Bridged 1-methylbisimidazoles as building blocks for mixed donor bi- and tridentate chelating ligands

Article abstract of DOI:10.1055/s-2001-12351

Novel bi- and tridentate imidazole chelate ligands consisting of varying donor sets were prepared using an efficient one- or two-step procedure. Keto- and methylene-bridged bisimidazoles 1, 2 served as versatile starting materials for the introduction of additional donor groups, thus allowing the facile variation of donor sets within a bisimidazole ligand framework.

Full text of DOI:10.1055/s-2001-12351

626
PAPER
Bridged 1-Methylbisimidazoles as Building Blocks for Mixed Donor Bi- and
Tridentate Chelating Ligands
Nathalie Braussaud, Thomas Rüther,*a Kingsley J. Cavell,*b Brian W. Skelton,c Allan H. Whitec
a Department of Chemistry, University of Tasmania, GPO Box 252 75, Hobart, Tasmania 7001, Australia
Fax+61(3)62262858; E-mail: thomas.ruether@unitas.edu.au
b Department of Chemistry, Cardiff University, P. O. Box 912, Cardiff, CF1 3TB, United Kingdom
Fax +44(0)1222874083; E-mail: cavellkj@cf.ac.uk
c Department of Chemistry, University of Western Australia, Nedlands, WA 6907, Australia
Fax +61(8)93801005
Received 31 August 2000; revised 3 January 2001
Abstract: Novel bi- and tridentate imidazole chelate ligands consist-
ing of varying donor sets were prepared using an efficient one- or
two-step procedure. Keto- and methylene-bridged bisimidazoles 1,
2 served as versatile starting materials for the introduction of addi-
tional donor groups, thus allowing the facile variation of donor sets
within a bisimidazole ligand framework.
Keywords: heterocycles, imidazoles, ligands, phosphines
Industrial requirements for high performance catalysts to
produce important classes of compounds have stimulated
the development of a wide range of ligand systems, most
of them coordinating through phosphorus. More recently
the synthesis of well tailored chelating ligands containing
nitrogen donors or a mixed set of donor atoms has re-
ceived considerable interest in homogeneous catalysis
and coordination chemistry.1–3
As part of our ongoing interest in functionalised ligand
systems,4 we have chosen the bridged bisimidazoles 1 and
2 (Scheme 1) as building blocks for the synthesis of novel
bi- and tridentate mixed donor ligands (N^P; N^N’;
N^O^N; N^P^N).
Chelate ligands derived from imidazole have found wide-
spread application in model systems to mimic active sites
of metalloenzymes.5–11 A number of rhodium,12,13 rutheni-
um,14,15 palladium,16–18 and platinum19 complexes bearing
polyimidazole ligands have also been reported, some of
them found to be catalytically active. In the present report,
we give a detailed description of the syntheses of novel
chelate ligands with mixed donor atoms derived from im-
Scheme 1
idazole derivatives.
product from aqueous solution was replaced by extracting
the product with CH2Cl2 or CHCl3 from the resulting
crude oil of the reaction. After removal of the solvent, the
pure product can be obtained by recrystallisation from ac-
etone. After the initial crystallisation stage, on allowing
the mother liquor to stand and slowly evaporate in air over
one week further product precipitates from the oily solu-
tion.
A general synthesis of the new ligands is outlined in
Scheme 1. Bis(1-methylimidazole-2-yl)ketone 1a13,14,16,20
and the methylene bridged bis(1-methylimidazoles)
2a13,14,16 and 2c12 were prepared by using modifications of
previously described procedures which in the case of 2a
gave improved yields. For the ketone 1a, we could show
that prolonged exposure to water leads to decomposition.
In a test experiment, 1a was allowed to stand for one week
in CH2Cl2/H2O after which only 1-methylimidazole was
recovered, indicating decomposition via hydrolysis and
final loss of CO2. Hence, liquid liquid extraction of the
Since the steric requirements of a given ligand system
may strongly influence the reactivity of its transition met-
al complexes, we became interested in synthesising a de-
rivative of the ketone 1a containing sterically demanding
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PAPER Bridged 1-Methylbisimidazoles as Building Blocks for Mixed Donor Bi- and Tridentate Chelating Ligands
627
substituents on the ring system. As a starting compound, cedure (2 3 times the amount of KOH and n-Bu4NCl;
we chose 1-isopropyl-4-tert-butylimidazole which has re- prolonged reaction time; GC monitoring) reported by
cently been reported by Sorell et al.7,21 The fact that the Stelzer et al.23 (Scheme 2). In some cases the formation of
tert-butyl group is linked to the imidazole ring in position Ph2P(O)CH3 (isolated and characterised by NMR and
4 was crucial to our choice since it guarantees that steric MS) as a by-product was observed, probably resulting
bulk will be in proximity of the coordination sphere in from initial hydrolysis of Ph2PCH2Cl and subsequent re-
metal complexes synthesised from the final chelate arrangement.
ligand. Due to its lower acidity, the starting imidazole was
added to a THF solution of BuLi and warming to room
temperature was necessary during the initial metallation
reaction. However, after reaction with diethylcarbonate
five compounds including unreacted starting material
were detected (TLC) in the reaction mixture, from which
1b could be isolated in 15.5% yield.
