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CAS No. : | 29841-69-8 | MDL No. : | MFCD00082751 |
Formula : | C14H16N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PONXTPCRRASWKW-KBPBESRZSA-N |
M.W : | 212.29 | Pubchem ID : | 6931238 |
Synonyms : |
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 66.12 |
TPSA : | 52.04 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.6 cm/s |
Log Po/w (iLOGP) : | 2.11 |
Log Po/w (XLOGP3) : | 1.4 |
Log Po/w (WLOGP) : | 1.74 |
Log Po/w (MLOGP) : | 2.41 |
Log Po/w (SILICOS-IT) : | 2.17 |
Consensus Log Po/w : | 1.97 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.4 |
Solubility : | 0.855 mg/ml ; 0.00403 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.1 |
Solubility : | 1.7 mg/ml ; 0.008 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.3 |
Solubility : | 0.0106 mg/ml ; 0.0000501 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.98 |
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 |
---|---|---|
88% | With sodium hydroxide In dichloromethane at 0 - 5℃; for 3 h; Inert atmosphere | Synthesis of Compound 2009: To a 2-L, three-neck, round-bottom flask equipped with a temperature probe, magnetic stir bar, nitrogen inlet, and addition funnel were added (lS,2S)-(-)-l,2-diphenylethylenediamine (20 g, 0.094 mol) and dichloromethane (160 mL). The mixture was cooled to 0-3 0C and a 1 M solution of sodium hydroxide (160 mL) was added dropwise while maintaining the temperature below 5 0C. To this mixture was added a solution of toluenesulfonyl chloride (17.9 g, 0.094 mol) in dichloromethane (320 mL) dropwise over a 2-h period. The biphasic mixture was stirred at 0-5 0C for an additional 1 h and the reaction was deemed complete by TLC (50percent EtO Ac/heptane, UV). Phases were separated and the organic phase was washed with water (2 x 320 mL) and brine (320 mL), dried over sodium sulfate and concentrated to a crude solid. The solid was dissolved in toluene (200 mL) at 70-80 0C and heptane (300 mL) was added portionwise while maintaining this temperature. The resulting slurry was cooled and stirred at 20-25 0C for 1 h and then cooled and stirred at 0-5 0C for 10 min. The solids were filtered and washed with a 50percent solution of toluene in heptane (3 x 1 bed volume) to give compound 2009 (30.24 g, 88percent) as a white powder. |
82.3% | With sodium hydroxide In dichloromethane; water at 0 - 20℃; for 3 h; | The procedure is the same as in Example 1,Except that (1S, 2S) -1,2-diphenylethylenediamine (3.0 g, 14.1 mmol)Added to 50mLDCM,After stirring and dissolving,A 15 mL aqueous solution of 2N NaOH was added,Cooling to 0 ,A solution of p-toluenesulfonyl chloride (2.65 g, 14.1 mmol)In dichloromethane (30 mL)After maintaining the reaction at 0 ° C for 1 hour,The temperature was raised to room temperature for 2 hours,HPLC detection reaction ended.The reaction solution was poured into saturated sodium chloride solution (30 mL)Stir for 10 minutes,After stratification,The aqueous phase was extracted once with DCM (30 mL)Combine organic phase,dry,The dichloromethane was removed by distillation under reduced pressure,Get crude.Recrystallization from petroleum ether / ethyl acetate system gave yellow solid Compound I (4.48 g, 82.3percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In tetrahydrofuran; water at 0 - 20℃; for 4h; | |
In ethanol Ambient temperature; | ||
With pyridine In benzene for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dmap; triethylamine In dichloromethane at 5 - 20℃; for 3h; | |
70% | With potassium carbonate In chloroform at 20℃; for 3.5h; Cooling with ice; | Synthesis of S-2 (1S, 2S)-1, 2-diphenylethane-1, 2-diamine (1.0 g, 4.7 mmol) wasdissolved in 30 mL of dried chloroform and cooled in the ice bath. 1.4 g (10 mmol) anhydrous K2CO3 was placed in the solution as th ebase. 2-Chloroacetyl chloride (1.6 g, 14.1 mmol) was dropwisely added to the mixture within 30 min. The mixture was then stirred at room temperature for 3 h. After filtration, the filtrate was collected and washed with 20 mL 10% HCl, saturated NaHCO3 and water respectively. The organic layer was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure.The residue was then purified by column chromatography on silicagel using CHCl3/MeOH (50:1) as eluent to obtain pure products a as a solid (1.20 g, 70%). |
843 mg | With dmap; triethylamine In dichloromethane for 3h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium hydroxide; In dichloromethane; at 0 - 5℃; for 3h;Inert atmosphere; | Synthesis of Compound 2009: To a 2-L, three-neck, round-bottom flask equipped with a temperature probe, magnetic stir bar, nitrogen inlet, and addition funnel were added (lS,2S)-(-)-l,2-diphenylethylenediamine (20 g, 0.094 mol) and dichloromethane (160 mL). The mixture was cooled to 0-3 0C and a 1 M solution of sodium hydroxide (160 mL) was added dropwise while maintaining the temperature below 5 0C. To this mixture was added a solution of toluenesulfonyl chloride (17.9 g, 0.094 mol) in dichloromethane (320 mL) dropwise over a 2-h period. The biphasic mixture was stirred at 0-5 0C for an additional 1 h and the reaction was deemed complete by TLC (50% EtO Ac/heptane, UV). Phases were separated and the organic phase was washed with water (2 x 320 mL) and brine (320 mL), dried over sodium sulfate and concentrated to a crude solid. The solid was dissolved in toluene (200 mL) at 70-80 0C and heptane (300 mL) was added portionwise while maintaining this temperature. The resulting slurry was cooled and stirred at 20-25 0C for 1 h and then cooled and stirred at 0-5 0C for 10 min. The solids were filtered and washed with a 50% solution of toluene in heptane (3 x 1 bed volume) to give compound 2009 (30.24 g, 88%) as a white powder. |
82.3% | With sodium hydroxide; In dichloromethane; water; at 0 - 20℃; for 3h; | The procedure is the same as in Example 1,Except that (1S, 2S) -1,2-diphenylethylenediamine (3.0 g, 14.1 mmol)Added to 50mLDCM,After stirring and dissolving,A 15 mL aqueous solution of 2N NaOH was added,Cooling to 0 ,A solution of p-toluenesulfonyl chloride (2.65 g, 14.1 mmol)In dichloromethane (30 mL)After maintaining the reaction at 0 C for 1 hour,The temperature was raised to room temperature for 2 hours,HPLC detection reaction ended.The reaction solution was poured into saturated sodium chloride solution (30 mL)Stir for 10 minutes,After stratification,The aqueous phase was extracted once with DCM (30 mL)Combine organic phase,dry,The dichloromethane was removed by distillation under reduced pressure,Get crude.Recrystallization from petroleum ether / ethyl acetate system gave yellow solid Compound I (4.48 g, 82.3%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With dmap; triethylamine In dichloromethane | |
With dmap; triethylamine In dichloromethane | ||
