PROCESS FOR SYNTHESIS OF INDENES

Abstract

The present invention relates to a new process for the synthesis of 2,3,4,5,6,7-substituted indenes, which are useful precursors for the formation of certain ansa-metallocene catalysts.

Claims

1. A process for the preparation of a compound of the formula I shown below: ##STR00028## wherein: R.sub.1 and R.sub.2 are each (1-10C)alkyl; and wherein the process comprises the steps of: (i) reacting a compound of formula A: ##STR00029## wherein R.sub.1 and R.sub.2 are each as defined above; with a chlorinating or brominating agent to form a compound of formula B: ##STR00030## wherein R.sub.1 and R.sub.2 are each as defined above and X is chloro or bromo; and adding 1,2,3,4-tetramethylbenzene and a Lewis acid catalyst to the reaction mixture to react with compound B to form a compound of formula C: ##STR00031## wherein R.sub.1 and R.sub.2 are each as defined above; (ii) reacting the compound of formula C with a solution of a hydride transfer reagent followed by adding a dehydrating agent to the reaction mixture to form a compound of Formula I.

2. The process according to claim 1, wherein R.sub.1 and R.sub.2 are each independently selected from (1-3C)alkyl.

3. The process according to claim 2, wherein R.sub.1 and R.sub.2 are both methyl.

4. The process according to claim 1, wherein in step (i) the chlorinating agent is selected from oxalyl chloride, PCl.sub.3, PCl.sub.5 and SOCl.sub.2 and the brominating agent is selected from the group consisting PBr.sub.3 and PBr.sub.5.

5. The process according to claim 1, wherein in step (i) a chlorinating agent is used and the chlorinating agent is selected from oxalyl chloride, PCl.sub.3 and PCl.sub.5.

6. The process according to claim 5, wherein the chlorinating agent is oxalyl chloride.

7. The process according to claim 1, wherein the Lewis acid catalyst is selected from AlCl.sub.3, AlBr.sub.3 and BCl.sub.3.

8. The process according to claim 7, wherein the Lewis acid catalyst is AlCl.sub.3.

9. The process according to claim 1, wherein the reaction between the compound of formula B and 1,2,3,4-tetramethylbenzene is quenched by the addition of an acid.

10. The process according to claim 1, wherein in step (ii) the solution of a hydride transfer reagent is selected from a solution of LiAlH.sub.4 and NaBH.sub.4.

11. The process according to claim 10, wherein the hydride transfer reagent is LiAlH.sub.4.

12. The process according to claim 1, wherein in step (ii) the dehydrating agent is an acid selected from sulphuric, hydrochloric or phosphoric acid.

13. A process for forming a compound of formula II ##STR00032## wherein R.sub.1, R.sub.2 are each (1-10C)alkyl; and L is a bridging group of the formula [C(R.sup.xR.sup.y)].sub.n wherein n is 1, 2 or 3 and R.sup.x and R.sup.y are each independently hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or (1-6C)alkoxy; or a group SiR.sub.aR.sub.b wherein R.sub.a and R.sub.b are each independently selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy or phenyl; wherein the process comprises: (i) forming a compound of formula I by a process comprising the steps of: (a) reacting a compound of formula A: ##STR00033## wherein R.sub.1 and R.sub.2 are each as defined above; with a chlorinating or brominating agent to form a compound of formula B: ##STR00034## wherein R.sub.1 and R.sub.2 are each as defined above and X is chloro or bromo; and adding 1,2,3,4-tetramethylbenzene and a Lewis acid catalyst to the reaction mixture to react with compound B to form a compound of formula C: ##STR00035## wherein R.sub.1 and R.sub.2 are each as defined above; (b) reacting the compound of formula C with a solution of a hydride transfer reagent followed by adding a dehydrating agent to the reaction mixture to form a compound of formula I shown below: ##STR00036## wherein R.sub.1 and R.sub.2 are each as defined above; (ii) reacting the compound of formula I with an organolithium, organosodium or organopotassium compound of the formula:
MQ wherein M is lithium, sodium, or potassium and Q is an (1-6C)alkyl or aryl group; to form a compound of formula D shown below: ##STR00037## (iii) reacting two equivalents of a compound of formula D shown above with one equivalent of a compound having formula E shown below:
Z.sub.1-L-Z.sub.2 (E) wherein L is as defined above and Z.sub.1 and Z.sub.2 are leaving groups to form a compound of formula II.

