Combinatorial synthesis and screening of supported organometallic compounds and catalysts

• US 20030100119A1
• Filed: 10/11/2002
• Published: 05/29/2003
• Est. Priority Date: 10/18/1994
• Status: Abandoned Application

• Current Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Powers, Tim, Murphy, Vince, Van Beek, Johannes A.M., Turner, Howard, Goldwasser, Isy, McFarland, Eric, Boussie, Thomas, Weinberg, W. Henry
• Application Number:
  US10/269,362
• Publication Number:
  US 20030100119A1
• Time in Patent Office: Days
• US Class Current: 436/37
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00443 Thin film deposition
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00515 in the shape of strings
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00644 : the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00738 : Organic catalysts
• CPC Class Codes: B01J 2219/00745 : Inorganic compounds
• CPC Class Codes: B01J 2219/0075 : Metal based compounds
• CPC Class Codes: B01J 2219/00754 : Metal oxides
• CPC Class Codes: C07F 15/0066 : without a metal-carbon linkage
• CPC Class Codes: C07F 15/045 : without a metal-carbon linkage
• CPC Class Codes: C08F 10/00 : Homopolymers and copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond
• CPC Class Codes: C08F 110/02 : Ethene
• CPC Class Codes: C08F 2500/03 : Narrow molecular weight distribution, i.e. Mw/Mn < 3
• CPC Class Codes: C08F 4/027 : Polymers
• CPC Class Codes: C08F 4/7006 : NN
• CPC Class Codes: C08F 4/7081 : Neutral ligand
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2291/106 : one or more transducer arrays
• CPC Class Codes: G01N 29/0681 : by acoustic microscopy, e.g. scanning acoustic microscopy
• CPC Class Codes: G01N 29/2418 : using optoacoustic interaction with the material, e.g. laser radiation, photoacoustics photoacoustic cells G01N21/1702; measuring characteristics of vibrations by using radiation-sensitive means G01H9/00; acousto-optical conversion techniques for short-range imaging G01S15/8965; sound-producing devices using laser bundle G10K15/046
• CPC Class Codes: G01N 29/348 : with frequency characteristics, e.g. single frequency signals, chirp signals measuring frequency of mechanical vibrations or acoustic waves in general G01H1/06, G01H3/04; measuring frequency or analysing frequency spectra G01R23/00
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention relates, inter alia, to methodologies for the synthesis, screening and characterization of organometallic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention provide for the combinatorial synthesis, screening and characterization of libraries of supported and unsupported organometallic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention can be applied to the preparation and screening of large numbers of organometallic compounds which can be used not only as catalysts (e.g., homogeneous catalysts), but also as additives and therapeutic agents.

Claims

1. A method of making an array of metal-ligand compounds, said method comprising:

(a) synthesizing a first metal-binding ligand and a second metal-binding ligand on first and second regions on a substrate; and

(b) delivering a first metal ion to said first metal-binding ligand and a second metal ion to said second metal-binding ligand to form a first metal-ligand compound and a second metal-ligand compound.

2. The method as recited in claim 1 further comprising the step of

(c) activating said first metal-ligand compound with a first activator to form a first activated metal-ligand compound and said second metal-ligand compound with a second activator to form a second activated metal-ligand compound.

3. The method as recited in claim 1 wherein step (a) comprises:

(i) synthesizing a first component of said first metal-binding ligand and a first component of said second metal-binding ligand on first and second regions of said substrate; and

(ii) synthesizing a second component of said first metal-binding ligand and a second component of said second metal-binding ligand on said first and second regions of said substrate.

4. The method as recited in claim 2 wherein said first and second activated metal-ligand compounds are organometallic compounds.

5. The method as recited in claim 2 wherein said first and second activated metal-ligand compounds are homogeneous catalysts.

6. The method as recited in claim 5 wherein said homogeneous catalysts are polymerization catalysts.

7. The method as recited in claim 2 wherein said first and second activated metal-ligand compounds are heterogeneous catalysts.