With triethylamine In dichloromethane at 0 - 20℃; | Synthesis of (1R, 2R)-N-p-styrenesulfonyl-1,2-diphenylethylenediamine General procedure: (1R, 2R)-N-p-styrenesulfonyl-1,2-diphenylethylenediamine was synthesized as follows: 1g of (1R, 2R)-1,2-diphenylethylenediamine (4.71mmol) was dissolved in 20mL of CH2Cl2 in the presence of excessive of triethylamine and cooled to 0°C, followed by the slow addition of 5mL of CH2Cl2 solution containing 1g of p-styrenesulfonyl chloride (4.78mmol), and stirred at room temperature overnight. The solution was washed with 5% NaOH aqueous solution, dried with MgSO4, and evaporated under vacuum to remove the solvent. The obtained solid was dissolved in diethyl ether, followed by the addition of 1mL of concentrated HCl (37wt%). The formed white precipitated was filtrated, treated with 5% NaOH aqueous, and then extracted with CH2Cl2 for 3 times. The combined organic phase was washed thoroughly with brine and dried over with MgSO4. The solvent was removed under vacuum and 1.28g of light yellow solid (72% yield) was obtained, which was denoted as V-TsDPEN [11]. 1H NMR (400MHz, DMSO-d6, 298K, TMS): δ6.64-7.38 (m, 14H), 6.64-6.67 (m, 1H), 5.87 (d, 1H, J=16.8Hz), 5.35 (d, 1H, J=11.2Hz), 4.33 (d, 1H, J=7.2Hz), 3.95 (d, 1H, J=6.6Hz) ppm. |
2.35 g | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane With triethylamine In dichloromethane at 0℃; Stage #2: 4-vinylbenzenesulfonyl chloride In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethylamine In tetrahydrofuran at 20℃; for 12h; Cooling with ice; | |
82% | With triethylamine In dichloromethane at 30℃; for 18h; | |
79% | With triethylamine In dichloromethane at 20℃; for 0.833333h; |
In dichloromethane | ||
With triethylamine In dichloromethane at 0℃; for 3h; | (B) Typical procedure for guanidine preparation A solution of sulfonyl chloride B (10 mmol) in dichloromethane (25 mL) was slowlyadded to a stirred solution of diamine A (10 mmol), NEt3 (11 mmol) in dichloromethane(25 mL). The resulting mixture was stirred for another 3 hr, washed twice with water (25mL) and dried over Na2SO4. The solvent was removed in vacuo to give a white solid C. Toa solution of D in CH2Cl2 (40 mL) was added NEt3 (11 mmol), isobutyl carbonochloridate(11 mmol) at 0 oC under stirring. After 10 min, C was added. The reaction was allowed towarm to room temperature for another 3 hr. The mixture was washed with 1 M KHSO4solution, saturated NaHCO3 solution, and brine, dried over anhydrous Na2SO4 andconcentrated to get a white solid E. Then, TFA (10 mL) was added to the CH2Cl2 (10 mL)solution of E, and stirred until the reaction finished (1 hr). The pH value of the mixture wasbrought into the range of 10-12 by the addition of 2 N NaOH solution. The aqueousphase was extracted with CH2Cl2 (3 × 30 mL). The combined organic phase was washedwith brine, dried over anhydrous Na2SO4, and concentrated and purified through flashchromatograph as a white solid F (70% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With acetic acid at 20℃; for 15h; | |
80% | In acetic acid at 20℃; for 15h; | |
80% | In acetic acid at 20℃; for 15h; |
With acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine In dichloromethane for 0.166667h; Heating; | |
97% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane; 5-chloro-5H-dibenzo[a,d]cycloheptene In dichloromethane at 20℃; for 2.16667h; Stage #2: With potassium carbonate In dichloromethane; water | |
97% | In dichloromethane at 20℃; for 2.16667h; | 1 Synthesis of (S,S)-1,2-bis(5H-dibenzo[a,d]cyclohepten-5-yl)-1,2-diphenylethanediamine (S,S-DPENtrop2) 667 mg of 5H-dibenzo[a,d]cyclohepten-5-yl chloride (2.95 mmol, 2 eq.) were added at room temperature to 313 mg of (S,S)-diphenylethanediamine (1.47 mmol) in 20 ml of CH2Cl2. After 10 min, a white precipitate formed. The suspension was stirred for a further 2 h and concentrated, and the residue was extracted with 10% by weight aqueous potassium carbonate solution and CH2Cl2. The organic phase was removed and the aqueous phase was extracted twice more with CH2Cl2. The collected organic phases were dried over sodium sulfate and concentrated. Chromatography on silica gel with hexane/diethyl ether (3:2 by volume) and subsequently diethyl ether as eluents gave rise to 846 mg of DPENtrop2 (1.43 mmol, 97%) as a colourless foam. In CDCl3, the compound is present in a symmetrical (approx. 68%) and an asymmetrical (approx. 32%) conformation. Symmetrical form:1H NMR (300 MHz, CDCl3): δ=2.48 (d, J=7.8 Hz, 2H, NH), 3.09 (s, 2H, CHNTrop), 4.49 (d, J=7.8 Hz, 2H, CH(Ph)(NHTrop)), 6.36 (d, J=11.8 Hz, 2H, CHolefin), 6.72 (d, J=11.8 Hz, 2H, CHolefin), 6.83-7.47 (m, 26H, CHaryl). 13C NMR (75 MHz, CDCl3):δ=65.4 (2C, CHNTrop), 66.4 (2C, CH(Ph)(NHTrop)), 126.7 (2C, CHaryl), 126.8 (2C, CHaryl), 126.9 (2C, CHaryl), 127.6 (2C, CHaryl), 128.0 (4C, CHaryl), 128.2 (4C, CHaryl), 128.6 (2C, CHaryl), 129.3 (2C, CHaryl), 129.8 (2C, CHaryl), 129.9 (2C, CHaryl), 130.0 (2C, CHaryl), 130.2 (2C, CHolefin), 130.3 (2C, CHolefin), 133.6 (2C, Cquart), 133.8 (2C, Cquart), 139.3 (2C, Cquart), 140.1 (2C, Cquart), 141.0 (2C, Cquart). IR: v=3317 m, (NH), 3020 m, 1599 w, 1489 m, 1451 s, 1436 s, 1071 m, 797 s, 760 s, 697 s. MS (70 eV, m/z, %): 538 (44), 476 (50), 296 (27), 207 (18), 191 (100). Selected data of asymmetrical form:1H NMR (300 MHz, CDCl3): δ=2.78 (br, 1H, NH), 3.13 (br, 1H, NH), 3.37 (d, J=7.0 Hz, 1H, CH(Ph)(NHTrop)), 3.74 (s, 1H, CHNTrop), 3.74 (d, J=7.0 Hz, 1H, CH(Ph)(NHTrop)), 4.74 (d, J=5.1 Hz, 1H, CHNTrop), 6.82-7.38 (m, 25H, CHaryl ) 7.7 (d, J=7.8 Hz, 1H, CHaryl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With triethylamine In dichloromethane at 0℃; for 2h; | |
With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 3,a Example 3: Preparation of RuCI[(1S,2S)-p-dansyl-NCH(C6H5)CH(C6H5)NH2](η6-p-cymene); a) Preparation of (S, S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1,2- diphenyl-ethyl)-amide. To a solution of (S,S)-diphenylethylenediamine (250 mg, 1.2 MMOL) and triethylamine (0.5 ml) in THF is added dropwise a solution of dansyl chloride (318 mg, 1.2 MMOL) in THF (2 ml) at 0 C. After stirring 16 h at RT the solvent is removed in vacuum and the residue is resolved in METHYLENCHLORIDE (20 ml). The organic solution is washed with NaHCO3 SOLUTION (5 ml), dried over Na2SO4 AND after filtration the solvent is removed. Flash chromatographie afford (S,S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1,2- diphenyl-ethyl)-amide as yellow oil which crystallizes by drying in vacuum. M: 445. 59. 1H-NMR (400 MHz, CDCI3): 8.36 (t, J=7.5 Hz, 2H), 8.17 (dd, J=7.2, 1.2 Hz, 1H), 7.47 (dd, J=8.8 Hz, 1H), 7.34 (dd, J=8.5 Hz, 1H), 7.24-7.16 (m, 4 H), 7.11 (d, J=7.5 Hz, 1H), 6.99-6.74 (m, 6 H), 4.61 (d, J=8.5 Hz, 1 H), 4.20 (d, J=8.5Hz, 1 H), 2.80 (s, 6 H). | |
With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 5.a To a solution of (S, S)-diphenylethylenediamine (250 mg, 1.2 mmol) and triethylamine (0.5 ml) in THF is added dropwise a solution of dansyl chloride (318 mg, 1.2 mmol) in THF (2 mi) at 0°C. After stirring for 16 h at RT the solvent is removed in vacuum and the residue is resolved in methylenchloride (20 ml). The organic solution is washed with NaHCO3 solution (5 ml), dried over Na2SO4, and after filtration the solvent is removed. Flash chromatography affords (S, S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1, 2-diphenyl-ethyl)- amide as yellow oil, which crystallizes by drying in vacuum. Molecular weight: 445. 59.'H- NMR (400 MHz, CDCI3) : 8.36 (t, J = 7.5 Hz, 2 H), 8.17 (dd, J = 7.2 Hz, 1.2 Hz, 1 H), 7.47 (dd, J = 8. 8 Hz, 1 H), 7.34 (dd, J = 8. 5 Hz, 1 H), 7.24-7. 16 (m, 4 H), 7.11 (d, J = 7. 5 Hz, 1 H), 6.99-6. 74 (m, 6 H), 4.61 (d, J = 8.5 Hz, 1 H), 4.20 (d, J = 8.5 Hz, 1 H), 2.80 (s, 6 H). |
