Direct Ortho-Metallation of Aryl Substituted Heteroaromatic
Ligands with TiCl4 and ZrCl4 - An Experimental and DFT Study
with 2-Phenyl Indole as the Ligand.
Gregory G. Arzoumanidis*†, Ernest Chamot**
*Oakwood Consulting, Inc., Wheaton, Illinois 60187
**Chamot Laboratories, Inc., Naperville, Illinois 60540
Supporting Information Placeholder
ABSTRACT: TiCl4 and ZrCl4 each react with aryl substituted heteroaromatic ligands such as 2-Phenyl-1H-indole, to
thermally undergo one-pot direct orthometallations, and yield new types of cyclometallated complexes. TiCl4
coordinates at ambient temperature to form the indole complex (1), which undergoes isomerization to the indolenine
(2). DFT calculations indicate that complex (2) is more stable than (1) by 6.4 kcal/mol. Upon warming to about 105°C,
extrusion of HCl takes place with simultaneous orthometallation (3), yielding a metallacyclic complex (4). The
mechanism of the orthometallation has been investigated by DFT, and the transition state confirmed by IRC. At the
elevated temperature the transition state (3) involves the synchronous transformation of four atoms, Ti, ortho C, H, and
the apical Cl. The ortho C of the phenyl group acquires a partial positive charge through conjugation, forming a
(C-H)δ+...Clδ- interaction, with a simultaneous elongation and breaking of the Ti-Cl bond, resulting in the formation of a
Ti-C bond. The latter bond i s created at the same time a Ti-Cl bond is breaking, and an HCl is being formed, as
illustrated in transition state (3). This HCl is retained in the crystal structure of the final product (4), by electrostatic
interaction with one of the chloride ligands. The reaction sequence may be repeated with ZrCl4 in place of TiCl4.
Complex (4) has been isolated and characterized by solid state 13
C NMR CPMAS/DDMAS spectra, X-ray photoelectron
spectroscopy (XPS), infrared and analytical data. The intermediate structures (1 through 4), as well as the sequence of
ligand transformations to produce the ortho-metallated complex are supported by DFT calculations. The new
cyclometallated complexes are thermally stable, unlike several other complexes featuring a Ti-C bond. They may have
important applications, such as in α-olefin polymerization catalysis, and as building blocks in metalodrugs for cancer
therapy.
INTRODUCTION
Addition compounds of titanium tetrachloride with
various amines have been widely used in synthetic
organic chemistry (1). Similarly, aromatic amines such
as carbazole, complexed with ZrCl4, have found
applications as catalysts in Ziegler-Natta polymerizations
(2).
Furthermore, Pt complexes of 2-phenyl indole
derivatives have been tested as cytotoxic agents against
ͦhuman breast adenocarcinoma cell lines (3).
Direct Caryl metallation with Ti or Zr compounds has
been very rare so far, although directed orthometallation
(DOM) by a regiospecific ortholithiation with RLi (4) and
subsequent transmetallation is the technique commonly
being followed to achieve cyclometallation. In fact, the
prevailing assumption up to now has been that "Early
transition metals like titanium and zirconium are unable
to undergo the necessary C-H activation step to form the
orthometallated complex" (5).
Others have shared
similar views (6), although some examples of direct
cyclometallation using titanium and zirconium tetra alkyls
(7), or using tetrachlorides, but not involving aromatic
carbons (8), have been reported. We have been able to
determine by DFT studies that in the titanium and
zirconium complexes we have studied, metal-hydrogen
interactions are weak, as indicated by the metal-ortho
hydrogen distance, and do not lead to ortho metallation
by C-H insertion of the metal. See below. However,
ortho metallation does occur by an HCl elimination
mechanism.
We now report the direct cyclometallation of 2-phenyl
indole with TiCl4 or ZrCl4, as an efficient one-pot
reaction. This reaction runs over a series of suggested
intermediates (1 through 3), until the formation of the
final product (4) at elevated temperature (up to 105°C).
DFT studies suggest that this orthometallation takes
place via an ortho phenyl hydrogen abstraction by the
chloride ligand, facilitated by being adjacent to a cationic
center. This unexpected reaction was discovered during
our investigations on the commercial Amoco CD catalyst
for propylene polymerization (9), through the introduction
of 2-phenyl indole as a new internal catalyst modifier.
