Supporting Information for
Unprecedented Negishi coupling at C-Br in the presence of a stannyl group as a convenient approach to pyridinylstannanes and their application in liquid crystal synthesis
Y. A. Getmanenko, R. J. Twieg Department of Chemistry Kent State University Kent, OH 44242 USA
[email protected] Table of Contents 1. Synthesis of 2-alkyl-5-tri-n-butylstannylpyridines 6b-e
S9
1.1. 2-n-Hexyl-5-(tri-n-butylstannyl)-pyridine (6b)
S9
1.2. 2-n-Nonyl-5-(tri-n-butylstannyl)-pyridine (6c)
S10
1.3. 2-n-Decyl-5-(tri-n-butylstannyl)-pyridine (6d)
S11
1.3.1.Synthesis of 6d from 2-n-decyl-5-bromopyridine (7a)
S11
1.3.2. Synthesis of 6d from 2-bromo-5-(tri-n-butylstannyl)-pyridine (1)
S12
1.4. 2-n-Tridecyl-5-(tri-n-butylstannyl)-pyridine (6e)
S13
2. 2-n-Decyl-5-bromopyridine (7a)
S14
3. Preparation of 2-(5-n-alkylthien-2-yl)-5-(tri-n-butylstannyl)-pyridines 8b,c
S15
3.1. 2-(5-n-Nonylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8b)
S15
3.2. 2-(5-n-Tridecylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8c)
S16
4. Preparation of 2-alkylthiophenes 9a-d and 2-bromo-5-alkylthiophenes 10a-d
S18
4.1. 2-n-Heptylthiophene (9a)
S18
4.2. 2-n-Nonylthiophene (9b)
S18
4.3. 2-n-Tridecylthiophene (9c)
S19
S1
4.4. 2-n-Undecylthiophene (9d)
S19
4.5. 2-Bromo-5-n-heptylthiophene (10a)
S20
4.6. 2-Bromo-5-n-nonylthiophene (10b)
S21
4.7. 2-Bromo-5-n-tridecylthiophene (10c)
S22
4.8. 2-Bromo-5-n-undecylthiophene (10d)
S23
5. 1-n-Heptyloxy-4-bromobenzene (12)
S24
6. Preparation of 3-alkylpyridines 13a-c
S24
6.1. 3-n-Hexylpyridine (13a)
S24
6.2. 3-n-Octylpyridine (13b)
S25
6.3. 3-n-Decylpyridine (13c)
S26
7. Synthesis of 2-tri-n-butylstannyl-5-alkylpyridines 14a,c
S26
7.1. 2-Tri-n-butylstannyl-5-n-hexylpyridine (14a)
S26
7.2. 2-Tri-n-butylstannyl-5-n-decylpyridine (14c)
S27
8.1 2-n-Pentyl-6-(tri-n-butylstannyl)-pyridine (15a)
S28
8.2. 2-n-Decyl-6-(tri-n-butylstannyl)-pyridine (15b)
S29
9.1 6-(5-n-Tridecylthien-2-yl)-2-(tri-n-butylstannyl)-pyridine (16)
S30
9.2. Isolation of 17: protio-de-stannylation of 6-(5-n-tridecylthien-2-yl)-2-(tri-nbutylstannyl)-pyridine (16)
S31
10. Stille coupling of pyridinyl stannanes with aryl halides
S32
10.1. 2,5-Bis-(2-n-tridecylpyridin-5-yl)-thiophene (18)
S32
10.2. Preparation of 2,5-bis-(2-(5-nonylthiophen-2-yl)-pyridin-5-yl)-thiophene (19)
S33
10.3. Scheme 1. Three synthetic approaches evaluated for the preparation of terpyridine liquid crystal 20
S34
10.4. 2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine (20)
S35
10.5. 2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine (20): Negishi coupling of 2,5-dibromopyridine (4) with 2-n-hexylpyridin-5-ylzinc chloride
S36
10.6. 2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine (20): Negishi coupling of 2-bromo-5-iodopyridine (22) with 2-n-hexyl-pyridin-5-ylzinc chloride
S37
10.7. 2,5-Di-(5-n-hexylpyridin-2-yl)-pyridine (23)
S37
10.8. Preparation of thiophene-bypyridine LCs 26a,b
S39
S2
10.8.1. Scheme 2. Stille coupling of 2-n-decyl-5-tri-n-butylstannylpyridine (6d) with aryl halides 25 producing thiophene-bipyridine liquid crystals 26a,b
S39
10.8.2. 2-(5-n-Nonylthiophen-2-yl)-5-bromopyridine (25a)
S39
10.8.3. 5-Bromo-2-(5-n-undecylthien-2-yl)-pyridine (25b)
S40
10.8.4. 6'-n-Decyl-6-(5-n-nonylthiophen-2-yl)-[3,3']-bipyridinyl (26a)
S42
10.9. 5-Heptyl-6'-(4-heptyloxy-phenyl)-[2,3']-bipyridinyl (27)
S44
10.10. 2-(5-n-Nonylthiophen-2-yl)-5-(5-n-undecylthiophen-2-yl)-pyridine (29)
S45
10.11. 6-(5-n-Tridecylthiophen-2-yl)-6'-(5-n-undecylthiophen-2-yl)[3,3']-bipyridinyl (30)
S46
10.12. 2,5-Di-(6-n-pentylpyridin-2-yl)-thiophene (31)
S47
10.13. 5,5’-Bis-(6-n-decylpyridin-2-yl)-2,2’-bithiophene (33)
S48
11. 5,5’-Dibromo-2,2’-bithiophene (32)
S49
12. Figure 1. DSC analysis of terpyridine LC 20: enlarged region with weak 1st/2nd order transitions (marked as 1, 2, and 3) 13. Figure 2. DSC thermogram of terpyridine 23
S50 S50
14. NMR spectra of the synthesized materials 14.1. 1H NMR spectrum of 2-bromo-5-(tri-n-butylstannyl)-pyridine (1)
S51
14.2. 13C NMR spectrum of 2-bromo-5-(tri-n-butylstannyl)-pyridine (1)
S51
14.3. 1H NMR spectrum of 2-bromo-6-(tri-n-butylstannyl)-pyridine (2)
S52
14.4. 13C NMR spectrum of 2-bromo-6-(tri-n-butylstannyl)-pyridine (2)
S52
14.5. 1H NMR spectrum of 2-(tri-n-butylstannyl)-5-bromopyridine (3)
S53
14.6. 13C NMR spectrum of 2-(tri-n-butylstannyl)-5-bromopyridine (3)
S53
14.7. 1H NMR spectrum of 2-n-pentyl-5-(tri-n-butylstannyl)-pyridine (6a)
S54
14.8. 13C NMR spectrum of 2-n-pentyl-5-(tri-n-butylstannyl)-pyridine (6a)
S54
14.9. 1H NMR spectrum of 2-n-hexyl-5-(tri-n-butylstannyl)-pyridine (6b)
S55
S3
14.10. 13C NMR spectrum of 2-n-hexyl-5-(tri-n-butylstannyl)-pyridine (6b)
S55
14.11. 1H NMR spectrum of 2-n-nonyl-5-(tri-n-butylstannyl)-pyridine (6c)
S56
14.12. 13C NMR spectrum of 2-n-nonyl-5-(tri-n-butylstannyl)-pyridine (6c)
S56
14.13. 1H NMR spectrum of 2-n-decyl-5-(tri-n-butylstannyl)-pyridine (6d)
S57
14.14. Aromatic region of 1H NMR spectrum of 2-n-decyl-5-(tri-n-butylstannyl)pyridine (6d)
S57
14.15. 13C NMR spectrum of 2-n-decyl-5-(tri-n-butylstannyl)-pyridine (6d)
S58
14.16. 1H NMR spectrum of 2-n-tridecyl-5-(tri-n-butylstannyl)-pyridine (6e)
S59
14.17. Aromatic region of 1H NMR spectrum of 2-n-tridecyl-5-(tri-n-butylstannyl)pyridine (6e)
S59
14.18. 13C NMR spectrum of 2-n-tridecyl-5-(tri-n-butylstannyl)-pyridine (6e)
S60
14.19. 1H NMR spectrum of 2-n-decyl-5-bromopyridine (7a)
S61
14.20. Aromatic region of 1H NMR spectrum 2-n-decyl-5-bromopyridine (7a)
S61
14.21. 1H NMR spectrum of 2-(5-n-heptylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8a)
S62
14.22. Aromatic region of 1H NMR spectrum of 2-(5-n-heptylthien-2-yl)-5(tri-n-butylstannyl)-pyridine (8a)
S62
14.23. 13C NMR spectrum of 2-(5-n-heptylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8a)
S63
14.24. 1H NMR spectrum of 2-(5-n-nonylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8b)
S64
14.25. Aromatic region of 1H NMR spectrum of 2-(5-n-nonylthien-2-yl)5-(tri-n-butylstannyl)-pyridine (8b)
S64
14.26. 13C NMR spectrum of 2-(5-n-nonylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8b)
S65
S4
14.27. 1H NMR spectrum of 2-(5-n-tridecylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8c)
S66
14.28. 13C NMR spectrum of 2-(5-n-tridecylthien-2-yl)-5-(tri-n-butylstannyl)pyridine (8c)
S66
14.29. 1H NMR spectrum of 2-bromo-5-n-tridecylthiophene (10c)
S67
14.30. 13C NMR spectrum of 2-bromo-5-n-tridecylthiophene (10c)
S67
14.31. 1H NMR spectrum of 2-(4-n-heptyloxyphenyl)-5-(tri-n-butylstannyl)pyridine (11)
S68
14.32. 13C NMR spectrum of 2-(4-n-heptyloxyphenyl)-5-(tri-n-butylstannyl)pyridine (11)
S68
14.33. 1H NMR spectrum of 2-tri-n-butylstannyl-5-n-hexylpyridine (14a)
S69
14.34. 13C NMR spectrum of 2-tri-n-butylstannyl-5-n-hexylpyridine (14a)
S69
14.35. 1H NMR spectrum of 2-tri-n-butylstannyl-5-n-octylpyridine (14b)
S70
14.36. 1H NMR spectrum of 2-tri-n-butylstannyl-5-n-decylpyridine (14c)
S70
14.37. 13C NMR spectrum of 2-tri-n-butylstannyl-5-n-decylpyridine (14c)
S71
14.38. 1H NMR spectrum of 2-n-pentyl-6-(tri-n-butylstannyl)-pyridine (15a)
S71
14.39. Aromatic region of 1H NMR spectrum of 2-n-pentyl-6(tri-n-butylstannyl)-pyridine (15a)
S72
14.40. 13C NMR spectrum of 2-n-pentyl-6-(tri-n-butylstannyl)-pyridine (15a)
S72
14.41. 1H NMR spectrum of 2-n-decyl-6-(tri-n-butylstannyl)-pyridine (15b)
S73
14.42. Aromatic region of 1H NMR spectrum of 2-n-decyl-6-(tri-n-butylstannyl)pyridine (15b)
S73
14.43. 13C NMR spectrum of 2-n-decyl-6-(tri-n-butylstannyl)-pyridine (15b)
S74
14.44. 1H NMR spectrum of 6-(5-n-tridecylthien-2-yl)-2-(tri-n-butylstannyl)pyridine (16)
S75
S5
14.45. Aromatic region of 1H NMR spectrum of 6-(5-n-tridecylthien-2-yl)2-(tri-n-butylstannyl)-pyridine (16)
S75
14.46. 13C NMR spectrum of 6-(5-n-tridecylthien-2-yl)-2-(tri-n-butylstannyl)pyridine (16)
S76
14.47. 1H NMR spectrum of 2-(5-tridecylthiophen-2-yl)-pyridine (17)
S77
14.48. Aromatic region of 1H NMR spectrum of 2-(5-tridecylthiophen-2-yl)pyridine (17)
S77
14.49. 13C NMR spectrum of -(5-tridecylthiophen-2-yl)pyridine (17)
S78
14.50. 1H NMR spectrum of 2,5-bis-(2-n-tridecylpyridin-5-yl)-thiophene (18)
S79
14.51. Aromatic region of 1H NMR spectrum of 2,5-bis-(2-n-tridecylpyridin5-yl)-thiophene (18)
S79
14.52. 13C NMR spectrum of 2,5-bis-(2-n-tridecylpyridin-5-yl)-thiophene (18)
S80
14.53. 1H NMR spectrum of 2,5-bis-(2-(5-nonylthiophen-2-yl)-pyridin-5-yl)thiophene (19)
S81
14.54. 13C NMR spectrum of 2,5-bis-(2-(5-nonylthiophen-2-yl)-pyridin-5-yl)thiophene (19)
S81
14.55. Aromatic region of 13C NMR spectrum of 2,5-bis-(2-(5-nonylthiophen2-yl)-pyridin-5-yl)-thiophene (19)
S82
14.56. 1H NMR spectrum of 2,5-di-(2-n-hexylpyridin-5-yl)-pyridine (20)
S83
14.57. Aromatic region of 1H NMR spectrum of 2,5-di-(2-n-hexylpyridin-5-yl)pyridine (20)
S83
14.58. 13C NMR spectrum of 2,5-di-(2-n-hexylpyridin-5-yl)-pyridine (20)
S84
14.59. Aromatic region of 13C NMR spectrum of 2,5-di-(2-n-hexylpyridin-5-yl)pyridine (20)
S84
S6
14.60. 1H NMR spectrum of 2,5-di-(5-n-hexylpyridin-2-yl)-pyridine (23)
S85
14.61. Aromatic region of 1H NMR spectrum of 2,5-di-(5-n-hexylpyridin-2-yl)pyridine (23)
S85
14.62. 13C NMR spectrum of 2,5-di-(5-n-hexylpyridin-2-yl)-pyridine (23)
S86
14.63. Aromatic region of 13C NMR spectrum of 2,5-di-(5-n-hexylpyridin-2-yl)pyridine (23)
S86
14.64. 1H NMR spectrum of 2-(5-n-nonylthiophen-2-yl)-5-bromopyridine (25a)
S87
14.65. 13C NMR spectrum of 2-(5-n-nonylthiophen-2-yl)-5-bromopyridine (25a)
S87
14.66. 1H NMR spectrum of 5-bromo-2-(5-n-undecylthien-2-yl)-pyridine (25b)
S88
14.67. 1H NMR spectrum of 6'-n-decyl-6-(5-n-nonylthiophen-2-yl)-[3,3']bipyridinyl (26a)
S88
14.68. Aromatic region of 1H NMR spectrum of 6'-n-decyl-6(5-n-nonylthiophen-2-yl)-[3,3']-bipyridinyl (26a)
S89
14.69. 13C NMR spectrum of 6'-n-decyl-6-(5-n-nonylthiophen-2-yl)-[3,3']bipyridinyl (26a)
S89
14.70. 1H NMR spectrum of 6'-decyl-6-(5-undecylthiophen-2-yl)-[3,3']bipyridinyl (26b)
S90
14.71. Aromatic region of 1H NMR spectrum of 6'-decyl-6(5-undecylthiophen-2-yl)-[3,3']-bipyridinyl (26b)
S90
14.72. 13C NMR spectrum of 6'-decyl-6-(5-undecylthiophen-2-yl)-[3,3']bipyridinyl (26b)
S91
14.73. 1H NMR spectrum of 5-heptyl-6'-(4-heptyloxy-phenyl)-[2,3']-bipyridinyl (27) S91 14.74. Aromatic region of 1H NMR spectrum of 5-heptyl-6'-(4-heptyloxyphenyl)-[2,3']-bipyridinyl (27)
S92
14.75. 1H NMR spectrum of 2-(5-n-nonylthiophen-2-yl)-5-(5-n-undecylthiophen-
S7
2-yl)-pyridine (29)
S92
14.76. Aromatic region of 1H NMR spectrum of 2-(5-n-nonylthiophen-2-yl)5-(5-n-undecylthiophen-2-yl)-pyridine (29)
S93
14.77. 13C NMR spectrum of 2-(5-n-nonylthiophen-2-yl)-5-(5-n-undecylthiophen2-yl)-pyridine (29)
S93
14.78. 1H NMR spectrum of 6-(5-n-tridecylthiophen-2-yl)-6'-(5-n-undecylthiophen2-yl)-[3,3']-bipyridinyl (30)
S94
14.79. Aromatic region of 1H NMR spectrum of 6-(5-n-tridecylthiophen-2-yl)6'-(5-n-undecylthiophen-2-yl)-[3,3']-bipyridinyl (30)
S94
14.80. 13C NMR spectrum of 6-(5-n-tridecylthiophen-2-yl)-6'(5-n-undecylthiophen-2-yl)-[3,3']-bipyridinyl (30)
S95
14.81. 1H NMR spectrum of 2,5-di-(6-n-pentylpyridin-2-yl)-thiophene (31)
S95
14.82. 13C NMR spectrum of 2,5-di-(6-n-pentylpyridin-2-yl)-thiophene (31)
S96
