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A one-step synthesis of protected functionalised titanocene dichlorides
Inorganic Chemistry Communications 3 Ž2000. 337–340 www.elsevier.nlrlocaterinoche
A one-step synthesis of protected functionalised titanocene dichlorides Margaret A.D. McGowan, Patrick C. McGowan ) School of Chemistry, UniÕersity of Leeds, Leeds LS2 9JT, UK Received 17 April 2000
Abstract We report a novel, high yield one-step synthesis of water stable and soluble titanocene dichloride dihydrochloride salts from the direct reaction of the neutral amino-substituted cyclopentadienes with TiCl 4 . The following novel complexes have been synthesised: C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 5 x 2 TiCl 2 Ž 5 . , w C 5 H 4 CH Ž CH 2 . 4 N M e x 2 TiCl 2 Ž 6 . , w C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 5 x 2 TiCl 2 P 2H Cl Ž 7 . , wC 5 H 4CHŽCH 2 .4 x 2 NMeTiCl 2 P 2HCl Ž8., wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiMe 2 Ž9.. q 2000 Elsevier Science S.A. All rights reserved. Keywords: Anti-tumour agents; Cyclopentadienyl; Functionalisd titanocene dichlorides; One step synthesis; Water soluble titanium ŽIV. complexes
Recently, interest in the chemistry of amino-functionalised titanocenes has increased because of their potential to act as highly active and selective olefin polymerisation catalyst precursors w1–6x. Previous work in our group has involved the synthesis of early and late transition metal amino-functionalised metallocenes w7x. In such systems, the neutral amino function can reversibly co-ordinate to the metal centre, stabilising the highly reactive intermediates formed during homogeneous catalytic processes w1,4x. It has been shown that quaternisation of the pendant amino group can result in water soluble species w3,4,6–8x. In addition to potentially developing water soluble and air stable catalytic compounds, increased stability of titanocenes could prove useful in determining the biologically active species of the anti-tumour drug titanocene dichloride. While titanocene dichloride has been shown to act as an efficient anti-tumour agent w9–11x, there have been difficulties understanding the mechanism of action due to the low solubility and instability of the compound in aqueous media w9,10x. In an attempt to increase the stability of the active anti tumour titanocene dichloride agents to hydrolysis, we set out to synthesise aminofunctionalised titanocenes dichlorides and their dihydrochloride derivatives. It has been shown that the nature of both the counterion of the protonated species ŽCly, BF4y etc.. and the groups bound directly to the metal centre may affect the biological activity of the complexes w12x. Our
)
Corresponding author.
aim is to systematically vary the constituents of the molecular framework to achieve maximum biological activity. Reported synthetic methods of amino functionalised titanocene dichlorides require initial deprotonation of the neutral cyclopentadiene species to give the lithium, sodium or thallium salts w4–7x. The reaction of the corresponding cyclopentadienide salts with TiCl 4 affords the neutral metallocene dichlorides, which can then be reacted with HCl to give the dihydrochloride salts. The novel, high yielding synthesis Ž78–89%. reported here gives the air and water stable titanocene dichloride dihydrochloride salts directly by reaction of the neutral amino-functionalised cyclopentadiene and TiCl 4 . Using this one-step reaction, we have the ability to synthesise the protected form of a titanocene dichloride directly, which can then be stored indefinitely without decomposition in air. The synthetic method utilises the presence of the amino function as an ‘internal base’ and effectively reduces the conventional three-step synthesis to a high yield, one-step reaction. The use of an external base as a HCl trap in the synthesis of cyclopentadienyl-amido titanium complexes has been previously reported w13x and the pendant amino-function has been observed to react as an auxiliary base in the synthesis of late transition metal cyclopentadienyl complexes w14,15x. However, to the best of our knowledge the method presented here represents a new and facile route to bisŽcyclopentadienyl. derivatives of early transition metals. We believe this is the first recorded synthesis of a group IV metallocene dichloride dihydrochloride from the direct reaction of a neutral amino-substituted cyclopentadienyl species and a simple homoleptic metal halide w16x.
