An intermolecular C-C coupling reaction of iridium complexes

Article abstract of DOI:10.1039/c0nj00158a

Novel imidazo[1,5-b]pyridazine-substituted (pyridyl-methyl)amines were synthesized via the nucleophilic ring transformation of oxadiazolium halides and (aminomethyl)pyridines, followed by a cyclocondensation reaction with 1,3-diketones. After deprotonatio

Full text of DOI:10.1039/c0nj00158a

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www.rsc.org/njc | New Journal of Chemistry
An intermolecular C–C coupling reaction of iridium complexesw
Kathrin Kutlescha,a Torsten Irrgangab and Rhett Kempe*a
Received (in Victoria, Australia) 26th February 2010, Accepted 31st March 2010
DOI: 10.1039/c0nj00158a
Novel imidazo[1,5-b]pyridazine-substituted (pyridyl-methyl)amines were synthesized via the
nucleophilic ring transformation of oxadiazolium halides and (aminomethyl)pyridines, followed
by a cyclocondensation reaction with 1,3-diketones. After deprotonation, these monoanionic
amido-pincer ligands are suitable for the stabilization of mononuclear iridium complexes.
For 2-(pyridyl-methyl)-amine-derived complexes, we observed the formation of dimers via an
intermolecular C–C coupling reaction, whilst the 3-(pyridyl-methyl)amine-derived complex did not
react. We propose that enamine tautomerization plays an important role in the C–C coupling
reaction.
in moderate yields and high purity. The molecular structure of
5a was confirmed by X-ray crystal structure analysis.8
Introduction
Recently, we described a novel ligand system for the stabilization
of early and late transition metal complexes—imidazopyridazine-
substituted bisamido ligands (Scheme 1).1 Since salt metathesis
reactions with group 9 metals (Ir, Rh) gave only dinuclear
amido complexes with trans binding modes, we were interested
in developing an amido-pincer type of ligand2 that allows for
the synthesis of mononuclear complexes (Scheme 1).
The lithiation of 5a at ꢀ78 1C using one equiv. of
n-butyllithium and the addition of 0.5 equiv. of [IrCl(cod)]2
(cod = 1,5-cyclooctadiene), afforded 6a as a dark green
crystalline material in moderate yield (Scheme 3).
An X-ray crystal structure analysis9 of 6a was performed to
determine the molecular structure (Scheme 3). The monoanionic
tridentate ligand coordinates the iridium atom via the
amido N atom (N4) and N1, forming a five-membered chelate.
Since the Ir1–N4 bond (2.050 A) is significantly shorter than
the Ir1–N1 bond (2.143 A), we propose that the anionic charge
of the ligand is localized on the amido N atom. The standard
deviation of the imidazopyridazine plane is 0.010 A. The
deviation of the Namido atom out of this plane is 0.043 A
and for Ir it is 0.054 A. The 2-pyridyl-methyl moiety is bent
out of the imidazopyridazine plane (N4–C15–C16 116.61) and
coordination by the pyridine nitrogen does not occur. The
NMR spectra of 6a show a single signal set of deprotonated 5a
and a double-coordinated cyclooctadiene ligand.
Our approach towards these novel amido-pincer ligands is
based on classical bench-top chemistry, realizing a large
variety of substitution patterns. Aryl amines are substantially
synthesized via palladium-catalyzed aryl amination, which is
highly efficient for the formation of C–N bonds but often
employs rather expensive catalysts.3
Herein, we report the synthesis of imidazo-[1,5-b]pyridazine-
substituted (pyridyl-methyl)amines 5 and their application as
monoanionic ligands for the stabilization of iridium complexes
6. For 6a and 6b, we observed an unusual intermolecular C–C
coupling reaction, giving rise to dinuclear complexes 7.
While compound 6a is stable as a solid, in solution we
observed the formation of orange-red crystalline material 7a
(Scheme 4) after a few weeks at room temperature. We were
able to synthesize 7a in moderate yields by the reaction of 5a
with 0.5 equiv. of [IrOCH3(cod)]2.10 The resulting green solution
was heated at 50 1C for 2 weeks and the precipitated red
crystalline material isolated (30%). An X-ray crystal structure
analysis11 of 7a (Fig. 1) revealed that intermolecular C–C
bond formation between the 2-pyridyl-methyl substituents of
two amido ligands had occurred. The two imidazopyridazine
Results and discussion
2-Amino-5-methyl-1,3,4-oxadiazolium halides4 1a and 1b
(Scheme 2) react with a large variety of N-nucleophiles,
such as primary and secondary amines, to yield 2-amino-
substituted 1-acetyl-amino-imidazoles via a nucleophilic ring
transformation.5,6 Thus, the reaction with (aminomethyl)-
pyridines affords N-{4-alkyl/aryl-2-[(pyridin-2/3-ylmethyl)-
amino]-imidazo-1-yl}-acetamides 2a–c. Deacetylation by
refluxing 2 in EtOH/HCl, followed by neutralization, gives
rise to 4a–c (Scheme 2). It is known that 1-amino-4-aryl-
imidazoles7 react with 1,3-diketones to yield imidazo-
[1,5-b]pyridazines.6 Analogously, 4 can be converted into
imidazo[1,5-b]-pyridazine-substituted (pyridyl-methyl)amines
5a–c (Scheme 2) via a cyclo-condensation with acetylacetone
a Lehrstuhl fur Anorganische Chemie 2, Universitat Bayreuth,
¨
¨
Bayreuth, Germany. E-mail: kempe@uni.bayreuth.de;
Fax: +49 (0) 921-55-2157; Tel: +49 (0) 921-55-2541
b AIKAA-Chemicals GmbH, Kammereigasse 11, Bayreuth, Germany
Scheme 1 Imidazo[1,5-b]pyridazine-substituted bisamido ligands and
amido-pincer ligands (R1–3 = aryl or alkyl substituents; Y, X = C
or N).
