With hydrogenchloride In 1,4-dioxane; ethyl acetate at 0 - 20℃; for 2 h;
Charging a 1000 mL round bottom flask with methanol (500 mL), 2,6-diisopropylaniline (63.8 mL, 340 mmol), glyoxal (40 wt percent soln in water, 19 mL, 170 mmol), and formic acid (1 mL).Stirring the resulting mixture for 3 hours at room temperature.Filtering the yellow precipitate, (3) (Diagram D)Washing precipitate with cold methanol.Drying precipitate in vacuo overnight (70percent, 44.2 g, 238 mmol).Charging a 5 L round bottom flask with precipitate (3) (200 g, 532 mmol) and ethyl acetate (2 L).Stirring the resulting mixture until (3) was dissolved.Cooling the solution to 0° C. but this can be carried out at room temperature.Charging a 500 mL Erlenmeyer flask with paraformaldehyde (20.7 g, 690 mmol), HCl (4N in dioxane, 212 mL, 851 mmol).Stirring this solution for 10 minutes, then added.Stirring the resulting mixture for 2 hours at room temperature.Filtering precipitateDissolving precipitate in methanol (200 mL).Adding 15.0 g of sodium bicarbonate.Stirring the solution for 1 hour or until there is no more carbonation.Filtering the solution to remove the solids.Reprecipitating the product with 250 mL of diethyl etherCollecting product by filtrationWashing product with diethyl ether.Drying the product in vacuo to yield IPr.HCl (4) as a white powder (70percent, 158.25 g, 371 mmol). 1H NMR (CDCl3, 400 MHz) δ 10.1 (s, 1H), 8.15 (s, 2H), 7.57 (t, 2H, J=7.8 Hz), 7.35 (d, 4H, J=8.4 Hz), 2.43(m, 4H), 1.28 (m, 24H) 13C NMR (CDCl3, 400 MHz) δ 145, 132.1, 129.9, 126.8, 124.7, 29.1, 24.7, 23.7. Synthesis of 1,3-Bis(2,6-diisopropylphenyl)imidazolium chloride (IPr.HCl, 4)A 1000 mL round bottom flask was charged with methanol (500 mL), 2,6-diisopropylaniline (63.8 mL, 340 mmol), glyoxal (40 wt percent soln in water, 19 mL, 170 mmol), and formic acid (1 mL). The resulting mixture was allowed to stir for 3 hours at room temperature. The yellow precipitate (3) was filtered, washed with cold methanol and dried in vacuo overnight (70percent, 44.2 g, 238 mmol). A 5 L round bottom flask was charged with 3 (200 g, 532 mmol) and ethyl acetate (2 L) and the resulting mixture was stirred until 3 was dissolved. The solution was cooled to 0° C. A 500 mL Erlenmeyer flask was charged with paraformaldehyde (20.7 g, 690 mmol), HCl (4N in dioxane, 212 mL, 851 mmol). This solution was stirred for 10 minutes, then added. The resulting mixture was then stirred for 2 hours at room temperature. The precipitate was filtered, dissolved in methanol (200 mL) and 15.0 g of sodium bicarbonate was added. The solution was stirred for 1 hour or until there was no more carbonation. The solution was filtered to remove the solids and the product was reprecipitated with 250 mL of diethyl ether, collected by filtration, washed with diethyl ether and dried in vacuo to yield IPr.HCl (4) as a white powder (70percent, 158.25 g, 371 mmol). 1H NMR (CDCl3, 400 MHz) δ 10.1 (s, 1H), 8.15 (s, 2H), 7.57 (t, 2H, J=7.8 Hz), 7.35 (d, 4H, J=8.4 Hz), 2.43(m, 4H), 1.28 (m, 24H) 13C NMR (CDCl3, 400 MHz) δ 145, 132.1, 129.9, 126.8, 124.7, 29.1, 24.7, 23.7.
