Efficient access to a versatile 5,6-dithio-1,10-phenanthroline building block and corresponding organometallic complexes

Article abstract of DOI:10.1021/ol802756w

(Chemical Equation Presented) A facile access to 5,6-bis(2- cyanoethylsulfanyl)-1,10-phenanthroline 1 and its ruthenium(II) bipyridil complex 2, as versatile building blocks for the straightforward synthesis of 5,6-dithio functionalized 1,10-phenanthroline based systems, is described.

Full text of DOI:10.1021/ol802756w

ORGANIC
LETTERS
2009
Vol. 11, No. 3
649-652
Efficient Access to a Versatile
5,6-Dithio-1,10-phenanthroline Building
Block and Corresponding
Organometallic Complexes
Bertrand Chesneau, Ange´lique Passelande, and Pie´trick Hudhomme*
UniVersite´ d‘Angers, CNRS, Laboratoire de Chimie et Inge´nierie Mole´culaire
d’Angers, CIMA UMR 6200, 2 BouleVard LaVoisier, 49045 Angers, France
pietrick.hudhomme@uniV-angers.fr
Received November 28, 2008
ABSTRACT
A facile access to 5,6-bis(2-cyanoethylsulfanyl)-1,10-phenanthroline 1 and its ruthenium(II) bipyridil complex 2, as versatile building blocks for
the straightforward synthesis of 5,6-dithio functionalized 1,10-phenanthroline based systems, is described.
Over the past few years, impressive development has been
carried out on transition metal complexes containing a
heterocyclic sp2 nitrogen donor based upon 2,2′-bipyridine
(bpy), [2,2′:6′,2′′]-terpyridine (tpy) or 1,10-phenanthroline
(phen) chelating ligands.1 Among them, 1,10-phenanthroline
ligand appears of particular interest for applications in
coordination chemistry.2 For instance, phenanthroline ligands
have been successfully used as cationic ionophores3 or for
homogeneous catalytic reaction.4 In addition, due to their
electronic, photophysical, redox, and luminescence proper-
ties, these ligands have known important development in the
field of supramolecular and macromolecular chemistry.5
Fascinating architectures based on copper(I)6 or ruthe-
nium(II)7 1,10-phenanthroline complexes were designed in
which photoinduced energy or electron transfer processes
could occur, in particular for applications in the field of
photonic devices.8 Such organometallic complexes have also
shown particular interest for their DNA-binding interactions,9
and the inhibition of gene transcription was demonstrated
with promising properties for the design of DNA markers
in photochemotherapy.10
(5) (a) Lehn, J.-M. Angew. Chem., Int. Ed. 1988, 27, 89–112. (b) Lehn,
J.-M. Angew. Chem., Int. Ed. 1990, 29, 1304–1319. (c) MacDonnell, F. M.;
Kim, M.-J.; Bodige, S. Coord. Chem. ReV. 1999, 185-186, 535–549.
(6) (a) Armaroli, N. Chem. Soc. ReV. 2001, 30, 113–124. (b) Armaroli,
N. Photochem. Photobiol. Sci. 2003, 2, 73–87.
(7) (a) Juris, A.; Balzani, V.; Barigelletti, F.; Campagna, S.; Belser, P.;
von Zelewsky, A. Coord. Chem. ReV. 1988, 84, 85–277. (b) Pourtois, G.;
Beljonne, D.; Moucheron, C.; Schumm, S.; Kirsch-De Mesmaeker, A.;
Lazzaroni, R.; Bre´das, J.-L. J. Am. Chem. Soc. 2004, 126, 683–692.
(8) (a) De Cola, L.; Belser, P. Coord. Chem. ReV. 1998, 177, 301–346.
(b) Bleser, P.; Bernhard, S.; Blum, C.; Beyeler, A.; De Cola, L.; Balzani,
V. Coord. Chem. ReV. 1999, 190-192, 155–169.
(1) Kaes, C.; Katz, A.; Hosseini, M. W. Chem. ReV. 2000, 100, 3553–
3590.
(2) (a) Sammes, P. G.; Yahioglu, G. Chem. Soc. ReV. 1994, 23, 327–
334. (b) Luman, C. R.; Castellano, F. N. In ComprehensiVe Coordination
Chemistry II; McCleverty, J. A., Meyer, T. J., Eds.; Elsevier: Oxford, U.K.,
2004; Vol. 1, pp 25-39.
