Syntheses of new binucleating heterocyclic ligands

Article abstract of DOI:10.1016/j.tetlet.2006.07.132

The syntheses of five new mixed azine-azole binucleating ligands are described.

Full text of DOI:10.1016/j.tetlet.2006.07.132

Tetrahedron Letters 47 (2006) 6941–6943
Syntheses of new binucleating heterocyclic ligands
Jonathan W. Slater and Peter J. Steel*
Department of Chemistry, University of Canterbury, Christchurch, New Zealand
Received 3 July 2006; revised 17 July 2006; accepted 25 July 2006
Abstract—The syntheses of five new mixed azine–azole binucleating ligands are described.
Ó 2006 Elsevier Ltd. All rights reserved.
(i) MeI, MeCN, 45 oC (75%)
We have long been interested in the synthesis and study
of new bridging heterocyclic ligands and their use in
coordination and metallosupramolecular chemistry.1
For example, we have recently reported investigations
of binuclear metal complexes of ligands such as 1–5
(Scheme 1).2 Within this context, we showed that the
binuclear ruthenium(II) complexes of ligands 1–4 exhi-
bit unusually strong metal–metal interactions, seemingly
mediated by the existence of the central azole ring.2a,c
In order to probe the origin of this intriguing phenome-
non, we have prepared a number of structurally related
ligands, the syntheses of which we now report.
(ii) K3Fe(CN)6, aq. NaOH, 5 oC (50%)
(iii) Br2, PPh3, MeCN, 0 oC (48%)
N
N
N
N
Br
(i) nBuLi
(ii) DMF
N
N
N
N
(i) NaCN
(ii) I2
N
N
O
O
CHO
6 (75%)
7 (48%)
S
S
RCHO
NH4OAc
AcOH
H2N
NH2
microwave
In view of the intense current interest in the use of tri-
dentate ligands related to 2,20,60,200-terpyridine,3 we
decided to prepare analogues of 3 and 4 with tridentate
binding domains. A key synthon for such compounds is
2,20-bipyridine-6-carboxaldehyde 6, which has previ-
ously been prepared by methylation of 2,20-bipyridine
and selenium dioxide oxidation,4 and by Swern oxida-
tion of the hydroxymethyl derivative.5 We have found
that this compound is more conveniently prepared by
the sequence shown in Scheme 2. Thus 2,20-bipyridine
N
N
S
N
N
S
N
N
N
N
N
NH
N
N
11 (61%)
R
8 R = H (41%)
9 R = Ph (48%)
Scheme 2. Preparations of doubly tridentate ligands.
N
S
N
N
S
was converted to the 6-bromo-derivative by a methyla-
tion, oxidation, bromination sequence6 and then con-
verted into 6 by lithium halogen exchange followed by
formylation with DMF.7 Subsequent benzoin condensa-
tion afforded the pyridoin, as its enediol tautomer,
which was readily oxidised to the pyridil 7.4b
N
N
N
N
N
5
X
1 X = O 2 X = S
3 X = CH- 4 X = CPh-
Scheme 1. Previously reported binucleating ligands.
Using an extension of the methodology used to prepare
ligands 3 and 4, the diketone 7 was reacted with formal-
dehyde (provided by hexamethylenetetramine) and
benzaldehyde in the presence of excess ammonium
acetate under microwave irradiation to provide the
Keywords: N-ligand; Pyridine; Imidazole; Tridentate ligand.
*
Corresponding author. Tel.: +64 3 3642432; fax: +64 3 3642110;
e-mail: peter.steel@canterbury.ac.nz
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.132