With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 4.a Example 4: Preparation of RuCI [ (1 S, 2S)-p-dansylNCH (C6H5) CH (C6H5) NH2] (rl6-p-cymene) a) Preparation of (S, S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1, 2-diphenyl- ethyl)-amide : To a solution of (S, S)-diphenylethylenediamine (250 mg, 1.2 mmol) and triethylamine (0.5 ml) in THF is added dropwise a solution of dansyl chloride (318 mg, 1.2 mmol) in THF (2 mi) at 0°C. After stirring 16 h at RT the solvent is removed in vacuum and the residue is resolved in methylenchloride (20 ml). The organic solution is washed with NaHCO3 solution (5 ml), dried over Na2SO4 and after filtration the solvent is removed. Flash chromatographie afford (S, S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1,2- diphenyl-ethyl)-amide as yellow oil which crystallizes by drying in vacuum. M: 445. 59. in- NMR (400 MHz, CDCl3) : 8.36 (t, J = 7.5 Hz, 2 H), 8.17 (dd, J = 7.2, 1.2 Hz, 1 H), 7.47 (dd, J = 8.8 Hz, 1 H), 7. 34 (dd, J = 8.5 Hz, 1 H), 7.24-7. 16 (m, 4 H), 7.11 (d, J = 7.5 Hz, 1 H), 6.99- 6.74 (m, 6 H), 4.61 (d, J = 8.5 Hz, 1 H), 4.20 (d, J = 8.5 Hz, 1 H), 2.80 (s, 6 H) | |
With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 3.a To a solution of (S,S)-diphenylethylenediamine (250 mg, 1.2 mmol) and triethylamine (0.5 ml) in THF is added dropwise a solution of dansyl chloride (318 mg, 1.2 mmol) in THF (2 ml) at 0° C. After stirring 16 h at RT the solvent is removed in vacuum and the residue is resolved in methylenchloride (20 ml). The organic solution is washed with NaHCO3 solution (5 ml), dried over Na2SO4 and after filtration the solvent is removed. Flash chromatographie afford (S,S)-5-dimethylamino-naphthalene-1-sulfonic acid (2-amino-1,2-diphenyl-ethyl)-amide as yellow oil which crystallizes by drying in vacuum. M: 445.59. 1H-NMR (400 MHz, CDCl3):8.36 (t, J=7.5 Hz, 2 H), 8.17 (dd, J=7.2, 1.2 Hz, 1 H), 7.47 (dd, J=8.8 Hz, 1 H), 7.34 (dd, J=8.5 Hz, 1 H), 7.24-7.16 (m, 4 H), 7.11 (d, J=7.5 Hz, 1 H), 6.99-6.74 (m, 6 H), 4.61 (d, J=8.5 Hz, 1 H), 4.20 (d, J=8.5 Hz, 1 H), 2.80 (s, 6 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In dichloromethane; water; at 0℃; for 2h; | In a 3-necked flask, 5.0 g of S,S-diphenylethylenediamine are dissolved in 40 ml of CH2C12. Subsequently, 40 ml of 1 M sodium hydroxide solution are added and the mixture is cooled by means of an ice bath. Afterwards, a solution of 4.49 g of p-toluenesulphonyl chloride in 80 ml of CH2C2 are added dropwise at 0 C. within 60 min. After 1 h at 0 C., the reaction is terminated. The organic phase is removed and washed with water, and the solvent is removed on a rotary evaporator. Crude diamine:mono-: disubstitution product: 3.5:93:3.5. Crystallization is effected from toluene: hexane. Yield: 7.8 g of crystalline product (91%), mono-: disubstitution product selectivity: 95.5:4.5. | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 5h; | In a 3-necked flask, 2.21 g of p-toluenesulphonyl chloride in 40 ml of CH2Cl2 are admixed with 3.0 ml of triethylamine (1.8 eq). The mixture is cooled to 0 C. and 2.46 g of S,S-diphenyethylenediamine are added. After 1 h at 0 C. and 4 h at RT, the reaction is worked up. The mixture is diluted with 50 ml of dichloromethane and washed with 50 ml of 0.5 M NaOH, the cloudy organic phase is removed and washed with 20 ml of water and 50 ml of NaCl solution and the solvent is removed on a rotary evaporator. The mixture is admixed with toluene and remaining triethylamine is removed azeotropically. Yield: 2.93 g (?69%?) of crude product, mono-: disubstitution product selectivity: 83:17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogen In dichloromethane for 1h; | 24.(2) (2); Synthesis of Rh+{2,2'-bis(diphenylphosphinyl)benzophenone} {(S,S)-DPEN}(SbF6-); Into [Rh+{2,2'-bis(diphenylphosphinyl)benzophenone}(cod)](SbF6-) obtained in the (1) after the distillation under reduced pressure were added 21.2 mg (0.1 mmol) of (S,S)-DPEN and 2 ml of methylene chloride, and then the solution was stirred under hydrogen atmosphere for 1 hour. The solvent was distilled off under reduced pressure and then the residue was dried to give 110 mg (yield: > 99%) of the title compound. 31p NMR (CDCl3) δ ppm; 48.28, 57.04 (2dd, Jp-p = 40.5 Hzo, Jp-Rh = 157.9 Hzo). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With triethylamine In water; isopropyl alcohol; toluene at 50℃; | 6 Ester S,R-10a (1.07 g; 2.36 mmol; 1.25 equiv) was combined with S,S-1,2-diphenylethylenediamine (400 mg; 1.88 mmol) and triethylamine (0.53 mL; 3.76 mmol; 2 equiv) in 5 mL of isopropanol, 2 mL of water, and 1 mL of toluene. The reaction mixture was heated overnight at 50° C. to completely consume 10a according to tlc analysis. The reaction mixture was diluted with ethyl acetate, water (10 mL), and 2 N sodium hydroxide (10 mL). The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic solution was dried (magnesium sulfate) and concentrated to afford 1.58 g of crude product. This material was filtered through a pad of flash silica gel and eluted with 1:4 ethyl acetate:heptane to remove impurities, and then with 1:1 ethyl acetate:heptane with 5% added triethylamine to afford 0.67 g (58%) of S,S-11c. A portion of this phosphinodiamine (0.57 g; 0.94 mmol) was combined with ester S,R-10a (534 mg; 1.17 mmol; 1.25 equiv) and triethylamine (0.20 mL; 1.41 mmol; 1.5 equiv) in 5 mL of isopropanol, 2 mL of water, and 1 mL of toluene, and the mixture was heated for 24 h at 50° C., at which point tlc analysis indicated no 10a but still some 11c residual. Additional S,R-10a (107 mg; 0.24 mmol; 0.25 equiv) and triethylamine (33 μL; 0.24 mmol; 0.25 equiv) were added and the mixture was stirred overnight at 50° C. to completely consume 11c. The reaction mixture was diluted with ethyl acetate and 1 N sodium hydroxide (20 mL). The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic solution was dried (magnesium sulfate) and concentrated to afford 1.07 g of crude product. This material was flash-chromatographed and eluted with 1:9 ethyl acetate:heptane to afford 0.70 g (74%) of S,S-8c. S,S-11c: 1H NMR (CDCl3) δ 7.8-7.2 (m, 10 H); 7.2-6.75 (m, 10H); 4.384 (br s, 1H); 4.27 (m, 1H); 3.910 (s, 5H); 3.82 (m, 1H); 3.714 (m, 1H); 3.482 (d, J=7.42 Hz, 1H); 2.05 (br s, 3H); 1.275 (d, J=6.59 Hz, 3H). FDMS: m/e 608.09 (M+) S,S-8c: 1H NMR (DMSO-d6) δ 7.6-6.5 (m, 30 H); 4.420 (m, 2H); 4.272 (m, 2H); 3.885 (s, 10H); 3.558 (m, 2H); 3.257 (m, 2H); 2.05 (m, 2H); 1.141 (d, J=7.14 Hz, 3H). FDMS: m/e 1005.22 (M+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With trifluoroacetic acid In water at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 18h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: Ru(cod)(O2CCF3)2; 2,2'-bis(diphenylphosphino)biphenyl In tetrahydrofuran; tert-butyl methyl ether at 100℃; for 1h; Stage #2: (S,S)-1,2-diphenyl-1,2-diaminoethane In tetrahydrofuran; tert-butyl methyl ether for 0.0833333h; | 3.1 Example 3; Catalytic hydrogenation of esters using complex [RUCI2(PP)(S-S-DPEN)]; General procedure for the catalytic hydrogenation of methyl benzoate as substrate: Under argon, a Keim autoclave was charged with [RuCl2(PP)(dmf)2] (0.01 mmol, 0.05 mol%) and S5S-DPEN (0.01 mmol, 0.05 mol%) followed by THF (2 ml) and the solution stirred for 5 minutes. Then a solution of methyl benzoate (20 mmol) in THF (2 ml), followed by more THF (2 x 1 ml), and a solution of tridecane (1 mmol) in