14. The process according to claim 13, wherein L is CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2- or a group SiR.sub.aR.sub.b wherein R.sub.a and R.sub.b are each independently selected from methyl, propyl and allyl.

15. The process according to claim 13, wherein in step (ii) the compound of formula I is reacted with an organolithium compound.

16. The process according to claim 15, wherein the organolithium compound is n-butyllithium.

17. The process according to claim 13, wherein Z.sub.1 and Z.sub.2 are the same and selected from chloro or bromo.

18. A process for forming a compound of formula III ##STR00038## wherein R.sub.1 and R.sub.2 are each (1-10C)alkyl; L is a bridging group of the formula [C(R.sup.xR.sup.y)].sub.n wherein n is 1, 2 or 3 and R.sup.x and R.sup.y are each independently hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or (1-6C)alkoxy; or a group SiR.sub.aR.sub.b wherein R.sub.a and R.sub.b are each independently selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy or phenyl; X is zirconium, hafnium or titanium; Y is selected from halo, hydride, a phosphonated or sulfonated anion, or a (1-6C)alkyl, (1-6C)alkoxy, aryl or aryloxy group which is optionally substituted with halo, nitro, amino, phenyl, (1-6C)alkoxy, or Si[(1-4C)alkyl].sub.3, wherein the process comprises: (i) forming a compound of formula II by a process comprising the steps of: (a) reacting a compound of formula A: ##STR00039## wherein R.sub.1 and R.sub.2 are each as defined above; with a chlorinating or brominating agent to form a compound of formula B: ##STR00040## wherein R.sub.1 and R.sub.2 are each as defined above and X is chloro or bromo; and adding 1,2,3,4-tetramethylbenzene and a Lewis acid catalyst to the reaction mixture to react with compound B to form a compound of formula C: ##STR00041## wherein R.sub.1 and R.sub.2 are each as defined above: (b) reacting the compound of formula C with a solution of a hydride transfer reagent followed by adding a dehydrating agent to the reaction mixture to form a compound of formula I shown below: ##STR00042## wherein R.sub.1 and R.sub.2 are each as defined above; (c) reacting the compound of formula I with an organolithium, organosodium or organopotassium compound of the formula:
MQ wherein M is lithium, sodium, or potassium and Q is an (1-6C)alkyl or aryl group; to form a compound of formula D shown below: ##STR00043## (d) reacting two equivalents of a compound of formula D shown above with one equivalent of a compound having formula E shown below:
Z.sub.1-L-Z.sub.2 (E) wherein L is as defined above and Z.sub.1 and Z.sub.2 are leaving groups to form a compound of formula II shown below: ##STR00044## (ii) reacting the compound of formula II, or a salt thereof, with a compound of the formula:
X(Y).sub.2(Z.sub.3).sub.2 wherein X and Y are as defined above and Z.sub.3 is a leaving group.

19. The process according to claim 18, wherein Z.sub.3 is a halide.

20. The process according to claim 18, wherein X is zirconium or hafnium.

Description

EXAMPLE

[0133] An example of the invention will now be described by reference to the accompanying figures, in which:

[0134] FIG. 1 shows the .sup.1H NMR spectra of hexamethylindanone (Ind.sup.#=O);

[0135] FIG. 2 shows the molecular structure of hexamethylindanone (Ind.sup.#=O);

[0136] FIG. 3 shows the .sup.1H NMR spectra of hexamethylindene (Ind.sup.#H); and

[0137] FIG. 4 shows the molecular structure of hexamethylindene, (Ind.sup.#H).