14.83. 1H NMR spectrum of 5,5’-bis-(6-n-decylpyridin-2-yl)-2,2’-bithiophene (33)
S97
14.84. Aromatic region of 1H NMR spectrum of 5,5’-bis-(6-n-decylpyridin-2-yl)2,2’-bithiophene (33)
S97
14.85. 13C NMR spectrum of 5,5’-bis-(6-n-decylpyridin-2-yl)-2,2’-bithiophene (33) S98
S8
Synthesis of 2-alkyl-5-(tri-n-butylstannyl)-pyridines 6b-e
Bu3Sn
Br
RZnCl Pd(PPh3)4, rt
N
Bu3Sn
R N 6b-e
1
2-n-Hexyl-5-(tri-n-butylstannyl)-pyridine (6b). An alkyl Grignard was prepared from 1bromohexane (1.5 equiv., 0.0266 mol, 4.39g) and Mg turnings (0.0319 mol, 0.78 g) in 25 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to the solution of ZnCl2 (0.0319 mol, 4.35 g) in 32 ml of anhydrous THF (ice-water bath). A white precipitate formed after several minutes of stirring, and the reaction mixture was stirred for an additional hour at room temperature. Next, 2-bromo-5-(tri-n-butylstannyl)-pyridine (1) (0.0177 mol, 7.92 g), Pd(PPh3)4 (0.5 mol%, 0.0885 mmol, 0.10 g) and 20ml of anhydrous THF were mixed in an oven-dried three-necked flask under a nitrogen atmosphere (clear yellow solution formed), and n-hexylzinc chloride solution (47 ml, 1.25 equiv.) was added dropwise via syringe to the yellow reaction mixture. The light yellow reaction mixture with a white precipitate was stirred overnight, transferred to another round bottom flask, and the solvent was removed by rotary evaporation. The residue was treated with 50 ml of water and 50 ml of petroleum ether, and the resulting mixture was vacuum filtered to remove insoluble matter. The organic phase was separated and the aqueous phase was extracted with petroleum ether (4×25 ml). The combined organic phases were dried with brine, then over MgSO4 and after filtration the solvent was removed by rotary evaporation to give 8.10 g of crude material. The product was purified by Kugelrohr distillation (150-164 ºC/0.055-0.065 mm Hg), and the desired material was isolated as yellow oil in 74.3% yield (5.95 g). MS analysis (APCI): 454.19, 456.63 (calculated FW 453.2417). FT-IR (cm-1): 3061, 2957, 2927, 2865, 2853, 1572, 1542, 1462, 1377, 1344, 1086, 1072, 1015, 877, 862, 816, 692. 1H NMR (CDCl3, 400 MHz): δ 0.84-0.91 (t, J=7.16 Hz, 12H), 1.03-1.10 (m, 6H), 1.24-1.40 (m, 12H), 1.50-1.60 (m, 6H), 1.64-1.77 (m, 2H), 2.71-2.78 (t, J=7.85 Hz, 2H), 7.07-7.12 (dd, J=7.66 Hz, 0.65 Hz, S9
1H), 7.63-7.67 (dd, J=7.49 Hz, 1.66 Hz, 1H), 8.48-8.55 (s, 1H);
13
C NMR (CDCl3, 100
MHz): δ 9.55, 13.64, 14.07, 22.58, 27.32, 29.02, 29.16, 29.84, 31.73, 38.41, 122.86 (CH), 132.87 (quaternary C), 144.31 (CH), 155.47 (CH), 161.82 (quaternary C).
2-n-Nonyl-5-(tri-n-butylstannyl)-pyridine (6c). An alkyl Grignard was prepared from 1bromononane (0.0225 mol, 4.66 g) and Mg turnings (0.027 mol, 0.65 g) in 25 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to the solution of ZnCl2 (0.027 mol, 4.41 g) in 30 ml of anhydrous THF (ice-water bath). A white precipitate formed, and the reaction mixture was stirred for additional hour under room temperature conditions. 2-Bromo-5-(tri-n-butylstannyl)-pyridine (1) (0.015 mol, 6.70 g), Pd(PPh3)4 (0.5 mol%, 0.075 mmol, 0.087 g) and 30 ml of anhydrous THF were mixed in an oven-dried three-necked flask under nitrogen atmosphere (clear yellow solution formed), and n-nonylzinc chloride solution was added dropwise via syringe to the bright yellow reaction mixture. After addition of the n-nonylzinc chloride the mixture became light yellow with white precipitate and warm to the touch. After addition of 44 ml of n-nonylzinc chloride (1.5 equivalent in 55 ml of THF was prepared) and stirring for an hour the 2-bromo-5-(tri-n-butylstannyl)-pyridine (1) was consumed (analyzed by TLC, CH2Cl2 + several drops of EtOAc as eluant), and the reaction mixture was quenched with 25 ml of water. Organic solvents were removed by rotary evaporation, 50 ml of hexanes was added and the resulting mixture was vacuum filtered to remove white insoluble matter. The organic phase was separated, and the aqueous phase was extracted with hexanes (2×50 ml, then 3×25 ml). The combined organic phases were dried with brine and then over MgSO4. The solvent was removed by rotary evaporation and the yellowish cloudy oil was chromatographed (225 g of silica gel, CH2Cl2 first, then CH2Cl2:EtOAc=50:1). The product was isolated in 46.6% yield (73-75% reaction yield). MS (APCI): 494.1, 496.1 (with satellites at 492.1, 493.1, 495.1) (calculated FW 495.2887).
S10
FT-IR (cm-1): 3061, 2957, 2924, 2870, 2853, 1572, 1542, 1462, 1377, 1344, 1067, 1015, 862, 691.
1
H NMR (CDCl3, 400 MHz): δ 0.83-0.91 (m, 12H), 1.03-1.10 (m, 6H), 1.20-1.40 (m,
18H), 1.48-1.60 (m, 6H), 1.63-1.74 (m, 2H), 2.67-2.80 (m, 2H), 7.07-7.12 (dd, J=7.54 Hz, 0.84 Hz, 1H), 7.62-7.66 (dd, J=7.51 Hz, 1.62 Hz, 1H), 8.47-8.53 (m, 1H); 13C NMR (CDCl3, 75 MHz): δ 9.56, 13.66, 14.12, 22.69, 27.33, 29.03, 29.32, 29.51, 29.53, 29.89, 31.90, 38.44, 122.87 (CH), 132.88 (quaternary C), 144.31 (CH), 155.50 (CH), 161.85 (quaternary C).
2-n-Decyl-5-(tri-n-butylstannyl)-pyridine (6d) Synthesis of 6d from 2-n-decyl-5-bromopyridine (7a)
Br N 7a
C10H21
1) n-BuLi, -72 ºC THF-hexanes 2) n-Bu3SnCl -70 ºC, 15 min; rt, 2 hours (R= n-C10H21)
Bu3Sn
N 6d
C10H21
An oven-dried three-necked flask was charged with 2-n-decyl-5-bromopyridine (7a) (9.05 mmol, 2.70 g) and 60 ml of anhydrous THF. The reaction mixture was cooled in an acetone/CO2 bath, and n-BuLi (2.5M in hexanes, 9.05 mmol, 3.62 ml) was added dropwise to the suspension of white solid (the starting material precipitated upon cooling). The reaction mixture turned yellow, and then orange during addition of n-BuLi (the internal temperature was kept at –73–72 ºC). The red mixture was stirred for about half an hour, analyzed by TLC (CH2Cl2 as eluant, several drops of the reaction mixture was quenched with water, the organic matter was extracted with hexanes and analyzed) and a solution of tri-n-butyltin chloride (9.05 mmol, 2.95 g) in 8 ml of anhydrous THF was added dropwise (the internal temperature was kept at –70 ºC). The red reaction mixture became lighter in color during addition of tri-n-butyltin chloride, and turned light yellow-orange after completion of addition. The reaction was stirred for 15 minutes, the cooling bath was removed and the mixture was warmed to room temperature. After stirring for two and a half hours the clear
S11
orange mixture was quenched with 15 ml of water and the organic solvent was removed by rotary evaporation. The organic matter was extracted with diethyl ether (50 ml, and 2×15 ml). The combined organic phases were washed with brine and then dried over MgSO4. The solvent was removed by rotary evaporation and the orange-brown oil (4.80 g, ~80% purity by NMR) was purified by column chromatography. Crude material (2.50 g) was applied to the top of the column (50 g of silica gel) and the product was eluted CH2Cl2 first, then with CH2Cl2:EtOAc~50:1. The purified material was isolated as yellowish oil (1.95 g, 74% recovery, 77.2% reaction yield). The product can be further purified by Kugelrohr distillation (140 ºC/0.15 mm Hg). MS (APCI): 509.0, 510.6 (calculated FW 509.3043).
1
H NMR
(CDCl3, 400 MHz): δ 0.85-0.91 (m, 12H), 1.03-1.11 (m, 6H), 1.22-1.40 (m, 20H), 1.48-1.58 (m, 6H), 1.68-1.76 (m, 2H), 2.71-2.76 (m, 2H), 7.06-7.12 (dd, J=7.55 Hz, 0.82 Hz, 1H), 7.617.68 (dd, J=7.51 Hz, 1.63 Hz, 1H), 8.48-8.53 (m, 1H); 13C NMR (CDCl3, 75 MHz): δ 9.55, 13.64, 14.11, 22.69, 27.32, 29.03, 29.33, 29.51, 29.52, 29.58, 29.61, 29.89, 31.91, 38.42, 122.86 (CH), 132.86 (quaternary C), 144.30 (CH), 155.48 (CH), 161.84 (quaternary C).
Synthesis of 6d from 2-bromo-5-(tri-n-butylstannyl)-pyridine (1) An alkyl Grignard was prepared from 1-bromodecane (0.0105 mol, 2.32 g) and Mg turnings (0.0126 mol, 0.31 g) in 10 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to the solution of ZnCl2 (0.0126 mol, 1.72 g) in 12 ml of anhydrous THF (ice-water bath). Precipitation took place after several minutes of stirring, and the reaction mixture was stirred for additional hour under room temperature conditions. 2-Bromo-5-(tri-nbutylstannyl)-pyridine (1) (0.007 mol, 3.13 g), Pd(PPh3)4 (1 mol%, 0.07 mmol, 0.081 g) and 20 ml of anhydrous THF were mixed in an oven-dried three-necked flask under nitrogen, and n-decylzinc chloride solution was added dropwise via syringe to the yellow reaction mixture. After addition of the n-decylzinc chloride the mixture turned orange for several seconds, but
S12
then the color changed back to yellowish (the mixture is cloudy; the initial n-decylzinc chloride had lots precipitate in it). After addition of 25 ml of n-decylzinc chloride (32 ml was the initial volume) and stirring for 35 minutes all the starting material was consumed (analyzed by TLC, CH2Cl2:hexanes=2:1 as eluant), and the reaction mixture was quenched with 20 ml of water. Organic solvents were removed by rotary evaporation, 50 ml of hexanes was added and the resulting mixture was vacuum filtered to remove white insoluble matter. The organic phase was separated and the aqueous phase was extracted with hexanes (50 ml, then 4×25 ml). The combined organic phases were dried over MgSO4, the solvent was removed by rotary evaporation, and the yellowish cloudy oil was chromatographed (100 g of silica gel, CH2Cl2 first, then CH2Cl2:EtOAc=30:1). The yellowish oil was isolated in 79.4% yield (2.72 g).
The NMR analysis matched the analysis of 2-n-decyl-5-tri-n-
butylstannylpyridine (6d) synthesized by a different method, described above.
2-n-Tridecyl-5-(tri-n-butylstannyl)-pyridine (6e). An alkyl Grignard was prepared from 1bromotridecane (0.0225 mol, 5.92 g), Mg turnings (0.027 mol, 0.66) in 22.5 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to the solution of dried ZnCl2 (0.027 mol, 3.68 g) in 22 ml of anhydrous THF (ice-water bath). White precipitate formed after several minutes of stirring, and the reaction mixture was stirred for additional hour under room temperature conditions. 2-Bromo-5-(tri-n-butylstannyl)-pyridine (1) (0.015 mol, 6.71 g), Pd(PPh3)4 (0.5 mol%, 0.075 mmol, 0.087 g) and 30ml of anhydrous THF were mixed in an oven-dried three-necked flask under a nitrogen atmosphere (a clear yellow solution formed), and n-tridecylzinc chloride solution (48 ml, 1.3 equiv.) was added dropwise via syringe to the yellow reaction mixture.
The light yellow reaction mixture with white
precipitate was stirred overnight, transferred to the round bottom flask, and the solvent was removed by rotary evaporation. The residue was treated with 25 ml of water and 50 ml of
S13
petroleum ether, and the resulting mixture was vacuum filtered to remove insoluble mater. The organic phase was removed and the aqueous phase was extracted with petroleum ether (3×25 ml). The combined organic phases were dried with brine, and then over dried over MgSO4, and the solvent was removed by rotary evaporation to give 10.3 g of crude material. After storage of the crude material in the refrigerator some solid formed. A Kugelrohr distillation was attempted (150-158 ºC/0.095 mm Hg), but it was very slow on a big scale (and higher pressure of 0.12 mm Hg) and was accompanied by decomposition.
