Titanocene dichloride

Titanocene dichloride

Names
IUPAC name Dichloridobis(η5-cyclopentadienyl)titanium
Other names titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV)
Identifiers
CAS Number	1271-19-8  Y
3D model (JSmol)	Interactive image
ChemSpider	34981141  Y
ECHA InfoCard	100.013.669
EC Number	215-035-9
PubChem CID	5284468
RTECS number	XR2050000
UNII	MJE0547U1U  Y
UN number	3261
CompTox Dashboard (EPA)	DTXSID3021354
InChI InChI=1S/2C5H5.2ClH.Ti/c2*1-2-4-5-3-1;;;/h2*1-5H;2*1H;/q2*-1;;;+4/p-2 N Key: YMNCCEXICREQQV-UHFFFAOYSA-L N InChI=1/2C5H5.2ClH.Ti/c2*1-2-4-5-3-1;;;/h2*1-5H;2*1H;/q2*-1;;;+4/p-2/r2C5H5.Cl2Ti/c2*1-2-4-5-3-1;1-3-2/h2*1-5H;/q2*-1;+2 Key: YMNCCEXICREQQV-JUFMQDBHAK
SMILES [cH-]1cccc1.[cH-]1cccc1.Cl[Ti+2]Cl
Properties
Chemical formula	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)
Solubility in water	sl. sol. with hydrolysis
Structure
Crystal structure	Triclinic
Coordination geometry	Dist. tetrahedral
Hazards [1]
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H315, H335
Precautionary statements	P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire 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). N  verify  (what is  YN ?) 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. ^[2] It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a chemotherapy drug. ^[3]

Preparation and structure

The standard preparations of Cp₂TiCl₂ start with titanium tetrachloride. The original synthesis by Wilkinson and Birmingham, using sodium cyclopentadienide, ^[4] is still commonly used: ^[5]

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

It can also be prepared by using freshly distilled cyclopentadiene rather than its sodium derivative: ^[6]

2 C₅H₆ + TiCl₄ → (C₅H₅)₂TiCl₂ + 2 HCl

Focusing on the geometry of the Ti center, Cp₂TiCl₂ 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°. ^[7]

Reactions

Halide replacement reactions

Cp₂TiCl₂ serves as a source of Cp₂Ti²⁺. A large range of nucleophiles will displace chloride. With NaSH and with polysulfide salts, one obtains the sulfido derivatives Cp₂Ti(SH)₂ and Cp₂TiS₅. ^[8]

The Petasis reagent, Cp₂Ti(CH₃)₂, is prepared from the action of methylmagnesium chloride ^[9] or methyllithium ^[10] on Cp₂TiCl₂. This reagent is useful for the conversion of esters into vinyl ethers.

The Tebbe reagent Cp₂TiCl(CH₂)Al(CH₃)₂, arises by the action of 2 equivalents Al(CH₃)₃ on Cp₂TiCl₂. ^{[11] [12]}

Reactions affecting Cp ligands

One Cp ligand can be removed from Cp₂TiCl₂ to give tetrahedral CpTiCl₃. This conversion can be effected with TiCl₄ or by reaction with SOCl₂. ^[13]

The sandwich complex (Cycloheptatrienyl)(cyclopentadienyl)titanium is prepared by treatment of titanocene dichloride with lithium cycloheptatrienyl. ^[14]

Titanocene itself, TiCp₂, is so highly reactive that it rearranges into a Ti^III hydride dimer 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 of benzene, a fulvalene complex, μ(η⁵:η⁵-fulvalene)-di-(μ-hydrido)-bis(η⁵-cyclopentadienyltitanium), can be prepared and the resulting solvate structurally characterised by X-ray crystallography. ^[17] The same compound had been reported earlier by a lithium aluminium hydride reduction ^[18] and sodium amalgam reduction ^[19] of titanocene dichloride, and studied by ¹H NMR ^[20] prior to its definitive characterisation. ^{[15] [16]}

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

Redox

Reduction with zinc gives the dimer of bis(cyclopentadienyl)titanium(III) chloride in a solvent-mediated chemical equilibrium: ^{[21] [22]}

Cp₂TiCl₂ 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: ^[23]

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

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

Alkyne derivatives of titanocene have the formula (C₅H₅)₂Ti(C₂R₂) and the corresponding benzyne 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 and B, which are both resonance 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 the Pauson–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 conjugated dienes such as 1,3-butadiene gives η³-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]

Derivatives of (C₅Me₅)₂TiCl₂

Many analogues of Cp₂TiCl₂ are known. Prominent examples are the ring-methylated derivatives (C₅H₄Me)₂TiCl₂ and (C₅Me₅)₂TiCl₂.

