –
opened (A) and closed (B) (Fig. 3). In conformation A, the
b-SPh
substituents (i.e. at C(4), C(7) or C(9)) are situated on a significantly
larger distance than in the conformation B (centroid–centroid
distances between the corresponding phenyl substituents for 3A
connection it is worth to note that in the crystal of 1 there is no p-
stacking interaction between the neighboring pyridine moieties.
˚
In both molecules 1A and 1B the intra-ring C–C and especially
and 3B are 8.54 and 6.58 A, respectively). Such a difference is due to
˚
C–N distances (Table 1) are somewhat (0.01–0.03 A) shorter than
the rotation of nearly 1808 of SPh group around the C(4)–S(2) bond
and some rotation of phenyl groups along S–Ph bond. Angles
between phenyl at S(2) and S(5) planes are 60.058 for 3A and 82.118
3B. However, it is interesting that the dihedral angles between
pyridine rings in both structures are similar (Table 1). The
in the nonfluorinated bipyridine [15]. Distribution of endocyclic
angles in 1 (CNC 116.0–117.1(3)8, avg. 116.68, NCC 123.9–
124.5(4)8, avg. 124.28 and the internal angle at the ring-connecting
carbon 115.6–116.7(3)8, avg. 116.38) is similar to the unsubstituted
bipyridine, alkyl substituted bipyridines and pyridines [16–19].
In the crystal structure of 2 (Fig. 2) the bipyridine core has a
conformation similar to 1 (Table 1). The molecule is on the
crystallographic twofold axis of rotation, thus only a half of the
molecule is independent. The amino N(3) atom has trigonal-planar
bond configuration (sum of bond angles is 3608) and a shortened
bond length C(1)–N(3) 1.358(3) A, that indicates the common for
the aminopyridines conjugation. In contrast the neighboring
distance C(1)–N(1) of 1.343(3) A is elongated in comparison with
the perfluorobipyridine and unsubstituted bipyridine, whereas the
intra-ring angle at C(1) is reduced to 117.0(2)8. That leads to the
opening up of the adjacent C(1)C(2)C(3) angle up to 122.8(2)8. All
the other angles are usual for bipyridines. The similar angles
conformations of
a-SPh substituents (i.e. at C(1), C(5), C(6) and
C(10)) are also close for 3A and 3B (the centroid–centroid distances
˚
˚
of phenyl groups are similar: 4.00, 4.09 A for 3A and 3.92, 3.96 A for
3B).
The endocyclic C–C bond in 3A is some longer than that in 3B
(Table 1). Angles distribution in the central bipyridine core of 3A
and 3B is slightly changed compared to the symmetrical 4,40-
bipyridines, the internal angle at the carbon bearing fluorine is
opened to 122.48 (averaged for both the structures). For example in
the nonsubstituted 4,40-bipyridine [15] corresponding angle is
119.28 and 119.38 in 1 averaged.
˚
˚
The C–F distances for all the studied compounds are similar,
however they slightly increased from 1 to 3 (Table 1) with the
Table 1
Geometrical parameters of the molecules 1–3 from X-ray diffraction and [B3LYP 6-31+G**] – calculations.
Molecule
Geometry parameters
˚
˚
˚
˚
Inter-ring dihedral angle(8)
Ring-connecting C–C bond (A)
C(2)-F, A or C(12)-F (A)
C–F (A) avg.
N–Cendo avg.
1A
53.0
64.7
59.1
80.4
81.9
61.0
1.487(5)
1.495(5)
1.492(4)
1.494(6)
1.475(7)
1.483
1.340(4)
1.344(4)
1.351(3)
1.362(5)
1.359(5)
1.341
1.33
1.34
1.35
1.36
1.36
1.34
1.30
1.31
1.33
1.33
1.34
1.31
1B
2
3A
3B
1(calculated)
Unsubstituted bipyridine in crystal [13]
Calculated
18.5
34.9
37.2
1.494(3)
1.494(3)
1.485
–
–
–
–
–
–
1.33
1.33
1.34

280
A.V. Gutov et al. / Journal of Fluorine Chemistry 131 (2010) 278–281
Fig. 2. The perspective view and numbering scheme of 2. Symmetry code: ꢀx, +y,
0.5 ꢀ z.
decreasing number of fluorine atoms and with the increasing
number of donor substituents in the molecule.
It is worth to note that the energy barrier of rotation along inter-
ring C–C bond is 66.73 kJ/mole for 1 and there is no
p-stacking in
its crystals, whereas in the unsubstituted 4,40-bipyridine barrier of
rotation along inter-ring C–C bond is only 8.61 kJ/mole, and in the
Fig. 3. A and B conformations of 3 in the crystal state.
solid state molecules tend to be planar and form
p-stacked
structure. For all the studied fluorinated bipyridines the central
bipyridine core is substantially twisted on 50–808 (Table 1) and it is
the scope of its lability in such systems.
and crystal structure peculiarities of the fluorine-containing 4,40-
bipyridines have been determined.
4. Experimental
3. Conclusion
4.1. General
It was found that octafluoro-4,40-bipyridine is a very electron
deficient system stable to the action of alkylating agents, mineral
acids and susceptible to nucleophilic substitution of fluorine
atoms. The isolated products are molecules in which nucleophiles
substituted two and six fluorine atoms in the bipyridine core,
depending on the reaction conditions and reagents. The molecular
Starting materials were obtained commercially. Solvents were
dried according to literature procedures. Mass spectra were
recorded on the Agilent 1100 LC/MS. NMR spectra were recorded
on the Bruker spectrometer, 282.2 MHz. Melting points were
recorded at the atmospheric pressure.
Table 2
Data collection, structure solution and refinement parameters.