The reaction sequence in the orthometallation was
studied computationally with density functional theory
(DFT), and the EDF2 functional was used because it
works well with transition metals and is optimized for
calculating spectra. In the course of this work, the EDF2
method was validated for its ability to reproduce agostic
interactions.
Each intermediate in the reaction sequence shown in
the abstract was modeled to understand its structure and
the mechanism for its formation. Each geometry was
confirmed to be a thermodynamically stable species, and
spectra were calculated to guide and corroborate the
interpretation of the experimental spectra. The calculated
energies provide an indication of how accessible each
intermediate is thermodynamically, and what the driving
force is for each reaction step.
The Ti/Zr orthometallation/cyclometallation reaction
may not be restricted to 2-phenyl indole, but it may be
applied to a great variety of heteroaromatic ligands with
a pendant aromatic ring in the 2-position from the
heteroatom, N, O, P or S.
These novel cyclometallated complexes, besides their
application in polymerization catalysis (10), may have
application in organic synthesis through the insertion
reaction of several small molecules into the metal-Caryl
bond (CO, CO2, etc.), including nitrogen fixation (11), or
by the insertion of certain unsaturated compounds such
as olefins. Their pharmacological potency as anticancer
agents may also be re-visited (12).
The new complexes may undergo several other types
of reactions such as reduction/alkylation with aluminum
alkyls, yielding new mixed-metal complexes.
The
reaction of the cyclotitanated 2-phenyl indole with triethyl
aluminum has been carried out, and data were recorded.
See discussion. Furthermore, we may project that 4 or 7
(the Zr equivalent of 4) may show a reactive profile
similar to Cp2TiCl2, like in the Petasis reaction, reacting
with MeLi or MeMgCl.
RESULTS AND DISCUSSION
Cyclotitanation of 2-Phenyl Indole with TiCl4. TiCl4
is a strong Lewis acid, forming 1:2 addition compounds
with aromatic amines (13), and 1:1 with imidazole, and
several other diamines like 2,2'- bipyridine and dabco
(14).
Upon mixing of TiCl4 and 2-phenyl indole at ambient
temperature, the five-coordinated complex (1) forms,
which isomerizes readily to the more stable indolenine
tautomeric form (2), with a shift of the double bond from
the 2,3- to the 1,2-position, and a simultaneous
hydrogen migration from the 1- to the 3-position. For
these two complexes we considered an alternative
coordination structure via an additional η6-phenyl bond to
Ti, but this possibility was eliminated by DFT
calculations. At ambient temperature, the solution of the
mixture is light yellow-orange. Upon slow (within 30 min)
warming, starting at about 80° C and up to 105°C, the
solution darkens to red-burgundy, with rapid formation of
burgundy crystals. During this time, orthometallation of
the phenyl group takes place, with a bathochromic color
shift due to the newly created π-conjugation, described
also in other heteroaromatic systems (15).
The
proposed structure of the crystalline product (4) is
corroborated by elemental analysis, solid 13
C NMR,
infrared (including far infrared) spectra, X-ray
photoelectron spectroscopy (XPS), and supported by
DFT calculations. The experimental results will be
discussed along with the DFT study, under
“orthometallated Product 4”, below.
In the reaction sequence, the HCl produced by the
orthometallation of the phenyl group is retained in the
structure 4, even in the presence of excess 2-phenyl
indole, which is not basic enough to remove the HCl
from the complex. DFT calculations indicate that the
∆G0 of a reaction for the removal of the HCl from 4 with
2-phenyl indole is slightly endothermic by 0.59 kcal/mol.
Therefore, there is no driving force for 2-phenyl indole to
neutralize HCl, in preference to the product 4 formed by
the orthometallation.
The oxidation state of Ti in 4 has been confirmed with
X-ray photoelectron spectroscopy (XPS). The binding
energy (BE) of Ti 2p3/2 photoelectrons in the complex
was found to be 458 eV from the XPS data. This value
of BE compared with the literature data on other Ti
compounds suggests a +4 oxidation state for Ti. The
XPS analysis also provided approximate quantitative
data on elemental atomic ratios. For the three key
elements Ti, N and Cl, the atomic ratios were determined
to be 1:0.8:2.7, a reasonable approximation to 1:1:3.
