A new synthetic route for the preparation of 1,10-phenanthroline derivatives

Article abstract of DOI:10.1002/ejoc.200600772

The intermediate resulting from the addition of an organolithium reagent to 1,10-phenanthroline has been quenched with benzyl bromide. The resulting protected dihydrophenanthroline intermediate is thus stabilized and can be used for further chemical trans

Full text of DOI:10.1002/ejoc.200600772

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600772
A New Synthetic Route for the Preparation of 1,10-Phenanthroline Derivatives
Omar Moudam,[a] Fettah Ajamaa,[a] Allan Ekouaga,[b] Hind Mamlouk,[b] Uwe Hahn,[a]
Michel Holler,[b] Richard Welter,[c] and Jean-François Nierengarten*[a]
Dedicated to Professor Nazario Martín on the occasion of his 50th birthday
Keywords: 1,10-Phenanthroline / Organolithium reagents / Cleavage reactions / Heterocycles
The intermediate resulting from the addition of an organo-
lithium reagent to 1,10-phenanthroline has been quenched
with benzyl bromide. The resulting protected dihydrophen-
anthroline intermediate is thus stabilized and can be used
for further chemical transformations. This strategy allows to
modify the reactivity of the phenanthroline backbone and of-
fers a unique opportunity to perform chemical modifications
that would not be possible when starting from 1,10-phenan-
throline.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Phenanthroline derivatives are important building blocks the addition product can be quenched with benzyl bromide.
for the preparation of coordination compounds[1] and The resulting protected dihydrophenanthroline intermedi-
metallosupramolecular ensembles.[2] The synthesis of func- ate is thus stabilized and can be used for further chemical
tionalized 1,10-phenanthroline derivatives can be achieved transformations. This strategy allows for the modification
by constructing the polycyclic aromatic scaffold under of the reactivity of the phenanthroline backbone and offers
Skraup conditions. This route, however, is tedious and the a unique opportunity to perform chemical modifications
overall yields are not always very good. Direct chemical that would not be possible when starting from the corre-
modification of 1,10-phenanthroline is also possible, but sponding aromatic derivative. Finally, the benzyl group can
only a few reactions allow for the regioselective intro- be removed to generate a modified phenanthroline product.
duction of substituents on the 1,10-phenanthroline back-
The reaction conditions were first adjusted with the
bone.[3,4] Among them, the addition of organolithium monoaddition product resulting from the reaction of 1,10-
derivatives followed by hydrolysis and MnO2 oxidation has phenanthroline (1 equiv.) with n-butyllithium (1.1 equiv.) in
proven to be a useful tool.[4] This reaction developed in the Et2O at 0 °C (Scheme 1). Under optimized conditions, a
Sauvage group is efficient for the preparation of 2-substi- slight excess of benzyl bromide (1.3 equiv.) was added to
tuted- and 2,9-disubstituted-1,10-phenanthroline deriva- the reaction mixture. After 3 h, the solvents were removed
tives. To the best of our knowledge, the intermediate re- under reduced pressure. The crude product was then di-
sulting from the addition of the organolithium reagent to rectly subjected to column chromatography to afford com-
1,10-phenanthroline has only been hydrolyzed to afford an pound 1a in 74% yield. Similarly, the treatment of 1,10-
air-sensitive dihydrophenanthroline intermediate that has phenanthroline with n-hexyllithium and phenyllithium fol-
been always directly aromatized. In this paper, we show that lowed by the quenching with benzyl bromide gave 1b and
1c, respectively. The same reaction conditions were also
used to prepare 3a–e from compound 2. The benzylated
dihydrophenanthroline derivatives 1a–c and 3a–e were
found reasonably stable under normal laboratory condi-
tions and could be easily characterized. The 1H NMR spec-
tra of 1a–c are characterized by two doublets with a coup-
ling constant of ca. –15 Hz for the diastereotopic benzylic
protons and three sets of signals (1a–b: δ = 3.8, 5.5, and
6.5 ppm; 1c: δ = 5.1, 5.9, and 6.6 ppm) for the three protons
of the nonaromatic six-membered ring. The same character-
[a] Groupe de Chimie des Fullerènes et des Systèmes Conjugués,
Laboratoire de Chimie de Coordination du CNRS,
205 route de Narbonne, 31077 Toulouse Cedex 4, France
Fax: +33-561-55-30-03
E-mail: jfnierengarten@lcc-toulouse.fr
[b] Laboratoire de Physico-Chimie Bioinorganique, Université
Louis Pasteur et CNRS (UMR 7509), Ecole Européenne de
Chimie, Polymères et Matériaux (ECPM),
25 rue Becquerel, 67087 Strasbourg Cedex 2, France
Fax: +33-390-24-26-39
E-mail: mholler@chimie.u-strasbg.fr
[c] Laboratoire DECOMET, Université Louis Pasteur,
4 rue Blaise Pascal, 67000 Strasbourg, France
E-mail: welter@chimie.u-strasbg.fr
1
istic features are observed in the H NMR spectra of 3a–e.
When 1,10-phenanthroline is treated with an excess of
nBuLi in Et2O at room temperature for 24 h and quenched
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2007, 417–419
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
417

