Titanocene dichloride is the
organotitanium compound
Organotitanium chemistry is the science of organotitanium compounds describing their physical properties, synthesis, and reactions. Organotitanium compounds in organometallic chemistry contain carbon-titanium chemical bonds. They are reagents in or ...
with the formula (
''η''5-C
5H
5)
2TiCl
2, commonly abbreviated as Cp
2TiCl
2. This
metallocene
A metallocene is a compound typically consisting of two cyclopentadienyl anions (, abbreviated Cp) bound to a metallic element, metal center (M) in the oxidation state II, with the resulting general formula Closely related to the metallocenes are ...
is a common reagent in
organometallic
Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...
and
organic synthesis
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
. It exists as a bright red solid that slowly
hydrolyzes in air. It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a
chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
drug.
Preparation and structure
The standard preparations of Cp
2TiCl
2 start with
titanium tetrachloride
Titanium tetrachloride is the inorganic compound with the formula . It is an important intermediate in the production of titanium metal and the pigment titanium dioxide. is a volatile liquid. Upon contact with humid air, it forms thick clouds o ...
. The original synthesis by
Wilkinson and Birmingham, using
sodium cyclopentadienide
Sodium cyclopentadienide is an organosodium compound with the formula C5H5Na. The compound is often abbreviated as NaCp, where Cp− is the cyclopentadienide anion. Sodium cyclopentadienide is a colorless solid, although samples often are pin ...
, is still commonly used:
:2 NaC
5H
5 + TiCl
4 → (C
5H
5)
2TiCl
2 + 2 NaCl
It can also be prepared by using freshly distilled
cyclopentadiene
Cyclopentadiene is an organic compound with the chemical formula, formula C5H6. It is often abbreviated CpH because the cyclopentadienyl anion is abbreviated Cp−.
This colorless liquid has a strong and unpleasant odor. At room temperature, ...
rather than its sodium derivative:
:2 C
5H
6 + TiCl
4 → (C
5H
5)
2TiCl
2 + 2 HCl
Focusing on the geometry of the Ti center, Cp
2TiCl
2 adopts a distorted
tetrahedral
In geometry, a tetrahedron (: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular Face (geometry), faces, six straight Edge (geometry), edges, and four vertex (geometry), vertices. The tet ...
geometry (counting Cp as a monodentate ligand). The Ti-Cl distance is 2.37 Å and the Cl-Ti-Cl angle is 95°.
Reactions
Halide replacement reactions
Cp
2TiCl
2 serves as a source of Cp
2Ti
2+. A large range of
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
s will displace chloride. With
NaSH and with
polysulfide
Polysulfides are a class of chemical compounds derived from anionic chains of sulfur atoms. There are two main classes of polysulfides: inorganic and organic. The inorganic polysulfides have the general formula . These anions are the conjugate bas ...
salts, one obtains the sulfido derivatives Cp
2Ti(SH)
2 and
Cp2TiS5.
The
Petasis reagent
The Petasis reagent, named after Nicos A. Petasis, is an organotitanium compound with the formula Cp2Ti(CH3)2. It is an orange-colored solid.
Preparation and use
The Petasis reagent is prepared by the salt metathesis reaction of methylmagnesiu ...
, Cp
2Ti(CH
3)
2, is prepared from the action of
methylmagnesium chloride
Methylmagnesium chloride is an organometallic compound with the general formula . This highly flammable, colorless, and moisture sensitive compound is the simplest Grignard reagent and is commercially available, usually as a solution in tetrahydro ...
or
methyllithium
Methyllithium is the simplest organolithium reagent, with the empirical formula LiCH3. This s-block organometallic compound adopts an oligomeric structure both in solution and in the solid state. This highly reactive compound, invariably used i ...
on Cp
2TiCl
2. This reagent is useful for the conversion of esters into vinyl ethers.
The
Tebbe reagent
Tebbe's reagent is the organometallic compound with the formula (C5H5)2TiCH2ClAl(CH3)2. It is used in the methylidenation of carbonyl compounds, that is it converts organic compounds containing the R2C=O group into the related R2C=CH2 derivative ...