(9) (a) Friedman, A. E.; Chambron, J.-C.; Sauvage, J.-P.; Turro, N. J.;
Barton, J. K. J. Am. Chem. Soc. 1990, 112, 4960–4962. (b) Turro, N. J.;
Barton, J. K.; Tomalia, D. A. Acc. Chem. Res. 1991, 24, 332–340. (c) Hiort,
C.; Lincoln, P.; Norde´n, B. J. Am. Chem. Soc. 1993, 115, 3448–3454. (d)
Mc Millin, D. R.; Mc Nett, K. M. Chem. ReV. 1998, 98, 1201–1219. (e)
Erkkila, K. E.; Odom, D. T.; Barton, J. K. Chem. ReV. 1999, 99, 2777–
2795.
(3) Sugihara, H.; Hiratani, K. Coord. Chem. ReV. 1996, 148, 285–299.
(4) (a) Chelucci, G.; Thummel, R. P. Chem. ReV. 2002, 102, 3129–
3170. (b) Durand, J.; Milani, B. Coord. Chem. ReV. 2006, 250, 542–560.
10.1021/ol802756w CCC: $40.75
Published on Web 01/08/2009
2009 American Chemical Society

In this context, straightforward synthetic access to 1,10-
phenanthroline building blocks appears of strong importance.
The functionalization of the 1,10-phenanthroline ligand
appears relatively limited.11 Substitution at the 2,9-positions
can be achieved using the nucleophilic addition of aryl-
lithium12 (or thienyl-lithium)13 compounds followed by an
oxidative rearomatization or using metal-catalyzed cross-
coupling reactions from the 2,9-dihalogenated derivative.14
Further extension of such organometallic reactions was
carried out using 3,8-dibromo-1,10-phenanthroline giving rise
to 3,8-disubstituted derivatives.15
Scheme 2. Applications of Compound 1 to the Synthesis of
Symmetrical, Unsymmetrical, and Heterocyclic 5,6-Dithio
Functionalized 1,10-Phenanthrolines
On the contrary, 5,6-disubstituted-1,10-phenanthroline
derivatives have been less explored despite their attractivity.
The most common functionalization corresponds to the
oxidation affording 1,10-phenanthroline-5,6-dione,16 which
plays an important role as a versatile building block with
well-known applications in biological chemistry and materi-
als science. Also, preparation of 5,6-dibromo-1,10-phenan-
throline was realized using bromine in fuming sulfuric acid
(containing 60%17 or 30%18 oleum). Functionalizations from
this starting material were carried out using the Suzuki cross-
coupling reaction.19 Very recently, a palladium cross-
coupling reaction was also described to reach 5,6-bis(ethy-
nylpyrene)-1,10-phenanthroline systems.20
In this context, the preparation of a 1,10-phenanthroline
building block allowing an easy functionalization on the 5,6-
positions by reaction with electrophilic species appears
complementary to these methods. To our knowledge, only
the synthesis of 5,6-dibenzylsulfanyl-1,10-phenanthroline was
very recently described.21 This work describes the synthesis
of 5,6-bis(2-cyanoethylsulfanyl)-1,10-phenanthroline 1 as an
attractive building block for further development of 5,6-
dithio-1,10-phenanthroline derivatives (Scheme 1). The
tetrathiafulvalene series22 and then applied into the thiophene
chemistry.23 This work is extended to the synthesis of
ruthenium(II) bipyridil complex 2 as an interesting model
for developing new metal-coordinated 5,6-dithio-1,10-
phenanthroline based architectures (Scheme 3).
5,6-Dibromo-1,10-phenanthroline 3 was synthesized in
62% yield by treating 1,10-phenanthroline monohydrate with
bromine in fuming sulfuric acid containing 20% oleum as a
modified procedure of previous reported methods.18 Pre-
liminary attempts to synthesize building block 1 in a one-
pot reaction from compound 3 after halogen-lithium ex-
change using butyllithium followed by addition of sulfur and
then thioalkylation with 3-bromopropionitrile were unsuc-
cessful. As an alternative, we investigated a palladium-
catalyzed cross-coupling reaction. Compound 3 was treated
in the presence of Pd(PPh3)4 with 3-(tributylstannylsulfa-
nyl)propanenitrile, which was prepared according to the
reported procedure.24 Finally, key compound 1 was isolated
in 63% yield (Scheme 1).