The
distillation was terminated and the residual material was chromatographed (75 g of silica gel, CH2Cl2:EtOAc=50:1 as eluant) and a light yellow oil was isolated in 42.6% yield (3.60 g). The reaction was repeated with omission of the Kugelrohr distillation and in this case the material was isolated in 65.4% yield using only column chromatography (silica gel, CH2Cl2, then CH2Cl2:EtOAc=50:1) as a purification step. MS (APCI): 550.2, 552.1 (calculated FW 551.3513). 1H NMR (CDCl3, 300 MHz): δ 0.85-0.90 (t, J=7.28 Hz, 12H), 1.02-1.10 (m, 6H), 1.20-1.40 (m, 26H), 1.50-1.61 (m, 6H), 1.65-1.78 (m, 2H), 2.70-2.77 (t, 2H), 7.08-7.12 (d, J=7.50 Hz, 1H), 7.60-7.68 (dd, J=7.47 Hz, 1.58 Hz, 1H), 8.50-8.53 (d, J=0.75 Hz, 1H);
13
C
NMR (CDCl3, 75 MHz): δ 9.70, 13.79, 14.27, 22.85, 27.09, 29.04, 29.18, 29.31, 29.51, 29.68, 29.73, 30.04, 32.08, 38.56, 123.02 (CH), 133.03 (quaternary C), 144.47 (CH), 155.61 (CH), 161.98 (quaternary C).
2-n-Decyl-5-bromopyridine (7a). A Grignard reagent was prepared from 1-bromodecane (0.03525 mol, 7.79 g) and Mg turnings (0.0423 mol, 1.03 g) in 40 ml of anhydrous THF. This freshly prepared n-decylmagnesium bromide was added dropwise to a flask containing ZnCl2 (0.0423 mol, 5.76 g) in 40 ml of anhydrous THF (ice-water cooling bath) and a white precipitate was obtained. The cooling bath was removed and the reaction mixture with a considerable amount of white precipitate was stirred for 1h. The resulting n-decylzinc
S14
chloride (55 ml, 0.024 mol, 1.2 equiv.) was added dropwise to a solution of 2,5dibromopyridine (4) (0.02 mol) and Pd(PPh3)4 (0.5 mol%, 0.12 g) in 10 ml of freshly distilled THF. The reaction mixture was stirred overnight at room temperature, poured into 20 ml of water, and 20 ml of CH2Cl2 was added. The resulting solution was vacuum filtered to separate a small amount of insoluble white solid, the organic phase was separated, and the aqueous phase was extracted with CH2Cl2. The organic phases were combined, washed with brine and then dried over MgSO4. The solvent was removed by rotary evaporation and the product was purified by Kugelrohr distillation (colorless oil, 100-105 ºC/0.095-0.10 mm Hg, 4.92 g, 82.6% yield). 297.1092).
1
MS (APCI): 298.1, 300.0 (1:1 intensity ratio) (calculated FW
H NMR (CDCl3, 400 MHz): δ 0.85-0.0.91 (t, J=6.88 Hz, 3H, CH3), 1.22-1.38
(m, 14H), 1.63-1.75 (m, 2H), 2.70-2.76 (t, J=7.78 Hz, 2H), 7.02-7.07 (d, J=8.27 Hz, 1H), 7.67-7.72 (dd, J=8.28 Hz, 2.42 Hz, 1H), 8.56-8.60 (d, J=2.31 Hz, 1H); 13C NMR (CDCl3, 75 MHz): δ 14.28, 22.84, 29.45, 29.60, 29.69, 29.74, 29.86, 29.93, 32.05, 37.87, 117.87 (C-Br), 124.23 (CH), 138.99 (CH), 150.25 (CH), 161.24 (quaternary C).
Preparation of 2-(5-n-alkylthien-2-yl)-5-(tri-n-butylstannyl)-pyridines 8b,c R1 Br
SnBu3
N
S
ZnCl
Pd(PPh3)4, THF, rt
R1
S
N
SnBu3
8b-c
1
2-(5-n-Nonylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8b). An oven-dried three-necked flask was charged with 2-bromo-5-n-nonylthiophene (10b) (7.16 mmol, 2.07 g), anhydrous THF (25 ml) was added, and the resulting mixture was cooled in an acetone/CO2 bath under nitrogen atmosphere. n-BuLi (2.5M in hexanes, 7.16 mmol, 2.9 ml) was added dropwise to a clear colorless solution (-75-70 ºC internal temperature). The light yellow reaction mixture was stirred for half an hour, analyzed by TLC, and an additional 0.6 ml of n-BuLi (20 mol%) was added since some unreacted starting material was detected.
S15
After stirring for an
additional 10 minutes (the starting bromide 10b was consumed as confirmed by TLC analysis) solution of ZnCl2 (8.6 mmol, 1.17 g) in 10 ml of anhydrous THF was added dropwise. After completion of the addition of ZnCl2 solution the cooling bath was removed, and the reaction mixture was stirred for 3 hours. 2-Bromo-5-(tri-n-butylstannyl)-pyridine (1) (6.82 mmol, 3.05 g) and Pd(PPh3)4 (0.5 mol%, 0.034 mmol, 0.039 g) were added in one portion.
After stirring for several minutes the solution became yellow with noticeable
fluorescence.
The reaction mixture was stirred for an hour, analyzed by TLC
(hexanes:CH2Cl2=2:1 as eluant), the yellow solution was transferred to the round bottom flask, 20 ml of water was added and the organic solvents were removed by rotary evaporation. The organic matter was extracted with organic solvents (3×50 ml of hexanes, 2×20 ml of hexanes, 2×10 ml of CH2Cl2), the organic phases were combined, washed with brine, then dried over MgSO4, and the solvents were removed by rotary evaporation. The orange oil was chromatographed (80 g of silica gel, hexanes:CH2Cl2=2:1 as eluant). The purified product was isolated as light yellow oil (3.05 g, 77.6% yield). MS (APCI): 576.6, 577.5, 578.3 (calculated FW 577.2764). 1H NMR (CDCl3, 400 MHz): δ 0.84-0.91 (m, 12H), 1.05-1.11 (m, 6H), 1.22-1.40 (m, 18H), 1.48-1.60 (m, 6H), 1.3-1.74 (m, 2H), 2.80-2.86 (t, J=7.53 Hz, 2H), 6.75-6.79 (d, J=3.67 Hz, 1H), 7.37-7.41 (d, J=3.62 Hz, 1H), 7.52-7.56 (dd, J=7.75 Hz, 0.95 Hz, 1H), 7.65-7.75 (dd, J=7.75 Hz, 1.55 Hz, 1H), 8.50-8.55 (m, 1H);
13
C
NMR (CDCl3, 100 MHz): δ 9.66, 13.67, 14.12, 22.69, 27.34, 29.05, 29.33, 29.40, 29.52, 30.44, 31.57, 31.90, 118.23 (CH), 124.07 (CH), 125.14 (CH), 134.39 (quaternary C), 142.40 (quaternary C), 144.51 (CH), 148.36 (quaternary C), 152.20 (quaternary C), 155.72 (CH).
2-(5-n-Tridecylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8c).
An oven-dried three-
necked flask was charged with 2-bromo-5-n-tridecylthiophene 10c (1.1 equiv., 7.7 mmol, 2.66 g), anhydrous THF (15 ml) was added, and the resulting mixture was cooled in an
S16
acetone/CO2 bath under nitrogen atmosphere. n-BuLi (2.5M in hexanes, 7.7 mmol, 3.1 ml) was added dropwise to the white suspension of 10c. The reaction mixture was stirred for 10 minutes, and then the cooling bath was removed for 10 minutes (the precipitate dissolved), and cooled again in acetone/CO2 bath for 10 minutes (reprecipitation took place). A solution of ZnCl2 (9.24 mmol, 1.26 g) in 10 ml of anhydrous THF was added dropwise (the precipitate started to dissolve), the cooling bath was removed, and the mixture was stirred for an hour and a half. This freshly prepared arylzinc chloride solution was added to the flask charged with 2-bromo-5-(tri-n-butylstannyl)-pyridine (1) (7.0 mmol, 3.13 g), Pd(PPh3)4 (0.5 mol%, 0.035 mmol, 0.040 g) and 10 ml of anhydrous THF (the flask became warm to the touch). The reaction mixture was stirred for an hour and a half, transferred to a round bottom flask, treated with 10 ml of water and the solvents were removed by rotary evaporation. The residue was treated with 20 ml of water and 50 ml of hexanes and vacuum filtered to remove insoluble matter. The organic phase was removed, the aqueous phase was extracted with hexanes (4×25 ml), and the combined organic phases were washed with brine, and then dried over MgSO4. The solvents were removed by rotary evaporation to give the crude product as a yellow oil which was purified by column chromatography (120 g of silica gel, hexanes:CH2Cl2 as eluant). The purified product was isolated as light yellow oil (3.40 g, 53.7 % yield). First two fractions collected were contaminated (1.35 g of mixture, ~1.1 g of 8c), but were repurified (4.5 g total yield, 70.6% reaction yield). MS (APCI): 632.4, 634.3 (calculated FW 633.3390).
1
H NMR (CDCl3, 400 MHz): δ 0.88-0.95 (m, 12H), 1.10-1.16
(m, 6H), 1.27-1.40 (m, 26H), 1.52-1.62 (m, 6H), 1.68-1.78 (m, 2H), 2.83-2.89 (t, 2H), 6.776.82 (d, J=3.62 Hz, 1H), 7.40-7.43 (d, J=3.62 Hz, 1H), 7.54-7.60 (m, 1H), 7.70-7.80 (dd, J=7.72 Hz, 1.46 Hz, 1H), 8.54-8.60 (m, 1H);
13
C NMR (CDCl3, 75 MHz): δ 9.66, 13.67,
14.14, 22.72, 27.34, 29.05, 29.39, 29.40, 29.57, 29.68, 30.44, 31.57, 31.95, 118.23 (CH), 124.07 (CH), 125.13 (CH), 134.37 (quaternary C), 142.40 (quaternary C), 144.50 (CH),
S17
148.35 (quaternary C), 152.20 (quaternary C), 155.72 (CH) (aromatic C(H) carbons showed satellite signals).
Preparation of 2-alkylthiophenes 9a-d and 2-bromo-5-alkylthiophenes 10a-d 2-n-Heptylthiophene (9a) was prepared using a literature procedure 1 from thiophene (0.18 mol, 15.14 g), n-BuLi (2.5M in hexanes, 0.15 mol, 93.75 ml) and 1-bromoheptane (0.15 mol, 26.86 g). The crude material was purified by vacuum distillation (18.45 g, 67.5%, b.p. 57-60 ºC/0.11 mm Hg; lit. b.p. 81.5 ºC/0.3 mm Hg 2 ). 1H NMR (CDCl3, 300 MHz): δ 0.82-0.93 (t, J=6.89 Hz, 3H), 1.17-1.40 (m, 8H), 1.60-1.72 (m, 2H), 2.75-2.85 (t, J=8.07 Hz, 2H), 6.746.78 (m, 1H), 6.88-6.92 (dd, J=5.11 Hz, 3.40 Hz, 1H), 7.08-7.11 (dd, J=5.12 Hz, 1.22 Hz, 1H);
13
C NMR (CDCl3, 75 MHz): δ 14.28, 22.84, 29.23, 29.28, 30.10, 31.97, 122.87 (CH),
124.04 (CH), 126.79 (CH), 146.06 (quaternary C).
2-n-Nonylthiophene (9b) was prepared using a literature procedure1 from thiophene (0.12 mol, 10.10 g), n-BuLi (2.5M in hexanes, 0.10 mol, 62.5 ml) and 1-bromononane (0.10 mol, 20.70 g). The crude material was purified by vacuum distillation (colorless oil, 12.0 g, 56%, b.p. 78-83 ºC/0.14 mm Hg, lit. b.p. 128-131 ºC/1 mm Hg 3 ). MS (APCI): 211.1 (calculated FW 210.1442). 1H NMR (CDCl3, 300 MHz): δ 0.82-0.92 (t, J=6.72 Hz, 3H), 1.15-1.40 (m, 12H), 1.58-1.72 (m, 2H), 2.75-2.85 (t, J=7.92 Hz, 2H), 6.74-6.78 (dd, J=4.37 Hz, 1.00 Hz, 1H), 6.87-6.92 (dd, J=5.11 Hz, 3.39 Hz, 1H), 7.07-7.10 (dd, J=5.14 Hz, 1.16 Hz, 1H);
13
C
NMR (CDCl3, 75 MHz): δ 14.31, 22.88, 29.34, 29.51, 29.58, 29.72, 30.11, 32.02, 32.09, 122.87 (CH), 124.04 (CH), 126.79 (CH), 146.05 (quaternary C).
(1) Endtner J.M.; Effenberger F.; Hartschuh A.; Port H. J. Am. Chem. Soc., 2000, 122, 3037. (2) Jeffery G.H.; Parker R.; Vogel A.I. J. Chem. Soc., 1961, 570. (3) Campaigne, E.; Diedrich, J. L. J. Am. Chem. Soc., 1948, 70, 391.
S18
2-n-Tridecylthiophene (9c) was prepared using a slightly modified literature procedure1. Anhydrous THF (75 ml) was mixed with n-BuLi (2.5M in hexanes, 0.15 mol, 60 ml), and the mixture was cooled down to -25ºC (nitrogen atmosphere). Thiophene (0.15 mol, 12.62 g) was added (-25-15 ºC), and the clear yellow reaction mixture was allowed to warm up to room temperature. The mixture was stirred for 2 hours and 1-bromotridecane (0.0125 mol, 32.91 g) was added. After completion of addition of 1-bromotridecane (no exotherm was observed) the reaction mixture was heated overnight at reflux (an exothermic reaction started when the bath temperature reached ~40-45 ºC). The orange reaction mixture with a white precipitate was transferred to a round bottom flask, several ml of water was added and the organic solvents were removed by rotary evaporation. Additional water was added, and the product was extracted with hexanes. The combined organic phases were dried with brine, then over MgSO4, and the solvent was removed by rotary evaporation. The low boiling point impurities were removed by distillation using a water aspirator, and the product was vacuum distilled (115-118 ºC/0.095 mm Hg). The purified material was isolated as yellowish oil in 79.0% yield (26.30 g). MS analysis (APCI): 267.25 (FW 266.2068). 1H NMR (CDCl3, 400 MHz): δ 0.90-1.00 (t, 3H), 1.30-1.50 (m, 20H), 1.70-1.80 (m, 2H), 2.83-2.92 (t, 2H), 6.836.86 (dd, J=3.39 Hz, 1.01 Hz, 1H), 6.96-6.99 (dd, J=5.12 Hz, 3.40 Hz, 1H), 7.15-7.17 (dd, J=5.12 Hz, 1.19 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 14.21, 22.81, 29.25, 29.49, 29.68, 29.78, 30.02, 31.92, 32.05, 122.73 (CH), 123.91 (CH), 126.64 (CH), 145.88 (quaternary C) (the 1H NMR of this compound without resolution of signals in aromatic region was reported in the literature 4 ).
2-n-Undecylthiophene (9d) was prepared by an adapted literature procedure1. The flask was charged with anhydrous THF (75 ml) and n-BuLi (0.15 mol, 60 ml), and the solution was
(4) Pomonis, J. G.; Fatland, C.L.; Taylor, F.R. J. Chem. Eng. Data., 1976, 233-236.
