S. Jakobsen, M. Tilset / Tetrahedron Letters 52 (2011) 3072–3074
3073
Scheme 1. Mono lithium addition and reoxidation.6
Scheme 2. Symmetrical double lithium addition and reoxidation.7
Scheme 3. Asymmetrical double lithium addition and reoxidation.9
Barends, S.; Gamez, P.; Turpeinen, U.; Mutikainen, I.; van Wezel, G. P.; Reedijk,
J. Dalton Trans. 2007, 3676–3683; (d) Kavita, D.; Legros, J.; Croisse, B.;
Chandrasekharan, S.; Bonnet-Delphin, D. Org. Biomol. Chem. 2011, 9, 347–350.
3. (a) Geissman, T. A.; Schlatter, J. M.; Webb, I. D.; Roberts, J. D. J. Org. Chem. 1946,
11, 741–750; (b) Buchecker, C. O. D.; Marnot, P. A.; Sauvage, J. P. Tetrahedron
Lett. 1982, 50, 5291–5294.
mono-substitution study. We knew that aryl- and alkyllithium
addition to the first C@N bond was very fast and very specific to
give mono substituted products only. To achieve the second addi-
tion without any reoxidation or purification would be beneficial.
Thus, by first adding exactly 1 equiv of the first lithium reagent
and allowing it to react for 5 min would give the 1,2-dihydro prod-
uct in solution. Adding a second lithium reagent at this point
should lead to exclusive addition over the second N@C bond (the
C9@N10 bond). After 35 min reaction time, the second addition
was complete and the usual procedure of reoxidation and purifica-
tion would give the desired asymmetrical product. Preparation of
2-butyl-9-phenyl-1,10-phenanthroline from 1,10-phenanthroline,
phenyllithium and n-butyllithium by this method was achieved
in a yield of 92% in under 2 h including the reoxidation and
work-up procedures (Scheme 3).9
In conclusion, a reliable, fast and high yielding method for the
preparation of asymmetrically 2,9-disubstituted 1,10-phenanthro-
lines has been developed. This is of great value, since 1,10-phen-
anthrolines are some of the most popular bidentate nitrogen
ligands in coordination chemistry. The method itself should be
easily applied to similar systems, for instance 2,20-bipyridines to
afford 6,60-disubstituted-2,20-bipyridines. A whole range of sym-
metrical and asymmetrical bidentate nitrogen-containing ligands
are now available within only a few hours using common reagents.
4. Wu, G.; Huang, M. Chem. Rev. 2006, 106, 2596–2616.
5. (a) Viton, V. H.; Desvergenes, V.; Jodry, J. J.; Buchecker, C. D.; Sauvage, J. P.;
Lacour, J. Dalton Trans. 2006, 2058–2065; (b) Buchecker, C. O. D.; Nierengarten,
J. F.; Sauvage, J. P.; Armaroli, N.; Balzani, V.; Cola, L. D. J. Am. Chem. Soc. 1993,
115, 11237–11244.
6. Synthesis of 2-subsituted-1,10-phenanthrolines from 1,10-phenanthroline. A
solution of 1,10-phenanthroline (1 g) in dry, degassed toluene (200 ml) was
cooled to 0 °C under argon and subjected to vigorous stirring. The pre-titrated
n-butyl- or phenyllithium solution was added dropwise via syringe in the
following way: on addition of the first few drops of alkylating reagent, no
permanent color change was observed. On further careful addition (typically
one drop) the solution became intensely colored, indicating formation of the
addition product. From this point 1.0 equiv of lithium reagent was added
slowly and the solution left to stir for 5 min. Quenching with H2O (30 ml),
extraction with CH2Cl2 (3 ꢀ 100 ml) and reoxidation by MnO2 gave the title
product. Work-up by filtration of the CH2Cl2 solution through a short plug of
alumina and additional washing with CH2Cl2 (2 ꢀ 100 ml) gave, after removal
of the solvent, the 2-substututed-1,10-phenanthroline in good yields (2-
phenyl-1,10-phenanthroline: 99% and 2-butyl-1,10-phenanthroline: 98%, as
white powders). NMR and HR-MS were in agreement with previously
published data.10
7. Synthesis of 2,9-diphenyl-1,10-phenanthroline from 1,10-phenanthroline. The
synthesis was carried out in a similar way as described for the mono alkylated
product, but employing 2.2 equiv of PhLi, a 40 min reaction time, and after
removal of solvent the resulting brown oil was chromatographed on alumina
with an EtOAc-iso-hexane solution (gradient from pure iso-hexane). Yield: 80%,
white solid. NMR and HR-MS were in agreement with previously published
data.11
Acknowledgment
8. Buchecker, C. D.; Jiménez, M. C.; Sauvage, J. P. Tetrahedron Lett. 1999, 40, 3395–
3396.
FUNMAT@UIO is acknowledged for financial support.
References and notes
9. Synthesis of 2-butyl-9-phenyl-1,10-phenanthroline from 1,10-phenanthroline.
A solution of 1,10-phenanthroline (590 mg) in dry, degassed toluene (150 ml)
was cooled to 0 °C under argon and subjected to vigorous stirring. The pre-
titrated PhLi solution was added dropwise via syringe in the following way: on
addition of the first few drops of arylating reagent, no permanent color change
was observed. On further careful addition (typically one drop) the solution
became intensely colored, indicating formation of the addition product. From
this point 1.0 equiv of PhLi solution (1.8 ml 1.9 M) was slowly added and the
solution left for 5 min. Next, 1.1 equiv of n-BuLi (1.5 ml, 2.3 M) were added
dropwise and the reaction left to stir for 35 min. Quenching with H2O (30 ml),
extraction with CH2Cl2 (3 ꢀ 100 ml) and reoxidation by MnO2 gave the title
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