Scheme 1. Synthesis of Building Block
5,6-Bis(2-cyanoethylsulfanyl)-1,10-phenanthroline 1
(14) (a) Lam, F.; Chan, K. S.; Liu, B.-J. Tetrahedron Lett. 1995, 36,
6261–6262. (b) Lam, F.; Feng, M.; Chan, K. S. Tetrahedron 1999, 55, 8377–
8384.
(15) (a) Sauvage, J.-P.; Kern, J.-M.; Bidan, G.; Divisia-Blohorn, B.;
Vidal, P.-L. New J. Chem. 2002, 26, 1287–1290. (b) Gavin˜a, P.; Tatay, S.
Tetrahedron Lett. 2006, 47, 3471–3473.
(16) Dickeson, J. E.; Summers, L. A. Aust. J. Chem. 1970, 23, 1023–
1027.
particular interest in this 2-cyanoethylsulfanyl group relies
on a very efficient and selective deprotection-alkylation
reaction of the highly nucleophilic thiolate groups (Scheme
2). This protecting group has been first introduced in the
(17) Mlochowski, J. J. Rocz. Chem. 1974, 48, 2145–2155.
(18) Feng, M.; Chan, K. S. Organometallics 2002, 21, 2743–2750.
(19) (a) Yam, V. W.-W.; Ko, C.-C.; Zhu, N. J. Am. Chem. Soc. 2004,
126, 12734–12735. (b) Ko, C.-C.; Kwok, W.-M.; Yam, V. W.-W.; Philips,
D. L. Chem. Eur. J. 2006, 12, 5840–5848. (c) Kuhni, J.; Adamo, V.; Belser,
P. Synthesis 2006, 12, 1946–1948.
(20) Goze, C.; Sabatini, C.; Barbieri, A.; Barigelletti, F.; Ziessel, R. Eur.
J. Inorg. Chem. 2008, 8, 1293–1299.
(10) Pauly, M.; Kayser, I.; Schmitz, M.; Dicato, M.; Del Guerzo, A.;
Kolber, I.; Moucheron, C.; Kirsch-De Mesmaeker, A. Chem. Commun. 2002,
1086–1087.
(21) Rabac¸a, S.; Duarte, M. C.; Santos, I. C.; Pereira, L. C. J.; Fourmigue´,
M.; Henriques, R. T.; Almeida, M. Polyhedron 2008, 27, 1999–2006.
(22) (a) Svenstrup, N.; Rasmussen, K. M.; Hansen, T. K.; Becher, J.
Synthesis 1994, 809–812. (b) Jeppesen, J. O.; Takimiya, K.; Thorup, N.;
Becher, J. Synthesis 1999, 5, 803–810. (c) Simonsen, K. B.; Becher, J.
Synlett 1997, 1211–1220.
(11) (a) Summers, L. A. AdV. Heterocycl. Chem. 1978, 22, 1–69. (b)
Summers, L. A. AdV. Heterocycl. Chem. 1984, 35, 281–374.
(12) Dietrich-Buchecker, C. O.; Marnot, P. A.; Sauvage, J.-P. Tetrahe-
dron Lett. 1982, 23, 5291–5294.
(13) (a) Vidal, P.-L.; Billon, M.; Divisia-Blohorn, B.; Bidan, G.; Kern,
J.-M.; Sauvage, J.-P. Chem. Commun. 1998, 629–630. (b) Ammann, M.;
Ba¨uerle, P. Org. Biomol. Chem. 2005, 3, 4143–4152.
(23) (a) Blanchard, P.; Jousselme, B.; Fre`re, P.; Roncali, J. J. Org. Chem.
2002, 67, 3961–3964. (b) Balog, M.; Rayah, H.; Le Derf, F.; Salle´, M.
New J. Chem. 2008, 32, 1183–1188.