¨
w CCDC reference numbers 729909–729912. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/c0nj00158a
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Scheme 4 Evolution of C–C coupled dimers 7a and 7b; the newly
formed C–C bond is highlighted by a dashed line.
(Ir2–N7), 2.084 (Ir2–N6), 2.013 (Ir1–N2) and 2.088 (Ir1–N1) A
indicate a rather localized bonding mode. No solution
NMR data could be obtained for 7a, since it is insoluble in
common solvents. MAS-NMR data are in accordance with the
signals expected for the C–C-coupled deprotonated ligand
and cod.
Scheme
2 Ring transformation with (aminomethyl)pyridines
[R = C6H5, Y = N, X = C (1a–5a); R = t-butyl, Y = N, X = C
(1b–5b); R = C6H5, Y = C, X = N (1c–5c)].
Due to the insolubility of 7a, we were interested in synthe-
sizing a more soluble derivative, namely t-butyl-substituted 7b.
When we tried to synthesize 6b via salt metathesis from
lithiated 5b and [IrCl(cod)]2 using the same protocol as for
6a, we observed that C–C coupling took place more rapidly;
thus, we chose an alcohol elimination reaction. The addition
of 0.5 equiv. of [IrOCH3(cod)]2 to a solution of 5b in THF
gave rise to a dark green material 6b in quantitative yield
(Scheme 3). The NMR spectra show a single signal set of
signals for deprotonated 5b and the signals for a double-
coordinated cyclooctadiene. The C–C coupling product, 7b,
was isolated in moderate yield (28%) using the same protocol
as for 7a (Scheme 4). An X-ray crystal structure analysis12 of
7b was performed to determine its molecular structure (Fig. 1).
The bond length of the new C–C bond (C14–C15) is 1.597 A.
Due to the bulky t-butyl substituents, the dihedral angle
between these planes is extended to 24.841 (2.241 in 7a). This
also has an effect on the deviation of the Namido atom out of
the imidazopyridazine plane (0.252 A for N2 and 0.055 A for
N7). The iridium is coordinated by the Namido and the Npyridine
via a five-membered chelate, resulting in N–Ir–N angles of
78.99 (N7–Ir2–N6) and 79.09 (N2–Ir1–N1)1. Since the
Ir–Namido bond lengths of 1.984 A (N7–Ir2) and 1.991 A
(N2–Ir1) are similar to the Ir–Npyridine bond lengths (2.090 A
(N6–Ir2); 2.085 A (N1–Ir1)), the bonding mode is localized.
The NMR spectra of 7b show a single signal set of signals for
the deprotonated ligand and the two double-coordinated
cyclooctadiene molecules. The new CH group, which was
formed due to the C–C coupling, is characterized as a doublet
(1H NMR) at 5.75 ppm with a coupling constant of 4.7 Hz.
Regarding C–C coupling reactions with pyridines, the reactivity
of the carbon atom can arise from the enamine tautomer. This
is reinforced by the fact that pyridines (or unsubstituted
aromatics), which are unable to tautomerize into enamines,
do not participate in the reactions.13
Scheme 3 Synthesis of iridium complexes 6a–c [R = C6H5, Y = N,
X = C (5a–6a); R = t-butyl, Y = N, X = C (5b–6b); R = C6H5, Y = C,
X = N (5c–6c)] and molecular structure of 6a. Selected bond lengths
[A] and angles [1]: Ir1–N1 2.143(3), Ir1–N4 2.05(3), C1–N2 1.360(4),
C1–N3 1.341(5), C1–N4 1.351(5), N1–N2 1.393(4); N1–Ir1–N4
80.61(11), Ir1–N1–N2 106.87(19), C1–N2–N1 121.5(3).
planes are orientated nearly parallel (dihedral angle 2.241) to
each other. The deviation of the Namido atom out of this plane
(0.085 A for N7 and 0.113 A for N2) is larger than in 6a, which
is due to the altered coordination mode. In contrast to 6a, the
iridium in 7a is coordinated by the Namido atom and the
Npyridine via a five-membered chelate, leading to smaller
N–Ir–N angles than in 6a of 78.71 (N7–Ir2–N6) and 79.51
(N2–Ir1–N1), respectively. The Ir–N bond lengths of 2.019
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Scheme 5 The proposed mechanism based on tautomerization into
an enamine and iridium-mediated hydride transfer.
Regarding the mechanism, double C–H activation followed
by an intermolecular dehydrogenative C–C coupling reaction
of the two iridium complexes 6a and 6b cannot be ruled out
completely. The addition of a radical scavenger doesn’t inhibit
the formation of dimer 7b and doesn’t decrease the rate
of dimer formation significantly. Thus, radical-based C–C
coupling reactions are not very likely.
The reaction does not proceed completely, yielding only
19% of 7b in 24 h and about 35% in 8 d.