THF (2 ml), as internal standard, followed by more THF (2 x 1 ml), were successively added to the autoclave. Finally, solid NaOMe (1 mmol, 5 mol%) was added and the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermostatted oil bath set at 600C. After 2 h, the autoclave was removed from the oil bath, and cooled in a cold-water bath. Then, an aliquot (0.4 ml) was taken, diluted with MTBE (5 ml), washed with aq. sat. NH4Cl (5 ml), and filtered over a plug of celite and analyzed by GC.Table 3 : Hydrogenation of methyl benzoate using [RUCI2(PP)(S5S-DPEN)] 2Com/Base: molar ratio in ppm relative to the substrate of complex and base.GC yield versus internal standard (in %, analysed by GC) of benzyl alcohol. Reaction conditions: H2 gas (50 bars), 600C, 2 h, NaOMe as base and THF (2 M).1} Catalyst generated in-situ by pre-heating a solution of [Ru(TFA)2(cod)] and the diphosphine in MTBE/THF (10/1) at 1000C for 1 h and the solution used as is for the reaction.2) The preformed complex was used here.3) Catalyst generated in-situ by pre-heating a solution of [RuCl2(pCym)]2 with the diphosphine in EtOH/CH2Cl2 (4/1) at 500C for 30 minutes. Followed by solvent evaporation, and heating the residue with S5S-DPEN in THF at 1400C for 1 h and the solution used as is for the reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine In dichloromethane at 0℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-Bromosuccinimide In dichloromethane at 0 - 20℃; Inert atmosphere; | |
95% | Stage #1: Isophthalaldehyde; (S,S)-1,2-diphenyl-1,2-diaminoethane In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: With N-Bromosuccinimide In dichloromethane at 0 - 20℃; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: dichloromethane / 5 h / 0 °C / Inert atmosphere 2: N-Bromosuccinimide / dichloromethane / 22 h / 0 - 20 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: dichloromethane / 1 h 2: N-Bromosuccinimide / dichloromethane / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 11 Synthesis of (S,S)-(2-(1-naphtyl)-ethane)SO2DPEN 0.833 g (3.93 mmol) of (S,S)-DPEN (MW: 212.3) was introduced into a 100-mL three-necked flask and subjected to argon-gas replacement. 40 mL of dehydrated methylene chloride and 0.58 mL (4.13 mmol) of triethylamine were added and cooled to 0° C. To this solution, a solution consisting of 1.0 g (3.93 mmol) of 2-(1-naphtyl)-ethanesulfonyl chloride (MW: 254.73) and 10 mL of dehydrated methylene chloride was slowly added dropwise, and stirred at 0° C. for 3 hr. This solution was washed twice with water, then the solvent in the organic layer was distilled away, and dried under reduced pressure to give a crude product. The crude product was purified by silica-gel column chromatography (silica gel 60N, n-hexane:AcOEt=1:1, then AcOEt 100%) to give 1.13 g of (S,S)-(2-(1-naphtyl)-ethane)SO2DPEN (67% yield). 1H NMR (400 MHz, CDCl3, rt, δ/ppm): 2.67 (ddd, J=14.2, 11.9, 5.0 Hz, 1H, SO2CH2C2), 2.79 (ddd, J=14.2, 11.9, 5.0 Hz, 1H, SO2CH2C2), 3.24 (ddd, J=14.2, 11.9, 5.0 Hz, 1H, SO2C2CH2), 3.32 (ddd, J=14.2, 11.9, 5.0Hz, 1H, SO2C2CH2), 4.27 (d, J=5.5 Hz, 1H, CNH2), 4.63 (d, J=5.5 Hz, 1H, CNSO2), 6.97-7.05 (m,2H, aromatic proton), 7.11-7.20 (m, 2H, aromatic proton), 7.22-7.38 (m, 8H, aromatic proton), 7.42-7.51 (m, 2H, aromatic proton), 7.65-7.74 (m, 2H, aromatic proton), 7.79-7.87 (m, 1H, aromatic proton). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 1 Synthesis of (S,S)-(2'-nitrophenyl)methane-SO2DPEN 2.25 g (10.61 mmol) of (S,S)-DPEN (MW: 212.3) was introduced into a 200-mL three-necked flask and subjected to argon-gas replacement. 100 mL of dehydrated methylene chloride and 1.55 mL (1.14 mmol) of triethylamine were added and cooled to 0° C. To this solution, a solution consisting of 2.50 g (10.61 mmol) of 2-nitro-α-toluenesulfonyl chloride (MW: 235.65) and 25 mL of dehydrated methylene chloride was slowly added dropwise, and stirred at 0° C. for one night. This solution was washed twice with water, the solvent in the organic layer was distilled away, and dried under reduced pressure to give 4.63 g of a crude product. The crude product was purified by silica-gel column chromatography (silica gel 60N, n-hexane:AcOEt=1:1, then AcOEt 100%) to give 1.88 g of (S,S)-(2-nitrophenyl)methane-SO2DPEN (43% yield). 1H NMR (400 MHz, CDCl3, rt, δ/ppm): 4.13 (d, J=13.7 Hz, 1H, C2C6H4NO2), 4.19 (d, J=13.7 Hz, 1H, C2C6H4NO2), 4.33 (d, J=6.0 Hz, 1H, CNH2), 4.62 (d, J=6.0 Hz, 1H, CNHSO2), 6.98-7.04 (m, 1H, aromatic proton), 7.15-7.38 (m, 10H, aromatic proton), 7.38-7.50 (m, 2H, aromatic proton), 7.87-7.95 (m, 1H, aromatic proton). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 9 Synthesis of (S,S)-2',6'-Me2PhCH2SO2DPEN 0.254 g (1.20mmol) of (S,S)-DPEN (MW: 212.3) was introduced into a 50-mL three-necked flask and subjected to argon-gas replacement. 10 mL of dehydrated methylene chloride and 0.200 mL (1.44 mmol) of triethylamine were added and cooled to 0° C. To this solution, a solution consisting of 0.262 g (1.20-mmol) of 2',6'-dimethylphenyl methanesulfonyl chloride (MW: 218.70) and 5 mL of dehydrated methylene chloride was slowly added dropwise, and stirred at 0° C. for one night. This solution was washed twice with water, then the solvent in the organic layer was distilled away, and dried under reduced pressure to give a crude product. The crude product was purified by silica-gel column chromatography (silica gel 60N, n-hexane:AcOEt=1:1, then AcOEt 100%) to give 0.255 g of (S,S)-2',6'-Me2PhCH2SO2DPEN (54% yield). 1H NMR (400 MHz, CDCl3, rt, δ/ppm): 2.20 (s, 6H, C6H3(C3)2), 3.59 (d, J=14.2 Hz, 1H, SO2C2Ar), 3.79 (d, J=14.2 Hz, 1H, SO2C2Ar), 4.25 (d, J=6.4 Hz, 1H, CNH2), 4.63 (d, J=6.4 Hz, 1H, CNHSO2), 6.93 (d, J=7.8 Hz, 2H, C63(CH3)2), 7.03 (d, J=7.8 Hz, 1H, C63(CH3)2), 7.15-7.45 (m, 10H, aromatic proton). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 3 Synthesis of (S,S)-(3',5'-dimethoxyphenyl)methane-SO2DPEN 0.440 g (2.07 mmol) of (S,S)-DPEN (MW: 212.3) was introduced into a 100-mL three-necked flask and subjected to argon-gas replacement. 20 mL of dehydrated methylene chloride and 0.303 mL (2.17 mmol) of triethylamine were added and cooled to 0° C. To this solution, a solution consisting of 0.520 g (2.07 mmol) of 3',5'-dimethoxyphenyl methanesulfonyl chloride (MW: 250.70) and 5 mL of dehydrated methylene chloride was slowly added dropwise, and stirred at 0° C. for 3 hr. This solution was washed twice with water, the solvent in the organic layer was distilled away, and dried under reduced pressure to give a crude product. The crude product was purified by silica-gel column chromatography (silica gel 60N, n-hexane:AcOEt=1:1, then AcOEt 100%) to give 0.51 g of (S,S)-(3',5'-dimethoxyphenyl)methane-SO2DPEN (58% yield). 1H NMR (400 MHz, CDCl3, rt, δ/ppm): 3.59 (d, J=13.7 Hz, 1H, SO2C2C6H3), 3.64 (d, J=13.7 Hz, 1H, SO2C2C6H3), 3.71 (s, 6H, (OC3)2), 4.23 (d, J=6.4 Hz, 1H, CNH2), 4.59 (d, J=6.4 Hz, 1H, CNHSO2), 6.29 (d, J=2.3 Hz, 2H, C62H (OCH3)2), 6.36 (d, J=2.3 Hz, 1H, C6H2(OCH3)2), 7.18-7.40 (m, 10H, aromatic proton). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 5 Synthesis of (S,S)-2'-PhOPhCH2SO2DPEN 0.518 g (2.44 mmol) of (S,S)-DPEN (MW:212.3) was introduced into a 50-mL three-necked flask and subjected to argon-gas replacement. 