Titanocene dichloride

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Titanocene dichloride
Titanocene dichloride Ball-and-stick model of titanocene dichloride
General
Systematic name dicholorobis(η5-2,4-
cyclopentadien-1-yl)
titanium
Other names titanocene dichloride
Molecular formula C10H10Cl2Ti
Molar mass 248.96 g/mol
Appearance bright red solid
CAS number 1271-19-8
Properties
Density and phase 1.60 g/cm3, solid
Solubility in water sl. sol. with hydrolysis
Other solvents CH2Cl2, THF
Melting point 289 °C
Structure
Coordination
geometry
Dist. tetrahedral
Crystal structure Triclinic
Dipole moment ? D
Hazards
MSDS External MSDS
Main hazards mild irritant
NFPA 704
NFPA 704.svg
0
2
1
 
R/S statement R: R37, R38
S: S36
RTECS number XR2050000
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
Related compounds
Related compounds Ferrocene
Zirconacene dichloride
TiCl4
Except where noted otherwise, data are given for
materials in their standard state (at 25 °C, 100 kPa)
Infobox disclaimer and references

Titanocene dichloride, or dicyclopentadienyl titanium dichloride is (η5-C5H5)2TiCl2 (commonly abbreviated as Cp2TiCl2); this metallocene is widely used in organometallic and organic synthesis both as a reagent and as a catalyst. It is exists as a bright red solid, forming acicular crystals when crystallized from toluene.[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 similarly to its original synthesis by Wilkinson and Birmingham:[3]

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

The reaction is conducted in THF. Work-up entails extraction into chloroform/hydrogen chloride and recrystallization from toluene. In the original literature, the structure was poorly understood. Each of the two Cp rings are attached to Ti(IV) through all five carbon atoms. In organometallic chemical jargon, this bonding is referred to as η5 (see hapticity).

Applications in synthesis

Cp2TiCl2 is a generally useful reagent that effctively behaves as a source of Cp2Ti2+. Thus 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.
  • Cp2TiCl2 undergoes anion exchange reactions. With NaSH and with polysulfide salts, one obtains the sulfido derivatives Cp2Ti(SH)2 and Cp2TiS5.
  • The Tebbe's reagent Cp2TiCl(CH2)Al(CH3)2, arises by the action of 2 equivalents Al(CH3)3 on Cp2TiCl2.

Cp2TiCl2 can be stripped of one Cp ligand to give tetrahedral CpTiCl3 by reaction with TiCl4 or by reaction with SOCl2.[4]

Ti(II) derivatives

Cp2TiCl2 is a versatile 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 prsence of ligands. Routes to generate this reactive species include the use of Mg and Li alkyls (for alkyls beyond methyl)

Cp2TiCl2 + 2 EtMgBr (or 2 BuLi, etc.) → "TiCp2" + 2 EtCl (or 2 BuCl, etc.)

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 &pi: acceptor ligands.[5]

Cp2TiCl2 + 2 CO + Mg → Cp2Ti(CO)2
+ MgCl2
Cp2TiCl2 + 2 PR3 + Mg → Cp2Ti(PR3)2 + MgCl2
Cp2TiCl2 + 2 Me3SiCCSiMe3 + Mg → Cp2TiMe3SiCCSiMe3 + MgCl2

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

Alkyne derivatives of titanocene have received considerable attention. "Cp2Ti" + RCC(CH2)nCCR + acid → (cyclo) C=CHR(CH2)nC=CHR or C=CHR(CH2)nCCH3 (E isomer only)[6] (n usually 2-6; this can also yield a linked chain of titanocyclopentadienes).[7]

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson-Khand reaction).[8] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.[9]

"Titanocene" reacts with conjugated dienes (such as 1,3-butadiene) form the η3-allyltitanium complex.[10]

"Titanocene" regiospecifically binds diynes. Furthermore, titanocene can catalyze C-C bond metathesis to form asymmetric diynes.[7]

Benzyne complexes

Heating Cp2TiPh2 appears to generate Cp2TiC6H4, although this species is not isolated ever. Instead it is generated in the presence of trapping ligands such as PhCCPh and CO2 to give the 5-membered metallacycles. Similarly, a titanocene-benzyne complex results from the reaction of Cp2Ti with o-bromoflurobenzene and diphenylacetylene in the presence of Mg at low temperatures. The corresponding Cp2Zr derivatives are still better developed.[6]

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.[6]

Medicinal uses

Titanocene dichloride has being investigated as a potential anticancer drug (currently in clinical trials). The mechanism by which it acts is not understood, but some conjecture that it might be due to its interactions with the protein transferrin.[11]

References

  1. S. Budaver, ed. (1989). The Merck Index (11th ed.). Merck & Co, Inc. 
  2. Clearfield; et al. (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: 1621–1629. 
  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. Chandra, K.; Sharma, R. K.; Kumar, N.; Garg, B. S. (1980,). "Preparatoin of η5-Cyclopentadienyltitanium Trichloride andη5-Methylcyclopentadienyltitanium Trichloride". Chem. Industry: 288–9. 
  5. e-EROS Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. 2003. 
  6. 6.0 6.1 6.2 S.L. Buchwald and R.B. Nielsen (1988). "Group 4 Metal Complexes of Benzynes, Cycloalkynes, Acyclic Alkynes, and Alkenes". Chemical Reviews. 88: 1047–1058. doi:10.1021/cr00089a004. 
  7. 7.0 7.1 U. Rosenthal; et al. (2000). "What Do Titano- and Zirconocenes Do with Diynes and Polyynes?". Chemical Reviews. 33: 119–129. doi:10.1021/ar9900109. 
  8. F.A. Hicks; et al. (1999). "Scope of the Intramolecular Titanocene-Catalyzed Pauson-Khand Type Reaction". Journal of the American Chemical Society. 121: 5881–5898. doi:10.1021/ja990682u. 
  9. 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: 3182–3191. doi:10.1021/ja954192n. 
  10. F. Sato (2000). "Synthesis of Organotitanium Complexes from Alkenes and Alkynes and Their Synthetic Applications". Chemical Reviews. 100: 2835–2886. doi:10.1021/cr990277l. 
  11. M. Guo; et al. (2000). "TiIV Uptake and Release by Human Serum Transferrin and Recognition of TiIV-Transferrin by Cancer Cells: Understanding the Mechanism of Action of the Anticancer Drug Titanocene Dichloride". Biochemistry. 39: 10023–10033. 

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. 

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