1387-7003r00r$ - see front matter q 2000 Elsevier Science S.A. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 Ž 0 0 . 0 0 0 9 4 - 0
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M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
The titanocene dichloride dihydrochloride salts wC 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 5 x 2 TiC l 2 P 2H C l and w C 5 H 4 C H ŽCH 2 .4 NMex 2TiCl 2 P 2HCl, Ž7,8. can be synthesised via Ži. the direct reaction of two equivalents of the neutral cyclopentadienes, C 5 H 5 Ž C H 2 . 2 N Ž C H 2 . 5 Ž 1 . and C 5 H 5 CHŽCH 2 .4 NMe Ž2. and TiCl 4 in toluene or Žii. the reaction of the sodium salts NaC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 Ž3. and NaC 5 H 4 CHŽCH 2 .4 NMe Ž4. with TiCl 4 , followed by reaction with HCl ŽScheme 1.. The substituted cyclopentadienes were synthesised as previously described w14,17x. The cyclopentadienyl sodium salts Ž3,4. were prepared by the reaction of sodium hydride and the neutral cyclopentadiene ligands in THF. The dihydrochloride salts are isolated as pale orange Ž7. or yellow Ž8. solids, which are soluble in polar solvents
such as methanol, water, and acetonitrile. They have been characterised by 1 H, 13 C, DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C.-COSY NMR spectroscopy and by FAB mass spectrometry. Elemental analysis was also obtained for 7. The ammonium protons are observed as broad signals in the low field region ca. d 10. The 1 H NMR of 7 in D 2 O shows no appreciable decomposition over 48 h and only partial decomposition is observed over 7 days. The neutral titanocene dichloride can be obtained by reaction of 7 with two equivalents of MeLi or by reaction of the sodium salt 3 with TiCl 4 in THF. The highly air and moisture sensitive titanocene dichloride, wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 Ž5. can be isolated as a crystalline, deep orange solid and is soluble in aprotic polar Ždiethyl ether, THF. and non-polar solvents Žtoluene, benzene.. An analytically pure sample
Scheme 1. Reagents and conditions: Ži. NaH, THF, 72–87%; Žii. TiCl 4 , THF, 67–73%; Žiii. HCl, 82–87%; Živ. MeLi, diethyl ether; and Žv. TiCl 4, toluene, 78–89%.
M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
was obtained by recrystallisation from diethyl ether and further characterisation data provided by 1 H and 13 C NMR spectroscopy. Full characterisation of wC 5 H 4 CHŽCH 2 .4NMex 2TiCl 2 , Ž6. proved difficult due to the formation of insoluble polymeric species, as previously observed for analogous amino-substituted titanocene dichloride complexes w4x. However, reaction with HCl yielded the expected titanocene dichloride dihydrochloride Ž8.. We have also found that reaction of 7 with four equivalents of MeLi ŽScheme 2. results in the formation of the thermally stable dimethylated species, wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiMe 2 Ž9. as a highly air sensitive red oil ŽScheme 2.. The complex was characterised by 1 H and13 C NMR and further characterisation is presently underway. Recent work carried out in our laboratory suggest that this synthetic method can be applied to a variety of amino-functionalised cyclopentadienyl systems and can be extended to the other