8. The method as recited in claim 1 wherein said first and second metal-ligand compounds are metallocene compounds.

9. The method as recited in claim 1 wherein said first and second metal-ligand compounds are activator-free catalysts.

10. The method as recited in claim 9 wherein said activator-free catalysts are homogeneous catalysts.

11. The method as recited in claim 9 wherein said activator-free catalysts are heterogeneous catalysts.

12. The method as recited in claim 1 wherein said first said second metal-binding ligands are neutral bidentate ligands.

13. The method as recited in claim 1 wherein said first and second metal-binding ligands are monoanionic bidentate ligands.

14. The method as recited in claim 1 wherein said first and second metal-binding ligands are chelating diamine ligands.

15. The method as recited in claim 14 wherein said chelating diamine ligands are 1,2-diamine ligands.

16. The method as recited in claim 1 wherein said first and second metal-binding ligands are salen ligands.

17. The method as recited in claim 1 wherein said first and second metal-binding ligands are ancillary ligands.

18. The method as recited in claim 1 wherein said first and second metal-binding ligands have a coordination number (CN) independently selected from the group consisting of 1, 2 and 3.

19. The method as recited in claim 1 wherein said first and second metal-binding ligands have a charge independently selected from the group consisting of 0, −

1, −

2, −

3 and −

4.

20. The method as recited in claim 1 wherein said first and second metal-binding ligands have a coordination number (CN) and charge independently selected from the group consisting of (i) CN=2, charge=−

2;

(ii) CN=2, charge=−

1;

(iii) CN=1, charge=−

1;

(iv) CN=2, charge=neutral;

(v) CN=3, charge −

1;

(vi) CN=1, charge=−

2;

(vii) CN=3, charge=−

2;

(viii) CN=2, charge=−

3; and

(ix) CN=3, charge=−

3.

21. The method as recited in claim 1 wherein said first and second metal-binding ligands are ancillary ligands each having a charge that is greater than the coordination number.

22. The method as recited in claim 1 wherein said first and second metal ions are each transition metal ions.

23. The method as recited in claim 22 wherein said first and second metal-binding ligands are neutral bidentate ligands, and each of said transition metal ions is stabilized by a labile neutral Lewis base.

24. The method as recited in claim 22 wherein said first and second metal-binding ligands are chelating diamine ligands, and each of said transition metal ions is a Group 10 transition metal.

25. The method as recited in claim 22 wherein said first and second metal-binding ligands are monoanionic bidentate ligands, and each of said transition metal ions is stabilized by a labile anionic leaving group ligand.

26. The method as recited in claim 2 wherein said first and second activators are independently selected from the group consisting of MAO, [Q]⁺[NCA]⁻

, [H(OEt₂)]⁺[BAr₄]⁻

and [H(OEt₂)]⁺[B(C₆F₅)₄]⁻

.

27. The method as recited in claim 2 wherein said first and second activators are independently selected and become counterions after activation.

28. The method as recited in claim 1 wherein said first and second metal ions are independently selected from the group consisting of Pd, Ni, Pt, Ir, Rh, Cr, Mo, W and Co.

29. The method as recited in claim 1 wherein said first and second metal-binding ligands are supported.

30. The method as recited in claim 29 wherein said first and second metal-binding ligands are attached directly to said substrate.

31. The method as recited in claim 29 wherein said first and second metal-binding ligands are attached to said substrate through first and second linker groups.

32. The method as recited in claim 29 wherein said first and second metal-binding ligands are attached to first and second synthesis support on said substrate.

33. The method as recited in claim 32 wherein said first and second metal-binding ligands are attached directly to said first and second synthesis support.

34. The method as recited in claim 32 wherein said first and second metal-binding ligands are attached to said first and second synthesis support through first and second linker groups.

35. The method as recited in claim 1 wherein said first and second metal-binding ligands are unsupported.

36. The method as recited in claim 1 further comprising the step of screening said array of metal-ligand compounds for a useful property.

