Synthesis of unsymmetrical imidazolium salts by direct quaternization of N-substituted imidazoles using arylboronic acids

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Electronic Supplementary Material (ESI) for Chemical Communications. This journal is The Royal Society of Chemistry 2014 Supporting Information Synthesis of unsymmetrical imidazolium salts by direct quaternization of -substituted imidazoles using arylboronic acids Shiqing Li, Fan Yang, Taiyong Lv, Jingbo Lan, Ge Gao* and Jingsong You* Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China E-mail: gg2b@scu.edu.cn; jsyou@scu.edu.cn Table of contents I. General Remarks...2 II. General procedure for the direct quaternization of -Substituted Imidazoles with arylboronic acids...2 III. Characterization data of the products...3 IV. References...9 V. Copies of 1 H and 13 C MR spectra...10 S1

I. General Remarks Unless otherwise noted, all reagents were obtained from commercial suppliers and used without further purification. CuI was washed with THF using a Soxhlet extractor prior to use. Reactions were carried out under ambient atmosphere unless otherwise specified. All the known -arylimidazole derivatives, 1-3 -mesitylimidazole, 4 -(2,6- diisopropylphenyl)imidazole, 5 -tert-butylimidazole 5 and (R)-1-(1-phenylethyl)-1Himidazole 6 were synthesized according to the literature procedures. MR spectra were obtained on a Bruker AMX-400. The 1 H MR (400 MHz) chemical shifts were reported relative to CDCl 3 or DMSO-d 6 as the internal reference (CDCl 3 : δ = 7.26 ppm; DMSO-d 6 : δ = 2.50 ppm; The 13 C MR (100 MHz) chemical shifts were given using CDCl 3 or DMSO-d 6 as the internal standard (CDCl 3 : δ = 77.16 ppm; DMSO-d 6 : δ = 39.52 ppm). High-resolution mass spectra (HR-MS) were obtained with a Waters- Q-TOF-Premier (ESI). Melting points were determined with XRC-1 and are uncorrected. The optical rotation was obtained on an Autopol V instrument and reported as: [α] D t (c g/100 ml, in CH 2 Cl 2 ). II. General procedure for the direct quaternization of -Substituted Imidazoles with arylboronic acids Cu(OAc) 2 H 2 O (10 mol%) B(OH) 2 FeCl 3 (10 mol%) + R R ' HBF R 4 /H 4 (1.0/2.5 equiv) DMF, 100 C, 10 h 1 2 3 R ' A Schlenck tube with a magnetic stir bar was charged with a -substituted imidazole (0.25 mmol, 1.0 equiv), an arylboronic acid (0.375 mmol, 1.5 equiv), Cu(OAc) 2 H 2 O (5 mg, 10 mol%), FeCl 3 (4 mg, 10 mol%), H (40 μl, 0.25 mmol, 1.0 equiv, 40% wt in aqueous solution), H 4 (66 mg, 2.5 equiv) and DMF (1 ml). The reaction mixture was stirred at 100 C for 10 h in an oil bath and then cooled down to room temperature. The solvent was removed under reduced pressure, and the residue was passed through a silica gel column eluted with dichloromethane/methanol (v/v, 70/1 20/1) to afford the desired product. S2

