Titanocene dichloride

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Titanocene dichloride
Titanocene dichloride
Ball-and-stick model of titanocene dichloride
Sample of titanocene dichloride
Names
IUPAC name
Dichloridobis(η5-cyclopentadienyl)titanium
Other names
titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV)
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.013.669
RTECS number XR2050000
Properties
C10H10Cl2Ti
Molar mass 248.96 g/mol
Appearance bright red solid
Density 1.60 g/cm3, solid
Melting point 289 °C (552 °F; 562 K)
sl. sol. with hydrolysis
Structure
Triclinic
Dist. tetrahedral
Hazards
R-phrases (outdated) R37, R38
S-phrases (outdated) S36
NFPA 704
Flammability (red): no hazard codeHealth code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroformReactivity code 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g., calciumSpecial hazards (white): no codeNFPA 704 four-colored diamond
2
1
Related compounds
Related compounds
Ferrocene
Zirconocene dichloride
Hafnocene dichloride
Vanadocene dichloride
Niobocene dichloride
Tantalocene dichloride
Molybdocene dichloride
Tungstenocene dichloride
TiCl4
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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] It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a chemotherapy drug.[3]

Preparation[edit]

The standard preparations of Cp2TiCl2 start with titanium tetrachloride. The original synthesis by Geoffrey Wilkinson and Birmingham uses sodium cyclopentadienide[4] is still commonly used:

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

The reaction is conducted in THF. Workup 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 rather than its sodium derivative:

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.[5]

The complex is pseudotetrahedral. Each of the two Cp rings are attached as η5 ligands.

Reactions[edit]

Use in organic synthesis[edit]

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

Precursor to unusual sulfur allotropes[edit]

Titanocene dichloride is used to prepare titanocene pentasulfide, a precursor to unusual alloptropes of sulfur:

Li2S5 + (C5H5)2TiCl2 → (C5H5)2TiS5 + LiCl
Structure of pentasulfur-titanocene complex

The resulting pentasulfur-titanocene complex is allowed to react with polysulfur dichloride to give the desired cyclosulfur of in the series:[10]

Reactions[edit]

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 with TiCl4 or by reaction with SOCl2.[11]

Reduction with zinc gives the dimer of bis(cyclopentadienyl)titanium(III) chloride in a solvent-mediated chemical equilibrium:[12][13]

N-RB equilibrium.jpg

Ti(II) derivatives, including titanocene[edit]

Cp2TiCl2 is a precursor to many TiII derivatives, though titanocene itself, TiCp2, is so highly reactive that it rearranges into a TiIII hydride dimer and has been the subject of much investigation.[14][15] 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(η55-fulvalene)-di-(μ-hydrido)-bis(η5-cyclopentadienyltitanium), can be prepared and the resulting solvate structurally characterised by X-ray crystallography.[16] The same compound had been reported earlier by a lithium aluminium hydride reduction[17] and sodium amalgam reduction[18] of titanocene dichloride, and studied by 1H NMR[19] prior to its definitive characterisation.[14][15]

"Titanocene" is not Ti(C5H5)2, but rather this isomer with a fulvalene dihydride structure.[15][16]

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:[20]

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

Alkyne derivatives of titanocene have the formula (C5H5)2Ti(C2R2). The corresponding benzyne complexes are known.[21] One family of derivatives are the titanocyclopentadienes.[22]

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson–Khand reaction).[23] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.[24]

Reduction of titanocene dichloride in the presence of conjugated dienes such as 1,3-butadiene gives η3-allyltitanium complexes.[25] Related reactions occur with diynes. Furthermore, titanocene can catalyze C-C bond metathesis to form asymmetric diynes.[22]

Derivatives of (C5Me5)2TiCl2[edit]

Many analogues of Cp2TiCl2 are known. Prominent examples are the ring-methylated derivatives (C5H4Me)2TiCl2 and (C5Me5)2TiCl2. The ethylene complex (C5Me5)2Ti(C2H4) can be synthesised by Na reduction of (C5Me5)2TiCl2 in the presence of ethylene. The Cp compound has not been prepared. This pentamethylcyclopentadienyl (Cp*) species undergoes many reactions such as cycloadditions of alkynes.[21]

Medicinal research[edit]

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.[3][26]

References[edit]

