A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

Article abstract of DOI:10.1016/j.tetlet.2008.05.128

The 2,2′:6′,2″-terpyridines 8a and 8b were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 1 (R¹ = ⁿPr and Ph) with the bis-amidrazone 7 and 2,5-norbornadiene 5 in ethanol at reflux.

Full text of DOI:10.1016/j.tetlet.2008.05.128

Tetrahedron Letters 49 (2008) 4720–4721
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Tetrahedron Letters
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A convenient synthesis of substituted 2,20:60,200-terpyridines
b
Alexander Gehre a, Stephen P. Stanforth a, , Brian Tarbit
*
a School of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK
b Vertellus Specialities Chemicals UK Ltd, Seal Sands Road, Seal Sands, Middlesbrough TS2 1UB, UK
a r t i c l e i n f o
a b s t r a c t
The 2,20:60,200-terpyridines 8a and 8b were prepared in good yield by reacting
a-acetoxy-a-chloro-b-keto-
Article history:
esters 1 (R1
=
nPr and Ph) with the bis-amidrazone 7 and 2,5-norbornadiene 5 in ethanol at reflux.
Received 11 April 2008
Revised 15 May 2008
Accepted 28 May 2008
Available online 2 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
2,20:60,200-Terpyridines
Aza Diels–Alder reaction
1,2,4-Triazines
2,20:60,200-Terpyridines have found extensive use in both coordi-
nation chemistry and supramolecular chemistry, and consequently
synthetic approaches to this important class of ligand have
attracted considerable attention.1 We have previously described
a convenient methodology that has enabled the preparation of
2,20-bipyridine derivatives,2–6 and in this Letter we disclose how
this work has been extended and adapted to allow the synthesis
of 2,20:60,200-terpyridines.
ters 2,5 which reacted with amidrazones 3 yielding triazines 4. An
aza Diels–Alder reaction of these triazines using 2,5-norbornadiene
5 as an acetylene equivalent (or with other aza dienophiles)5,6 fur-
nished pyridine derivatives 6 (Scheme 1). The substituted pyridines
6 could also be produced in a ‘one-pot’ reaction directly from
compounds 1, amidrazones 3 and 2,5-norbornadiene 5 in ethanol
solution at reflux without isolating the triazines 4. When the amid-
razone 3 had R2 = 2-pyridyl, then 2,20-bipyridines were formed.
We have demonstrated that readily available
chloro-b-keto-esters 1 are synthetic equivalents of
a
-acetoxy-
a
-
When the bis-amidrazone
7 (available from the reaction
a,b-diketo-es-
of 2,6-dicyanopyridine with hydrazine)7 was reacted with
Scheme 1. Synthesis of substituted pyridines.5
* Corresponding author. Tel.: +44 191 2274784; fax: +44 191 2273519.
E-mail address: steven.stanforth@unn.ac.uk (S. P. Stanforth).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.05.128

