Synthesis of multitopic verdazyl radical ligands. Paramagnetic supramolecular synthons

Article abstract of DOI:10.1021/ol049746i

Equation presented. The syntheses of several verdazyl radical and diradicals containing pyridine-based multitopic coordination sites are described. These compounds were designed to be paramagnetic analogues of oligopyridine metallosupramolecular building blocks.

Full text of DOI:10.1021/ol049746i

ORGANIC
LETTERS
2004
Vol. 6, No. 12
1887-1890
Synthesis of Multitopic Verdazyl Radical
Ligands. Paramagnetic Supramolecular
Synthons
Robin G. Hicks,* Bryan D. Koivisto, and Martin T. Lemaire
Department of Chemistry, UniVersity of Victoria, P.O. Box 3065, STN CSC,
Victoria, B.C. V8W 3V6, Canada
rhicks@uVic.ca
Received February 12, 2004
ABSTRACT
The syntheses of several verdazyl radical and diradicals containing pyridine-based multitopic coordination sites are described. These compounds
were designed to be paramagnetic analogues of oligopyridine metallosupramolecular building blocks.
Verdazyls 1 are one of the few families of organic radicals
stable enough to be prepared, handled, and isolated using
conventional techniques.1 In recent years, derivatives of 1
have attracted interest as open-shell ligands in coordination
chemistry, as alternatives to the established complex chem-
istry of nitroxide radicals2 and semiquinone radical anions.3
The chelating capabilities of multidentate verdazyls such as
2,4 3,5 and 46 (among others7) render them excellent ligands
for transition metals, and the magnetic interactions between
verdazyl- and metal-based spins can be exceptionally strong
and ferromagnetic.4a,5a As such, verdazyl radicals are out-
standing candidates for the construction of metal-radical-
based molecular magnetic materials.
The chelating environments offered by verdazyls 2-4 are
structurally analogous to those found in 2,2′-bipyridine, 2,2′:
6′,2”-terpyridine, and 2,2′-bipyrimidine, respectively. The
parent oligopyridines are, of course, part of one of the
benchmark families of ligands in coordination chemistry.
Nitrogen-containing aromatics have also been tremendously
important in the burgeoning field of supramolecular coor-
(1) (a) Neugebauer, F. A. Angew. Chem., Int. Ed. Engl. 1973, 12, 455.
(b) Neugebauer, F. A.; Fischer, H.; Siegel, R. Chem. Ber. 1988, 121, 815.
(2) Caneshi, A.; Gatteschi, D.; Rey, P. Prog. Inorg. Chem. 1991, 39,
331.
(3) Pierpont, C. G.; Lange, C. W. Prog. Inorg. Chem. 1994, 41, 331.
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J. Am. Chem. Soc. 2000, 122, 8077. (b) Brook, D. J. R.; Fornell, S.;
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M. T.; Thompson, L. K. Inorg. Chem. 2001, 40, 6521. (c) Barclay, T. M.;
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1688.
10.1021/ol049746i CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/11/2004

dination chemistry. A huge array of metallosupramolecular
architectures have been realized,8 including discrete 2D and
3D objects (grids, racks, ladders, polygons, cages, polyhe-
dra),9 intertwined or interlocked structures (helices, knots,
catenanes, rotaxanes),10 dendrimers,11 and extended coordina-
tion networks.12 This has been facilitated by the development
of efficient synthetic routes to oligopyridine-based ligands
with well-defined coordination topologies.13
Scheme 1. Generic Verdazyl Synthesis
Nearly all of the azaheterocyclic ligands employed in
metallosupramolecular chemistry play either a passive role
or are inactive (beyond their structure-dictating purpose) in
determining the possible functions of the structures which
they comprise. It occurred to us that judicious design of
ligands combining verdazyl and pyridine moieties could
facilitate the construction of metal-ligand architectures in
which the magnetic, redox, etc. properties of the assembled
structure are derived from the ligands as well as (or in place
of) the metal ions. Herein we describe the synthesis of
verdazyl-containing multitopic ligands 5-9 which will be
of broad interest to the supramolecular and magnetism
communities.
reagent 2,4-dimethylcarbohydrazide 10 yield tetrazanes 11.
The bis(hydrazide) reagent 10 can made by the reaction of
methylhydrazine with either phosgene14 or triphosgene.15 The
tetrazanes 11 can subsequently be oxidized to the radical
using a number of different oxidants (Scheme 1). These
reactions are general and were employed in the synthesis of
the target molecules shown above.
The synthesis of pyridine-bridged diradical 5, a structural
analogue of terpyridine, is shown in Scheme 2. Swern
Scheme 2. Synthesis of 5a
a Key: (i) oxalyl chloride/DMSO, CH2Cl2, NEt3, -78 °C, 86%;
(ii) 10, MeOH, reflux 16 h, 89%; (iii) NaIO4, H2O, 83%.
All of the verdazyl coordination chemistry reported to date
is based on derivatives of the carbonyl-containing verdazyl
1b. The general synthetic route to so-called “6-oxoverdazyls”
is shown in Scheme 1. Condensations of aldehydes with the
oxidation of 2,6-pyridinedimethanol 12 (in a modification
of literature procedures16) gives the corresponding dicarbox-
aldehyde 13 in excellent yield. Dialdehyde 13 is then
condensed with 10 to give bis-tetrazane 14. Oxidation to the
diradical 5 was carried out in water using sodium periodate,
and the product was isolated as a red precipitate from water.
The quaterpyridine mimic bis(verdazyl) 6 is prepared as
shown in Scheme 3. Monolithiation of 2,6-dibromopyridine
15 followed by oxidative coupling yields 6,6′-dibromo-2′2-
bipyridine 16, which is then converted to the dialdehyde 17
via double lithium-halogen exchange followed by quenching
with DMF.17 Condensation of 17 with 10 yields bis-tetrazane
18, which was subsequently oxidized using ferricyanide in
DMF/water owing to the insolubility of 18 in pure water.
The diradical 6 precipitates on formation as a red solid.
The synthesis of bis(verdazyl) 7, a diradical analogue of
quinquepyridine, is shown in Scheme 4. Dibromopyridine
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1888
Org. Lett., Vol. 6, No. 12, 2004