The closest reactivity pattern we could find is the coupling
reaction of zinc complexes of N-substituted (2-pyridyl-methyl)-
amines via oxidative pathways due to addition of white
phosphorous or dimethylzinc by Westerhausen et al. Since
no radicals were observed by ESR, they propose that the
reaction is strongly based on the redox potential of the metal,
and that the driving force of the reaction is the regeneration of
aromaticity after metalation of the methylene group and
charge migration to the pyridine nitrogen.14
Conclusions
In conclusion, imidazo[1,5-b]pyridazine-substituted (pyridyl-
methyl)amines can be synthesized via the nucleophilic
ring transformation of oxadiazolium halides 1 with 2- or
3-(aminomethyl)pyridine, followed by deacetylation and
cyclo-condensation with 1,3-diketones, in moderate yields
and high purity. The deprotonated amines can act as amido
ligands, binding transition metals as five-membered chelates
via the amido N-atom and N-1 of the imidazopyridazine.
An unusual intermolecular C–C coupling reaction for
2-(aminomethyl)pyridine derived complexes 6a and 6b takes
place in solution, giving rise to dinuclear complexes 7. We have
proposed a mechanism based on enamine tautomerization,
and intermolecular attack accompanied by iridium-mediated
activation and hydride transfer, thereby evolving molecular
hydrogen.
Fig. 1 The molecular structures of 7a and 7b; selected bond lengths
[A] and angles [1]: 7a (the asymmetric unit contained two independent
molecules of 7a, one molecule is omitted for clarity): Ir1–N1 2.088(8),
Ir1–N2 2.013 (8), Ir2–N6 2.084(8), Ir2–N7 2.019(8), C14–C15
1.589(11), C14–N2 1.448(13), C15–N7 1.432(13); N2–Ir–1–N1
79.5(3), N7–Ir2–N6 78.7(3), N2–C14–C15 111.7(8), N7–C15–C14
112.2(7), C14–N2–Ir1 115.6(6), C15–N7–Ir2 117.2(6); 7b: Ir1–N1
2.084(5), Ir2–N6 2.090(4), Ir1–N2 1.992(6), Ir2–N7 1.983(7),
C15–N7 1.447(8), C14–N2 1.468(8), C14–C15 1.597(8); N2–Ir1–N1
79.1(2), N7–Ir2–N6 79.0(2), C14–N2–Ir2 117.4(3), C6–N2–Ir2
117.7(5), N2–C14–C15 112.4(5), N7–C15–C14 112.0(5).
Therefore, we additionally synthesized the 3-(aminomethyl)-
pyridine derivative of ligand 5c; herein, the formation of an
enamine tautomer is not possible. Complex 6c was obtained
via salt metathesis upon deprotonation with nBuLi. Since the
formation of a C–C coupling product could not be detected via
NMR for 6c, we propose a coupling mechanism based on the
formation of the enamine tautomer, followed by an inter-
molecular attack of the carbon atom next to the pyridine
moiety (Scheme 5). The altered coordination mode in 7 cannot
be realized in ligand 5c, which might additionally hinder the
C–C coupling reaction.
Experimental section
General procedures
Syntheses of the starting materials and ligands were performed
under standard conditions. Complex syntheses were conducted
in an oven (95 1C) and in vacuum dried glassware under an
inert atmosphere of dry argon 5.0 via standard Schlenk or
glove box techniques. NMR spectra were recorded on a
Bruker ARX 250/300 (250 or 300 MHz) or a Varian Inova
300/400 (300/400 MHz) NMR spectrometer. Chemical shifts
are reported in ppm from tetramethylsilane, with the solvent
The iridium is thought to mediate the reaction via activation
of the enamine and hydride transfer, thereby generating
molecular hydrogen. Hydrogen evolution could be detected
via NMR studies; a small singlet appeared at 4.21 ppm
([d8]THF).
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resonance resulting from incomplete deuteration as the inter-
nal standard. Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
br = broad, m = multiplet or combinations thereof), integration
and coupling constant. Mass spectra were recorded on a
Finnigan MAT 8500 spectrometer via electron ionization
(70 eV). Melting points were determined in sealed capillaries
by using a Stuart SMP3 melting point apparatus. Elemental
analysis was performed with a Vario Elementar EL III or Leco
CHN-932 elemental analyser.
(C-2, imidazole), 144.64 (C-60 0, pyridine), 143.19 (C-40 0,
pyridine), 135.63 (C-10, C6H5), 129.16, 125.13 (Co,m, C6H5),
128.47 (Cp, C6H5), 127.80 (C-4, imidazole), 124.97, 124.10
(C-30 0, C-50 0, pyridine), 115.97 (C-5, imidazole) and 45.54
(CH2); m/z = 265 (M+), 249, 118, 93, 77 and 36.
4-Phenyl-N2-pyridine-2-ylmethyl-imidazol-1,2-diamine semi-
hydrate (4a). 2.12 g (5.66 mmol) of 3a was dissolved in water
(10 mL) and 1 N NaOH was added until a weak basic reaction
(pH 8) occurred. The white precipitate was washed with water
and recrystallized from water–ethanol (1 : 4 ratio) yielding 4a
(1.55 g, 100%); mp 152 1C (decomposition). Found: C, 65.7;
H, 5.9; N, 25.5. Calc. for C15H16N5O0.5: C, 65.6; H, 5.7; N,
25.2%. dH (400.13 MHz, CDCl3, 298 K, TMS) 8.72–8.70 (m,
1H, H-60 0, pyridine), 7.94–7.23 (m, 8H, C6H5/pyridine), 7.32
(s, 1H, H-5, imidazole), 6.36–6.33 (t, 1H, NH–CH2, J = 6.2),
5.83 (s, 2H, NH2) and 4.77–4.76 (d, 2H, CH2, J = 6.2); dC
(100.63 MHz, CDCl3, 298 K, TMS) 159.80 (C-20 0, pyridine),
150.01 (C-2, imidazole), 149.01 (C-60 0, pyridine), 136.86 (C-40 0,
pyridine), 135.67 (C-10, C6H5), 132.79 (C-4, imidazole), 128.2,
123.87 (Co,m, C6H5), 125.52 (Cp, C6H5), 122.31, 121.67 (C-30 0,
C-50 0, pyridine), 113.83 (C-5, imidazole) and 48.14 (CH2).