A. Gehre et al. / Tetrahedron Letters 49 (2008) 4720–4721
4721
-acetoxy-a
-chloro-b-keto-esters 1 (R1 = nPr or Ph) in the presence
3. Stanforth, S. P.; Tarbit, B.; Watson, M. D. Tetrahedron Lett. 2003, 44, 693–
694.
4. Stanforth, S. P.; Tarbit, B.; Watson, M. D. Tetrahedron 2004, 60, 8893–8897.
5. Altuna-Urquijo, M.; Stanforth, S. P.; Tarbit, B. Tetrahedron Lett. 2005, 46,
6111–6113.
a
of an excess of 2,5-norbornadiene 5 in ethanol at reflux, the 2,20:
60,200-terpyridine derivatives 8a (60%) and 8b (76%) were obtained
following the general sequence outlined above in Scheme 1 with-
out isolation of the corresponding triazine intermediates 9a and
9b.8,9 The structures of the products 8a and 8b were fully sup-
ported by their spectroscopic data.8 This method of constructing
the 2,20:60,200-terpyridine nucleus is versatile in view of the avail-
ability of compounds 1 (from b-keto-esters)5 and 2,6-dicyanopyri-
dine (commercially available or readily prepared from the
inexpensive pyridine-2,6-dicarboxylic acid). Additionally, the reac-
tivity of 1,2,4-triazines towards aza dienophiles other than 2,5-
norbornadiene 5 is well known (e.g., enamines)10 and hence the
introduction of additional substituents in the lateral pyridine rings
of the 2,20:60,200-terpyridine system should be feasible.
6. Gehre, A.; Stanforth, S. P.; Tarbit, B. Tetrahedron Lett. 2007, 48, 6974–6976.
7. Case, F. H. J. Heterocycl. Chem. 1971, 8, 1043–1046.
8. Compound 8a: To a solution of compound 1 (R1
=
nPr) (501 mg; 2.00 mmol;
2.0 equiv) in EtOH (3 mL) was added MeNH92 (0.49 mL; 33% w/w in EtOH;
4.00 mmol; 4.0 equiv) and the mixture was stirred at room temperature for 1 h.
The bis-amidrazone 7 (193 mg; 1.00 mmol) and 2,5-norbornadiene 5 (2.15 mL;
20.0 mmol; 20.0 equiv) were added and the mixture was heated under reflux
for 20 h. The solvent was evaporated under reduced pressure and the residue
was purified by column chromatography [ethyl acetate/petroleum ether (bp
40–60 °C) (1:4)] giving compound 8a as an off-white solid (279 mg; 60%), mp
105–106 °C (from EtOH). IR (diamond anvil):
m .
1721 cmꢀ1 1H NMR: (270 MHz,
CDCl3) d 8.59 (d, 2H, J = 7.9 Hz), 8.47 (d, 2H, J = 8.3 Hz), 8.30 (d, 2H, J = 8.3 Hz),
7.91 (t, 1H, J = 7.9 Hz), 4.42 (q, 4H, J = 7.2 Hz), 3.26–3.20 (m, 4H), 1.94–1.80 (m,
4 H), 1.44 (t, 6H, J = 7.2 Hz), 1.06 (t, 6H, J = 7.2 Hz) ppm. 13C NMR: (65 MHz,
CDCl3) d 167.01, 162.79, 157.48, 154.94, 139.42, 137.95, 125.41, 122.31, 117.85,
61.34, 39.05, 23.02, 14.37, 14.30 ppm. HRMS (ES) for C27H32N3O4 [M+H]+:
calcd: 462.2387; measured: 462.2394. Compound 8b (76%) was prepared using
a similar procedure to that described above, mp 156–157 °C (from EtOH). IR
We have therefore demonstrated that our general route to pyr-
idine derivatives depicted in Scheme 1 can be conveniently applied
to 2,20:60,200-terpyridine synthesis.
(diamond anvil)
m .
1704 cmꢀ1 1H NMR: (270 MHz, CDCl3) d 8.67 (d, 2H, J =
8.2 Hz), 8.62 (d, 2H, J = 7.9 Hz), 8.27 (d, 2H, J = 8.2 Hz), 7.93 (t, 1H, J = 7.9 Hz),
7.69–7.63 (m, 4H), 7.51–7.43 (m, 6H), 4.19 (q, 4H, J = 7.2 Hz), 1.07 (t, 6H,
J = 7.2 Hz) ppm. 13C NMR: (65 MHz, CDCl3) d 168.42, 158.35, 157.17, 154.60,
140.49, 139.04, 138.01, 128.92, 128.76, 128.15, 127.13, 122.57, 118.76, 61.57,
13.78 ppm. HRMS (EI) for C33H28N3O4 [M+H]+: calcd: 530.2074; measured:
530.2079.
Acknowledgement
We thank Vertellus Specialities Chemicals UK Ltd for generous
financial support and the EPSRC mass spectrometry service (Swan-
sea) for high resolution mass spectra.
9. Methylamine is added to compounds
amidrazones. We believe that the methylamine reacts at the acetoxy carbonyl
group generating compounds by de-acylation followed by chloride
1 prior to their reactions with
2
References and notes
elimination. If methylamine is not added, then we have found that 2 equiv of
the chloroacetate 1 are required for each R(NH2)C@NNH2 functional group.
10. For a recent example in 2,20:60,200-terpyridine chemistry see: Kozhevnikov, V.
N.; Whitwood, A. C.; Bruce, D. W. Chem. Commun. 2007, 3826–3828.
1. Constable, E. C. Chem. Soc. Rev. 2007, 36, 246–253.
2. Stanforth, S. P.; Tarbit, B.; Watson, M. D. Tetrahedron Lett. 2002, 43, 6015–6017.