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CAS No. : | 1134-35-6 | MDL No. : | MFCD00006441 |
Formula : | C12H12N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NBPGPQJFYXNFKN-UHFFFAOYSA-N |
M.W : | 184.24 | Pubchem ID : | 14338 |
Synonyms : |
4,4'-Dimethyl-2,2'-bipyridine
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.17 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 57.4 |
TPSA : | 25.78 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.85 cm/s |
Log Po/w (iLOGP) : | 2.53 |
Log Po/w (XLOGP3) : | 2.21 |
Log Po/w (WLOGP) : | 2.76 |
Log Po/w (MLOGP) : | 1.49 |
Log Po/w (SILICOS-IT) : | 3.43 |
Consensus Log Po/w : | 2.48 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.94 |
Solubility : | 0.21 mg/ml ; 0.00114 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.39 |
Solubility : | 0.758 mg/ml ; 0.00411 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.94 |
Solubility : | 0.0021 mg/ml ; 0.0000114 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | at 65℃; for 6 h; | 1.0 g of 4,4-dimethyl-2,2-bipyridine(5.4mmol) was added to the reaction flask, 18mL concentrated sulfuric acid was slowly added dropwise and stirred, the process a lot of heat until the solution was cooled to room temperature and then added potassium dichromate 3.3g (11.3mmol), then the solution becomes dark green, Then reacted at 65 ° C for 6 h. The reaction was completed and cooled to room temperature, the reaction was added to 1000mL of water, a large number of white flocculent precipitate was generated at this time, suction filtration, and then washed with water and methanol to the filtrate was white precipitate was clarified, and then dried in a vacuum oven at 60 18h, Yield 98percent |
96% | With potassium permanganate; nitric acid In water at 80℃; for 6 h; | In a four-necked flask equipped with a thermometer, a magnet and a reflux condenser,3.7 g (0.02 mol) of analytically pure 4,4'-dimethyl-2,2'-bipyridine was added,Was dissolved in a mixed system of 40 mL of water and 0.4 mL of nitric acid and heated to 80 ° C with stirring,And the temperature was maintained five times by adding potassium permanganate solid (12.6 g, 0.08 mol)Until the previous addition of potassium permanganate reaction to dissolve, then add the next batch of potassium permanganate,The reaction was stopped after 6 hours. After cooling to room temperature, the reaction solution is decompressed under reduced pressure, and after the insoluble matter is to be filtered out,Concentrate hydrochloric acid was added to the filtrate to adjust the pH to 1.Static crystallization, a white crystal precipitation.After crystallization was complete, the filtrate was decompressed under reduced pressure and the resulting white crystals were washed with deionized water.The product was then dried in vacuo to give 4.69 g of the desired product, 2,2'-bipyridyl-4,4'-dicarboxylic acid, in 96percent yield. |
95% | Stage #1: for 0.25 h; Stage #2: at 70 - 80℃; for 1 h; |
To a 125 ml of sulfuric acid (98percent), 5.0 g (0.021 mol) of 4,4’-dimethyl-2,2’-bipyridine was added. The obtained mixture was stirred for about 15 min, and a clarified solution with a light pink color was achieved. Then 24 g (0.082 mol) of potassium dichromate was addedcarefully in small portions. And the temperature was held consistently between 70 and 80 °C during this process. After all the dichromate was added, the reaction was stirred for another one hour. The deep green mixture was then poured over 1000 mL of ice H2O and filtered. The solid was washed with H2O and allowed to dry. The resulting light yellow solid was thenrefluxed in 170 mL of 50percent HNO3 for 4h. This reaction solution was poured into into 1 L ofice water. A white powder was isolated by suction filtration and washed with H2O (6.1 g,95percent). |
81% | at 70℃; for 1 h; | A solution of 4,4'-dimethyl-2,2'-bipyridine (2.00 g, 10.9 mmol) in concentratedsulfuric acid (50 mL) was heated to 70 C. Potassium dichromate(9.63 g, 32.6 mmol) was added very slowly. Heating and stirring was maintained for 1 h, and then the hot solution was poured onto ice (300 g) and stirred for 1 h. A fine yellow solid formed. This was filtered and washed with water. The crude product was suspendedin 50percent aqueous nitric acid (50 mL) and heated to 120 C for 4 h. Thesuspension was allowed to cool to room temperature and then poured onto ice (300 g). The suspension was allowed to sit overnight,and the resulting white solid was collected by vacuum filtrationand washed with water. The solid was then thoroughly dried in a flask under vacuum to yield a white solid |
77% | With chromium(VI) oxide; sulfuric acid In water for 48 h; | Approximately 1 gram (5.43 mmol) 4,4'-dimethyl-2,2'-bipyridine was added to 40 ml of concentrated H2SO4. The solution was cooled to 0° C., and 3.3 grams of CrO3 was added slowly, forming a yellow solution. The solution was stirred for two days, after which the solution had turned dark green, and was then poured into ice water. A green precipitate formed that was filtered off and washed with water. The precipitate was then suspended in 50 ml water followed by the addition of a 10 M solution of KOH until the solution was basic, about pH equal to or greater than 8. The solution was filtered, the filtrate containing the desired product. The solution was acidified with HCl to precipitate the diacid product as a white solid, which was washed with water, methanol, and ether, and then dried to yield 1.017 grams of product, which was 77percent of the theoretical yield |
34% | Stage #1: With selenium(IV) oxide In 1,4-dioxane for 3.5 h; Reflux Stage #2: for 4 h; Reflux |
4,4'-Dicarboxy-2,2'-bipyridine was synthesized via oxidation of4,4'-dimethyl-2,2'-bipyridine. The procedure outlined below ismodified from that previously reported [110]; however, NMR peakassignments are consistent with the literature [110]. Seleniumoxide (5.27 g, 0.0475 mol) was added to 4,4'-dimethyl-2,2'-bipyridine(2.04 g, 0.0111 mol) in 135 mL of 1,4-dioxane. The reactionmixture was heated to reflux with stirring for 3.5 h. After coolingto room temperature, black solid byproduct was removed by vacuumfiltration; the solvent was removed from the filtrate by rotaryevaporation, yielding a red solid. The resulting red solid was dissolvedin 35 mL of concentrated nitric acid. The solution wasslowly heated to reflux with stirring for 4 h. Red fumes were producedupon the addition of the nitric acid and throughout thereflux. The solution was cooled to room temperature and pouredover 180 mL of ice water to crystallize the yellow solid. The productwas isolated from the solution by vacuum filtration. Yield:0.92 g, 34percent. 1H NMR (CDCl3/TMS, 60 MHz): δ/ppm = 8.62 (d, 2H),8.22 (s, 2H), 7.27 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45 %Chromat. | With nickel(II) bromide hydrate; sodium iodide In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; Inert atmosphere | General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm.x.3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7percent or 20percent of NiBr2*xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35 %Chromat. | With nickel(II) bromide hydrate; sodium iodide In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; Inert atmosphere | General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm.x.3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7percent or 20percent of NiBr2*xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With selenium(IV) oxide In 1,4-dioxane for 44 h; Inert atmosphere; Reflux | General procedure: To a 100ml two-necked RB, dimethyl bipyridine 1 (500 mg, 0.00271 mol, 1.0 equiv.)was taken, added 100 mL of 1,4-dioxane drop wise and stirred to get a homogenous mixtureand the solution was purged with nitrogen for 15 min bubbling nitrogen into the dioxane withstirring. 0. 663 mg of SeO2 (2.2 equiv) was added and refluxed under N2 atmosphere for 44hours. After the completion of the reaction (Monitored by TLC), the reaction mixture waswashed with warm 1,4-dioxane for 2 to 3 minutes and filtered and 1, 4-dioxane was removedunder reduced pressure. The residue was then dissolved in hot distilled ethyl acetate, filteredand again washed with hot ethyl acetate. The ethyl acetate layer was washed with 1MNa2CO3 (250ml) to remove additional carboxylic acid. The organic layer was dried withanhydrous Na2SO4 and concentrated and the residue was purified on alumina using 60percent ethylacetate in petroleum ether to afford the newly synthesized 2,2'-bipyridine 4,4'-dicarbaldehyde was thoroughly characterized by spectroscopic technique such as IR, 1HNMR, 13C NMR and HRMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With n-butyllithium; diisopropylamine In tetrahydrofuran at 0 - 20℃; for 15 h; Inert atmosphere | Diisopropylamine (28.0 mL, 0.160 mol, 2.66 equiv.) was dissolved in dry THF (60 mL) under an argon atmosphere. n-butylithium (107.0 mL, 0.160 mol, 2.66 equiv.) was added dropwise at 0 °C and the solution was stirred for 1 h. Afterwards, a solution of 4,4′-dimethyl-2,2′-bipyridine (11.0 g, 0.060 mol, 1 eq.) in dry THF (300 mL) was slowly added and the orange solution was stirred for 3 h. The reaction mixture was kept at 0 °C and bromooctane (28.0 mL, 0.160 mol, 2.66 equiv.) in dry THF (20 mL) was added. The reaction mixture was then allowed to warm to room temperature. After stirring for 12 h the reaction was quenched first with water (20 mL), then poured into an ice/ water mixture and extracted with diethylether. The resulting yellow oil was recrystallized from hexane, redissolved in DCM, extracted with diluted NaOH, dried over MgSO4, filtered and the solvent removed in vacuo. Drying in high vacuum yielded the desired product (11.02 g, 0.027 mol, 45 percent). 1H NMR (500 MHz, DMSO) δ in ppm= 8.85 (s, 1H), 8.83 (s, 1H), 7.28 (s, 1H), 7.27 (s, 1H), 2.68 (t, J= 7.6 Hz, 4H), 1.62 (p, J= 8.2, 6.9 Hz, 4H), 1.32–1.11 (m, 24H), 0.83 (t, J= 6.5 Hz, 6H). HRMS (ESI) m/z: [M+H]+ calcd. for (C28H44) 409.358; found 409.3581. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With chromium(VI) oxide; sulfuric acid; orthoperiodic acid In lithium hydroxide monohydrate at 20℃; for 24h; | Synthesis of 4,4’-dicarboxy-2,2’-bipyridine 2 (Table 2, entry 7) H5IO6 (1.37g, 6.0 mmol) was dissolved in the mixture of conc. H2SO4(10 mL) and H2O (5 mL) with stirring at room temperature. CrO 3 (0.10g, 1.0 mmol) was added to the solution and dissolved with stirring. Powdered 4,4’-dimethyl-2,2’-bipyridine 1(0.184g, 1.0 mmol) was added in one portion to the solution. The resulted mixture was stirred vigorously at room temperature for 24h. The solution was poured slowly into ice-water (200 mL) with stirring, and the mixture was stirred for 10 min. White precipitate appeared immediately. The precipitate was collected by filtration, and washed well successively with H 2 O and methanol. Vacuum drying gave 0.243g (99%) 4,4’-dicarboxy-2,2’-bipyridine 2 as white powder. |
99% | With potassium permanganate In lithium hydroxide monohydrate for 6h; Reflux; | 5.1.2.3 Preparation of [2,2'-bipyridine]-4,4'-dicarboxylic acid (16) A solution of 4,4'-dimethyl-2,2'-bipyridine (1.02g, 5.43mmol) and potassium permanganate (3.20g, 20.4mmol) in H2O (35mL) was heated at reflux temperature for 6h. The reaction mixture was filtered through Celite and ether was added to the residue to remove the unreacted starting material. The water layer was separated and acidified with 6N aqueous HCl solution. The precipitate was collected by filtration and washed with water to give 16 (1.34g, 99%) as a white powder: mp>300°C; 1H NMR (DMSO-d6, 300MHz, δ; ppm), 8.92 (2H, d, J=4.2Hz), 8.85 (2H, s), 7.91 (2H, d, J=3.3Hz); 13C NMR (DMSO-d6, 75MHz, δ; ppm), 166.5, 156.0, 151.1, 140.0, 123.9, 120.0; MS (ESI) m/z 244.1 (MH+). |
99% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines In sulfuric acid at 65℃; Stage #2: With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 In sulfuric acid at 65℃; for 6h; |
98% | With chromium(VI) oxide; sulfuric acid | |
98% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid | |
98% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 65℃; for 6h; | 2.1.1 1) Synthesis of 4,4'-dicarboxy-2,2'-bipyridine 1.0 g of 4,4-dimethyl-2,2-bipyridine(5.4mmol) was added to the reaction flask, 18mL concentrated sulfuric acid was slowly added dropwise and stirred, the process a lot of heat until the solution was cooled to room temperature and then added potassium dichromate 3.3g (11.3mmol), then the solution becomes dark green, Then reacted at 65 ° C for 6 h. The reaction was completed and cooled to room temperature, the reaction was added to 1000mL of water, a large number of white flocculent precipitate was generated at this time, suction filtration, and then washed with water and methanol to the filtrate was white precipitate was clarified, and then dried in a vacuum oven at 60 18h, Yield 98% |