Reagents
Non-halogenated solvents were distilled from sodium
benzophenone ketyl and halogenated solvents from P2O5.
Deuterated solvents were obtained from Cambridge Isotope
Laboratories and were de-gassed, dried and distilled prior to
use. All chemicals were purchased from commercial vendors
and used without further purification.
N-{4-Phenyl-2-[(pyridin-2-ylmethyl)-amino]imidazo-1-yl}-
acetamide monohydrate (2a). 2.00 g (6.71 mmol) 2-amino-5-
methyl-3-phenacyl-1,3,4-oxadiazoliumbromide and 1.37 mL
(1.45 g; 13.43 mmol) 2-(aminomethyl)pyridine were stirred
for 1 min on a hot plate (250 1C). Then, the reaction mixture
was allowed to cool to room temperature. Water (20 mL)
was added and colourless crystals formed after several
hours. After recrystallization from ethanol–water (1 : 1
ratio) N-{4-phenyl-2-[(pyridin-2-yl-methyl)amino]imidazo-
1-yl}acetamide monohydrate (2a) (1.95 g, 89%) was
obtained; mp 180 1C (decomposition). Found: C, 62.3; H,
5.7; N, 21.5. Calc. for C17H7N5O2: C, 62.8; H, 5.9; N,
21.5%. dH (400.13 MHz, [d6]DMSO, 298 K, TMS) 10.94
(s, 1H, NH, acetylamino), 8.58–8.56 (m, 1H, pyridine),
7.80–7.15 (m, 8H, C6H5/pyridine), 7.23 (s, 1H, H-5,
(2,4-Dimethyl-5-phenyl-imidazo[1,5-b]pyridazin-7-yl)pyridin-
2-ylmethyl-amine (5a). To a suspension of 1.10 g (4.01 mmol)
of 4a in 7 mL glacial acetic acid 0.40 g (0.41 mL; 4.01 mmol)
acetylacetone was added. The reaction mixture was refluxed
for 2 h; afterwards, the solvent was evaporated and 20 mL of
water was added. After a few days, orange needles were
obtained. Recrystallization from water–ethanol (1 : 2 ratio)
yielded 5a (0.55 g, 42%); mp 110 1C. Found: C, 73.2; H, 5.8;
N, 21.4. Calc. for C20H19N5: C, 72.9; H, 5.8; N, 21.3%. dH
(400.13 MHz, CDCl3, 298 K, TMS) 8.51–8.50 (d, 1H, H-60 0,
pyridine), 7.57–7.06 (m, 8H, C6H5/pyridine), 5.82–5.81 (d, 1H,
H-3, imidazopyridazine, 4J
= 1.2), 5.76–5.73 (t, 1H,
imidazole), 6.77–6.74 (t, 1H, NH–CH2,
J = 6.1),
NH–CH2, J = 5.8), 4.84–4.82 (d, 2H, CH2–NH, J = 5.8),
2.23 (s, 3H, C(2)–CH3) and 2.08–2.07 (d, 3H, C(4)–CH3,
4J = 1.2); dC (100.61 MHz, CDCl3, 298 K, TMS) 158.59
(C-20 0, pyridine), 152.00 (C-7, imidazopyridazine), 149.52
(C-60 0, pyridine), 143.68 (C-2, imidazopyridazine), 139.30
(C-4, imidazopyridazine), 136.94 (C-40 0, pyridine), 136.44
(C-10, C6H5), 130.70, 128.24 (Co,m, C6H5), 128.91 (C-4a,
imidazopyridazine), 127.38 (Cp, C6H5), 122.55, 122.50 (C-30 0,
C-50 0, pyridine), 118.18 (C-5, imidazopyridazine), 112.01 (C-3,
imidazopyridazine), 48.14 (CH2), 21.85 (C(2)–CH3) and 19.86
(C(4)–CH3).
4.66–4.65 (d, 2H, CH2–NH, J = 6.1) and 2.08 (s, 3H,
CH3); dC (100.63 MHz, [d6]DMSO, 298 K, TMS) 169.53
(CQO), 160.34 (C-20 0, pyridine), 149.43 (C-2, imidazole),
148.97 (C-60 0, pyridine), 136.82 (C-40 0, pyridine), 135.12
(C-10, C6H5), 133.85 (C-4, imidazole), 128.57, 124.08
(Co,m, C6H5), 125.99 (Cp, C6H5), 122.23 (C-30 0, pyridine),
121.28 (C-50 0, pyridine), 112.60 (C-5, imidazole), 47.87
(CH2) and 21.16 (CH3); m/z = 307 (M+), 249, 118, 93
and 43.
4-Phenyl-N2-pyridine-2-ylmethyl-imidazol-1,2-diamine dihydro-
chloride dihydrate (3a). To a suspension of 3.00 g (9.22 mmol)
of 2a in 20 mL ethanol was added 2 mL of concentrated HCl.
