Synthesis, characterization, and applications of novel di-2-pyridyl imine ligands

Article abstract of DOI:10.1016/j.inoche.2009.10.013

Two novel di-2-pyridyl imines, 2,4,6-trimethyl-(di-2-pyridylmethylene)aniline (1) and 2,6-di-isopropyl-(di-2-pyridylmethylene)aniline (2), were prepared through condensation reactions between 2,2′-dipyridyl ketone and 2,4,6-trimethylaniline and 2,6-di-isopropylaniline. They reacted readily with bis(benzonitrile)dichloropalladium(II) to afford palladium imine complexes. The crystal structure of the palladium complex (3) bearing the 2,4,6-trimethyl-(di-2-pyridylmethylene)aniline ligand revealed coordination of a pyridyl group and an imine group to the metal center. The novel ligands were successfully employed in the Suzuki coupling reaction of p-bromoanisole and phenylboronic acid.

Full text of DOI:10.1016/j.inoche.2009.10.013

Inorganic Chemistry Communications 13 (2010) 54–57
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Synthesis, characterization, and applications of novel di-2-pyridyl imine ligands
Jake Yorke a, Catlin Dent a, Andreas Decken b, Aibing Xia a,
*
a Department of Chemistry, Mount Saint Vincent University, Halifax, Nova Scotia, Canada B3M 2J6
b Department of Chemistry, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3
a r t i c l e i n f o
a b s t r a c t
Article history:
Two novel di-2-pyridyl imines, 2,4,6-trimethyl-(di-2-pyridylmethylene)aniline (1) and 2,6-di-isopropyl-
(di-2-pyridylmethylene)aniline (2), were prepared through condensation reactions between 2,20-dipyri-
dyl ketone and 2,4,6-trimethylaniline and 2,6-di-isopropylaniline. They reacted readily with bis(benzoni-
trile)dichloropalladium(II) to afford palladium imine complexes. The crystal structure of the palladium
complex (3) bearing the 2,4,6-trimethyl-(di-2-pyridylmethylene)aniline ligand revealed coordination of
a pyridyl group and an imine group to the metal center. The novel ligands were successfully employed
in the Suzuki coupling reaction of p-bromoanisole and phenylboronic acid.
Received 18 June 2009
Accepted 25 October 2009
Available online 28 October 2009
Keywords:
Di-2-pyridyl imines
Phosphine ligands
Palladium complexes
The Suzuki reaction
Ó 2009 Elsevier B.V. All rights reserved.
Palladium-catalyzed Suzuki cross-coupling reaction of an aryl
halide and an arylboronic acid is a powerful and versatile tool in
organic synthesis [1–4]. The most commonly used ancillary ligands
for the palladium catalyst are bulky tertiary phosphines. However,
some phosphines are air-sensitive and require air-free handling in
order to avoid ligand oxidation. Recently, alternative ligands such
as N-heterocyclic carbenes (NHCs) [5–8], as well as ligand free
systems [9–12], have been employed in the coupling reactions.
Nitrogen ligands, such as amines [13], diazabutadienes [14], and
salicylaldimines [15], have attracted considerable interest due to
their stability and excellent activity. Unsymmetrical iminopyridine
ligands containing one imino group and one pyridyl group have
been extensively investigated and successfully employed recently
in catalytic transformations including olefin polymerization and
oligomerization [16–20], alkyne dimerization and cyclotrimeriza-
tion [21–24], hydroboration and aromatic C–H borylation [25,26],
hydrogenation of unsaturated hydrocarbons [27], and pyridine for-
mation [28], and have been evaluated as potential anti-cancer
agents [29]. In comparison, the chemistry of iminopyridine ligands
containing two pyridyl groups is relatively unexplored [30–32].
Here we wish to report the synthesis, characterization, and cata-
lytic application of air-stable di-2-pyridyl imine ligands, which
contain two pyridyl groups and one imino (C@N) group.
(2) [34] (Scheme 1). Both compounds could be handled and stored
in air for months without decomposition. The 1H NMR spectra of 1
and 2 in CDCl3 showed eight distinct signals for the eight pyridyl
hydrogen atoms, indicating the two pyridyl groups are non-equiv-
alent after the introduction of the bulky trimethyl and di-isopropyl
aryl imine groups. In 2, the two methyl groups in the isopropyl
moiety are also non-equivalent (1.15 and 1.97 ppm, respectively).
Both compounds showed strong absorption at 1630 cmꢀ1 for
m(C@N) in the FTIR spectra.