group IV metals. Work is presently underway to investigate the efficiency as a general synthetic route for both early and late transition metals and initial results appear promising w18x. In conclusion, we have shown that the direct combination of a neutral cyclopentadiene containing a pendant Lewis base with TiCl 4 can lead directly to the air stable and water soluble titanocene dichloride dihydrochloride, avoiding a number of synthetic steps in which the reagents are air and water sensitive. The ‘protected’ complex can be stored in air without decomposition and the neutral titanocene can be generated by reaction with MeLi. Furthermore, reaction with four equivalents of an alkylating agent may generate the dialkyl substituted titanocene. This novel synthetic route represents a high yielding and highly convenient method of generating metallocene complexes. Typical procedures are as follows. Synthesis of [C 5 H 4(CH 2 )2 N(CH 2 )5 ]2 TiCl 2 (5) Method 1: From NaC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 Ž3. and TiCl 4
339
To a solution of TiCl 4 Ž0.38 ml, 0.66 g, 0.0034 mol. in THF Ž100 ml. was added a slurry of NaC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 Ž1.37 g, 0.0069 mol. in THF Ž75 ml.. On addition an orange colour developed in the THF and a colourless precipitate formed. The reaction mixture was left to stir for 1 h, after which the solvent was removed under reduced pressure. The product was extracted in 100 ml of toluene. Recrystallisation from toluene afforded the product 5 as dark orange crystals. Ž1.07 g, 67%.. Method 2: From wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x2TiCl 2 P 2HCl and MeLi To a suspension of wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 P 2HCl Ž0.48 g, 0.00088 mol. in toluene Ž60 ml. was added dropwise, with stirring MeLi Ž0.0018 mol, 1.26 ml, 1.4 M solution in diethyl ether.. The mixture was stirred for 2 h after which an orange colour had developed in the toluene. The solution was filtered and the solvent removed under reduced pressure leaving 5 as a dark orange solid Ž0.24 g, 58%.. Selected Data: peaks were assigned using DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C. COSY NMR Spectroscopy: 1 H NMR Ž500 MHz, C 6 D6 , ref.: C 6 D6 .: d 2.54 Žt, 4H, C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 2 .0 7 Ž t, 4 H , C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 2 .3 6 Ž m , 8 H , C 5 H 4 Ž CH 2 . 2 N Ž C H 2 . 2 Ž CH 2 . 3 . d 1.55 Ž m, 8H, C 5 H 4 ŽCH 2 . 2 NŽCH 2 . 2 ŽC H 2 . 2 CH 2 ., d 1.37 Žm, 4H, C 5 H 4 Ž CH 2 . 2 N Ž CH . 4 C H 2 . , 6.26, 5.89 Ž pt, 8H, C 5 H4ŽCH 2 . 2 NŽCH 2 .5 .. 13 C NMR Ž500 MHz, C 6 D6 , ref.: C 6 D6 .: d 29.16 ŽC 5 H 4 C H 2 CH 2 NŽCH 2 .5 ., d 59.6 ŽC 5 H 4 C H 2 C H 2 N ŽC H 2 .5 ., d 5 5 .1 0 ŽC 5 H 4 ŽC H 2 . 2 N Ž C H 2 . 2 ŽC H 2 . 3 . d 2 6 .7 4 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 2 Ž C H 2 . 2 C H 2 . , d 25.16 Ž C 5 H 4 Ž CH 2 . 2 N Ž CH . 4 C H 2 . , d 114.98, 123.31 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 5 rin g C . , d 1 3 6 .6 5 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 .5 ring quaternary.. Anal. Calcd for wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 ; C, 61.2; H, 7.7; N, 5.9. Found: C, 61.4; H,7.8; N, 6.1.
