Titanocene dichloride

{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 439751940 | ImageFile = Cp2TiCl2.png | ImageSize = 150px | ImageName = Titanocene dichloride | ImageFile1 = Titanocene-dichloride-3D-balls.png | ImageSize1 = 150px | ImageName1 = Ball-and-stick model of titanocene dichloride | ImageFile2 = Cp2TiCl2Sample.jpg | ImageSize2 = 150px | ImageName2 = Sample of titanocene dichloride | IUPACName = Dichloridobis(η⁵-cyclopentadienyl)titanium | OtherNames = titanocene dichloride, dichlorobis(cyclopentadienyl)titanium(IV) |Section1={{Chembox Identifiers | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 1271-19-8 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 34981141 | EC_number = 215-035-9 | PubChem = 5284468 | RTECS = XR2050000 | UNNumber = 3261 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = MJE0547U1U | 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 | InChIKey = YMNCCEXICREQQV-JUFMQDBHAK | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/2C5H5.2ClH.Ti/c2*1-2-4-5-3-1;;;/h2*1-5H;2*1H;/q2*-1;;;+4/p-2 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = YMNCCEXICREQQV-UHFFFAOYSA-L | SMILES = [cH-]1cccc1.[cH-]1cccc1.Cl[Ti+2]Cl

}} |Section2={{Chembox Properties | Formula = C₁₀H₁₀Cl₂Ti | MolarMass = 248.96 g/mol | Appearance = bright red solid | Density = 1.60 g/cm³, solid | Solubility = sl. sol. with hydrolysis | MeltingPtC = 289 | MeltingPt_notes = }} |Section3={{Chembox Structure | Coordination = Dist. tetrahedral | CrystalStruct = Triclinic | Dipole = }} |Section7={{Chembox Hazards | ExternalSDS = | NFPA-H = 2 | NFPA-F = | NFPA-R = 1 | Hazards_ref=<ref>{{cite web |title=Summary of Classification and Labelling |url=https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/41331 |access-date=5 December 2021}}</ref> | GHSPictograms = {{GHS07}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|315|335}} | PPhrases = {{P-phrases|201|202|261|264|270|271|280|281|301+310|301+312|302+352|304+340|305+351+338|308+313|312|330|332+313|337+313|362|403+233|405|501}} }} |Section8={{Chembox Related | OtherCompounds = Ferrocene<br /> Zirconocene dichloride<br> Hafnocene dichloride<br>Vanadocene dichloride<br> Niobocene dichloride<br>Tantalocene dichloride<br>Molybdocene dichloride<br> Tungstenocene dichloride<br> TiCl₄}} }} '''Titanocene dichloride''' is the organotitanium compound with the formula (''η''⁵-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.<ref>{{cite book | editor-first=S. |editor-last=Budaver | title=The Merck Index |edition=11th |publisher=Merck & Co., Inc. | year=1989 }}</ref> It shows antitumour activity and was the first non-platinum complex to undergo clinical trials as a chemotherapy drug.<ref name = "anti-cancer" />

==Preparation and structure== The standard preparations of Cp₂TiCl₂ start with titanium tetrachloride. The original synthesis by Wilkinson and Birmingham, using sodium cyclopentadienide,<ref>{{cite journal | author1-link=Geoffrey Wilkinson |first1= G.|last1= Wilkinson |first2=J.G. |last2=Birmingham | title = Bis-cyclopentadienyl Compounds of Ti, Zr, V, Nb and Ta | journal = J. Am. Chem. Soc. | volume = 76 | issue = 17 | year = 1954 | pages = 4281–4284 | doi = 10.1021/ja01646a008|bibcode= 1954JAChS..76.4281W}}</ref> is still commonly used:<ref>{{cite journal |title=Cp₂TiCl₂: Synthesis, Characterization, Modeling and Catalysis|author1=Sara E. Johnson |author2=Taylor A. Bell |author3=Joseph K. West|journal=Journal of Chemical Education|year=2022|volume=99|number=5|pages=2121–2128|doi=10.1021/acs.jchemed.1c01272|bibcode=2022JChEd..99.2121J |s2cid=248287682 }}</ref>