These data indicate that the fourth Cl is not "bound"
directly to Ti.
Zirconium Chloride 2-Phenyl Indole Complex. The
methodology described above was followed for the
preparation and characterization of the reaction product
between ZrCl4 and 2-phenyl indole. The IR and solid
state CPMAS and DDMAS 13
C NMR spectra of the
complex were recorded. The significant features of the
spectra were very similar to those from the Ti 2-phenyl
indole complex. Details are discussed under Zr complex
7, DFT study.
A
key
functional
difference
between
the
cyclometallated class of polymerization catalysts like 4,
and other catalytic complexes (metallocenes, FI
catalysts (16) etc.) is the insertion reaction into the
metal-Caryl bond.
Small molecules such as O2, CO, CO2,
CS2, COS, SO2, are capable of inserting, as well as
multiple compounds with functional groups, and of
course alkenes and alkynes (17). The insertion reaction
provides a platform for the discovery of new advanced
catalysts from cyclometallated complexes.
Density Functional Study of the Ortho-Metallation of
2-Phenyl Indole.
Addition Compound 1. The first step in this
synthesis, is the addition of TiCl4 to 2-phenyl-1,H-indole.
This is expected to first complex by electron donation
from the lone pair of electrons on the nitrogen, to form
intermediate 1. The structure of 1 was found by DFT with
EDF2/6-31G* to have the indole nitrogen occupying a
fifth coordination site on Ti, as an equatorial ligand in a
roughly trigonal bipyramidal coordination sphere, with a
Ti-N bond distance of 2.39 Å. The aromatic rings are
nearly coplanar, with a C-C-C-N dihedral angle of only
4.7°. See Figure 1a.
Titanium was not found to also form an η6 bond to the
phenyl ring of phenyl indole and adopt an octahedral
configuration. To do so would twist the phenyl group
perpendicular to the plane of the indole ring, and
interrupt the extended conjugation of the two aromatic pi
systems. Instead, the two rings are coplanar in the
ground state, and the Highest Occupied Molecular
Orbital (HOMO) was found to be delocalized over both
rings, extending the conjugation.
The EDF2 result was checked with BLYP and MP2
calculations, neither of which found Ti coordinating to the
phenyl ring. The MP2 calculation did give a slightly
different minimum energy geometry from the two DFT
calculations, with a Ti-N distance of 2.56 Å and the rings
partly twisted (with a C-C-C-N dihedral of 40.8°), but the
HOMO still shows extended conjugation with
delocalization over both rings.
At a lower level of theory, a semiempirical PM3
calculation did find an η6-phenyl bonding geometry, but
when this starting geometry was refined by EDF2, BLYP,
or MP2 it was found to be a false minimum, and quickly
flattened out to the structure with extended conjugation
shown in Figure 1a.
This vinyl C-H would appear at 116.0 ppm in the 13
C
NMR (See Figure 2a) and at 7.20 ppm in the 1 H NMR.
The phenyl substituted indole C next to N (position 2) is
at 149.4 ppm in the 13
C NMR. The UV-Vis spectrum is
calculated to have electronic transitions in the visible
range, 437-675 nm, but with low absorbance intensities:
below 0.007.
Tautomerized Complex 2.
Next, the indolenine
tautomer arising from a 1,3 H-shift from N to C in the
indole 5-membered ring was modeled by DFT with
EDF2/6-31G*, and its energy calculated. See Table 1.
Tautomer 2 is found to be lower in energy than 1 by 6.9
kcal/mol (∆H° = -6.9 kcal/mol, ∆G° = -7.1 kcal/mol). So
this 1,3 H-shift should occur spontaneously.
Interestingly, the ring geometry is slightly different:
although a metastable geometry with the two aromatic
rings coplanar can be found, the lowest energy
conformation actually has the phenyl group rotated by
37° to bring the ortho hydrogen within 2.89 Å of the
titanium, see Fig. 1b. This is evidence of an agostic
type interaction. (The EDF2 method was validated for
describing agostic interactions, and is described in the
supplemental material.) The Ti-N distance in 2 is slightly
shorter than in 1, at 2.23 Å. The Ti is still roughly
trigonal bipyramidal, with the N in an equatorial position.
The agostic bonded geometry, 2, is 2.0 kcal more stable
than the alternative geometry, in which the phenyl is
perpendicular to the indole.
