The [1,2,3]Triazolo[1,5-a]pyridine ring: A sensitive sensor for the electronic profile of phosphorus substituents

Article abstract of DOI:10.1039/b906034k

The unique nature of the [1,2,3]triazolo[1,5-a]pyridine reveals without any external perturbation the electronic contribution of various substituents to the phosphorus atom in phosphines, based on the equilibrium of two possible ring-chain isomers.

Full text of DOI:10.1039/b906034k

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The [1,2,3]Triazolo[1,5-a]pyridine ring: A sensitive sensor for the electronic
profile of phosphorus substituents†
Rafael Ballesteros-Garrido,a Laurence Bonnafoux,a Fre´de´ric R. Leroux,*a Bele´n Abarca*b and
Franc¸oise Colobert*a
Received 27th March 2009, Accepted 24th April 2009
First published as an Advance Article on the web 8th May 2009
DOI: 10.1039/b906034k
The unique nature of the [1,2,3]triazolo[1,5-a]pyridine reveals
without any external perturbation the electronic contribution
of various substituents to the phosphorus atom in phos-
phines, based on the equilibrium of two possible ring-chain
isomers.
In the context of our study on the chemistry of [1,2,3]triazolo[1,5-
a]pyridines we have reported their importance in coordination
chemistry.1 Their use in the field of magnetic materials,2 and as
fluorophores3 that allow the formation of molecular chemosensors
have been documented.4 Quite recently, we could experimen-
tally and theoretically show that 3-(2¢-pyridyl)[1,2,3]triazolo[1,5-
a]pyridine (1)5 undergoes a regioselective metalation at C7. How-
ever, after trapping with an electrophile, a ring-chain isomerisation
between the two regioisomers A and B via a diazo form occurs
(Scheme 1).
We proved that the A–B ratio depends exclusively on the
electronic properties of the El substituent.5 Electron-donating
substituents favour the A form, electron-withdrawing substituents
favour the B form, and only in the case where El = Me both forms
are present (75% of A, 25% of B).
Substituents having both variable acceptor and donor character
are expected to provide a mixture of these two structures. Thus, the
ratio between structures A and B should reflect the relative value
Scheme 1 Triazole-ring rearrangement.
of the global electronic effect. For example, with A/B > 1 the
substituent has essentially donor properties, while with A/B < 1,
the acceptor capacity dominates.
Phosphines are typical substituents owing an “amphoteric”
electronic character as they have both s-donor- and p-acceptor
properties. Therefore, we became interested in the synthesis
of phosphine ligands based on the [1,2,3]triazolo[1,5-a]pyridine
moiety due to its unusual electronic and chemical properties.
3-(2¢-Pyridyl)-[1,2,3]triazolo[1,5-a]pyridine (1) was treated with
Scheme 2 Synthesis of triazolopyridine-based phosphines.
butyllithium in toluene at -40 ◦C, followed by trapping of
the 7-lithiated intermediate with various aliphatic and aromatic
chlorophosphines. In each case, a different ratio between the two
regioisomers A and B was obtained (Scheme 2 and Table 1). The
different isomers cannot be isolated separately, but can be perfectly
identified by 1H NMR as they show distinct signals (see ESI†).
When the phosphine acts essentially as an electron-donor, the
2¢-phosphino-pyridyl ring-nitrogen is more nucleophilic and can
attack the diazo intermediate giving rise to the triazole according
to structure A. However, with phosphines withdrawing the electron
density, the ring-nitrogen of the unsubstituted pyridine in the
diazo intermediate is the most nucleophilic one leading to triazole
structure B (Fig. 1).
