Titanocene dichloride

Titanocene dichloride
IUPAC name dichloridobis (η5- cyclopentadienyl) titanium
Other names titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV)
Identifiers
CAS number	1271-19-8 Y
RTECS number	XR2050000
Properties
Molecular formula	C10H10Cl2Ti
Molar mass	248.96 g/mol
Appearance	bright red solid
Density	1.60 g/cm3, solid
Melting point	289 °C
Solubility in water	sl. sol. with hydrolysis
Structure
Crystal structure	Triclinic
Coordination geometry	Dist. tetrahedral
Hazards
R-phrases	R37, R38
S-phrases	S36
NFPA 704	0 2 1
Related compounds
Related compounds	Ferrocene Zirconocene dichloride Hafnocene dichloride Vanadocene dichloride Niobocene dichloride Tantalocene dichloride Molybdenocene dichloride Tungstenocene dichloride TiCl4
Y dichloride (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Titanocene dichloride is the organotitanium compound with the formula (η⁵-C₅H₅)₂TiCl₂, commonly abbreviated as Cp₂TiCl₂. This metallocene is a common reagent in organometallic and organic synthesis. It exists as a bright red solid that slowly hydrolyzes in air.^[1] Cp₂TiCl₂ does not adopt the typical "sandwich" structure like ferrocene due to the 4 ligands around the metal centre, but rather takes on a distorted tetrahedral shape.^[2]

Preparation

Cp₂TiCl₂ continues to be prepared from titanium tetrachloride, in the same way as its original synthesis by Wilkinson and Birmingham:^[3]

2 NaC₅H₅ + TiCl₄ → (C₅H₅)₂TiCl₂ + 2 NaCl

The reaction is conducted in THF. Work-up sometimes washing with hydrochloric acid to convert hydrolysis derivatives to the dichloride. Recrystallization from toluene forms acicular crystals.

Cp₂TiCl₂ can also be prepared by using freshly distilled cyclopentadiene:

2 C₅H₆ + TiCl₄ → (C₅H₅)₂TiCl₂ + 2 HCl

This reaction is conducted under a nitrogen atmosphere and by using THF as solvent. The product is purified by soxhlet extraction using toluene as solvent.^[4]

The complex is pseudotetrahedral. Each of the two Cp rings are attached as η⁵ ligands. Viewing the Cp ligands as tridentate, the complex has a coordination number of 8.

Applications in organic synthesis

Cp₂TiCl₂ is a generally useful reagent that effectively behaves as a source of Cp₂Ti²⁺. A large range of nucleophiles will displace chloride. Examples:

• The Petasis reagent, Cp₂Ti(CH₃)₂, is prepared from the action of CH₃MgCl or MeLi on Cp₂TiCl₂. This reagent is useful for the conversion of esters into vinyl ethers.
• The Tebbe's reagent Cp₂TiCl(CH₂)Al(CH₃)₂, arises by the action of 2 equivalents Al(CH₃)₃ on Cp₂TiCl₂.

Reactions

Cp₂TiCl₂ undergoes anion exchange reactions, e.g. to give the pseudohalides. With NaSH and with polysulfide salts, one obtains the sulfido derivatives Cp₂Ti(SH)₂ and Cp₂TiS₅.

One Cp ligand can be removed from Cp₂TiCl₂ to give tetrahedral CpTiCl₃. This conversion can be effected by with TiCl₄ or by reaction with SOCl₂.^[5]

Ti(II) derivatives

Cp₂TiCl₂ is a precursor to many Ti(II) derivatives. Titanocene, TiCp₂, is itself so highly reactive that it is not known but it can be trapped by conducting the reduction in the presence of ligands. Reduction of titanocene dichloride results in the fulvalene complex shown in the figure.^{[citation needed]}

"Titanocene" is not Ti(C₅H₅)₂, but this fulvalene dihydride complex.

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.^[6]

Cp₂TiCl₂ + 2 CO + Mg → Cp₂Ti(CO)₂
+ MgCl₂

Cp₂TiCl₂ + 2 PR₃ + Mg → Cp₂Ti(PR₃)₂ + MgCl₂

Cp₂TiCl₂ + 2 Me₃SiCCSiMe₃ + Mg → Cp₂TiMe₃SiCCSiMe₃ + MgCl₂

With only one equivalent of reducing agent, Ti(III) species result, i.e. Cp₂TiCl.