S19
cooled (acetone/CO2 bath). Thiophene (0.165 mol, 13.88 g) was added, and the internal temperature quickly increased from –60 ºC up to –5 ºC. The mixture was allowed to warm up to room temperature and stirred for 2.5 hours. Half of this freshly prepared solution was treated with 1-iodoundecane (0.073 mol, 20.60 g), and the mixture was heated up. An exothermic reaction started once the mixture was heated, and after several minutes white precipitate formed. The mixture was refluxed for 16 hours, cooled to room temperature and the yellow solution with white precipitate was transferred to a round bottom flask. The solvent was removed by rotary evaporation; the residue (dark brown) was treated with 25 ml of water and 25 ml of hexanes. The organic phase was separated; the aqueous phase was extracted with hexanes (3×15 ml, 3×10 ml). The combined organic extracts were dried over MgSO4, and the solvent was removed from yellow solution by rotary evaporation to give crude material as yellow oil (29 g).
Purified material was obtained by the Kugelrohr
distillation (126-134 ºC/0.2 mm Hg) in 80.5% yield (14.0 g). 1H NMR (CDCl3, 400 MHz): δ 0.83-0.91 (t, J=6.88 Hz, 3H), 1.21-1.40 (m, 16H), 1.62-1.71 (m, 2H), 2.68-2.83 (t, J=7.99 Hz, 2H), 6.76-6.79 (m, 1H), 6.89-6.93 (dd, J=5.12 Hz, 3.39 Hz, 1H), 7.08-7.11 (dd, J=5.15 Hz, 1.19 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ 14.13, 22.70, 29.15, 29.36, 29.38, 29.57,
29.63, 29.65, 29.93, 31.82, 31.93, 122.70 (CH), 123.88 (CH), 126.63 (CH), 145.91 (quaternary C).
2-Bromo-5-n-heptylthiophene (10a).
An oven-dried three-necked flask equipped with
magnetic stir bar, additional funnel, and bubbler was charged with 2-n-heptylthiophene (9a) (0.06 mol, 10.94 g) and anhydrous DMF (40 ml) under nitrogen atmosphere (ice-water bath). A solution of N-bromosuccinimide (1.1 equiv., 0.066 mol, 11.75 g) in 30 ml of anhydrous DMF was added dropwise to the colorless solution of 2-n-heptylthiophene (9a) over a half an hour period, and the cooling bath was removed. The yellow mixture was stirred for 45
S20
minutes and poured into 200 ml of ice water. The product was extracted with hexanes (50 ml, then 10×25 ml), the combined organic phases were dried with brine, then over MgSO4, and the solvent was removed by rotary evaporation. The residual solvent was removed by vacuum distillation (water aspirator), and the crude material was purified by vacuum distillation (90 ºC/0.1 mm Hg) to give the product as colorless oil in 88.8% yield (13.92 g). 1
H NMR (CDCl3, 300 MHz): δ 0.82-0.0.90 (t, J=6.78 Hz, 3H), 1.20-1.40 (m, 8H), 1.53-1.64
(m, 2H), 2.70-2.75 (t, J=7.52 Hz, 2H), 6.50-6.54 (d, J=3.69 Hz, 1H), 6.81-6.85 (d, J=3.64 Hz, 1H); 13C NMR (CDCl3, 75 MHz): δ 14.26, 22.82, 29.13, 29.17, 30.51, 31.64, 31.93, 108.72 (C-Br), 124.49 (CH), 129.53 (CH), 147.82 (quaternary C) (no characterization was reported for this known material 5 ).
2-Bromo-5-n-nonylthiophene (10b).
An oven-dried three-necked flask equipped with
magnetic stir bar, additional funnel, and bubbler was charged with 2-n-nonylthiophene (9b) (0.057 mol, 12.0 g) and anhydrous DMF (35 ml) under nitrogen atmosphere.
N-
bromosuccinimide (1.1 equiv., 0.0627 mol, 11.16 g) was dissolved in 30 ml of anhydrous DMF under nitrogen atmosphere, the yellow solution was transferred via syringe to the additional funnel and added dropwise to the colorless solution of 2-n-nonylthiophene over a half an hour period. The reaction was analyzed by TLC (hexanes as eluant, the product is less polar than starting material) after 15 minutes of stirring, and the yellow mixture was poured into 150 ml of ice water. The product was extracted with hexanes (3×50 ml, then 6×20 ml), the combined organic phases were dried over MgSO4, and the solvent was removed by rotary evaporation. The bright yellow oil was filtered thought silica gel (25 g, petroleum ether). The light yellow solution was collected, and the solvent was removed by rotary evaporation and then by distillation using water aspirator. The product was distilled at (5) Bartle, K.; Camplbell, N.; Duffy, W.L.; Kelly, S.; Minter, V.; O’Neill, M.; Tuffin, R.P. Mol. Cryst. Liq. Cryst., 2001, 364, 881.
S21
117 ºC/0.12 mm Hg as colorless oil (13.15 g, 79.7% yield). A bulb used to increase the space in case of foaming was removed and additional amount of the product was collected (1.35 g, 8.2%). The purified material was isolated in 89.7% (total 14.50 g). MS (APCI): 290.0, 291.4 (calculated FW 288.0547).
1
H NMR (CDCl3, 300 MHz): δ 0.86-0.0.95 (t, J=6.70 Hz, 3H),
1.20-1.40 (m, 12H), 1.55-1.65 (m, 2H), 2.70-2.75 (t, J=7.51 Hz, 2H), 6.50-6.55 (d, J=3.61 Hz, 1H), 6.80-6.85 (d, J=3.64 Hz, 1H);
13
C NMR (CDCl3, 75 MHz): δ 14.30, 22.86, 29.17,
29.48, 29.50, 29.68, 30.51, 31.64, 32.06, 108.72 (C-Br), 124.48 (CH), 129.52 (CH), 147.81 (quaternary C).
2-Bromo-5-n-tridecylthiophene (10c). An oven-dried three-necked flask equipped with magnetic stir bar, nitrogen inlet, and a bubbler was charged with 2-n-tridecylthiophene (9c) (0.05 mol, 13.32 g) and anhydrous DMF (40 ml) under nitrogen atmosphere.
N-
bromosuccinimide (1.1 equiv., 0.055 mol, 9.79 g) was dissolved in 20 ml of anhydrous DMF under nitrogen atmosphere, and the solution was added dropwise to the reaction mixture cooled in an ice-water bath.
After completion of addition of the N-bromosuccinimide
solution the cooling bath was removed, the bright yellow cloudy mixture was stirred for an hour (two phases formed once the stirring was stopped) and poured into 200 ml of ice water. The product was extracted with hexanes (8×75 ml), the yellow organic phases were combined, washed with brine, then dried over MgSO4, and the solvent was removed by rotary evaporation. The crude product was vacuum distilled (145-148 ºC/0.085-0.090 mm Hg), and the purified material was collected as yellow oil (14.97 g, 86.7% yield). MS analysis (APCI): 345.56, 347.13 (1:1 ratio) (calculated FW 344.117).
1
H NMR (CDCl3, 400 MHz): δ 0.87-
0.94 (t, J=6.86 Hz, 3H), 1.23-1.40 (m, 20H), 1.60-1.67 (m, 2H), 2.71-2.77 (t, J=7.95 Hz, 2H), 6.53-6.56 (m, 1H), 6.80-6.85 (d, J=3.63 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ 14.15,
22.73, 29.01, 29.34, 29.39, 29.55, 29.68, 29.70, 30.35, 31.48, 31.96, 108.56 (C-Br), 124.33
S22
(CH), 129.37 (CH), 147.67 (quaternary C) (two signal for alkyl carbon are missing due to overlap)
2-Bromo-5-n-undecylthiophene (10d). An oven-dried three-necked flask equipped with magnetic stir bar, additional funnel, and bubbler was charged with 2-n-undecylthiophene (9d) (0.0658 mol, 15.70 g) and anhydrous DMF (40 ml) under nitrogen atmosphere. Nbromosuccinimide (1.1 equiv., 0.072 mol, 12.89 g) was dissolved in 30 ml of anhydrous DMF under nitrogen atmosphere, the yellow solution was transferred via syringe to the additional funnel and added dropwise to the colorless solution of 2-n-undecylthiophene over a one hour period. The reaction was analyzed by TLC (hexanes as eluant, the product is less polar than starting material) after several minutes, and the orange mixture was poured into 200 ml of ice water.
The product was extracted with hexanes (3×100 ml), then with
dichloromethane (3×25 ml). The combined organic phases were brine, then over MgSO4, and the solvents were removed by rotary evaporation. DMF was removed by vacuum distillation (water aspirator, 55 ºC). The brown oil was filtered thought silica gel (30 g, petroleum ether). The light yellow solution was collected (the brown strip appeared on the very top of the column with a pink strip a bit below the brown on), and the solvent was removed by rotary evaporation. Crude material was isolated in 27.8 g (theoretical yield 20.89 g, probably some solvent was left). The crude material was transferred to the vacuum distillation flask, the round bottom flask was rinsed with several ml of hexanes, and the solvent was removed by vacuum distillation (water aspirator). The product was collected at 138-139 ºC/0.095-0.1 mm Hg as colorless oil (18.93 g, 90.6% yield).
1
H NMR (CDCl3, 300 MHz): δ 0.83-0.90 (t,
J=6.70 Hz, 3H), 1.20-1.40 (m, 16H), 1.55-1.65 (m, 2H), 2.65-2.75 (t, J=8.00 Hz, 2H), 6.506.55 (m, 1H), 6.80-6.85 (d, J=3.67 Hz, 2H);
13
C NMR (CDCl3, 75 MHz): δ 14.29, 22.86,
S23
29.14, 29.48, 29.51, 29.69, 29.79, 30.49, 31.62, 32.08, 108.7, 124.48, 129.52, 147.82 (one signal for alkyl carbon is missing due to overlap).
1-n-Heptyloxy-4-bromobenzene (12). The reagents 4-bromophenol (0.105 mol, 18.17 g), 1bromoheptane (0.1 mol, 17.9 g), K2CO3 (0.21 mol, 29.0g) and NMP (25 ml) were placed into a round bottom flask. This reaction mixture was heated for 90 minutes (115-120 ºC internal temperature), cooled to room temperature and poured into 200 ml of ice water. The organic material was extracted with hexanes (2×75 ml, then 3×25 ml) and the combined organic phases were dried with brine and then over MgSO4. The solvent was removed by rotary evaporation, low boiling point impurities were removed by distillation using a water aspirator and then the product was distilled (100 ºC/0.085-0.090 mm Hg; lit. b.p. 127 ºC/1 mm Hg 6 ). The product was isolated as colorless oil in 81.5% yield (22.10 g). MS (APCI): 270.3, 272.0 (calculated FW 270.0619).
1
H NMR (CDCl3, 300 MHz): δ 0.83-1.00 (t, J=6.76 Hz, 3H),
1.25-50 (m, 8H), 1.73-1.80 (m, 2H), 3.80-4.00 (t, J=6.55 Hz, 2H), 6.73-6.80 (m, 2H), 7.307.37 (m, 2H); 13C NMR (CDCl3, 75 MHz): δ 14.25, 22.78, 26.14, 29.22, 29.35, 31.94, 68.15, 112.70 (C-Br), 116.45 (2 CH), 132.34 (2 CH), 158.42 (C-O).
Preparation of 3-alkyl-pyridines 13a-c. A slightly modified literature procedure 7 was used for the preparation of 3-alkylpyridines. Br N
R
RMgBr NiCl2(dppe)
N
3-Hexylpyridine (13a). Magnesium turnings (0.12 mol, 2.91 g) and freshly distilled Et2O (30 ml) were placed into an oven-dried three-necked round bottom flask, equipped with a condenser and an additional funnel (N2 atmosphere). The solution of 1-bromohexane (0.11 (6) Bumagin N.A., Luzikova E.V., Beletskaya I.P., Russ. J. Org. Chem., 1995, 31, 11, 1480. (7) Tamao, K., Kodama, S., Nakajima, I., Kumada, M., Minato, A., Suzuki, K. Tetrahedron, 1982, 38, 3347.
S24
mol, 18.16 g) in 120 ml of anhydrous Et2O was added dropwise via the additional funnel, the reaction mixture was refluxed for half an hour and then cooled down to room temperature. This freshly prepared Grignard solution was added dropwise via a syringe into the threenecked found bottom flask charged with 3-bromopyridine (0.1 mol, 15.8 g), NiCl2(dppe) (0.5 mol%, 0.5 mmol, 0.264 g), and 50 ml of freshly distilled Et2O. After the addition of the several drops of the Grignard the reaction mixture became yellow-orange and the precipitation of the white solid took place. The reaction mixture was refluxed for several hours after the completion of the additions of Grignard reagent, cooled to room temperature and poured into ice water. The organic layer was separated; the water layer was extracted with Et2O (3×30 ml). The combined organic extracts were washed with brine, and then dried over MgSO4. Evaporation of the solvent gave the crude product (14.3 g, 87.5%), which was vacuum distilled (60-61 ºC/0.09-0.13 mm Hg) to give title compound as a colorless oil (11.0 g, 67.3%). 1H NMR (CDCl3, 300 MHz): δ 0.85-0.90 (t, J=6.56 Hz, 3H), 1.05-1.48 (m, 5H), 1.50-1.80 (m, 2H), 2.50-2.70 (t, J=7.75 Hz, 2H), 7.10-7.21 (m, 1H), 7.45-7.51 (m, 1H), 8.408.45 (m, 2H);
13
C NMR (CDCl3, 75 MHz): δ 14.18, 22.69, 28.94, 31.23, 31.73, 33.14,
123.35, 135.91, 138.11, 147.25, 150.06.
3-n-Octylpyridine (13b). The title compound was prepared in a similar way described for (13a) (colorless oil, 44.5% yield, b.p. 95-96 ºC/0.3 mm Hg). 1H NMR (CDCl3, 300 MHz): δ 0.85-0.90 (t, J=6.52 Hz, 3H), 1.20-1.45 (m, 10 H), 1.50-1.70 (m, 2H), 2.51-2.62 (t, J=7.73 Hz, 2H), 7.16-7.22 (dd J=4.85 Hz, J=7.73 Hz, 1H), 7.46-7.51 (m, 1H), 8.40-8.45 (m, 2H); 13C (CDCl3, 75 MHz): δ 14.21, 22.78, 29.28, 29.35, 29.51, 31.29, 31.97, 33.14, 123.31 (CH), 135.84 (CH), 138.07 (quaternary C), 147.29 (CH), 150.11 (CH).
S25
3-n-Decylpyridine (13c). The title compound was prepared in a similar way described for (13a) from 3-bromopyridine (0.075 mol, 11.85 g), NiCl2(dppe) (5 mol%, 0.375 mmol, 1.98 g) and Grignard prepared from 1-bromodecane (1.3 eq., 0.0975 mol, 21.56 g), Mg turnings (1.2 eq., 0.117 mol, 2.84 g) and anhydrous THF (75 ml). The crude material was purified by vacuum distillation (98-100 ºC/0.1 mm Hg) and the title compound was isolated as colorless oil with unpleasant smell (11.13 g, 67.7% yield). 219.1987).