37. The method as recited in claim 36 wherein said useful property is a polymerization characteristic.

38. The method as recited in claim 36 wherein said useful property is a mechanical property.

39. The method as recited in claim 36 wherein said useful property is an optical property.

40. The method as recited in claim 36 wherein said useful property is a physical property.

41. The method as recited in claim 36 wherein said useful property is a morphological property.

42. The method as recited in claim 36 wherein said useful property is the lifetime of said metal-ligand compounds.

43. The method as recited in claim 36 wherein said useful property is the stability of said metal-ligand compounds with respect to specific reaction conditions.

44. The method as recited in claim 36 wherein said useful property is the selectivity of said metal-ligand compounds for a particular reaction.

45. The method as recited in claim 36 wherein said useful property is the conversion efficiency of said metal-ligand compounds for a particular reaction.

46. The method as recited in claim 36 wherein said useful property is the activity of said metal-ligand compounds for a particular reaction.

47. The method as recited in claim 1 wherein said substrate has a configuration selected from the group consisting of:

(i) a porous or non-porous substrate, wherein a sample chamber is filled with reactant gas at pressure P and each of said catalysts is selectively activated; and

(ii) a porous substrate, wherein reactant gas at pressure P is driven through the supported catalyst and substrate into a region of lower pressure, wherein each of said catalysts is selectively activated.

48. The method as recited in claim 1 wherein the components of said homogeneous catalysts are delivered to a synthesis support material contained on said substrate, said synthesis support material and said substrate having a configuration selected from the group consisting of (i) a porous or non-porous synthesis support material contained in wells wherein the components flow to or from the top of said wells through a hole in the bottom of said wells;

(ii) a porous or non-porous synthesis support material contained in wells wherein the components flow into and out of the top of said wells; and

(iii) a porous or non-porous support which serves as both said synthesis support material and said substrate, wherein the components are deposited directly onto the surface of said substrate.

49. The method as recited in claim 36 wherein said array is screened in a manner selected from the group consisting of:

(i) screening said array simultaneously, (ii) screening said array serially; and

(iii) screening said array in a spatially selective manner, wherein the detector is distanced from said array, said array is screened, and then the detector is repositioned so that a portion of said array is screened.

50. The method as recited in claim 36 wherein said useful property is screened for using a technique selected from the group consisting of scanned mass spectrometry, chromatography, ultraviolet imaging, visible imaging, infrared imaging, electromagnetic imaging, ultraviolet spectroscopy, visible spectroscopy, infrared spectroscopy, electromagnetic spectroscopy and acoustical methods.

51. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 25 cm².

52. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 10 cm².

53. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 1 cm².

54. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 1 mm².

55. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 10,000 μ

m².

56. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 1,000 μ

m².

57. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 100 μ

m².

58. The method as recited in claim 1 wherein each of said metal-ligand compounds is synthesized in an area of less than 1 μ

m².

59. The method as recited in claim 1 wherein at least 10 different metal-ligand compounds are synthesized on said substrate.

60. The method as recited in claim 1 wherein at least 20 different metal-ligand compounds are synthesized on said substrate.

61. The method as recited in claim 1 wherein at least 50 different metal-ligand compounds are synthesized on said substrate.

62. The method as recited in claim 1 wherein at least 100 different metal-ligand compounds are synthesized on said substrate.

63. The method as recited in claim 1 wherein at least 200 different metal-ligand compounds are synthesized on said substrate.

64. The method as recited in claim 1 wherein at least 500 different metal-ligand compounds are synthesized on said substrate.

65. The method as recited in claim 1 wherein at least 1,000 different metal-ligand compounds are synthesized on said substrate.

66. The method as recited in claim 1 wherein at least 1,000 different metal-ligand compounds are synthesized on said substrate.

67. The method as recited in claim 1 wherein at least 10⁶ different metal-ligand compounds are synthesized on said substrate.

