A practical and inexpensive one-pot synthesis of bis(indenyl) dimethyltitanium with aqueous workup procedure

Article abstract of DOI:10.1002/zaac.201300433

A simple, reliable, and reproducible procedure for the multi-gram synthesis of highly pure bis(indenyl)dimethyltitanium is presented. The procedure relies on a one-pot conversion of inexpensive indene, methyllithium, and titanium tetrachloride to [Ind₂TiMe₂] and a convenient and quick aqueous workup protocol. Overall, quantities of several grams of [Ind ₂TiMe₂] can be synthesized within a few hours. The procedure can also be used for the synthesis of [Cp₂TiMe₂] from cyclopentadiene, methyllithium, and titanium tetrachloride.

Full text of DOI:10.1002/zaac.201300433

ARTICLE
DOI: 10.1002/zaac.201300433
A Practical and Inexpensive One-Pot Synthesis of
Bis(indenyl)dimethyltitanium with Aqueous Workup Procedure
Jan H. Ross,[a] Till Preuß,[a] Christian Brahms,[a] and Sven Doye*[a]
Keywords: Catalyst; Metalation; Metallocenes; Synthetic methods; Titanium
Abstract. A simple, reliable, and reproducible procedure for the multi-
gram synthesis of highly pure bis(indenyl)dimethyltitanium is pre-
a convenient and quick aqueous workup protocol. Overall, quantities
of several grams of [Ind2TiMe2] can be synthesized within a few hours.
sented. The procedure relies on a one-pot conversion of inexpensive The procedure can also be used for the synthesis of [Cp2TiMe2] from
indene, methyllithium, and titanium tetrachloride to [Ind2TiMe2] and
cyclopentadiene, methyllithium, and titanium tetrachloride.
to use this catalyst for a number of future synthetic applica-
tions, we recently focused the problem to synthesize multi-
gram amounts of highly pure [Ind2TiMe2] in a most cost-ef-
ficient and convenient way.
Introduction
During the past few years bis(indenyl)dimethyltitanium be-
came an increasingly important catalyst precursor for polyme-
rization,[1] hydroamination,[2] and hydroaminoalkylation[3] re-
actions. For example, [Ind2TiMe2] (Ind = η5-indenyl) was
found to be a highly active and general catalyst for the inter-
molecular hydroamination of alkynes.[2a] It catalyzes the reac-
tion of primary aryl- and alkylamines with internal and ter-
minal alkynes giving access to imines, which can subsequently
be reduced to secondary amines. In the case of unsymmetri-
cally substituted 1-phenyl-2-alkylalkynes, the hydroamination
reactions occur with high regioselectivities, whereby formation
of the anti-Markovnikov regioisomer is always favored. Corre-
spondingly, it is possible to synthesize biologically interesting
2-phenylethylamine derivatives from 1-phenyl-2-alkylalkynes
and methylamine by a simple hydroamination/reduction se-
quence (Scheme 1).[2c] In addition, [Ind2TiMe2] represents a
versatile catalyst for hydroaminoalkylation reactions, which al-
low the 100% atom-efficient addition of α-C–H bonds of pri-
mary or secondary amines to C–C double bonds of alk-
enes,[3a,3b] styrenes,[3b] or 1,3-butadienes.[3c] With this catalyst,
1-alkenes react with N-methylanilines to give the correspond-
ing branched hydroaminomethylation products with very high
regioselectivity (usually Ͼ 99:1) and catalysis can be achieved
at temperatures as low as 80 °C (Scheme 1). Interestingly, sig-
nificantly diminished regioselectivities in favor of the
branched product (≈ 85:15) are observed when styrenes or 1,3-
butadienes are used as substrates. However, due to the wide
applicability of [Ind2TiMe2] in amine synthesis and our plan
Scheme 1. [Ind2TiMe2]-catalyzed intermolecular hydroamination and
hydroaminoalkylation reactions.