The reaction mixture was refluxed for 1 h, during which a
precipitate was formed after 30 min. After cooling to room
temperature and evaporation of the solvent, the colourless
product was recrystallized from water–ethanol (1 : 4 ratio) to
yield 3a (2.17 g, 63%). Found: C, 48.1; H, 5.8; N, 18.7. Calc.
for C15H21N5O2Cl2: C, 48.1; H, 5.7; N, 18.7%. dH (400.13
MHz, [d6]DMSO, 298 K, TMS) 8.91–8.89 (m, 1H, H-600,
pyridine), 8.71–8.68 (t, 1H, NH–CH2, J = 5.9), 8.39–7.48
(m, 8H, C6H5/pyridine), 7.79 (s, 1H, H-5, imidazole) and
5.34–5.32 (d, 2H, CH2–NH, J = 5.9); dC (100.63 MHz,
[d6]DMSO, 298 K, TMS) 154.85 (C-200, pyridine), 147.51
The ligands’ synthesis was simplified for 5b and 5c by
sparing the characterization and purification of the
intermediates.
(5-tert-Butyl-2,4-dimethyl-imidazo[1,5-b]pyridazin-7-yl)pyridin-
2-ylmethyl-amine hydrate (5b). 4.00 g (14.38 mmol) 2-amino-3-
(3,3-dimethyl-2-oxo-butyl)-5-methyl-1,3,4-oxadiazolium bromide
and 3.23 mL (31.68 mmol; 3.42 g) 2-(aminomethyl)pyridine
were stirred for 1 min on a hot plate (250 1C) and allowed to
cool to room temperature. Next, the reaction mixture was
extracted with CHCl3 (20 mL) to separate the insoluble
2-(aminomethyl)pyridine hydrobromide by-product. After
filtration, the solvent was evaporated, the residue dissolved
in 20 mL of ethanol, and 1.49 mL (1.44 g; 14.38 mmol)
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acetylacetone and 2 mL concentrated HCl were added. After
refluxing the orange solution for 2 h, the solvent was
evaporated, and the red-orange product dissolved in water
(20 mL) and filtrated. Then, 1 N NaOH was added to the
filtrate until a weak basic reaction was observed and no more
product precipitated. Afterwards, red viscid product 5b (1.1 g,
25%) was dried in vacuo. Found: C, 65.75; H, 7.2; N 21.85.
Calc. for C18H25N5O: C, 65.9; H, 7.7; N 21.4%. dH (250.13
MHz, CDCl3, 298 K, TMS) 8.47–8.44 (d, 1H, H-60 0, pyridine,
J = 4.9), 7.51–7.47 (t, 1H, H-500, pyridine, J = 7.7), 7.36–7.33
(d, 1H, H-30 0, pyridine, J = 7.8), 7.07–7.04 (m, 1H,
H-40 0, pyridine), 5.71–5.70 (d, 1H, H-3, imidazopyridazine,
4J = 1.1), 5.43–5.38 (t, 1H, NH–CH2, J = 6.2), 4.75–4.72
(d, 2H, CH2–NH, J = 6.2 Hz), 2.43–2.32 (d, 3H, C(4)–CH3,
4J = 1.1), 2.13 (s, 3H, C(2)–CH3) and 1.32 (s, 9H, C(CH3)3);
Preparation of 6a. To an orange solution of 0.55 g
(1.66 mmol) (2,4-dimethyl-5-phenyl-imidazo[1,5-b]pyridazin-
7-yl)pyridine-2-ylmethyl-amine (5a) in THF (20 mL) were
added carefully (at ꢀ78 1C) 1.0 mL (1.66 mmol) n-butyllithium
(1.6 M in n-hexane). The purple reaction mixture was stirred at
ꢀ78 1C for another 30 min and was then allowed to warm to
room temperature. At room temperature, an orange solution
of 0.56 g (0.83 mmol) chloro-1,5-cyclooctadiene iridium(I)
dimer in THF (10 mL) was added. The green solution was
stirred for 16 h. Next, the solvent was evaporated and the
residue dissolved in toluene, filtrated and washed with ether.
At ꢀ30 1C, a dark green crystalline product 6a (0.45 g, 44%)
was obtained from the combined filtrates. Found: C, 53.2; H,
5.1; N, 10.7. Calc. for C28H30IrN5: C, 53.5; H, 4.8, N, 11.1%.
dH (300.13 MHz, CD2Cl2, 298 K, TMS) 8.03–8.02 (d, 2H,
H-60 0, pyridine, J = 5.5), 7.72–7.67 (t, 1H, pyridine, J = 7.7),
7.50–7.45 (t, 2H, C6H5, J = 8.0), 7.35–7.21 (m, 3H, C6H5/
pyridine), 7.12–7.10 (m, 2H, C6H5), 5.93, 5.90 (2 s, 1H, H-3,
imidazopyridazine), 5.24, 5.22 (2s, 2H, CH2–NH), 3.97 (br s,
2H, CH cod), 3.17 (br s, 2H, CH cod), 2.26 (s, 3H,
C(2/4)–CH3), 2.13 (s, 3H, C(4/2)–CH3), 2.25–2.09 (br m, 4H,
CH2 cod) and 1.60–1.57 (br d, 4H, CH2 cod); dC (75.48 MHz,
CD2Cl2, 298 K, TMS) 146.60, 139.35, 137.22, 136.91, 134.38,
130.57, 130.42, 128.75 (Co,m, C6H5), 128.04, 127.06, 122.22,
121.07, 118.64 (C-5, imidazopyridazine), 112.20, 111.93 (C-3,
imidazopyridazine), 66.83 (4 ꢂ CH, cod), 55.14 (CH2–N),
31.77 (4 ꢂ CH2 cod), 21.70, 21.31 (C(2/4)–CH3) and 19.84
(C(4/2)–CH3).
d
C (62.89 MHz, CDCl3, 298 K, TMS) 158.91 (C-20 0, pyridine),
150.45 (C-7, imidazopyridazine), 148.88 (C-60 0, pyridine),
140.63 (C-2, imidazopyridazine), 138.16 (C-4, imidazopyridazine),
137.81 (C-4a, imidazopyridazine), 110.34 (C-3, imidazo-
pyridazine), 48.31 (CH2), 33.00 (CH–(CH3)3), 32.24
(CH–(CH3)3), 23.09 (C(4)–CH3) and 20.95 (C(2)–CH3); m/z
= 309 (M+), 294, 218, 203, 93, 65 and 41.