98% | With chromium(VI) oxide; sulfuric acid In lithium hydroxide monohydrate | |
98% | With chromium(VI) oxide; sulfuric acid; lithium hydroxide monohydrate at 75℃; for 14h; Inert atmosphere; | |
97.8% | With sodium dichromate; sulfuric acid at 20℃; for 0.5h; | |
96% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid In lithium hydroxide monohydrate at 70 - 80℃; Stage #2: With HNO3 In lithium hydroxide monohydrate for 6h; Heating; | |
96% | With potassium permanganate; HNO3 In lithium hydroxide monohydrate at 80℃; for 6h; | 7 Synthesis of 2,2'-bipyridyl-4,4'-dicarboxylic acid In a four-necked flask equipped with a thermometer, a magnet and a reflux condenser,3.7 g (0.02 mol) of analytically pure 4,4'-dimethyl-2,2'-bipyridine was added,Was dissolved in a mixed system of 40 mL of water and 0.4 mL of nitric acid and heated to 80 ° C with stirring,And the temperature was maintained five times by adding potassium permanganate solid (12.6 g, 0.08 mol)Until the previous addition of potassium permanganate reaction to dissolve, then add the next batch of potassium permanganate,The reaction was stopped after 6 hours. After cooling to room temperature, the reaction solution is decompressed under reduced pressure, and after the insoluble matter is to be filtered out,Concentrate hydrochloric acid was added to the filtrate to adjust the pH to 1.Static crystallization, a white crystal precipitation.After crystallization was complete, the filtrate was decompressed under reduced pressure and the resulting white crystals were washed with deionized water.The product was then dried in vacuo to give 4.69 g of the desired product, 2,2'-bipyridyl-4,4'-dicarboxylic acid, in 96% yield. |
95% | With chromium(VI) oxide; sulfuric acid at 75℃; for 4h; | |
95% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70℃; for 2h; | |
95% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With sulfuric acid for 0.25h; Stage #2: With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 at 70 - 80℃; for 1h; | Synthesis of 4,4’-dicarboxy-2,2’-bipyridine (3) To a 125 ml of sulfuric acid (98%), 5.0 g (0.021 mol) of 4,4’-dimethyl-2,2’-bipyridine was added. The obtained mixture was stirred for about 15 min, and a clarified solution with a light pink color was achieved. Then 24 g (0.082 mol) of potassium dichromate was addedcarefully in small portions. And the temperature was held consistently between 70 and 80 °C during this process. After all the dichromate was added, the reaction was stirred for another one hour. The deep green mixture was then poured over 1000 mL of ice H2O and filtered. The solid was washed with H2O and allowed to dry. The resulting light yellow solid was thenrefluxed in 170 mL of 50% HNO3 for 4h. This reaction solution was poured into into 1 L ofice water. A white powder was isolated by suction filtration and washed with H2O (6.1 g,95%). |
95% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 50℃; for 17h; Cooling with ice; | In a 1 L three neck flask, 4,4′-Dimethyl-2,2′-bipyridine (36.8 g, 0.2 mol) was dissolved in 250 mL sulfuric acid (98%) under stirring. The flask was then placed in an ice bath and potassium dichromate (129 g, 0.44 mol) was added slowly in one hour. After addition, the ice bath was replaced with an oil bath and solution was heated to 50° C. under stirring. The temperature was maintained for 16 h to finish the reaction. After cooled down to room temperature, the solution was poured into 3 L cold deionized (DI) water. The afforded precipitates were filtered and subsequently dissolved in 2 L potassium hydroxide solution (1 M). The solution was then acidified by adding 1 L of 2.5 M hydrochloric acid, resulting in white precipitates. The precipitates were filtered, washed with cold DI water and acetone. The white solid was dried in vacuum at 60° C. for 3 days. (46.5 g, yield 95%). 1H NMR (DMSO-d6, 500 MHz): δ (ppm), 7.91 (dd, 2H), 8.85 (d, 2H), 8.91 (dd, 2H), 13.78 (s, 2H). 13C NMR (D2O): δ (ppm), 121.17, 123.26, 146.31, 149.65, 155.64, 172.89. |
94% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid 80 deg C -> 40 deg C; | |
93% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70 - 80℃; for 2h; | |
93% | With sodium dichromate; sulfuric acid for 0.5h; Cooling with ice; | |
93% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70 - 80℃; Stage #2: With HNO3 In lithium hydroxide monohydrate for 4h; Reflux; | 4,4’-Dimethyl-2,2’-bipyridine (5 g) was dissolved in 125 mE of H2504 (98%). K2Cr2O7 was added and the tempera- ture was maintained between .-40-80° C. The reaction was quenched when the solution changed from yellow to black. A yellow solid was obtained after filtration and concentration. This yellow solid was dissolved in 170 mE Of HNO3Q,q) (50%) and refluxed for 4 hours. The solution was then diluted to 1 E, filtered, and washed with water and acetone. After concentrating the solution, the product was obtained (6.12 g, 93%) as a white solid and identified using ‘H NMR spectroscopy. |
93% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70 - 80℃; Stage #2: With HNO3 In lithium hydroxide monohydrate for 4h; Reflux; | 1 4,4'-Dimethyl-2,2'-bipyridine (5 g) was dissolved in 125 mL of H2SO4 (98%).Add K2 Cr2 O7 and maintain the temperature between ~ 70-80 ° C.When the solution changed from yellow to black, the reaction was quenched.A yellow solid was obtained after filtration and concentration.This yellow solid was dissolved in 170 mL of HNO3 (aq) (50%) and refluxed for 4 hours.The solution was then diluted to 1 L, filtered, and washed with water and acetone.After concentrating the solution, the product was obtained as a white solid (6.12 g, 93%) and identified using 1 H NMR spectroscopy. |
92% | With chromium(VI) oxide; sulfuric acid | |
92% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 In sulfuric acid at 80℃; for 12h; | |
91% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 In sulfuric acid at 20℃; for 20h; Stage #2: With HNO3 In lithium hydroxide monohydrate for 4h; Reflux; | |
91% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid Stage #2: With HNO3 | |
91% | With potassium dichromate; sulfuric acid at 40 - 80℃; for 16h; | |
90% | With chromium(VI) oxide In sulfuric acid | |
90% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70 - 80℃; Stage #2: With HNO3 for 4h; Heating; | |
90% | With sodium dichromate; sulfuric acid at 75℃; for 1h; | |
90% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid for 3h; Cooling with ice; | |
90% | With sodium dichromate; sulfuric acid at 75℃; for 0.5h; | |
88% | With sodium dichromate; sulfuric acid at 75℃; for 0.5h; | |
88% | With sodium dichromate; sulfuric acid at 75℃; for 0.5h; | |
87% | With chromium(VI) oxide; sulfuric acid | |
87% | With chromium(III) oxide; sulfuric acid at 0 - 75℃; for 4h; | |
87% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70℃; for 1h; Stage #2: With HNO3 In lithium hydroxide monohydrate for 4h; Reflux; | |
86% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 50℃; for 1h; Stage #2: With lithium hydroxide monohydrate; HNO3 for 4h; Reflux; | |
85% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid | |
85% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 40 - 80℃; | |
84% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With sulfuric acid at 0℃; Inert atmosphere; Stage #2: With chromium(VI) oxide at 0 - 75℃; for 22h; Inert atmosphere; | |
84% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid Stage #2: With HNO3 | |
83% | With chromium(VI) oxide; sulfuric acid at 0 - 80℃; for 8h; | |
81% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 70℃; for 1h; | 4.3.1. [2,2'-Bipyridine]-4,4'-dicarboxylic acid (1). A solution of 4,4'-dimethyl-2,2'-bipyridine (2.00 g, 10.9 mmol) in concentratedsulfuric acid (50 mL) was heated to 70 C. Potassium dichromate(9.63 g, 32.6 mmol) was added very slowly. Heating and stirring was maintained for 1 h, and then the hot solution was poured onto ice (300 g) and stirred for 1 h. A fine yellow solid formed. This was filtered and washed with water. The crude product was suspendedin 50% aqueous nitric acid (50 mL) and heated to 120 C for 4 h. Thesuspension was allowed to cool to room temperature and then poured onto ice (300 g). The suspension was allowed to sit overnight,and the resulting white solid was collected by vacuum filtrationand washed with water. The solid was then thoroughly dried in a flask under vacuum to yield a white solid |
80% | With sodium dichromate; sulfuric acid | |
77% | With chromium(VI) oxide; sulfuric acid In lithium hydroxide monohydrate for 48h; | 2 Approximately 1 gram (5.43 mmol) 4,4'-dimethyl-2,2'-bipyridine was added to 40 ml of concentrated H2SO4. The solution was cooled to 0° C., and 3.3 grams of CrO3 was added slowly, forming a yellow solution. The solution was stirred for two days, after which the solution had turned dark green, and was then poured into ice water. A green precipitate formed that was filtered off and washed with water. The precipitate was then suspended in 50 ml water followed by the addition of a 10 M solution of KOH until the solution was basic, about pH equal to or greater than 8. The solution was filtered, the filtrate containing the desired product. The solution was acidified with HCl to precipitate the diacid product as a white solid, which was washed with water, methanol, and ether, and then dried to yield 1.017 grams of product, which was 77% of the theoretical yield |
75% | With potassium permanganate; lithium hydroxide monohydrate | |
74% | With chromium(VI) oxide; sulfuric acid at 75℃; Cooling with ice; | |
70% | With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid; lithium hydroxide monohydrate; HNO3 at 160℃; for 36h; | |
63% | With potassium-t-butoxide; oxygen In N,N-dimethyl-formamide | |
52% | With sulfuric acid; permanganate(VII) ion | |
50% | With potassium permanganate; sulfuric acid for 12h; Heating; | |
50% | With potassium permanganate; sulfuric acid for 24h; Reflux; | |
50% | With potassium permanganate; sulfuric acid In lithium hydroxide monohydrate for 12h; Reflux; | |
34% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With selenium(IV) dioxide In 1,4-dioxane for 3.5h; Reflux; Stage #2: With HNO3 for 4h; Reflux; | 2.4. Synthesis of 4,4'-dicarboxy-2,2'-bipyridine 4,4'-Dicarboxy-2,2'-bipyridine was synthesized via oxidation of4,4'-dimethyl-2,2'-bipyridine. The procedure outlined below ismodified from that previously reported [110]; however, NMR peakassignments are consistent with the literature [110]. Seleniumoxide (5.27 g, 0.0475 mol) was added to 4,4'-dimethyl-2,2'-bipyridine(2.04 g, 0.0111 mol) in 135 mL of 1,4-dioxane. The reactionmixture was heated to reflux with stirring for 3.5 h. After coolingto room temperature, black solid byproduct was removed by vacuumfiltration; the solvent was removed from the filtrate by rotaryevaporation, yielding a red solid. The resulting red solid was dissolvedin 35 mL of concentrated nitric acid. The solution wasslowly heated to reflux with stirring for 4 h. Red fumes were producedupon the addition of the nitric acid and throughout thereflux. The solution was cooled to room temperature and pouredover 180 mL of ice water to crystallize the yellow solid. The productwas isolated from the solution by vacuum filtration. Yield:0.92 g, 34%. 1H NMR (CDCl3/TMS, 60 MHz): δ/ppm = 8.62 (d, 2H),8.22 (s, 2H), 7.27 (d, 2H). |
31% | With potassium permanganate Reflux; | |
21% | With potassium permanganate In lithium hydroxide monohydrate for 14h; Heating; | |
With potassium permanganate; lithium hydroxide monohydrate | ||
With potassium permanganate | ||
With potassium permanganate In lithium hydroxide monohydrate for 12h; Heating; | ||
With chromium(VI) oxide; sulfuric acid 1) 75 deg C, 4 h, 2) r.t., 10 h; Yield given; | ||
oxidation; | ||
With potassium permanganate In lithium hydroxide monohydrate for 7h; Heating; | ||
With sulfuric acid | ||
With potassium permanganate In acidic aq. solution Heating; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid Heating; | ||
With hydrogenchloride; potassium permanganate In lithium hydroxide monohydrate at 120℃; | ||
With chromium(VI) oxide; sulfuric acid at 0℃; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid In lithium hydroxide monohydrate at 0 - 75℃; | ||
With potassium permanganate; lithium hydroxide monohydrate Heating; | ||
With chromium(VI) oxide; sulfuric acid at 0 - 75℃; for 72h; Inert atmosphere; | ||
1.12 g | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With sulfuric acid; potassium dichromate at 20 - 80℃; for 16h; Stage #2: With HNO3 for 8h; Reflux; | |