650
Org. Lett., Vol. 11, No. 3, 2009

69% yields, respectively. These two compounds constitute
potential precursors for further applications in tetrathiaful-
valene (TTF) chemistry.27
Scheme 3. Synthesis and Applications of
5,6-Bis(2-cyanoethylsulfanyl)-1,10-phenanthroline Ruthenium(II)
As extensive research is focused on applications of
ruthenium(II) complexes from the 1,10-phenanthroline ligand,
we were interested in the development of the new organo-
metallic building block 2 (Scheme 3). For this purpose,
compound 1 was treated in refluxing ethanol with cis-
dichloro-bis(2,2′-bipyridine)ruthenium, which was prepared
according to reported procedure.28 Corresponding ruthe-
nium(II) bipyridil complex 2 was isolated in 67% yield after
anionic metathesis treatment using an aqueous solution of
ammonium hexafluorophosphate. The selective monodepro-
tection-alkylation strategy was efficiently carried out to
reach unsymmetrical complex 9 in 73% yield. Access to the
dithiolate using the procedure described above and subse-
quent quenching with thiophosgene afforded the new com-
plex 10 in 83% yield.
Bipyridil Complex 2
The 1H NMR spectrum of compound 1 shows that the H2
proton of the 1,10-phenanthroline moiety resonates at lowest
field (δ ) 9.26 ppm) with the expected 3J coupling constant
4
(3JH -H ) 4.5 Hz and JH -H ) 1.5 Hz). The closed H4
2
3
2
4
3
proton (δ ) 9.21 ppm) presents the highest J coupling
constant (3JH -H ) 8.5 Hz and JH -H ) 1.5 Hz), whereas
4
3
4
2
4
The 2-cyanoethylsulfanyl protecting group is well-known
for its deprotection using cesium hydroxide as reagent.25
Considering 1,10-phenanthroline derivative 1, potassium tert-
butoxide in DMF/MeOH (1:1 v/v) proved to be the most
efficient reagent to generate selectively the corresponding
mono- or dithiolate (Scheme 2).
the H3 proton is shielded (δ ) 7.78 ppm).
1
The H NMR spectrum of complex 2 was assigned with
the aid of 1H-13C HMQC experiments in the aromatic region
(Figure 1). Concerning the three phenanthroline protons, the
After generation of the dithiolate by treatment with a slight
excess of base, subsequent alkylation using 1-iodopentane
afforded 5,6-bis(2-pentylsulfanyl)-1,10-phenanthroline 4 in
57% yield, demonstrating the efficiency of the deprotection-
alkylation process.
The selective access to one thiolate group gives ready
access to unsymmetrical derivatives. For instance, derivative
6 could be attained in two steps. First the mild and selective
deprotection of one 2-cyanoethylsulfanyl group was cleanly
achieved by treatment with 1 equiv of base. Subsequent
quenching of the thiolate anion with 1-iodopentane afforded
compound 5 in 82% yield. The second deprotection-alkylation
sequence was carried out as above leading to unsymmetrical
1,10-phenanthroline 6 in 74% yield.
The presence of an intermediate vicinal dithiolate could
be exploited to synthesize the 2-oxo or 2-thioxo-1,3-dithiole
heterocycle fused to the 1,10-phenanthroline system.26 The
dithiolate intermediate was trapped by addition of phosgene
or thiophosgene to give the 2-oxo-1,3-dithiole 7 or 2-thioxo-
1,3-dithiole 8 as particularly insoluble materials in 66% and
1
Figure 1
.
Aromatic part of the H NMR spectrum of 5,6-bis(2-
cyanoethylsulfanyl)-1,10-phenanthroline ruthenium(II) bipyridil
complex 2.
(24) Demeter, D.; Blanchard, P.; Grosu, I.; Roncali, J. Electrochem.
Commun. 2007, 9, 1587–1591.
chemical shift of the H2 proton is significantly highfield-
shifted by 1.14 ppm (δ ) 8.12 ppm) compared to ligand 1,
while H3 and H4 protons are not affected by the formation
of the octahedral [Ru(bpy)2Phen]2+ complex. This shielding
of H2 by comparison with H4 is in accordance with previous
NMR assignments reported for [Ru(bpy)2Phen]2+ com-
plexes.29 This is also in agreement with the 13C spectrum
(25) (a) Becher, J.; Lau, J.; Leriche, P.; Mørk, P.; Svenstrup, N. J. Chem.
Soc., Chem. Commun. 1994, 2715–2716. (b) Simonsen, K. B.; Svenstrup,
N.; Lau, J.; Simonsen, O.; Mørk, P.; Kristensen, G. J.; Becher, J. Synthesis
1996, 407–418.