Addition of solution of
a
1 in CH2Cl2 to a solution of
(PhCN)2PdCl2 in CH2Cl2 afforded palladium complex 3 as an orange
solid [35]. Its 1H NMR spectrum showed downfield shift of up to
1.0 ppm in one pyridyl group and 0.3 ppm in the methyl groups
of the mesityl moiety, while the chemical shifts of the other pyridyl
group were almost unchanged. This suggested ligand coordination
to Pd through the imino group and only one pyridyl group in the
complex. Its IR spectrum showed red-shift of m(C@N) from 1630
to 1608 cmꢀ1 upon coordination to the metal center. Slow evapo-
ration of a solution of 3 in acetone afforded orange crystals suitable
for X-ray diffraction analysis [36]. The crystal structure confirmed
the coordination mode of the ligand (Fig. 1). In the solid state, the
complex exists as a monomer, with Pd(II) ion adopting a distorted
square-planar geometry. The Pd–N bond distances of 2.022(2) and
2.026(2) Å are similar to the reported Pd–N values in related com-
plexes [15,19,37]. The reaction of 2 and (PhCN)2PdCl2 in CH2Cl2
afforded a yellow precipitate. Its 1H NMR spectrum contained mul-
tiple isopropyl signals, indicating the existence of a mixture. This
suggested multiple coordination modes of the ligand, whereas it
can bond through one pyridyl group and the imine group or both
pyridyl groups. We were unable to grow suitable crystals for X-
ray analysis from the mixture.
Reactions of 2,20-dipyridyl ketone and 2,6-di-isopropylaniline
or 2,4,6-trimethylaniline in toluene afforded the corresponding
di-2-pyridyl imines, 2,4,6-trimethyl-(di-2-pyridylmethylene)ani-
line (1) [33] and 2,6-di-isopropyl-(di-2-pyridylmethylene)aniline
* Corresponding author. Tel.: +1 902 457 6543.
E-mail address: aibing.xia@msvu.ca (A. Xia).
1387-7003/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2009.10.013

J. Yorke et al. / Inorganic Chemistry Communications 13 (2010) 54–57
55
Toluene
+
RNH2
reflux
N
N
N
N
O
N
R
R = 2,4,6-Me3C6H2 (1), 93%;
2,6-iPr2C6H3 (2), 74%
(PhCN)2PdCl2
CH2Cl2
N
N
N
Pd
Cl
Cl
3, 98%
Scheme 1.
We investigated the Suzuki cross-coupling reaction between
phenylboronic acid and p-bromoanisole, which is a deactivated
and fairly inert halide [38]. Compound 2 was used for the screening
of solvent and base for the reaction. The conditions and results are
listed in Table 1. We examined a few common solvents and bases
for the Suzuki reaction [1–3], and found that the combination of
dioxane as the solvent and Cs2CO3 as the base afforded the best re-
sult (entry 6).
Next we evaluated the efficiency of the novel di-2-pyridyl imi-
nes and related bidentate nitrogen ligands under similar condi-
tions. Palladium acetate and imine 1, as well as palladium
complex 3 bearing the imine, gave excellent yields (entries 7 and
8). Compound 2 was found to be more efficient than 1 as a ligand.
This may be attributed to more steric hindrance and better donat-
ing ability in 2 which are beneficial factors in the catalytic systems
[1–4]. We compared the efficiency of related iminopyridines con-
taining only one pyridyl group, 2,4,6-trimethyl-(2-pyridylmethyl-
ene)aniline (4) and 2,6-di-isopropyl-(2-pyridylmethylene)aniline
(5) [37]. In our studies, the monopyridyl imines gave good but low-
er yields than the novel dipyridyl imines (entries 9 and 10). The
improved efficiency of the dipyridyl imines over the monopyridyl
imines is likely due to the extra basic pyridyl group which provides
additional nitrogen functionality that is beneficial to catalytic
properties [39,40]. Furthermore, good yields (entries 11 and 12)
were obtained when the reactions were carried out in air using pal-
ladium acetate and the dipyridyl imine ligands, suggesting the li-
gand systems are rather robust in air.
In conclusion, we have prepared and characterized two novel
di-2-pyridyl imines and a palladium complex bearing one of the
imines. They were successfully employed in the Suzuki reaction
of p-bromoanisole and phenylboronic acid. They demonstrated
better catalytic efficiency than related monopyridyl imines. Both
imines were easy to prepare and stable in air, making them poten-
tial alternative ligands to the commonly used yet air-sensitive
phosphine ligands.
Appendix A. Supplementary material
Fig. 1. Molecular Structure of 3 with ellipsoids drawn at the 30% probability level.