The strong 408 and 440 cm-1 Ti-Cl absorbances
dominate the calculated IR of 2, as they did in 1. But the
5-membered ring, no longer aromatic,
is now
characterized by having methylene C-H's that appear as
a weak symmetric stretch at 2943 cm-1, instead of the
N-H stretch in 1. The lack of a 3347 cm-1 peak in the
experimental IR confirms that tautomerization has taken
place. The mono substituted phenyl still has the 5 C-H's
absorbing at 684 cm-1, and the 4 adjacent C-H's of the
indole ring at 751 cm-1.
The methylene H’s are calculated to appear at 3.95
and 4.44 ppm in the 1 H NMR, and the C at 41.4 ppm in
the 13
C NMR. See Figure 2b. The ortho carbon with the
agostic hydrogen is still at 128.3 ppm, but the bridge C
next to N (indole position 7a) is at 151.7 ppm. The
electronic, UV-Vis, transitions are now mostly below the
visible region, 375-461 nm, and have absorption
intensities all below 0.009, so there would be little
observable color at this stage of the reaction sequence.
Transition State 3. Ti ultimately metallated the phenyl
ring, replacing the ortho hydrogen in 2. Although initially
close to the Ti in 2, the ortho H does not transfer to the
Ti and then insert into a Ti-Cl bond before eliminating
HCl. Instead, it has been found to transfer to the
neighboring, axial Cl ligand on Ti by way of 4-membered
cyclic transition state 3, shown in Figure 3.
Attempts to find an intermediate step with transfer of H
to Ti failed to find a stable geometry by DFT. They either
spontaneously eliminated Cl2, chlorinated the phenyl
ring, or collapsed back to 2. But the transition state, 3,
was found with the ortho H halfway between the C and
the Cl: with C-H 1.58 Å and H-Cl 1.42 Å. This was
confirmed to be a true transition state for this reaction,
being a minimum in energy with respect to all degrees of
freedom except for along the reaction coordinate, which
leads directly back to reactant, 2, and forward to the
ortho-metallated product, 4a. This was verified by an
Intrinsic Reaction Coordinate search. A four-membered
cyclic transition state for metallation of an aromatic ring
is consistent with the observation of cyclic transition
states
for
intermolecular
C-H
bond
metallation-deprotanation (18) and specifically with
four-membered cyclic transition states proposed for
[Ru-OH] and [Ir-OMe] complexes (19).
In transition state 3 the two rings are once again nearly
coplanar, with a C-C-C-N dihedral angle of 8.1°. The
Ti-N distance is still 2.23 Å. The Ti at this stage has
become roughly octahedral, with the Ti-C bond being
formed occupying one coordination site at a distance of
2.24 Å.
Figure 1. Calculated IR spectra of Ti complexes, highlighting differentiation between (a) initial donor complex 1, (b)
tautomerized complex with agostic contacts 2, and (c) orthometallated complex 4b, with associated HCl above plane.
Figure 2. Calculated 13
C NMR spectra highlighting differentiation between (a) initial donor complex 1, (b) tautomerized
complex with agostic contact 2, and (c) orthometallated complex 3, with HCl above plane.
Table 1. EDF2/6-31G* Energies and Geometries
Molecule
H°, au
G°, au
Dipole
Moment, D
C-C-C-N
Dihedral, °
M-N, Å
M-C, Å
Ti adduct, 1
-3284.84982
-3284.90990
6.05
4.7
2.39
3.79
Ti tautomer, 2
-3284.86087
-3284.92125
8.30
37.3
2.23
3.39
TS, 3
-3284.80606
-3284.86682
8.77
8.1
2.23
2.24
Titanacycle, 4a
-3284.81851
-3284.88048
10.43
-0.3
2.20
2.12
HCl above, 4b
-3284.81989
-3284.88134
6.69
-0.6
2.20
2.11
Zr adduct, 5
-2481.93700
-2481.99760
6.89
6.4
2.49
3.84
Zr tautomer, 6
-2481.94874
-2482.00969
9.36
36.5
2.36
3.33
Zirconacycle, 7
-2481.89575
-2481.95850
10.82
0.42
2.33
2.27
An appreciable activation energy is calculated for this
reaction, however, with 3 being 34.4 kcal/mol higher in
energy than 2, see Table 2. This is in line with
calculations by Goddard’s group (20), which calculated
an activation energy of 39.8 kcal/mol for the
4-membered ring transition state for intermolecular
metallation of benzene by an iridium hydroxide complex.