Scheme 2
The synthesis of bis(1-methylimidazole)methane (2a) has
previously been reported.12,14,16 It is formed by heating a
mixture of 1a, hydrazine hydrate and sodium hydroxide in
a reaction bomb to 140 150 °C for 4 hours. We found that
careful control of the temperature is crucial to the relative
success of the reaction. Replacing the reaction bomb with
a round bottomed flask equipped with a reflux condenser
resulted in the formation of a yellow solid at 60 °C and the
reaction mixture becoming clear and colourless when the
temperature reached 116 °C. The reaction was kept at
120 °C for 1 hour after which time the temperature was
raised to 150 °C for another 3 hours. In experiments in
which the temperature was instantly raised to 150 °C, the
solution became dark brown and yields were low. These
observations indicate that the initial hydrazone formation
has to be completed prior to the final reduction step at el-
evated temperature. Extraction with and recrystallisation
of the crude product from acetone14 leads to a consider-
able loss of product possibly due to aldol condensation be-
tween 2a and acetone. A pure product was obtained in
83% yield by recrystallisation from THF. Under the same
conditions the benzimimidazole ketone 1c22 could be re-
duced to the methylene bridged derivative 2c12 in 63%
yield.
Coupling between Ph2PCH2Cl and metallated 2a was car-
ried out in the same manner as that described for 3 al-
though the less electrophilic Ph2PCH2Cl required longer
reaction times at room temperature. Compound 4 was iso-
lated as a pale air sensitive viscous oil in 85% yield. The
methine hydrogen displays a pseudo quartet (4.95 ppm;
3JH-H = 8.2 Hz) in the 1H NMR spectrum due to coupling
with the methylene protons and phosphorus. The respec-
tive bridging carbon appears as a doublet at 31.5 ppm
(3JC-P = 12.9 Hz) in the 13C NMR spectrum.
The structurally related N^O^N ligand 5 was prepared by
reacting metallated 2a with 1-bromopinacolone and iso-
lated as colourless crystals containing 1.5 moles H2O in
67% yield. The methine hydrogen appears as a triplet at
4.75 ppm (3JC-H = 6.9 Hz) in the 1H NMR spectrum. The
keto group gives rise to a singlet at 213.9 ppm in the 13C
NMR spectrum. A by-product 6 was obtained in this reac-
tion (approx. 6%), which was identified by 1H NMR spec-
troscopy (methine hydrogen: 5.81 ppm; N-CH3: 3.64
ppm) and x-ray diffraction as the C-C coupling product
between two bis(1-methylimidazole-2-yl)methane units.
Single crystals of 5 and 6 suitable for x-ray diffraction
were obtained by slow solvent evaporation from an ether/
petrol spirit solution and a chloroform solution respective-
ly.
Metallation of 2a at the bridging methylene group with
BuLi at low temperature provides the nucleophile for fur-
ther coupling reactions. The respective electrophiles were
then added in situ. Canty et al. prepared a tripodal nitrogen
donor ligand in a similar manner using 2-bromopyridine
as an electrophile and phenyl lithium as metallating
agent.17 Slow addition of Ph2PCl to metallated 2a in THF
at 80 °C gave the phosphinated bis(1-methylimidazole)
3 as a white air sensitive solid in 85% yield. The doublet
of the methine proton was observed at 5.37 ppm (2JP-
H = 2.4 Hz), while the bridging carbon appears as a dou-
blet at 39.47 ppm (2JC-P = 17.7 Hz), in the 13C NMR spec-
trum. Compared to 2a both signals are shifted to lower
field by 1.13 ppm (1H NMR) and 12.25 ppm (13C NMR),
respectively.
5. C15H22N4O 1.5H2O, M = 301.4. Monoclinic, space
group P21/c (C52h, No.14), a = 7.927(2), b = 26.269(6),
c = 8.453(2) Å, = 105.391(3)°, V = 1690(1) Å3. Dc
3
(Z = 4) = 1.179 g cm . 16421 CCD area-detector absorp-
tion-corrected reflections (specimen: 0.45 0.40 0.20;
T
min,max = 0.67, 0.91) reduced to 4259 unique
(Rint = 0.035), 3380 ( = No) with F > 4 (F) considered 'ob-
served' and used in the full matrix least squares refinement
(C, N, O displacement parameters anisotropic; (x, y, z,
Uiso)H (parent molecule) refined), T ca 153 K; Mo-K ra-
diation, = 0.71073 Å, 2 max = 58°. A string of difference
map residues was modelled as water molecule oxygen
fragments, without associated hydrogens, site occupan-
2
1
cies 0.5. Final R, Rw (weights: ( (F) + 0.0004 F2) ; re-
According to the synthetic approach outlined in Scheme
1, the synthesis of the N^P^N ligand 4 requires an electro-
phile in which the leaving group and the diphenyl phos-
phine group are linked to the same carbon. We prepared
the electrophile Ph2PCH2Cl according to a modified pro-
3
finement on |F|): 0.061, 0.070. | max| = 0.44(2) e Å .