70%
With hydrogenchloride In 1,4-dioxane; ethyl acetate at 0 - 20℃; for 2 h;
Synthesizing of l,3-Bis(2,6-dsopropylphenyl)imidazolium chloride (IPr HCl, 4) by:; Charging a 1000 mL round bottom flask with methanol (500 mL), 2,6- diisopropylaniline (63.8 mL, 340 mmol), glyoxal (40wt percent soln in water, 19 mL, 170 mmol), and formic acid (ImL).Stirring the resulting mixture for 3 hours at room temperature. Filtering the yellow precipitate, (3) (Diagram D)Washing precipitate with cold methanol.Drying precipitate in vacuo overnight (70percent, 44.2 g, 238 mmol).Charging a 5 L round bottom flask with precipitate (3) (200 g, 532 mmol) and ethyl acetate (2 L). Stirring the resulting mixture until (3) was dissolved.Cooling the solution to 0° C but this can be carried out at room temperature.Charging a 500 mL Erlenmeyer flask with paraformaldehyde (20.7 g, 690 mmol), HCl (4N in dioxane, 212 mL, 851 mmol).Stirring this solution for 10 minutes, then added. Stirring the resulting mixture for 2 hours at room temperature.Filtering precipitateDissolving precipitate in methanol (20OmL).Adding 15.Og of sodium bicarbonate.Stirring the solution for 1 hour or until there is no more carbonation. Filtering the solution to remove the solids.Reprecipitating the product with 250 mL of diethyl etherCollecting product by filtrationWashing product with diethyl ether.Drying the product in vacuo to yield IPrHCl (4) as a white powder (70percent, 158.25g, 371 mmol). 1H NMR (CDCl3, 400 MHz) δ 10.1 (s, IH), 8.15 (s, 2H), 7.57 (t,2H, J = 7.8 Hz), 7.35 (d, 4H, J = 8.4 Hz), 2.43(m, 4H), 1.28 (m, 24H) 13C NMR (CDCl3, 400 MHz) δ 145, 132.1, 129.9, 126.8, 124.7, 29.1, 24.7, 23.7.; Synthesis of l,3-Bis(2,6-diisopropyIphenyl)imidazolium chloride (IPrηCl, 4); A l 000 mL round bottom flask was charged with methanol (500 mL), 2,6- diisopropylamline (63.8 mL, 340 mmol), glyoxal (40wt percent soln in water, 19 mL, 170 mmol), and formic acid (ImL). The resulting mixture was allowed to stir for 3 hours at room temperature. The yellow precipitate (3) was filtered, washed with cold methanol and dried in vacuo overnight (70percent, 44.2 g, 238 mmol). A 5 L round bottom flask was charged with 3 (200 g, 532 mmol) and ethyl acetate (2 L) and the resulting mixture was stirred until 3 was dissolved. The solution was cooled to 0° C. A 500 mL Erlenmeyer flask was charged with paraformaldehyde (20.7 g, 690 mmol), HCl (4N in dioxane, 212 mL, 851 mmol). This solution was stirred for 10 minutes, then added. The resulting mixture was then stirred for 2 hours at room temperature. The precipitate was filtered, dissolved in methanol (20OmL) and 15.Og of sodium bicarbonate was added. The solution was stirred for 1 hour or until there was no more carbonation. The solution was filtered to remove the solids and the product was reprecipitated with 250 mL of diethyl ether, collected by filtration, washed with <n="10"/>diethyl ether and dried in vacuo to yield IPrHCl (4) as a white powder (70percent, 158.25g, 371 mmol). 1H NMR (CDCl3, 400 MHz) δ 10.1 (s, IH), 8.15 (s, 2H), 7.57 (t, 2H, J = 7.8 Hz), 7.35 (d, 4H, J = 8.4 Hz), 2.43(m, 4H), 1.28 (m, 24H) 13C NMR (CDCl3, 400 MHz) δ 145, 132.1, 129.9, 126.8, 124.7, 29.1, 24.7, 23.7.