With sodium dichromate | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 40 - 75℃; for 6h; Inert atmosphere; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid | ||
Multi-step reaction with 2 steps 1: sulfuric acid; potassium dichromate / 2 h / 70 - 80 °C 2: HNO3 / 2 h / Reflux | ||
With chromium(VI) oxide; sulfuric acid at -0.16 - 74.84℃; for 15h; | 3.1 Synthesis and characterization of homogeneous catalysts 4,4′-Dicarbonyl-2,2′-bipyridine chloride was obtained by reaction of 4,4′-dimethyl-2,2′-bipyridine (Me2bpy) with concentrated sulfuric acid (H2SO4) and chromium oxide (CrO3). The (CO2H)2bpy intermediary product was characterized by 1H and 13C NMR in its sodium salt form using deuterated water as solvent and was found to be similar to the literature report. | |
With sodium dichromate; sulfuric acid In lithium hydroxide monohydrate for 0.5h; | 1 Synthesis of 2,20-bipyridine-4,40-dicarboxylic acid (dcbH2) 2.1 Synthesis of 2,2'-bipyridine-4,4'-dicarboxylic acid (dcbH2) The compound 2,2'-bipyridine-4,4'-dicarboxylic acid (dcbH2) was synthesized as described in the literature [18] . Briefly, 1.60 g (8.6 mmol) of 4,4'-dimethyl-2,2'-bipyridine was added to a solution of 6.28 g (19.4 mmol) of Na2Cr2O7 dissolved in 21 mL of concentrated H2SO4, and the mixture was stirred for 30 min. The resulting solution was added to 220 mL of cold water, and the solid was removed and dissolved in 10% NaOH. The final product was precipitated by the addition of HCl to the solution until it reached pH 2, and the white solid was collected. Yield: 70-80%. Anal. Calc. for C12H10N2O5: C, 57.60; H, 3.49; N, 11.20. Found: C, 57.84; H, 3.34; N, 11.27%. | |
With potassium permanganate | ||
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 75℃; for 1h; Stage #2: With HNO3 for 2h; Reflux; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid | ||
With chromium(VI) oxide; sulfuric acid | ||
With chromium(VI) oxide; sulfuric acid at -0.16 - 74.84℃; for 19h; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 20℃; for 3h; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid at 0 - 80℃; for 0.333333h; | As demonstrated in Scheme 2, to a stirred solution of 4,4'-dimethyl-2,2'-bipyridine 1 ( 10 g, 41 mmol) in sulfuric acid (95-98%, 250 ml) at 0°C was added potassium dichromate (48 g, 163 mmol) in small portions over 20 min. The inside temperature of the mixture was maintained at 70-80°C by occasional cooling using ice/water bath. The resultant mixture was stirred at RT until the inside temperature fell below 40°C (3-4 h) while the color turned deep green. The reaction mixture was poured into ice, filtered and washed with cold water until the filtrate became colorless. The solid was dried, reflux ed in 50% HN03for 4 h and the solution was poured over ice and diluted with water (2 1). The aqueous mixture was cooled to | |
Multi-step reaction with 2 steps 1.1: selenium(IV) dioxide / 1,4-dioxane / 72 h / 115 °C 2.1: silver(I) nitrate; glacial acetic acid / ethanol; lithium hydroxide monohydrate / 24 h 2.2: 0.33 h | ||
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With sulfuric acid for 0.5h; Stage #2: With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 at 70 - 80℃; for 2h; Stage #3: With HNO3 for 6h; Reflux; | ||
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2 In sulfuric acid at 80℃; Inert atmosphere; | ||
With potassium permanganate; lithium hydroxide monohydrate; sodium hydroxide In ethanol for 12h; Reflux; | ||
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid Stage #2: With HNO3 In lithium hydroxide monohydrate for 4h; Reflux; | 1.1 Synthesis of 4,4'-dicarboxy-2,2'-bipyridine (BCB) 4,4'-dimethyl-2,2'-bipyridine (1.0 g) was dissolved in 50 mL of concentrated sulfuric acid, and the temperature was kept slowly. 5.0 g of potassium dichromate was added slowly to carry out oxidation to produce a dark green mixture liquid.The reaction solution was poured into 80 mL of ice water to give a pale yellow precipitate, washed with water, and the solid was refluxed in 30 mL of 50% nitric acid for 4 hours.The reaction solution was poured into ice and diluted with 800 mL of water. A large amount of white precipitate was obtained by suction filtration and washed with water to obtain BCB. | |
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; sulfuric acid In lithium hydroxide monohydrate at 65℃; for 6h; | 1.1.1 (1) Synthesis of 4,4'-dibromomethyl-2,2'-bipyridine and pyridine salt ligands 4,4'-dimethyl-2,2'-bipyridine 5 g was added to a 250 mL single-necked flask equipped with a stirrer, and 80 mL of 98% concentrated H2SO4 was added to the column under vigorous stirring and slowly (to ensure that the temperature did not rise sharply) Add 17g K2Cr2O7, then place it at 65 ° C for 6 h, cool to room temperature, add water and filter, and dry the white powder. | |
With chromium(VI) oxide; sulfuric acid | ||
With potassium permanganate | ||
With sulfuric acid; potassium carbonate at 100℃; for 18h; Inert atmosphere; Schlenk technique; | 2,2'-bipyridine-4,4'-dicarboxylic acid: 4,4’-Dimethyl-2,2’-bipyridal (15.00 g, 81 mmol) wasadded to a 500 mL round bottom flask containing a stir bar and stirred in an ice-bath at 0 °C.Concentrated sulfuric acid (325 mL) was slowly poured into the flask over a 5 min period.Potassium dichromate (54.175 g, 184 mmol) was added slowly with vigorous stirring. Themixture was heated to reflux and stirred in an oil bath at 100 °C for 18 hours until a greensolution was obtained. The solution was then poured over crushed ice into two 1000 mL beakersand the resulting white precipitate was collected via filtration. The solid was then washed withwater (~300 mL) and methanol (~100 mL; three times). The solid was dried in a vacuum ovenand used without any further purification or characterization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: 1 ,6-dibromohexane In tetrahydrofuran at 0℃; for 1.5h; | |
58% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1 ,6-dibromohexane In tetrahydrofuran; hexane for 1.5h; | |
With lithium diisopropyl amide 1.) THF, 20 min, 2.) THF, 0 deg C, 1 h; Yield given. Multistep reaction; |
With lithium diisopropyl amide 1.) THF, -78 deg C, 3.5 h; 2.) THF, -78 deg C, 1 h then to room temp., 1.5 h; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran Inert atmosphere; Cooling; Stage #2: hexadecanyl bromide In tetrahydrofuran at 20℃; Inert atmosphere; Cooling; | 1 Synthesis of fRufbpyhfbpy-Cl 7)1(PF6)2 Synthesis of fRufbpyhfbpy-Cl 7)1(PF6)2 [0129] RubpyC17 refers to the compound [Ru(bpy)2(bpy-C17)](PF6)2. In several embodiments, a 17-carbon tail has been conjugated to one of the three bipyridines to allow for stable insertion into the plasma membrane (Figure 1A). The bpy-C17 ligand was synthesized following established protocols. Briefly, 0.7 mL lithium diisopropylamide (LDA) (2 M) was added dropwise to a cold tetrahydrofuran (THF) solution of 4,4'-dimethyl- 2,2.-bipyridine (0.25g, 1.3 mmol) under an argon atmosphere. After 30 min, into this brown solution was cannulated a solution of dry THF containing 1-bromohexadecane (0.46g, 1.5 mmol). After the reaction mixture had been stirred for several hours at room temperature, the solvent was removed under vacuum. The residue was then dissolved in CH2C12 and washed with 150 mL brine. The product was isolated as an off-white powder. Yield: 345 mg, 65%. |
65% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran for 0.5h; Inert atmosphere; Stage #2: hexadecanyl bromide In tetrahydrofuran at 20℃; | 1 Synthesis of [Ru(hp )2(bp -C17)](PF6)2: RubpyCl ? refers to the compound [Ru(bpy)2(bpy-C17)](PF6)2. In several embodiments, a 17-carbon tail has been conjugated to one of the three bipyridines to allow for stable insertion into the plasma membrane (see Figure 17a). The bpy-C17 ligand was synthesized following established protocols. Briefly, 0.7 mL lithium, diisopropylamide (LDA) (2 M) can be added dropwise to a cold tetrahydrofuran (THF) solution of 4,4'-dimethyl-2,2.-bipyridine (0.25g, 1.3 mmol) under an argon atmosphere. After 30 min, into this brown solution was cannulated a solution of dry THF containing 1 -bromohexadecane (0.46g, 1.5 mmol). After the reaction mixture had been stirred for several hours at room temperature, the solvent was removed under vacuum. The residue was then dissolved in CH2C12 and washed with 150 mL brine. The product was isolated as an off-white powder. Yield: 345 mg, 65%. The desired metal complex was prepared by refluxing for 3 h a methanol solution containing bpy-C17 ligand (0.10 g, 0.25 mmol) and Ru(bpy)2Cl2 (0.09g, 0.21 mmol) and was isolated as the PF6 salt. To obtain the desired counter ion ratio, RubpyCl ? was dissolved in methanol and mixed with a 100 mM aqueous solution of sodium chloride and ammonium hexafluorophosphate. RubpyCl 7 was then extracted into CH2C12 and the solvent was removed. The experimentally determined mass for the product is m/z = 411.195 [M1•] (calculated: 411.196). lH NMR (DMSO-de, 400 MHz) 8.82 (4H, d) 8,76 (1 H, d) 8.70 (1H, d) 8.15 (4H, t) 7.72 (4H, q) 7.53 (6H, m), 7.37 (2H, t) 2.07 (5H, s) 1.25 (30H, m) 0.84 (3H, t). |
50% | With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane for 12h; Ambient temperature; |
With lithium diisopropyl amide 1.) THF, 1.5 h; 2.) THF, 0 deg C, 1.5 h; Yield given. Multistep reaction; | ||
With methyllithium 1) 1.5 h; 2) reflux, 1 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35%Spectr.; 6%Spectr. | With chromium(VI) oxide; periodic acid; In dichloromethane; acetonitrile; at 20℃; for 16h; | (Table 1, entry 5) H5IO6 (1.60g, 7.0 mmol) was dissolved in acetonitrile (30 mL) by vigorous stirring at room temperature. CrO 3 (0.30g, 3.0 mmol) was added to the solution and dissolved with stirring. 4,4?-Dimethyl-2,2?-bipyridine 1 (0.184g, 1.0 mmol) dissolved in CH 2 Cl 2 (3 mL) was added in one portion to the above solution with stirring. The resulted mixture was stirred at room temperature overnight (16h). H 2 O (50 mL) was added to the mixture, and the mixture was stirred for 10 min. NaHSO 3 powder was added portion-wise with stirring until the color of the aqueous layer turned to green. The white precipitate was collected by filtration, and washed successively with H 2 O and methanol. Vacuum drying gave 0.099g white powder that contained 4,4?-dicarboxy-2,2?-bipyridine 2(35%) and 4-carboxy-4?-methyl-2,2?- bipyridine 3 (6%). The ratios of 4,4?-dicarboxy-2,2?-bipyridine 2 and 4-carboxy-4?-methyl-2,2?-bipyridine3 were determined by 1 H-NMR comparing the integrations of 2 at 8.66 and methyl protons of 3 at 2.33 (see Figure S1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With selenium(IV) oxide; sodium metabisulfite In 1,4-dioxane Reflux; | |
75% | With selenium(IV) oxide | |
59% | With selenium(IV) oxide In 1,4-dioxane for 24h; Inert atmosphere; Reflux; |
57% | With selenium(IV) oxide In 1,4-dioxane for 24h; Heating; | |
55% | With selenium(IV) oxide In 1,4-dioxane for 24h; Inert atmosphere; Schlenk technique; Reflux; | |
52% | With selenium(IV) oxide In 1,4-dioxane for 24h; Inert atmosphere; Reflux; | 2.1 Preparation of bipyridine mono aldehyde 2 General procedure: mL) was added drop wise and stirred vigorously to get a homogenous mixture and theresulted solution was purged with nitrogen gas for 15 min. Then 0.3316 g of SeO2 (1.1 equiv)was added and refluxed under N2 atmosphere for 24 hours. After completion of the reaction(Monitored by TLC), the reaction mixture was washed with warm 1,4-dioxane for 3 to 5times and filtered. Later 1,4-dioxane was removed from the reaction mixture under reducedpressure. The residue was then dissolved in hot distilled ethyl acetate, filtered and againwashed with hot ethyl acetate. The ethyl acetate layer was washed with 1M Na2CO3 (250mL) to remove additional carboxylic acid. The organic layer was dried with anhydrousNa2SO4 and chromatographed on silicagel using 40% ethyl acetate in petroleum ether,afforded the product 2 in 52% yield. 279 mg. The newly synthesized bipyridine aldehydewas thoroughly characterized by 1H NMR, 13C NMR, IR and HRMS. |
50% | With selenium(IV) oxide In 1,4-dioxane for 24h; Heating; | |
49.1% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; Inert atmosphere; | |
46% | With selenium(IV) oxide In 1,4-dioxane | |
46.7% | With selenium(IV) oxide for 24h; Reflux; | SeO2 (1.34g,12.1mmol) was added to the solution of 4,4′-dimethyl-2,2′-dipyridyl (2.12g,11.5mmol) in 1,4-dioazne (100mL) and heated to refluxed for 24h. The reaction mixture was filtrated immediately to remove the insoluble solid, the solvent was removed under reduced pressure. Super saturated NaHCO3 (50mL) was added to the residues, then extracted with dichloromethane (CH2Cl2, 40mL*3), after drying over with MgSO4, the organic phase was collected and evaporated. 0.3mol/L Na2S2O5 was added to the residues and stirred for 0.5h, then the mixture was filtrated to remove insoluble solid. Na2CO3 was added to adjust the filtrate to pH=10, the product was extracted with CH2Cl2 (40mL*3), then the organic phase was dry with MgSO4 and evaporated to dryness and dried in vacuum, obtained 1 (4′-methyl-[2,2′-bipyridine]-4-carbaldehyde) as a colorless solid. Yield: 2.5g, 46.7%. |