Results and Discussion
In the literature, different procedures for the synthesis of
[Ind2TiMe2] can be found.[2b,4] For example, Resconi et al.
described a one-pot synthesis starting from inexpensive in-
dene, methyllithium, and titanium tetrachloride involving a fi-
nal soxhlet-extraction, which delivers the catalyst as a yellow-
brown powder.[4] In contrast, we described a synthesis of
[Ind2TiMe2] from commercially available bis(indenyl)dichlo-
rotitanium, which can easily be methylated with methyllithium
in diethyl ether.[2b] In this case, purification of the catalyst was
accomplished by a classical aqueous workup procedure, which
gave [Ind2TiMe2] as a yellow crystalline compound of high
* Prof. Dr. S. Doye
Fax: +49-441-798-3329
E-Mail: doye@uni-oldenburg.de
[a] Institut für Chemie
Universität Oldenburg
Carl-von-Ossietzky-Straße 9–11
26111 Oldenburg, Germany
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201300433 or from the au-
thor.
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Z. Anorg. Allg. Chem. 2014, 640, (1), 118–121

One-Pot Synthesis of Bis(indenyl)dimethyltitanium
purity. In this context, it must be noted that [Ind2TiMe2] is a vacuum at 35 °C (rotary evaporator). After washing of the resi-
surprisingly water stable compound with only limited stability due with hexanes at –50 °C,[7] [Ind2TiMe2] was obtained as
orange needles in pure form as gauged by H and 13C NMR
(see Supporting Information) and it was possible to obtain an
accurate elemental analysis. Five runs of the described pro-
cedure were carried out by three different persons on a 20
or 40 mmol scale (based on TiCl4) and the average yield was
determined to be 61%. In single experiments, the yields varied
from 56 to 64% proving the very good reproducibility of the
procedure, which can entirely be carried out within a few
hours. Due to its facile decomposition at room temperature,
[Ind2TiMe2] was stored at –30 °C in the freezer. Although no
loss of its catalytic activity (e.g. in hydroaminoalkylation reac-
tions) could be determined over a period of several months,
the color of the solid material slowly changed from orange to
yellow. In general, storage of [Ind2TiMe2] at room temperature
or in solution leads to rapid decomposition, which is always
accompanied by a color change from yellow-orange to brown
and finally to dark brown. In an inert atmosphere of nitrogen,
the thermal decomposition point was determined to be 79–
80 °C. This facile thermal decomposition could additionally be
confirmed by NMR and ESR spectroscopy. Heating a sample
of diamagnetic [Ind2TiMe2] in [D6]benzene to a temperature
of 80 °C for 3 h resulted in the total disappearance of all NMR
signals of the titanium complex. On the other hand, the appear-
ance of an ESR signal strongly indicates the formation of para-
magnetic titanium species under these conditions. Interestingly,
no corresponding ESR signal could be detected after storing
[Ind2TiMe2] for six months at –30 °C in an inert atmosphere
proving the good storability of the complex under these condi-
tions.
1
in the solid state and in solution at room temperature. Unfortu-
nately, both synthetic approaches combine advantages and dis-
advantages. While the first synthetic approach starting from
indene, methyllithium, and titanium tetrachloride is the most
inexpensive option, the final purification procedure, the
soxhlet-extraction, is a time-consuming method that also leads
to decomposition of the temperature labile product
[Ind2TiMe2]. The presence of thermally formed impurities in
the finally isolated material is strongly indicated by the re-
ported yellow-brown color[5] of the product and the inaccurate
elemental analysis in the mentioned publication.[4] In contrast,
our quick aqueous workup procedure, which is usually per-
formed at room temperature (or below) offers the advantage
that thermal decomposition of [Ind2TiMe2] is minimized. In
addition, [Ind2TiMe2] is efficiently separated from all other
water labile lithium or titanium species present in the reaction
mixture. Unfortunately, bis(indenyl)dichlorotitanium is an ex-
pensive starting material, which represents a severe drawback
especially when [Ind2TiMe2] needs to be synthesized on a
multi-gram scale.