J.-F. Nierengarten et al.
SHORT COMMUNICATION
1
anthrolinone 5a–d and 6a–b was based on H- and 13C-,
2D-COSY- and NOESY NMR spectroscopic data. It is
worth noting that the signal corresponding to the benzylic
protons appeared as a broad singlet in the 1H NMR spectra
recorded at room temperature for all of these compounds.
Variable-temperature NMR studies revealed a perfectly re-
versible narrowing of this signal and a sharp singlet was
observed at ca. 80 °C. In contrast, an AB quartet was ob-
served at low temperature (–40 °C). The later observations
indicate restricted rotation of the benzyl substituent. Crys-
tals suitable for X-ray crystal structure analysis were ob-
tained for 5a and 5d (Figure 1).[7] In both cases, analysis
Scheme 1.
with water, a tetrahydrophenanthroline derivative is ob-
tained. MnO2 oxidation of this oxygen-sensitive intermedi-
ate yields 2,9-dibutyl-1,10-phenanthroline.[4] When the
treatment with nBuLi is followed by reaction with an excess
of benzyl bromide, compound 4a can be isolated in 79%
yield. Benzylation at the two N atoms was never observed
even in the presence of a large excess of benzyl bromide,
most probably for steric reasons. Interestingly, the mono-
benzylated tetrahydrophenanthroline intermediate was
readily oxidized under air to afford 4a and the use of MnO2
or other oxidant was not required.[5] The reaction of 1,10-
phenanthroline with an excess of n-hexyllithium and phen-
yllithium followed by the quenching with benzyl bromide
afforded 4b and 3e, respectively. Whereas 4a and 4b were
thus obtained in good yields, compound 3e was only iso-
lated in 34% yield. This is mainly associated with the poor
solubility in Et2O of the intermediate resulting from the
addition of 2 equiv. of PhLi to 1,10-phenanthroline
(Scheme 2).
Scheme 3.
Scheme 2.
Derivative 1a was first treated with MnO2 in order to see
if this reagent could achieve the debenzylation/aromatiza-
tion to afford the corresponding phenanthroline. To our
surprise, an oxidative carbon–carbon bond cleavage oc-
curred thus leading to compound 5a (Scheme 3). This be-
havior was indeed general and treatment of the benzylated
dihydrophenanthroline derivative bearing a methyl, n-butyl
or n-hexyl substituent with MnO2 gave the corresponding
benzylated phenanthrolin-2-one derivative in excellent
yields. Compound 5d was also obtained by reaction of 3c
(sBu) or 3d (tBu) with MnO2. The yields were however low.
Indeed, the oxidation of 3c and 3d was very slow. After
24 h, the starting material was not completely consumed
and decomposition occurred. However, except for 5d and
unreacted starting material, no other product could be iso-
lated. In contrast, no oxidative cleavage of the phenyl–C
bond occurred upon treatment of 1c and 3e with MnO2. In
both cases, oxidation took place at the 4-position of the
phenanthroline core thus leading to phenanthrolin-4-one
Figure 1. (A) ORTEP view with partial numbering of compound
5b, thermal ellipsoids include 50% of the electron density. (B)
ORTEP view with partial numbering of compound 5d, thermal el-
derivatives 6a and 6b.[6] Structural assignment of the phen- lipsoids include 30% of the electron density.
418
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Eur. J. Org. Chem. 2007, 417–419