:2&nbsp;NaC₅H₅ + TiCl₄ → (C₅H₅)₂TiCl₂ + 2&nbsp;NaCl

It can also be prepared by using freshly distilled cyclopentadiene rather than its sodium derivative:<ref>{{cite book | first = J. M. | last = Birmingham | title = Synthesis of Cyclopentadienyl Metal Compounds | series = Advances in Organometallic Chemistry | volume = 2 | year = 1965 | pages = 365–413 | doi = 10.1016/S0065-3055(08)60082-9 | isbn = 9780120311026 }}</ref>

:2&nbsp;C₅H₆ + TiCl₄ → (C₅H₅)₂TiCl₂ + 2&nbsp;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°.<ref>{{cite journal | last1=Clearfield|first1=Abraham | title=Structural Studies of (π-C₅H₅)₂MX₂ Complexes and their Derivatives. The Structure of Bis(π-cyclopentadienyl)titanium Dichloride | journal=Can. J. Chem. | volume=53 | year=1975 | issue=11 | pages=1621–1629 | doi=10.1139/v75-228 | last2=Warner | first2=David Keith | last3=Saldarriaga Molina | first3=Carlos Hermán | last4=Ropal | first4=Ramanathan | last5=Bernal | first5=Ivan|display-authors=etal}}</ref>

==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.<ref>{{cite book|first1=Alan |last1=Shaver |first2=James M. |last2=McCall |first3=Gabriela |last3=Marmolejo |title=Inorganic Syntheses |chapter=Cyclometallapolysulfanes (And Selanes) of Bis(η ⁵ -Cyclopentadienyl) Titanium(IV), Zirconium(IV), Molybdenum(IV), and Tungsten(IV) |date=1990 |volume=27 |pages=59–65 |doi=10.1002/9780470132586.ch11|isbn=9780470132586 }}</ref>

The Petasis reagent, Cp₂Ti(CH₃)₂, is prepared from the action of methylmagnesium chloride<ref>{{OrgSynth | last1= Payack |first1=J. F. |last2=Hughes |first2=D. L.|last3=Cai |first3=D. |last4=Cottrell |first4=I. F. |last5=Verhoeven |first5=T. R. | prep = v79p0019 | volume = 79 | pages = 19 | year = 2002 | title = Dimethyltitanocene}}</ref> or methyllithium<ref>{{cite journal | last1= Claus |first1=K. |last2=Bestian |first2=H. | journal = Justus Liebigs Ann. Chem. | year = 1962 | volume = 654 | pages = 8–19 | doi = 10.1002/jlac.19626540103 | title = Über die Einwirkung von Wasserstoff auf einige metallorganische Verbindungen und Komplexe}}</ref> 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.<ref name="Herrmann">{{cite book | last1 = Herrmann | first1 = W.A. | title = The Methylene Bridge | series = Advances in Organometallic Chemistry | year = 1982 | volume = 20 | pages = 159–263 | doi=10.1016/s0065-3055(08)60522-5 | isbn = 9780120311200 }}</ref><ref name="Strauss">{{cite encyclopedia|last=Straus |first=D. A.|title=''μ''-Chlorobis(cyclopentadienyl)(dimethylaluminium)-''μ''-methylenetitanium |encyclopedia=Encyclopedia of Reagents for Organic Synthesis |publisher=John Wiley |location=London |date=2000}}</ref>

===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.<ref>{{cite journal|last1 = Chandra|first1 = K.|last2 = Sharma|first2 = R. K.|last3 = Kumar|first3 = N.|last4 = Garg|first4 = B. S.|title = Preparation of ''η''⁵-Cyclopentadienyltitanium Trichloride and ''η''⁵-Methylcyclopentadienyltitanium Trichloride|journal = Chem. Ind. - London|year = 1980|volume = 44|pages = 288–289}}</ref>

The sandwich complex (Cycloheptatrienyl)(cyclopentadienyl)titanium is prepared by treatment of titanocene dichloride with lithium cycloheptatrienyl.<ref>{{cite journal |doi=10.1002/anie.202009634|title=Exploring the Organometallic Route to Molecular Spin Qubits: The &#91;Cp ''Ti''(cot)&#93; Case|year=2021|last1=Camargo|first1=Luana C.|last2=Briganti|first2=Matteo|last3=Santana|first3=Francielli S.|last4=Stinghen|first4=Danilo|last5=Ribeiro|first5=Ronny R.|last6=Nunes|first6=Giovana G.|last7=Soares|first7=Jaísa F.|last8=Salvadori|first8=Enrico|last9=Chiesa|first9=Mario|last10=Benci|first10=Stefano|last11=Torre|first11=Renato|last12=Sorace|first12=Lorenzo|last13=Totti|first13=Federico|last14=Sessoli|first14=Roberta|journal=Angewandte Chemie International Edition|volume=60|issue=5|pages=2588–2593|pmid=33051985|bibcode=2021ACIE...60.2588D |hdl=2318/1765157|s2cid=222351619|url=https://zenodo.org/record/4926051 |hdl-access=free}}</ref>