1
MS (APCI): 220.2 (calculated FW
H NMR (CDCl3, 400 MHz): δ 0.77-0.85 (t, J=6.82 Hz, 3H), 1.15-1.30 (m, 14
H), 1.49-1.58 (m, 2H), 2.48-2.55 (t, J=7.73 Hz, 2H), 7.08-7.13 (dd, J=7.73 Hz, J=4.82 Hz, 1H), 7.38-7.42 (m, 1H), 8.33-38 (m, 2H);
13
C NMR (CDCl3, 100 MHz): δ 14.09, 22.67,
29.15, 29.31, 29.40, 29.54, 29.70, 31.14, 31.88, 33.01, 123.17 (CH), 135.70 (CH), 137.93 (quaternary C), 147.15 (CH), 149.97 (CH) (this compound was reported in the literature 8 , but no spectral data was found). Synthesis of 2-tri-n-butylstannyl-5-alkylpyridines 14a,c 1) n-BuLi-LiDMAE -40-30 ºC, hexanes R N
Bu3Sn
2) n-Bu3SnCl -70 ºC, 1-4 h
R N 14a,c
13a,c
2-Tri-n-butylstannyl-5-n-hexylpyridine (14a).
N,N-Dimethylaminoethanol (0.075 mol,
6.69 g) and 65 ml of hexanes were placed into an oven-dried three-necked round bottom flask. n-BuLi (2.5M in hexanes, 0.15 mol, 60 ml) was added slowly (–60–0 ºC, acetone/CO2 bath), the reaction mixture was stirred for half an hour (~0 ºC), and cooled down to –45 ºC. The solution of 3-n-hexylpyridine (13a) (0.025 mol, 4.08 g) in 6 ml of hexanes was added dropwise (–42–40 ºC internal temperature), and the color of the reaction changed from colorless to orange and then deep red. The reaction mixture was stirred for an hour, cooled down to –70 ºC and a solution of tri-n-butyltin chloride (3.5 eq., 0.0875 mol, 28.5 g) in
(8) Tereshko, A.B.; Tarasevich, V.A.; Kozlov, N.G. Zhurnal Org. Khim., 1995, 31, 289.
S26
anhydrous THF (75 ml) was added dropwise (–70–55 ºC internal temperature during addition), and the color of the mixture changed from red to bright yellow with white precipitate. The reaction mixture was stirred for 4 hours, the cooling bath was removed and the mixture was allowed to warm up to room temperature. The yellow reaction mixture with white precipitate was transferred to a round bottom flask, and the solvents were removed by rotary evaporation. The residue (yellow oil with white solid) was treated with 75 ml of water, and the organic matter was extracted with hexanes (25 ml, then 4×10 ml). The light yellow combined organic extracts were dried over MgSO4, and the solvent was removed by rotary evaporation. The crude material isolated as light yellow oil was subjected to Kugelrohr distillation, and the contaminated product was collected at 160-170 ºC/0.14 mm Hg (7.91 g), while the last fraction (1.1 g) contained pure compound. The contaminated product (7.91 g) was further purified by column chromatography (40 g of silica gel was mixed with a solution of Et3N in 125 ml for the slurry preparation; hexanes:EtOAc = 10:1 as eluant). The solvent was removed by rotary evaporation to give almost colorless oil (5 g), which was Kugelrohr distilled (155-167 ºC/0.12 mm) to give product (4.95 g) (total yield of 6.05 g (53 %), 85% purity by NMR). FT-IR (cm-1): 3054, 2957, 2928, 2872, 2854, 1545, 1462, 1377, 1340, 1291, 1248, 1072, 1024, 960, 878, 745, 692. 1H NMR (CDCl3, 400 MHz): δ 0.82-0.91 (m, 12H*), 1.08-1.13 (m, 6H), 1.24-1.40 (m, 12H*), 1.45-1.60 (m, 8H*), 2.50-2.57 (t, J=7.61 Hz, 2H), 7.28-7.33 (m, 2H), 8.58-8.60 (appears as s, 1H) (* - the observed integration is higher due to inseparable impurity);
13
C NMR (CDCl3, 100 MHz): δ 9.74, 13.67, 14.05, 22.58,
27.36, 28.90, 31.09, 31.65, 31.65, 33.11, 131.89 (CH), 133.25 (CH), 136.08 (quaternary C), 151.00 (CH), 169.96 (CH).
2-Tri-n-butylstannyl-5-n-decylpyridine (14c) was prepared in the same manner as described for 14a using N,N-dimethylaminoethanol (0.045 mol, 4.01 g), 15 ml of hexanes, n-
S27
BuLi (2.5M in hexanes, 0.09 mol, 36 ml), 3-n-decylpyridine (13c) (0.015 mol, 3.29 g), and solution of tri-n-butyltin chloride (0.0525 mol, 17.09 g) in 45 ml of anhydrous THF. The crude material was subjected to Kugelrohr distillation, and the product was collected as yellowish oil at 170 ºC/0.1 mm Hg (2.28 g, 30% yield). MS (APCI): 508.4, 510.2 (calculated FW 509.3043). 1H NMR (CDCl3, 400 MHz): δ 0.84-0.91 (m, 15H), 1.09-1.13 (m, 6H), 1.221.38 (m, 17H), 1.52-1.63 (m, 8H), 2.51-2.57 (m, 2H), 7.28-7.33 (d, J=1.62 Hz, 2H), 8.57-8.61 (appears as t, J=1.44 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ 9.74, 13.69, 14.12, 22.69,
27.36, 29.10, 29.23, 29.33, 29.45, 29.57, 29.60, 31.12, 31.90, 33.11, 131.91 (CH), 133.30 (CH), 136.12 (quaternary C), 150.98 (CH), 169.92 (CH).
2-n-Pentyl-6-(tri-n-butylstannyl)-pyridine (15a). An alkyl Grignard was prepared from 1bromopentane (2 equiv., 0.014 mol, 2.11 g), Mg turnings (0.0168 mol, 0.41 g) and 14 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to a solution of ZnCl2 (0.0168 mol, 2.29 g) in 17 ml of anhydrous THF (ice-water bath). A white precipitate formed after several minutes of stirring, and the reaction mixture was stirred for additional hour at room temperature. Next, 2-bromo-6-(tri-n-butylstannyl)-pyridine (2) (0.007 mol, 3.13 g), Pd(PPh3)4 (0.5 mol%, 0.035 mmol, 0.04 g) and 7 ml of anhydrous THF were mixed in an oven-dried three-necked flask under a nitrogen atmosphere (clear yellow solution formed), and the freshly prepared n-pentylzinc chloride solution (~1.5 equiv., ~23 ml) was added dropwise via syringe to the yellow reaction mixture (the flask became warm to touch). The reaction mixture was stirred for 3 hours at room temperature, transferred to another round bottom flask, and the solvent was removed by rotary evaporation. The residue was treated with 25 ml of water and 50 ml of petroleum ether, and the resulting mixture was vacuum filtered to remove insoluble matter. The organic phase was separated and the aqueous phase was extracted with petroleum ether (4×10ml). The combined organic phases were dried over
S28
MgSO4, and the solvent was removed by rotary evaporation to give 3.37 g of light yellow oil as crude material. The product was purified by Kugelrohr distillation (120-125 ºC/0.16 mm Hg), and the desired material was isolated as yellowish oil in 66.0% yield (2.02 g). MS (APCI): 438.8, 440.2 (calculated FW 439.2261).
1
H NMR (CDCl3, 400 MHz): δ 0.85-0.91
(m, 12H), 1.05-1.11 (m, 6H), 1.28-1.38 (m, 10H), 1.53-1.61 (m, 6H), 1.68-1.77 (m, 2H), 2.73-2.78 (m, 2H), 6.90-6.95 (dd, J=7.81 Hz, 1.19 Hz, 1H), 7.14-7.21 (dd, J=7.29 Hz, 1.19 Hz, 1H), 7.32-7.39 (m, 1H); 13C NMR (CDCl3, 100 MHz): δ 9.55, 13.72, 14.05, 22.61, 27.34, 29.11, 29.39, 31.58, 38.55, 120.83 (CH), 129.40 (CH), 133.16 (CH), 162.47 (quaternary C), 172.97 (quaternary C).
2-n-Decyl-6-(tri-n-butylstannyl)-pyridine (15b). An alkyl Grignard reagent was prepared from 1-bromodecane (1.5 equiv., 0.0105 mol, 2.32 g), Mg turnings (0.0126 mol, 0.31 g) and 17 ml of anhydrous THF. This freshly prepared Grignard was added dropwise to the solution of ZnCl2 (0.0126 mol, 1.72 g) in 13 ml of anhydrous THF (ice-water bath). A white precipitate formed after several minutes of stirring, and the reaction mixture was stirred for additional hour at room temperature.
Next, 2-bromo-6-(tri-n-butylstannyl)-pyridine (2)
(0.007 mol, 3.13 g), Pd(PPh3)4 (1 mol%, 0.07 mmol, 0.08 g) and 4 ml of anhydrous THF were mixed in an oven-dried three-necked flask under a nitrogen atmosphere (clear yellow solution formed), and the freshly prepared n-decylzinc chloride solution) was added dropwise via syringe to give a clear bright yellow reaction mixture (the flask became warm to the touch). The reaction mixture was stirred for 2 hours at room temperature, transferred to another round bottom flask, and the solvent was removed by rotary evaporation. The residue was treated with 25 ml of water and 25 ml of petroleum ether, and the resulting mixture was vacuum filtered to remove insoluble matter. The organic phase was separated and the aqueous phase was extracted with petroleum ether (4×10ml). The combined organic phases
S29
were dried over MgSO4, and the solvent was removed by rotary evaporation to give 4.7 g of light yellow oil as crude material. The product was purified by Kugelrohr distillation (135145 ºC/0.16 mm Hg), and the desired material was isolated as yellowish oil in 73.6% yield (2.62 g). MS (APCI): 508.8, 510.4 (calculated FW 509.3043). FT-IR (cm-1): 3043 (weak), 2957, 2923, 2878, 2852, 1572, 1554, 1463, 1435, 1072, 877, 785, 748, 693.
1
H NMR
(CDCl3, 400 MHz): δ 0.85-0.91 (m, 12H), 1.06-1.12 (m, 6H), 1.24-1.39 (m, 20H), 1.53-1.62 (m, 6H), 1.67-1.77 (m, 2H), 2.73-2.78 (m, 2H), 6.90-6.95 (dd, J=7.83 Hz, 1.19 Hz, 1H), 7.157.21 (dd, J=7.27 Hz, 1.22 Hz, 1H), 7.31-7.39 (m, 1H); 13C NMR (CDCl3, 100 MHz): δ 9.92, 13.73, 14.13, 22.72, 27.35, 29.12, 29.40, 29.66, 29.69, 29.72, 31.95, 38.60, 120.83 (CH), 129.39 (CH), 133.16 (CH), 162.48 (quaternary C), 172.96 (quaternary C).
6-(5-n-Tridecylthien-2-yl)-2-(tri-n-butylstannyl)-pyridine (16) C13H27 Br
N 2
SnBu3
S
ZnCl
Pd(PPh3)4 THF, rt
C13H27
S
N
SnBu3
16
An oven-dried three-necked flask was charged with 2-bromo-5-n-tridecylthiophene (10c) (7.7 mmol), anhydrous THF (15 ml) was added, and the resulting mixture was cooled in an acetone/CO2 bath under a nitrogen atmosphere. n-BuLi (2.5M in hexanes, 18 mmol, 7.2 ml) was added dropwise to the white suspension of 10c, and the cooling bath was removed for 10 minutes to warm the reaction mixture.
The clear solution was then cooled again
(acetone/CO2 bath), and the solution of ZnCl2 (9.24 mmol, 1.26 g) in 10 ml of anhydrous THF was added to the suspension (precipitate formed on cooling). After completion of addition the precipitate started to dissolve, and the cooling bath was removed. The reaction mixture was stirred for an hour and a half, and the 6-bromo-2-(tri-n-butylstannyl)-pyridine (2) (0.007 mol, 3.13 g) was added via syringe followed by Pd(PPh3)4 (0.5 mol%, 0.035 mmol,
S30
40 mg). The resulting mixture was stirred for an hour, the contents of the flask were transferred to a round bottom flask, treated with ~1 ml of water, and the organic solvents were removed by rotary evaporation. The residue was treated with 25 ml of water and 50 ml of hexanes, the resulting mixture was vacuum filtered to remove insoluble solid. The organic phase was separated; the aqueous phase was extracted with hexanes (2×15 ml).
The
combined organic phases were dried with brine, then over MgSO4, and the solvent was removed by rotary evaporation to give crude material as orange oil (5.13 g). The crude material was chromatographed using silica gel treated with Et3N (150 g of silica gel, hexanes as eluant). The solvent was removed by rotary evaporation, and the product was obtained as thick yellow oil in 79.5% yield in 85% purity by 1H NMR (3.52 g). MS (APCI): 632.7, 634.3 (calculated FW 633.3390).
1
H NMR (CDCl3, 400 MHz): δ 0.88-0.97 (m, 12H*), 1.12-1.19
(m, 6H), 1.20-1.44 (m, 26H*), 1.58-1.69 (m, 6H), 1.70-1.77 (m, 2H), 2.81-2.87 (t, J=7.50 Hz, 2H), 6.76-7.79 (d, J=3.59 Hz, 1H), 7.19-7.23 (dd, J=6.57 Hz, 1.76 Hz, 1H), 7.37-7.39 (d, J=3.64 Hz, 1H), 7.40-7.48 (m, 2H) (* - the observed integration is higher due to the presence of inseparable impurity); 13C NMR (CDCl3, 100 MHz): δ 10.08, 13.78, 14.16, 22.74, 27.42, 29.13 (2 C), 29.16, 29.41, 29.45, 29.61, 29.71 (3 C), 30.50, 31.69, 31.97, 116.37 (CH), 123.57 (CH), 124.86 (CH), 130.02 (CH), 133.51 (CH), 143.51 (quaternary C), 148.40 (quaternary C), 145.65 (quaternary C), 173.74 (quaternary C).