6. (Similar procedure) C18H22N8 2CDCl3, M = 591.2.
Monoclinic, space group P21/n (No. 14, variant),
a = 8.766(1),
b = 8.356(1),
c = 17.962(2)
Å,
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628
N. Braussaud et al.
PAPER
Table Chelate Parameters for {(Tetrahedral C)(im)2} Metal Chelates
e
f
MetalRef.
Cu9
rc
bd
1.998(3), 2.000(2)
2.048(3) 2.071(3)
2.113(5) 2.169(6)
2.139(5), 2.181(5)
2.45(2), 2.50(2)
2.882(4)
87.7(1)
44.9(2)
Rha,12
Fea,11
Ru14
2.78(1)/ 2.76(1)
2.812(8)/ 2.822(7)
2.908(8)
87.6(1)/ 87.1(1)
82.1(2)/ 82.7(2)
84.7(2)
39.4(6)/ 38.36(6)
6.3(3)/ 9.0(3)
20.9(4)
Hb
3.218(2)
81.1(7)
69.14(8)
aThe Rh and Fe complexes have two ligands.
bThis work.
c r = the metal-nitrogen distances (Å).
d b = N…N bite (Å).
e
= N-M-N bite angle (°).
= C3N2/C3N2 interplanar dihedral angle (°).
f
= 95.737(2)°, V = 1309.0(5) Å3. Dc (Z = 2) = 1.500 g 176.8(2), 113.8(2)°; the C3N2/C3N2 interplanar dihedral
3
1
cm . µMo = 6.8 cm ; specimen: 0.45 0.35 0.25; angle is 89.85(9)° and N(15)…N(25) 3.766(3)°, a more
T
min,max = 0.76, 0.93. Nt = 12455, N = 3230 (Rint = 0.018), haphazard array, devoid of any approach to intrinsic sym-
2
1
No = 2887; R, Rw (weights: ( (F) + 0.0004 F2) ; refine-
3
ment on |F|): 0.038, 0.048. | max| = 0.76(1) e Å . (x, y, z,
Uiso)H,D refined throughout.
The results of 153 K single crystal X-ray structure deter-
mination* of 5 and 6 are consistent with the above formu-
lation in terms of stoichiometry and connectivity, with
stereochemistries/conformations as shown in Figure 1;
the parent molecules are accompanied by residues in the
lattice modelled as water molecule oxygen fragments for
5, and as CDCL3 molecules of solvation in 6, the latter dis-
playing significant interaction with the parent. One half of
the 6 2CDCl3 array comprises the asymmetric unit of the
latter structure, a crystallographic inversion centre being
located at the centre of the central C-C bond. The solvent
'deuterium' approaches N(15,25) of the parent molecule
symmetrically, contacting them at 2.45(2), 2.50(2) Å. The
dihedral angle between the pair of gem-C3N2 planes is
69.14(8)°; C(1')-C(1)-C(n1)-N(n5) (n = 1,2) are 52.1(2),
51.8(2), cf. C(1')-C(1)-C(n1)-N(n2)
128.8(2),
131.6(2)°, contacts between H(1) on the central carbon
and the two methyl substituents being congenially packed
around van der Waals expectations, with N(15)…N(25)
3.218(2) Å, the symmetry of the aggregate putatively 2/m,
beyond i. Geometries associated with similar {(tetrahe-
dral C)(im)2} arrays as ligands about a metal atom, which
are structurally defined are compared with the present (re-
garding the deuterium as a 'pseudo-metal') in the Table.
While the angles between the pair of nitrogen donor atoms
lies above 80° in all cases, the remaining parameters are
very variable, the ligand seemingly very flexible in re-
sponse to electronic and structural vicissitudes, and, de-
spite the appealing symmetry of the deuterium
environment in the present, the interaction must be fairly
weak.