In order to provide the synthetic community with a simple,
inexpensive, reliable, and reproducible procedure for a multi-
gram synthesis of bis(indenyl)dimethyltitanium of high purity,
we now combined the one-pot approach starting from inexpen-
sive indene, methyllithium and titanium tetrachloride with a
quick aqueous workup procedure (Scheme 2).
Finally, it must be noted that the optimized procedure can
also be used for the synthesis of the closely related metallocene
bis(cyclopentadienyl)dimethyltitanium[8] from cyclopentadi-
ene, methyllithium, and titanium tetrachloride. Due to the fact
that in the solid state [Cp2TiMe2] (Cp = η5-cyclopentadienyl)
is not stable at room temperature, the compound was isolated
as a 0.22 m solution in toluene (53% yield; for details, see the
Experimental Section).
Scheme 2. One-pot synthesis of bis(indenyl)dimethyltitanium.
Initial preparation of an equimolar mixture of methyllithium
and the indenyllithium salt was achieved by combining four
equivalents of methyllithium with two equivalents of indene in
diethyl ether at 0–25 °C. Rapid treatment of the obtained
orange solution with one equivalent of titanium tetrachloride
dissolved in hexanes at 0 °C gave a dark brown suspension.
For the addition of titanium tetrachloride, a dropping funnel
without a pressure equalizing tube equipped with a separate
argon inlet was used to obtain an ether-free atmosphere in the
funnel. This avoids the formation of any titanium tetrachloro
ether complexes, which could disturb rapid addition of the tita-
nium tetrachloride solution. Subsequent hydrolysis with ice-
cold water and extraction of the aqueous layer with diethyl
ether[6] afforded an ether solution of [Ind2TiMe2], from which
Conclusions
A simple, reliable, and reproducible one-pot procedure for
the multi-gram synthesis of highly pure bis(indenyl)dimethylti-
tanium was developed, which relies on the use of indene,
methyllithium, and titanium tetrachloride as inexpensive start-
ing materials. The isolation of the product is achieved by a
convenient and quick aqueous workup procedure. Overall,
quantities of several grams of [Ind2TiMe2] can easily be syn-
thesized within a few hours. The successful application of the
same procedure towards the synthesis of bis(cyclopenta-
dienyl)dimethyltitanium shows that the new protocol might
also be useful for the synthesis of other related metallocene
the desired complex could be isolated by concentration under derivatives.
Z. Anorg. Allg. Chem. 2014, 118–121
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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119

J. H. Ross, T. Preuß, C. Brahms, S. Doye
ARTICLE
80.0 mmol) was slowly added via syringe and the resulting mixture
was stirred at 25 °C for 30 min to give a white suspension. The drop-
ping funnel was charged with titanium tetrachloride (3.79 g,
20.0 mmol) and hexanes (50 mL). After the reaction vessel had been
cooled to 0 °C, the solution of titanium tetrachloride in hexanes was
added rapidly to form a yellow-brown suspension, which was stirred
at 25 °C for 2.5 h in the absence of light. The mixture was poured into
ice-cold water (300 mL) and the layers were separated.[6] The aqueous
layer was extracted with diethyl ether (100 mL) and the combined or-
ganic layers were dried with MgSO4 and filtered into a 500 mL round-
bottom Schlenk flask. After concentration under vacuum (rotary evap-
orator, 35 °C) to a volume of approximately 10 mL[10] the flask was
flushed with argon and cooled to 0 °C. The orange solution was diluted
with dry toluene (30 mL) and concentrated under vacuum at 0 °C to a
volume of approximately 10 mL[10] to remove remaining diethyl ether
and hexanes. Finally, the residue was diluted with dry toluene (40 mL)
to give an orange solution of the title compound [Cp2TiMe2] (48 mL,
c = 0.22 mol·L–1 in toluene, 10.6 mmol, 53%). This solution was
stored in an inert atmosphere (argon or nitrogen) in the dark at –30 °C.