(2,4-Dimethyl-5-phenyl-imidazo[1,5-b]pyridazin-7-yl)-pyridin-
3-ylmethyl-amine (5c). 2.50 g (8.39 mmol) 2-amino-5-methyl-3-
phenacyl-1,3,4-oxadiazolium bromide and 1.88 mL (2.0 g;
18.46 mmol) 3-(aminomethyl)pyridine were stirred for 1 min
on a hot plate (250 1C) and allowed to cool to room temperature.
Next, water was added and the white precipitate recrystallized
from water–ethanol (1 : 2). 3.00 g (9.76 mmol) N-{4-phenyl-2-
[(pyridin-3-ylmethyl)amino]imidazo-1-yl}acetamide was dissolved
in 10 mL of ethanol and 2–3 mL concentrated HCl was added.
The solution was refluxed for 1 h and afterwards the solvent
evaporated. The residue was dissolved in water and 1 N
NaOH was added until a weak basic reaction occurred and
no more product precipitated. The white product was filtered
and dried. To a suspension of 1.48 g (5.58 mmol) 4-phenyl-N2-
Preparation of 6b. To an orange solution of 0.20 g (0.65
mmol) (5-tert-butyl-2,4-dimethyl-imidazo[1,5-b]pyridazin-7-
yl)pyridin-2-ylmethyl-amine (5b) in THF (5 mL) was added
a yellow solution of 0.21 g (0.32 mmol) 1,5-cyclooctadiene-
methoxy iridium(I) dimer in THF (10 mL). The dark green
solution was immediately concentrated to dryness in vacuo,
yielding 6b (0.39 g, 100%). Found: C, 51.5; H, 6.1; N, 11.2.
Calc. for C26H34IrN5: C, 51.3; H, 5.6; N, 11.5%. dH (250.13
MHz, [d8]THF, 298 K, TMS) 8.15–8.13 (d, 1H, H-60 0,
pyridine, J = 4.7), 7.59–7.53 (t, 1H, H-50 0, pyridine, J =
7.4), 7.39–7.36 (d, 1H, H-300, pyridine, J = 7.8), 7.07–7.02
(t, 1H, H-40 0, pyridine, J = 8.3), 5.76 (s, 1H, H-3, imidazo-
pyridazine), 5.08 (s, 2H, CH2–N), 4.12 (br s, 2H, CH cod),
3.55–3.49 (m, 2H, CH cod), 2.49 (d, 3H, C(2)–CH3), 2.22 (s,
3H C(4)–CH3), 2.03 (b s, 4H, CH2 cod), 1.59 (b s, 4H, CH2
cod) and 1.24 (s, 9H, (CH3)3); dC (75.39 MHz, C6D6, 298 K,
TMS) 147.42, 139.91, 139.00, 136.33, 121.71, 121.18, 118.53
(C-5, imidazopyridazine), 110.04 (C-3, imidazopyridazine),
68.15 (CH2–N), 57.04, 53.35, 52.33 (CH cod), 32.46, 31.95,
26.17 (CH2 cod), 23.22 (C(2)–CH3) and 21.00 (C(4)–CH3).
Although different solvents, such as C6D6, [d8]THF and
CD2Cl2, were tested and up to 10 000 scans performed, not
all of the quaternary C atoms could be detected.
pyridine-3-ylmethyl-imidazol-1,2-diamine in
7 mL glacial
acetic acid was added 578 mL (5.58 mmol) acetylacetone and
the reaction mixture refluxed for 2 h. Afterwards, the solvent
was evaporated and 20 mL of water was added. After a few
days, orange needles of 5c (0.66 g, 24%) were obtained.
Found; C, 72.7; H, 6.05; N, 21.7. Calc. for C20H19N5: C,
72.9; H, 5.8; N, 21.3%. dH (250.13 MHz, CDCl3 298 K) 8.65
(s, 1H, C-200, pyridine), 8.46–8.45 (d, 1H, C-60 0, pyridine,
J = 3.8), 7.75–7.62 (d, 1H, C-40 0, pyridine, J = 7.8),
7.52–7.40 (d, 2H, Co C6H5, J = 7.0), 7.36–7.30 (m, 4 H,
C-500, pyridine/C6H5), 5.86 (s, 1H, H3, imidazopyridazine),
4.98–4.94 (t, 1H, NH, J = 5.8), 5.21–5.16 (d, 2H, CH2, J =
5.8), 2.23 (s, 3H, c(2)–CH3) and 2.12 (s, 3H, C(4)–CH3); dC
(75.39 MHz, CDCl3, 298 K) 151.22 (C-7, imidazopyridazine),
148.87 (C-20 0, pyridine), 148.11 (C-600, pyridine), 142.34 (C-2,
imidazopyridazine), 138.53 (C-4, imidazopyridazine), 135.33
(C-300, pyridine), 135.20 (C-50 0, pyridine), 134.70 (C-10, C6H5),
129.72, 127.36 (Co,m, C6H5), 128.04 (C-4a, imidazopyridazine),
126.55 (Cp, C6H5), 122.92 (C-40 0, pyridine), 117.27 (C-5,
imidazopyridazine), 111.15 (C-3, imidazopyridazine), 44.20
(CH2), 20.86 (C(2)–CH3) and 18.94 (C(4)–CH3).