Isolation
of
17:
protio-de-stannylation
of
6-(5-n-tridecylthien-2-yl)-2-(tri-n-
butylstannyl)-pyridine (16). The crude material isolated from the synthesis of 16 was chromatographed using silica gel (47 g, hexanes as eluant first, then CH2Cl2). The first several fractions contained contaminated 16 (0.63 g, ~10% yield, ~70% purity by NMR) (eluted with hexanes), and the major product 17 (more polar, eluted with CH2Cl2) was isolated as yellowish solid in 73.6% yield (1.77 g), which was recrystallized from ~30 ml of
S31
EtOH to get off-white shiny crystals (1.31 g, 74% recovery). MS (APCI): 344.4 (calculated FW 343.2334). FT-IR (cm-1): 3075 (weak), 2951, 2912, 2846, 1586, 1560, 1548, 1489, 1485, 1466, 1455, 1430, 1294, 1263, 1217, 1150, 1090, 1065, 991, 964, 879, 814, 801, 772, 739, 721, 710, 620, 602. DSC analysis: 43.5 ºC (m.p.). 1H NMR (CDCl3, 400 MHz): δ 0.84-0.92 (t, J=6.86 Hz, 3H), 1.22-1.43 (m, 20H), 1.68-1.77 (m, 2H), 2.81-2.87 (t, J=7.50 Hz, 2H), 6.77-6.82 (d, J=3.62 Hz, 1H), 7.07-7.13 (m, 1H), 7.38-7.41 (d, J=3.63 Hz, 1H), 7.57-7.63 (m, 1H), 7.63-67 (m, 1H), 8.53-56 (m, 1H); 13C NMR (CDCl3, 100 MHz): δ 14.14, 22.71, 29.08, 29.39, 29.56, 29.67 (5 CH2), 30.42, 31.57, 31.94, 118.30 (CH), 121.35 (CH), 124.37 (CH), 125.18 (CH), 136.48 (CH), 141.97 (quaternary C), 148.73 (quaternary C), 149.48 (CH), 152.92 (quaternary C). Anal. Calcd. for C22H33NS: C, 76.91; H, 9.68; N, 4.08, S, 9.33. Found: C, 76.76, H, 9.43; N, 3.97; S, 9.34.
Stille coupling of pyridinyl stannanes with aryl halides 2,5-Bis-(2-n-tridecylpyridin-5-yl)-thiophene (18)
C13H27
SnBu3
N
+
Pd(PPh3)4 (2 mol%) DMF, 130-140 ºC, 1h Br
S
Br
C13H27
N
S 18
N
C13H27
6e
An oven-dried flask was charged with 2,5-dibromothiophene (0.7 mmol, 0.17 g), 2-ntridecyl-5-tri-n-butylstannylpyridine (6e) (1.5 mmol, 0.82 g), Pd(PPh3)4 (2 mol%, 0.014 mmol, 0.017 g) and anhydrous DMF (5 ml) under a nitrogen atmosphere. The light yellow reaction mixture became dark after 1 hour of heating (130-140 ºC). The reaction mixture was cooled to room temperature and poured into 60 ml of ice water. The green solid, which separated, was isolated by vacuum filtration, washed with several ml of EtOH, and dried (0.34 g, 81% crude material). The material was dissolved in several ml of CH2Cl2, and applied to a column (10 g of basic Al2O3). The column was eluted with petroleum ether (75 ml), followed by CH2Cl2 (the desired material was collected) and CHCl3 (50 ml,
S32
contaminated desired material was collected). The solvent was removed and the residue was recrystallized from 15-20 ml of EtOH to give off-white shiny crystals (0.16 g, 38% yield). Additional product (0.08 g, 19%) was obtained after evaporation of CHCl3 fractions and recrystallization (total yield 0.24 g, 57.1%). MS (APCI): 603.5 (calculated FW 602.4634). UV-Vis (DMSO, λmax): 288, 351.
1
H NMR (CDCl3, 400 MHz): δ 0.85-0.91 (t, J=6.87 Hz,
6H), 1.20-1.42 (m, 40H), 1.70-1.78 (m, 4H), 2.78-2.83 (t, J=7.77 Hz, 4H), 7.15-7.20 (d, J=8.13 Hz, 2H), 7.30-7.33 (s, 2H), 7.76-7.81 (dd, J=8.07 Hz, 2.42 Hz, 2H), 8.78-8.83 (m, 2H);
13
C NMR (CDCl3, 100 MHz): δ 14.13 (CH3), 22.70 (CH2), 29.37 (CH2), 29.40 (CH2),
29.52 (CH2), 29.58 (3 CH2), 29.67 (CH2), 29.70 (CH2), 29.88 (CH2), 31.93 (CH2), 38.17 (CH2), 122.69 (CH), 124.65 (CH), 127.40 (quaternary C), 133.18 (CH), 140.69 (quaternary C), 146.17 (CH), 161.91 (quaternary C). Anal. Calcd. for C40H62N2S: C, 79.67; H, 10.36; N, 4.65, S, 5.32. Found: C, 79.38, H, 10.21; N, 4.65; S, 5.54.
Preparation of 2,5-bis-(2-(5-nonylthiophen-2-yl)-pyridin-5-yl)-thiophene (19) Br C9H19
S
N 8b
SnBu3
S
Br
Pd(PPh3)4 (2 mol%) DMF, 130-140 ºC, 1h
C9H19
S
S N
19
S N
C9H19
An oven-dried three-necked flask was charged with 2,5-dibromothiophene (0.75 mmol, 0.18 g) and 2-(5-n-nonylthien-2-yl)-5-tri-n-butylstannylpyridine (8b) (2.17 equiv., 1.63 mmol, 0.94 g). Anhydrous DMF (5 ml) and Pd(PPh3)4 (5 mol%, 0.043 g) were added under nitrogen atmosphere and the reaction mixture was heated for 4 hours (internal temperature of 110-115 ºC). The reaction mixture was cooled to room temperature and an orange solid precipitated. The contents of the reaction flask were poured into 40 ml of ice water and the orange-yellow precipitate was separated by vacuum filtration and washed with EtOH. The crude material, isolated as an orange-yellow powder (0.43 g, 87.8% crude yield), was dissolved with heating in 30 ml of CHCl3 and the bright yellow fluorescent solution was applied to the to top of the S33
column (50 g of basic Al2O3, hexanes:CH2Cl2=3:1, then 1:1 as eluents).
The material
isolated from this column was further purified using a pre-packed Biotage column (CHCl3:hexanes=3:1 as eluant).
The solid obtained after removal of solvents was
recrystallized from 1,4-dioxane (10-15 ml) and this purified compound was isolated as bright yellow powder in 40.8% yield (0.20 g). MS (APCI): 655.20 (calculated FW 654.3136). FTIR (cm-1): 3079 (weak), 2957, 2920, 2849, 1561, 1541, 1487, 1460, 1393, 1375, 1298, 1215, 1142, 968, 833, 797, 751, 721. UV-Vis (DMSO, λmax): 281, 393.
1
H NMR (CDCl3, 400
MHz): δ 0.84-0.92 (t, J=6.79Hz, 6H), 1.20-1.42 (m, 24H), 1.65-1.78 (m, 4H), 2.80-2.90 (t, J=7.54 Hz, 4H), 6.78-6.81 (d, J=3.59 Hz, 2H), 7.32-7.38 (s, 2H), 7.40-7.44 (d, J=3.61 Hz, 2H), 7.58-7.63 (d, J=8.34 Hz, 2H), 7.80-7.87 (dd, J=8.34 Hz, 2.32 Hz, 2H), 8.80-8.84 (d, J=2.09 Hz, 2H);
13
C NMR (CDCl3, 100 MHz): δ 14.13, 22.69, 29.10, 29.33, 29.40, 29.53,
30.47, 31.57, 31.90, 118.25 (CH), 124.69 (CH), 124.80 (CH), 125.40 (CH), 127.63 (quaternary C), 133.20 (CH), 140.61 (quaternary C), 141.47 (quaternary C), 146.26 (CH), 149.24 (quaternary C), 151.86 (quaternary C). Anal. Calcd. for C40H50N2S3: C, 73.34; H, 7.69; N, 4.28, S, 14.69. Found: C, 73.03, H, 7.75; N, 4.21; S, 14.62.
Scheme 1. Three synthetic approaches evaluated for the preparation of terpyridine liquid crystal 20. C6H13
C6H13
N 6b
Pd(PPh3)4
SnBu3 + 4
DMF 130-140 ºC Pd(PPh3)4
ZnCl + 4 21 21 + Br
I N
C6H13
THF reflux
N
N
N
N 20
Pd(PPh3)4 THF, rt
22
S34
C6H13
2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine (20). 2,5-Dibromopyridine (4) (0.0025 mol, 0.59 g), 2-n-hexyl-5-(tri-n-butylstannyl)-pyridine (6b) (2 equiv., 0.005 mol, 2.26 g) and Pd(PPh3)4 (1 mol% based on (4), 0.025 mmol, 0.029 g) were mixed in an oven-dried three-necked flask. Anhydrous DMF (5 ml) was added under a nitrogen atmosphere and the resulting mixture was heated. After heating for an hour at 120 ºC all the 2,5-dibromopyridine was consumed (analyzed by TLC), but no product was observed. The reaction temperature was increased to 145 ºC, and after heating for 2 hours and addition of 2-n-hexyl-5-(tri-n-butylstannyl)-pyridine (6b) (10 mol%, 0.22 g) the dark solution was cooled to room temperature. The reaction mixture was poured into 75 ml of ice water, and the gray solid was separated by vacuum filtration. The crude material was dissolved in 50 ml of CH2Cl2, the solution was dried with brine and then over MgSO4, concentrated and filtered through Al2O3 (basic, 15 g). The solvent was removed from the combined fractions, and the material was recrystallized from hexanes. A yellowish solid was isolated in 44.0% yield (0.44 g). The crystals formed in the mother liquor and the yellowish solid were combined, dissolved in CH2Cl2 and chromatographed (15 g of silica gel, CH2Cl2 as eluant first, then CH2Cl2:EtOAc=5:1). The solvent was removed from combined fractions and the product was recrystallized from hexanes to give white shiny plates (0.43 g, 43% yield). MS (APCI): 402.3, 403.0 (calculated FW 401.2831). FT-IR (cm-1): 3018, 2955, 2919, 2850, 1596, 1565, 1470, 1379, 1346, 1012, 996, 821, 763, 723, 641.
1
H NMR (CDCl3, 400 MHz): δ 0.84-0.95 (m, 6H), 1.24-1.43 (m,
12H), 1.72-1.82 (m, 4H), 2.82-2.90 (t, 7.74 Hz, 4H), 7.26-7.31 (d, J=8.03 Hz, 2H), 7.82-7.86 (m, 2H), 7.95-7.99 (dd, J=8.22 Hz, 2.37 Hz, 1H), 8.26-8.30 (dd, J=8.08 Hz, 2.36 Hz, 1H), 8.78-8.83 (dd, J=2.30 Hz, 0.47 Hz, 1H), 8.91-8.8.94 (dd, J=2.35 Hz, 0.73 Hz, 1H), 9.14-9.17 (dd, J=2.25 Hz, 0.44 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ 14.09, 22.59, 29.08, 29.09,
29.86, 31.72, 38.18, 38.29, 120.24 (CH), 122.73 (CH), 122.89 (CH), 130.30 (quaternary C), 131.66 (quaternary C), 132.34 (quaternary C), 134.50 (CH), 134.56 (CH), 135.05 (CH),
S35
147.41 (CH), 147.58 (CH), 148.14 (CH), 154.32 (quaternary C), 162.56 (quaternary C), 163.36 (quaternary C). Anal. Calcd. for C27H35N3: C, 80.75; H, 8.78; N, 10.46. Found: C, 80.38, H, 8.53; N, 10.42.
2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine (20): Negishi coupling of 2,5-dibromopyridine (4) with 2-n-hexylpyridin-5-ylzinc chloride.
2-n-Hexyl-5-bromopyridine (7b) (7.846
mmol, 1.90 g) was placed into an oven-dried three-neck round bottom flask equipped with magnetic stirrer bar. Anhydrous THF (30 ml) was added and the reaction mixture was cooled in a CO2/acetone bath (nitrogen atmosphere). n-BuLi (2.5M in hexanes, 3.14 ml) was added dropwise to a colorless solution of 2-n-hexyl-5-bromopyridine. The reaction mixture became pinkish, then pink, and finally to pink-red (it looked like red wine) during addition of n-BuLi. The mixture was stirred for half an hour and a solution of zinc chloride (9.42 mmol, 1.28g) in 10 ml of anhydrous THF was added dropwise (internal temperature was kept below –65 ºC). After an hour of stirring the cooling bath was removed and the reaction mixture was allowed to warm up to room temperature. A half of this arylzinc chloride was transferred to a syringe and added dropwise to a flask charged with 2,5-dibromopyridine (4) (1.78 mmol, 0.42 g) and Pd(PPh3)4 (2 mol%, 0.036 mmol, 0.04 g). The reaction mixture was refluxed for several hours and then left to stir overnight under room temperature. The solvent was removed by rotary evaporation, and the organic matter was extracted with CH2Cl2. The organic solution was concentrated and chromatographed (silica gel, CH2Cl2 first to elute a byproduct, then CH2Cl2:acetone=4:1 to elute the product). The material isolated after evaporation of the solvents from combined fractions was recrystallized from hexanes to give off white solid (0.12 g, 16.9% yield). NMR and DSC analysis matched the ones obtained for the material (20) prepared by Stille coupling.
S36
2,5-Di-(2-n-hexylpyridin-5-yl)-pyridine
(20):
Negishi
coupling
iodopyridine (22) with 2-n-hexylpyridin-5-ylzinc chloride.
of
2-bromo-5-
A solution of 2-n-
hexylpyridin-5-ylzinc chloride was prepared from 2-n-hexyl-5-bromopyridine (7b) (8.67 mmol, 2.1 g), 60 ml of anhydrous THF, n-BuLi (2.5M in hexanes, 3.5 ml) and ZnCl2 (10.4 mmol). Third of this freshly prepared arylzinc chloride (24.5 ml, 2.89 mmol) was added dropwise to the three-necked flask charged with 2-bromo-5-iodopyridine (22) (1.445 mmol, 0.41 g), Pd(PPh3)4 (2 mol%, 0.0289 mmol, 0.033 g) and 5 ml of anhydrous THF. The mixture was stirred overnight, poured into 10 ml of water and vacuum filtered to remove insoluble matter. Dichloromethane (40 ml) was added, the organic phase was separated, dried over MgSO4, and the solvents were removed by rotary evaporation. The product was purified by column chromatography (30 g of silica gel, ~50:1 ratio, CH2Cl2 first to elute minor byproduct, then CH2Cl2:EtOAc (1:1) to elute the desired material (it appears as a bright blue spot on TLC). The product was recrystallized from hexanes to give white fluffy needles (0.20 g, 34.5% yield). NMR and DSC analysis matched the ones obtained for (20) prepared by Stille coupling.
2,5-Di-(5-n-hexylpyridin-2-yl)-pyridine (23) C6H13
N 14a
SnBu3
+
Br
C6H13
Br N 4
N
N
N
C6H13
23
2,5-Dibromopyridine (4) (1.1 mmol, 0.26 g), 5-tri-n-butylstannyl-5-n-hexylpyridine (14a) (2.8 eq., 85% purity, 3.1 mmol, 1.4 g) were mixed in an oven dried flask. Anhydrous DMF (5 ml), Pd(PPh3)4 (1 mol% based on 2,5-dibromopyridine (4), 0.011 mmol, 0.013 g), and CuI (2 mol% based on 4, 2.2 mmol, 0.004 g) were added under nitrogen atmosphere, and the resulting mixture was heated for 4 hours (125-135 ºC internal temperature).