aCNRS and University of Strasbourg (ECPM), UMR 7509, 25 rue
Becquerel, 67087, Strasbourg, France. E-mail: frederic.leroux@unistra.fr;
francoise.colobert@unistra.fr; Fax: +33 (0)3-90-24-27-42
bDepartament de Quimica Orga`nica, Facultad de Farmacia, Universidad de
Valencia, Avda. Vicente Andre´s Estelle´s s/n, 46100, Burjassot, Valencia,
Spain. E-mail: Belen.Abarca@uv.es
† Electronic supplementary information (ESI) available: Experimental
details, characterization data, as well as X-ray crystallographic data for
2d (B) and 3e (B). CCDC reference numbers 705762 & 705763. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b906034k
The results obtained with the dicyclohexyl-, di-iso-propyl- and
diphenyl phosphines (entries 1, 3 and 4 in Table 1) reflect the
s-donor properties of alkyl phosphines which are superior to those
of aryl phosphines. However, the triazolopyridine system reflects
5068 | Dalton Trans., 2009, 5068–5070
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Table 1 Ratios of the donor/acceptor structures A and B
Entry
PR2
A/Ba
A/Bb
Yield (%)
1
2
3
4
5
6
7
PCy2 (2a)
1.39
1.23
1.04
0.72
0.71
0.40
0.18
1.00
0.88
0.75
0.52
0.51
0.28
0.13
22
10
13
40
22
66
46
P(p-PhOCH3)2 (2b)
Pi-Pr2 (2c)
PPh2 (2d)
P(p-PhCH3)2 (2e)
P(p-PhF)2 (2f)
P(p-PhCF3)2 (2g)
a Ratio determined by 1H-NMR before and after purification.
b Normalized A/B ratio.
Fig. 2 Solid-state molecular structure of 2d (B). Hydrogen atoms are
omitted for clarity. For details see ESI.†
towards the electron-acceptor structure B. This allowed us to
determine the s-donor properties of these phosphines according
to the selenide method. The structure of these selenides could also
be confirmed by single crystal X-ray analysis (Fig. 3).
Fig. 1 Influence on the ring-chain isomers depending on the donor/
acceptor-properties of the phosphines.
at the same time the dual property of phosphines. For instance,
in the case of di-iso-propyl phosphine, there is no preferential
structure. A and B are in equilibrium with a ratio of 1.04:1.00
(entry 3 in Table 1). In terms of electron density, this phosphine has
equal properties of an acceptor and a donor. This observation is
in accordance with calculations by Pacchioni and Bagus revealing
that the p-acidity of PR3 increases along the series PMe3 < PH3 <
P(OMe)3 < PF3 with PMe3 having a “remarkable” p-acidity.6
When the phenyl-ring in diphenyl phosphine is substituted in
the para position by electron-accepting groups like F or CF3, the
triazolopyridine B is obtained as the major compound. Thus, the
acceptor capacity dominates largely. The presence of a methyl
group in the para position has almost no influence on the global
properties of the phosphine (entries 4 and 5 in Table 1). However,
our study revealed that a para-methoxy diphenyl phosphine
provides higher electron density to the triazole system, than
di-iso-propyl phosphine (entries 2 and 3 in Table 1).
Fig. 3 Solid-state molecular structure of 3e (B). Hydrogen atoms are
omitted for clarity. For details see ESI.†
The range of selenium coupling constants is relatively small
having the highest value for the smallest s-donor effect (R =
1
31 77
p-PhCF3, entry 7 in Table 2) of J(
Se) = 1.00 (normalized) and
P–
the lowest value (R = Cy, entry 1 in Table 2) for the highest
1
31 77
s-donor effect of J(
Se) = 0.93. Thus, the method is less
P–
sensitive than the triazolopyridine moiety (Fig. 4).
The studies described here reveal the high sensitivity of the
[1,2,3]triazolo[1,5-a]pyridine ring towards electronic perturbation.
The electronic influence of different alkyl and aryl substituents
on phosphorus was shown without any external perturbation (as
is the case for the selenide method). For the first time different
We were able to isolate a single crystal from the ring-chain
isomer 2d (B) and confirm its structure by single crystal X-ray
analysis (Fig. 2). In solution, the pure isomer 2d (B) undergoes
once again equilibration and affords the equilibrium ratio with
isomer 2d (A) reported in Table 1 (entry 4).