Scheme 2. Reagents and conditions: Ži. MeLi, diethyl ether, 53%
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M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
Synthesis of [C 5 H 4(CH 2 )2 N(CH 2 )5 ]2 TiCl 2 P 2HCl (7) Method 1: From C 5 H 5 ŽCH 2 . 2 NŽCH 2 .5 and TiCl 4 To a solution of TiCl 4 Ž1.6 g, 0.0085 mol. in toluene Ž150 ml. at y788C was added freshly distilled C 5 H 5 ŽCH 2 . 2 NŽCH 2 .5 Ž3.0 g, 0.0169 mol. in toluene Ž50 ml.. The solution was stirred for 30 min during which time a dark orange solid precipitated. The mixture was warmed to room temperature and stirred for an additional 4 h. The toluene was removed under reduced pressure and the solid was washed with diethyl ether Ž75 ml. and dried under reduced pressure to afford 7 as a pale orange solid Ž4.1 g, 89%.. Method 2: From wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 and HCl To a solution of wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 Ž0.67g, 0.0014 mols. in toluene Ž50 ml. was added HCl Ž2.8 ml, 0.0028 mols, 1.0 M solution in diethyl ether. dropwise. On addition an orange solid immediately precipitated. The mixture was stirred for 30 min and then the solvent was decanted from the reaction flask leaving a pale orange solid. The solid was washed with diethyl ether and dried under reduced pressure affording 7 as a pale orange amorphous solid Ž0.66 g, 87%.. Selected data: peaks were assigned using DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C. COSY NMR Spectroscopy: 1 H NMR Ž500 MHz, MeOD, ref.: MeOD.: d 3.31 Žt, 4H, C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 3 .4 5 Ž t, 4 H , C 5 H 4 CH 2 C H 2 N ŽCH 2 . 5 ., d 3.61, 3.00 Žm, 8H, C 5 H 4ŽCH 2 . 2 NŽC H2 . 2 ŽCH 2 . 3 . d 1.95, 1.87 Žm, 8H, C 5 H 4 ŽCH 2 . 2 NŽCH 2 . 2 ŽC H 2 . 2 CH 2 ., d 1.54 Žm, 4H, C 5 H 4 ŽCH 2 . 2 N ŽCH 2 . 4 C H 2 ., 6.72, 6.48 Žpt, 8H, C 5 H4ŽCH 2 . 2 NŽCH 2 .5 .. 13 C NMR NMR Ž500 MHz, MeOD, ref.: MeOD.: d 26.43 ŽC 5 H 4Ž C H 2 . 2 NŽCH 2 .5 ., d 5 7 .1 0 Ž C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 5 4 .3 9 ŽC 5 H 4 ŽC H 2 . 2 N Ž C H 2 . 2 ŽC H 2 . 3 . d 2 4 .2 3 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 2 Ž C H 2 . 2 C H 2 . , d 22.64 Ž C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 4 C H 2 . , d 124.64, 116.95 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 . 5 ring C., d 133.33 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 .5 ring quaternary.. FAB MS: mrz Ž%.:
472 wM –2Clxq Ž7.43.. Anal. Calcd for wC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 x2TiCl 2 P 2HCl; C, 53.0; H, 7.0; N, 5.2. Found: C, 53.5; H, 7.2; N, 5.4.
Acknowledgements Kymed GB Ltd. are acknowledged for financial support for this work.
References w1x J.C. Flores, J.C.W.Chien, M.D. Rausch, Organometallics 13 Ž1994. 4140. w2x J.C. Flores, J.C.W. Chien, M.D. Rausch, Macromolecules 29 Ž1996. 8030. w3x P. Jutzi, T. Redeker, Eur. J. Inorg. Chem. Ž1998. 663. w4x P. Jutzi, T. Redeker, B. Neumann, H.-G. Stammler, Organometallics 15 Ž1996. 4153. w5x M.S. Blais, J.C.W. Chien, M.D. Rausch, Organometallics 17 Ž1998. 3775. w6x P. Jutzi, J. Kleimeier, J. Organomet. Chem. 486 Ž1995. 287. w7x S. Bradley, P.C. McGowan, K.A. Oughton, M. Thornton-Pett, M.E. Walsh, Chem. Commun. Ž1999. 77. w8x P. Jolly, K. Ionas, G.P.I. Verkovnic, German Patent 19630580A1 Ž1998.. w9x P. Kopf-Maier, B.K Keppler, in: Complexes in Cancer Chemotherapy, VCH Weinheim, New York, 1993, p. 259. w10x J.H. Toney, T.J. Marks, J. Am. Chem. Soc. 107 Ž1995. 947. w11x Z. Guo, P.J. Sadler, Angew. Chem. Int. Ed. 38 Ž1999. 1512. w12x T.M. Klaptotke, H. Kopf, I.C. Tornieporth-Oetting, P.S. White, ¨ Angew. Chem. Int. Ed. Engl. 33 Ž1994. 1518. w13x P.-J. Sinnema, L. van der Veen, A.L. Spek, N. Veldman, J.H. Tauben, Organometallics 16 Ž1997. 4245. w14x P.C. McGowan, C.E. Hart, B. Donnadieu, R. Poilblanc, J. Organomet. Chem. 528 Ž1997. 191. w15x A.I. Philippopoulos, N. Hadjiliadis, C.E. Hart, B. Donnadieu, P.C. McGowan, R. Poilblanc, Inorg. Chem. 36 Ž1997. 1842. w16x M.A.D. McGowan, P.C. McGowan, British Patent .99293553.2 Ž1999.. w17x W.A. Herrmann, T.P. Morawietz, K. Mashima, J. Organomet. Chem. 486 Ž1995. 291. w18x M.A.D. McGowan, P.C. McGowan, unpublished.