By contrast, the counterpart array in 5, without co-crystal-
lised CDCl3, is less restrained. Here C(2)-C(1)-C(n1)-
N(n5) are 4.1(3), -64.3(2), and C(2)-C(1)-C(n1)-N(n2)
Figure 1 Projections of individual molecules of 5 and 6, the latter
in association with CDCl3 solvent. 50% ellipsoids are shown for the
non-hydrogen atoms, hydrogen atoms having arbitrary radii of 0.1 Å
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PAPER Bridged 1-Methylbisimidazoles as Building Blocks for Mixed Donor Bi- and Tridentate Chelating Ligands
629
All manipulations were carried out under an atmosphere of dry,
deoxygenated N2 using standard Schlenk techniques, unless other-
wise indicated. All solvents for use in an inert atmosphere were pu-
rified by standard procedures and distilled under N2 immediately
prior to use. Mps were determined with a Gallenkamp apparatus and
are uncorrected. NMR spectra were recorded on a Varian Gemini
200 NMR spectrometer and on a Varian Unity Inova 400 WB NMR
spectrometer. Elemental analysis (Carlo Erba EA 1108), IR (Bruker
IFS-66 FTIR), and MS (Kratos Concept ICQ) were carried out at the
Central Science Laboratory (CSL), University of Tasmania. 1-Bro-
mopinacolon, BuLi, diethylcarbonate, diphenylphosphine chloride,
and 1-methylimidazole were purchased from Aldrich and used as
received. Diphenylphosphine was prepared according to a pub-
lished procedure.25
metry. In both 5 and 6, bond lengths and angles are gener-
ally as expected.
The compounds 1a, c were also converted into the respec-
tive imines 7a, c. Since initial attempts to react 1a with
aniline by using classical methods failed, we employed a
method first reported by Weingarten et al.24 Hence, 1a
was reacted with a slight excess of aniline in the presence
of TiCl4 (Scheme 1). After 72 hours at room temperature,
a mixture of the desired product and 1a was obtained from
which the imine 7a could be separated as yellow crystals
by recrystallisation from acetone/ether in 32% yield. Un-
der the same conditions, the benzimidazole derivative 7c
could be prepared in 28% yield from 1c. Due to the intro-
For new compounds satisfactory microanalyses were obtained: C,
1
duction of the H2N-C6H5 function, the H and 13C NMR H, N 0.4% of that expected, except for 4, which gave C 0.25,
H +0.44, N 0.92%.
spectra display two sets of signals for the inequivalent im-
idazole rings (Figure 2). A full assignment of all signals
was obtained by gCOSY, gHMQC and gHMBC experi-
ments.
X-ray data: Crystallographic data for the structures reported in this
paper have been deposited with the Cambridge Crystallographic
Data Centre, nos. CCDC-152 806 (5) and 152 807 (6). Copies of the
data can be obtained free of charge on application to The Director,
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax
+441223336033; E-mail: deposit@ccdc.cam.ac.uk).
Bis(1-methylimidazol-2-yl)ketone (1a)
A modification of the method described by Elgafi and coworkers
was used in this work.14 A solution of 1-methylimidazole (10.7 g,
0.13 mol) in dry THF (100 mL) was cooled to 45 °C and n-BuLi
(1.6 M in hexane) (81.2 mL, 0.13 mol) was slowly added. The yel-
low solution was stirred at 45 °C for 30 min and then cooled to
80 °C. Diethylcarbonate (7.7 g, 0.065 mol) was then added drop-
wise. The solution changed colour from pale yellow to purple and
thickened. The reaction mixture was allowed to warm to 20 °C
over 5 h and was then quenched by addition of H2O (10 mL). After
warming to r.t., THF was removed in vacuo and the residue extract-
ed with CH2Cl2 (3 50 mL). The CH2Cl2 layers were pooled, dried
(NaSO4), filtered, and evaporated to give a brown orange oil. The
pure product was obtained as colourless crystals after recrystallisa-
tion from acetone, and from the resulting mother liquor after slow
evaporation in air; yield: 8.4 g (68%); mp 154 155 °C (Lit.14 mp
154 155.5 °C).
1
Figure 2 Assignment of H and 13C NMR signals for 7a (CDCl3)
and 7c (1H: CDCl3, 13C: CD3OD, 50 °C)
In conclusion, the metallation of bis(1-methylimida-
zole)methane (2a) and subsequent reaction with electro-
philes is an effective method for the preparation of novel
chelating ligands containing a bisimidazole backbone.
Various electrophiles carrying donor functions may be
readily introduced, hence providing a convenient synthet-
ic route to ligands with various donor sets within structur-
ally related chelate systems. Since bis(1-methyl-
imidazole)methane (2a) is an important building block for
many of these new ligands it is essential that it be readily
available. Consequently, an improved method for its prep-
aration was developed. Including the previously reported
tris[2-(-methylimidazolyl)]methoxymethane,6 a set of
N^N^N; N^P^N and N^O^N tripodal ligands is available,
thus allowing a study of the effect of varying donor sets
on the properties of co-ordination compounds consisting
of a structurally similar ligand environment. The mixed
donor compounds 1 and 3 can also co-ordinate either in an
N^O, N^P or an N^N fashion. The co-ordination chemis-
try of these ligands is currently under investigation by our
group and will be reported elsewhere.18
1
IR (KBr): = 1632 (C=O) cm .