Table 2 31P–77Se coupling constants measured in CDCl3 of the selenides
3a–g
b
Entry
PR2
1JP–Se (Hz)a
1JP-Se
1
2
3
4
5
6
7
PCy2 (3a)
705.5
725.4
713.5
736.4
729.6
744.4
760.6
0.93
0.95
0.94
0.97
0.96
0.98
1.00
The s-donor ability of phosphine ligands is most often deter-
P(p-PhOCH3)2 (3b)
Pi-Pr2 (3c)
1
31 77
mined by measuring the magnitude of the J(
Se) in the 77Se
P–
PPh2 (3d)
isotopomer of the corresponding selenide. According to Allen and
Taylor, an increase in this coupling constant indicates an increase
in the s character of the phosphorus lone-pair orbital (i.e., a less
basic phosphine = lower s-donor ability).7
P(p-PhCH3)2 (3e)
P(p-PhF)2 (3f)
P(p-PhCF3)2 (3g)
a Selenides were prepared according to the procedure described in the
As expected, when the phosphines 2a–g were converted into
their selenides 3a–g, the equilibrium was completely shifted
literature. b Normalized 1JP,Se values.
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funded by the Ministe`re de la Recherche (France), the Ministerio
de Educacio´n y Ciencia (Spain) (Project CTQ2006-15672-C05-03),
the CNRS (France) and LONZA AG (Switzerland).
Notes and references
1 B. Abarca, B. R. Ballesteros, R. Ballesteros-Garrido, F. Colobert
and F. R. Leroux, Tetrahedron, 2007, 63, 10479–10485; F. Colobert,
R. Ballesteros-Garrido, F. R. Leroux, R. Ballesteros and B. Abarca,
Tetrahedron Lett., 2007, 48, 6896–6899; B. Abarca, R. Ballesteros, R.
Ballesteros-Garrido, F. Colobert and F. R. Leroux, Tetrahedron, 2008,
64, 3794–3801; R. Ballesteros-Garrido, F. R. Leroux, R. Ballesteros, B.
Abarca and F. Colobert, Tetrahedron, 2009, 65, 4410–4417.
2 V. Niel, A. B. Gaspar, M. C. Mun˜oz, B. Abarca, R. Ballesteros and
J. A. Real, Inorg. Chem., 2003, 42, 4782–4788; B. Abarca, R. Ballesteros,
M. Chadlaoui, C. Ramirez de Arellano and J. A. Real, Eur. J. Inorg.
Chem., 2007, 4574–4578; A. K. Boudalis, C. P. Raptpoulo, B. Abarca,
R. Ballesteros, M. Chadlaoui, J. P. Tuchagues and A. Terzis, Angew.
Chem., Int. Ed., 2006, 45, 432–435; A. K. Boudalis, C. P. Raptopoulou,
V. Psycharis, Y. Sanakis, B. Abarca, R. Ballesteros and M. Chadlaoui,
J. Chem. Soc., Dalton Trans., 2007, 3582–3589.
Fig. 4 Comparison between normalized 1JP-Se and normalized A/B ratio
for the different couple of phosphines 2a–g.
ratios of the ring-chain equilibrium were obtained with respect to
the s-donor/p-acceptor properties of the investigated phosphines.
Further experimental and computational studies are in progress
and will be reported soon.
3 B. Abarca, R. Aucejo, R. Ballesteros, F. Blanco and E. Garc´ıa-Espan˜a,
Tetrahedron Lett., 2006, 47, 8101–8103.
4 M. Chadlaoui, B. Abarca, R. Ballesteros, C. Ram´ırezde Arellano, J.
Aguilar, R. Aucejo and E. Garc´ıa-Espan˜a, J. Org. Chem., 2006, 71,
9030–9034.
5 B. Abarca, I. Alkorta, R. Ballesteros, F. Blanco, M. Chadlaoui, J. Elguero
and F. Mojarrad, Org. Biomol. Chem., 2005, 3, 3905–3910; F. Blanco, I.
Alkorta, J. Elguero, V. Cruz, B. Abarca and R. Ballesteros, Tetrahedron,
2008, 64, 11150–11158.
Acknowledgements
We are very grateful to Dr Rafael Ballesteros (University of
Valencia, Spain) for his advice concerning the chemistry of tria-
zolopyridines. We are indebted to Dr Lydia Brelot (Service de Ra-
diocristallographie, University of Strasbourg, France) for her as-
sistance with the single crystal structure elucidation. This work was
6 G. Pacchioni and P. S. Bagus, Inorg. Chem., 1992, 31, 4391–4398.
7 D. W. Allen and B. F. Taylor, J. Chem. Soc., Dalton Trans., 1982, 51–54.
5070 | Dalton Trans., 2009, 5068–5070
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The Royal Society of Chemistry 2009
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