(26) (a) Gotthardt, H. In ComprehensiVe Heterocyclic Chemistry I;
Katritzky, A. R., Rees, C. W., Eds.; Elsevier: Oxford, 1984; Vol. 6, pp
813-850. (b) Csuk, R.; Gla¨nzer, B. I. In ComprehensiVe Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier:
Oxford, 1995; Vol. 3, pp 607-658.
Org. Lett., Vol. 11, No. 3, 2009
651

and the expected chemical shift of C2 at 152 ppm, which is
deshielded compared to C4 at 138 ppm. The H NMR
waves at E0red1 ) -1.61 V and E0red2 ) -1.88 V (vs Fc+/Fc
1
in CH2Cl2/CH3CN 9:1) and one reversible one-electron
spectrum shows that the two bipyridil ligands are magneti-
cally equivalent. This leaves eight signals identifiable with
four protons for each bipyridil ligand defined as Ha, Hb, Hc
and Hd for one pyridine unit (Ha′, Hb′, Hc′, and Hd′ for the
second pyridine moiety). The protons of bipyridil ligands
show characteristic chemical shifts with Hd and Hd′ > Hc
and Hc′ > Ha and Ha′ > Hb and Hb′.
Whereas 1,10-phenanthroline presents a maximum absorp-
tion at 265 nm in CH3CN, the UV-vis spectrum of 1 shows
a maximum absorption band at 269 nm, and this band is
bathochromatically shifted to 286 nm in corresponding
ruthenium(II) complex 2. Moreover, the UV-vis spectrum
of complex 2 exhibits the characteristic metal to ligand
charge transfer (MLCT) band between 400 and 500 nm
(Figure 2).
oxidation wave at E0 ) +0.95 V that could be assigned
ox1
to the RuII/RuIII couple (Supporting Information). These
redox potentials could be compared with those of
[Ru(phen)(bpy)2](PF6)2 (E0red1 ) -1.74 V and E0red2 ) -1.98
V, E0
) +0.97 V vs Fc+/Fc), which was prepared
ox1
according to literature.30 Such shift of reduction potentials
can be assigned to the electron-withdrawing effect induced
by both 2-cyanoethylsulfanyl groups.
In conclusion, we propose an efficient synthesis of a new
synthetic building block in the 1,10-phenanthroline series
and its corresponding ruthenium(II) complex. The interest
in such systems is supported by the use of the 2-cyanoeth-
ylsulfanyl protecting group and the high efficiency of the
selective sequence of deprotection-alkylation reactions of
thiolate groups. This attractive thiofunctionalization in both
the 5 and 6 positions offers a broad range of possibilities
for an approach to new symmetrical and unsymmetrical 1,10-
phenanthroline-based systems and related organometallic
complexes. Moreover, the ready access to the dithiolate
intermediates from building blocks 1 and 2 gives rise to two
distinct coordinating sites. This opens a wide range of
possibilities for an easy access to multinuclear complexes
exhibiting promising electrochemical and physical properties.
Acknowledgment. This work was supported by the French
National Research Agency in the frame of the program ANR
PNANO entitled TTF-based Nanomat.
Supporting Information Available: Experimental details
and characterization data for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL802756W
(27) Trialkylphosphite-mediated coupling reaction from compounds 7
and 8 to build the TTF core has not been successful up to now. (a) Narita,
M., Jr. Synthesis 1976, 489–514. (b) Krief, A. Tetrahedron 1986, 42, 1209–
1252. (c) Fabre, J.-M. Chem. ReV. 2004, 104, 5133–5150. (d) Gorgues, A.;
Hudhomme, P.; Salle´, M. Chem. ReV. 2004, 104, 5151–5184.
(28) Sullivan, B. P.; Salmon, D. J.; Meyer, T. J. Inorg. Chem. 1978,
17, 3334–3341.
Figure 2. Absorption spectra of 1,10-phenanthroline (solid line),
1 (dotted line), and 2 (dashed line) in CH3CN (c ) 5 × 10-5 M).
Electrochemical properties of the electroactive ruthe-
nium(II) complex 2 were investigated by cyclic voltammetry.
Compound 2 exhibits two reversible one-electron reduction
(29) Ye, B.-H.; Ji, L.-N.; Xue, F.; Mak, T. C. W. Transition Met. Chem.
1999, 24, 8–12.
(30) Huang, W.; Ogawa, T. Polyhedron 2006, 25, 1379–1385.
652
Org. Lett., Vol. 11, No. 3, 2009