1H NMR (200 MHz, CDCl3): = 7.23 (s, 1H, Himid), 7.04 (s, 1H,
Himid), 3.94 (s, 3H, NCH3).
13C NMR (200 MHz, CDCl3): = 174.31 (C=O), 143.3 (C=N),
130.8 (Cimid), 127.2 (Cimid), 36.4 (NCH3).
Bis(1-isopropyl-4-tert-butylimidazol-2-yl)ketone (1b)
A solution of 1-isopropy-4-tert-butylimidazole21 (2.1 g, 12.6 mmol)
in THF (10 mL) was slowly added to a solution of n-BuLi (1.6 M in
hexane) (8.1 mL, 13 mmol) in THF (30 mL) at 80 °C. The solution
was stirred at this temperature for 1 h and was then allowed to warm
to r.t. over 1 h. The orange red solution was cooled to 80 °C and
diethylcarbonate (0.75 g, 6.3 mmol) in THF (10 mL) was added
dropwise. The solution was stirred for 3 h at 60 °C to 45 °C, al-
lowed to warm to 5 °C over 15 min, and then quenched with H2O
(10 mL). THF was removed in vacuo and the oily residue extracted
with Et2O (3 30 mL). The pooled Et2O extracts were washed with
brine (2 10 mL), dried (NaSO4), filtered, and concentrated. Cool-
ing of the Et2O solution to 20 °C resulted in precipitation of 1b as
an off-white solid. A second crop could be obtained from the concd
mother liquor. A pure product was obtained after washing with a
small amount of petroleum spirit and drying in a high vacuum;
yield: 0.35 g (15.5%); mp 124 125 °C.
1
IR (KBr): = 1635 (C=O) cm .
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N. Braussaud et al.
PAPER
1H NMR (200 MHz, CDCl3): = 6.99 (s, 1H, Himid), 5.14 [sept, 1H,
13C NMR (200 MHz, CDCl3): = 149.65 (C=N), 142.77, 136.64,
123.24, 122.66, 119.96, 109.8 (Carom), 30.9 (NCH3), 29.2 (CH2).
3
3JH-H = 6.8 Hz, NCH(CH3)2], 1.47 [d, 6H, JH-H = 6.7 Hz,
CH(CH3)2], 1.31 (s, 9H, t-Bu).
MS: m/z (%) = 276 (100) [M+], 261 (21) [M CH3 ], 145 (62)
+
13C NMR (200 MHz, CDCl3): = 176.11 (C=O), 153.52 [Cimid(t-
Bu)], 143.3 (C=N), 115.09 (Cimid), 49.39 [NCH(CH3)2], 32.55
[C(CH3)3], 30.66 [CH3(t-Bu)], 24.39 [CH3(i-Pr)].
[M 1-methylbenzimidazole+], 131 (40) [1-methylbenzimidazole].
Chloromethyl Diphenylphosphine
MS: m/z (%) = 358 (62) [M+], 343 (38) [M CH3 ], 315 (100) [M
+
A solution of KOH (3 g 53.5 mmol) in H2O (2.5 mL) was mixed
with a solution of n-BuNCl4 hydrate (0.5 g 1.8 mmol) in CH2Cl2
(30 mL) and toluene (5 mL). Freshly distilled diphenylphosphine (2
g, 10.7 mmol) dissolved in CH2Cl2 (5 mL) was then added to the
emulsion under vigorous stirring over 2 h. The reaction mixture was
stirred for 14 h at r.t., washed with H2O (3 10 mL), and the organic
layer separated. Evaporation of the solvent and drying in a high vac-
uum gave the pure product as a clear oil. Any Ph2P(O)CH3 that
formed could be separated by addition of H2O (15 mL) to the oil,
extraction of the product into petroleum spirit (3 7 mL), and re-
moval of the solvent in vacuo; yield: 2.4 g (95%).
i-Pr+].
Bis(1-methylimidazol-2-yl)methane (2a); Typical Procedure
Compound 1a (4 g, 21.04 mmol) and ground KOH (4 g, 71.3 mmol)
were placed into a Schlenk flask. Hydrazine hydrate (35 mL,
0.72 mol) was added and the flask immersed into an oil bath. On
heating a yellow solid began to form at 60 °C. The reaction mixture
became clear and almost colourless between 110 °C and 120 °C.