Alkyne and benzyne derivatives of titanocene are well known.^[7] One family of derivatives are the titanocyclopentadienes.^[8]

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson-Khand reaction).^[9] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.^[10]

Reduction of titanocene dichloride in the presence of conjugated dienes such as 1,3-butadiene gives η³-allyltitanium complexes.^[11] Related reactions occur with diynes. Furthermore, titanocene can catalyze C-C bond metathesis to form asymmetric diynes.^[8]

Derivatives of (C₅Me₅)₂TiCl₂

The closest relative to titanocene-ethylene complex is that derived by Na reduction of (C₅Me₅)₂TiCl₂ in the presence of ethylene. The Cp compound cannot be made. This pentamethylcyclopentadienyl (Cp*) species undergoes many reactions such as cycloadditions of alkynes.^[7]

Medicinal uses

Titanocene dichloride was investigated as an anticancer drug.^[12] The mechanism by which it acts is not understood, but some conjecture that it might be due to its interactions with the protein transferrin.^[13]

References

1. ^ S. Budaver, ed. (1989). The Merck Index (11th ed.). Merck & Co, Inc.. 
2. ^ Clearfield, et al.; Warner, David Keith; Saldarriaga-Molina, Carlos Herman; Ropal, Ramanathan; Bernal, Ivan (1975). "Structural Studies of (π-C₅H₅)₂ MX₂ Complexes and their Derivatives. The Structure of Bis(π-cyclopentadienyl)titanium Dichloride". Canadian Journal of Chemistry 53 (11): 1621–1629. doi:10.1139/v75-228. 
3. ^ G. Wilkinson and J.G. Birmingham (1954). "Bis-cyclopentadienyl Compounds of Ti, Zr, V, Nb and Ta". Journal of the American Chemical Society 76 (17): 4281–4284. doi:10.1021/ja01646a008. 
4. ^ J.M. Birmingham; Birmingham, J. M. (1964). "Synthesis of Cyclopentadienyl Metal Compounds". Adv. Organometal. Chem. 2 (17): 373. doi:10.1021/ja01646a008. 
5. ^ Chandra, K.; Sharma, R. K.; Kumar, N.; Garg, B. S. (1980,). "Preparation of η⁵-Cyclopentadienyltitanium Trichloride and η⁵-Methylcyclopentadienyltitanium Trichloride". Chem. Industry: 288–9. 
6. ^ Erik Kuester "Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium" Encyclopedia of Reagents for Organic Synthesis, 2002, John Wiley.doi:10.1002/047084289X.rn00022.
7. ^ ^{a b} S.L. Buchwald and R.B. Nielsen (1988). "Group 4 Metal Complexes of Benzynes, Cycloalkynes, Acyclic Alkynes, and Alkenes". Chemical Reviews 88 (7): 1047–1058. doi:10.1021/cr00089a004. 
8. ^ ^{a b} U. Rosenthal, et al. (2000). "What Do Titano- and Zirconocenes Do with Diynes and Polyynes?". Chemical Reviews 33 (2): 119–129. doi:10.1021/ar9900109. 
9. ^ F.A. Hicks, et al. (1999). "Scope of the Intramolecular Titanocene-Catalyzed Pauson-Khand Type Reaction". Journal of the American Chemical Society 121 (25): 5881–5898. doi:10.1021/ja990682u. 
10. ^ N.M. Kablaoui and S.l. Buchwald (1998). "Development of a Method for the Reductive Cyclization of Enones by a Titanium Catalyst". Journal of the American Chemical Society 118 (13): 3182–3191. doi:10.1021/ja954192n. 
11. ^ F. Sato; Urabe, Hirokazu; Okamoto, Sentaro (2000). "Synthesis of Organotitanium Complexes from Alkenes and Alkynes and Their Synthetic Applications". Chemical Reviews 100 (8): 2835–2886. doi:10.1021/cr990277l. 
12. ^ R. J. Knox and P. C. McGowan. "Metallocenes as Anti-Tumour Reagents". International patent application, WO 2004/005305. 
13. ^ M. Guo, et al. (2000). "Ti^IV Uptake and Release by Human Serum Transferrin and Recognition of Ti^IV-Transferrin by Cancer Cells: Understanding the Mechanism of Action of the Anticancer Drug Titanocene Dichloride". Biochemistry 39 (33): 10023–10033. doi:10.1021/bi000798z. PMID 10955990. 

Further reading

• Payack, J. F.; Hughes, D. L.; Cai, D.; Cottrell, I. F.; Verhoeven, T. R. "Dimethyltitanocene Titanium, bis(η5-2,4-cyclopentadien-1-yl)dimethyl-" Organic Syntheses, Coll. Vol. 10, p. 355 (2004); Vol. 79, p. 19 (2002).
• S. Gambarotta, C. Floriani, A. Chiesi-Villa and C. Guastini (1983). "Cyclopentadienyldichlorotitanium(III): a free-radical-like reagent for reducing azo (N:N) multiple bonds in azo and diazo compounds". J. Am. Chem. Soc. 105 (25): 7295–7301. doi:10.1021/ja00363a015. 
• P. J. Chirik (2010). "Group 4 Transition Metal Sandwich Complexes: Still Fresh after Almost 60 Years". Organometallics 29 (7): 1500–1517. doi:10.1021/om100016p.