Titanocene dichloride

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Titanocene dichloride
Titanocene dichloride
Ball-and-stick model of titanocene dichloride
Names
IUPAC name
Dichloridobis(η5-cyclopentadienyl)titanium
Other names
titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV)
Identifiers
CAS number 1271-19-8 YesY
PubChem 5284468
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
Crystal structure Triclinic
Dist. tetrahedral
Hazards
R-phrases R37, R38
S-phrases S36
NFPA 704
Flammability (red): no hazard code Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g., calcium Special hazards (white): no codeNFPA 704 four-colored diamond
Related compounds
Related compounds
Ferrocene
Zirconocene dichloride
Hafnocene dichloride
Vanadocene dichloride
Niobocene dichloride
Tantalocene dichloride
Molybdocene dichloride
Tungstenocene dichloride
TiCl4
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY verify (what isYesY/N?)
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]

Cp2TiCl2 continues to be prepared from titanium tetrachloride, in the same way as its original synthesis by Wilkinson and Birmingham:[4]

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.[5]

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[edit]

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

Application in preparing 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 cyclo-sulfur 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 by with TiCl4 or by reaction with SOCl2.[11]

Ti(II) derivatives[edit]

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.[12]

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.[13] One family of derivatives are the titanocyclopentadienes.[14]

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson-Khand reaction).[15] A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.[16]

Reduction of titanocene dichloride in the presence of conjugated dienes such as 1,3-butadiene gives η3-allyltitanium complexes.[17] Related reactions occur with diynes. Furthermore, titanocene can catalyze C-C bond metathesis to form asymmetric diynes.[14]

Derivatives of (C5Me5)2TiCl2[edit]

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.[13]

Medicinal uses[edit]

Titanocene dichloride was investigated as an anticancer drug.[18] In fact, it was both the first non-platinum coordination complex and the first metallocene to undergo a clinic trial.[3] The mechanism by which it acts is not fully understood; however, it has been conjectured that its activity might be attributable to the compound's interactions with the protein transferrin.[3][19]

References[edit]

  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. ^ a b c 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. ^ 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. 
  5. ^ J.M. Birmingham (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". Org. Synth. 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". Advances in Organometallic Chemistry 20: 159–263. doi:10.1016/s0065-3055(08)60522-5. 
  9. ^ Straus, D. A., "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium": Encyclopedia of Reagents for Organic Synthesis. John Wiley, London, 2000.
  10. ^ Catherine E. Housecroft; Alan G. Sharpe (2008). "Chapter 16: The group 16 elements". Inorganic Chemistry, 3rd Edition. 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. Industry: 288–9. 
  12. ^ Erik Kuester "Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium" Encyclopedia of Reagents for Organic Synthesis, 2002, John Wiley.doi:10.1002/047084289X.rn00022.
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. PMID 11749307. 
  18. ^ R. J. Knox and P. C. McGowan. "Metallocenes as Anti-Tumour Reagents". International patent application, WO 2004/005305. 
  19. ^ Waern, J. B.; Harris, H. H.; Lai, B.; Cai, Z.; Harding, M. M.; Dillon, C. T. (2005). "Intracellular Mapping of the Distribution of Metals Derived from the Antitumor Metallocenes". J. Biol. Inorg. Chem. 10 (5): 443–452. doi:10.1007/s00775-005-0649-1. 

Further reading[edit]

  • 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.