Stirring at 120 °C was continued for 1 h. The temperature was then
raised to 150 °C and stirring was continued for 3 h at this tempera-
ture. Some white solid precipitated at the end of this period. The re-
action mixture was allowed to cool to r.t. during which a white waxy
solid formed. At this point all following operations were carried out
in air; CH2Cl2 (40 mL) was added and the solution transferred to a
separatory funnel. The CH2Cl2 layer was separated and the remain-
ing light brown liquid extracted with CH2Cl2 (2 40 mL). The
pooled CH2Cl2 extracts were washed twice with H2O (2 15 mL)
to remove excess hydrazine hydrate. The combined H2O extracts
were then repeatedly extracted with CH2Cl2 (12 20 mL; crucial to
obtain good yields). The pooled CH2Cl2 extracts were dried
(Na2SO4), filtered, and rotary evaporated to give an off-white solid
(3.37 g, almost pure product by 1H NMR). The product was recrys-
tallised from THF (36 mL), and colourless rhombic crystals separat-
ed on cooling to r.t.. The light yellow THF solution was decanted,
the crystals washed with a few mL of THF and dried under vacuum
(1st crop 2.65 g). A second (0.35 g) and a third crop (0.08 g) were
collected after concentration of the mother liquor and cooling to
20 °C; yield: 3.08 g (83%); mp 154 156 °C (Lit.14 mp 152
154 °C).
1H NMR (200 MHz, CDCl3): = 7.35 7.6 (m, 10H, Harom), 4.08 (d,
2H, 2JH-P = 5.1 Hz, CH2).
13C NMR (200 MHz, CDCl3): = 134.6 (d, 2JC-P = 17.1 Hz, ipso C),
133.5 (d, 3JC-P = 19.1 Hz, ortho C), 129.9 (s, para C), 129.2 (d, 4JC-
P = 11.2 Hz, meta C), 41.3 (d, 3JC-P = 28.4 Hz, CH2).
31P NMR (400 MHz, CDCl3):
= 10.86.
2-[(Diphenylphosphino)(1-methyl-1H-imidazol-2yl)methyl]-1-
methyl-1H-imidazole (3)
A solution of 2a (1 g, 5.7 mmol) in THF (35 mL) was cooled to
80 °C. n-BuLi (1.6 M in hexane; 3.65 mL, 5.8 mmol) was added
slowly. The yellow solution was stirred at 80 °C to 45 °C for 1.5
h and then re-cooled to 80 °C. A solution of diphenylphosphine
chloride (1.25 g, 5.7 mmol) in THF (10 mL) was added dropwise.
A white precipitate formed. The reaction mixture was allowed to
warm to 30 °C and then quenched with degassed H2O (30 mL).
After warming to r.t., the solvent was removed in vacuo and the res-
idue extracted with CH2Cl2 (3 15 mL). The CH2Cl2 layers were
pooled and evaporated to dryness giving the product as a white sol-
id. If partial oxidation of the product occurs, it can be purified by
washing with Et2O (3 5 mL); yield: 1.74 g (85%).
1H NMR (200 MHz, CDCl3): = 7.20 7.35 (m, 10H, Harom), 6.83
(s, 2H, Himid), 6.65 (s, 2H, Himid), 5.37 (d, 1H, 2JH-P = 2.4 Hz, CH),
3.63 (s, 6H, NCH3).
13C NMR (200 MHz, CDCl3): = 144.02 (d, 2JC-P = 11 Hz, C = N),
136.7 (d, 2JC-P = 16.6 Hz, ipso C), 133.64 (d, 3JC-P = 20 Hz, ortho C),
129.49 (s, para C), 128.9 (d, 4JC-P = 6.9 Hz, meta C), 127.6 (s, Cimid),
122.3 (s, Cimid), 39.5 (d, 2JC-P = 17.7 Hz, CH), 34.4 (d, 4JC-P = 7.4 Hz,
NCH3).
1H NMR (200 MHz, CDCl3): = 6.90 (d, 2H, JH-H = 1.58
3
3
Hz, =CH), 6.78 (d, 2H, JH-H = 1.58 Hz, =CH), 4.24 (s, 2H, CH2),
3.66 (s, 6H, NCH3).
13C NMR (200 MHz, CDCl3): = 143.91 (C=N), 127.57 (Cimid),
122.02 (Cimid), 33.69 (NCH3), 27.25 (CH2).
MS: m/z (%) = 176 (100) [M+], 95 (43.5) [1,2-dimethylimidazole +
H+].
Bis(1-methylbenzimidazole-2-yl)methane (2c)
The reaction was carried out as described for 2a: 1c22 (0.35 g,
1.2 mmol), KOH (0.3 g, 4.1 mmol), hydrazine hydrate (2 mL,
41.2 mmol).
31P NMR (400 MHz, CDCl3):
= 12.82 (s).
MS: m/z (%) = 361 (50) [MH+], 176 (100) [2a+].