The dark
reaction mixture was cooled to room temperature and poured into 60 ml of ice water. The
S37
organic matter was extracted with CH2Cl2:hexanes mixture (1:1), the combined extracts were concentrated, and the gray solution was filtered through Al2O3 (neutral, 20 g, 100 ml of CH2Cl2:hexanes (1:1) as eluant). The solvent was removed by rotary evaporation, and the crude material was chromatographed (25 g of silica gel, CH2Cl2, then CH2Cl2:EtOAc (30:1) as eluents). The solvent was removed from the combined fractions and the residue was recrystallized from several ml of MeOH. The product was isolated as white shiny solid in 34.5% purified yield (0.152 g). FT-IR (cm-1): 3045, 3001, 2956, 2926, 2871, 2853, 159, 1566, 1461, 1409, 1372, 1216, 1068, 1024, 1012, 838, 760, 743, 724, 607.5.
1
H NMR
(CDCl3, 400 MHz): δ 0.86-0.95 (m, 6H), 1.27-1.43 (m, 12H), 1.61-1.72 (m, 4H), 2.63-2.70 (m, 4H), 7.58-7.63 (dd, J=8.12 Hz, 2.28 Hz, 1H), 7.63-7.67 (dd, J=8.14 Hz, 2.27 Hz, 1H), 7.71-7.75 (d, J=8.01 Hz, 1H), 8.35-8.39 (d, J=8.06 Hz, 1H), 8.41-8.45 (dd, J=8.34 Hz, 2.19 Hz, 1H), 8.45-8.49 (dd, J=8.30 Hz, 0.86 Hz, 1H), 8.51-8.58 (d, J=1.95 Hz, 1H), 8.55-8.58 (d, J=1.97 Hz, 1H), 9.22-9.26 (dd, J=2.15 Hz, 0.88 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ
14.08, 22.59, 28.83, 31.08, 31.10, 31.64, 32.78, 32.91, 120.13 (CH), 120.64 (CH), 120.88 (CH), 134.39 (quaternary C), 134.91 (CH), 136.77 (CH), 136.79 (CH), 137.36 (quaternary C), 138.41 (quaternary C), 147.46 (CH), 149.44 (CH), 150.26 (CH), 152.25 (quaternary C), 153.58 (quaternary C), 156.12 (quaternary C). Anal. Calcd. for C27H35N3: C, 80.75; H, 8.78; N, 10.46. Found: C, 80.39, H, 8.54; N, 10.39.
S38
Preparation of thiophene-bypyridine LCs 26a,b Scheme 2. Stille coupling of 2-n-decyl-5-tri-n-butylstannylpyridine (6d) with aryl halides 25 producing thiophene-bipyridine liquid crystals 26a,b (R= C9H19, C11H23). Br
1) n-BuLi THF, (-78 ºC) R
S 10b,d
Br
2) ZnCl2 (-78 ºC), then rt
Br N 4
R
S 24
ZnCl
Br
Pd(PPh3)4 THF, rt
Bu3Sn
R
N 6d S
R
S
N 25a,b
C10H21
N 26a,b
Pd(PPh3)4 DMF heating
N
C10H21
2-(5-n-Nonylthiophen-2-yl)-5-bromopyridine (25a). An oven-dried three-necked flask was charged with 2-bromo-5-n-nonylthiophene (10b) (0.025 mol, 7.23 g), anhydrous THF (85 ml) was added, and the resulting mixture was cooled in an acetone/CO2 bath under nitrogen atmosphere. n-BuLi (2.5M in hexanes, 0.025 mol, 10 ml) was added dropwise to clear solution over a period of 10 minutes, and the mixture became light yellow. The reaction mixture was stirred for an hour, solution of ZnCl2 (0.03 mol, 4.08 g) in 30 ml of anhydrous THF was added, and the cooling bath was removed. The mixture was stirred for an hour and 2,5-dibromopyridine (4) (0.024 mol, 5.69 g) and Pd(PPh3)4 (0.5 mol%, 0.12 mmol, 0.13 g) were added in one portion. The mixture became warm to the touch after stirring for several minutes. The bright orange-yellow mixture was stirred overnight; the color changed to light green, and the mixture was quenched with 10 ml of water. The organic solvents were removed by rotary evaporation, CH2Cl2 (30 ml) was added, and the resulting mixture was vacuum filtered to remove insoluble matter. The organic phase was separated; the aqueous phase was extracted with dichloromethane (2×15 ml). The combined organic fractions were dried over MgSO4, the solvent was removed by rotary evaporation, and the product was S39
refluxed in hexanes (75 ml) with clay (Montmorillonite KSF, 3.3 g). The clay was removed by hot gravity filtration, the solution was concentrated down to ~35 ml and cooled in freezer. Vacuum filtration gave 7.35 g of the crude material (beige solid, 83.6% crude yield). The crude material was dissolved in 100 ml of boiling EtOH and then the yellow-orange solution was cooled in freezer. Vacuum filtration gave 5.35 g (72.8% recovery) of the purified off white solid (additional amount of product can be obtained from the mother liquor). The 2nd crop of crystals was recrystallized to get additional amount of product (1.63 g). The product was isolated in 79.4% yield (6.98 g).
The material can be also purified by column
chromatography (silica gel, hexanes:CH2Cl2=3:2 as eluant). MS (APCI): 366.3, 368.0 (1:1 intensity ratio, calculated FW 365.0813). DSC analysis: 53.2 ºC (m.p.). FT-IR (cm-1): 3071 (weak), 3044 (weak), 2953, 2926, 2848, 1572, 1480, 1469, 1428, 1369, 1267, 1228, 1200, 1129, 1094, 1055, 1040, 1002, 969, 943, 895, 818, 798, 765, 742, 720, 630, 612, 603.
1
H
NMR (CDCl3, 400 MHz): δ 0.84-0.0.92 (t, J=6.89 Hz, 3H), 1.20-1.43 (m, 12H), 1.65-1.76 (m, 2H), 2.78-2.86 (t, J=7.54 Hz, 2H), 6.75-6.80 (d, J=3.63 Hz, 1H), 7.36-7.40 (d, J=3.68 Hz, 1H), 7.44-7.50 (dd, J=8.50 Hz, 0.44 Hz, 1H), 7.72-7.77 (dd, J=8.53Hz, 2.40 Hz, 1H), 8.548.58 (dd, J=2.33 Hz, 0.55 Hz, 1H);
13
C NMR (CDCl3, 100 MHz): δ 14.13 (CH3), 22.69
(CH2), 29.07 (CH2), 29.32 (CH2), 29.37 (CH2), 29.51 (CH2), 30.43 (CH2), 31.53 (CH2), 31.89 (CH2), 117.74 (C-Br), 119.43 (CH), 125.03 (CH), 125.37 (CH), 139.02 (CH), 140.70 (quaternary C), 149.42 (quaternary C), 150.39 (CH), 151.45 (quaternary C).
5-Bromo-2-(5-n-undecylthien-2-yl)-pyridine (25b). An oven-dried three-necked flask was charged with 2-bromo-5-n-undecylthiophene (10d) (0.03 mol, 9.52 g) and anhydrous THF (120 ml), and the resulting mixture was cooled (acetone/CO2 bath, N2 atmosphere). n-BuLi (2.5M in hexanes, 0.03 mol, 12 ml) was added dropwise to the thick white suspension (the starting material precipitated under cooling) over a period of 10 minutes. During addition on
S40
n-BuLi the white precipitate started to dissolve, and the solution became light yellow. The reaction mixture was stirred for half an hour (it became a very thick suspension again), analyzed by TLC, and additional 2 ml of n-BuLi was added since some starting material was detected. After stirring for additional 15 minutes (the starting material was consumed by TLC analysis) a solution of ZnCl2 (0.036 mol, 4.90 g) in 40 ml of anhydrous THF was added in portions.
After addition of 10 ml and stirring for several minutes the precipitate
disappeared, and the rest of the ZnCl2 solution was added to the clear yellow mixture. After completion of addition of ZnCl2 solution the cooling bath was removed, and the mixture was stirred for an hour. 2,5-Dibromopyridine (4) (0.03 mol, 7.11 g) and Pd(PPh3)4 (0.5 mol%, 0.15 mmol, 0.17 g) were added in one portion. After stirring for several minutes the mixture became hot to the touch, and external cooling was used to cool it down to room temperature (ice water bath). The bright yellow mixture was stirred overnight, and quenched with several ml of water (the flask became warm to the touch). The organic solvents were removed by rotary evaporation, 50 ml of water and 50 ml of dichloromethane were added, and the resulted mixture was vacuum filtered to remove insoluble matter. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×50 ml). The combined organic fractions were dried over MgSO4, the solvent was removed by rotary evaporation, and the product was refluxed in hexanes (200 ml) with clay (Montmorillonite KSF, 3 g). The clay was removed by hot gravity filtration, and the solution was concentrated down to ~100 ml and cooled in freezer. Vacuum filtration gave 11.0 g of the crude material (93% crude yield). The product was purified by column chromatography (280 g of silica gel, hexanes:CH2Cl2=1:1 as eluant). The yellowish solid was refluxed with 400 ml of ethanol, gravity filtered while hot to remove yellow insoluble material, the solution was concentrated down to ~250 ml), and the light yellow solution was cooled. Yellowish solid was isolated in 74.0% (8.76 g). The material contained ~10% (by NMR) of yellow impurity (more polar
S41
than product) which was not removed by column chromatography and crystallization, and it was used as is without further purification. 393.1126).
1
MS (APCI): 394.4, 396.2 (calculated FW
H NMR (CDCl3, 400 MHz): δ 0.854-0.91 (t, J=6.85 Hz, 3H), 1.20-1.43 (m,
16H), 1.63-1.75 (m, 2H), 2.78-2.85 (t, J=7.55 Hz, 2H), 6.76-6.80 (d, J=3.64 Hz, 1H), 7.347.39 (d, J=3.66 Hz, 1H), 7.43-7.49 (dd, J=8.51 Hz, 0.63 Hz, 1H), 7.71-7.76 (dd, J=8.50 Hz, 2.36 Hz, 1H), 8.54-8.58 (dd, J=2.34 Hz, 0.59 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 14.15, 22.71, 29.08, 29.38, 29.56, 29.64, 29.66, 30.43, 31.53, 31.93, 117.74 (quaternary C), 119.43 (CH), 125.03 (CH), 125.37 (CH), 139.02 (CH), 140.70 (quaternary C), 149.42 (quaternary C), 150.39 (CH), 151.45 (quaternary C) (one alkyl carbon is missing due to overlap).
6'-n-Decyl-6-(5-n-nonylthiophen-2-yl)-[3,3']-bipyridinyl (26a). The three-necked round bottom flask was charged with 2-(5-n-nonylthiophen-2-yl)-5-bromopyridine (25a) (3.22 mmol, 1.18 g), 2-n-decyl-5-tri-n-butylstannylpyridine (6d) (1.05 equiv., 3.38 mmol, 1.72 g), Pd(PPh3)4 (2.5 mol%, 0.0805 mmol, 0.093 g) and 15 ml of anhydrous DMF (nitrogen atmosphere). After heating (116 ºC internal temperature) for two hours the yellow-orange clear mixture became dark. Several drops of the reaction mixture were quenched with water, and the organic matter was extracted with EtOAc and analyzed by TLC (CH2Cl2:EtOAc=20:1 as eluant). No starting aryl bromide 25a was detected; the mixture was cooled to room temperature and applied to the top of the basic Al2O3 column (60 g). The column was eluted with hexanes (200 ml), followed by dichloromethane (200 ml). The solvents were removed from combined fractions, and material was recrystallized from 20 ml of EtOH (cooled in freezer).
Beige-grey solid (1.19 g, 73.5% yield) was further purified by column
chromatography (35 g of silica gel, CH2Cl2:EtOAc=20:1 as eluant).
The solvent was
removed from combined fractions by rotary evaporation, the yellowish solid was dissolved in 100 ml of boiling hexanes, and the resulted solution was refluxed with Montmorillonite KSF
S42
clay (2 g) for 4 hours, gravity filtered while hot, the light yellow solution was concentrated down to 20-25 ml, and then cooled to room temperature and then in freezer. The product was isolated as off white solid (0.82 g, 68.9% recovery, 50.6% yield of purified material). MS (APCI): 505.5 (calculated FW 504.3538). FT-IR (cm-1): 3079 (weak), 3018 (weak), 2955, 2916, 2849, 1597, 1544, 1483, 1469, 1428, 1402, 1025, 995, 968, 818, 798, 755, 720, 649. 1
H NMR (CDCl3, 400 MHz): δ 0.82-0.91 (t, J=6.50 Hz, 6H, 2CH3), 1.20-1.43 (m, 26H),
1.68-1.81 (m, 4H), 2.80-2.88 (m, 4H), 6.78-6.83 (d, J=3.53 Hz, 1H), 7.22-7.27 (d, J=8.08 Hz, 1H), 7.41-7.47 (d, J=3.61 Hz, 1H), 7.65-7.70 (d, J=8.26 Hz, 1H), 7.76-7.83 (dd, J=8.02 Hz, 2.32 Hz, 1H), 7.83-7.87 (dd, J=8.28 Hz, 2.25 Hz, 1H), 8.73-8.80 (m, 2H); 13C NMR (CDCl3, 75 MHz): δ 14.13, 22.69, 29.09, 29.34, 29.40, 29.44, 29.52, 29.59, 29.62, 29.91, 30.46, 30.60, 31.56, 31.91, 38.17, 118.32 (CH), 122.83 (CH), 124.74 (CH), 125.37 (CH), 130.52 (quaternary C), 131.07 (quaternary C), 134.26 (CH), 134.63 (CH), 141.43 (quaternary C), 147.24 (CH), 147.58 (CH), 149.22 (quaternary C), 152.24 (quaternary C), 162.24 (quaternary C) (several alkyl carbons are missing due to overlap). Anal. Calcd. for C33H48N2S : C, 78.51; H, 9.58; N, 5.55, S, 6.35. Found: C, 78.34, H, 9.44; N, 5.58; S, 6.39.