Titanocene itself, TiCp₂, is so highly reactive that it rearranges into a Ti^III hydride dimer and has been the subject of much investigation.<ref name = TiCp2-A>{{cite book|title = Organometallic Chemistry of Titanium, Zirconium, and Hafnium|pages = 229–237|chapter = Titanocene|first1 = P. C.|last1 = Wailes|first2 = R. S. P.|last2 = Coutts|first3 = H.|last3 = Weigold|publisher = Academic Press|year = 1974|chapter-url = https://books.google.com/books?id=wIlsA73iqpEC&pg=PA229|isbn = 9780323156479}}</ref><ref name = TiCp2-B>{{cite book|title = Organometallic Chemistry: A Unified Approach|first1 = R. C.|last1 = Mehrotra|first2 = A.|last2 = Singh|edition = 2nd|publisher = New Age International Publishers|location = New Delhi|year = 2000|chapter = 4.3.6 η⁵-Cyclopentadienyl d-Block Metal Complexes|pages = 243–268|chapter-url = https://books.google.com/books?id=NSQy3mFKRM8C&pg=PA258|isbn = 9788122412581}}</ref> 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, {{nowrap|μ(η⁵:η⁵-fulvalene)-di-(μ-hydrido)-bis(η⁵-cyclopentadienyltitanium),}} can be prepared and the resulting solvate structurally characterised by X-ray crystallography.<ref name = TitanoceneXRay>{{cite journal|first1 = Sergei I.|last1 = Troyanov|first2 = Helena|last2 = Antropiusová|first3 = Karel|last3 = Mach|journal = J. Organomet. Chem.|title = 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|volume = 427|issue = 1|year = 1992|pages = 49–55|doi = 10.1016/0022-328X(92)83204-U}}</ref> The same compound had been reported earlier by a lithium aluminium hydride reduction<ref>{{cite journal|title = Preparation of μ-(η⁵:η⁵-Fulvalene)-di-μ-hydrido-bis(η⁵-cyclopentadienyltitanium) by the reduction of Cp₂TiCl₂ with LiAlH₄ in aromatic solvents|first1 = Helena|last1 = Antropiusová|first2 = Alena|last2 = Dosedlová|first3 = Vladimir|last3 = Hanuš|last4 = Karel|first4 = Mach|journal = Transition Met. Chem.|year = 1981|volume = 6|issue = 2|pages = 90–93|doi = 10.1007/BF00626113|s2cid = 101189483}}</ref> and sodium amalgam reduction<ref>{{cite journal|title = Chemistry of oxophilic transition metals. 2. Novel derivatives of titanocene and zirconocene|first1 = Tomas|last1 = Cuenca|first2 = Wolfgang A.|last2 = Herrmann|first3 = Terence V.|last3 = Ashworth|journal = Organometallics|year = 1986|volume = 5|issue = 12|pages = 2514–2517|doi = 10.1021/om00143a019}}</ref> of titanocene dichloride, and studied by ¹H NMR<ref>{{cite journal|journal = J. Organomet. Chem.|volume = 290|issue = 3|year = 1985|pages = 301–305|title = ¹H NMR Spectra and electronic structure of binuclear niobocene and titanocene containing fulvalene ligands|first1 = D. A.|last1 = Lemenovskii|first2 = I. F.|last2 = Urazowski|first3 = Yu K.|last3 = Grishin|first4 = V. A.|last4 = Roznyatovsky|doi = 10.1016/0022-328X(85)87293-4}}</ref> prior to its definitive characterisation.<ref name = TiCp2-A /><ref name = TiCp2-B /> 200px|thumb|left|"Titanocene" is not Ti(C₅H₅)₂, but rather this isomer with a fulvalene dihydride structure.<ref name = TiCp2-B /><ref name = TitanoceneXRay />