EXAMPLE 1

General Reaction Scheme:

[0138] ##STR00022##

[0139] 41.8 g tiglic acid [trans-2-methylbutenoic acid] (417 mmol, 1 eq.) was dissolved in 1 L DCM. To this mixture, 52.9 g oxalyl chloride (417 mmol, 1 eq.) was added which was washed in with a 100 mL portion of dichloromethane (DCM). Five drops of N,N-dimethylformamide was pipetted into the vigorously stirred solution causing a large amount of effervescence. The reaction was left stirring under nitrogen for 12 h before cooling to 8 C. 61.2 g aluminium trichloride (459 mmol, 1.1 eq.) was quickly added under a flow of N.sub.2, causing a small temperature rise and the resulting DCM slurry to become light orange. 50 g 1,2,3,4-tetramethylbenzene (TMB) (372 mmol, 0.90 eq.) was mixed with 100 mL DCM and transferred to a pressure-equalising dropping-funnel. The TMB solution was added to the stirred reaction mixture in a fast-dropwise manner effecting a colour change through dark-orange to red. After stirring for a further four hours at room temperature, a solution of 500 mL conc. HCl and 500 g ice was made-up and was transferred to the reaction mixture to quench it, dropwise at first and then more quickly over 10 minutes. This caused the dark-red slurry to decolourise to a light pink solution. The stirring was stopped and the DCM layer was decanted before extracting the aqueous layer with 500 mL DCM twice more. The combined organic layer was washed with 500 mL deionised water, drying with magnesium sulfate, filtering and reducing in vacuo (40 C., 550 mbar). The product was obtained as a light brown oil in 96% yield (77.25 g, 357 mmol).

[0140] The proton NMR for the Ind.sup.#=O is shown in FIG. 1 and the molecular structure is shown in FIG. 2.

[0141] 100 mL LiAlH.sub.4 (2.0 M in THF; 200 mmol, 0.5 eq.) was combined with 100 mL dry, degassed THF and the mixture was cooled to 8 C. under N.sub.2. 86.53 g Ind.sup.#=O (400 mmol, 1 eq.) was dissolved in 150 mL dry, degassed THF and this was added to the stirred reaction mixture in a fast dropwise manner over the course of 10 minutes causing a small rise in temperature. The reaction was stirred for four hours before careful, portionwise quenching with 14.4 mL H.sub.2O (800 mmol, 2 eq.) over approximately 30 minutes. 113 mL conc. H.sub.2SO.sub.4 (>95%; 2 mol, 5 eq.) was added, slowly at first, causing the colour to change to a medium-dark grey over 30 minutes. The reaction was quenched with an additional 500 mL H.sub.2O and extracted with DCM (3500 mL). The combined organic layer was washed with a further 500 mL H.sub.2O, dried over magnesium sulphate and reduced in vacuo (40 C., 250 mbar), affording the product as a dark brown oil in 98% yield (78.51 g, 392 mmol).

[0142] The proton NMR for the Ind.sup.#H is shown in FIG. 3 and the molecular structure is shown in FIG. 4.

EXAMPLE 2

[0143] This synthesis is based on R.sub.1CH.sub.3 and R.sub.2C.sub.2H.sub.5

Synthesis of 3-ethyl-tigloyl chloride

[0144] ##STR00023##

(E)-2-methylpent-2-enoyl chloride

[0145] One equivalent of oxalyl chloride (26.45 g, 208 mmol) was added to a 2 L reaction vessel containing one equivalent of (E)-2-methylpent-2-enoic acid (23.85 g, 208 mmol) in DCM (500 mL) under a flow of N.sub.2. While stirring, five drops of dry DMF were pipetted into the mixture creating effervescence. The reaction was left in a state a reflux for 2 hours. An aliquot was taken after 90 minutes showing that the reaction had gone to completion.