68. The method as recited in claim 1 wherein said first and second metal-binding ligands are [2,2] or [2,1] ligands and wherein each of said metal-binding ligands is contacted with a main group metal alkyl complex such that said first and second metal-ligand compounds are each in the mono- or di-protic form.

69. The method as recited in claim 68 wherein said main group metal alkyl complex is a trialkylaluminum complex.

70. A method as recited in claim 68 wherein said array of metal-ligand compounds is useful for an organic transformation reaction requiring Lewis acidic sites.

71. A method as recited in claim 70 wherein said organic transformation reaction is selected from the group consisting of stereo-selective coupling reactions, olefin oligomerization reactions and olefin polymerization reactions.

72. The method as recited in claim 68 wherein said array of metal-ligand compounds is further modified by reaction with an ion-exchange activator to produce an array of ligand-stabilized cationic aluminum reagents.

73. The method as recited in claim 72 wherein said ion-exchange activator is [PhNMe₂H][B(C₆F₅)₄].

74. The method as recited in claim 72 wherein said ligand-stabilized cationic aluminum reagents can be used as catalysts for a reaction selected from the group consisting of organic coupling reactions, olefin oligomerization reactions and olefin polymerization reactions.

75. The method as recited in claim 1 wherein the components of said first and second metal-ligand compounds are delivered to said substrate using a liquid dispensing techniques in combination with a masking technique.

76. A method for preparing a polymer blend, said method comprising contacting at least two metal-ligand compounds prepared in accordance with the method recited in claim 1 with a cocatalyst and a monomer.

77. A method for polymerizing olefins, diolefins and acetylenically unsaturated monomers, said method comprising contacting at least one metal-ligand compounds prepared in accordance with the method recited in claim 1 with a cocatalyst and a monomer.

78. A method of making an array of metal-ligand compounds, said method comprising:

(a) delivering a first metal-binding ligand and a second metal-binding ligand on first and second regions on a substrate; and

(b) delivering a first metal ion to said first metal-binding ligand and a second metal ion to said second metal-binding ligand to form a first metal-ligand compound and a second metal-ligand compound.

79. A method of making and screening an array of metal-ligand compounds, said method comprising:

(a) synthesizing a spatially segregated array of ligands;

(b) delivering a suitable metal precursor to each element of said array of ligands to create an array of metal-ligand compounds;

(c) optionally activating said array of metal-ligand compounds with a suitable cocatalyst;

(d) optionally modifying said array of metal-ligand compounds with a third component; and

(e) screening said array of metal-ligand compounds for a useful property using a parallel or rapid serial screening technique selected from the group consisting of optical imaging, optical spectroscopy, mass spectrometry, chromatography, acoustic imaging, acoustic spectroscopy, infrared imaging and infrared spectroscopy.

80. An array of at least 10 different metal-ligand compounds at known locations on a substrate.

81. The array as recited in claim 80 wherein said array contains more than 20 different metal-ligand compounds at known locations on said substrate.

82. The array as recited in claim 80 wherein said array contains more than 50 different metal-ligand compounds at known locations on said substrate.

83. The array as recited in claim 80 wherein said array contains more than 100 different metal-ligand compounds at known locations on said substrate.

84. The array as recited in claim 80 wherein said array contains more than 200 different metal-ligand compounds at known locations on said substrate.

85. The array as recited in claim 80 wherein said array contains more than 500 different metal-ligand compounds at known locations on said substrate.

86. The array as recited in claim 80 wherein said array contains more than 1,000 different metal-ligand compounds at known locations on said substrate.

87. The array as recited in claim 80 wherein said array contains more than 10,000 different metal-ligand compounds at known locations on said substrate.

88. The array as recited in claim 80 wherein said array contains more than 10⁶ different metal-ligand compounds at known locations on said substrate.

89. The array as recited in claim 80 wherein each of the metal-ligand compounds of said array has similar functionality, thereby allowing the metal-ligand compounds of said array to be compared for a selected property.