A one-step synthesis of protected functionalised titanocene dichlorides Margaret A.D. McGowan, Patrick C. McGowan ) School of Chemistry, UniÕersity of Leeds, Leeds LS2 9JT, UK Received 17 April 2000
Abstract We report a novel, high yield one-step synthesis of water stable and soluble titanocene dichloride dihydrochloride salts from the direct reaction of the neutral amino-substituted cyclopentadienes with TiCl 4 . The following novel complexes have been synthesised: C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 5 x 2 TiCl 2 Ž 5 . , w C 5 H 4 CH Ž CH 2 . 4 N M e x 2 TiCl 2 Ž 6 . , w C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 5 x 2 TiCl 2 P 2H Cl Ž 7 . , wC 5 H 4CHŽCH 2 .4 x 2 NMeTiCl 2 P 2HCl Ž8., wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiMe 2 Ž9.. q 2000 Elsevier Science S.A. All rights reserved. Keywords: Anti-tumour agents; Cyclopentadienyl; Functionalisd titanocene dichlorides; One step synthesis; Water soluble titanium ŽIV. complexes
Recently, interest in the chemistry of amino-functionalised titanocenes has increased because of their potential to act as highly active and selective olefin polymerisation catalyst precursors w1–6x. Previous work in our group has involved the synthesis of early and late transition metal amino-functionalised metallocenes w7x. In such systems, the neutral amino function can reversibly co-ordinate to the metal centre, stabilising the highly reactive intermediates formed during homogeneous catalytic processes w1,4x. It has been shown that quaternisation of the pendant amino group can result in water soluble species w3,4,6–8x. In addition to potentially developing water soluble and air stable catalytic compounds, increased stability of titanocenes could prove useful in determining the biologically active species of the anti-tumour drug titanocene dichloride. While titanocene dichloride has been shown to act as an efficient anti-tumour agent w9–11x, there have been difficulties understanding the mechanism of action due to the low solubility and instability of the compound in aqueous media w9,10x. In an attempt to increase the stability of the active anti tumour titanocene dichloride agents to hydrolysis, we set out to synthesise aminofunctionalised titanocenes dichlorides and their dihydrochloride derivatives. It has been shown that the nature of both the counterion of the protonated species ŽCly, BF4y etc.. and the groups bound directly to the metal centre may affect the biological activity of the complexes w12x. Our
)
Corresponding author.