III. Characterization data of the products 1,3-Diphenyl-1H-imidazol-3-ium Tetrafluoroborate (3aa). 7 A white solid (71 mg, 92% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.64 (t, J = 7.4 Hz, 2H), 7.72 (t, J = 7.8 Hz, 4H), 7.93 (d, J = 7.6 Hz, 4H), 8.58 (d, J = 1.2 Hz, 2H), 10.34 (t, J = 1.6 Hz, 1H) ppm. 3-Phenyl-1-o-tolyl-1H-imidazol-3-ium Tetrafluoroborate (3ba or 3ab). 7 A gray solid (66 mg, 81% yield; 3ab: 25 mg, 31% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 2.33 (s, 3H), 7.52 7.74 (m, 7H), 7.91 (d, J = 8.0 Hz, 2H), 8.35 (t, J = 1.6 Hz, 1H), 8.59 (t, J = 1.8 Hz, 1H), 10.11 (s, 1H) ppm. MeO 1-(3-Methoxyphenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ca or 3ac). 7 A gray solid (3ca: 59 mg, 70% yield; 3ac: 55 mg, 65% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 3.89 (s, 3H), 7.21 (dd, J = 8.4, 2.4 Hz, 1H), 7.50 (dd, J = 8.0, 2.0 Hz, 1H), 7.55 (t, J = 2.2 Hz, 1H), 7.61 7.66 (m, 2H), 7.73 (t, J = 7.6 Hz, 2H), 7.93 (d, J = 7.6 Hz, 2H), 8.59 (t, J = 1.8, 1H), 8.61 (t, J = 1.8, 1H), 10.34 (t, J = 1.6, 1H) ppm. MeO 1-(4-Methoxyphenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3da or 3ad). 7 A gray solid (3da: 60 mg, 71% yield; 3ad: 59 mg, 70% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 3.87 (s, 3H), 7.25 (d, J = 6.4 Hz, 2H), 7.63 (br, 1H), 7.71 (br, 2H), 7.84 (d, J = 6.4 Hz, 2H), 7.91 (d, J = 4.8 Hz, 2H), 8.49 (s, 1H), 8.54 (s, 1H), S3

10.25 (s, 1H) ppm. Cl 1-(4-Chlorophenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ea). 7 A gray solid (57 mg, 67% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.64 (t, J = 7.4 Hz, 1H), 7.72 (t, J = 7.8 Hz, 2H), 7.83 (d, J = 9.2 Hz, 2H), 7.91 (d, J = 7.6 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 8.58 (s, 2H), 10.36 (s, 1H) ppm. Br 1-(2-Bromophenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3fa or 3ah). 7 A white solid (3fa: 63 mg, 66% yield; 3ah: 77 mg, 80% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.65 (t, J = 7.4 Hz, 1H), 7.73 (t, J = 7.8 Hz, 2H), 7.89 7.93 (m, 4H), 7.97 (d, J = 8.8 Hz, 2H), 8.588 (s, 1H), 8.59 (s, 1H), 10.36 (s, 1H) ppm. 1-(4-Ethynylphenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ga). 7 A yellow solid (47 mg, 57% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 4.46 (s, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.72 (t, J = 7.6 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 8.59 (s, 1H), 8.61 (s, 1H), 10.38 (s, 1H) ppm. MeOOC 1-(4-(Methoxycarbonyl)phenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ha). 7 A yellow solid (82 mg, 90% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 3.92 (s, 3H), 7.64 (t, J = 7.4 Hz, 1H), 7.73 (t, J = 7.6 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H), 8.10 (d, J = 8.8 Hz, 2H), 8.27 (d, J = 8.8 Hz, 2H), 8.61 (t, J = 1.8 Hz, 1H), 8.67 (t, J = 1.8 Hz, 1H), 10.47 (s, 1H) ppm. S4

1-[4-(Dimethylamino)phenyl]-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ia). 7 A yellow solid (57 mg, 65% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 3.01 (s, 6H), 6.92 (d, J = 9.2 Hz, 2H), 7. 60 7. 64 (m, 1H), 7. 68 7. 72 (m, 4H), 7.91 (d, J = 8.0 Hz, 2H), 8.44 (t, J = 2.0 Hz, 1H), 8.51 (t, J = 1.8 Hz, 1H), 10.17 (t, J = 1.6 Hz, 1H) ppm. 1-Mesityl-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ja). 7 A gray solid (58 mg, 66% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 2.13 (s, 6H), 2.35 (s, 3H), 7.19 (s, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.71 (t, J = 7.6 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H), 8.20 (t, J = 1.6 Hz, 1H), 8.65 (t, J = 1.8 Hz, 1H), 10.03 (t, J = 1.4 Hz, 1H) ppm. 1-(2,6-Diisopropylphenyl)-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ka). 7 A gray solid (48 mg, 49% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 1.17 (d, J = 6.8 Hz, 6H), 1.19 (d, J = 6.8 Hz, 6H), 2.42 2.47 (m, 2H), 7.50 (d, J = 7.6 Hz, 2H), 7.62 7.74 (m, 4H), 7.91 (d, J = 8.0 Hz, 2H), 8.37 (s, 1H), 8.71 (s, 1H), 10.24 (s, 1H) ppm. 3-Phenyl-1-(pyridin-2-yl)-1H-imidazol-3-ium Tetrafluoroborate (3la). 7 A gray solid (58 mg, 75% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.63 7.66 (m, 1H), 7.69 7.72 (m, 3H), 7.94 (d, J = 8.0 Hz, 2H), 8.16 (d, J = 8.4 Hz, 1H), 8.28 (td, J = 7.8, 2.0 Hz, 1H), 8.58 (t, J = 2.0 Hz, 1H), 8.71 8.72 (m, 1H), 8.76 (t, J = 2.0 Hz, 1H), S5