Hydrogen atoms were omitted for clarity. Selected bond lengths (Å) and angles (°):
Pd(1)–N(1) 2.022(2); Pd(1)–N(3) 2.026(2); Pd(1)–Cl(1) 2.2702(7); Pd(1)–Cl(2)
2.2931(6); N(1)–Pd(1)–N(3) 80.48(8); N(1)–Pd(1)–Cl(1) 173.22(6); N(3)–Pd(1)–
Cl(1) 94.62(6); N(1)–Pd(1)–Cl(2) 94.89(6); N(3)–Pd(1)–Cl(2) 171.52(6); Cl(1)–
Pd(1)–Cl(2) 90.55(3).
CCDC 736562 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Center via http://www.ccdc.ca-
m.ac.uk/data_request/cif.

56
J. Yorke et al. / Inorganic Chemistry Communications 13 (2010) 54–57
Table 1
Suzuki reactions using imine ligands.a
Ligand, Pd(OAc)2
MeO
Br +
PhB(OH)2
MeO
Ph
Base, solvent, reflux
Entry
Solvent
Base
Ligand
Yield (%)b
1
2
3
4
5
6
7
8
Toluene
Toluene
Toluene
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
K3PO4
2
2
2
2
2
2
1
3
4
5
1
2
70
67
76
82
84
99
88
88c
78
81
77d
89d
K2CO3
Cs2CO3
K3PO4
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
9
10
11
12
a
1 mmol, p-bromoanisole; 1.5 mmol, phenylboronic acid; 2 mol%, Pd(OAc)2 and 2 mol%, ligand or 2 mol%, palladium imine complex 3; 1.5 mmol, Cs2CO3; 10 mL, dioxane,
reflux.
b
c
GC yield based on p-bromoanisole.
Palladium complex 3 was used instead of palladium acetate and a ligand.
Experiments carried out in air.
d
[28] K. Kase, A. Goswami, K. Ohtaki, E. Tanabe, N. Saino, S. Okamoto, Org. Lett. 9
(2007) 931.
Acknowledgements
[29] M.L. Conrad, J.E. Enman, S.J. Scales, H. Zhang, C.M. Vogels, M.T. Saleh, A.
Decken, S.A. Westcott, Inorg. Chim. Acta 358 (2005) 63.
[30] Y. Oso, D. Kanatsuki, S. Saito, T. Nogami, T. Ishida, Chem. Lett. 37 (2008) 760.
[31] P. Barbaro, C. Bianchini, G. Giambastiani, I.G. Rios, A. Meli, W. Oberhauser, A.M.
Segarra, L. Sorace, A. Toti, Organometallics 26 (2007) 4639.
We thank Natural Science and Engineering Research Council of
Canada (NSERC) and Canada Foundation for Innovation (CFI) for
financial support.
[32] N. Chatani, M. Tobisu, T. Asaumi, S. Murai, Synthesis 7 (2000) 925.
[33] Preparation of 1: A 40 mL solution of di-2-pyridyl ketone (3.68 g, 20.0 mmol)
and trimethylanaline (2.70 g, 20.0 mmol) in toluene was refluxed in the
presence of Amberlyst-15 (0.020 g) in a 100 mL Schlenk flask. The flask was
equipped with a Dean-Stark trap to remove water. After three days the
mixture was cooled to room temperature and filtered. The volatiles were
removed under a reduced pressure to afford orange solids. Recrystallization
from ethanol afforded yellow crystalline solids (5.59 g, 93%). M.p. 121–123 °C.
Anal. Calc. for C20H19N3: C, 79.70; H, 6.35; N, 13.94. Found: C, 79.99; H, 6.59; N,
13.97. 1H (CDCl3, 250.14 MHz, ppm): d 8.61 (m, 2H, overlapping Hpyridine),
8.29 (d, 1H, J = 7.5 Hz, Hpyridine), 7.85 (dt, 1H, J = 7.5, 2.5 Hz, Hpyridine), 7.52
(dt, 1H, J = 7.5, 2.5 Hz, Hpyridine), 7.37 (ddd, 1H, J = 7.5, 5.0, 2.5 Hz, Hpyridine),
7.17 (ddd, 1H, J = 7.5, 5.0, 2.5 Hz, Hpyridine), 7.02 (t, 1H, J = 7.5 Hz, Hpyridine),
6.70 (s, 2H, C6H2), 2.19 (s, 3H, CH3), 2.05 (s, 6H, CH3). GC/MS (EI): 301 (M+). IR
(KBr, cmꢀ1): 2963 (s), 2923 (s), 2865 (s), 1630 (s), 1582 (s), 1568 (m), 1478 (s),
1469 (s), 1321 (s), 1138 (s), 934 (s), 854 (m), 804 (m), 748 (s), 661 (s).