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. ^{[3] [31]}

References

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3. 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. Sara E. Johnson; Taylor A. Bell; Joseph K. West (2022). "Cp₂TiCl₂: Synthesis, Characterization, Modeling and Catalysis". Journal of Chemical Education. 99 (5): 2121–2128. Bibcode:2022JChEd..99.2121J. doi:10.1021/acs.jchemed.1c01272. S2CID   248287682.
6. Birmingham, J. M. (1965). "Synthesis of Cyclopentadienyl Metal Compounds". Adv. Organometal. Chem. Advances in Organometallic Chemistry. 2: 365–413. doi:10.1016/S0065-3055(08)60082-9. ISBN   9780120311026.
7. 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.
8. 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. ISBN   9780470132586.
9. Payack, J. F.; Hughes, D. L.; Cai, D.; Cottrell, I. F.; Verhoeven, T. R. (2002). "Dimethyltitanocene". Organic Syntheses . 79: 19.
10. Claus, K.; Bestian, H. (1962). "Über die Einwirkung von Wasserstoff auf einige metallorganische Verbindungen und Komplexe". Justus Liebigs Ann. Chem. 654: 8–19. doi:10.1002/jlac.19626540103.
11. Herrmann, W.A. (1982). "The Methylene Bridge". Adv. Organomet. Chem. Advances in Organometallic Chemistry. 20: 159–263. doi:10.1016/s0065-3055(08)60522-5. ISBN   9780120311200.
12. Straus, D. A. (2000). "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium". Encyclopedia of Reagents for Organic Synthesis. London: John Wiley.
13. 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.
14. Camargo, Luana C.; Briganti, Matteo; Santana, Francielli S.; Stinghen, Danilo; Ribeiro, Ronny R.; Nunes, Giovana G.; Soares, Jaísa F.; Salvadori, Enrico; Chiesa, Mario; Benci, Stefano; Torre, Renato; Sorace, Lorenzo; Totti, Federico; Sessoli, Roberta (2021). "Exploring the Organometallic Route to Molecular Spin Qubits: The [Cp Ti(cot)] Case". Angewandte Chemie International Edition. 60 (5): 2588–2593. doi:10.1002/anie.202009634. hdl: 2318/1765157 . PMID   33051985. S2CID   222351619.
15. Wailes, P. C.; Coutts, R. S. P.; Weigold, H. (1974). "Titanocene". Organometallic Chemistry of Titanium, Zirconium, and Hafnium. Academic Press. pp. 229–237. ISBN   9780323156479.
16. 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.
17. Troyanov, 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.
18. 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. S2CID   101189483.
19. 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.
20. 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.
21. 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. ISBN   9780470132524.{{cite book}}: |journal= ignored (help)
22. 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.
23. Kuester, Erik (2002). "Bis(η5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium". Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium. Encyclopedia of Reagents for Organic Synthesis . John Wiley. doi:10.1002/047084289X.rn00022. ISBN   0471936235.
24. 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.
25. Rosenthal, 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. PMID   10673320.
26. 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.
27. 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.
28. 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.
29. 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.
30. Zhang, Zhenhua; Hilche, Tobias; Slak, Daniel; Rietdijk, Niels R.; Oloyede, Ugochinyere N.; Flowers, Robert A.; Gansäuer, Andreas (2020-06-08). "Titanocenes as Photoredox Catalysts Using Green-Light Irradiation". Angewandte Chemie International Edition. 59 (24): 9355–9359. doi:10.1002/anie.202001508. ISSN   1433-7851. PMC   7317808 . PMID   32216162.
31. Cini, M.; Bradshaw, T. D.; Woodward, S. (2017). "Using titanium complexes to defeat cancer: the view from the shoulders of Titans" (PDF). Chem. Soc. Rev. 46 (4): 1040–1051. doi:10.1039/C6CS00860G. PMID   28124046. Archived from the original (PDF) on 2018-07-19. Retrieved 2019-07-13.

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 . 79: 19; Collected Volumes, vol. 10..
• 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.
• Chirik, P. J. (2010). "Group 4 Transition Metal Sandwich Complexes: Still Fresh after Almost 60 Years". Organometallics . 29 (7): 1500–1517. doi:10.1021/om100016p.