Titanocene dichloride is theorganotitanium compound with the formula (η5-C5H5)2TiCl2, commonly abbreviated as Cp2TiCl2. Thismetallocene is a common reagent inorganometallic andorganic synthesis. It exists as a bright red solid that slowlyhydrolyzes in air.[2] It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as achemotherapy drug.[3]
It can also be prepared by using freshly distilledcyclopentadiene rather than its sodium derivative:[6]
2 C5H6 + TiCl4 → (C5H5)2TiCl2 + 2 HCl
Focusing on the geometry of the Ti center, Cp2TiCl2 adopts a distortedtetrahedral geometry (counting Cp as a monodentate ligand). The Ti-Cl distance is 2.37 Å and the Cl-Ti-Cl angle is 95°.[7]
Cp2TiCl2 serves as a source of Cp2Ti2+. A large range ofnucleophiles will displace chloride. WithNaSH and withpolysulfide salts, one obtains the sulfido derivatives Cp2Ti(SH)2 andCp2TiS5.[8]
Titanocene itself, TiCp2, is so highly reactive that it rearranges into a TiIII hydridedimer and has been the subject of much investigation.[15][16] This dimer can be trapped by conducting the reduction of titanocene dichloride in the presence of ligands; in the presence ofbenzene, afulvalene complex,μ(η5:η5-fulvalene)-di-(μ-hydrido)-bis(η5-cyclopentadienyltitanium), can be prepared and the resultingsolvate structurally characterised byX-ray crystallography.[17] The same compound had been reported earlier by alithium aluminium hydride reduction[18] andsodium amalgam reduction[19] of titanocene dichloride, and studied by1H NMR[20] prior to its definitive characterisation.[15][16]
"Titanocene" is not Ti(C5H5)2, but rather this isomer with a fulvalene dihydride structure.[16][17]
Cp2TiCl2 is a precursor to TiII 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:[23]
Alkyne derivatives of titanocene have the formula (C5H5)2Ti(C2R2) and the correspondingbenzyne complexes are known.[24] One family of derivatives are the titanocyclopentadienes.[25]Rosenthal's reagent, Cp2Ti(η2-Me3SiC≡CSiMe3), can be prepared by this method. Two structures are shown,A andB, which are bothresonance contributors to the actual structure of Rosenthal's reagent.[26]
Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to thePauson–Khand reaction.[27] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.[28]
Reduction of titanocene dichloride in the presence of conjugateddienes such as1,3-butadiene givesη3-allyltitanium complexes.[29] Related reactions occur with diynes. Furthermore, titanocene can catalyze C–C bond metathesis to form asymmetric diynes.[25]
Titanocene dichloride as a photoredox catalyst to open epoxides in green light.[30]
Titanocene dichloride was investigated as an anticancer drug. In fact, it was both the first non-platinumcoordination complex and the first metallocene to undergo a clinical trial.[3][31]
^Clearfield, Abraham; Warner, David Keith; Saldarriaga Molina, Carlos Hermán; Ropal, Ramanathan; Bernal, Ivan; et al. (1975). "Structural Studies of (π-C5H5)2MX2 Complexes and their Derivatives. The Structure of Bis(π-cyclopentadienyl)titanium Dichloride".Can. J. Chem.53 (11):1621–1629.doi:10.1139/v75-228.
^Shaver, Alan; McCall, James M.; Marmolejo, Gabriela (1990). "Cyclometallapolysulfanes (And Selanes) of Bis(η5-Cyclopentadienyl) Titanium(IV), Zirconium(IV), Molybdenum(IV), and Tungsten(IV)".Cyclometallapolysulfanes (and Selanes) of Bis(η5-Cyclopentadienyl) Titanium(IV), Zirconium(IV), Molybdenum(IV), and Tungsten(IV). Inorganic Syntheses. Vol. 27. pp. 59–65.doi:10.1002/9780470132586.ch11.ISBN9780470132586.
^Straus, D. A. (2000). "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium".Encyclopedia of Reagents for Organic Synthesis. London: John Wiley.
^Chandra, K.; Sharma, R. K.; Kumar, N.; Garg, B. S. (1980). "Preparation ofη5-Cyclopentadienyltitanium Trichloride andη5-Methylcyclopentadienyltitanium Trichloride".Chem. Ind. - London.44:288–289.
^abTroyanov, Sergei I.; Antropiusová, Helena; Mach, Karel (1992). "Direct proof of the molecular structure of dimeric titanocene; The X-ray structure of μ(η5:η5-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.
^Antropiusová, Helena; Dosedlová, Alena; Hanuš, Vladimir; Karel, Mach (1981). "Preparation of μ-(η5:η5-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.S2CID101189483.
^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.
^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.
^Manzer, L. E.; Mintz, E. A.; Marks, T. J. (1982). "18. Cyclopentadienyl Complexes of Titanium(III) and Vanadium(III)".Inorganic Syntheses. Vol. 21. pp. 84–86.doi:10.1002/9780470132524.ch18.ISBN9780470132524.{{cite book}}:|journal= ignored (help)
^Nugent, William A.; RajanBabu, T. V. (1988). "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.
^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.
^abRosenthal, Uwe; Pellny, Paul-Michael; Kirchbauer, Frank G.; Burlakov, Vladimir V. (2000). "What Do Titano- and Zirconocenes Do with Diynes and Polyynes?".Chem. Rev.33 (2):119–129.doi:10.1021/ar9900109.PMID10673320.
^Rosenthal, Uwe; Burlakov, Vladimir V.; Arndt, Perdita; Baumann, Wolfgang; Spannenberg, Anke (2003). "The Titanocene Complex of Bis(trimethylsilyl)acetylene: Synthesis, Structure, and Chemistry".Organometallics.22 (5):884–900.doi:10.1021/om0208570.
^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.
^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.
^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.PMID11749307.
Gambarotta, S.; Floriani, C.; Chiesi-Villa, A.; Guastini, C. (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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