References
[1] B. Martin, S.L. Buchwald, Acc. Chem. Res. 41 (2008) 1461.
[2] H. Doucet, Eur. J. Org. Chem. 12 (2008) 2013.
[3] A. Suzuki, Chem. Commun. 38 (2005) 4759.
[4] J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, UK, 2004. p. 288.
[5] S. Würtz, F. Glorius, Acc. Chem. Res. 41 (2008) 1523.
[6] G.A. Grasa, M.S. Viciu, J. Huang, C. Zhang, M. Trudell, S.P. Nolan,
Organometallics 21 (2002) 2866.
[7] C.W.K. Gstöttmayr, V.P.W. Böhm, E. Herdtweck, M. Grosche, W.A. Hermann,
Angew. Chem., Int. Ed. 41 (2002) 1363.
[8] W.A. Hermann, M. Elison, J. Fischer, C. Kocher, G.R.J. Artus, Angew. Chem., Int.
Ed. 34 (1995) 2371.
[34] Preparation of 2: In
a
manner similar to the preparation of 1, di-
as
[9] D. Saha, K. Chattopadhyay, B.C. Ranu, Tetrahedron Lett. 50 (2009) 1003.
[10] W. Han, C. Liu, Z. Jin, Adv. Synth. Catal. 350 (2008) 501.
[11] Y. Kitamura, S. Sato, T. Udzu, A. Tsutsui, T. Maegawa, Y. Monguchi, H. Sajiki,
Chem. Commun. 47 (2007) 5069.
[12] L. Liu, Y. Zhang, B. Xin, J. Org. Chem. 71 (2006) 3994.
[13] B. Tao, D.W. Boykin, J. Org. Chem. 69 (2004) 4330.
[14] G.A. Grasa, A.C. Hiller, S.P. Nolan, Org. Lett. 3 (2001) 1077.
[15] B.J. Tardiff, J.C. Smith, S.J. Duffy, C.M. Vogels, S.A. Westcott, Can. J. Chem. 85
(2007) 392.
[16] Z. Huang, K. Song, F. Liu, J. Long, H. Hu, H. Gao, Q. Wu, J. Polym. Sci. Part A:
Polym. Chem. 46 (2008) 1618.
[17] G.J.P. Britovsek, S.P.D. Baugh, O. Hoarau, V.C. Gibson, D.F. Wass, A.J.P. White,
D.J. Williams, Inorg. Chim. Acta 345 (2003) 279.
[18] V.C. Gibson, R.K. O’Reilly, D.F. Wass, A.J.P. White, D.J. Williams, Dalton Trans.
14 (2003) 2824.
[19] T.V. Laine, U. Piironen, K. Lappalainen, M. Klinga, E. Aitola, M. Leskelä, J.
Organomet. Chem. 606 (2000) 112.
[20] A. Koppl, H.G. Alt, J. Mol. Catal. A: Chem. 54 (2000) 45.
[21] A. Goswami, T. Ito, N. Saino, K. Kase, C. Matsuno, S. Okamoto, Chem. Commun.
4 (2009) 439.
[22] A. Goswami, T. Ito, S. Okamoto, Adv. Synth. Catal. 349 (2007) 2368.
[23] N. Saino, F. Amemiya, E. Tanabe, K. Kase, S. Okamoto, Org. Lett. 8 (2006)
1439.
isopropylaniline and di-2-pyridyl ketone were condensed to afford
2
yellow solids (5.05 g, 74%). M.p. 143–145 °C. Anal. Calc. for C23H25N3: C, 80.43;
H, 7.34; N, 12.23. Found: C, 80.22; H, 7.63; N, 12.35. 1H (CDCl3, 250.14 MHz,
ppm): d 8.62 (t, 2H, J = 7.5 Hz, Hpyridine), 8.31 (d, 1H, J = 7.5 Hz, Hpyridine),
7.87 (t, 1H, J = 7.5 Hz, Hpyridine), 7.48 (t, 1H, J = 7.5 Hz, Hpyridine), 7.38 (t, 1H,
J = 7.5 Hz, Hpyridine), 7.15 (t, 1H, J = 7.5 Hz, Hpyridine), 7.00 (m, 4H,
overlapping Hpyridine and C6H3), 2.97 (sept, 2H, J = 7.5 Hz, CH(CH3)2), 1.15
(d, 6H, J = 7.5 Hz, CH(CH3)2), 0.97 (d, 6H, J = 7.5 Hz, CH(CH3)2). GC/MS (EI): 343
(M+). IR (KBr, cmꢀ1): 3047 (m), 2999 (m), 2964 (s), 2958 (m), 2915 (m), 1630
(s), 151 (s), 1567 (s), 1463 (s), 1433 (s), 1360 (m), 1320 (s), 994 (s), 971 (m),
783 (s), 760 (m), 745 (s), 735 (s), 685 (m).