10.59 (t, J = 1.6 Hz, 1H) ppm. 1-tert-Butyl-3-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ma). 7 A gray solid (65 mg, 91% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 1.66 (s, 9H), 7.59 (t, J = 7.2 Hz, 1H), 7.67 (t, J = 7.8 Hz, 2H), 7.85 (d, J = 8.0 Hz, 2H), 8.28 (t, J = 2.0 Hz, 1H), 8.38 (t, J = 1.8 Hz, 1H), 9.69 (t, J = 1.6 Hz, 1H) ppm. 1,3-Diphenyl-1H-benzo[d]imidazol-3-ium Tetrafluoroborate (3na). 7 A gray solid (41 mg, 46% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.74 7.83 (m, 8H), 7.93 7.98 (m, 6H), 10.58 (s, 1H) ppm. (R)-3-Phenyl-1-(1-phenylethyl)-1H-imidazol-3-ium Tetrafluoroborate (3oa). A gray semisolid (76 mg, 90% yield). [α] 12.7 D = +36.3 (c = 3.01, CH 2 Cl 2 ). 1 H MR (400 MHz, CDCl 3 ): δ = 1.97 (d, J = 6.8 Hz, 3H), 5.91 (q, J = 6.8 Hz, 1H), 7.34 7.39 (m, 3H), 7.43 7.48 (m, 6H),7.60 (d, J = 6.8 Hz, 2H), 7.66 (s, 1H), 9.33 (s, 1H) ppm. 13 C MR (100 MHz, CDCl 3 ): δ = 20.6, 60.6, 121.7, 121.8, 122.1, 127.3, 129.6, 129.7, 130.4, 130.6, 133.5, 134.5, 137.6 ppm. HRMS (ESI): calcd for C 15 H 12 3 O 2 + ([M ] + ) 249.1386, found 249.1395. 3-([1,1'-Biphenyl]-4-yl)-1-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ae). A gray solid (62 mg, 65% yield). M.p.: 169-171 ºC. 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.45 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.4 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.74 (t, J S6

= 7.8 Hz, 2H), 7.81 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 7.6 Hz, 2H), 8.03 (s, 4H), 8.61 (t, J = 2.0 Hz, 1H), 8.65 (t, J = 1.8 Hz, 1H), 10. 41 (t, J = 1.6 Hz, 1H) ppm. 13 C MR (100 MHz, DMSO-d 6 ): δ = 121.9, 122.0, 122.1, 122.5, 127.0, 128.3, 128.4, 129.2, 130.1, 130.2, 133.9, 134.5, 134.7, 138.4, 141.7 ppm. HRMS (ESI): calcd for C 21 H 17 + 2 ([M ] + ) 297.1386, found 297.1380. O 2 3-(3-itrophenyl)-1-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3af). A brown solid (63 mg, 72% yield). M.p.: 176-178 ºC. 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.66 (t, J = 7.2 Hz, 1H), 7.74 (t, J = 7.6 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H), 8.03 (t, J = 8.4 Hz, 1H), 8.39 (dd, J = 8.4, 2.4 Hz, 1H), 8.49 (dd, J = 8.4, 1.6 Hz, 1H), 8.63 (t, J = 1.8 Hz, 1H), 8.72 (t, J = 2.0 Hz, 1H), 8.89 (t, J = 2.2 Hz, 1H), 10. 54 (t, J = 1.6 Hz, 1H) ppm. 13 C MR (100 MHz, DMSO-d 6 ): δ = 117.6, 122.01, 122.02, 122.2, 124.7, 128.6, 130.26, 130.30, 131.8, 134.6, 135.5, 135.6, 148.5 ppm. HRMS (ESI): calcd for C 15 H 12 3 O + 2 ([M ] + ) 266.0924, found 266.0926. O 3-(4-Acetylphenyl)-1-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ag). 7 A yellow solid (51 mg, 57% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 2.68 (s, 3H), 7.65 (t, J = 7.4 Hz, 1H), 7.73 (t, J = 7.8 Hz, 2H), 7.93 (d, J = 7.6 Hz, 2H), 8.09 (d, J = 8.8 Hz, 2H), 8.27 (d, J = 8.8 Hz, 2H), 8.62 (t, J = 2.0 Hz, 1H), 8.69 (t, J = 2.0 Hz, 1H), 10. 47 (t, J = 1.6 Hz, 1H) ppm. F 3-(4-Fluorophenyl)-1-phenyl-1H-imidazol-3-ium Tetrafluoroborate (3ah). 7 A white solid (64 mg, 73% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.59 7.64 (m, 3H), 7.73 (t, J = 7.8 Hz, 2H), 7.91 (d, J = 7.6 Hz, 2H), 7.95 7.98 (m, 2H), 8.54 (t, J = 1.8 Hz, 1H), 8.58 (t, J = 1.8 Hz, 1H), 10.32 (t, J = 1.6 Hz, 1H) ppm. S7