20 mL of dehydrated methylene chloride and 0.357 mL (2.56 mmol) of triethylamine were added and cooled to 0° C. To this solution, a solution consisting of 0.690 g (2.44 mmol) of 2'-phenoxyphenyl methanesulfonyl chloride (MW: 282.74) and 5 mL of dehydrated methylene chloride was slowly added dropwise, and stirred at 0° C. for one night. This solution was washed twice with water, then the solvent in the organic layer was distilled away, and dried under reduced pressure to give a crude product. The crude product was purified by silica-gel column chromatography (silica gel 60N, n-hexane:AcOEt=1:1, then AcOEt 100%) to give 0.615 g of (S,S)-2'-PhOPhCH2SO2DPEN (55% yield). 1H NMR (400 MHz, CDCl3, rt, δ/ppm): 3.57 (d, J=13.7 Hz, 1H, SO2C2Ar), 3.65 (d, J=13.7 Hz, 1H, SO2C2Ar), 4.20 (d, J=6.4 Hz, 1H, CNH2), 4.59 (d, J=6.4 Hz, 1H, CNHSO2), 6.75-6.80 (m, 1H, aromatic proton), 6.80-6.88 (m, 1H, aromatic proton), 6.88-6.94 (m, 1H, aromatic proton), 6.94-7.10 (m, 1H, aromatic proton), 7.07-7.15 (m, 1H, aromatic proton), 7.15-7.38 (m, 13H, aromatic proton). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine In tetrahydrofuran at 20℃; for 12h; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With N-Bromosuccinimide In dichloromethane at 0 - 20℃; | To a stirred solution of5-(tert-butyl)isophthalaldehyde (660.1 mg, 3.47 mmol) and (1S,2S)-1,2-diphenylethane-1,2-diamine (1.473 g, 6.94 mmol, 2 equiv.) in CH2Cl2 (50 mL),NBS (1.235 g, 6.94 mmol, 2 equiv.) was slowly added at 0 oC. Then, the reaction mixturewas warmed to room temperature and stirred overnight. After the reaction was completed,saturated aqueous NaHCO3 was added, and the mixture was extracted with CH2Cl2. Thecombined organic layer was washed by saturated aqueous brine, dried over Na2SO4, filteredand concentrated in vacuum. The crude product was purified by column chromatography onsilica gel (petroleum ether/EtOAc/Et3N = 6:1:0 to 2:1:0.03) to give the bis(imidazoline)compound A (1.952 g, 98%). |
80% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane; 5-tert-butylbenzene-1,3-dicarbaldehyde In dichloromethane at 0℃; for 2h; Inert atmosphere; Stage #2: With N-Bromosuccinimide In dichloromethane at 0 - 20℃; Inert atmosphere; | 4.3.4. 5-tert-Butyl-bisimidazoline 7 5-(tert-Butyl)isophthalalyde (7d) (50.3 mg, 0.264 mmol) and (S,S)-1,2-diphenyl ethylenediamine (123.3 mg, 0.581 mmol) were dissolved in CH2Cl2 (6 mL) and stirred for 2 h at 0 °C under N2. The resulting solution was added NBS (103.4 mg, 0.581 mmol) at 0 °C and the mixture was stirred overnight at room temperature. The reaction mixture was added to Na2S2O5 aq and 5% NaOH aq, and extracted with CH2Cl2. Organic layer was dried over Na2SO4 and evaporated in vacuo. The residue was purified by SiO2 column chromatography (hexane/AcOEt/triethylamine=2/1/0.03) to give 7 (151.7 mg, 80%) as colorless solid. 1H NMR (400 MHz CDCl3): δ=8.29 (t, J=1.8 Hz, 1H), 8.15 (d, J=1.8 Hz, 2H), 7.39-7.29 (m, 20H), 5.49 (s, 2H), 5.14 (d, J=8.1 Hz, 2H), 4.33 (dd, J=1.8, 8.1 Hz, 2H), 1.42 ppm (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; for 5h; | General procedure: To a stirred solution of triethylamine (1.39 mL, 10 mmol) and (1S,2S)-1,2-diphenylethane-1,2-diamine (1.06 g, 5 mmol) in CH2Cl2 (15 mL) at 0 C, (1S)-(+)-10-camphorsulfonyl chloride 1 (1.25 g, 5 mmol) in CH2Cl2 (5 mL) was added dropwise. Then after stirring at the same temperature for 1 h, and then at room temperature for another 4 h, the reaction mixture was quenched with water and extracted with CH2Cl2. The organic phase was separated and dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by crystallization with ethyl acetate and methanol to afford (S,S,S)-CsDPEN as a white solid (1.04 g, 48% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In methanol at 0 - 20℃; for 12h; | 2.2. Synthesis of chiral monomeric macrocyclic salen ligands 1' and 2' In a single-necked 50 mL round-bottom flask bis-aldehyde c (0.72 g, 1.5 mmol) was taken in dry MeOH (10 mL) and was stirred at 0 °C, and a solution of 1S,2S-(+)-1,2-diaminocyclohexane (0.18 g,1.6 mmol)/1S, 2S-(-)-1,2-diphenylethane-1,2-diamine (0.34 g,1.6 mmol) in dry MeOH (5 mL) was added drop wise to the above solution. After complete addition, the resulting solution was further stirred at room temperature. After an interval of 12 h, solvent was completely removed under reduced pressure, and the bright yellow solid was extracted with dichloromethane (50 mL). The organic layer was washed with water (3 × 50 mL) and with brine (3 × 50 mL) and finally dried over anhydrous Na2SO4. After removal of dichloromethane under reduced pressure, the chiral ligands 1' and 2' purified by silica gel column chromatography (100-200 mesh) in 20% (EtOAc: Hexane) resulted in yellowish solid monomeric macrocyclic ligands, 1' and 2'.1': Yield 85%. m.p. 104 °C. 1H NMR (500 MHz, CDCl3): δ 1.44 (18 H, s), 1.73-1.91 (8H, m), 3.23-3.25 (2H, m), 3.31-3.33 (4H, m), 3.51-3.62 (8H, m), 4.19 (2H, d, J = 11), 4.43 (2H, d, J = 11), 6.72 (2H, s), 7.27 (2H, s), 8.07 (2H, s), 11.78 (2H, br) ppm. 13C NMR (125 MHz, CDCl3): 24.3, 29.4, 32.7, 34.8, 68.5, 69.2, 70.7, 72.3, 76.4, 118.3, 127.3, 129.8, 137.4, 160.0, 166.2 ppm. FT-IR (KBr): ν 3432, 2942, 2863, 2359, 1629, 1558, 1442, 1387, 1259, 1212, 1099, 970, 845, 768, 728, 668, 594 cm-1. (c = 0.052, CH2Cl2). Anal. Calcd. for C36H52N2O6: C, 71.02; H, 8.61; N, 4.60. Found C, 71.0; H, 8.58; N, 4.58. TOF-MS (ESI+): m/z Calcd. for [C36H52N2O6] 608.81, Found 610.2 [M+H].2': Yield 90%. m.p. 98 °C. 1H NMR (200 MHz, CDCl3): δ 1.46 (18H, s), 3.30-3.36 (4H, m), 3.57-3.68 (8H, m), 4.19 (2H, d, J = 10), 4.47 (2H, d, J = 10), 4.56 (2H, s), 6.72 (2H, d, J = 1.8), 7.18-7.30 (12H, m), 8.24 (2H, s), 13.86 (2H, br) ppm. 13C NMR (50 MHz, CDCl3): 29.5, 33.9, 69.0, 70.8, 72.5, 78.6, 118.3, 127.5, 128.3, 128.4, 129.2, 137.4, 139.8, 160.1, 166.8 ppm. IR (KBr): ν 3452, 2929, 2865, 1626, 1553, 1440, 1263, 1096, 848, 726, 585, 464 cm-1. (c = 0.206, CHCl3). Anal. Calcd. for C44H54N2O6 C, 74.76; H, 7.70; N, 3.96. Found C, 74.73; H, 7.68; N, 3.93. TOF-MS (ESI+): m/z Calcd. for [C44H54N2O6] 706.91, Found 708.45 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In tetrahydrofuran at 20℃; for 2h; | 2.3. Synthesis of chiral dimeric macrocyclic salen ligands 3' and 4' Bis-aldehyde c (0.53 g,1.1 mmol) in dry THF (1.2 mL) was taken in a single-necked 50 mL round-bottom flask to which the solution of 1S,2S-(+)-1,2-diaminocyclohexane (0.14 g,1.2 mmol)/1S,2S-(-)-1,2-diphenylethane-1,2-diamine (0.27 g, 1.2 mmol) in dry THF (0.6 mL) was added slowly and the resultant solutions were stirred at room temperature. After completion of the reaction (2 h) checked on TLC, the solvent was removed completely under reduced pressure. The bright yellow solids were extracted with dichloromethane (50 mL), and the organic layer was washed with water (3 × 50 mL), brine (3 × 50 mL) and finally dried over anhydrous Na2SO4. After removal of dichloromethane under reduced pressure, the chiral dimeric macrocyclic ligands 3' and 4' were purified by silica gel chromatography (100-200 mesh) with a EtOAc-to-Hexane of 3:2.3': Yield 96%. m.p. 76 °C. 1H NMR (500 MHz, CDCl3): δ 1.38 (36H, s),1.67-1.93 (16H, m), 3.32 (4H, m), 3.55 (8H, t, J = 5), 3.61 (16H, t, J = 7), 4.37 (8H, s), 6.97 (4H, s), 7.20 (4H, s), 8.26 (4H, s), 13.86 (4H, br) ppm. 13C NMR (125 MHz, CDCl3): 25.0, 31.0, 34.7, 70.7, 72.2, 74.0, 74.8, 79.0, 119.8, 128.7, 