[35] Preparation of 3: Compound 1 (0.602 g, 2.00 mmol) was dissolved in 5 mL
CH2Cl2 and added to a solution of (PhCN)2PdCl2 (0.767 g, 2.00 mmol) in 5 mL
CH2Cl2. The mixture was stirred overnight and filtered to afford orange solids
(0.940 g, 98%). M.p. 354 °C (dec.). Anal. Calc. for C20H19Cl2N3Pd: C, 50.18; H,
4.00; N, 8.78. Found: C, 49.96; H, 4.03; N, 8.70. 1H (CDCl3, 250.14 MHz, ppm): d
9.62 (d, 1H, J = 7.5 Hz, Hpyridine), 8.69 (d, 1H, J = 7.5 Hz, Hpyridine), 8.05 (dt,
1H, J = 7.5, 2.5 Hz, Hpyridine), 7.76 (dt, 1H, J = 7.5, 2.5 Hz, Hpyridine), 7.63 (dt,
1H, J = 7.5, 2.5 Hz, Hpyridine), 7.47 (d, 1H, J = 7.5 Hz, Hpyridine), 7.38 (t, 1H,
J = 7.5 Hz, Hpyridine), 7.06 (d, 1H, J = 7.5 Hz, Hpyridine), 6.71 (s, 2H, C6H2),
2.33 (s, 6H, CH3), 2.16 (s, 3H, CH3). IR (KBr, cmꢀ1): 3070 (m), 2970 (m), 2914
(m), 1608 (w), 1588 (s), 1578 (s), 1474 (s), 1462 (m), 1374 (w), 1345 (m), 1143
(m), 996 (m), 855 (m), 750 (s), 633 (m), 612 (m).
[24] N. Saino, D. Kogure, K. Kase, S. Okamoto, J. Organomet. Chem. 691 (2006)
3129.
[36] The crystal data for 3 were collected on a Simens SMART diffractometer with
graphite monochromated Mo K
C20H19Cl2N3Pd, M = 478.68, monoclinic, P2(1)/c, Z = 4, T = 198 K, a =
15.566(3) Å, b = 7.177(1) Å, c = 18.225(3) Å, = 90°, b = 105.353(2)°. V =
1963.4(6) Å3, Dcalc = 1.619 Mg/m3, = 1.226 mmꢀ1, F(0 0 0) = 960. Refinement
method was full-matrix least squares on F2 using SHELXTL-97 program, 6928
a radiation (k = 0.71073 Å). Crystal data:
[25] D.A. Kanas, S.J. Geier, C.M. Vogels, A. Decken, S.A. Westcott, Inorg. Chem. 47
(2008) 8727.
[26] T. Tagata, M. Nishida, Adv. Synth. Catal. 346 (2004) 1655.
[27] M.W. van Laren, M.A. Duin, C. Klerk, M. Naglia, D. Rogolino, P. Pelagatti, A.
Bacchi, C. Pelizzi, C.J. Elsevier, Organometallics 21 (2002) 1546.
a = c
l

J. Yorke et al. / Inorganic Chemistry Communications 13 (2010) 54–57
57
observed reflections, 6928 independent reflections with R1 = 0.0322,
wR2 = 0.0881.
[37] T.V. Laine, M. Klinga, M. Leskelä, Eur. J. Inorg. Chem. 6 (1999) 959.
[38] General procedures for the Suzuki reaction: a reaction tube was charged with
the aryl halide, phenylboronic acid, Pd(OAc)2, a ligand, and a base in 5 mL of
solvent under argon and heated to 100 °C for 18 h. The mixture was then
reduced pressure. The organic products were extracted with ether and
analyzed on an Agilent 6890 GC-FID instrument. The GC yield was based on
p-bromoanisole and calibrated relative to a standard containing authentic
samples of p-bromoanisole and p-methoxybiphenyl.
[39] I.G. Jung, S.U. Son, K.H. Park, K.-C. Chung, J.W. Lee, Y.K. Chung, Organometallics
22 (2003) 4715.
cooled to room temperature, filtered, and removed off volatiles under
a
[40] T. Schareina, R. Kempe, Angew. Chem., Int. Ed. 41 (2002) 1521.