Br Br 1,3-Bis(4-bromophenyl)-1H-imidazol-3-ium Tetrafluoroborate (3fi). 7 A gray solid (50 mg, 43% yield). 1 H MR (400 MHz, DMSO-d 6 ): δ = 7.88 (d, J = 8.4 Hz, 4H), 7.96 (d, J = 8.8 Hz, 4H), 8.58 (d, J = 1.6 Hz, 2H), 10.41 (d, J = 1.6 Hz, 1H) ppm. Br COOEt 1-(4-Bromophenyl)-3-(4-(ethoxycarbonyl)phenyl)-1H-imidazol-3-ium Tetrafluoroborate (3fj). A gray solid (50 mg, 44% yield). M.p.: 198-200 ºC. 1 H MR (400 MHz, DMSO-d 6 ): δ = 1.37 (s, 3H), 4.38 (d, J = 6.4 Hz, 2H), 7.91 (br, 2H), 7.96 (br, 2H), 8.08 (d, J = 7.6 Hz, 2H), 8.26 (d, J = 7.2 Hz, 2H), 8.61 (s, 1H), 8.67 (s, 1H), 10.49 (s, 1H) ppm. 13 C MR (100 MHz, DMSO-d 6 ): δ = 14.2, 61.4, 121.8, 122.15, 122.19, 123.2, 124.2, 131.1, 133.1, 133.9, 135.3, 138.0, 138.9, 164.7 ppm. HRMS (ESI): calcd for C 15 H 12 3 O + 2 ([M ] + ) 371.0390, found 371.0390. Cl 1,3-Diphenyl-1H-imidazol-3-ium chloride (3aa'). 3aa' was prepared by following a modified procedure. 8 A mixture of about 5 g Dowex 1 4-50 anion exchange resin in the chloride form and 5 ml water was packed in a column. 1,3-Diphenyl-1Himidazol-3-ium tetrafluoroborate 3aa (77 mg) was dissolved in 5 ml methanol and 2 ml water. The solution was passed through the column and the resin was then washed with methanol/water. The solution obtained was concentrated and run through a short silica gel column (3 cm) with methanol. Vacuum concentration of the collected methanol solution afforded the diphenylimidazolium chloride salt 3aa' as a gray solid (60 mg, 94% yield). 1 H MR (400 MHz, DMSO-d 6 ): 7.63 (t, J = 7.2 Hz, 2H), 7.71 (t, J = 7.8 Hz, 4H), 7.99 (d, J = 8.0 Hz, 4H), 8.65 (d, J = 0.8 Hz, 2H), 10.54 (s, 1H) ppm. S8

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V. Copies of 1 H and 13 C MR spectra 1 H MR of 3aa in DMSO S10

1 H MR of 3oa in CDCl 3 13 C MR of 3oa in CDCl 3 S11

1 H MR of 3ae in DMSO 13 C MR of 3ae in DMSO S12

1 H MR of 3af in DMSO 13 C MR of 3af in DMSO S13

1 H MR of 3fj in DMSO S14

13 C MR of 3fj in DMSO 1 H MR 3aa' in DMSO S15