45% | With selenium(IV) oxide In 1,4-dioxane for 24h; Heating; | |
45% | With selenium(IV) oxide In 1,4-dioxane at 102℃; for 24h; Inert atmosphere; | 1.1 Synthesis of 4-methyl-4'-aldehyde-2,2'-bipyridine 5.27 g of 4,4'-dimethyl-2,2'-bipyridine(28 mmol) and SeO (23.84 g, 34.6 mmol) were added and 260 mL of 1,4-dioxane was added. The mixture was evacuated and subjected to thermal filtration under a nitrogen atmosphere of 102 ° C. for 24 h. The filtrate was spin- Ethyl acetate and then filtered again to remove the undissolved solids to give a yellow solution which was extracted twice with 1.0 M Na2CO3 (2 x 100 mL) and the organic phase was taken; then the organic phase was taken up with 0.3 M (3 x 100 mL) Na2S2O5 and treated with The inorganic phase was adjusted to pH 10 with Na2CO3 and then extracted with CH2Cl2 (4 x 100 mL). Spin drying gave 2.5 g of a white solid in 45% yield. |
44% | With selenium(IV) oxide In 1,4-dioxane for 24h; Inert atmosphere; Reflux; | |
44% | With selenium(IV) oxide In 1,4-dioxane; water at 90℃; for 24h; Inert atmosphere; | 2.3 Synthesis of 2 4,4-dimethyl-2,2′-bipyridine (10 mmol, 1.8 mg), SeO2 (12 mmol, 1.3mg) and water (3 mL) were dissolved in 20mL dioxane and stirred at 90°C for 24h under Ar. After cooling to the room temperature, 0.3M sodium pyrosulfite (Na2S2O5) solution (50 mL) was added and stirred again at room temperature. Then, the pH value was adjusted by NaHCO3 to neutralized value and the mixture was extracted by CH2Cl2 (50 mLX3). The target compound was finally obtained after distillation to give the white solid compound in a 44% yield (870.2 mg). 1H NMR (CDCl3, 600MHz, ppm) δ 10.21 (1H), 8.92 (d, J=12Hz, 2H), 8.61 (s, 1H), 8.31 (s, 1H), 8.74 (s, 1H), 2.49 (s, 3H). |
41% | With selenium(IV) oxide In 1,4-dioxane for 40h; Inert atmosphere; Reflux; Schlenk technique; | 4’-Methyl-2,2’-bipyridine-4-carboxaldehyde Selenium dioxide (0.36 g, 3.2 mmol) was added to a solution of 4,4’-dimethyl-2,2’-bipyridine (0.50 g, 2.7 mmol) in 1,4-dioxane (30 ml) and heated to reflux for 40 h. Over the course of the reaction, the mixture became deep yellow and a black precipitate of metallic selenium appeared. After cooling to room temperature, the selenium metal was filtered off, disposed off properly, and the filtrate evaporated to dryness to give a beige solid. The residue was suspended in ethyl acetate (100 ml), stirred for 30 min, and filtered to remove the remaining brown solid. The light yellow filtrate was extracted with 1.0 M sodium carbonate solution (2 125 ml) and then with 0.3 M sodium metabisulfite solution (2 125 ml). The combined bisulfite extracts were adjusted to pH 10 with solid sodium carbonate and extracted with dichloromethane (5 100 ml). After drying over magnesium sulfate and evaporation of the solvent, the product was obtained as a white solid. Yield: 41% (215 mg, 1.1 mmol). |
41% | With selenium(IV) oxide In 1,4-dioxane at 115℃; for 72h; | 2 4'-Methyl-2,2'-bipyridine-4-carbaldhyde(1) 3-neck round bottom flask (250 mL) in 4,4 '-Dimethyl-2, 2'-bipyridine (5.00 g, 27.1 mmol) and 1,4-Dioxane (120 mL) to dissolve the selenium Selenium dioxide (3.00 g, 27.1 It is added mol).For 3 days under reflux to 115°C, and stirred. After the reaction was completed and concentrate washed with ethanol and then filtered on Celite with hot.NaHCO3 saturated aqueous solution put in the flask was concentrated and extracted with Dichloromethane.Concentrated and dried by MgSO4 put to the organic layer solution was filtered.Put 0.3M Na2S2O5 aqueous solution was concentrated to a flask and stirred and filtered on filter paper for 30 minutes.The aqueous layer washed with ethyl Ethyl acetate is added NaHCO3 (90.0 g).And extracted with Dichloromethane was dried and concentrated to put the MgSO4 solution to the organic layer was filtered.Dichloromethane was recrystallized to give a white solid product.(Yield: 41.0%). |
40% | With selenium(IV) oxide In diethylene glycol dimethyl ether at 130 - 135℃; for 6h; | |
40% | With selenium(IV) oxide In diethylene glycol dimethyl ether for 6h; Heating; | |
40% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; Inert atmosphere; | |
38% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; Inert atmosphere; | |
37% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; | |
37% | With selenium(IV) oxide In 1,4-dioxane for 48h; Reflux; | |
36% | With selenium(IV) oxide In 1,4-dioxane at 101℃; Inert atmosphere; | |
35% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; | |
32% | With selenium(IV) oxide In diethylene glycol dimethyl ether for 12h; Heating; | |
30% | With selenium(IV) oxide In 1,4-dioxane at 20℃; for 12h; Reflux; | |
25% | With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; | 1.1 1,Preparation of polypyridyl ruthenium complex Ru1 4,4'-Dimethyl-2,2'-bipyridine (1.5 g, 8 mmol) and selenium dioxide (887.68 mg, 8 mmol) were refluxed in 100 ml of 1,4-dioxane for 24 hours, after cooling to room temperature, the black solid was filtered off and solvent was removed by evaporation to give a white solid. This solid was dissolved by stirring with 100 ml of ethyl acetate, the insoluble material was filtered off, and the filtrate was washed three times with 20 ml of a 1.0 M sodium carbonate solution. The organic phase was extracted three times with 50 ml of 0.3 M sodium metabisulfite solution, the aqueous phase was combined, the pH was adjusted to 10 with sodium carbonate solution, and extracted four times with 20 ml of chloroform, the organic phase was combined, which was dried over anhydrous sodium sulfate and solvent was removed by evaporation to give a crude product. The crude product was purified by column chromatography eluting with petroleum ether / ethyl acetate (1: 4) to give aldehyde-substituted bipyridine 398 mg was obtained in a yield of 25%. The aldehyde-substituted bipyridine was dissolved in 20 ml of ethanol, stirred with 4 ml of a silver nitrate aqueous solution, then 10 ml of a 1.0 M aqueous sodium hydroxide solution was slowly added and reacted at room temperature for 15 hours. The solvent was removed by evaporation and the solid was washed twice with 4 ml of 1.3 M sodium hydroxide and 4 ml of water, the combined filtrate was extracted three times with 10 ml of chloroform, aqueous phase pH was 3.5 with 4 M hydrochloric acid, the resulting white solid was filtered and dried in vacuo to give carboxy-substituted bipyridine 258 mg, yield 60%. The resulting carboxyl substituted bipyridine (1.3 mmol) was all dissolved in 20 ml DMF, then aminothiazole compound (300 mg, 1.3 mmol), 1-hydroxy-7-azobenzotriazole (1.3 mmol, 177 mg), 4-dimethylaminopyridine (1.3 mmol, 146 mg), 1-ethyl-carbonyldiimide hydrochloride (1.3 mmol, 87 mg) were added thereto, and stirred at room temperature for 6 hours. The obtained solid was filtered, washed four times with 25 ml of water and dried in vacuo to give the Aminothiazole functional group-substituted polypyridine ligand (L1) 457 mg, yield 82%. All the obtained L1 (1.06 mmol) and the compound cis-[Ru(bpy)2Cl2].2H2O (442 mg, 0.85 mmol) were refluxed under 20 ml of ethylene glycol and argon gas protection for 8 hours. After cooling to room temperature, 10 ml of a saturated aqueous solution of ammonium hexafluorophosphate was added,the obtained orange precipitate was filtered, washed once with 15 ml of water, washed three times with 30 ml of anhydrous diethyl ether and dried in vacuo to give crude product. The crude product is subjected to neutral alumina column chromatography, and the only orange component is eluted with acetonitrile to obtain the target polypyridyl ruthenium complex Ru1, amount 616 mg, yield 64% |
23% | With selenium(IV) oxide In 1,4-dioxane | |
17% | With selenium(IV) oxide In 1,4-dioxane for 72h; Reflux; Inert atmosphere; | |
With selenium(IV) oxide | ||
With selenium(IV) oxide In 1,4-dioxane for 24h; Heating; | ||
With selenium(IV) oxide In 1,4-dioxane for 24h; Heating; | ||
Multi-step reaction with 3 steps 1: 83 percent / 3-chloroperoxybenzoic acid / CHCl3 / 48 h / Ambient temperature 2: 1.) acetic anhydride, 2.) 10percent aq. NaOH / 1.) 60-65 deg C, 24 h, 2.) aq. EtOH, reflux, 30 min 3: 58 percent / MnO2 / CH2Cl2 / Ambient temperature; overnight | ||
With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane at 120℃; | ||
With selenium(IV) oxide In 1,4-dioxane | ||
With selenium(IV) oxide In 1,4-dioxane at 110℃; for 24h; | ||
With selenium(IV) oxide In 1,4-dioxane Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane for 4h; Reflux; Inert atmosphere; | ||
With selenium(IV) oxide | FIG. 9 depicts, by way of example, the route for synthesis of ligands bpy-R of staining dye of the present invention.4,4’-Dimethyl-2,2’-bipyridine was oxidized to 4-aldehyde-4’-methyl-2,2’-bipyridine by selenium oxide. Further oxidation of the aldehyde compound by Ag20 (generated in situ by reaction of silver nitrate and sodium hydroxide) gave 4-carboxy-4’-methyl-2,2’-bipyridine (bpy-COOH) as whitepowdet Reductive amination of the aldehyde compoundwith tris(hydroxymethyl)aminomethane in the presenceNaBH4 yielded the bpy-tris ligand. | |
With selenium(IV) oxide In 1,4-dioxane Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane at 110℃; | ||
With selenium(IV) oxide In 1,4-dioxane | ||
With selenium(IV) oxide | ||
With selenium(IV) oxide for 24h; Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane Inert atmosphere; | ||
2.5 g | With selenium(IV) oxide In 1,4-dioxane at 102℃; for 24h; Inert atmosphere; | Preparation of Compound 2: Weigh 1 (5.27 g, 28 mmol), SeO2 (3.84 g, 34.6 mmol), add 260 mL of 1,4-dioxane, vacuum, and heat at 102 ° C for 24 h under nitrogen protection. Filtration; the filtrate was spun dry, and dissolved in 500 mL of ethyl acetate, and then filtered again to remove insoluble solids to give a yellow solution, which was extracted twice with 1.0 M Na2CO3 (2×100 mL) to take the organic phase; 0.3M (3 x 100 mL) of Na2S2O5 was taken as an inorganic phase, and the pH of the inorganic phase was adjusted to 10 with Na2CO3, then extracted with CH2C12 (4×100 mL) and then evaporated to dryness to give 2.5 g of white solid. |
With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane at 120℃; for 24h; | ||
With selenium(IV) oxide In 1,4-dioxane Reflux; | ||
With selenium(IV) oxide In 1,4-dioxane at 102℃; for 24h; | 1.1 1) Synthesis of compound 1 Weigh bipyridine (6.0mmol, 1.1g) and selenium dioxide (18mmol, 2.0g) in a two-neck flask, add the solvent 1,4-dioxane, and react at 102°C for 24h; after the reaction, take advantage of Hot suction filtration, spin-drying; column chromatography separation, the polarity is dichloromethane: methanol (200:1→150:1) to obtain compound 1; | |
With selenium(IV) oxide | ||
With selenium(IV) oxide In 1,4-dioxane | ||
With selenium(IV) oxide In 1,4-dioxane for 168h; Reflux; | ||
Multi-step reaction with 2 steps 1: selenium(IV) oxide / 1,4-dioxane / 22 h / 120 °C 2: sodium carbonate / water; ethyl acetate / 22 h / 120 °C | ||
With selenium(IV) oxide In 1,4-dioxane for 24h; Reflux; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dihydrogen peroxide; trifluoroacetic acid In water at 20℃; | 4.3. General procedure for the synthesis of 4,4'-di-R-bipy-N-oxides 5 and 7a-d General procedure: 30% Aqueous H2O2 (2.25 mL, 22.0 mmol) was slowly added to a solution (suspension in the case of 4a) of 4,4'-di-R-2,2'-bipyridine 2 or 4a-d (15.0 mmol) in TFA (10.0 mL). The reaction mixture was stirred at ambient temperature for 2-4 h (TLC monitoring) and diluted with water (60 mL). The precipitated 7a was filtered off, washed successively with water and acetone, dried in air and used in subsequent reactions without further purification. For isolationof 5 and 7b-d, pH of the aqueous solution was carefully adjusted to 7 with 5 M aqueous NaOH and the products were extracted with CHCl3 (320 mL). The combined extracts were dried over anhydrous MgSO4 and evaporated under reduced pressure (10 Torr). Theresidue was washed with n-hexane (5 mL) affording analytically pure samples of 5 and 7 b-d. 4.3.1. 4,40-Dimethyl-2,20-bipyridine, N-oxide (5). Colorless crystals,yield 2.94 g (98%), mp 94e95 C (lit.15c mp 83e84 C); Rf (Silica gel,eluent CHCl3/MeOH (19:1)) 0.55. The 1H NMR spectra was consistentwith reported data. |
83% | With 3-chloro-benzenecarboperoxoic acid In chloroform for 48h; Ambient temperature; | |