Cp
2TiCl(CH
2)Al(CH
3)
2, arises by the action of 2 equivalents Al(CH
3)
3 on Cp
2TiCl
2.
Reactions affecting Cp ligands
One Cp ligand can be removed from Cp
2TiCl
2 to give tetrahedral
CpTiCl3. This conversion can be effected with TiCl
4 or by reaction with
SOCl2.
The sandwich complex
(Cycloheptatrienyl)(cyclopentadienyl)titanium is prepared by treatment of titanocene dichloride with lithium cycloheptatrienyl.
Titanocene itself, TiCp
2, is so highly reactive that it rearranges into a Ti
III hydride
dimer and has been the subject of much investigation.
This dimer can be trapped by conducting the reduction of titanocene dichloride in the presence of ligands; in the presence of
benzene
Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...
, a
fulvalene complex, can be prepared and the resulting
solvate structurally characterised by
X-ray crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
.
The same compound had been reported earlier by a
lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula or . It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthe ...
reduction and
sodium amalgam
Sodium amalgam, with the common formula Na(Hg), is an alloy of mercury and sodium. The term amalgam is used for alloys, intermetallic compounds, and solutions (both solid solutions and liquid solutions) involving mercury as a major component. ...
reduction of titanocene dichloride, and studied by
1H NMR prior to its definitive characterisation.
Redox
Reduction with zinc gives the
dimer of
bis(cyclopentadienyl)titanium(III) chloride in a solvent-mediated
chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which both the Reagent, reactants and Product (chemistry), products are present in concentrations which have no further tendency to change with time, so that there is no observable chan ...
:

Cp
2TiCl
2 is a precursor to Ti
II derivatives.
Reductions have been investigated using Grignard reagent and alkyl lithium compounds. More conveniently handled reductants include Mg, Al, or Zn. The following syntheses demonstrate some of the compounds that can be generated by reduction of titanocene dichloride in the presence of π acceptor ligands:
:Cp
2TiCl
2 + 2 CO + Mg →
Cp2Ti(CO)2 + MgCl
2
:Cp
2TiCl
2 + 2 PR
3 + Mg → Cp
2Ti(PR
3)
2 + MgCl
2
Alkyne derivatives of titanocene have the formula (C
5H
5)
2Ti(C
2R
2) and the corresponding
benzyne complexes are known.
One family of derivatives are the titanocyclopentadienes.
Rosenthal's reagent, Cp
2Ti(η
2-Me
3SiC≡CSiMe
3), can be prepared by this method. Two structures are shown, A and B, which are both
resonance contributors to the actual structure of Rosenthal's reagent.

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the
Pauson–Khand reaction. A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.
Reduction of titanocene dichloride in the presence of conjugated
diene
In organic chemistry, a diene ( ); also diolefin, ) or alkadiene) is a covalent compound that contains two double bonds, usually among carbon atoms. They thus contain two alk''ene'' units, with the standard prefix ''di'' of systematic nome ...
s such as
1,3-butadiene
1,3-Butadiene () is the organic compound with the formula CH2=CH-CH=CH2. It is a colorless gas that is easily condensed to a liquid. It is important industrially as a precursor to synthetic rubber. The molecule can be viewed as the union of two ...
gives ''η''
3-allyltitanium complexes. Related reactions occur with diynes. Furthermore, titanocene can catalyze C–C bond metathesis to form asymmetric diynes.
Titanocene dichloride as a photoredox catalyst to open epoxides in green light.
Derivatives of (C5Me5)2TiCl2
Many analogues of Cp
2TiCl
2 are known. Prominent examples are the ring-methylated derivatives (C
5H
4Me)
2TiCl
2 and
(C5Me5)2TiCl2.
Medicinal research
Titanocene dichloride was investigated as an anticancer drug. In fact, it was both the first non-platinum
coordination complex
A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...
and the first metallocene to undergo a clinical trial.
References
Further reading
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{{DEFAULTSORT:Titanocene Dichloride
Titanocenes
Chloro complexes
Titanium(IV) compounds