aim is to systematically vary the constituents of the molecular framework to achieve maximum biological activity. Reported synthetic methods of amino functionalised titanocene dichlorides require initial deprotonation of the neutral cyclopentadiene species to give the lithium, sodium or thallium salts w4–7x. The reaction of the corresponding cyclopentadienide salts with TiCl 4 affords the neutral metallocene dichlorides, which can then be reacted with HCl to give the dihydrochloride salts. The novel, high yielding synthesis Ž78–89%. reported here gives the air and water stable titanocene dichloride dihydrochloride salts directly by reaction of the neutral amino-functionalised cyclopentadiene and TiCl 4 . Using this one-step reaction, we have the ability to synthesise the protected form of a titanocene dichloride directly, which can then be stored indefinitely without decomposition in air. The synthetic method utilises the presence of the amino function as an ‘internal base’ and effectively reduces the conventional three-step synthesis to a high yield, one-step reaction. The use of an external base as a HCl trap in the synthesis of cyclopentadienyl-amido titanium complexes has been previously reported w13x and the pendant amino-function has been observed to react as an auxiliary base in the synthesis of late transition metal cyclopentadienyl complexes w14,15x. However, to the best of our knowledge the method presented here represents a new and facile route to bisŽcyclopentadienyl. derivatives of early transition metals. We believe this is the first recorded synthesis of a group IV metallocene dichloride dihydrochloride from the direct reaction of a neutral amino-substituted cyclopentadienyl species and a simple homoleptic metal halide w16x.
1387-7003r00r$ - see front matter q 2000 Elsevier Science S.A. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 Ž 0 0 . 0 0 0 9 4 - 0
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M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
The titanocene dichloride dihydrochloride salts wC 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 5 x 2 TiC l 2 P 2H C l and w C 5 H 4 C H ŽCH 2 .4 NMex 2TiCl 2 P 2HCl, Ž7,8. can be synthesised via Ži. the direct reaction of two equivalents of the neutral cyclopentadienes, C 5 H 5 Ž C H 2 . 2 N Ž C H 2 . 5 Ž 1 . and C 5 H 5 CHŽCH 2 .4 NMe Ž2. and TiCl 4 in toluene or Žii. the reaction of the sodium salts NaC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 Ž3. and NaC 5 H 4 CHŽCH 2 .4 NMe Ž4. with TiCl 4 , followed by reaction with HCl ŽScheme 1.. The substituted cyclopentadienes were synthesised as previously described w14,17x. The cyclopentadienyl sodium salts Ž3,4. were prepared by the reaction of sodium hydride and the neutral cyclopentadiene ligands in THF. The dihydrochloride salts are isolated as pale orange Ž7. or yellow Ž8. solids, which are soluble in polar solvents
such as methanol, water, and acetonitrile. They have been characterised by 1 H, 13 C, DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C.-COSY NMR spectroscopy and by FAB mass spectrometry. Elemental analysis was also obtained for 7. The ammonium protons are observed as broad signals in the low field region ca. d 10. The 1 H NMR of 7 in D 2 O shows no appreciable decomposition over 48 h and only partial decomposition is observed over 7 days. The neutral titanocene dichloride can be obtained by reaction of 7 with two equivalents of MeLi or by reaction of the sodium salt 3 with TiCl 4 in THF. The highly air and moisture sensitive titanocene dichloride, wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 Ž5. can be isolated as a crystalline, deep orange solid and is soluble in aprotic polar Ždiethyl ether, THF. and non-polar solvents Žtoluene, benzene.. An analytically pure sample
Scheme 1. Reagents and conditions: Ži. NaH, THF, 72–87%; Žii. TiCl 4 , THF, 67–73%; Žiii. HCl, 82–87%; Živ. MeLi, diethyl ether; and Žv. TiCl 4, toluene, 78–89%.