74.6% | With 3-chloro-benzenecarboperoxoic acid In chloroform at 0 - 20℃; for 30h; | Synthesis of 4,4’-dimethyl-2,2’-bipyridine N-oxide (14) General procedure: A solution ofm-chloroperbenzoic acid (3.50 g, 14.0 mmol, purity 69.0 - 75.0%) in150 mL of chloroform was added dropwise into a solution of 13(2.01 g, 10.9 mmol) in chloroform (10 mL) at 0 °C over 3 h. Afterstirring at room temperature for 27 h, the solution was washed with5% aqueous NaHCO3 solution (70 mL × 3). The organic layer wasdried over anhydrous Na2SO4, concentrated and dried under vacuum to give yellowishwhite solid 14 (1.63 g, 8.14 mmol, 74.6 %). When further purification was needed,recrystallization from ether gave yellowish white solid.1H NMR (CDCl3): = 8.73 (s, 1H), 8.57 (d, J = 5.0 Hz, 1H), 8.21 (d, J = 6.6 Hz, 1H),7.94 (d, J = 2.7 Hz, 1H), 7.16 (d, J = 5.0 Hz, 1H), 7.06 (dd, J1 = 6.6 Hz, J2 = 2.7 Hz, 1H),2.44 (s, 3H), 2.40 (s, 3H). IR (KBr): = 3392, 2924, 1588, 1467, 1369, 1291, 1251,1189, 1152, 838, 822, 788, 530 cm-1. Mp: 83-84 °C. |
71% | With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; for 24h; | 69 Reference Example 69 Reference Example 69 4,4'-Dimethyl-2,2'-bipyridyl N-oxide 4,4'-Dimethyl-2,2'-bipyridyl (4.8 g, 26 mmol) and 3-chloroperbenzoic acid (77 %, 8.7 g, 39 mmol) were dissolved in chloroform (25 ml), and the mixture was stirred at room temperature for 24 hrs.. The solvent was evaporated, and the residue was subjected to a silica gel column chromatography.. The fractions eluted with ethyl acetate-methanol (4:1, v/v) were collected, concentrated and crystallized from dimethyl ether to give the titled compound (3.7 g, 71 %).1H-NMR (CDCl3) δ: 2.39 (3H, s), 2.44 (3H, s), 7.06 (1H, dd, J = 2.5, 6.7 Hz), 7.16 (1H, dd, J = 0.7, 4.9 Hz), 7.93 (1H, d, J = 2.5 Hz), 8.20 (1H, d, J = 6.7 Hz), 8.56 (1H, d, J = 4.9 Hz), 8.72 (1H, s). |
66% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 5 - 10℃; for 0.833333h; | |
41.7% | With 3-chloro-benzenecarboperoxoic acid In chloroform 1.) 0-5 deg C, 1 h, 2.) 16 h, 20 deg C; | |
With 3-chloro-benzenecarboperoxoic acid Inert atmosphere; Schlenk technique; Glovebox; | ||
With 3-chloro-benzenecarboperoxoic acid at 20℃; for 48h; Cooling with ice; | 2.1 2.2.1 4,4'-Dimethyl 2,2'-bipyridine N-oxide (2) A solution of freshly crystallized 3-chloroperbenzoic acid (31.30 g, 0.18 mol) in CHCl3 (1.2 L) was slowly dropped (3 h) into a solution of 4,4'-Dimethyl 2,2'-bipyridine 1 (33.42 g, 0.18 mol) in CHCl3 (0.6 L) in ice bath, and let under stirring at r.t. for 48 h. The solvent was evaporated and the residue neutralized with 1 M K2CO3 and heated at 95 °C for 30 min, in order to filter the unreacted 1; the solution was extracted with CHCl3, dried over Na2SO4 and evaporated. The crude product (light brown solid, 27.97 g, η = 77%) was used in the following step; it was further purified by chromatography (EtOAc/MeOH = 9/1) before proceeding to crystallization [1,6]. 1H NMR (CDCl3): δ = 8.70 (t, J = 0.8 Hz, H3'), 8.54 (d, J = 5.0 Hz, H6'), 8.18 (d, J = 6.7 Hz, H6), 7.91 (d, J = 2.7, H3), 7.14 (dq, J5',6' = 5.0, J5',3' = 0.8 Hz, H5'), 7.04 (dd, J5,6 = 6.7, J5,3 = 2.7 Hz, H5), 2.41 (s, CH3), 2.36 (s, CH3) [1,6]. 13C NMR (CDCl3): 149.7, 149.1, 147.6, 146.6, 140.1, 137.4, 128.4, 126.5, 126.59, 126.1, 125.3, 21.4, 20.5. GC-MS (EI): m/z (%) = 201 (41), 200 (77, M+), 199 (77), 184 (70), 183 (68), 172 (62), 171 (100), 157 (40), 156 (58), 144 (69), 142 (32), 132 (81), 119 (65), 93 (37), 92 (72). | |
89 g | With 3-chloro-benzenecarboperoxoic acid In chloroform at 20 - 60℃; for 6h; | 4.1 first step : Preparation of N-oxy-4,4'-dimethyl-2,2'-bipyridine (Compound 9) First, the compound (8) 4,4'-dimethyl-2,2'-bipyridine (100g) and chloroform (600mL) was added to a 2L three-necked flask, stirred and cooled to 0 deg.C uniformly, slowly dropwise m-chloroperbenzoic acid (180g) in chloroform solution (500mL).Gradually raised to room temperature, the reaction was stirred for 3 hours; heating was continued to 60°C , the reaction was three hours.Cooled to room temperature, concentrated under reduced pressure off chloroform, washed with water (1000mL) was diluted, adjusted with solid sodium carbonate to pH 8-9.The mixture was heated to 90-95 deg. C for half an hour, cooled, suction filtered to remove unreacted starting material completely 4,4'-dimethyl-2,2'-bipyridine.The obtained filtrate (1000mL + 500mL × 3) and extracted with dichloromethane and the combined organic phase was dried over anhydrous sulfate.Filtered and the filtrate was concentrated to give a yellow pressurized oil which was recrystallized from petroleum ether to give pale yellow crystals 89g. |
With dihydrogen peroxide; acetic acid; trifluoroacetic acid | ||
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 16.25h; Stage #2: With triphenylphosphine In dichloromethane at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran at 0℃; for 1h; Stage #2: allyl bromide In tetrahydrofuran at 0 - 20℃; | |
95% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: allyl bromide In tetrahydrofuran for 1h; | 1.1 4,4'-Dimethyl-2,2'-bipyridine (10.0 grams) was reacted with 1 equivalent of lithium diisopropylamine in dry tetrahydrofuran (250 ml) at -78 0C for a period of 30 minutes. AIIyI bromide (1 equivalent) was then added, and the reaction mixture stirred for a further hour. The solution was allowed to warm to room temperature, 10 ml of water was then added to the reaction mixture, prior to removal of the solvent using a rotary evaporator. The resultant viscous material was extracted 3 times with diethylether (3 x 50 ml), the combined extracts were then dried using anhydrous sodium sulfate, filtered and then rotary evaporated to yield 4-(3-butenyl)-4'-methyl-2,2'-bipyridyl, a yellow oil. Yield 95 %. |
80% | With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane 1.) 0 deg C, 1 h, 2.) 0 deg C, 30 min; 25 deg C, overnight; |
72% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran; hexane at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1.08333h; Inert atmosphere; Stage #2: 1-bromo-hexane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | |
75% | With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; | |
71% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide at -78℃; for 4h; Inert atmosphere; Stage #2: 1-bromo-hexane at 20℃; for 16h; | Synthesis of Compound 6-2 The THF (100 mL) solution of 4,4’-Dimethyl-2,2’-bipyridine (5) (1.10 g, 6.0 mmol) was added dropwise to the stirred solution of LDA (40 mL, 1.5 M) at -78 protected under argon in 2 hours. Keep -78 for another 2 hours and then 1-Bromhexane (2.2 mL, 15.0 mmol) was added dropwise. After that, the system was allowed to stirring at room temperature for 16 hours. After reaction, the solution was washed with saturated NH4Cl solution and brine. The solution was dried with MgSO4. Purification was carried by running a silica gel column eluted with hexane and ethyl acetate (v/v = 20/1). 1.50 g brown crystal was collected as the final product. Yield: 71%. |
60% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide at -75℃; for 1.5h; Inert atmosphere; Stage #2: 1-bromo-hexane In tetrahydrofuran at -75℃; for 0.5h; Inert atmosphere; | 2.3. Synthesis of 4,4'-dialkyl-2,2'-bipyridine ligands General procedure: Synthesis was carried out using modified procedure [20]. Undernitrogen atmosphere a solution LDA (4.075 ml, 8.1 mmol), waschilled to a preset temperature of -75 °C. This solution was stirredfor 15 min. A solution of 4,4'-dimethyl-2,2'-bipyridine (0.5 g,2.7 mmol in 10 ml THF) was added drop wise to LDA solution.The mixture was further magnetically stirred for another 90 minutes.A solution of 1-bromoalkane (5.9 mmol, 0.80 g for C5, 0.89 gfor C6, 0.97 for C7, 1.06 for C8, 1.11 g for C9) in 10 ml of THF wasadded drop wise to the reaction mixture. The resultant magneticallystirred reaction mixture was kept for 30 minutes at -75 °Cand further slowly heated to temperature 26 °C under nitrogenatmosphere. The yellow coloured solution after 12 h was pouredin 100 ml of millipore water and the organic layer was extractedin ethyl acetate and dried over anhydrous sodium sulphate. Theproduct was purified using column chromatography with ethylacetate in petroleum-ether. The yellow fraction was collected at10% ethyl acetate in petroleum ether and the solvent was reducedby rotary evaporator. The resulting off-white crystalline productwas recrystallized in petroleum ether subsequently and dried invacuum (Scheme 1). |
With lithium diisopropyl amide 1.) THF, heptane, ethylbenzene, -78 deg C, 1 h, 2.) THF, heptane, ethylbenzene, from -78 deg C to RT, overnight; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sulfuric acid; hydrogen bromide; for 6h;Reflux; | The bipyridine (0.90 g, 4.2 mmol) was dissolved in a mixture of 48% HBr (20 mL) and concentrated sulfuric acid (6.7 mL). The resulting solution was refluxed for 6 h and then allowed to cool to room temperature, and 40 mL of water was added. The pH was adjusted to neutral with NaOH solution and the resulting precipitate filtered, washed with water (pH = 7), and air-dried. The product was dissolved in chloroform (40 mL) and filtered. The solution was dried over magnesium sulfate and evaporated to get a white powder. Yield: 1.2 g (85%). 1H NMR (300 MHz, CDCl3) δ (ppm) 4.50 (s, 4H), 7.38 (d, 2H), 8.45 (s, 2H), 8.68 (d, 2H). |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 8h;Inert atmosphere; | 4,40-Dimethyl-2,20-bipyridine (1.23 g, 6.82 mmol), N-bromosuccinimide(2.47 g, 14.3 mmol), and azobis(isobutyronitrile) (0.06 g,0.34 mmol) were stirred under nitrogen in 50 mL carbon tetrachloride.Reflux was maintained near 80 C for 8 h, yielding a clear,dark orange solution and a brown solid. The solid succinimidebyproduct was removed via gravity filtration, and the solventwas removed by rotary evaporation, yielding an orange-yellowoil. 1H NMR (CDCl3/TMS, 300 MHz): δ/ppm = 8.76 (d, 2H), 8.55(s, 2H), 7.59 (d, 2H), 4.50 (s, 4H, CH2). | |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃;Inert atmosphere; | This compound was prepared by modification of two published procedures5, 6 without isolatingthe bromo-bipyridine intermediate product. The starting reagents 4,4'-dimethyl-2,2'-bipyridine(5.0 g, 27 mmol), N-bromosuccinimide (NBS) (10 g, 57 mmol) and azobisisobutyronitrile(AIBN) (0.3 g, 2 mmol) in anhydrous CCl4 (100mL) were heated at 80 C under argon for 12hrs. The mixture was allowed to cool to RT and filtered to remove insoluble solid particles. Thefiltrate was evaporated to near dryness under reduced pressure. The 4,4’-bis(bromomethyl)-2,2′-bipyridine formed was not purified but proceeded to the next reaction step by addingtriethylphosphite (20mL) and heated neat under an argon atmosphere at 100 oC for 8 h. Thesolution was allowed to cool to RT and precipitated in cold hexane to obtain a black oily residue.A short silica gel column was run with acetone to remove most of the black contaminant in theoily residue and then concentrated. The crude product was eluted with ethyl acetate: hexane (2:1,v/v) to remove unreacted 4, 4’-dimethyl-2, 2'-bipyridine, and flushed with acetone: hexane (1:1,v/v) to elute the mono and di functionalized bipyridine phosphonate. The desired product was abrown solid (1.7 g, 14 % overall yield) 1H NMR (500MHz, RT, CDCl3): δ (ppm) 8.60 (d, J = 5.0Hz, 2H), 8.33 (s, 2H), 7.32 (d, J = 5.0 Hz, 2H), 4.04-4.07 (m, 8H), 3.25 (d, JH-P = 22.5 Hz, 4H),1.33 (t, J = 7.0 Hz, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | General procedure: Synthesis was carried out using modified procedure [20]. Undernitrogen atmosphere a solution LDA (4.075 ml, 8.1 mmol), waschilled to a preset temperature of -75 C. This solution was stirredfor 15 min. A solution of 4,4'-dimethyl-2,2'-bipyridine (0.5 g,2.7 mmol in 10 ml THF) was added drop wise to LDA solution.The mixture was further magnetically stirred for another 90 minutes.A solution of 1-bromoalkane (5.9 mmol, 0.80 g for C5, 0.89 gfor C6, 0.97 for C7, 1.06 for C8, 1.11 g for C9) in 10 ml of THF wasadded drop wise to the reaction mixture. The resultant magneticallystirred reaction mixture was kept for 30 minutes at -75 Cand further slowly heated to temperature 26 C under nitrogenatmosphere. The yellow coloured solution after 12 h was pouredin 100 ml of millipore water and the organic layer was extractedin ethyl acetate and dried over anhydrous sodium sulphate. Theproduct was purified using column chromatography with ethylacetate in petroleum-ether. The yellow fraction was collected at10% ethyl acetate in petroleum ether and the solvent was reducedby rotary evaporator. The resulting off-white crystalline productwas recrystallized in petroleum ether subsequently and dried invacuum (Scheme 1). | |