===Redox=== Reduction with zinc gives the dimer of bis(cyclopentadienyl)titanium(III) chloride in a solvent-mediated chemical equilibrium:<ref>{{cite book |first1 = L. E.|last1 = Manzer|first2 = E. A.|last2 = Mintz|first3 = T. J.|last3 = Marks | title=Inorganic Syntheses | chapter=18. Cyclopentadienyl Complexes of Titanium(III) and Vanadium(III) |doi = 10.1002/9780470132524.ch18|volume = 21|year = 1982|pages = 84–86|isbn = 9780470132524}}</ref><ref>{{cite journal|last1 = Nugent|first1 = William A.|last2 = RajanBabu|first2 = T. V.|title = Transition-metal-centered radicals in organic synthesis. Titanium(III)-induced cyclization of epoxy olefins|journal = J. Am. Chem. Soc.|volume = 110|issue = 25|pages = 8561–8562|doi = 10.1021/ja00233a051|year = 1988 | bibcode=1988JAChS.110.8561N }}</ref>

600px|center

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:<ref>{{cite encyclopedia|first=Erik |last=Kuester |title=Bis(5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium |encyclopedia=Encyclopedia of Reagents for Organic Synthesis |date=2002 |publisher=John Wiley|doi=10.1002/047084289X.rn00022|chapter=Bis(η5-2,4-cyclopentadienyl)bis(trimethylphosphine)titanium |isbn=0471936235 }}</ref> :Cp₂TiCl₂ + 2&nbsp;CO + Mg → Cp₂Ti(CO)₂ + MgCl₂ :Cp₂TiCl₂ + 2&nbsp;PR₃ + Mg → Cp₂Ti(PR₃)₂ + MgCl₂

Alkyne derivatives of titanocene have the formula (C₅H₅)₂Ti(C₂R₂) and the corresponding benzyne complexes are known.<ref name="buchwald">{{cite journal | first1=S. L. |last1=Buchwald |first2=R. B. |last2=Nielsen | title=Group 4 Metal Complexes of Benzynes, Cycloalkynes, Acyclic Alkynes, and Alkenes | journal=Chem. Rev. | volume=88 | year=1988 | issue=7 | pages = 1047–1058 | doi = 10.1021/cr00089a004}}</ref> One family of derivatives are the titanocyclopentadienes.<ref name="rosenthal">{{cite journal | first1 = Uwe | last1 = Rosenthal | first2 = Paul-Michael |last2 = Pellny | first3 = Frank G. | last3 = Kirchbauer | first4 = Vladimir V. | last4 = Burlakov | title = What Do Titano- and Zirconocenes Do with Diynes and Polyynes? | journal = Chem. Rev. | volume = 33 | year = 2000 | issue = 2 | pages = 119–129 | doi = 10.1021/ar9900109 | pmid = 10673320}}</ref> 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.<ref>{{Cite journal|last1 = Rosenthal|first1 = Uwe|last2 = Burlakov|first2 = Vladimir V.|last3 = Arndt|first3 = Perdita|last4 = Baumann|first4 = Wolfgang|last5 = Spannenberg|first5 = Anke|year = 2003|title = The Titanocene Complex of Bis(trimethylsilyl)acetylene: Synthesis, Structure, and Chemistry|journal = Organometallics|volume = 22|issue = 5|pages = 884–900|doi = 10.1021/om0208570}}</ref> center|frameless|686x686px

Titanocene equivalents react with alkenyl alkynes followed by carbonylation and hydrolysis to form bicyclic cyclopentadienones, related to the Pauson–Khand reaction.<ref>{{cite journal | first=F. A. |last=Hicks| title=Scope of the Intramolecular Titanocene-Catalyzed Pauson-Khand Type Reaction | journal=J. Am. Chem. Soc. | volume=121 | year=1999 | issue=25 | pages=5881–5898 | doi = 10.1021/ja990682u|display-authors=etal}}</ref> A similar reaction is the reductive cyclization of enones to form the corresponding alcohol in a stereoselective manner.<ref>{{cite journal | first1= N. M. |last1=Kablaoui |first2=S. L. |last2=Buchwald | title = Development of a Method for the Reductive Cyclization of Enones by a Titanium Catalyst | journal = J. Am. Chem. Soc. | volume = 118 | year = 1998 | issue = 13 | pages = 3182–3191 | doi = 10.1021/ja954192n}}</ref>