Scheme 3. Synthesis of 6a
Scheme 4. Synthesis of 7a
a Key: (a) BuLi, -78 °C; (b) CuCl2, O2; (c) BuLi, -78 °C; (d)
DMF; (e) (i) 10, MeOH, reflux 16 h, 90%, (ii) K3Fe(CN)6, Na2CO3,
H2O/DMF, 91%.
15 was converted to aldehyde 19 via a lithium-halogen
exchange/DMF sequence, based on modification of literature
procedures.18 The aldehyde is protected as its dimethyl acetal
2019 and subsequently cross-coupled with 15 under Negishi
conditions20 to yield terpyridine derivative 21. An excess of
20 is required to minimize the formation of 6-bromo-6′-
carboxaldehyde dimethyl acetal-2,2′-bipyridine. The terpy-
ridine product precipitates from the reaction as a zinc
complex; extraction with EDTA yields the 21 in very high
purity and good yield. The acetal groups are deprotected to
give dialdehyde 22 which is then converted to bis(tetrazane)
23 by condensation with 10 in methanol/chloroform, the latter
solvent being required to improve the solubility of 22. The
bis(tetrazane) was then oxidized using K3Fe(CN)6 to afford
diradical 7 as a red solid.
a Key: (a) n-BuLi, -78 °C, THF; (b) DMF, -78 °C, THF, 89%
(two steps); (c) HC(OMe)3, cat. TsOH, MeOH, 96%; (d) n-BuLi,
-78 °C, THF; (e) ZnCl2, -78 °C to rt, THF; (f) 15, Pd(PPh3)4,
THF, 70 °C, 24 h, 74% (three steps); (g) HOAc, H2O, 100 °C,
93%; (h) 10, MeOH/CHCl3, 65 °C, 16 h, 87%; (i) K3Fe(CN)6,
Na2CO3, water/DMF, 96%.
hydrazide 10 gave tetrazane 28. Finally, oxidation using
periodate in water was facilitated by protonation (HCl/H2O)
to solubilize the tetrazane; the resulting radical 8 precipitated
as a dark orange solid.
Two other verdazyl ligands were prepared containing
pyrimidine as well as pyridine rings. The first of these is
verdazyl monoradical 8 carrying a 3,5-di(2-pyridyl)-2,6-
pyrimidin-1-yl substituent at C3. We are not aware of any
nonradical analogue with the binding topology inherent in
8; the most closely related bis-tridentate ligand appears to
be tetrakis(2-pyridyl)pyrazine.21 The synthesis of 8 is shown
in Scheme 5. 2-Acetylpyridine is condensed with 2-pyridi-
necarboxaldehyde under basic conditions22 to give chalcone
24, which could not be isolated because of its decomposition
on attempted purification by chromatography.23 The reaction
of the in situ generated enone with acetamidine gave methyl
substituted pyrimidine 25. Oxidation of the methyl group
with SeO2 gave the corresponding aldehyde 26 as well as
the carboxylic acid 27 as a side product. Reaction with bis-
The structure of diradical 9 was inspired by oligo-tridentate
ligands designed to form grid/rack structures upon self-
assembly with metal ions.13b-d Its synthesis is shown in
Scheme 6. Protected aldehyde 20 (Scheme 4) was converted
separately to monoprotected bis-aldehyde 29 and acetyl
Scheme 5. Synthesis of 9a
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1971, 10, 2472.
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M.; Kankare, J.; Takalo, H. HelV. Chim. Acta 1992, 75,1621.
(20) Fang, Y. Q.; Hanan, G. S. Synlett 2003, 852.
(21) (a) Brewer, R. G.; Jensen, G. E.; Brewer, K. J. Inorg. Chem. 1994,
33, 124. (b) Constable, E. C.; Edwards, A. J.; Phillips, D.; Raithby, P. R.
Supramol. Chem. 1995, 5, 93. (c) Burkholder, E.; Zubieta, J. Chem.
Commun. 2001, 2056. (d) Bera, J. K.; Campos-Fernandez, C. S.; Clerac,
R.; Dunbar, K. R. Chem, Commun. 2002, 2536.
(22) Jones, P. D.; Glass, T. E. Tetrahedron Lett. 2001, 42, 2265.
(23) A practical route to 24 in pure form has recently been reported:
Zhang, Z.; Dong, Y. W.; Wang, G. W. Chem. Lett. 2003, 32, 966.
a Key: (a) 2-pyrdinecarboxaldehyde, NaOH, H2O, 0.5 h, 62%;
(b) acetamidine hydrochloride, EtOH, reflux, 4 h, 40%; (c) SeO2,
dioxane, reflux 72 h, 28%; (d) 10, MeOH, reflux, 8 h, 79%; (e)
NaIO4, HCl/H2O, 95%.
Org. Lett., Vol. 6, No. 12, 2004
1889