The Ti in 4a has returned to a trigonal bipyramid, with
the N and the H-bonded Cl occupying the axial positions.
The rings are coplanar with a dihedral angle of 0.3°, the
Ti-N bond is 2.20 Å, and the Ti-C bond is 2.12 Å. The Cl
H-bond distance is 2.44 Å. These bond distances are
virtually unchanged in the slightly more stable (by 0.9
kcal/mol) lowest energy orientation, 4b, with the HCl
above the plane of the rings and oriented with the H
toward an equatorial Cl on Ti.
The Cl—H-Cl structure is calculated to have a very
strong IR vibration (back and forth between the Cl’s in
4b) at 2726 cm-1. It also has a pair of weak side-to-side
vibrations at 309 and 249 cm-1 in 4a: side-to-side and up
and down vibrations at 380 and 302 cm-1 in 4b.
Figure 3. Cyclic transition state, 3, for orthometallation.
Table 2. Reaction Sequence Thermodynamics
Step
∆H°(rxn),
kcal/mol
∆G°(rxn),
kcal/mol
1 → 2
-6.93
-7.12
2→ [3]
34.39
34.16
2 → 4b
25.72
34.16
5→ 6
-7.37
-7.59
6 → 7
33.25
32.12
Orthometallated Product 4. The Intrinsic Reaction
Coordinate (IRC) search from transition state, 3, leads
directly to formation of a Ti-C bond at the ortho position
of the phenyl group, with elimination of an HCl molecule.
In the absence of polar solvation, HCl remains paired up
with the Ti-phenyl indole complex, forming a bimolecular
complex: the partially positive H being attracted to one of
the electronegative Cl ligands on titanium. Several
orientations of the HCl around the orthometallated,
phenyl indole complex were found by DFT to be nearly
equivalent energetically, but the initially formed structure
from transition state 3, has the HCl projecting out from
the in-plane Cl, and angles a little up from the plane:
structure 4a in Figure 4.
Figure 4. Initial bimolecular complex
orthometallated phenyl indole, 4a.
of
HCl
and
The calculated HCl/[HCl2] IR absorbance is
ambiguous, due to the variety of equivalent orientations
the HCl can adopt around the orthometallated complex.
Although the H-bonded Cl-H-Cl structure is in a linear
configuration, it is in a significantly different environment
than the free HCl2- ion: either in the gas phase, or in the
ionic solids studied by Ward et. al. (21). One of the
chlorines is chemically bonded to another molecule and
there is not a net negative charge, so the Cl-H distances
are not equal, and any Cl-H vibrational mode will be
strongly coupled to the rest of the system. Ward has
reported IR absorbances for HCl2- in ionic solids at 200,
1080-1210, and an overtone band at 1525-1660 cm-1.
The experimentally observed 1595 and 1566 cm-1 bands
would be consistent with an [HCl2], but were not found by
DFT, because overtones are not calculated.
The experimentally observed 2723 and 2680 cm-1
bands are consistent with the calculated 2726 cm-1
in-line H vibration in 4b, and the medium 203 cm-1 band
is consistent with the side-to-side vibration calculated at
249 cm-1 in 4a. Calculated IR absorbances at 1183 and
1091 cm-1 (for 4b) are near the observed 1195 and 1079
cm-1, but these are CH2 wag and in-plane aromatic C-H
bending vibrations, respectively.
The Ti-Cl vibrations are complex modes, with
frequencies of 371, 380, and 413 cm-1 that dominate the
IR, as they did in 2. These compare with the
experimentally observed strong absorptions at 383, 394,
and 419 cm-1.
,
Figure 5. Calculated IR spectra of Zr complexes, highlighting differentiation between (a) initial donor complex 5,
(b)tautomerized complex.. with agostic contact 6, and (c) orthometallated complex 7, with associated HCl
The 5 C-H wag of the phenyl group at 684 cm-1 is
gone, replaced by a 747 cm-1 absorbance for 4 adjacent
C-H's in ortho substituted rings, overlapping the 752 cm-1
absorbance of the indole's 4 adjacent C-H's serving as
an indicator for orthometallation. The corresponding
observed strong absorption is at 728 cm-1.