6942
J. W. Slater, P. J. Steel / Tetrahedron Letters 47 (2006) 6941–6943
Acknowledgements
N
N
N
N
N
N
H
N
NH4OAc
AcOH
We thank the University of Canterbury and the Royal
Society of New Zealand Marsden Fund for generous
funding.
N
O
O
+
microwave
N
H
N
OHC
CHO
10 (43%)
References and notes
O
NH2
N
O
N
1. (a) Steel, P. J. Coord. Chem. Rev. 1990, 106, 227–265; (b)
Downard, A. J.; Phillips, I. G.; Steel, P. J. Aust. J. Chem.
2004, 57, 865–868, and references cited therein; (c) Sumby,
C. J.; Steel, P. J. New J. Chem. 2005, 29, 1077–1081;
(d) Steel, P. J. Acc. Chem. Res. 2005, 38, 243–250; (e)
Fitchett, C. M.; Steel, P. J. Aust. J. Chem. 2006, 59, 19–
21.
CHO
+
N
EtOH
piperidine
N
O
N
H2N
O
12 (17%)
Scheme 3. Preparations of ligands 10 and 12.
2. (a) Richardson, C.; Steel, P. J.; D’Alessandro, D. M.;
Junk, P. C.; Keene, F. R. J. Chem. Soc., Dalton Trans.
2002, 2775–2785; (b) Zampese, J. A.; Keene, F. R.; Steel,
P. J. Dalton Trans. 2004, 4124–4129; (c) Slater, J. W.;
D’Alessandro, D. M.; Keene, F. R.; Steel, P. J. Dalton
Trans. 2006, 1954–1962.
3. (a) Heller, M.; Schubert, U. S. Eur. J. Org. Chem. 2003,
947–961; (b) Baranoff, E.; Collin, J.-P.; Flamigni, L.;
Sauvage, J.-P. Chem. Soc. Rev. 2004, 33, 147–155; (c)
Hofmeier, H.; Schubert, U. S. Chem. Soc. Rev. 2004, 33,
373–399; (d) Constable, E. C.; Housecroft, C. E.; Tao, Y.
Synthesis 2004, 869–874; (e) Andres, P. R.; Schubert, U. S.
Adv. Mater. 2004, 16, 1043–1068; (f) Medlycott, E. A.;
Hanan, G. S. Chem. Soc. Rev. 2005, 34, 133–142; (g)
Constable, E. C.; Dunphy, E. L.; Housecroft, C. E.;
Kylberg, W.; Neuberger, M.; Schaffner, S.; Schofield, E.
R.; Smith, C. B. Chem. Eur. J. 2006, 12, 4600–4610; (h)
Chow, H. S.; Constable, E. C.; Housecroft, C. E.;
Neuberger, M.; Schaffner, S. Dalton Trans. 2006, 2881–
2890.
new ligands 8 and 9, respectively.8,9 This microwave
procedure10 avoided the formation of by-products con-
taining a fused imidazolo[1,5-a]pyridine ring system.11
These ligands contain tridentate binding domains
arranged in an ‘angular’ fashion.12 As was previously
1
observed with ligands 3 and 4,2c the H NMR spectra
of these compounds showed significant broadening of
the signals of the pyridine protons due to a slow exchange
on the NMR timescale of the tautomeric imidazole
hydrogens resulting from intramolecular hydrogen
bonding to the pyridine ring.
We next considered the possibility of extending this
ligand design strategy to the preparation of a potentially
tetranucleating ligand. Thus, we reacted terephthalalde-
hyde with 2,20-pyridil, under similar reaction conditions,
which pleasingly furnished the new ligand 10 in 43%
yield (Scheme 3).13 Once again the signals for the
pyridine ring protons were broadened due to slow proto-
tropic tautomerism of the imidazole NH. Double depro-
tonation of this ligand would potentially lead to exciting
new tetranuclear metal complexes, the possibility of
which is under current investigation.
4. (a) Onggo, D.; Craig, D. C.; Rae, A. D.; Goodwin, H. A.
Aust. J. Chem. 1991, 44, 331–341; (b) Heirtzler, F. R.;
Neuburger, M.; Zehnder, M.; Constable, E. C. Liebigs
Ann./Recueil 1997, 297–301.
5. Stroh, C.; Ziessel, R. Tetrahedron Lett. 1999, 40, 4543–
4546.
6. Norrby, T.; Boerje, A.; Zhang, L.; Akermark, B. Acta
Chem. Scand. 1998, 52, 77–85.
Based upon the interesting results we obtained from the
doubly-bidentate ligand 5, containing the unusual thi-
azolo[5,4-d]thiazole fused heterocyclic ring system,2b we
also sought to extend this ligand design strategy towards
a doubly tridentate analogue. Thus, reaction of 6 with
rubeanic acid led to the new ligand 11 in 61% yield
(Scheme 2).14 This ligand contains two tridentate bind-
ing domains arranged in a ‘stepped-parallel’ manner.12
7. Uenishi, J.; Nishiwaki, K.; Hata, S. Tetrahedron Lett.
1994, 35, 7973–7976.
8. Selected data for 8: grey powder, mp 84 °C. 1H NMR
(500 MHz, CDCl3) d: 8.75 (2H, br d, H600); 8.33 (4H, br m,
H30/H300); 7.84 (1H, s, H2); 7.78 (4H, br m, H40/H400); 7.34
(4H, br m, H50/H500). ESMS: calcd C23H17N6 (MH+)
377.1515. Found: 377.1759.
9. Selected data for 9: colourless powder, mp 98 °C. 1H
NMR (500 MHz, CDCl3) d: 8.71 (2H, d, J = 5 Hz, H600);
8.31 (4H, br d, J = 8 Hz, H30/H300); 8.10 (2H, d, J = 8 Hz,
Hortho); 7.78 (4H, br s, H40/H400); 7.50 (2H, t, J = 8 Hz,
Hmeta); 7.42 (1H, t, J = 8 Hz, Hpara); 7.32 (4H, br t, H50/
H500). ESMS: calcd C29H21N6 (MH+) 453.1828. Found:
453.2196.
Finally, in order to explore the possibility of tuning the
metal–metal interactions in complexes of ligands such as
5, we considered the option of introducing a benzene
ring between the fused rings. This proved easier to do
with the oxygen, rather than sulfur, analogue and, by
reacting 2,5-diaminobenzoquinone15 with pyridine-2-
carbaldehyde, we obtained the new ‘stepped-parallel’12
ligand 12, albeit in only 17% yield (Scheme 3).16,17
10. Wolkenberh, S. E.; Wisnoski, D. D.; Leister, W. H.;
Wang, Y.; Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6,
1453–1456.
11. Wang, J.; Mason, R.; VanDerveer, D.; Feng, K.; Bu, X.
R. J. Org. Chem. 2003, 68, 5415–5418.
All five new ligands showed spectroscopic and charac-
terisation data in accord with the proposed structures.
Studies are currently underway employing these ligands
as synthons in coordination and metallosupramolecular
chemistry.
12. D’Alessandro, D. M.; Keene, F. R. New J. Chem. 2006,
30, 228–237.
13. Selected data for 10: orange powder, mp 253 °C. 1H NMR
(300 MHz, CDCl3) d: 11.08 (2H, br s, NH); 8.60 (4H, br d,
H60); 8.37 (4H, br d, H30); 8.07 (4H, s, H2,3,5,6); 7.75 (4H,