45% | With n-butyllithium; diisopropylamine; In tetrahydrofuran; at 0 - 20℃; for 15h;Inert atmosphere; | Diisopropylamine (28.0 mL, 0.160 mol, 2.66 equiv.) was dissolved in dry THF (60 mL) under an argon atmosphere. n-butylithium (107.0 mL, 0.160 mol, 2.66 equiv.) was added dropwise at 0 C and the solution was stirred for 1 h. Afterwards, a solution of 4,4?-dimethyl-2,2?-bipyridine (11.0 g, 0.060 mol, 1 eq.) in dry THF (300 mL) was slowly added and the orange solution was stirred for 3 h. The reaction mixture was kept at 0 C and bromooctane (28.0 mL, 0.160 mol, 2.66 equiv.) in dry THF (20 mL) was added. The reaction mixture was then allowed to warm to room temperature. After stirring for 12 h the reaction was quenched first with water (20 mL), then poured into an ice/ water mixture and extracted with diethylether. The resulting yellow oil was recrystallized from hexane, redissolved in DCM, extracted with diluted NaOH, dried over MgSO4, filtered and the solvent removed in vacuo. Drying in high vacuum yielded the desired product (11.02 g, 0.027 mol, 45 %). 1H NMR (500 MHz, DMSO) delta in ppm= 8.85 (s, 1H), 8.83 (s, 1H), 7.28 (s, 1H), 7.27 (s, 1H), 2.68 (t, J= 7.6 Hz, 4H), 1.62 (p, J= 8.2, 6.9 Hz, 4H), 1.32-1.11 (m, 24H), 0.83 (t, J= 6.5 Hz, 6H). HRMS (ESI) m/z: [M+H]+ calcd. for (C28H44) 409.358; found 409.3581. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With selenium(IV) oxide; In 1,4-dioxane; for 24h;Reflux; | A mixture of 1,4-dioxane (250 mL), SeO2 (3.07 g, 27.7 mmol,1.2 eq) and 4,4'-dimethyl-2,2'-bipyridine (3.07 g, 27.7 mmol, 1.2 eq) was stirred and refluxed for 24 h. When the reaction mixture turned pale yellow, Se was filtered off using afilter agent (Celite 545). The mixture was then cooled down and the solution was stored in a vacuum to remove solvent. The solid was subsequently recovered and dispersed in 95% ethanol (150 mL), followed by the addition of water (40 mL) containing AgNO3 (4.31 g, 25.4 mmol, 1.1 eq); 1.0 M NaOH (100 mL) was dropped for 20 min. The black mixture was stirred vigorously for 15 h at room temperature; the solvent was evaporated. Ag2O and Ag were filtered off and washed with 1.3 M NaOH aqueous solution. The solution was then extracted with dichloromethane to remove unreacted phenanthroline. The water layer was acidified with 1:1 (v/v) 4.0 N HCl/Acetic acid to a pH of 3.5 and allowed to cool to 0 C over 12 h. The white precipitate was collected by filtration. The solid was dried under vacuum and extracted with purified acetone for 3 d using a Soxhlet apparatus. The solvent was evaporated to obtain the product (2.52 g, 51 %) (Scheme 1). |
With potassium dichromate; sulfuric acid; at 23 - 65℃;Product distribution / selectivity; | Example 1; Synthesis of ligand; 40 g of 4,4'-dimethyl-2,2'-bipyridine was added to 1 liter of concentrated sulfuric acid having a concentration of 98 wt% little by little under stirring to be dissolved in the concentrated sulfuric acid. 55 g of potassium dichromate was added to the resulting solution little by little while the temperature of the solution was maintained at 65C or lower. The reaction mixture was left to be cooled to room temperature (23C) and poured into 12 liters of iced water under stirring. After 2 hours of stirring, the precipitate was collected by filtration and rinsed with water. The obtained solid was re-dissolved in ether and the resulting solution was let pass through a silica gel column to be purified, and the solvent was removed to obtain 3.8 g of a product. It was found that the product was 4-carboxy-4'-methyl-2,2'-bipyridine by 1H-NMR analysis. | |
Example 5; Synthesis of ligand; 6.39 g of 4,4'-dimethyl-2,2'-bipyridine, 4.16 g of selenium dioxide and 375 ml (386.4 g) of 1,4-dioxane were charged into a vessel, refluxed for 24 hours and thermally filtered. After the filtrate was concentrated, 225 ml of ethanol and an aqueous solution of silver nitrate (6.48 g/50 ml) were added to the concentrated filtrate, and further 100 ml of an aqueous solution of sodium hydroxide having a concentration of 1.5 mol/l was added to the resulting solution. This solution was stirred at room temperature for 15 hours. The solution was then filtered. The ethanol in the filtrate was removed under reduced pressure. The residual solution was washed with 150 ml of chloroform. When a mixed solution of acetic acid and 4N hydrochloric acid in a volume ratio of 1:1 was added to the solution after washing to adjust the pH of the solution to 3.5, a white solid precipitated out. This solid was left to stand at 10C for 24 hours, separated by filtration and dried. This solid was extracted with isopropyl alcohol, then the solvent was removed under reduced pressure to obtain 2.26 g of a product. It was found that the product was 4-carboxy-4'-methyl-2,2'-bipyridine by 1H-NMR analysis. 1H-NMR (DMSO-d6,298K, 270MHz, delta(ppm)) ; delta = 8.86 (d, 1H), 8.82 (s, 1H), 8.58 (d, 1H), 8.27 (s, 1H), 7.86 (s, 1H), 7.33 (d, 1H), 2.44 (s, 3H, Me) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1.08333h; Inert atmosphere; Stage #2: 1-Bromopentane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | |
70% | With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0℃; for 3h; | |
65% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide at -75℃; for 1.5h; Inert atmosphere; Stage #2: 1-Bromopentane In tetrahydrofuran at -75℃; for 0.5h; Inert atmosphere; | 2.3. Synthesis of 4,4'-dialkyl-2,2'-bipyridine ligands General procedure: Synthesis was carried out using modified procedure [20]. Undernitrogen atmosphere a solution LDA (4.075 ml, 8.1 mmol), waschilled to a preset temperature of -75 °C. This solution was stirredfor 15 min. A solution of 4,4'-dimethyl-2,2'-bipyridine (0.5 g,2.7 mmol in 10 ml THF) was added drop wise to LDA solution.The mixture was further magnetically stirred for another 90 minutes.A solution of 1-bromoalkane (5.9 mmol, 0.80 g for C5, 0.89 gfor C6, 0.97 for C7, 1.06 for C8, 1.11 g for C9) in 10 ml of THF wasadded drop wise to the reaction mixture. The resultant magneticallystirred reaction mixture was kept for 30 minutes at -75 °Cand further slowly heated to temperature 26 °C under nitrogenatmosphere. The yellow coloured solution after 12 h was pouredin 100 ml of millipore water and the organic layer was extractedin ethyl acetate and dried over anhydrous sodium sulphate. Theproduct was purified using column chromatography with ethylacetate in petroleum-ether. The yellow fraction was collected at10% ethyl acetate in petroleum ether and the solvent was reducedby rotary evaporator. The resulting off-white crystalline productwas recrystallized in petroleum ether subsequently and dried invacuum (Scheme 1). |
Yield | Reaction Conditions | Operation in experiment |
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45% | With selenium(IV) oxide; In 1,4-dioxane; for 44h;Inert atmosphere; Reflux; | General procedure: To a 100ml two-necked RB, dimethyl bipyridine 1 (500 mg, 0.00271 mol, 1.0 equiv.)was taken, added 100 mL of 1,4-dioxane drop wise and stirred to get a homogenous mixtureand the solution was purged with nitrogen for 15 min bubbling nitrogen into the dioxane withstirring. 0. 663 mg of SeO2 (2.2 equiv) was added and refluxed under N2 atmosphere for 44hours. After the completion of the reaction (Monitored by TLC), the reaction mixture waswashed with warm 1,4-dioxane for 2 to 3 minutes and filtered and 1, 4-dioxane was removedunder reduced pressure. The residue was then dissolved in hot distilled ethyl acetate, filteredand again washed with hot ethyl acetate. The ethyl acetate layer was washed with 1MNa2CO3 (250ml) to remove additional carboxylic acid. The organic layer was dried withanhydrous Na2SO4 and concentrated and the residue was purified on alumina using 60% ethylacetate in petroleum ether to afford the newly synthesized 2,2'-bipyridine 4,4'-dicarbaldehyde was thoroughly characterized by spectroscopic technique such as IR, 1HNMR, 13C NMR and HRMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide at -75℃; for 1.5h; Inert atmosphere; Stage #2: 1-bromo-butane In tetrahydrofuran at -75℃; for 0.5h; Inert atmosphere; | 2.3. Synthesis of 4,4'-dialkyl-2,2'-bipyridine ligands General procedure: Synthesis was carried out using modified procedure [20]. Undernitrogen atmosphere a solution LDA (4.075 ml, 8.1 mmol), waschilled to a preset temperature of -75 °C. This solution was stirredfor 15 min. A solution of 4,4'-dimethyl-2,2'-bipyridine (0.5 g,2.7 mmol in 10 ml THF) was added drop wise to LDA solution.The mixture was further magnetically stirred for another 90 minutes.A solution of 1-bromoalkane (5.9 mmol, 0.80 g for C5, 0.89 gfor C6, 0.97 for C7, 1.06 for C8, 1.11 g for C9) in 10 ml of THF wasadded drop wise to the reaction mixture. The resultant magneticallystirred reaction mixture was kept for 30 minutes at -75 °Cand further slowly heated to temperature 26 °C under nitrogenatmosphere. The yellow coloured solution after 12 h was pouredin 100 ml of millipore water and the organic layer was extractedin ethyl acetate and dried over anhydrous sodium sulphate. Theproduct was purified using column chromatography with ethylacetate in petroleum-ether. The yellow fraction was collected at10% ethyl acetate in petroleum ether and the solvent was reducedby rotary evaporator. The resulting off-white crystalline productwas recrystallized in petroleum ether subsequently and dried invacuum (Scheme 1). |
57% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -40 - -5℃; for 1h; Stage #2: 1-bromo-butane In tetrahydrofuran at -20 - 0℃; for 2h; Further stages.; | |
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -0.15℃; for 1h; Stage #2: 1-bromo-butane In tetrahydrofuran; hexane at 24.85℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1.5h; Stage #2: 4-trimethylsilylbenzaldehyde In tetrahydrofuran at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
I) oxidation: heating 4, the 4 [...] -dimethyl -2, the 2-dipyridyl [...] 5g with the sample added to the 250 ml shan Kouping, by adding 80 ml of concentrated H2SO4is placed in the water bath under the condition of stirring vigorously, slowly (ensure that temperature will not be violent rise) by adding 17gK2Cr2O7, then put it in 65 C stirring 6h, cooling to room temperature, water filtration, dried to obtain white powder. II) methoxy : taking the resulting product I 2g and 10mLH2SO4, 100mLCH3OH single-mouth bottle with the sample added, 105 C reflux sleepovers, a large amount of water added to the reaction is finished in white flocculent precipitate, by adding NaOH solution to adjust pH of about 9.0, using CH2Cl2a phase extraction, anhydrous Na2SO4drying, turns on lathe solvent to obtain white crystal, yield 88%. III) reduction of ester: heating II the resulting product 630 mg and NaBH41g with the sample added to the 250 ml single-port the bottle, by adding 80 ml of heavy evaporation of ethanol solution, 80 C reflux 3h, reaction into 20 ml saturated NH4Cl solution, ethanol turns on lathe eliminates, by ethyl acetate extraction with water, reserved ethyl acetate layer, adding anhydrous Na2SO4drying, solvent turns on lathe eliminates, vacuum drying to obtain white powder. IV) hydrogen to replace bromate: the intermediate product obtained in III 100 mg, 6m L48% HBr shan Koupingadds to the belt of the sample solution, slowly adding 9 ml concentrated H2SO4, raw material dissolution, the 100 C oil bath stirring pot reflux 6h, end of the reaction, by adding a small amount of water, stirred, adding KOH to adjust pH to 7.0, producing white precipitation, filtration, CH2Cl2dissolved product, without water Na2SO4drying, filtering turns on lathe eliminates solvent, vacuum dried to obtain 4,4 the- [...]two bromine methyl -2, the 2-dipyridyl [...], yield 45%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.7% | With ammonium acetate; sodium hydroxide; acetic acid; In tetrahydrofuran; toluene; | EXAMPLE 1 Synthesis of 4,4'-dimethyl-2,2'-dipyridyl (V) 4.06 g (0.030 mol) of <strong>[59576-26-0]4-methyl-2-acetylpyridine</strong> and 3.56 g (0.032 mol) of 2-methyl-3-dimethylaminopropenal were dissolved in 40 ml of tetrahydrofuran, 3.63 g (0.032 mol) of potassiumt-butoxidewas added, and heated at 60° C. for 30 minutes. To this mixture solution were added 23.12 g (0.30 mol) of ammonium acetate and 30 ml of acetic acid and, after allowing to react at 60° C. for 2 hours, the internal temperature was raised up to 105° C. to remove tetrahydrofuran, followed by allowing to react at 105° C. for 2 hours. After the reaction solution was allowed to cool, 80 ml of a 25percent NaOH aqueous solution was added, then extracted with4*100 ml ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Toluene was added to the concentrate to recrystallize, thus 3.30 g (yield: 59.7percent) of pale yellow powder being obtained. HPLC analysis (column: ODS-80TM; detecting UV: 254 nm; flow rate: 1.0 ml/min; eluant: methanol/water=40/60; buffer: triethylamine 0.1percent, acetic acid 0.1percent) revealed that purity of the product was 98.0percent, melting point: 170° C. to 172° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.8% | Preparation of 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine, A; A three-neck 250 mL round bottomed flask was charged with 2.475 g [24.46 mmol] of diisopropylamine dissolved in 100 mL of THF. The ambient atmosphere in the flask was replaced with nitrogen and was cooled to -78 C. Addition of 8.78 mL of n-BuLi in hexanes (2.541M) [21.52 mmol] was completed over a 5-minute period via syringe. After 20 minutes the reaction mixture was warmed to 0 C., stirred for 30 minutes, then cooled to -78 C. 1.992 g [10.81 mmol] of 4,4'-dimethyl-2,2'-bipyridine, dissolved in 20 mL of THF, was added via syringe and stirring was continued for 3 hours after which 4.863 g [22.11 mmol] of 3,3,3-trifluoro-1-iodopropane dissolved in 50 mL of THF was added via syringe. After an hour the reaction mixture was allowed to warm slowly to ambient temperature overnight. The reaction was quenched with 150 mL of brine; the residue was extracted into Et2O and dried over Na2SO4. Evaporation afforded crude product. After recrystallization from MeOH, 2.15 g [5.71 mmol] was isolated as a white solid (52.8% yield). Characterization of 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine, A Elemental Analysis: Calcd for C18H18F6N2: C, 57.45; H, 4.82; N, 7.44. Found: C, 57.73; H, 4.74; N, 7.53. (Desert Analytics: sample IB No.96) NMR: 1H (400 MHz, 298K, CDCl3): delta 8.62 (d, 3JHH=5.0 Hz 2H, C-H 6,6') 8.28 (d, 4JHH=1.0 Hz 2H, C-H 3,3') 7.17 (d,d 3JHH=5.0 Hz, 4JHH=1.0 Hz 2H, C-H 5,5') 2.81 (t, 3JHH=7.7 Hz, 4H, CF3CH2CH2CH2-Ar) 2.14 (m,4H, CF3CH2CH2CH2-Ar) 2.01 (m,4H, CF3CH2CH2CH2-Ar) 13C{1H}(100 MHz, 298K, CDCl3): delta 156.45 (2C, 2/2') 150.87 (2C, 4/4') 149.50 (2C, 6/6') 126.9(q, 1JFC=276 Hz, 2C CF3CH2CH2CH2-Ar) 123.97 (2C, 3/3') 121.33 (2C, 5/5') 34.35 (2C CF3CH2CH2CH2-Ar) 33.30 (q, 2JFC=29 Hz, 2C CF3CH2CH2CH2-Ar) 22.73 (2C CF3CH2CH2CH2-Ar) 19F (376 MHz, 298K, CDCl3): delta-71.17 (t, 6F, 3JHF=10 Hz) MS (EI: 70 eV, m/z) 376.35 (M+, 4%), 357.25 (M+-F, 1%), 307.35 (M+-CF3, 6%), 293.25 (M+-CH2CF3, 13%), 280.30 (M+-CH2CH2CF3, 100%), 265.30 (M+-CH2CH2CH2CF3, 2%), UV-Vis (CH2Cl2, 25 C.) lambda, nm (c: cm-1,M-1) 282.2 (18400), 249.2 (12500), 241.9 (12700). IR (microcrystalline powder, cm-1) v 3057 (w), 3027 (m), 3007 (m), 2958 (s), 2878 (s), 1931 (m), 1599 (s), 1557 (s), 1464 (s), 1397 (s), 1268 (s), 1142 (s), 1070 (m), 1019 (m), 975 (m), 911 (m), 839 (s), 816 (w), 784 (w), 764 (w). ; Preparation of 4,4'-bis(4,4,4-trifluorobutyl)-2,2'-bipyridine, 1 A three-neck 250 mL round bottomed flask was charged with 2.475 g [24.46 mmol] of diisopropylamine dissolved in 100 mL of THF. The ambient atmosphere in the flask was replaced with nitrogen and was cooled to -78 C. Addition of 8.78 mL of n-BuLi in hexanes (2.541M) [21.52 mmol] was completed over a 5-minute period via syringe. After 20 minutes the reaction mixture was warmed to 0 C., stirred for 30 minutes, then cooled to -78 C. 1.992 g [10.81 mmol] of 4,4'-dimethyl-2,2'-bipyridine, dissolved in 20 mL of THF, was added via syringe and stirring was continued for 3 hours after which 4.863 g [22.11 mmol] of 3,3,3-trifluoro-1-iodopropane dissolved in 50 mL of THF was added via syringe. After an hour the reaction mixture was allowed to warm slowly to ambient temperature overnight. The reaction was quenched with 150 mL of brine; the residue was extracted into Et2O and dried over Na2SO4. Evaporation afforded crude product. After recrystallization from MeOH, 2.15 g [5.71 mmol] was isolated as a white solid (52.8% yield). Anal. Calcd for C18H18F6N2: C, 57.45; H, 4.82; N, 7.44. Found: C, 57.73; H, 4.74; N, 7.53. NMR (298K, CDCl3): 1H delta 8.62 (d, 3JHH=5.0 Hz 2H, C-H 6,6') 8.28 (d, 4JHH=1.0 Hz 2H, C-H 3,3') 7.17 (d,d 3JHH=5.0 Hz, 4JHH=1.0 Hz 2H, C-H 5,5') 2.81 (t, 3JHH=7.7 Hz, 4H, CF3CH2CH2CH2-Ar) 2.14 (m, 4H, CF3CH2CH2CH2-Ar) 2.01 (m, 4H, CF3CH2CH2CH2-Ar); 13C{1H} delta 156.5 (2C, 2/2') 150.9 (2C, 4/4') 149.5 (2C, 6/6') 126.9 (q, 1JFC=276 Hz, 2C CF3CH2CH2CH2-Ar) 124.0 (2C, 3/3') 121.3 (2C, 5/5') 34.4 (2C CF3CH2CH2CH2-Ar) 33.3 (q, 2JFC=29 Hz, 2C CF3CH2CH2CH2-Ar) 22.7 (2C CF3CH2CH2CH2-Ar); 19F delta-71.17 (t, 6F, 3JHF=10 Hz); MS (EI: 70 eV, m/z) 376.35 (M+, 4%), 357.25 (M+-F, 1%), 307.35 (M+-CF3, 6%), 293.25 (M+-CH2CF3, 13%), 280.30 (M+-CH2CH2CF3, 100%), 265.30 (M+-CH2CH2CH2CF3, 2%), UV-Vis (CH2Cl2, 25 C.) lambda, nm (epsilon: cm-1M-1) 282.2 (18400), 249.2 (12500), 241.9 (12700). IR (microcrystalline powder, cm-1) v 3057 (w), 3027 (m), 3007 (m), 2958 (s), 2878 (s), 1931 (m), 1599 (s), 1557 (s), 1464 (s), 1397 (s), 1268 (s), 1142 (s), 1070 (m), 1019 (m), 975 (m), 911 (m), 839 (s), 816 (w), 784 (w), 764 (w). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -0.16℃; for 0.5h; Stage #2: 9-(bromomethyl)nonadecane In tetrahydrofuran; hexane at 19.84℃; for 168h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0℃; for 1.25h; Stage #2: 5-hexylthiophene-2-carbaldehyde In tetrahydrofuran; hexane at 0 - 20℃; for 6.33333h; Stage #3: With water In tetrahydrofuran; methanol; hexane | 1.2 (2) Synthesis of 4,4'-bis[2-hydroxy-2-(5-hexyl-2-thienyl)ethyl]-2,2'-bipyrid ine Under a nitrogen atmosphere at 0°C, 16ml (0.0256mol) of n-butyllithium (1.6M in hexane) were added to a dry tetrahydrofuran (60ml) solution of diisopropylamine (3.1ml, 0.0123mol). The light yellow solution was then stirred for 20 minutes at 0°C. A dry tetrahydrofuran (50ml) solution of 4,4'-dimethyl-2,2'-bipyridine (1.74g, 0.0135mol) was then added by dripping. The reaction solution, which became dark orange-red in color, was stirred at 0°C for 75 minutes, and then a dry tetrahydrofuran (25ml) solution of 5-hexylthiophene-2-carbaldehyde (3.72g, 0.027mol) was added over a period of 5 minutes. This was stirred at 0°C for 75 minutes and then stirred further at room temperature for 5 hours. Thereafter, 3ml of methanol was added to the solution to stop the reaction. 50ml of water were then added, and a product was extracted three times with 50ml of methylene chloride. 50ml of an organic layer was washed with 50ml of saline water and dried with anhydrous magnesium sulfate. After distillation, 3.0g of a white-colored product was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With lithium diisopropyl amide In tetrahydrofuran at -40℃; for 0.5h; Inert atmosphere; Stage #2: 5-hexylthiophene-2-carbaldehyde In tetrahydrofuran at -40℃; for 6h; Inert atmosphere; Stage #3: With trifluoroacetic anhydride In dichloromethane for 12h; | 2.a Under an argon atmosphere, a solution of 2.0 M-lithium diisopropylamide (LDA) in THF (2.5 mL, 5 mmol) was slowly added dropwise to a solution of 4,4-dimethylbipyridine (0.5 g, 2.48 mmol) in anhydrous THF (80 mL, -78°C). Next, after the obtained reaction system was stirred at -40°C for 30 minutes, a solution of a thiophene ligand (0.98 g, 5.0 mmol) in THF (50 mL) was added and the mixture was further stirred for 6 hours and then the reaction system was heated to room temperature. Successively, water (100 mL) and dichloromethane (200 mL) were added to the obtained reaction system to carry out phase separation. The obtained organic layer product was dissolved in dichloromethane (100 mL) and trifluoroacetic anhydride (TFAA, 2 mL, 14.3 mmol) was added thereto and the mixture was allowed to react for 12 hours. The obtained product was refined by an aluminum column (dichloromethane) to obtain a bipyridine ligand represented by the formula (45) (yield 53%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 54 %Chromat. 2: 21 %Chromat. 3: 20 %Chromat. | With nickel(II) bromide hydrate; sodium iodide In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; Inert atmosphere; | General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm×3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7% or 20% of NiBr2·xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
695.3 mg (2.24 mmol) of BMDBM and 154.8 mg (0.84 mmol) of 4,4'-dimethyl-2,2'-bipyridine (4dm-Bpy) were dissolved in 25.0 g of methanol. To the liquid, a solution prepared by dissolving 109.2 mg (2.73 mmol) of sodium hydrate in 10.0 g of methanol was added dropwise, and then stirred for one hour. Subsequently, a solution prepared by dissolving 256.5 mg (0.7 mmol) of europium (III) chloride hexahydrate in 5.0 g of methanol was added dropwise to the mixture, and continued to stirr for two hours. The produced precipitate was suction filtrated, washed with methanol, and dried to obtain Eu(BMDBM)34dm-Bpy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With chloro-trimethyl-silane; In N,N-dimethyl-formamide; at 100℃; for 48h; | The antenna ligand for NC-11 was synthesized in a pressure tube containing 4,4'- dimethyl-2,2'-bipyridine (2g, 0.0108 mol) and 9-benzyl- H-carbazole-3-carbaldehyde (6.19g, 0.0217mol) and 0.065mol of trimethylchlorosilane, and magnetic stirrer bar in 70ml DMF. The reaction temperature was raised to 100C and allowed to run for 48 hours with continuous stirring. During the course of the reaction, the color of the reaction mixture changed to yellow and turned orange on cooling and release of pressure from the tube. The solvent was removed using rotary evaporator, and the orange product was recovered by addition of water and filtration under vacuum to furnish the ancillary ligand in 84% yield. Scheme 3 shows a schematic of the synthesis of the antenna ligand for NC-11. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With chloro-trimethyl-silane In N,N-dimethyl-formamide at 100℃; for 48h; | 1 Synthesis of the antenna ligand 4,4'-bis((E)-2-(9-ethyl-9H-carbazol-3-yl)vinyl)-2,2'-bipyridine for NC-10 The antenna ligand for NC-10 was synthesized in a pressure tube containing 4,4'- dimethyl-2,2'-bipyridine (2g, 0.0108 mol) 9-ethyl-9H-carbazole-3-carbaldehyde (4.86g, 0.0217mol) and 0.065mol of trimethylchlorosilane, and a magnetic stirrer bar in 70ml DMF. The reaction temperature was raised to 100 °C and allowed to run for 48 hours with continuous stirring. During the course of the reaction, the color of the reaction mixture changed to yellow and turned orange on cooling and release of pressure from the tube. The solvent was removed using rotary evaporator, and the orange product was recovered by addition of water and filtration under vacuum to furnish the ancillary ligand in 81% yield. Scheme 1 shows a schematic of the synthesis of the antenna ligand for NC-10. |
81% | With chloro-trimethyl-silane In N,N-dimethyl-formamide at 100℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51.5% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; for 2h; Inert atmosphere; Stage #2: 4-(diphenylamino)benzaldehyde In tetrahydrofuran; hexane at -78 - 20℃; for 12h; Inert atmosphere; | Diisopropylamine (2.10 mL, 13.3 mmol, 1.70 equiv.) was dissolved in dry THF (30.0 mL) under a nitrogen atmosphere and the solution cooled to 0 °C. n-butyl lithium in hexane (2.50 M in hexane, 5.60 mL, 14.1 mmol, 1.80 equiv.) was added and the solution stirred for 1 h. The solution was then cooled to-78 °C, 4,4′-dimethyl-2,2′-bipyridine (2.00 g, 10.9 mmol, 1.50 equiv.) added, warmed to 0 °C and stirred for 2 h. 4-(N,N-diphenylamino)benzaldehyde (2.00 g, 7.30 mmol, 1.00 equiv.) was added at-78 °C and the mixture was allowed to warm to r.t. and stirred for 12 h. The reaction was quenched with an excess of ammonium chloride solution (0.83 g, 15.5 mmol, 2.20 equiv.) and filtered. THF was removed in vacuo and the residue extracted with DCM and water (3 × 50.0 mL). The organic layer was dried over MgSO4 prior to removal of the solvent. The crude product was purified by column chromatography (eluent DCM:EtOAc=6:1) affording 1-(4-(N,N-diphenylamino)phenyl)-2-(4′-methyl- 2,2′-bipyridin- 4-yl)ethanol) 12 as a yellow solid (1.70 g, 3.72 mmol, 51.5 %). 1H NMR (700 MHz; CDCl3): in ppm= 8.53 (ddd, J= 1.9, 7.8, 3.9 Hz, 2H), 8.24 (dd, J= 12.2, 1.9 Hz, 2H), 7.25-6.98 (m, 16H), 4.99 (dd, J= 12.0, 5.6 Hz, 1H), 4.00-3.93 (m, 1H), 3.10 (d, J= 5.5 Hz, 1H), 2.93-2.87 (m, 1H), 2.78-2.71 (m, 1H), 2.44 (d, J= 2.3 Hz, 1H), 1.58-1.51 (m, 2H), 1.37-1.22 (m, 10H), 0.88 (t, J= 6.8Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium sulfate; dibenzoyl peroxide; In tetrachloromethane; water; | 3. Synthesis of a mono-anionic ligand (salt form): sodium (4'-methyl-2,2'-bipyridin-4-yl)methanesulfonate (6) To 4,4'-dimethyl-2,2'-bipyridine (20 g, 108.5 mmol) in 400 mL of anhydrous tetrachloromethane was added 19 g (106.8 mmol) of N-Bromosuccinimide and 2.6 g of benzoyl peroxide. The mixture was refluxed overnight and cooled to room temperature. The solid was removed by filtration and the filtrate concentrated by rotary-evaporation. The column chromatography with triethylamine treated silica column afforded 6 g of 4-(bromomethyl)-4'-methyl-2,2'-bipyridine (5), which was mixed with 4.9 g (38.9 mmol) of Na2SO3 in 100 mL of water. The cloudy mixture was refluxed for six hours. When it was still hot, the supernatant was concentrated to about 30 mL and cooled to room temperature. The yellow precipitate was collected by filtration and washed with dichloromethane to afford 3.6 g of 4'-methyl-2,2'-bipyridin-4-yl)methanesulfonate (6). 