Reduction of titanocene dichloride in the presence of conjugated dienes such as 1,3-butadiene gives ''η''³-allyltitanium complexes.<ref>{{cite journal | first1= F. |last1=Sato | title = Synthesis of Organotitanium Complexes from Alkenes and Alkynes and Their Synthetic Applications | journal = Chem. Rev. | volume = 100 | issue = 8 | year = 2000 | pages = 2835–2886 | doi = 10.1021/cr990277l | last2 = Urabe | first2 = Hirokazu | last3 = Okamoto | first3 = Sentaro | pmid=11749307}}</ref> Related reactions occur with diynes. Furthermore, titanocene can catalyze C&ndash;C bond metathesis to form asymmetric diynes.<ref name="rosenthal" />

Titanocene dichloride as a photoredox catalyst to open epoxides in green light.<ref>{{Cite journal |last1=Zhang |first1=Zhenhua |last2=Hilche |first2=Tobias |last3=Slak |first3=Daniel |last4=Rietdijk |first4=Niels R. |last5=Oloyede |first5=Ugochinyere N. |last6=Flowers |first6=Robert A. |last7=Gansäuer |first7=Andreas |date=2020-06-08 |title=Titanocenes as Photoredox Catalysts Using Green-Light Irradiation |journal=Angewandte Chemie International Edition |language=en |volume=59 |issue=24 |pages=9355–9359 |doi=10.1002/anie.202001508 |issn=1433-7851 |pmc=7317808 |pmid=32216162 |bibcode=2020ACIE...59.9355Z }}</ref>

===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.<ref name = "anti-cancer">{{cite book|title = Bioinorganic Chemistry: A Short Course|first = R. M.|last = Roat-Malone|edition = 2nd|year = 2007|publisher = John Wiley & Sons|pages = 19–20|isbn = 978-0-471-76113-6|url = https://books.google.com/books?id=Ykx54y7LdK8C&q=molybdocene+dichloride&pg=PA20}}</ref><ref>{{cite journal|doi=10.1039/C6CS00860G|pmid=28124046|author1=Cini, M.|author2=Bradshaw, T. D.|author3=Woodward, S.|title=Using titanium complexes to defeat cancer: the view from the shoulders of Titans|journal=Chem. Soc. Rev.|year=2017|volume=46|issue=4|pages=1040–1051|url=http://eprints.nottingham.ac.uk/40186/1/ChemSocRev-ForNottsEPrints.pdf|access-date=2019-07-13|archive-date=2018-07-19|archive-url=https://web.archive.org/web/20180719211541/http://eprints.nottingham.ac.uk/40186/1/ChemSocRev-ForNottsEPrints.pdf|url-status=dead}}</ref>

==References== {{reflist|30em}}

==Further reading== * {{OrgSynth|prep=V79P0019|last1=Payack|first1= J. F.|last2= Hughes|first2= D. L.|last3= Cai|first3= D.|last4= Cottrell |first4=I. F.|last5= Verhoeven |first5=T. R. |title=Dimethyltitanocene Titanium, bis(''η''⁵-2,4-cyclopentadien-1-yl)dimethyl- |collvol=10 |collvolpage=355 |volume= 79 |page=19 |date=2002}}. * {{cite journal | first1= S.|last1= Gambarotta |first2=C. |last2=Floriani |first3=A. |last3=Chiesi-Villa |first4=C. |last4=Guastini | title = Cyclopentadienyldichlorotitanium(III): a free-radical-like reagent for reducing azo (N:N) multiple bonds in azo and diazo compounds | year = 1983 | journal = J. Am. Chem. Soc. | volume = 105 | issue = 25 | pages = 7295–7301 | doi = 10.1021/ja00363a015 |bibcode= 1983JAChS.105.7295G }} * {{cite journal | first= P. J.|last= Chirik | title = Group 4 Transition Metal Sandwich Complexes: Still Fresh after Almost 60 Years | year = 2010 | journal = Organometallics | volume = 29 | issue = 7 | pages = 1500–1517 | doi = 10.1021/om100016p}}

{{Titanium compounds}} {{Cyclopentadiene complexes}}

{{DEFAULTSORT:Titanocene Dichloride}} Category:Titanocenes Category:Chloro complexes Category:Titanium(IV) compounds