51.7%
Stage #1: With hydrogenchloride In toluene at 50℃; for 1 h; Stage #2: With hydrogenchloride In 1,4-dioxane at 40℃; for 40 h;
37.6 g (100 mmol) of bis(2,6-diisopropylphenyl)diazabutadiene, 1.68 g (100 mmol) of formaldehyde solid, 160 mL of toluene were added to a 500 mL three-neck round bottom flask. Stirred refluxed at 50° C. for 1 h until most of the formaldehyde dissolved. The reaction mixture was cooled to 40° C. and a solution of HCl in dioxane 58 mL (100 mmol, 1.723 mol/L) was added with a syringe.The color of the solution changed from yellow to red to brown, with the development of a white solid. The reaction was stirred and refluxed at 40° C. for 40 h, suction filtered and washed three times with THF to give a pink solid mass. About 40 mL of anhydrous ethanol was added to dissolve, the solvent was derotated, the solid was turned into a powder, and washed three times with THF to obtain 21.94 g of an off-white powder HIPrCl (yield 51.7percent).
Reference：
[1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 4, p. 622 - 630
[2] Journal of the American Chemical Society, 2011, vol. 133, # 30, p. 11482 - 11484
[3] Inorganic Chemistry, 2017, vol. 56, # 8, p. 4568 - 4575
[4] Organic Process Research and Development, 2014, vol. 18, # 8, p. 1041 - 1044
[5] Patent: US7109348, 2006, B1, . Location in patent: Page/Page column 4-7
[6] Patent: WO2008/36084, 2008, A1, . Location in patent: Page/Page column 4; 6-7; 8-9
[7] European Journal of Organic Chemistry, 2012, # 31, p. 6218 - 6227
[8] Patent: CN106432307, 2017, A, . Location in patent: Paragraph 0031; 0032
[9] Journal of Organometallic Chemistry, 2007, vol. 692, # 24, p. 5390 - 5394
[10] Green Chemistry, 2018, vol. 20, # 5, p. 964 - 968
[11] ChemCatChem, 2018, vol. 10, # 11, p. 2450 - 2457
2
[ 74663-75-5 ]
[ 3188-13-4 ]
[ 250285-32-6 ]
Reference：
[1] Chemical Communications, 2011, vol. 47, # 5, p. 1559 - 1561
[2] Tetrahedron, 1999, vol. 55, # 51, p. 14523 - 14534
[3] Journal of Organic Chemistry, 2008, vol. 73, # 7, p. 2784 - 2791
[4] Journal of the American Chemical Society, 2008, vol. 130, # 31, p. 10082 - 10083
[5] Advanced Synthesis and Catalysis, 2014, vol. 356, # 11-12, p. 2539 - 2546
[6] Tetrahedron, 2012, vol. 68, # 38, p. 7949 - 7955
[7] Journal of Organometallic Chemistry, 2016, vol. 825-826, p. 55 - 62
3
[ 244187-81-3 ]
[ 250285-32-6 ]
Reference：
[1] Angewandte Chemie, International Edition, 2009, vol. 48, p. 5683 - 5686[2] Angewandte Chemie, 2009, vol. 121, p. 5793 - 5796
4
[ 50-00-0 ]
[ 74663-75-5 ]
[ 250285-32-6 ]
Reference：
[1] Angewandte Chemie - International Edition, 2018, vol. 57, # 17, p. 4668 - 4672[2] Angew. Chem., 2018, vol. 130, # 17, p. 4758 - 4762,5
[3] Journal of Organometallic Chemistry, 2000, vol. 606, # 1, p. 49 - 54