Compound
1
2
3A
3B
Empirical formula
Formula weight
Crystal system
Space group
C10F8N2
300.11
triclinic
P-1
C18H20F6N4
406.38
C46H30F2N2S6
841.08
C46H30F2N2S6
841.08
monoclinic
C 2/c
monoclinic
P 21/n
monoclinic
P 21/n
˚
Unit cell dimensions (A and8)
a
b
c
10.082(6)
10.533(9)
11.777(5)
66.49(5)
25.269(2)
8.7702(11)
9.0067(10)
90.0
18.2214(14)
11.6368(9)
19.4795(17)
90.0
14.038(4)
17.659(4)
16.886(5)
90.0
a
b
g
83.75(4)
109.606(6)
90.0
97.440(2)
90.0
105.957(16)
90.0
65.67(6)
3
˚
Volume (A )
1042.7(14)
1880.3(4)
4095.6(6)
4024.9(18)
Z
4
4
4
4
dcalc (g/cm3)
1.91
0.217
584
1.44
0.129
840
1.36
1.39
m
(Mo-K ) (mmꢀ1
)
0.379
1736
2.0–25.1
0.386
1736
1.9–26.5
a
F(0 0 0)
Range for data collection (8)
u
1.9–25.0
1.7–28.4
Limiting indices
0 ꢂ h ꢂ 11
ꢀ11 ꢂ k ꢂ 12
ꢀ13 ꢂ l ꢂ 13
3893/3664
0.017
ꢀ33 ꢂ h ꢂ 30
ꢀ6 ꢂ kꢂ 11
ꢀ10 ꢂ l ꢂ 12
6186/2309
0.021
ꢀ20 ꢂ h ꢂ 21
ꢀ13 ꢂ k ꢂ 13
ꢀ23 ꢂ l ꢂ 14
22110/7110
0.062
ꢀ15 ꢂ h ꢂ 17
ꢀ21 ꢂ k ꢂ 20
ꢀ15 ꢂ l ꢂ 21
16673/8152
0.081
Reflections: collected/unique
R(int)
GOF
1.087
1.090
0.966
0.922
Final R indices:
R(F)
0.049
–
–
–
–
R1(F)
0.056
–
0.081
–
0.066
–
Rw(F)
wR2(F2)
0.054
–
0.179
0.151
0.113
3
˚
Largest diff. peak/hole (e/A )
0.23/ꢀ0.27
0.19/ꢀ0.16
0.45/ꢀ0.23
0.22/ꢀ0.27
CCDC number
740216
740217
740218
740219

A.V. Gutov et al. / Journal of Fluorine Chemistry 131 (2010) 278–281
281
The calculations of the equilibrium molecular geometry of 1 in
the ground state were performed by using the Gaussian 98
software [22]. The optimisation procedure has included consecu-
tively the calculation in the AM1 method (as an initial approxima-
tion), then Hartree–Fock (HF) with different basis sets (3–21G**,
6–31+G**) and finally the DFT Becke3LYP method with 6–31+G**
basis set. After finishing of the geometry optimisation procedure,
force constants and the resulting vibrational frequencies were
calculated. The charges at atoms were obtained using the Natural
Bond Orbital analysis (NBO).
carbonate. The progress of the reaction was monitored by LC–MS.
The mixture was diluted with water, filtered and the precipitate
was recrystallized from dimethylformamide. The yield of 3 as
yellow crystals was 0.06 g (43%) m.p. 63 8C. 19F NMR (282.2 MHz,
CCl3F):
d
ꢀ125.2 (s, 2F, F-3).
Acknowledgements
The authors are grateful to Yu.L. Yagupolskii, L.M. Yagupolskii
and Yu.G. Shermolovich for fruitful discussions.
4.2. Crystal structure determination
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4.3.1. Perfluoro-4,40-bipyridine (1)
1.478 g (0.00874 mol) of pentafluoropyridine was dissolved in
10 ml of anhydrous ether and cooled to ꢀ10 8C. 1.08 g
(0.00437 mol) of hexaethyltriamidophosphite in 5 ml of ether
was added during 1 h. The mixture was stirred at ꢀ10 8C for 10 h
and additional 10 h at the room temperature. Then diluted
hydrochloric acid was added to the mixture. The ether layer
was separated, washed with water and dried over sodium
sulphate. The solvent was removed in vacuum and the product
was distilled (70 8C at 0.4 Torr). Yield 1.1 g (84%) of white solid,
m.p. 83 8C. 19F NMR (282.2 MHz, CCl3F):
30, F-50), ꢀ138.1 (m, 4F, F-2, F-6, F-20, F-60).
d
ꢀ89.4 (m, 4F, F-3, F-5, F-
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Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H.
Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
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University of Go¨ttingem, 1997.
4.3.2. 2,20-Di-N,N0-diethylamino-3,30,5,50,6,60-hexafluoro-4,40-
bipyridine (2)
0.1 g of 1 was refluxed with 0.1 g (excess) of diethylamine for
10 h in 1 ml of EtOH. The progress of the reaction was monitored by
the LC–MS. Then the mixture was diluted with water, filtered and
air-dried. The recrystallization from cyclohexane afforded 0.068 g
(50%) of 2 as a white solid. m.p. 67 8C. 19F NMR (282.2 MHz, CCl3F):
d
ꢀ93.1 (m, 2F, F-5), ꢀ135.9 (d, 2F, J = 32.3 Hz, F-6), ꢀ158.1 (d, 2F,
J = 24.3 Hz, F-3).
4.3.3. 3,30-Difluoro-2,20,5,50,6,60-hexaphenylthio-4,40-bipyridine (3)
0.05 g of 1 was refluxed with stirring for 8 h in 1 ml of EtOH
with 0.15 g (excess) of thiophenol and 0.15 g (excess) of sodium
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