M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
was obtained by recrystallisation from diethyl ether and further characterisation data provided by 1 H and 13 C NMR spectroscopy. Full characterisation of wC 5 H 4 CHŽCH 2 .4NMex 2TiCl 2 , Ž6. proved difficult due to the formation of insoluble polymeric species, as previously observed for analogous amino-substituted titanocene dichloride complexes w4x. However, reaction with HCl yielded the expected titanocene dichloride dihydrochloride Ž8.. We have also found that reaction of 7 with four equivalents of MeLi ŽScheme 2. results in the formation of the thermally stable dimethylated species, wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiMe 2 Ž9. as a highly air sensitive red oil ŽScheme 2.. The complex was characterised by 1 H and13 C NMR and further characterisation is presently underway. Recent work carried out in our laboratory suggest that this synthetic method can be applied to a variety of amino-functionalised cyclopentadienyl systems and can be extended to the other group IV metals. Work is presently underway to investigate the efficiency as a general synthetic route for both early and late transition metals and initial results appear promising w18x. In conclusion, we have shown that the direct combination of a neutral cyclopentadiene containing a pendant Lewis base with TiCl 4 can lead directly to the air stable and water soluble titanocene dichloride dihydrochloride, avoiding a number of synthetic steps in which the reagents are air and water sensitive. The ‘protected’ complex can be stored in air without decomposition and the neutral titanocene can be generated by reaction with MeLi. Furthermore, reaction with four equivalents of an alkylating agent may generate the dialkyl substituted titanocene. This novel synthetic route represents a high yielding and highly convenient method of generating metallocene complexes. Typical procedures are as follows. Synthesis of [C 5 H 4(CH 2 )2 N(CH 2 )5 ]2 TiCl 2 (5) Method 1: From NaC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 Ž3. and TiCl 4
339
To a solution of TiCl 4 Ž0.38 ml, 0.66 g, 0.0034 mol. in THF Ž100 ml. was added a slurry of NaC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 Ž1.37 g, 0.0069 mol. in THF Ž75 ml.. On addition an orange colour developed in the THF and a colourless precipitate formed. The reaction mixture was left to stir for 1 h, after which the solvent was removed under reduced pressure. The product was extracted in 100 ml of toluene. Recrystallisation from toluene afforded the product 5 as dark orange crystals. Ž1.07 g, 67%.. Method 2: From wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x2TiCl 2 P 2HCl and MeLi To a suspension of wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 P 2HCl Ž0.48 g, 0.00088 mol. in toluene Ž60 ml. was added dropwise, with stirring MeLi Ž0.0018 mol, 1.26 ml, 1.4 M solution in diethyl ether.. The mixture was stirred for 2 h after which an orange colour had developed in the toluene. The solution was filtered and the solvent removed under reduced pressure leaving 5 as a dark orange solid Ž0.24 g, 58%.. Selected Data: peaks were assigned using DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C. COSY NMR Spectroscopy: 1 H NMR Ž500 MHz, C 6 D6 , ref.: C 6 D6 .: d 2.54 Žt, 4H, C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 2 .0 7 Ž t, 4 H , C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 2 .3 6 Ž m , 8 H , C 5 H 4 Ž CH 2 . 2 N Ž C H 2 . 2 Ž CH 2 . 3 . d 1.55 Ž m, 8H, C 5 H 4 ŽCH 2 . 2 NŽCH 2 . 2 ŽC H 2 . 2 CH 2 ., d 1.37 Žm, 4H, C 5 H 4 Ž CH 2 . 2 N Ž CH . 4 C H 2 . , 6.26, 5.89 Ž pt, 8H, C 5 H4ŽCH 2 . 2 NŽCH 2 .5 .. 13 C NMR Ž500 MHz, C 6 D6 , ref.: C 6 D6 .: d 29.16 ŽC 5 H 4 C H 2 CH 2 NŽCH 2 .5 ., d 59.6 ŽC 5 H 4 C H 2 C H 2 N ŽC H 2 .5 ., d 5 5 .1 0 ŽC 5 H 4 ŽC H 2 . 2 N Ž C H 2 . 2 ŽC H 2 . 3 . d 2 6 .7 4 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 2 Ž C H 2 . 2 C H 2 . , d 25.16 Ž C 5 H 4 Ž CH 2 . 2 N Ž CH . 4 C H 2 . , d 114.98, 123.31 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 5 rin g C . , d 1 3 6 .6 5 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 .5 ring quaternary.. Anal. Calcd for wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 ; C, 61.2; H, 7.7; N, 5.9. Found: C, 61.4; H,7.8; N, 6.1.