Synthetic Route for the Preparation of 1,10-Phenanthroline Derivatives
SHORT COMMUNICATION
of the crystal lattice revealed stacked pairs of enantiomeric in our laboratories to extend this new concept for the prepa-
conformers having their benzylic groups in opposite orien- ration of other families of phenanthroline derivatives.
tations (Figure S1, Supporting Information). This is in per-
fect agreement with the H NMR observations.
Supporting Information (see also the footnote on the first page of
this article): Experimental details for the preparation of com-
pounds 1–8 and spectroscopic data for all new compounds.
1
Debenzylation of 5a–d and 6a–b was easily achieved by
treatment with a 47% aqueous HBr solution (Scheme 4).[8]
Phenanthrolinone derivatives 7a–d and 8a–b were thus ob-
tained in excellent yields (90–98%). The 1H- and 13C NMR
spectroscopic data and elemental analyses were in full
agreement with the proposed structures. Furthermore, the
structure of compound 7d was confirmed by X-ray crystal
diffraction (Figure 2).[7]
Acknowledgments
This work was supported by the Centre National de la Recherche
Scientifique (CNRS), the EU (project: Organic LEDs for lighting
and ICT applications, OLLA, FP6-2003-IST-2) and a post-doctoral
fellowship from the Deutscher Akademischer Austausch Dienst
(DAAD) to U. H. We further thank M. Schmitt for the high-field
NMR measurements.
[1] a) N. Armaroli, Chem. Soc. Rev. 2001, 30, 113–124; b) D. R.
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[3] For selected examples, see: a) S. Toyota, C. R. Woods, M. Be-
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Can. J. Chem. 1997, 75, 1336–1339.
Scheme 4.
[4] C. O. Dietrich-Buchecker, P. A. Marnot, J.-P. Sauvage, Tetrahe-
dron Lett. 1982, 23, 5291–5294.
[5] The oxidation of di- or tetrahydrophenanthroline intermediates
resulting from the reaction of 1,10-phenanthroline with an
organolithium reagent followed by quenching with water oc-
curs under air but is not very efficient and in addition unde-
fined degradation products are obtained. In this case, the use
of an oxidant (MnO2) is necessary to perform clean aromatiza-
tion, see ref.[4]
[6] The oxidation at the 4-position of the phenanthroline core
leading to phenanthrolin-4-one derivatives is in line with pre-
vious experimental observations. Indeed, treatment of N-alk-
ylphenanthrolinium salts with MnO2 led to 1-alkyl-1,10-phen-
anthrolin-2-one; see: M. R. Johnson, D. Bell, L. Shanaman,
Heterocycles 1997, 45, 1059–1069.
[7] Full data collection parameters and structural data are avail-
able as CIF files. CCDC-615458 (for 5b), -615459 (for 5d), and
615460 (for 7d) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Figure 2. ORTEP view with partial numbering of the H-bonded
dimer of compound 7d, thermal ellipsoids include 50% of the elec-
tron density (a: 2.108 Å; b: 2.168 Å).
In conclusion, we have developed a new synthetic
method for the preparation of phenanthrolinone derivatives
based on the peculiar chemical reactivity of benzylated di-
hydrophenanthroline derivatives. Further work is under way
[8] H. Ban, M. Muraoka, N. Ohashi, Tetrahedron Lett. 2003, 44,
6021–6023.
Received: September 4, 2006
Published Online: November 29, 2006
Eur. J. Org. Chem. 2007, 417–419
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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