three target radicals were identified by high-resolution mass
spectra. EPR spectra,25 though informative with respect to
the electronic structure of the radicals, are not good indicators
of product purity or yield. Other spectroscopic methods are
more effective for radical characterization (Supporting
Information). The IR carbonyl stretching frequency shifts
from ∼1620 cm-1 in tetrazanes to ∼1690 cm-1 in the
radicals. The radicals are also characterized by the absence
of NH stretches above 3000 cm-1 in comparison to the
tetrazanes, which have multiple bands in this region. The
UV-vis spectra of the radicals are also diagnostic as they
exhibit two absorption bands with maxima near 410 and 450
nm. The less than optimal stability of verdazyls is not
anticipated to be a serious problem for the preparation of
supramolecular complexes: There is ample evidence that
verdazyl stability improves upon coordination, and it is also
possible to prepare metal-verdazyl complexes via in situ
tetrazane oxidation in the presence of metal ions.4b,7c
In summary, we have synthesized a series of oligopyridine-
based verdazyl radicals that can be used as functionalized
building blocks in metallosupramolecular chemistry. Al-
though oligopyridine-derivatized nitroxide radicals have been
reported,26 the binding sites offered by these radicals are quite
different from the parent bipyridine binding pocket. The close
structural relationship between verdazyls and aza-aromatics
renders the family of compounds described herein promising
building blocks for functional self-assembled coordination
complexes. Work to this end, as well as studies on the
intramolecular spin exchange interactions in the diradicals,
will be reported in due course.
Scheme 6. Synthesis of 9a
a Key: (a) n-BuLi, -78 °C, THF; (b) DMF, -78 °C, THF, 86%
two steps; (c) DMA, -78 °C, THF, 76% (two steps); (d) KOH,
H2O/MeOH; (e) KOH, benzamidine-HCl, air, MeOH, 42% (two
steps; (f) HOAc, H2O, 100 °C, 2 h, 95%; (g) 10, CHCl3, 65 °C, 16
h, 85%; (h) p-benzoquinone, CHCl3, 40 °C, 0.5 h, 65%.
derivative 30. These two products were then reacted with
each other in a Claisen-Schmidt reaction to give chalcone
31 which, like its counterpart 24, was used without purifica-
tion. Crude 31 was condensed with benzamidine to give
pyrimidine 32; deprotection of the acetal groups of 32 gave
dialdehyde 33, which was then condensed with 10 to yield
bis(tetrazane) 34. The tetrazane has limited solubility in polar
solvents; its oxidation to diradical 9 was carried out in
chloroform with p-benzoquinone.
Acknowledgment. We thank the University of Victoria
and the Natural Sciences and Engineering Research Council
of Canada for their support.
Supporting Information Available: Synthetic procedures
and characterization data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The characterization of verdazyl radicals can be hindered
by their lack of long term stability, particularly in solution;
half-lives in solution range from hours to months.24 Accept-
able elemental analyses were obtained for 7 and 9; the other
OL049746I
(25) The solution EPR spectrum of 8 is typical of verdazyl monoradicals
(ref 15), and the EPR of diradicals 9 and 7 show no evidence of exchange
coupling (see the Supporting Information). The EPR of 5 and 6 are more
complex and will be reported in more detail in a forthcoming publication.
(26) (a) Stroh, C.; Ziessel, R. Tetrahedron Lett. 1999, 40, 4543. (b)
Ziessel, R.; Ulrich, G.; Lawson, R. C.; Echegoyen, L. J. Mater. Chem. 1999,
9, 1435. (c) Ziessel, R.; Stroh, C. Org. Lett. 2003, 5, 2397.
(24) (a) Brook, D. J. R.; Fox, H. H.; Lynch, V.; Fox, M. A. J. Phys.
Chem. 1996, 100, 2066. (b) Fico, R. M., Jr.; Hay, M. F.; Reese, S.;
Hammond, S.; Lambert, E.; Fox, M. A. J. Org. Chem. 1999, 64, 9386.
1890
Org. Lett., Vol. 6, No. 12, 2004