1H NMR (D2O, 400 MHz, See ) delta 8.81 (1H), 8.67 (1H), 8.44 (1H), 8.30 (1H), 7.88 (1H), 7.76 (1H), 4.42 (2H), 2.73 (3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In methanol; for 0.5h; | General procedure: A solution of Cu(ClO4)2 (13.1 mg, 0.05 mmol) in water (10 mL) was added to a stirred solution of Hsf (20.0 mg, 0.05 mmol) in MeOH-EtOH (1:1, 10 mL). The mixture was stirred for 30 min, and then, the precipitate was filtered off. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With sodium hydroxide In ethanol; water at 70℃; for 12h; | 2.2. Synthesis of [Eu(btfa)3(dmbpy)] 1 An ethanolic solution (20 mL) containing EuCl36H2O (366 mg,1 mmol) and 4,40-dimethyl-2,20-bipyridine (dmbpy) (184 mg,1 mmol) was added dropwise to an ethanolic solution (10 mL) of4,4,4-trifluoro-1-phenyl-1,3-butanedione (btfa) (648 mg, 3 mmol)previously deprotonated with NaOH aqueous solution (3 mL,1 mol.L1). The mixture was stirred, under reflux (70 C) for 12hs. The resulting solution was allowed to stand and after one week,light pink block crystals suitable for single crystal X-ray diffractionanalysis were obtained. Yield: 57%. Anal. Calc. for C42H30EuF9N2O6:C, 51.2; H, 3.38%; N, 2.84 Found: C, 51.1; H, 3.37%; N, 2.86. Thecompound is stable in air, non hygroscopic and soluble in ethanol,methanol and acetone. When exposed to UV light, the compoundexhibited very intense red luminescence. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.7% | Stage #1: ruthenium trichloride; 4,4'-dimethyl-2,2'-bipyridines With lithium chloride In N,N-dimethyl-formamide at 140℃; for 8h; Inert atmosphere; Stage #2: water | 2.5 Synthesis of cis- [Ru (dmb) 2 (Cl) 2] · 2H2O In a 50 mL three-necked flask, dmb (0.73 g, 4 mmol), lithium chloride (1.26 g, 30 mmol), ruthenium trichloride (0.6 g, 2 mmol) were mixed in DMF and heated at 140 ° C under argon Reflux reaction 8h. After stopping the reaction, the mixture was cooled to room temperature, acetone was added, and the mixture was allowed to stand overnight at -4 ° C, and the mixture was purged to obtain a purple-black crystal. The crystals were eluted with ice water and acetone and dried in vacuo to give a purpleish crystal in 85.7% yield. |
85.7% | With lithium chloride In N,N-dimethyl-formamide at 140℃; for 8h; Inert atmosphere; | 5.1 1-Preparation of cis-[Ru(dmb)2Cl2]·2H2O: In a 50 mL three-neck flask: dmb (0.73 g, 4 mmol), lithium chloride (1.26 g, 30 mmol), ruthenium trichloride(0.6g, 2mmol) was dissolved in 10ml DMF, heated to 140°C under argon protection and refluxed for 8h; after the reaction was completed,Cool to room temperature and transfer to a single-mouth flask. Rotary evaporation removes most of the DMF. The remainder is washed with tap water and then added.30 ml of acetone was stirred well, then allowed to stand at -4°C overnight, and suction-filtered to obtain purple-black crude product; and then rinsed with ice water and acetone.The body was dried in vacuum to obtain purple-black crystals, namely cis-[Ru(dmb)2Cl2]·2H2O, with a yield of 85.7% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | Stage #1: 1-Phenyl-4,4,4-trifluorobutane-1,3-dione With sodium hydroxide In ethanol; water Stage #2: 4,4'-dimethyl-2,2'-bipyridines; ytterbium(III) chloride hexahydrate In ethanol; water at 70℃; for 12h; | 2.2. Synthesis of [Ln(btfa)3(4,4′-dmbpy)] complexes An ethanolic solution (20 mL) containing YbCl3·6H2O (386 mg,1 mmol) and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmbpy) (184 mg,1 mmol) was added dropwise to an ethanolic solution (10 mL) of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (btfa) (648 mg, 3 mmol) previouslydeprotonated with NaOH aqueous solution (3 mL, 1 mol·L-1). The mixturewas stirred, under reflux (70 °C) for 12 h. The solution was allowedto stand and after one week, light green block crystals were obtained.[Yb(btfa)3(4,4′-dmbpy)] 1: green; yield: 57%. Anal. Calc. forC42H30YbF9N2O6: C, 50.3; H, 3.02; N, 2.79 ; Yb: 17.2. Found: C, 50.5; H,3.04; N, 2.77; Yb: 17.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: 1-Phenyl-4,4,4-trifluorobutane-1,3-dione With sodium hydroxide In ethanol; water Stage #2: 4,4'-dimethyl-2,2'-bipyridines; gadolinium(III) chloride hexahydrate In ethanol; water at 70℃; for 12h; | 2.2. Synthesis of [Ln(btfa)3(4,4′-dmbpy)] complexes General procedure: An ethanolic solution (20 mL) containing YbCl3·6H2O (386 mg,1 mmol) and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmbpy) (184 mg,1 mmol) was added dropwise to an ethanolic solution (10 mL) of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (btfa) (648 mg, 3 mmol) previouslydeprotonated with NaOH aqueous solution (3 mL, 1 mol·L-1). The mixturewas stirred, under reflux (70 °C) for 12 h. The solution was allowedto stand and after one week, light green block crystals were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: 1-Phenyl-4,4,4-trifluorobutane-1,3-dione With sodium hydroxide In ethanol; water Stage #2: 4,4'-dimethyl-2,2'-bipyridines; neodymium(III) chloride hexahydrate In ethanol; water at 70℃; for 12h; | 2.2. Synthesis of [Ln(btfa)3(4,4′-dmbpy)] complexes General procedure: An ethanolic solution (20 mL) containing YbCl3·6H2O (386 mg,1 mmol) and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmbpy) (184 mg,1 mmol) was added dropwise to an ethanolic solution (10 mL) of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (btfa) (648 mg, 3 mmol) previouslydeprotonated with NaOH aqueous solution (3 mL, 1 mol·L-1). The mixturewas stirred, under reflux (70 °C) for 12 h. The solution was allowedto stand and after one week, light green block crystals were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.26% | at 80℃; for 72h; | General procedure: Three novel Ln(III) complexes, namely, 1e3, were synthesized byadministering 2.0mmol H-ClQ and 1.0mmol dmbpy to the mixedchelating ligands with 1.0mmol Pm(NO3)36H2O, Yb(NO3)36H2O,and Lu(NO3)36H2O in CH3OH/CH2Cl2 (2.5mL:0.3 mL) at 80 C for 3days (Scheme 1). The Ln(III) complexes 1e3 were characterizedthrough IR spectroscopy (Figs. S1eS3), single-crystal X-ray diffractionanalysis (Figs.1e3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.11% | at 80℃; for 72h; | General procedure: Three novel Ln(III) complexes, namely, 1e3, were synthesized byadministering 2.0mmol H-ClQ and 1.0mmol dmbpy to the mixedchelating ligands with 1.0mmol Pm(NO3)36H2O, Yb(NO3)36H2O,and Lu(NO3)36H2O in CH3OH/CH2Cl2 (2.5mL:0.3 mL) at 80 C for 3days (Scheme 1). The Ln(III) complexes 1e3 were characterizedthrough IR spectroscopy (Figs. S1eS3), single-crystal X-ray diffractionanalysis (Figs.1e3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.65% | at 80℃; for 72h; | General procedure: Three novel Ln(III) complexes, namely, 1e3, were synthesized byadministering 2.0mmol H-ClQ and 1.0mmol dmbpy to the mixedchelating ligands with 1.0mmol Pm(NO3)36H2O, Yb(NO3)36H2O,and Lu(NO3)36H2O in CH3OH/CH2Cl2 (2.5mL:0.3 mL) at 80 C for 3days (Scheme 1). The Ln(III) complexes 1e3 were characterizedthrough IR spectroscopy (Figs. S1eS3), single-crystal X-ray diffractionanalysis (Figs.1e3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | 4,4-dimethyl-2,2-bipyridine (921 mg, 5.00mmol) and diisopropylamine(1.48 mL, 10.5mmol) were dissolved in THF (50mL), and the solution was cooled to 78 C. A hexane solutionof n-butyllithium (1.5 M, 6.91 mL, 10.5mmol) was added tothe solution dropwise. After stirring for 2 h, 1 (1.78 g, 11.0mmol) was added. The solution was additionally stirred at78 C for 2 h, and then gradually warmed up to r.t. withcontinuous stirring overnight. H2O was added to the solutionand the product was extracted twice with ether. The combinedorganic layers were washed with brine and dried over MgSO4.The solvent was removed under reduced pressure to obtain thecrude material, which was purified by silica-gel chromatography(eluent: CH2Cl2/MeOH 95:5 v/v) to obtain a whitesolid. Yield: 1.54 g (70%). 1HNMR (400 MHz, CDCl3): /ppm, 8.58 (d, J = 5.2 Hz, 2H), 8.29 (s, 2H), 8.29 (d, J = 4.8Hz, 2H), 7.18 (s, 2H), 7.10 (dd, J = 4.8 Hz, 1.6 Hz, 2H), 7.04(dd, J = 5.2 Hz, 1.2 Hz, 2H), 3.00 (m, 8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In ethanol; water; for 3h;pH 6 - 7; | General procedure: The aqueous solution of Eu(NO3)3.6H2O (1mmol) was treated with threefold excess of ethanolic solution of HIPA (3mmol) and the resulting mixture was thoroughly mixed on magnetic stirrer. The aqueous solution of NaOH was added drop wise to adjust the pH of mixture by 6-7. After constant stirring of 3 hr, off white precipitates of C1 binary complex were appeared which were isolated by vacuum filtration, washed with ethanol and water respectively, and then dried in desiccators.[19] Similarly, ternary complexes C2-C5 were synthesized by adding ethanolic solution of dmbipy, dipy, dmph and phen (1mmol) respectively, to the reaction mixture of europium(III) nitrate (1mmol) and ligand HIPA (3mmol) prior to adjustment of pH of the solution. Binary complex of gadolinium ion with ligand HIPA [Gd(IPA)3.2H2O] is synthesized by similar method as of C1 to calculate the triplet state of ligand. The synthetic routes of ligand HIPA and europium (III) complexes C1-C5 are shown in Fig. 1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium <i>tert</i>-butylate In dimethyl amine at 90℃; for 20.5h; Inert atmosphere; | |
64% | Stage #1: 4,4'-dimethyl-2,2'-bipyridines With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide for 1.5h; Inert atmosphere; Stage #2: 4-dimethylamino-benzaldehyde In N,N-dimethyl-formamide at 90℃; for 19h; Inert atmosphere; | 1 4,4'-Bis[p-(N,N-dimethylamino)styryl]-2,2'-bipyridine The synthesis of 4,4'-Bis[p-(N,N-dimethylamino)styryl]-2,2'-bipyridine is already published (Wu, Q. et al) but in this study another synthetic route was employed.4,4'- Dimethyl-2,2'-bipyridine (1000 mg, 5.43 mmol, 1.0 equiv.) was dissolved in dry DMF (100 mL) under nitrogen atmosphere and potassium tert-butoxide (2437 mg, 21.72 mmol, 4.0 equiv.) was added slowly. After 1.5 h of stirring, 4- (Dimethylamino)benzaldehyde (1701 mg, 11.40 mmol, 2.1 equiv.) was added to the reaction mixture. The colour of the solution turned to yellow and the mixture was heated at 90 °C for 19 h. After that the mixture was poured into H2O (400 mL) and the suspension cooled down to 5 °C. The crude product which precipitated, was filtered and washed with H2O and Et2O. The product was isolated by recrystallization from DCM/Pentane.1541 mg of (E,E’)-4,4'-Bis[p-(N,N-dimethylamino)styryl]-2,2'-bipyridine (3.45 mmol, 64 %) were yielded as a yellow solid. |
With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 90℃; for 19h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In water; N,N-dimethyl-formamide at 120℃; for 72h; Sealed tube; | 2.2. Synthesis of [Zn(DBT) (4,40-dmbpy) (H2O)]n (1) A mixture of Zn(NO3)26H2O (29.7 mg, 0.1 mmol), 4,40-dmbpy (18.4mg, 0.1 mmol) and H2DBT (32.4 mg, 0.1 mmol) in 6 mL of DMF/H2O (v/v 1:2) was sealed in a 25 mL Teflon-lined autoclave and heated at 120C for 3 days. Colorless block crystals of 1 were obtained by filtration andrinsed with ethanol and water three times with a yield of 70% based onH2DBT. Element analysis for C20H16Br2N2O5Zn (589.54), C, 40.75; H,2.74; N, 4.75. Found: C, 40.58; H, 2.80; N, 4.72. IR (KBr): ν (cm1) 3620(m), 3409(s), 2971 (s), 1697 (w), 1545(s), 1512 (s), 1477 (m), 1443(m), 1395 (s), 1325 (w), 1055 (m), 829 (w), 802 (w), 775 (w), 610 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In ethanol; water at 20℃; | 2.3. Synthesis General procedure: Complexes 1, 2 and 4 are prepared by the following general method:an aqueous solution of metal(II) acetate (0.3 mmol) and an ethanol solutionof corresponding polypyridine ligand (0.3 mmol) were mixed andthe resulting solution was stirred for 5 min. To the mixture was added anethanol solution of HL (0.6 mmol). The complexes precipitated quicklyafter stirring the mixture at room temperature and filtered off, washedwith ethanol and dried in air. |
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H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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