The HCl hydrogen in 4b is calculated to appear at 2.01
ppm in the 1 H NMR, but presumably this will be highly
dependent on the solvent.
The 5-membered ring
methylene group should show up at 3.98 and 4.36 ppm
in the 1 H NMR and at 35.6 ppm in the 13
C NMR. The
experimentally observed is at 42 ppm.
Solid state 13
C NMR cross-polarization with magic
angle spinning (CPMAS) was used to investigate the
shift changes in the Ti complex 4 in order to confirm the
Ti-Caryl bond. A dipolar dephasing spectrum DDMAS
(containing the expected five peaks from quarternary
carbons only) showed shifts at 183, 140, 132, 128 and
126 ppm. The 183 ppm shift has been assigned to the
phenyl 2-position bonded to Ti, and the other four to the
existing quarternary carbons in the complex (phenyl to
indole bonded C, indole C next to N, C in indole 2
position, and indole ring fused C between 3 and 4
positions, respectively). The corresponding four shifts of
quarternary carbons in free indole are 135.8, 137.1,
137.6, and 128.2 ppm, in relatively good agreement.
The DFT calculated quarternary carbon shifts of
complex 4b were at 212.0, 182.1, 152.1, 138.7, and
133.1 ppm, following the same order. Here we do not
have good agreement between the calculated and the
experimental values. This could be attributed to a
number of reasons, like our calculations were made for
gas phase, and we are dealing with a solid, with possible
strong intermolecular interactions. Also, the effect of HCl
in shielding or deshielding certain carbon centers could
be substantial (21).
There may be some other indications that the
experimental 183 ppm may indeed belong to the
metallated phenyl carbon. First, it is the one extra
quarternary
shift
appearing upfield after the
ortho-metallation of 2-phenyl indole. The reaction of 4
with AlEt3 produces a Ti (III) bimetallic complex which
shows the peak now at 196 ppm. Finally, in the Zr
complex 7 the fifth quarternary peak is at 181.8 ppm,
similar to the shift in 4.
Zirconium Adduct 5.
Zirconium was found
experimentally to behave similarly to titanium in the
same synthetic sequence, so it was examined with
EDF2/6-31G* calculations, also. The Zr analogue of 1
was first modeled by DFT, to study the corresponding
ZrCl4 adduct, 5, shown in Figure 6.
The remaining peaks, at 144.8, 134.7, 132.0, 129.9,
128.0, 124.3, 123.9, and 121.0 ppm, are all within the
experimentally observed envelope for the protonated
carbons, from 146 to 115 ppm.
The electronic transitions are calculated to absorb
more strongly in the UV, with intensities up to 0.04, and
to extend into the visible region: 379-518 nm. Absorbing
the violet, blue, and green colors would leave the red
end of the spectrum, and is consistent with the observed
burgundy color of the reaction product.
Two other orientations for HCl in the bimolecular
complex were found to be very close in energy. In one
the HCl is still oriented toward the axial Cl, but projects
up from the plane of the rings, 4a. In another, the HCl
lies above the ring, with the H oriented toward an
equatorial Cl, 4b,
This latter is the most stable
bimolecular pair, being 1.0 kcal lower in energy than 4a.
The stability is due, in part, to the reduced charge
separation by having HCl’s dipole aligned to oppose the
dipole of the organometallic complex. While this is the
preferred geometry, these energy differences are small,
and may be within the accuracy of the calculation. The
more so, because density functional methods typically
do poorly for intermolecular interactions, so the
bimolecular complex relative energies may be less
accurate than the other calculations reported here.
The calculated spectra of 4a and 4b have similar
absorbances for the Cl-H-Cl modes: 4a should have a
strong 2770 cm-1 in-line stretch and weak 309 and 209
cm-1 side-to-side modes, and 4b should have a strong
2726 in-line stretch and weak 380 and 302 cm-1
side-to-side modes.
Molecule pair 4b, the lowest energy configuration, is
calculated to be 8.7 kcal/mol lower in energy than
transition state, 3, but is still 26 kcal/mol higher in energy
than 2. See Table 2. So this reaction would not proceed
spontaneously.