S43
5-Heptyl-6'-(4-heptyloxy-phenyl)-[2,3']-bipyridinyl (27) I C7H15O
N 11
SnBu3
N 28
C7H15 C7H15O
Pd(PPh3)4, DMF
N 27
N
C7H15
An oven-dried three-necked flask was charged with 2-iodo-5-n-heptylpyridine (28) (5.3 mmol, 1.60 g), 2-(4-n-heptyloxyphenyl)-5-tri-n-butylstannylpyridine (11) (5.3 mmol, 2.95 g). Catalyst Pd(PPh3)4 (0.8 mol%, 0.043 mmol, 0.050 g) and anhydrous DMF were added under nitrogen atmosphere, and the yellow solution was heated for 9 hours (135 ºC internal temperature). The dark reaction mixture was cooled to room temperature and poured into 150 ml of ice water. The soft brown precipitate was separated by vacuum filtration and dissolved in 75 ml of CH2Cl2. The dark yellow-orange solution was washed with brine, then dried over MgSO4, concentrated down to 20 ml and applied to the top of the Al2O3 (basic, 25 g). The product was eluted with 50 ml of CH2Cl2, the solvent was removed from combined fractions and the crude material was recrystallized from ~75 ml of EtOH to give off-white solid in 43.9% yield (1.08 g). The material was further purified by recrystallization from MeOH (the material was dissolved in 250 ml of MeOH, and the solution was concentrated down to ~120 ml when crystallization started). The product was isolated as white solid (0.81 g, 75% recovery). MS (APCI): 445.2 (calculated FW 444.3141). DSC analysis: 59.5, 124.9, 152.5, 203.9, 206.0 (on heating); 18.7, 35.9, 123.7, 151.4, 202.7, 205.1 (on cooling). FT-IR (cm-1): 3044 (weak), 2964, 2934, 2926, 2872, 2856, 1606, 1589, 1581, 1514, 1420, 1397, 1313, 1273, 1243, 1174, 1113, 1042, 1008, 831, 811, 774, 724, 678, 640, 630, 614, 590. 1H NMR (CDCl3, 400 MHz): δ 0.86-0.93 (m, 6H, 2CH3), 1.22-1.40 (m, 14H), 1.40-1.52 (m, 2H), 1.60-1.71 (m, 2H), 1.75-1.84 (m, 2H), 2.60-2.70 (t, J=7.68 Hz, 2H), 3.95-4.10 (t, J=6.60 Hz, 2H), 6.98-7.03 (d, J=8.86 Hz, 2H), 7.56-7.60 (dd, J=8.11 Hz, 2.16 Hz, 1H), 7.67-7.73 (d, J=8.06 Hz, 1H), 7.74-7.80 (d, J=8.34 Hz, 1H), 7.98-8.04 (d, J=8.85 Hz, 2H), 8.32-8.38 (dd,
S44
J=8.35 Hz, 2.33 Hz, 1H), 8.51-8.57 (d, J=1.97 Hz, 1H), 9.17-9.22 (dd, J=2.32 Hz, 0.68 Hz, 1H) (1H NMR matched the analysis of the sample reported in literature 9 ).
2-(5-n-Nonylthiophen-2-yl)-5-(5-n-undecylthiophen-2-yl)-pyridine (29)
C9H19
S
N 8b
SnBu3
+
Pd(PPh3)4 DMF Br
S
C11H23
10d
C9H19
S
N 29
S
C11H23
An oven-dried three-necked flask was charged with 2-bromo-5-n-undecylthiophene (10d) (1 mmol, 0.32 g) and 2-(5-n-nonylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8b) (1 mmol, 0.58 g). Anhydrous DMF (5 ml) and Pd(PPh3)4 (1 mol%, 0.011 g) were added under nitrogen atmosphere, and the reaction mixture was heated for hour and a half (internal temperature 115 ºC). The reaction mixture was cooled to room temperature and poured into 40 ml of ice water. The yellow-green precipitate was vacuum filtered, washed with 15-20 ml of EtOH, and dried (0.47 g, 90.4% crude yield). The material was purified by column chromatography (50 g of silica gel, hexanes:CH2Cl2=3:1 as eluant). The yellowish solid was obtained after recrystallization from MeOH:EtOH (1:1) (0.25 g, 48.1% purified material yield).
MS
(APCI): 524.4 (calculated FW 523.3306). FT-IR (cm-1): 3080 (weak), 3069 (weak), 3032 (weak), 2955, 2917, 2849, 1562, 1499, 1465, 1388, 1206, 1144, 968, 946, 925, 816, 797, 753, 719. 1H NMR (CDCl3, 400 MHz): δ 0.85-0.91 (t, J=6.87 Hz, 6H), 1.20-1.42 (m, 28H), 1.651.1.77 (m, 4H), 2.79-2.86 (m, 4H), 6.75-6.80 (m, 2H), 7.14-7.18 (d, J=3.56 Hz, 1H), 7.377.41 (d, J=3.65 Hz, 1H), 7.54-7.58 (dd, J=8.28 Hz, 0.63 Hz, 1H), 7.74-7.80 (dd, J=8.35 Hz, 2.36 Hz, 1H), 8.73-8.77 (dd, J=2.34 Hz, 0.74 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 14.13, 22.70, 29.09, 29.12, 29.33, 29.38, 29.53, 29.57, 29.64, 29.66, 30.29, 30.45, 31.58, 31.67, 31.90, 31.93, 118.16 (CH), 123.40 (CH), 125.29 (two CH), 128.45 (quaternary C), 132.94
(9) Getmanenko, Y.A.; Twieg, R.J.; Ellman, B.D. Liq. Cryst., 2006, 33, 267.
S45
(CH), 137.79 (quaternary C), 141.71 (quaternary C), 146.09 (CH), 146.82 (quaternary C), 148.75 (quaternary C), 151.14 (quaternary C) (four alkyl carbons are missing due to overlap).
6-(5-n-Tridecylthiophen-2-yl)-6'-(5-n-undecylthiophen-2-yl)-[3,3']-bipyridinyl (30)
C13H27
S
N
SnBu3
+
Pd(PPh3)4 DMF
Br S
N 25b
8c
R C13H27
S
N
N 30
S
C11H23
A mixture of 2-(5-n-tridecylthien-2-yl)-5-(tri-n-butylstannyl)-pyridine (8c) (1.5 mmol, 0.95 g), 5-bromo-2-(5-n-nonylthien-2-yl)-pyridine (25b), Pd(PPh3)4 (0.5 mol%) in 5 ml of anhydrous DMF was heated for 2 hours (140-145 ºC internal temperature), and dark green mixture was cooled. The contents of the reaction flask were transferred to a beaker with 50 ml of ice water; greenish-gray precipitate was separated by vacuum filtration, rinsed with several ml of EtOH and dried. The crude material was isolated as gray powder in 98% yield (0.96 g). The crude product was dissolved in boiling CH2Cl2 (25 ml), and gray solution with blue fluorescence was applied to the column (10 g of basic Al2O3, hot CH2Cl2 as eluant). The compound isolated after evaporation of CH2Cl2 was heated with 30 ml of EtOH (not soluble), and the yellowish powder was isolated by vacuum filtration (0.84 g, 87.5% recovery). The material was recrystallized from 50 ml of EtOAc, and the title compound was isolated as offwhite solid (0.58 g, 69% recovery). MS (APCI): 657.2, 658.0 (3:1 ratio) (calculated FW 656.4198). FT-IR (cm-1): 3082 (weak), 3024, 3007, 2954, 2921, 2916, 2849, 1592, 1493, 1465, 1454, 1433, 1352, 1216, 993, 967, 947, 923, 829, 815, 797, 752, 720, 646, 641, 612, 583, 570. 1H NMR (CDCl3, 400 MHz): δ 0.84-0.91 (t, J=6.85 Hz, 6H), 1.21-1.42 (m, 36H), 1.68-1.77 (m, 4H), 2.81-2.88 (t, J=7.53 Hz, 4H), 6.80-6.83 (d, J=3.63 Hz, 2H), 7.42-7.46 (d, J=3.66 Hz, 2H), 7.66-7.70 (d, J=8.34 Hz, 2H), 7.83-7.88 (dd, J=8.31 Hz, 2.37 Hz, 2H), 8.778.81 (dd, J=2.35 Hz, 0.73 Hz, 2H);
13
C NMR (CDCl3, 100 MHz): δ 14.14, 22.71, 29.09,
S46
29.39, 29.57, 29.67, 30.47, 31.56, 31.93, 118.37 (CH), 124.82 (CH), 125.41 (CH), 130.74 (quaternary C), 134.36 (CH), 141.41 (quaternary C), 147.40 (CH), 149.34 (quaternary C), 152.33 (quaternary C) (several alkyl carbons are missing due to overlap). Anal. Calcd. for C42H60N2S2 : C, 76.77; H, 9.20; N, 4.26, S, 9.76. Found: C, 76.49, H, 9.00; N, 4.26; S, 9.48.
2,5-Di-(6-n-pentylpyridin-2-yl)-thiophene (31)
C5H11
N
SnBu3
+
C5H11 Br
S
Br
N
N
C5H11
S 31
15a
An oven-dried three-necked flask was charged with 2,5-dibromothiophene (1 mmol, 0.24 g) and 2-n-pentyl-6-tri-n-butylstannylpyridine (15a) (2 equiv., 2 mmol, 0.88 g). The catalysts Pd(PPh3)4 (2 mol% based on 2,5-dibromothiophene, 0.02 mmol, 0.023 g), CuI (4 mol% based on 2,5-dibromothiophene, 0.04 mmol, 7.6 mg) and anhydrous DMF (5 ml) were added under a nitrogen atmosphere and the reaction mixture was heated for 2 hours (internal temperature of 107-112 ºC). The dark reaction mixture was cooled to room temperature, poured into 40 ml of ice-water, hexanes (50 ml) was added and the resulting mixture was vacuum filtered to remove a small amount of insoluble matter. The organic phase was separated, the aqueous phase was extracted with hexanes (3×10 ml), and the combined organic phases were dried over MgSO4. Most of the solvent was removed by rotary evaporation and the remaining yellow solution was applied to an Al2O3 column (basic, 20 g, hexanes, then hexanes:EtOAc=8:1 as eluants). A yellow solution was collected when the second eluant was used and solvent was removed and the product was recrystallized from EtOH. A yellow powder was isolated in 47.6% yield (0.18 g, 90% purity by 1H NMR), which was further purified by column chromatography (15 g of silica gel, hexanes:EtOAc=50:1 as eluant). MS (APCI): 379.1 (calculated FW 378.2130). FT-IR (cm-1): 3055 (weak), 2949, 2926, 1586, 1566, 1541, 1444, 1315, 1299, 1218, 1158, 1104, 1082, 990, 840, 816, 792, 739, 683, 657.
S47
UV-Vis (DMSO, λmax): 288, 351. DSC analysis: 65.7 ºC (m.p.).
1
H NMR (CDCl3, 400
MHz): δ 0.90-0.96 (m, 6H), 1.32-1.43 (m, 8H), 1.75-1.85 (m, 4H), 2.78-2.83 (t, J=7.78 Hz, 4H), 6.98-7.02 (d, J=7.56 Hz, 2H), 7.46-7.50 (d, J=7.77 Hz, 2H), 7.55-7.60 (m, 4H);
13
C
NMR (CDCl3, 100 MHz): δ 14.09, 22.60, 29.30, 31.64, 38.28, 115.97 (CH), 120.91 (CH), 125.14 (CH), 136.60 (CH), 146.52 (quaternary C), 151.88 (quaternary C), 162.54 (quaternary C). Anal. Calcd. for C24H30N2S : C, 76.14; H, 7.99; N, 7.40, S, 8.47. Found: C, 76.31, H, 8.31; N, 7.50; S, 8.39.
5,5’-Bis-(6-n-decylpyridin-2-yl)-2,2’-bithiophene (33)
C10H21
N 15b
SnBu3
+
Br
S S
Br
C10H21
N
S S
32
N 33
C10H21
An oven-dried three-necked flask was charged with 5,5’-dibromo-2,2’-bithiophene (32) (1 mmol, 0.32 g) and 2-n-decyl-6-tri-n-butylstannylpyridine (15b) (2 equiv., 2 mmol, 1.02 g). Catalysts Pd(PPh3)4 (2 mol% based on 5,5’-dibromo-2,2’-bithiophene, 0.02 mmol, 0.023 g), CuI (4 mol% based on 5,5’-dibromo-2,2’-bithiophene, 0.04 mmol, 7.6 mg) and anhydrous DMF (10 ml) were added under a nitrogen atmosphere and the reaction mixture was heated for 2 hours (internal temperature of 100-105 ºC). The reaction mixture was cooled to room temperature, poured into 60 ml of ice water, and the organic matter was extracted with CH2Cl2 (30 ml, 2×15 ml). The combined organic phases were dried over MgSO4, the bright yellow solution was concentrated to 10-15 ml, and chromatographed twice (30 g of silica gel, hexanes:CH2Cl2=5:1 for the 1st column; 20 g of silica gel, hexanes:CH2Cl2=1:1 for the 2nd column). The yellow powder isolated after the removal of the solvents was recrystallized from 1-PrOH to give the product in 55% yield (0.33 g, 95% purity by 1H NMR). MS (APCI): 601.2 (calculated FW 600.3579). FT-IR (cm-1): 3091 (weak), 3069 (weak), 2958, 2952, 2941, 2849, 1580, 1567, 1470, 1455, 1443, 1422, 1181, 1014, 988, 882, 801, 777, 753, S48
719, 678. UV-Vis (DMSO, λmax): 258, 298. DSC analysis: 55.2 ºC, 83.2 ºC (on heating); 49.5 ºC, 80.6 ºC (on cooling). 1H NMR (CDCl3, 400 MHz): δ 0.84-0.90 (t, J=6.87 Hz, 6H), 1.20-1.42 (m, 28H), 1.73-1.81 (m, 4H), 2.77-2.83 (t, J=7.76 Hz, 4H), 6.96-7.00 (d, J=7.50 Hz, 2H), 7.23-7.25 (d, J=3.84 Hz, 2H), 7.41-7.45 (d, J=7.75 Hz, 2H), 7.45-7.48 (d, J=3.86 Hz, 2H), 7.53-7.69 (m, 2H);
13
C NMR (CDCl3, 100 MHz): δ 14.15, 22.72, 29.38, 29.42,
29.56, 29.66, 31.95, 38.25, 115.61 (CH), 120.85 (CH), 124.60 (CH), 124.86 (CH), 136.61 (CH), 139.23 (quaternary C), 144.44 (quaternary C), 151.57 (quaternary C), 162.56 (quaternary C) (two alkyl signals are missing due to overlap). Anal. Calcd. for C38H52N2S2: C, 75.95; H, 8.72; N, 4.66, S, 10.67. Found: C, 75.95, H, 8.59; N, 4.81; S, 10.78.
5,5’-Dibromo-2,2’-bithiophene (32) was obtained using the literature procedure 10 from 2,2’bithiophene (0.075 mol, 12.47 g), NBS (0.15 mol, 26.7 g) and anhydrous DMF (200 ml) (the ice-water cooling bath was used during addition of NBS solution, 3-8 ºC internal temperature). The reaction mixture was poured into 200 ml of ice water and the beige solid was separated by vacuum filtration. The crude material was isolated in an amount of 25.3 g (104% crude yield). A portion of this material (5 g) was dissolved in 340 ml of hot hexanes, gravity filtered and the filtrate concentrated down to about 100 ml (crystallization started) and cooled. The yellowish shiny plates were isolated by vacuum filtration (4.20 g, 84% recovery, 87.5% purified yield). DSC analysis: 147.0 ºC (lit. m.p. 146.0-146.5 ºC) 11 . NMR (CDCl3, 300 MHz): δ 6.83-6.87 (d, J=3.86 Hz, 2H), 6.94-6.97 (d, J=3.87 Hz, 2H).
(10) Bäuerle P., Würthner F., Götz G., Effenberger F. Synthesis, 1993, 11, 1099. (11) Wynberg, H.; Bantjes, A. J. Org. Chem., 1959, 24, 1421.
S49
1
H
Figure 1. DSC analysis of terpyridine LC 20: enlarged region with weak 1st/2nd order
Heat Flow (W/g)
transitions (marked as 1, 2, and 3).
-0.4 -0.9 -1.4 1
-1.9 130
Exo down
3
2
140
150
160
Temperature (ºC)
Heat Flow (W/g)
Figure 2. DSC thermogram of terpyridine 23.
2
-2
-6 -20
Exo down
30
80
130
Temperature (ºC)
S50
180