Observations: the colour of the suspension began to fade above
44 °C and further solid formed between 65 °C and 90 °C; at 110 °C
the reaction mixture became yellow; on cooling to r.t. a light brown
waxy solid formed. Work up: addition of CH2Cl2 (10 mL) to the re-
action mixture at r.t.; after separation of the CH2Cl2 layer the re-
maining light brown liquid was extracted with CH2Cl2 (2 5 mL);
washing of the combined CH2Cl2 extracts with H2O (2 5 mL); ex-
traction of the combined aqueous extracts with CH2Cl2 (12 20
mL). 0.28 g off-white solid (almost pure product by 1H NMR) was
obtained after drying (Na2SO4) of the pooled CH2Cl2 extracts, filtra-
tion, and rotary evaporation. The product was recrystallised from
THF (6 mL). Colourless crystals separated on cooling to r.t. (0.18
g) and a second crop (0.03 g) was obtained from the mother liquor;
yield: 0.21 g (63%); mp 205 207 °C (Lit.12 mp 206.5 208.5 °C).
2-[2-(Diphenylphosphino)-1-(1-methyl-1H-imidazol-2yl)ethyl]-
1-methyl-1H-imidazole (4)
A solution of 2a (1 g, 5.7 mmol) in THF (50 mL) was cooled to
80 °C. n-BuLi (1.6 M in hexane) (3.64 mL, 5.8 mmol) was added
slowly. The yellow solution was allowed to warm to 45 °C, stirred
for 30 min, and then cooled to 70 °C. A solution of diphenylphos-
phinemethane chloride (1.4 g, 5.96 mmol) in THF (5 mL) was add-
ed dropwise. On warming to r.t. a white solid formed and the lemon
yellow reaction mixture was stirred for another 48 h. Degassed H2O
was then added until almost all solid had dissolved (3 4 mL). THF
was removed in vacuo and degassed H2O (15 mL) was added to the
pale yellow residue. The product was extracted with Et2O (3 10
mL). The combined Et2O extracts were evaporated giving the prod-
uct as a pale oil; yield: 1.83 g (85%).
1H NMR (200 MHz, CDCl3): = 7.74 (m, 2H, Harom), 7.28 (m, 6H,
Harom), 4.69 (s, 2H, CH2), 3.90 (s, 6H, NCH3).
Synthesis 2001, No. 4, 626–632 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER Bridged 1-Methylbisimidazoles as Building Blocks for Mixed Donor Bi- and Tridentate Chelating Ligands
631
1H NMR (200 MHz, CDCl3): = 7.28 7.52 (m, 10H, Harom), 6.94
(d, 2H, 2JH-H = 1.25 Hz, Himid), 6.69 (d, 2H, 2JH-H = 1.25 Hz, Himid),
4.95 (pseudo q, 1H, 3JH-H = 8.2 Hz, CH), 3.41 (s, 6H, NCH3), 3.12
(d, 2H, 3JH-H = 8.3 Hz, CH2P).
red, a precipitate formed, and the colour deepened during the course
of the reaction. After the addition was completed, the dropping fun-
nel was rinsed with CH2Cl2 (2 5mL) and stirring was continued
for 1 h at 20 °C, after which the reaction mixture was allowed to
warm to r.t. The mixture became yellow overnight. Stirring was
continued for 48 h when the contents were filtered through Celite.
The reaction flask was rinsed with CH2Cl2 (3 10 mL), the light
yellow solid that was collected on the frit was extracted with
CH2Cl2 (100 mL), and the combined CH2Cl2 extracts were evapo-
rated leaving a orange yellow oil. At this stage, exclusion of air is
no longer necessary. NaOH (10%, 20 mL) was added followed by
H2O (40 mL) and the solution extracted with Et2O/petroleum spirit
(5:2) (4 28 mL). Light yellow needles (0.23 g) of 7a separated
upon slow evaporation in air at r.t. and after concentration and cool-
ing ( 20 °C) of the mother liquor (0.2 g). Additional product was
obtained by extraction of the remaining aqueous phase (contains
some white solid material, TiO2) with CH2Cl2 (4 25 mL). The
pooled CH2Cl2 extracts were washed with brine (3 20 mL), dried
(Na2SO4), filtered, and evaporated to a yellow sticky solid (1.13 g).
The crude product was recrystallised from boiling Et2O/acetone
(2:1). A first crop of 7a (0.8 g) separated as light yellow needles
upon cooling to r.t. and storage at 20 °C. A second crop (0.12 g)
was isolated after concentration of the mother liquor and storage at
20 °C. A third crop consisted of a mixture of 1a and 7a (1.5:1);
yield 1.35 g (32.4%); mp 131 133 °C.
3
13C NMR (200 MHz, CDCl3): = 146.3 (d, JC-P = 6.5 Hz, C=N),
2
3
138.3 (d, JC-P = 13.4 Hz, ipso C), 133.4 (d, JC-P = 19.1 Hz, ortho
C), 129.1 (s, para C), 128.8 (d, 4JC-P = 6.7 Hz, meta C), 127.5 (s, Cim-
id), 122.5 (s, Cimid), 36.4 (d, 2JC-P = 21.1 Hz, CH2), 33.3 (s, NCH3),
31.5 (d, 3JC-P = 12.9 Hz, CH).
31P NMR (400 MHz, CDCl3):
= 22.38.