Experimental Section
General Remarks: The reactions were carried out in an atmosphere
of argon using standard Schlenk line techniques. Unless otherwise
noted, all reagents were purchased from Acros Organics. Indene (90%,
stabilized) was purified by distillation (25 cm Vigreux column) at
3.00 Torr and stored in an argon atmosphere over molecular sieves
(4 Å) at –30 °C prior to use. Cyclopentadiene was freshly distilled
from dicyclopentadiene (93%, stabilized, purchased from Merck
Chemicals) and iron powder in an atmosphere of argon. Methyllithium
(1.6 mol·L–1 in diethyl ether), titanium tetrachloride (99.9%) and tolu-
ene (99.85%, toluene extra dry with molecular sieves) were used as
received. Diethyl ether, hexanes and [D6]benzene were distilled from
sodium in an argon atmosphere. NMR spectra were recorded with a
Bruker Avance III spectrometer (1H, 500 MHz; 13C, 126 MHz) at
305 K. Chemical shifts (δ) are reported in ppm relative to the solvent
residual peak of [D6]benzene (1H, 7.16 ppm; 13C, 128.00 ppm). The
IR spectrum was recorded with a Bruker Tensor 27 spectrometer using
an attenuated total reflection method (ATR). The decomposition point
was determined in a sealed capillary with a Schorpp-Gerätetechnik
melting point MPM-H2 apparatus. Elemental analysis was performed
with a HEKAtech Euro EA-CHNS Analyzer. The ESR experiments
were carried out with a magnet tech MiniScope MS 300 spectrometer.
1
The concentration of the [Cp2TiMe2] solution was determined by H
1
NMR spectroscopy. H NMR (500 MHz, C6D6, 305 K): δ = 5.69 (s,
10 H, C5H5), 0.06 (s, 6 H, CH3) ppm. 13C{1H} NMR (126 MHz, C6D6,
DEPT, 305 K): δ = 113.2 (CH), 46.1 (CH3) ppm.
Preparation of Bis(indenyl)dimethyltitanium:
A
flame-dried
Supporting Information (see footnote on the first page of this article):
Copies of the 1H and 13C NMR spectra of bis(indenyl)dimethyltita-
nium and dimethyltitanocene, pictures of the experimental setup.
500 mL three-necked round-bottom flask, equipped with a Teflon®-
coated oval stirring bar (2.5 cm), a septum, an argon inlet, and a drop-
ping funnel[9] was charged with indene (4.65 g, 40.0 mmol) and diethyl
ether (50 mL) and cooled to 0 °C. A solution of methyllithium
(35.00 g, c = 1.6 mol·L–1 in diethyl ether, 80.0 mmol) was slowly
added via syringe and the resulting mixture was stirred at 25 °C for
30 min to give an orange solution. The dropping funnel was charged
with titanium tetrachloride (3.79 g, 20.0 mmol) and hexanes (50 mL).
After the reaction vessel had been cooled to 0 °C, the solution of tita-
nium tetrachloride in hexanes was added rapidly to form a dark brown
suspension, which was stirred at 25 °C for 2.5 h. The mixture was
poured into ice-cold water (300 mL) and the layers were separated.[6]
The aqueous layer was extracted with diethyl ether (2ϫ100 mL) and
the combined organic layers were dried with MgSO4 and filtered into
a 500 mL round-bottom Schlenk flask. After concentration under vac-
uum (rotary evaporator, 35 °C) the flask was flushed with argon and
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft for financial support
of our research.
References
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hexanes (50 mL) at –50 °C and dried under vacuum to give the title
compound [Ind2TiMe2] as orange needles (3.91 g, 12.7 mmol, 64%).
The product was stored in an inert atmosphere (argon or nitrogen) at
–30 °C. Mp. 79–80 °C (dec.). C20H20Ti (308.24): C 77.66 (calcd.