Scheme 2. Reagents and conditions: Ži. MeLi, diethyl ether, 53%
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M.A.D. McGowan, P.C. McGowanr Inorganic Chemistry Communications 3 (2000) 337–340
Synthesis of [C 5 H 4(CH 2 )2 N(CH 2 )5 ]2 TiCl 2 P 2HCl (7) Method 1: From C 5 H 5 ŽCH 2 . 2 NŽCH 2 .5 and TiCl 4 To a solution of TiCl 4 Ž1.6 g, 0.0085 mol. in toluene Ž150 ml. at y788C was added freshly distilled C 5 H 5 ŽCH 2 . 2 NŽCH 2 .5 Ž3.0 g, 0.0169 mol. in toluene Ž50 ml.. The solution was stirred for 30 min during which time a dark orange solid precipitated. The mixture was warmed to room temperature and stirred for an additional 4 h. The toluene was removed under reduced pressure and the solid was washed with diethyl ether Ž75 ml. and dried under reduced pressure to afford 7 as a pale orange solid Ž4.1 g, 89%.. Method 2: From wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 and HCl To a solution of wC 5 H 4ŽCH 2 . 2 NŽCH 2 .5 x 2TiCl 2 Ž0.67g, 0.0014 mols. in toluene Ž50 ml. was added HCl Ž2.8 ml, 0.0028 mols, 1.0 M solution in diethyl ether. dropwise. On addition an orange solid immediately precipitated. The mixture was stirred for 30 min and then the solvent was decanted from the reaction flask leaving a pale orange solid. The solid was washed with diethyl ether and dried under reduced pressure affording 7 as a pale orange amorphous solid Ž0.66 g, 87%.. Selected data: peaks were assigned using DEPT, Ž1 H,1 H.-COSY and Ž1 H,13 C. COSY NMR Spectroscopy: 1 H NMR Ž500 MHz, MeOD, ref.: MeOD.: d 3.31 Žt, 4H, C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 3 .4 5 Ž t, 4 H , C 5 H 4 CH 2 C H 2 N ŽCH 2 . 5 ., d 3.61, 3.00 Žm, 8H, C 5 H 4ŽCH 2 . 2 NŽC H2 . 2 ŽCH 2 . 3 . d 1.95, 1.87 Žm, 8H, C 5 H 4 ŽCH 2 . 2 NŽCH 2 . 2 ŽC H 2 . 2 CH 2 ., d 1.54 Žm, 4H, C 5 H 4 ŽCH 2 . 2 N ŽCH 2 . 4 C H 2 ., 6.72, 6.48 Žpt, 8H, C 5 H4ŽCH 2 . 2 NŽCH 2 .5 .. 13 C NMR NMR Ž500 MHz, MeOD, ref.: MeOD.: d 26.43 ŽC 5 H 4Ž C H 2 . 2 NŽCH 2 .5 ., d 5 7 .1 0 Ž C 5 H 4 C H 2 C H 2 N Ž C H 2 . 5 . , d 5 4 .3 9 ŽC 5 H 4 ŽC H 2 . 2 N Ž C H 2 . 2 ŽC H 2 . 3 . d 2 4 .2 3 Ž C 5 H 4 Ž C H 2 . 2 N Ž C H 2 . 2 Ž C H 2 . 2 C H 2 . , d 22.64 Ž C 5 H 4 Ž CH 2 . 2 N Ž CH 2 . 4 C H 2 . , d 124.64, 116.95 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 . 5 ring C., d 133.33 Ž C5 H 4 ŽCH 2 . 2 NŽCH 2 .5 ring quaternary.. FAB MS: mrz Ž%.:
472 wM –2Clxq Ž7.43.. Anal. Calcd for wC 5 H 4 ŽCH 2 . 2 NŽCH 2 .5 x2TiCl 2 P 2HCl; C, 53.0; H, 7.0; N, 5.2. Found: C, 53.5; H, 7.2; N, 5.4.
Acknowledgements Kymed GB Ltd. are acknowledged for financial support for this work.
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