Preparation of 6c. To an orange solution of 0.56 g
(1.70 mmol) (2,4-dimethyl-5-phenyl-imidazo[1,5-b]pyridazin-
7-yl)pyridin-3-ylmethyl-amine (5c) in THF (15 mL) was added
carefully (at ꢀ78 1C) 1.06 mL (1.70 mmol) n-butyllithium
(1.6 M in n-hexane). The purple reaction mixture was stirred at
ꢀ78 1C for another 30 min and then allowed to warm to room
ꢁc
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temperature. At room temperature, an orange solution of
0.57 g (0.85 mmol) chloro-1,5-cyclooctadiene iridium(I) dimer
in THF (10 mL) was added. The green solution was stirred for
16 h, the solvent evaporated, and the residue dissolved in
toluene, filtrated and washed with ether. At ꢀ30 1C, from the
combined filtrates in toluene, the dark green crystalline
product 6c (0.33 g, 32%) was obtained. Found: C, 53.25; H,
5.3; N, 10.7. Calc. for C28H30IrN5: C, 53.5; H, 4.8; N 11.1%.
166.67, 148.12, 144.90, 136.04, 127.78 (C-7, C-2, C-4, C-4a,
imidazopyridazine; C-100, pyridine), 143.56, 134.74, 126.71,
121.46 (CH, pyridine), 116.59 (C-5, imidazopyridazine),
109.85 (C-3, imidazopyridazine), 74.88 (CH), 65.56,
67.96, 54.03, 52.08 (CH cod), 33.42, 33.11, 30.17, 28.82
(CH2 cod), 32.71 (C(CH)3), 31.98 (C(CH)3), 22.40 and 20.55
(C(2/4)–CH3).
d
H (250.13 MHz, CDCl3, 298 K, TMS) 8.61 (s, 1H, pyridine),
Acknowledgements
8.41–8.39 (d, 1H, pyridine, J = 4.3), 7.69–7.66 (d, 1H,
pyridine, J = 5.5), 7.51–7.12 (m, 6H, pyridine/phenyl), 5.75
(s, 1H, H-3, imidazopyridazine), 4.95 (s, 2H, CH2), 4.41 (br s,
2H, CH cod), 4.08 (br s, 2H, CH cod), 2.48 (s, 3H, C(2)–CH3),
2.28 (s, 3H, C(4)–CH3), 2.33–2.16 (m, 4H, CH2 cod) and
1.82–1.61 (m, 4 H, CH2 cod); dC (62.89 MHz, CDCl3,
298 K, TMS) 160.41 (C-7, imidazopyridazine), 156.86 (C-300,
pyridine), 148.78, 147.52 (C-200, C-60 0, pyridine), 141.90 (C-2,
imidazopyridazine), 138.11 (C-40 0, pyridine), 136.15 (C-10,
C6H5), 134.54 (C-500, pyridine), 130.02, 127.94 (Co,m, C6H5),
128.98 (C-4a, imidazopyridazine), 127.52 (Cp, C6H5), 119.20
(C-5, imidazopyridazine), 110.17 (C-3, imidazopyridazine),
62.86, 53.12 (CH cod), 46.03 (CH2), 31.65, 30.40 (CH2 cod),
20.29 (C(2)–CH3) and 19.03 (C(4)–CH3).
We thank Wolfgang Saak, Germund Glatz and Tobias Bauer
for their support in the X-ray laboratories.
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solution of 0.21 g (0.65 mmol) (2,4-dimethyl-5-phenyl-imidazo-
[1,5-b]pyridazin-7-yl)pyridin-2-ylmethyl-amine (5a) in THF
(10 mL) was added 0.21 g (0.32 mmol) 1,5-cyclooctadiene-
methoxy iridium(I) dimer. The solution immediately changed
its colour to dark green. The solution was heated at 50 1C for
several days, while its colour changed to brown and red
crystals formed. The crystalline material, 7a (0.12 g, 30%),
was filtered and washed three times with THF. Found: C, 53.2;
H, 4.8; N, 10.8. Calc. for C56H58Ir2N10: C, 53.6; H, 4.7; N,
11.2%). 7a is insoluble in all common solvents, such as
methanol, isopropanol, CH2Cl2, THF, toluene, benzene and
DMSO; due to this, no solution NMR data is available.) MAS
solid state 13C NMR: dC 166.31, 149.78, 148.29, 143.20,
137.02, 128.51, 122.91 (imidazopyridazine, pyridine, C6H5),
118.08 (C-5, imidazopyridazine), 110.73 (C-3, imidazopyridazine),
75.37 (CH), 67.64, 63.00, 54.69 (CH cod), 32.85, 26.28 (CH2
cod) and 21.84 (C(2/4)–CH3).