MS: m/z (%) = 374 (1.6) [M+], 297 (100) [M C6H5 ], 189 (24)
+
+
[M P(C6H5)2 ].
4,4-Dimethyl-1,1-bis(1-methyl-1H-imidazol-2-yl)pentan-3-one
(5)
A solution of 2a (1.7 g, 9.7 mmol) in dry THF (140 mL) was cooled
to 70 °C. n-BuLi (1.6 M in hexane; 6.21 mL, 9.94 mmol) was add-
ed slowly. The yellow solution was allowed to warm to 40 °C over
1 h and kept at 40 °C for about 10 min. The solution was then
cooled to 75 °C and 1-bromopinacolon (1.727 g, 9.7 mmol) was
added causing the reaction mixture to become cloudy. The lemon
yellow mixture was stirred for 3.5 h at 70 °C to 45 °C and kept
at 20 °C overnight. The now white suspension was allowed to
warm to 10 °C and quenched with H2O (5 mL) until almost all solid
material had dissolved. At this stage, exclusion of air is no longer
required. THF was removed under reduced pressure, CH2Cl2 (45
mL) was added, followed by H2O (15 mL), and the mixture was
transferred to a separatory funnel. The CH2Cl2 layer was separated
and washed with brine (15 mL). The pooled aqueous layers were ex-
tracted with CH2Cl2 (3 5mL). Drying of the combined CH2Cl2 ex-
tracts (Na2SO4), filtration, and rotary evaporation gave 2.82 g of a
light brown oil. On treatment with Et2O (20 mL) the by-product 6
precipitated as a fluffy solid (0.21 g), which was separated by filtra-
tion through a frit. Addition of brine (8 mL) to the yellow Et2O so-
lution resulted in the formation of three layers from which the Et2O
layer was separated. After addition of further brine (8 mL) to the re-
maining two layers, the aqueous layer and the brown oil layer were
extracted with Et2O (3 15 mL). The combined Et2O layers were
dried (Na2SO4), filtered, and allowed to slowly evaporate in air. The
pure product separated as colourless crystals. The mother liquor
was decanted, the product washed with a small amount of Et2O, and
dried under vacuum. The total amount of product was collected by
repeated crystallisation of the combined mother liquors and Et2O
washings; yield: 1.78 g (67%); mp 52 54 °C.
MS: m/z (%) = 264 (100) [M H+].
N-[Bis(1-methyl-1H-benzimidazol-2yl)methylene]-N-pheny-
lamine (7c)
The reaction was carried out as described for 7a: 1c (0.282 g,
0.97 mmol), aniline (0.3 g, 3.2 mmol), TiCl4 1 M in CH2Cl2 (0.54
mL, 0.54 mmol), CH2Cl2 (10 mL).
Workup: CH2Cl2 was removed under reduced pressure and the
green yellow solid washed with Et2O, taken up in CH2Cl2 (50 mL)
and poured into H2O (25 mL) upon which some white solid material
formed (TiO2). H2O (25 mL) was added, the CH2Cl2 layer separated
and washed with H2O (2 10 mL). The pooled H2O washings were
extracted with CH2Cl2 (15 mL). The combined CH2Cl2 layers were
dried (Na2SO4), filtered, and rotary evaporated. The obtained green
1
yellow solid consisted of a mixture of 1c and 7c (2:1, H NMR)
from which 1c was separated by washing with acetone (2 3 mL).
Drying in air and recrystallisation from EtOAc afforded 7c as a light
yellow solid; yield 0.1 g (28%); mp 270 °C (dec.).
+
MS: m/z (%) = 365 (100) [M+], 350 (19) [M CH3 ].
1
IR (KBr): = 1704 (C=O) cm .
1H NMR (200 MHz, CDCl3): = 6.67 (d, 2H, 3JCH = 1.2 Hz, Himid),
Acknowledgement
6.55 (d, 2H, 3JCH = 1.2 Hz, Himid), 4.75 (t, 1H, 3JC-H = 6.9 Hz, CH),
This work was financially supported by the SPIRT Scheme. We are
grateful to Dr Evan J. Peacock (CSL) for his help in assignments by
NMR experiments.
3
3.35 (d, 2H, JC-H = 6.9 Hz, CH2), 3.32 (s, 6H, NCH3), 2.3 (s, 3H,
H2O), 0.92 (s, 9H, tBu).
13C NMR (200 MHz, CDCl3): = 213.9 (C=O), 146.6 (C=N), 127.6
(Cimid), 122.1 (Cimid), 44.6 (CH2), 40.1 (CH), 33.3 (NCH3), 32.6
[C(CH3)3], 26.8 (tBu).
References
MS: m/z (%) = 275 (3) [MH+], 217 (57) [M t-Bu+], 189 (100)
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Article Identifier:
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Synthesis 2001, No. 4, 626–632 ISSN 0039-7881 © Thieme Stuttgart · New York