  1. ^ Budaver, S., ed. (1989). The Merck Index (11th ed.). Merck & Co., Inc. 
  2. ^ Clearfield, Abraham; Warner, David Keith; Saldarriaga Molina, Carlos Hermán; Ropal, Ramanathan; Bernal, Ivan; et al. (1975). "Structural Studies of (π-C5H5)2 MX2 Complexes and their Derivatives. The Structure of Bis(π-cyclopentadienyl)titanium Dichloride". Can. J. Chem. 53 (11): 1621–1629. doi:10.1139/v75-228. 
  3. ^ a b Roat-Malone, R. M. (2007). Bioinorganic Chemistry: A Short Course (2nd ed.). John Wiley & Sons. pp. 19–20. ISBN 978-0-471-76113-6. 
  4. ^ Wilkinson, G.; Birmingham, J.G. (1954). "Bis-cyclopentadienyl Compounds of Ti, Zr, V, Nb and Ta". J. Am. Chem. Soc. 76 (17): 4281–4284. doi:10.1021/ja01646a008. 
  5. ^ Birmingham, J. M. (1965). "Synthesis of Cyclopentadienyl Metal Compounds". Adv. Organometal. Chem. 2: 365–413. doi:10.1016/S0065-3055(08)60082-9. 
  6. ^ Payack, J. F.; Hughes, D. L.; Cai, D.; Cottrell, I. F.; Verhoeven, T. R. (2002). "Dimethyltitanocene". Organic Syntheses. 79: 19. 
  7. ^ Claus, K.; Bestian, H. (1962). "Über die Einwirkung von Wasserstoff auf einige metallorganische Verbindungen und Komplexe". Justus Liebigs Ann. Chem. 654: 8. doi:10.1002/jlac.19626540103. 
  8. ^ Herrmann, W.A. (1982). "The Methylene Bridge". Adv. Organomet. Chem. 20: 159–263. doi:10.1016/s0065-3055(08)60522-5. 
  9. ^ Straus, D. A. (2000). "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium". Encyclopedia of Reagents for Organic Synthesis. London: John Wiley. 
  10. ^ Housecroft, Catherine E.; Sharpe, Alan G. (2008). "Chapter 16: The group 16 elements". Inorganic Chemistry (3rd ed.). Pearson. p. 498. ISBN 978-0-13-175553-6. 
  11. ^ Chandra, K.; Sharma, R. K.; Kumar, N.; Garg, B. S. (1980). "Preparation of η5-Cyclopentadienyltitanium Trichloride and η5-Methylcyclopentadienyltitanium Trichloride". Chem. Ind. - London. 44: 288–289. 
  12. ^ Manzer, L. E.; Mintz, E. A.; Marks, T. J. (1982). "Cyclopentadienyl Complexes of Titanium(III) and Vanadium(III)". Inorg. Synth. 21: 84–86. doi:10.1002/9780470132524.ch18. 
  13. ^ Nugent, William A.; RajanBabu, T. V. "Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins". J. Am. Chem. Soc. 110 (25): 8561–8562. doi:10.1021/ja00233a051. 
  14. ^ a b Wailes, P. C.; Coutts, R. S. P.; Weigold, H. (1974). "Titanocene". Organometallic Chemistry of Titanium, Zirconium, and Hafnium. Organometallic Chemistry. Academic Press. pp. 229–237. ISBN 9780323156479. 
  15. ^ a b c Mehrotra, R. C.; Singh, A. (2000). "4.3.6 η5-Cyclopentadienyl d-Block Metal Complexes". Organometallic Chemistry: A Unified Approach (2nd ed.). New Delhi: New Age International Publishers. pp. 243–268. ISBN 9788122412581. 
  16. ^ a b Troyanov, Sergei I.; Antropiusová, Helena; Mach, Karel (1992). "Direct proof of the molecular structure of dimeric titanocene; The X-ray structure of μ(η55-fulvalene)-di-(μ-hydrido)-bis(η5-cyclopentadienyltitanium)·1.5 benzene". J. Organomet. Chem. 427 (1): 49–55. doi:10.1016/0022-328X(92)83204-U. 
  17. ^ Antropiusová, Helena; Dosedlová, Alena; Hanuš, Vladimir; Karel, Mach (1981). "Preparation of μ-(η55-Fulvalene)-di-μ-hydrido-bis(η5-cyclopentadienyltitanium) by the reduction of Cp2TiCl2 with LiAlH4 in aromatic solvents". Transition Met. Chem. 6 (2): 90–93. doi:10.1007/BF00626113. 
  18. ^ Cuenca, Tomas; Herrmann, Wolfgang A.; Ashworth, Terence V. (1986). "Chemistry of oxophilic transition metals. 2. Novel derivatives of titanocene and zirconocene". Organometallics. 5 (12): 2514–2517. doi:10.1021/om00143a019. 
  19. ^ Lemenovskii, D. A.; Urazowski, I. F.; Grishin, Yu K.; Roznyatovsky, V. A. (1985). "1H NMR Spectra and electronic structure of binuclear niobocene and titanocene containing fulvalene ligands". J. Organomet. Chem. 290 (3): 301–305. doi:10.1016/0022-328X(85)87293-4. 
  20. ^ Kuester, Erik (2002). "Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium". Encyclopedia of Reagents for Organic Synthesis. John Wiley. doi:10.1002/047084289X.rn00022. 
  21. ^ a b Buchwald, S.L.; Nielsen, R.B. (1988). "Group 4 Metal Complexes of Benzynes, Cycloalkynes, Acyclic Alkynes, and Alkenes". Chem. Rev. 88 (7): 1047–1058. doi:10.1021/cr00089a004. 
  22. ^ a b Rosenthal, U.; et al. (2000). "What Do Titano- and Zirconocenes Do with Diynes and Polyynes?". Chem. Rev. 33 (2): 119–129. doi:10.1021/ar9900109. 
  23. ^ Hicks, F. A.; et al. (1999). "Scope of the Intramolecular Titanocene-Catalyzed Pauson-Khand Type Reaction". J. Am. Chem. Soc. 121 (25): 5881–5898. doi:10.1021/ja990682u. 
  24. ^ Kablaoui, N. M.; Buchwald, S. L. (1998). "Development of a Method for the Reductive Cyclization of Enones by a Titanium Catalyst". J. Am. Chem. Soc. 118 (13): 3182–3191. doi:10.1021/ja954192n. 
  25. ^ Sato, F.; Urabe, Hirokazu; Okamoto, Sentaro (2000). "Synthesis of Organotitanium Complexes from Alkenes and Alkynes and Their Synthetic Applications". Chem. Rev. 100 (8): 2835–2886. doi:10.1021/cr990277l. PMID 11749307. 
  26. ^ Cini, M.; Bradshaw, T. D.; Woodward, S. (2017). "Using titanium complexes to defeat cancer: the view from the shoulders of Titans". Chem. Soc. Rev. 46: 1040–1051. doi:10.1039/C6CS00860G. 

Further reading[edit]