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Preparation of 7b. Into a pressure tube containing an orange
solution of 0.20 g (0.65 mmol) (5-tert-butyl-2,4-dimethyl-
imidazo[1,5-b]pyridazin-7-yl)pyridin-2-ylmethyl-amine (5b) in
hexane (10 mL) was added 0.21 g (0.32 mmol) 1,5-cyclo-
octadiene-methoxy iridium(I) dimer. The solution immediately
changed its colour to dark green. After several weeks, a red
crystalline material, 7b (0.11 g, 28%), was obtained. Found: C,
51.2; H, 5.7; N, 11.2. Calc. for C52H66Ir2N10: C, 51.3; H, 5.5;
N, 11.5%. dH (250.13 MHz, [d8]THF, 298 K, TMS) 9.38–9.35
(d, 1H, pyridine, J = 7.8), 8.14–8.11 (t, 1H, pyridine, J = 8.3),
7.59–7.57 (d, 1H, pyridine, J = 5.6), 7.19–7.14 (t, 1H,
pyridine, J = 7.1), 5.75–5.74 (m, 2H, CH–N, H-3, imidazo-
pyridazine), 2.69 (m, 2H, CH cod), 2.37–2.33 (m, 2H, CH
cod), 2.59 (s, 3H, C(2/4)–CH3), 1.79 (s, 3H, C(4/2)–CH3),
1.99–1.86 (m, 4H, CH2 cod), 1.49–1.28 (m, 4H, CH2 cod) and
1.53 (s, 9H, C(CH3)3); dC (62.89 MHz, [d8]THF, 298 K, TMS)
8 X-Ray crystal structure analysis of 5a. STOE-IDPS II equipped
with an Oxford Cryostream low-temperature unit, graphite mono-
chromatized Mo-Ka radiation, l = 0.71069 A. Structure solution
and refinements were accomplished using SHELXL-97
(G. M. Sheldrick, SHELXL-97, Program for Crystal Structure
Analysis Release 97-2, University of Gottingen, Germany, 1997),
¨
WinGX (L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837–838)
and SIR97 (A. Altomare, M. C. Burla, M. Camalli,
G. L. Cascarano, C. Giacovazzo, A. Guagliardi, A. G.
G. Moliterni, G. Polidori and R. Spagna, J. Appl. Crystallogr.,
1999, 32, 115–119). Crystal size 0.40 ꢂ 0.19 ꢂ 0.07 mm, symmetry
space group P21/c, monoclinic, a = 7.2845(5), b = 13.4530(8),
c = 17.5656(14) A, b = 92.241(9)1, V = 1720.1(2) A3, Z = 4,
rcalc
= 1.272 g , 3256 reflections, 1989 independent
cmꢀ3
reflections, R = 0.0391 [I 4 2s(I)], wR2 (all data) = 0.0879, 226
parameters. CCDC 729909w.
9 X-Ray crystal structure analysis of 6a. Crystal size 0.38 ꢂ 0.10 ꢂ
ꢀ
0.05 mm, symmetry space group P1, triclinic, a = 7.9017(4), b =
8.9335(6), c = 16.8930(10) A, b = 80.191(6)1, V = 1174.39(12) A3,
ꢁc
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Z = 2, rcalc = 1.778 g cmꢀ3, 14134 reflections, 4192 independent
reflections, R = 0.0200 [I 4 2s(I)], wR2 (all data) = 0.0487,
620 parameters. CCDC 729910w.
13 B. Blank and R. Kempe, J. Am. Chem. Soc., 2010, 132, 924–925;
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11 X-Ray crystal structure analysis of 7a. Crystal size 0.26 ꢂ 0.20 ꢂ
Eur. J. Inorg. Chem., 2008, 1067–1077; M. Westerhausen,
A. N. Kneifel and P. Mayer, Z. Anorg. Allg. Chem., 2006, 632,
634–638; M. Westerhausen, T. Bollwein, P. Mayer and
H. Piotrowski, Z. Anorg. Allg. Chem., 2002, 628, 1425–1432;
0.20 mm, symmetry space group P21/n, monoclinic,
a =
15.5840(7), b = 22.6799(8), c = 26.5520(12) A, b = 98.245(3)1,
V = 9287.6(7) A3, Z = 8, rcalc = 1.796 g cmꢀ3, 17540 reflections,
9598 independent reflections, R = 0.0501 [I 4 2s(I)], wR2 (all
data) = 0.0924, 1233 parameters. CCDC 729911w.
M.
Westerhausen,
T.
Bollwein,
K.
S. Schneiderbauer, M. Vogt and H. Noth, Organometallics, 2002,
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¨
21, 906–911; M. Westerhausen, T. Bollwein, N. Makropoulos,
12 X-Ray crystal structure analysis of 7b. Crystal size 0.64 ꢂ 0.53 ꢂ
0.19 mm, symmetry space group P21/n, monoclinic,
a
=
S. Schneiderbauer, M. Suter, H. Noth, P. Mayer, H. Piotrowski,
¨
K. Polborn and A. Pfitzner, Eur. J. Inorg. Chem., 2002, 389–404;
14.2110(6), b = 23.5720(10), c = 14.6060(6) A, b = 103.436(3)1,
V = 4758.8(3) A3, Z = 4, rcalc = 1.697 g cmꢀ3, 8987 reflections,
6493 independent reflections, R = 0.0361 [I 4 2s(I)], wR2 (all
data) = 0.0764, 587 parameters. CCDC 729912w.
M. Westerhausen, T. Bollwein, N. Makropoulos, T. M. Rotter,
T. Habereder, M. Suter and H. Noth, Eur. J. Inorg. Chem., 2001,
851–857.
¨
ꢁc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010
1960 | New J. Chem., 2010, 34, 1954–1960