But experimentally, the
product
precipitates out of solution, which drives the reaction.
These reactions were carried out experimentally in
nonpolar solvents, such as toluene. Each intermediate,
however, is calculated to have a significant dipole, which
changes throughout the reaction sequence. See Table
1. So a polar solvent should shift the thermodynamics,
by stabilizing the more polar intermediates more than the
less polar ones. In particular, the dipole moment is
calculated to be a maximum for the transition state, 3,
and for the initially formed molecule pair, 4. Therefore, a
polar solvent should lower the activation energy for
formation of 4 and 5.
Figure 6. Zirconium adduct 5, Zr analogue of 1.
In 5 the Zr is roughly a trigonal bipyramid with N
equatorial, as was the case with titanium. The Zr-Cl IR
vibrations at 362-384 cm-1 dominate, and aromatic ring
breathing vibrations absorb at 1600 and 1567 cm-1. The
N-H vibration is at 3343 cm-1 and the vinyl C-H stretch is
a shoulder at 3147 cm-1.
Zirconium Tautomer 6. A 1,3 H-shift from N to C in
the 5-membered ring to give the indolenine tautomer
analogue of 2 with Zr gives 6, shown in Figure 7. Once
again, as in the case with Ti, there appears to be an
agostic interaction with the phenyl’s ortho hydrogen.
The Zr in 6 is more nearly trigonal bipyramidal, however,
rather than octahedral, and the N is equatorial. The
Zr-Cl vibrations are at 358 to 377 cm-1, the iminium C=N
stretch is a strong absorbance at 1541 cm-1, and the
characteristic 5 C-H wag of the mono substituted phenyl
is at 745 cm-1. The UV-Vis transitions absorb up to 345
nm with a maximum intensity of 0.2. 6 is 7.4 kcal/mol
lower in energy than 5, so this tautomerization should
proceed spontaneously, as was the case with Ti. See
Table 2.
Orthometallated Zirconium Complex 7.
The
orthometallated zirconium analogue of 4a was modeled,
and again found to be a stable molecule pair with HCl.
See Figure 8. The Zr is roughly a trigonal bipyramid,
with the N axial, the Zr-C distance 2.27 Å, Zr-N 2.33 Å,
Cl-HCl 2.43 Å, and H-Cl 1.30 Å.
CONCLUSIONS
Cyclometallated complexes of titanium and zirconium
with 2-phenyl indole, promising olefin polymerization
catalysts when activated with TEA, have been described
for the first time. They may represent a new class of
materials with diverse applications, as catalysts in
general, in cancer therapy, photoluminescence (3b), and
as starting materials in synthetic organic chemistry,
through insertion reactions into the metal-Caryl bond, and
reactions with aluminum alkyls, among others.
This type of thermal orthometallation may not be
restricted to 2-phenyl-indole, but could be expanded to
Figure 7. Zirconium tautomer, 6, Zr analogue of 2.
The calculated IR shows a Cl-H-Cl absorbance at
2787 cm-1, which compares favorably with the observed
at 2750 cm-1. The phenyl 5 C-H absorbance is gone,
replaced by a 4 C-H wag at 754 cm-1, coalesced with the
indole 4 C-H wag. This is consistent with the observed
strong 792 cm-1 indicating orthometallation in 7. The
calculated Zr-Cl sym stretch is at 355 cm-1 and the asym
at 383 cm-1. They compare with the observed 366 cm-1
and 386 cm-1 strong absorptions. The calculated
asym/sym absorptions for the Zr-Cl...HCl are at 331/350
cm-1, vs the observed 301/341 cm-1.
From the solid state CPMAS study, the five 13
C NMR
shifts experimentally recorded for this complex were
124.4, 132.0 140.9, 141.6, and 181.8 ppm, the latter
attributed to the Zr-C bond. Analogous DFT values
could not be calculated.
Thermal Stability of Complexes 4 and 7.
Compounds with a Ti-C bond are in general thermally
unstable, unless structural conditions or the lower
oxidation state of Ti, contributes to their stability.