[0146] .sup.1H NMR (CDCl.sub.3): 1.08 (t, 3H, J=7.6 Hz, Me.sub.b), 1.88 (q, 3H, J=1.0 Hz, Me.sub.a), 2.26 (quinq, 2H, J=7.5, 0.9 Hz, CH.sub.2), 6.87 (tq, 1H, J=7.4 Hz, 1.3 Hz, vinylic-H)

[0147] .sup.13C{.sup.1H} NMR (CDCl.sub.3): 12.57 (Me.sub.b), 13.23 (Me.sub.a), 22.93 (CH.sub.2), 154.23 (Vinylic-H)

Synthesis of (Ind.SUP.#3-Ethyl.)=O

[0148] ##STR00024##

3-ethyl-2,4,5,6,7-pentamethyl-2,3-dihydro-1H-inden-1-one

[0149] The reactor was cooled to 8 C. and allowed to equilibrate. 1.1 equivalents of aluminium trichloride (30.6 g, 230 mmol) was added, under a flow of N.sub.2, to the reactor. The mixture changed from a pale yellow to a deep orange almost instantly. 0.9 equivalents of tetramethylbenzene (25.0 g, 176 mmol) was diluted in 100 mL DCM and transferred to a pressure equalising funnel. This mixture was added to the reaction vessel dropwise over 15 minutes where a colour change from deep orange to blood red was observed. The solution was then left to stir for two hours, after which a solution of 100 mL conc. HCl and 100 g ice was made up and used to quench the reaction. The reaction mixture changed colour from blood red to a light orange solution during this workup. The product was extracted with DCM (3100 mL) and the combined organic layer washed with deionised water (3100 mL) before being dried using anhydrous MgSO.sub.4. This was filtered and the DCM solvent removed in vacuo to afford a beige solid in 100% yield (41.8 g, 214 mmol).

[0150] .sup.1H NMR (CDCl.sub.3): 0.56 (t, 3H, J=7.5 Hz, Me.sub.b), 1.28 (d, 3H, J=7.2 Hz, Me.sub.a), 1.70 (m, 2H, CH.sub.2), 2.23 (s, 3H, Ar-Me), 2.28 (s, 3H, Ar-Me), 2.28 (s, 3H, Ar-Me), 2.62 (s, 3H, Ar-Me), 2.74 (quin, 1H, J=7.3 Hz, CH), 2.74 (quin, 1H, J=7.3 Hz, CH), 3.45 (ddd, 1H, J=7.4, 6.1, 3.6 Hz, CH)

[0151] MS (ESI): found 231.17446; calculated 231.17434.

Synthesis of (Ind.SUP.#,3-ethyl.)H

[0152] ##STR00025##

1-ethyl-2,4,5,6,7-pentamethyl-1H-indene

[0153] One equivalent of 3-ethyl-2,4,5,6,7-pentamethyl-2,3-dihydro-1H-inden-1-one (22.4 g, 97 mmol) was added to 50 mL of dry, degassed THF in a schlenk tube. 0.5 equivalents of LiAlH.sub.4 (24.2 mL, 48 mmol) were added dropwise over 30 minutes and the resultant mixture left to stir for 2 hours under nitrogen. This caused the reaction mixture to turn light orange. The schlenk was cooled to 0 C. and the reaction quenched by adding one equivalent of deionised water (1.74 mL, 97 mmol) dropwise. Upon addition of five equivalents of conc. H.sub.2SO.sub.4 (26.1 mL, 483 mmol) dropwise over 20 minutes the reaction mixture turned dark brown. The resultant solution was transferred to a 2 L reaction vessel and stirred for 30 minutes under a flow of N.sub.2. The reaction was then quenched with 250 mL deionised water and extracted with DCM (3500 mL). The combined organic layer was washed with deionised water (3100 mL), dried over anhydrous MgSO.sub.4, filtered, and the solvent removed in vacuo to give a light brown solid (16.8 g, 78 mmol) in 80.6% yield.