[4] Organic Letters, 2016, vol. 18, # 3, p. 432 - 435
Reference：
[1] Angewandte Chemie - International Edition, 2013, vol. 52, # 52, p. 14204 - 14208[2] Angew. Chem., 2013, vol. 125, # 52, p. 14454 - 14458,5
13
[ 131543-46-9 ]
[ 24544-04-5 ]
[ 3188-13-4 ]
[ 250285-32-6 ]
Reference：
[1] Angewandte Chemie - International Edition, 2010, vol. 49, # 16, p. 2929 - 2932
14
[ 250285-32-6 ]
[ 578743-87-0 ]
Yield
Reaction Conditions
Operation in experiment
94%
With sodium t-butanolate In tetrahydrofuran at 20℃; for 20 h;
Synthesis of [(IPr)CuCl]. This synthesis is as reported in the literature; see H. Kaur et al., Organometallics 2004, 23, 1157-1160. In a 250 mL Schlenk flask were added copper(I) chloride (1.0 g, 10.10 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IPr.HCl; 4.29 g, 10.10 mmol), and sodium tert-butoxide (0.97 g, 10.10 mmol). To this flask, dry tetrahydrofuran (100 mL) was added under an inert atmosphere of argon, and the mixture was magnetically stirred for 20 hours at room temperature. After the mixture was filtered through a plug of Celite and then evaporating the solvent under vacuum, a white solid was obtained (4.59 g, 9.40 mmol, 94percent). 1H NMR: (400 MHz, acetone-d6, ppm) δ=1.21 (d, J=6.8 Hz, 12H); 1.30 (d, J=6.8 Hz, 12H); 2.57 (hep, J=6.8 Hz, 4H); 7.12 (s, 2H). 7.29 (d, J=7.8 Hz, 4H); 7.49 (t, J=7.8 Hz, 2H). 13C NMR: (100 MHz, acetone-d6, ppm) δ=182.32; 145.61; 134.41; 130.62; 124.25; 123.13; 28.76; 24.82; 23.87. Elemental analysis calcd for C27H36ClCuN2: C 66.64percent, H, 7.46percent, N, 5.76percent; found C, 66.70percent, H, 7.48percent, N, 6.06percent.
Reference：
[1] Organometallics, 2004, vol. 23, # 5, p. 1157 - 1160
[2] Patent: US2009/69569, 2009, A1, . Location in patent: Page/Page column 6
[3] Organometallics, 2013, vol. 32, # 15, p. 4279 - 4283
[4] Organic and Biomolecular Chemistry, 2012, vol. 10, # 47, p. 9334 - 9337
[5] Journal of the American Chemical Society, 2017, vol. 139, # 36, p. 12855 - 12862
[6] Journal of the American Chemical Society, 2015, vol. 137, # 4, p. 1424 - 1427
[7] Dalton Transactions, 2017, vol. 46, # 27, p. 8756 - 8762
15
[ 12775-96-1 ]
[ 250285-32-6 ]
[ 578743-87-0 ]
Yield
Reaction Conditions
Operation in experiment
40%
at 80 - 90℃; for 30 h;
Add ligand L8850mg (2.0mmol), copper powder 128mg (2.0mmol) in 50mL flask, water 30 mL, 80 ~ 90 in an oil bath, the reaction was stirred for 30 hours, the reaction mixture was cooled to room temperature, filtered, the filter cake was washed 3 times with water, the filter cake dissolved in acetonitrile and filtered to remove unreacted copper powder, the solvent was evaporated under reduced pressure to give 390 mg of colorless crystals, a yield of 40percent.