Tetraphenyl Ti prepared at -78°C, decomposes at -10° C
to form a room temperature stable (but pyrophoric in air)
Ti (II) compound Ti(C6H5)2 (22). In RnTiX4-n compounds
stability increases with increasing electronegativity of R:
butyl<methyl<acetylenyl <p-anisyl <phenyl<a-naphthyl
<indenyl (23). Derivatives of Cp2TiX2 are more stable, in
the order of x=C6H5<CH3<C6F5 (22). Complexes 4 and 7
exhibit remarkable thermal stability, perhaps higher than
any known Ti organometallic derivative.
They are
formed at the high temperature of 105° C, and they
remain unchanged at room temperature under Nitrogen.
The reason for their stability is the coordination with a
donor-N (24), but also the pi-conjugating system of the
indole ligand, This stability is an important characteristic
of 4 and 7 in applications as reagents.
Figure 8. Zirconium bimolecular complex 7, Zr analogue of
4.
several other ligand types, capable of undergoing
ortho-metallation, as
for example, tetraphenyl
cyclopentadienone (25).
The Density Functional calculations with the EDF2
functional and the 6-31G* basis set were found to
support the proposed mechanism shown in the abstract
for the formation of a phenyl indole complexed titanium
catalyst.
The tautomerization step would proceed
spontaneously, based on the thermodynamic analysis.
A 4-membered cyclic transition state was found for
ortho-metallation, but the elimination of HCl to complete
the reaction needs to be driven, since it is calculated to
be endothermic. Excess phenyl indole is insufficiently
basic to remove the HCl. More polar solvents may lower
the activation energy, due to the increased polarity of the
transition state. Zirconium was found to give similar
intermediates.
COMPUTATIONAL METHODS
All calculations were carried out with the Spartan program
(Spartan’14, Wavefunction, Inc. Irvine, CA) (25), using the
EDF2 functional with the 6-31G* basis set. In some instances,
additional calculations were carried out with the MP2
post-Hartree Fock method, also with the 6-31G* basis set, to
check the Density Functional results. All structures were fully
optimized, and characterized by vibrational analysis to confirm
that they were in fact stationary points: reactants,
intermediates, complexes, or transition states.
When
necessary, the default convergence criteria were tightened up
to a TOLG=0.00006, to eliminate any negative frequencies.
Zero-point (vibrational) energies (ZPEs) and IR absorbances
were also calculated, and Thermodynamic values derived:
enthalpy (H°), entropy (S°), and Gibbs free energy (G°). NMR
spectra were calculated with the GIAO method, and select
6-31G* calculations were repeated with the 6-31G+G** basis
set, to confirm their accuracy.
AUTHOR INFORMATION
Corresponding Authors
* E-mail for G.G.A.: arzoumandis@gmail.com.
** E-mail for E.C.: echamot@chamotlabs.com.
Notes
†This research was conducted in part at the former Amoco
Research Center, Naperville, Illinois 60566.
ACKNOWLEDGMENT
Naresh K. Sethi conducted the solid 13C NMR study and
interpreted the data.
EXPERIMENTAL SECTION
REFERENCES
Materials were used as received. Solvents (toluene, hexane)
were dried using standard procedures. Experiments were
carried-out in a dry-box, under dry, purified nitrogen.
Cross-polarization with magic angle spinning (CPMAS) solid
state 13
C NMR technique was used for all cyclometallated
complexes. The samples were packed into MAS rotors in dry
box, and dry nitrogen was used for sample spinning to prevent
exposure to air and moisture. Typical CPMAS experimental
conditions used were: external magnet = 2.35 tesla: CP
contact time = 2 milliseconds; proton spin-lock radio-frequency
field = 40 KHz; recycle delay = 3 seconds. Dipolar dephasing
(DDMAS) technique, with 40 microseconds dephasing time,
was used to obtain quaternary (and methyl) carbons only
spectra, to aid in spectral assignment.
Preparation of the 2-phenyl indole/TiCl4 cyclometallated
complex. Inside a dry box, 25 ml of 1.0 molar solution of
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washed four times with toluene. It was further washed three
times with hexane, and dried in vacuum. Yield 91% based on
TiCl4. Spectroscopic evidence indicates that the product may be
about 97% pure, the rest being hexane that could not be
removed by the vacuum.
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H,
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on
the ACS Publications website.
Additional calculations of indole-HCl affinity and validating
EDF2/6-31G* for agostic interactions (PDF)
A text file of all computed molecule Cartesian coordinates in
.xyz format for convenient visualization (XYZ)
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Ernest Chamot