[0154] .sup.1H NMR (CDCl.sub.3): 0.46 (t, 3H, J=7.4 Hz, Me.sub.b), 1.97 (dqd, 1H, J=13.9, 7.4, 3.7 Hz, CH), 2.09 (d, 1H, J=0.8 Hz, Me.sub.a) 2.14 (m, 1H, CH), 2.29 (s, 3H, Ar-Me), 2.29 (s, 3H, Ar-Me), 2.36 (s, 3H, Ar-Me), 2.37 (s, 3H, Ar-Me), 3.36 (t, 1H, J=4.5 Hz, CH), 6.62 (quin, 1H, J=1.5 Hz)

[0155] MS (ESI): found 215.17966; expected 215.17943.

Synthesis of Ind.SUP.#,3-ethyl.Li

[0156] ##STR00026##

1-ethyl-2,4,5,6,7-pentamethyl indenyllithium

[0157] One equivalent of 1-ethyl-2,4,5,6,7-pentamethyl-1H-indene (16.8 g, 78 mmol) was dissolved in 50 mL DCM and transferred to a schlenk tube. The solvent was removed in vacuo before 100 mL pentane was added. 1.1 equivalents of n-butyllithium (34.5 mL, 86 mmol) was added dropwise, at 0 C., to the dark brown mixture while stirring. The solution was allowed to warm up to room temperature and left stirring for 16 hours. The resulting yellow suspension was filtered on an air sensitive frit. The powder was washed with pentane (250 mL) and then dried under vacuum to form a white solid in 52.4% yield (9.05 g, 41 mmol)

[0158] .sup.1H NMR (C.sub.5D.sub.5N): 1.47 (t, 3H, J=7.3 Hz, Me.sub.b), 2.45 (s, 3H, Ar-Me), 2.46 (s, 3H, Ar-Me), 2.65 (s, 3H, Ar-Me), 2.66 (s, 3H, Ar-Me), 2.89 (s, 3H, Me.sub.a), 3.31 (q, 2H, J=7.3 Hz, CH.sub.2), 6.37 (s, 1H, Ar-H)

[0159] .sup.7Li NMR (C.sub.5D.sub.5N): 1.06 (s)

Synthesis of (Ind.SUP.*,3-ethyl.).SUB.2.ZrCl.SUB.2

[0160] ##STR00027##

[0161] Two equivalents of Ind.sup.#,3-ethylLi (3 g, 13.6 mmol) were added to one equivalent of ZrCl.sub.4 (1.59 g, 6.84 mmol) in a schlenk tube inside a glovebox, and were stirred in 100 mL benzene under nitrogen for 16 hours at room temperature. The mixture was allowed to settle, and the mixture filtered. The solution was dried to afford an orange solid in 27.0% yield (1.09 g, 1.85 mmol). This solid comprised an equal mixture of both rac- and meso-isomeric forms which proved inseparable by fractional crystallisation from hexane, pentane, Et.sub.2O and benzene. A further recrystallization from toluene yielded a light yellow precipitate of rac-(Ind.sup.*,3-ethyl).sub.2ZrCl.sub.2 which was isolated.

[0162] .sup.1H NMR (C.sub.6D.sub.6): 1.00 (t, 6H, J=7.6 Hz, Me), 1.58 (s, 6H, Ar-Me), 2.09 (s, 6H, Ar-Me), 2.16 (s, 6H, Ar-Me), 2.38 (s, 6H, Ar-Me), 2.60 (s, 6H, Ar-Me), 2.81 (dq, 2H, J=15.3, 7.7 Hz, CH.sub.2), 3.31 (dq, 2H, J=15.1, 7.5 Hz, CH.sub.2), 6.09 (s, 2H, ArH)

[0163] The features disclosed in the foregoing description, in the claims and the accompanying drawings may, both separately and in any combination, be material for realizing the invention in diverse forms thereof.