J. W. Slater, P. J. Steel / Tetrahedron Letters 47 (2006) 6941–6943
6943
br t, H40); 7.20 (4H, br d, H50). ESMS: calcd C32H23N8
(MH+) 519.2046. Found: 519.2036.
16. Selected data for 12: yellow powder, mp 276 °C. 1H NMR
(300 MHz, CDCl3) d: 8.86 (2H, d, J = 5 Hz, H60); 8.40
(2H, d, J = 8 Hz, H30); 8.09 (2H, s, H3,6); 7.94 (2H, t,
J = 8 Hz, H40); 7.50 (2H, dd, J = 8, 5 Hz, H50). ESMS:
calcd C18H11N4O2 (MH+) 315.0882. Found: 315.1482.
17. The binuclear bis(2,20-bipyridine)ruthenium(II) complex
of this ligand does not show any observable metal–metal
interaction, based on cyclic voltammetric electrochemical
measurements.
1
14. Selected data for 11: H NMR (300 MHz, CDCl3) d: 8.72
(2H, d, J = 5 Hz, H600); 8.61 (2H, d, J = 8 Hz, H300); 8.52
(2H, d, J = 8 Hz, H50); 8.24 (2H, d, J = 8 Hz, H30); 7.97
(2H, t, J = 8 Hz, H40); 7.93 (2H, t, J = 8 Hz, H400); 7.38
(2H, dd, J = 8, 5 Hz, H500). ESMS: calcd C24H15N6S2
(MH+) 451.0800. Found: 451.1549.
15. Osman, A.-M. J. Am. Chem. Soc. 1957, 79, 966–969.