# Titanocene dichloride

Titanocene dichloride is the organotitanium compound with the formula (η$^5$-C$_5$H$_5$)$_2$TiCl$_2$, commonly abbreviated as Cp$_2$TiCl$_2$. This metallocene is a common reagent in organometallic and organic synthesis. 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 drug.

## Preparation and structure

The standard preparations of Cp$_2$TiCl$_2$ start with titanium tetrachloride. The original synthesis by Wilkinson and Birmingham, using sodium cyclopentadienide, is still commonly used:
    2 NaC$_5$H$_5$ + TiCl$_4$ → (C$_5$H$_5$)$_2$TiCl$_2$ + 2 NaCl
It can also be prepared by using freshly distilled cyclopentadiene rather than its sodium derivative:
    2 C$_5$H$_6$ + TiCl$_4$ → (C$_5$H$_5$)$_2$TiCl$_2$ + 2 HCl
Focusing on the geometry of the Ti center, Cp$_2$TiCl$_2$ adopts a distorted tetrahedral 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$_2$TiCl$_2$ serves as a source of Cp$_2$Ti$^{2+}$. A large range of nucleophiles will displace chloride. With NaSH and with polysulfide salts, one obtains the sulfido derivatives Cp$_2$Ti(SH)$_2$ and Cp$_2$TiS$_5$.
The Petasis reagent, Cp$_2$Ti(CH$_3$)$_2$, is prepared from the action of methylmagnesium chloride or methyllithium on Cp$_2$TiCl$_2$. This reagent is useful for the conversion of esters into vinyl ethers.
The Tebbe reagent Cp$_2$TiCl(CH$_2$)Al(CH$_3$)$_2$, arises by the action of 2 equivalents Al(CH$_3$)$_3$ on Cp$_2$TiCl$_2$.

### Reactions affecting Cp ligands

One Cp ligand can be removed from Cp$_2$TiCl$_2$ to give tetrahedral CpTiCl$_3$. This conversion can be effected with TiCl$_4$ or by reaction with SOCl$_2$.
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, a fulvalene complex, μ(η$^5$:η$^5$-fulvalene)-di-(μ-hydrido)-bis(η$^5$-cyclopentadienyltitanium), can be prepared and the resulting solvate structurally characterised by X-ray crystallography. The same compound had been reported earlier by a lithium aluminium hydride reduction and sodium amalgam reduction of titanocene dichloride, and studied by $^1$H 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:
Cp$_2$TiCl$_2$ 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$_2$TiCl$_2$ + 2 CO + Mg → Cp$_2$Ti(CO)$_2$ + MgCl$_2$
    Cp$_2$TiCl$_2$ + 2 PR$_3$ + Mg → Cp$_2$Ti(PR$_3$)$_2$ + MgCl$_2$
Alkyne derivatives of titanocene have the formula (C$_5$H$_5$)$_2$Ti(C$_2$R$_2$) and the corresponding benzyne complexes are known. One family of derivatives are the titanocyclopentadienes. Rosenthal's reagent, Cp$_2$Ti(η$^2$-Me$_3$SiC≡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 dienes such as 1,3-butadiene 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 (C$_5$Me$_5$)$_2$TiCl$_2$

Many analogues of Cp$_2$TiCl$_2$ are known. Prominent examples are the ring-methylated derivatives (C$_5$H$_4$Me)$_2$TiCl$_2$ and (C$_5$Me$_5$)$_2$TiCl$_2$.

## Medicinal research

Titanocene dichloride was investigated as an anticancer drug. In fact, it was both the first non-platinum coordination complex and the first metallocene to undergo a clinical trial.