Reference：
[1] Dalton Transactions, 2015, vol. 44, # 4, p. 1836 - 1844
[2] Chemical Science, 2017, vol. 8, # 2, p. 1086 - 1089
[3] Chemical Communications, 2012, vol. 48, # 40, p. 4887 - 4889
[4] Patent: CN105585584, 2016, A, . Location in patent: Paragraph 0046; 0047; 0048
With sodium t-butanolate; In tetrahydrofuran; at 20℃; for 20h;
Synthesis of [(IPr)CuCl]. This synthesis is as reported in the literature; see H. Kaur et al., Organometallics 2004, 23, 1157-1160. In a 250 mL Schlenk flask were added copper(I) chloride (1.0 g, 10.10 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IPr.HCl; 4.29 g, 10.10 mmol), and sodium tert-butoxide (0.97 g, 10.10 mmol). To this flask, dry tetrahydrofuran (100 mL) was added under an inert atmosphere of argon, and the mixture was magnetically stirred for 20 hours at room temperature. After the mixture was filtered through a plug of Celite and then evaporating the solvent under vacuum, a white solid was obtained (4.59 g, 9.40 mmol, 94%). 1H NMR: (400 MHz, acetone-d6, ppm) delta=1.21 (d, J=6.8 Hz, 12H); 1.30 (d, J=6.8 Hz, 12H); 2.57 (hep, J=6.8 Hz, 4H); 7.12 (s, 2H). 7.29 (d, J=7.8 Hz, 4H); 7.49 (t, J=7.8 Hz, 2H). 13C NMR: (100 MHz, acetone-d6, ppm) delta=182.32; 145.61; 134.41; 130.62; 124.25; 123.13; 28.76; 24.82; 23.87. Elemental analysis calcd for C27H36ClCuN2: C 66.64%, H, 7.46%, N, 5.76%; found C, 66.70%, H, 7.48%, N, 6.06%.
Add ligand L8850mg (2.0mmol), copper powder 128mg (2.0mmol) in 50mL flask, water 30 mL, 80 ~ 90 in an oil bath, the reaction was stirred for 30 hours, the reaction mixture was cooled to room temperature, filtered, the filter cake was washed 3 times with water, the filter cake dissolved in acetonitrile and filtered to remove unreacted copper powder, the solvent was evaporated under reduced pressure to give 390 mg of colorless crystals, a yield of 40%.
With potassium carbonate; In tetrahydrofuran; at 65℃; for 16h;Inert atmosphere;
Tris [4- (pyridin-4-yl) phenyl] amine compound (47.6 mg, 0.10 mmol)1,3-bis (2,6-diisopropylphenyl) imidazolium chloride (IPr.HCl) (127.5 mg, 0.30 mmol),PdCl2 (53.2 mg, 0.30 mmol)And potassium carbonate (41.5 mg, 0.30 mmol) were added to a 25 mL single neck flask,Tetrahydrofuran (5 mL) was then added,The reaction was stirred at 65 C for 16 h under argon atmosphere.Stop the reaction,Cool to room temperature,concentrate,Thin layer chromatography to give compound I,Yield 57%.
With potassium carbonate; In tetrahydrofuran; for 12h;Inert atmosphere; Reflux;
General procedure: Under an N2 atmosphere, a mixture of the imidazolium salt (1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium chloride, 2.2 mmol), the required N-heterocycle (1.0 mmol), PdCl2(2.2 mmol) and K2CO3(2.2 mmol) was stirred in anhydrous THF (10 mL) under reflux for 12 h. After cooling, filtration and evaporation, the residue was purified by preparative TLC on silica gel plates, eluting with CH2Cl2 to afford the corresponding dinuclear N-heterocyclic carbene?palladium(II) complexes 1?4.
With water; oxygen; In dimethylsulfoxide-d6; at 150℃; for 155h;Sealed tube;Kinetics;
General procedure: Cu(I)-NHC 1a-g (0.04 mmol, 1.0 equiv) and CDCl3 (0.4 mL, degassed by bubbling argon for 30 min) were added into a flame-dried NMR tube. (CD3)2SO (0.4 mL) was used for 1h (0.04 mmol), 1i (0.02 mmol), and 1j (0.02 mmol). The NMR tube was closed with a septum and equipped with an air balloon (approximate 500 mL) containing approximately 100 mL of O2 (4.5 mmol, 112 equiv.) and approximately 12.6 mL of H2O (gas, 0.56 mmol, 14 equiv., air relative humidity = 75%). The solution (not agitated) was placed at room temperature and was monitored by 1H NMR. 100 C was used for the decomposition of 1h, and 150 C was used for the decomposition of 1i and 1j. The precipitate in the NMR tube was removed by quick filtration using a membrane filter before each 1H NMR measurement. The ratio of Cu-NHC, urea, and imidazolium were calculated through the integration of 1H NMR, using the normalization method. The characterization of products could be found in the previous study [32].
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