77.93), H 6.63 (6.54)%. 1H NMR (500 MHz, C6D6, 305 K): δ = 7.18–
3
7.22 (m, 4 H, CH), 6.92–6.96 (m, 4 H, CH), 5.80 (d, JH,H = 3.3 Hz,
4 H, CH), 5.38 (t, 3JH,H = 3.3 Hz, 2 H, CH), –0.50 (s, 6 H, CH3) ppm.
13C{1H} NMR (126 MHz, C6D6, DEPT, 305 K): δ = 125.6 (CH), 125.5
(C), 125.4 (CH), 117.5 (CH), 105.3 (CH), 51.5 (CH3) ppm. IR (neat):
ν˜ = 3103 (vw), 3036 (w), 2951 (m), 2882 (m), 2792 (w), 1949 (vw),
1920 (w), 1896 (vw), 1818 (w), 1791 (w), 1721 (vw), 1698 (w), 1622
(w), 1595 (w), 1530 (w), 1483 (w), 1448 (w), 1410 (m), 1346 (s),
1338 (s), 1259 (w), 1214 (m), 1192 (w), 1151 (w), 1119 (w), 1104 (w),
1090 (w), 1046 (m), 994 (w), 976 (vw), 950 (w), 914 (m), 873 (w),
847 (w), 834 (w), 806 (vs), 748 (vs), 689 (m) cm–1.
[3] For [Ind2TiMe2]-catalyzed hydroaminoalkylation reactions of alk-
enes, see: a) R. Kubiak, I. Prochnow, S. Doye, Angew. Chem.
2009, 121, 1173–1176; Angew. Chem. Int. Ed. 2009, 48, 1153–
1156; b) R. Kubiak, I. Prochnow, S. Doye, Angew. Chem. 2010,
122, 2683–2686; Angew. Chem. Int. Ed. 2010, 49, 2626–2629; c)
T. Preuß, W. Saak, S. Doye, Chem. Eur. J. 2013, 19, 3833–3837.
[4] D. Balboni, I. Camurati, G. Prini, L. Resconi, Inorg. Chem. 2001,
40, 6588–6597.
[5] Heating of [Ind2TiMe2] generally causes decomposition of the
complex and a color change from yellow-orange to dark brown.
[6] During the aqueous workup procedure, occasionally, formation of
an emulsion is observed. In this case, swirling of the separation
funnel leads to a better phase separation.
Preparation of Bis(cyclopentadienyl)dimethyltitanium: A flame-
dried 500 mL three-necked round-bottom flask, equipped with a Tef-
lon®-coated oval stirring bar (2.5 cm), a septum, an argon inlet, and a
dropping funnel[9] was charged with freshly distilled cyclopentadiene
(2.64 g, 40.0 mmol) and diethyl ether (50 mL) and cooled to 0 °C. A
solution of methyllithium (35.00 g, c = 1.6 mol·L–1 in diethyl ether,
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Z. Anorg. Allg. Chem. 2014, 118–121

One-Pot Synthesis of Bis(indenyl)dimethyltitanium
[7] Washing with hexanes results in a significantly improved purity
of the product due to removal of unreacted indene.
[8] N. A. Petasis, in: Encyclopedia of Reagents for Organic Synthesis
Vol. 1 (Ed.: L. A. Paquette), Wiley, New York, 1995, pp. 470–
473.
[9] To obtain an ether-free atmosphere in the dropping funnel, a fun-
nel without a pressure equalizing tube equipped with a separate
argon inlet was used.
[10] CAUTION: Due to the fact that solid [Cp2TiMe2] can undergo
spontaneous explosive decomposition, removal of the entire sol-
vent must be avoided.
Received: August 28, 2013
Published Online: October 24, 2013
Z. Anorg. Allg. Chem. 2014, 118–121
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.zaac.wiley-vch.de
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