131.2, 138.8, 161.6, 167.0 ppm; FT-IR (KBr): ν 3424, 2934, 2863, 2361, 1628, 1537, 1446, 1384, 1317, 1239, 1098, 940, 868, 785, 671, 563, 420 cm-1. (c = 0.052, CH2Cl2). Anal. Calcd. for C72H104N4O12 C, 71.02; H, 8.61; N, 4.60. Found C, 71.05; H, 8.63; N, 4.62. MALDI-TOF: m/z Calcd. for [C72H104N4O12] 1217.62, Found 1218.19 [M+H].4': Yield 93%. m.p. 95 °C. 1H NMR (200 MHz, CDCl3): δ 1.40 (36H, s), 3.53-3.63 (24H, m), 4.37 (8H, s), 4.71 (4H, s), 6.97 (4H, s), 7.19-7.29 (24H, m), 8.32 (4H, s), 13.78 (4H, br) ppm. 13C NMR (50 MHz, CDCl3): 29.3, 34.8, 69.1, 70.6, 73.1, 80.0, 118.1, 127.6, 128.1, 128.3, 129.8, 137.3, 139.5, 159.9, 166.7 ppm. FT-IR (KBr): ν 3452, 2952, 2865, 2361, 1626, 1446, 1386, 1357, 1320, 1266, 1208, 1100, 1035, 936, 871, 801, 775, 573 cm-1. (c = 0.108, CHCl3). Anal. Calcd. for C88H108N4O12 C, 74.76; H, 7.70; N, 3.96. Found C, 74.75; H, 7.73; N, 3.98. MALDI-TOF: m/z Calcd. for [C88H108N4O12] 1413.82, Found 1414.19 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium carbonate In 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 120℃; for 2h; Inert atmosphere; | 4.2.2.1. (1S,2S)-N,N'-Bis(bis(4-methylbiphenyl-3-yl)methyl)-1,2-diphenylethane-1,2-diamine (6g) General procedure: Prepared by an analogous procedure to that reported.25 A mixture of (1S,2S)-1,2-diphenylethane-1,2-diamine (1.1 g, 5.2 mmol), 5g (4.7 g, 11 mmol), and Na2CO3 (2.1 g, 20 mmol) in DMPU (15 mL) was stirred for 2 h at 120 °C, and then 50 mL of water was added. The whole was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and then concentrated to give pale yellow oil. Column chromatography (hexane/EtOAc=15/1) gave the titled compound as pale yellow amorphous solid (1.6 g, 54%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With sodium carbonate In 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 120℃; for 2h; Inert atmosphere; | 4.2.2.1. (1S,2S)-N,N'-Bis(bis(4-methylbiphenyl-3-yl)methyl)-1,2-diphenylethane-1,2-diamine (6g) Prepared by an analogous procedure to that reported.25 A mixture of (1S,2S)-1,2-diphenylethane-1,2-diamine (1.1 g, 5.2 mmol), 5g (4.7 g, 11 mmol), and Na2CO3 (2.1 g, 20 mmol) in DMPU (15 mL) was stirred for 2 h at 120 °C, and then 50 mL of water was added. The whole was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and then concentrated to give pale yellow oil. Column chromatography (hexane/EtOAc=15/1) gave the titled compound as pale yellow amorphous solid (1.6 g, 54%) of mp 108-110 °C and -30.4 (c 1.02, CHCl3). 1H NMR: 1.85 (6H, s), 2.05 (6H, s), 2.79 (2H, s), 3.98 (2H, s), 4.97 (2H, s), 7.00-7.02 (4H, m), 7.07-7.13 (10H, m), 7.17-7.20 (8H, m), 7.22-7.25 (4H, m), 7.32-7.34 (6H, m), 7.37-7.39 (2H, m), 7.43-7.47 (6H, m), 7.91 (2H, s). 13C NMR: 18.8 (CH3), 56.8 (CH), 65.9 (CH), 125.1 (CH), 125.4 (CH), 126.1 (CH), 126.67 (CH), 126.72 (CH), 126.75 (CH), 126.81 (CH), 127.1 (CH), 127.3 (CH), 127.9 (CH), 128.5 (CH), 128.6 (CH), 128.7 (CH), 131.0 (CH), 131.2 (CH), 135.6 (C), 135.7 (C), 138.5 (C), 138.6 (C), 140.0 (C), 141.0 (C), 141.1 (C), 141.3 (C). IR: 3325, 3024, 1481, 1450, 756, 694. EIMS m/z: 452 (M/2). Anal. Calcd for C68H60N2: C, 90.22; H, 6.68; N, 3.09. Found: C, 90.22; H, 6.86; N, 3.03. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With sodium carbonate In 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 120℃; for 2h; Inert atmosphere; | 4.2.2.1. (1S,2S)-N,N'-Bis(bis(4-methylbiphenyl-3-yl)methyl)-1,2-diphenylethane-1,2-diamine (6g) General procedure: Prepared by an analogous procedure to that reported.25 A mixture of (1S,2S)-1,2-diphenylethane-1,2-diamine (1.1 g, 5.2 mmol), 5g (4.7 g, 11 mmol), and Na2CO3 (2.1 g, 20 mmol) in DMPU (15 mL) was stirred for 2 h at 120 °C, and then 50 mL of water was added. The whole was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and then concentrated to give pale yellow oil. Column chromatography (hexane/EtOAc=15/1) gave the titled compound as pale yellow amorphous solid (1.6 g, 54%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane With potassium carbonate In acetonitrile at 20℃; for 0.5h; Large scale; Stage #2: 3,5-di-tert-butylbenzyl bromide In acetonitrile at 20℃; for 12h; Large scale; | (1) Synthesis of chiral di-secondary amine 3 Add the reaction solvent to the 50L reactor:Acetonitrile (22.0L),Then add chiral ethylenediamine 1 (1.00kg, 4.71mol, 1.00equiv.) andAcid binding agent,The acid binding agent is preferably potassium carbonate (2.00kg, 14.47mol, 3.07equiv.),After stirring for 30 minutes at room temperature,Benzyl bromide 2 (2.81kg, 9.89mol, 2.10equiv.) was slowly added dropwise to the reaction kettle,Then it was stirred at room temperature for 12 hours.After TLC and HPLC are qualified, water (15L) is slowly added to the reaction kettle and stirred at room temperature for 1 hour. The lower aqueous phase was removed by liquid separation, and the upper organic phase was concentrated to obtain a pale yellow solid intermediate 3 (2.91 kg, yield 100%). |
83% | With potassium carbonate In acetonitrile at 20℃; for 24h; | |
80% | With tetrabutylammomium bromide; potassium carbonate In acetonitrile at 20℃; for 24h; |
With potassium carbonate In acetonitrile at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.69% | Stage #1: chloropropionic acid; (S,S)-1,2-diphenyl-1,2-diaminoethane With sodium hydroxide In water at 90℃; for 4h; Cooling with ice; Stage #2: With hydrogenchloride In diethyl ether; ethanol; water | Preparation of meso-1,2-diphenyl-ethylenediamine-N,N'-di-3-propanoic acid dihydrohloride-hydrate, H2 -1,2-dpheddp*2HCl*H2O 3-Chloro-propanoic acid (4.34 g, 0.04 mol) was dissolved in 5.0 mL of water on ice bath and carefully neutralized with cold water solution of 5.0 mL NaOH (1.60 g, 0.04 mol). Meso-1,2-diphenyl-ethylenediamine (4.24 g, 0.02 mol) was added to this solution. The mixture was being stirred for 4 h at 90 C, and during this period 5.0 mL NaOH water soltion (1.60 g, 0.04 mol) was introduced. After that, 5.6 mL 6 mol/L HCl was added and resulting solution was evaporated to the volume of 7.0 mL; 6.0 mL conc. HCl, 6.0 mL of ethanol and 6.0 mL of ether were added to the mixture. The white precipitate of meso-1,2-diphenyl-ethylenediamine-N,N'-di-3-propanoic acid dihydrochloride monohydrate, H2-1,2-dpheddp 2HCl H2O was separated by filtration and refined with solution water: ethanol = 1: 2. Yield: 4.00 g (44.69%). Anal. Calcd. for H2-1,2-dpheddp*2HCl*H2O = C20H28Cl2N2O5 (Mr = 447.344): C, 53.69; H, 6.31; N, 6.26. Found: C, 53.88; H, 6.70; N, 6.08. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 100℃; for 10h; Inert atmosphere; | |
60% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 18h; Glovebox; | 1 In a glove box, into a 50 mL single-port flask added were 2-phenylbromobenzene 2a (2.33 g, 10.0 mmol), (S,S)-1,2-phenyl-1,2-ethylenediamine 1a (4.24 g, 20.0 mmol, 2.0 equiv), Pd2(dba)3 (230 mg, 0.25 mmol), racemic BINAP (310 mg, 0.5 mmol), sodium tert-butoxide (1.34 g, 14.0 mmol, 1.4 equiv) and 15 mL of toluene, refluxed at 110° C. for 18 h. The mixture was cooled to room temperature, and then added with 20 mL of ethyl acetate for dilution, and washed with 20 mL of water. Then the organic phase was separated, and the aqueous phase was extracted with ethyl acetate for three times (3×20 mL). Then the organic phases were combined, dried with anhydrous sodium sulfate and filtered. The mother liquor was concentrated and separated by column chromatography (petroleum ether/ethyl acetate=10:1) to obtain 2.19 g of a light yellow solid of the compound of formula 3a, with a yield of 60%. Upon detection, the NMR (nuclear magnetic resonance) data of the compound of formula 3a as obtained in this example was: 1H NMR (400 MHz, CDCl3) δ 7.48 (dd, J=14.1, 6.8 Hz, 1H), 7.39 (t, J=8.8 Hz, 1H), 7.28 (d, J=4.0 Hz, 2H), 7.19 (dd, J=12.5, 5.2 Hz, 2H), 7.14 (d, J=7.2 Hz, 1H), 7.01 (d, J=7.2 Hz, 1H), 6.92 (t, J=7.6 Hz, 1H), 6.59 (t, J=7.2 Hz, 1H), 6.20 (d, J=8.0 Hz, 1H), 5.33 (s, 1H), 4.45 (s, 1H), 4.24 (d, J=3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 144.0, 142.5, 141.2, 139.5, 129.8, 129.5, 129.5, 128.7, 128.5, 128.3, 128.1, 127.6, 127.2, 127.2, 127.1, 126.8, 126.6, 116.2, 111.3, 63.5, 60.7; HRMS (ESI) calcd for C26H24N2 ([M+H]+) 365.2012, found 365.2015. |
55% | With 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl; palladium diacetate; sodium butanolate In toluene at 110℃; for 48h; Inert atmosphere; Schlenk technique; |
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 100℃; for 10h; Inert atmosphere; | ||
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 90℃; for 24h; Inert atmosphere; Glovebox; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 48h; Schlenk technique; Inert atmosphere; | |
65% | With 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl; palladium diacetate; sodium butanolate In toluene at 110℃; for 48h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 32h; Inert atmosphere; | 4.2.3 Monoaryl diamine 6 At first, NaOtBu (1.56g, 16.4mmol, 3.0equiv) was placed in a 100-mL Schlenk flask and was dried under vacuum at 110°C for 10min. After cooling to room temperature, rac-BINAP (718mg, 1.15mmol, 0.2equiv), Pd(OAc)2 (122mg, 0.54mmol, 0.1equiv), and toluene (47mL) were added and the resulting dark red solution was stirred for 0.5h at room temperature. Bromide 5 (2.00g, 5.42mmol, 1.0equiv) and (1S,2S)-(-)-diphenylethylenediamine (1.73g, 8.15mmol, 1.5equiv) were added to the solution and the mixture was stirred at 110°C for 32h. After cooling to room temperature, the reaction mixture was diluted with CH2Cl2 and the organic layer was washed with water, dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (3:1 to 2:1 hexane/EtOAc) to give 6 as a light yellow solid (2.33g, 86% yield). Title compound 6 exists as a mixture of atropisomers and the ratio (6:4) was determined by 1H NMR analysis. Mp: 73-75°C. 1H NMR (CDCl3): δ 1.32 (br s, 2H), 2.99 (s 1.2H), 3.31 (s, 1.8H), 3.82 (s, 3H), 4.20 (d, J=4.7Hz, 0.4H), 4.25 (d, J=3.6Hz, 0.6H), 4.43 (br s, 0.6H), 4.50 (br s, 0.4H), 5.13 (d, J=5.8Hz, 0.4H), 5.35 (d, J=6.6Hz, 0.6H), 6.19 (d, J=8.0Hz, 0.6 H), 6.30 (d, J=8.3Hz, 0.4 H), 6.61 (q, J=7.2Hz, 1H), 6.93-7.46 (m, 19H). 13C NMR (CDCl3): Due to the complexity of the spectra, signal assignment based on the atropisomerism is difficult and not shown here. δ 55.52, 60.31, 60.76, 61.19, 63.29, 63.82, 110.90, 111.08, 111.49, 115.95, 116.36, 120.32, 120.34, 123.57, 123.61, 124.73, 125.30, 126.92, 127.02, 127.09, 127.14, 128.02-128.74 (m), 130.26 130.54, 131.28, 131.32, 131.53, 131.78, 132.04, 132.22, 132.48, 132.55, 132.97, 141.37, 141.90, 142.59, 142.82, 144.40, 144.47, 156.15, 157.00. HRMS-ESI (m/z): [M+H]+ calcd for C34H33N2O2, 501.25365; found: 501.25302. [α]21D=-41.85[α]D21=-41.85 (c 1.07, CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With N-Bromosuccinimide In methanol at 20℃; for 1h; Inert atmosphere; | |
98% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane; Glyoxilic acid In methanol Stage #2: With N-Bromosuccinimide | |
With N-Bromosuccinimide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium fluoride; triethylamine In chloroform; acetonitrile at 20℃; for 72h; Inert atmosphere; Glovebox; Schlenk technique; | 7 2.7. Synthesis and characterization of [DPEN(ImiPrH)NH2][BF4] (6) Acetonitrile (30 mL) was added to a mixture of 3.03 g(10.0 mmol; 1 eq) of 1, 2.45 g (11.5 mmol; 1.15 eq) of (1S,2S)-()-1,2-diphenylethylenediamine and 3.49 g (60.1 mmol; 6 eq) ofKF. To the resulting suspension, 4.2 mL (30 mmol; 3 eq) of NEt3were added. The mixture was stirred at room temperature for3 days to afford a white suspension in a colorless solution. Whilestirring, 30 mL of CHCl3 were added. The mixture was filteredthrough Celite. The Celite filtrate was extracted once with 10 mLof CHCl3. The clear solution was shaken once with a solution of5.5 g (50 mmol) of NaBF4 in 150 mL of water. The organic phasewas then washed once with a dilute NaOH solution (2.3 g in150 mL of water) and once with a dilute NaBF4 solution (5.5 g in150 mL of water). The organic layer was dried over Na2SO4, andthe solvent was then removed in vacuo, affording the product asa pale brown sticky solid (4.47 g, 9.34 mmol, 93%). 1H NMR(400 MHz; CDCl3): d 7.20-7.08 (m, 10H, HAr) 6.21 (bs, 1H, NH),5.00 (sept, 2H, JHH 7.0 Hz, CHMe2), 4.62 (d, 1H, JHH 9.0 Hz, NH2-HCH(Ph)CH), 3.96 (d, 1H, JHH 9.0 Hz, CNHCH(Ph)CH), 2.19 (s, 6H,CCH3), 2.10 (bs, 2H, NH2), 1.54 (d, 6H, JHH 7.0 Hz, CH(CH3)2), 1.03(d, 6H, JHH 7.0 Hz, CH(CH3)2) ppm. 13C NMR (100 MHz; CDCl3): d143.2 (N2CNH), 142.1 (ipso-CAr(CHNH2)), 139.9 (ipso-CAr(CHNH)),128.9 (CAr), 128.4 (CAr), 128.3 (CAr), 127.7 (m-CAr(CHNH2)), 127.5(m-CAr(CHNH), 127.0 (CAr), 123.2 (CMe) 72.5 (CNHCH(Ph)CH),60.2 (NH2HCH(Ph)CH), 49.9 (CHMe2), 21.2 (CH(CH3)2), 20.9(CH(CH3)2), 10.2 (CCH3) ppm. 19F NMR (188 MHz; CDCl3): d152.08 (BF4) ppm. Anal. Calc. for (C25H35BF4N4): C, 62.77; H,7.37; N, 11.71. Found: C, 62.87; H, 7.59; N, 11.22%. ESI-MS:[(M)+]: Calcd.: 391.29; Found: 391.30. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 125℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.5% | With triethylamine In dichloromethane at 0 - 20℃; for 4h; | Synthesis of modifi ed TsDPEN ligand. General procedure: (1R, 2R)- or(1S, 2S)-DPEN (0.318 g, 1.5 mmol) was dissolved in 15mL of CH2Cl2 with 0.3 mL of triethylamine, a solutionof 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane(0.38 g, 1.12 mmol) in 15 mL CH2Cl2 was then addeddropwise at 0°C in 50 mL fl asks. After the dropping wascompleted, the mixture was slowly warmed to roomtemperature and unceasingly stirred for 4 h, then thesolvent was removed in vacuo. The residue subsequentlyfast passed through a 15 cm silica gel column (eluent:Et3N : CH3OH : CH2Cl2 = 1 : 10 : 100), concentrated,and dried in vacuo to obtain 90.5% yield of modifi edDPEN. 1H NMR (400 MHz, CDCl3): 1.95 (s, 2H), 2.03(s, 1H), 3.56 (s, 9H), 4.32 (d, J = 5.3 Hz, 1H), 4.51 (d,J = 5.3 Hz, 1H), 7.02-7.41 (m, 14H). IR (KBr): 3352,3295, 3170, 3061, 3027, 2942, 2840, 1901, 1690, 1603,1494, 1453, 1411, 1342, 1266, 1192, 1153, 1089, and1014 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: (2S,4R)-4-(but-3-en-1-yloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: (S,S)-1,2-diphenyl-1,2-diaminoethane In dichloromethane at 40℃; for 24h; | 2 Embodiment 2 Compound3 (0.97g, 3 . 60mmol) dissolved in dichloromethane (10 ml), 0 °C stirring, add triethylamine (0.81 ml, 5 . 85mmol) and ethyl chloroformate (0.36 ml, 3 . 82mmol), maintaining 0 °C stirring 30 min, then adding (1S, 2S)-bisphenylmethyl ethylenediamin (0.47g, 2 . 25mmol), 40 °C reaction 24h. After the reaction, solution concentration, column chromatography (methanol/dichloromethane = 1/45, volume ratio), vacuum drying to obtain white solid4a (1.03g, 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.8% | With triethylamine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | 4.2.1 Representative procedure for the preparation of compounds 6, 8, 10, 11, 13, 14, 18, 20, 21, 23, 24 and 25 derived from thiophenylphosphonic dicholoride. General procedure: The dual nucleophile (1 mmol) and triethylamine (2 mmol) were mixed in dry DCM under nitrogen. The mixture was cooled to 0 °C and then thiophenylphosphonic dichloride (1 mmol) was added. The mixture was slowly warmed to room temperature and stirred for 2 hours. The product was purified via flash column chromatography and dried under high vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With 1,3-bis(2,6-diisopropylphenyl)-4,5-dimethyl-3-imidazolium chloride; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate at 115℃; for 20h; Inert atmosphere; Glovebox; Sealed tube; | |
70% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride In toluene at 110℃; for 24h; Inert atmosphere; | 2.1 (1) Synthesis of diamine compound 2b: Add 5mmol of (1S,2S)-(-)-1,2-diphenylethylenediamine, 18mmol of tBuONa, 15mmol of 2,4,6-triisopropyl bromobenzene, 1.5mmol of IPrMe·HCl, Mix 0.5 mmol of Pd(dba)2, add 20 mL of anhydrous toluene, and react at 110°C for 24 hours under a nitrogen atmosphere. After the reaction is completed, it is diluted with water, extracted with ethyl acetate 3 times, and dried with anhydrous Na2SO4. The solvent was spin-dried under reduced pressure, and the crude product was subjected to silica gel column chromatography to obtain a white solid (eluent: petroleum ether/dichloromethane = 10:1). Product yield: 2.15 g, yield: 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In (2)H8-toluene at 20℃; for 2h; | 13 Example 13: Synthesis of the complex [Ru(OAc)(CO)((S,S)-dpen)(R-Josiphos)]OAc (15) In an NMR tube the complex Ru(OAc)2(CO)(R-Josiphos) (34) (29.9 mg, 0.04 mmol, 1 equiv) suspended in 0.6 mL of toluene-d8, was reacted with the ligand (S,S)-dpen (8.0 mg, 0.04 mmol, 1 equiv). After stirring at room temperature for 2 h, the sample was characterized by NMR, showing that 2 isomers of the desired product was obtained in a 7/3 ratio. The sample was then dried under low pressure. Yield: 36.7 mg (98%). Anal. Calcd (%) for C55H54FeN2O5P2Ru: C, 63.40; H, 5.22; N, 2.69; Found: C, 63.30; H, 5.50; N, 2.60. 31 P NMR (81 .0 MHz, toluene-d8) δ 53.8 (d, J = 36.0 Hz, minor dia), 52.6 (d, J =34.4 Hz, major dia), 41 .9 (d, J = 34.5 Hz, major dia), 36.1 (d, J = 36.1 Hz, minor dia). IR (cm-1): 1956, 1602, 1562. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With triethylamine In dichloromethane at 0 - 20℃; for 0.5h; | 2.2. The synthesis of 3 To a solution of (S,S)-1,2-diphenylethane-1,2-diamine (424 mg,2 mmol) and triethylamine (280 μL, 2 mmol) in CH2Cl2 (10 mL), 4-(bromomethyl)phenylsulfonyl chloride 1 (525 mg, 1.96 mmol) in dichloromethane(10 mL) were added dropwise at 0 °C. The reactionmixture was stirred at room temperature for 0.5 h. After removal ofsolvents under reduced pressure, the residue was purified by silica gelcolumn chromatography. The product 3 was obtained as white solid(0.45 g, 60%). 1H NMR (400 MHz, CDCl3) δ 7.46-7.31 (m, 2H),7.27-6.98 (m, 12H), 4.50 (s, 2H), 4.45 (d, J=5.1 Hz, 1H), 4.20 (d,J=5.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 141.5, 140.0, 136.9,129.0, 128.6, 128.3, 128.2, 127.7, 127.5, 127.5, 127.4, 63.0, 60.0,31.7. HRMS (ESI): m/z calculated for C21H21N2O2SBr [M+H]+:445.0580; found: 445.0583. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In methanol at 20℃; | 4.2 Synthesis of 4-6 (General procedure) General procedure: Dimethyl squarate (0.70g, 4.91mmol) was added to a solution of corresponding diamine 1, 2 or 3 (2.33mmol) in MeOH (2mL) in one portion. After 20h of stirring at room temperature the precipitate was filtered, washed with EtOAc (3×10mL) and dried under reduced pressure (10Torr) to afford corresponding compound 4, 5 or 6. |
62% | In methanol for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane; 2-Hydroxy-2'-methoxy-<1,1'-biphenyl>-3-carboxaldehyde With acetic acid In ethanol Inert atmosphere; Molecular sieve; Reflux; Stage #2: With sodium tetrahydroborate at 0 - 20℃; | 1 Preparation of ligand L3 (R is 2-methoxyphenyl) (1S,2S)-1,2-diphenylethylenediamine (1.0 mmol, 212 mg, 1.0 equiv) was dissolved in 50 mL of absolute ethanol under argon. Then 3-(2-methoxy)phenyl salicylaldehyde (2.0 mmol, 456 mg, 2.0 equiv) was added. Stirring was continued for 10 min, then 5 drops of acetic acid, molecular sieves were added in sequence. The reaction solution was refluxed overnight to react. The temperature was lowered to 0 ° C, and NaBH 4 (3.0 mmol, 113 mg, 3.0 equi) was added portionwise and stirred at room temperature overnight. After the reaction is completed, the resulting mixed solution is evaporated to dryness. The resulting solid is then quenched with NH4Cl.Stir for 30 min and extract 3 times with CH2Cl2. Washed twice with saturated brine, dried over anhydrous NaSO4, The solvent was evaporated to dryness, recrystallized from ethanol to give L3 (541mg, 0.85mmol, 85% yield). |
Multi-step reaction with 2 steps 1: ethanol / 10 h / Inert atmosphere; Schlenk technique; Reflux 2: sodium tetrahydroborate / ethanol / 3 h / 20 °C / Inert atmosphere; Schlenk technique; Cooling with ice |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 2,2'-bipyridyl-6-carbonitrile With sodium methylate In methanol for 0.5h; Reflux; Stage #2: (S,S)-1,2-diphenyl-1,2-diaminoethane In dichloromethane Reflux; Stage #3: benzenesulfonyl chloride With dmap In dichloromethane at 0 - 20℃; for 4h; | 3.1 (1) Preparation of 6-((4S,5S)-4,5-diphenyl-1-(phenylsulfonyl)-4,5-dihydro-1H-imidazol-2-yl)-2,2'-bipyridine a: 2,2'-bipyridyl-6-carbonitrile (1.0 g, 5.52 mmol) and sodium methoxide (120 mg, 2.21 mmol) were added to a 50 mL Shrek bottle.Then add 20 mL of anhydrous methanol and reflux for 30 min.After the reaction was completed, the pH was adjusted to neutral by the addition of glacial acetic acid.The solvent is then spun and dried in a vacuum oven to obtain a white solid;b: the resulting white solidAnd (1S,2S)-1,2-diphenylethylenediamine (1.29 g, 6.07 mmol) was added to a 100 mL round bottom flask.Then, it was refluxed by adding 50 mL of anhydrous dichloromethane overnight.After the reaction is completed, the solvent is spin-dried and separated by column chromatography (PE/EA = 1/1) to give an intermediate; c: The intermediate (376.5 mg, 1.0 mmol) and DMAP (366.5 mg, 3.0 mmol) were added to a 50 mL Shrek bottle.Then add 20 mL of dichloromethane and cool the solution to 0 oC.Add benzenesulfonyl chloride (387.1 mg, 2.2 mmol) and react the reaction at room temperature for 4 h.Then washed with a saturated aqueous solution of ammonium chloride,The aqueous phase was washed three times with dichloromethane.The organic phase was combined, dried over anhydrous magnesiumThin layer chromatography (PE/EA = 1/1) gave the title compound.White solid; yield: 0.50 g, 96% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride In toluene at 110℃; for 24h; Inert atmosphere; | 5.1 (1) Synthesis of monoamine compound 2e-1: Add 5mmol (1S, 2S)-(-)-1,2-diphenylethylenediamine, 9mmol of tBuONa, 6mmol of 2,6-diisopropyl-4-methoxybromobenzene, 1.5mmol of IPrMe ·Mix HCl and 0.5mmol Pd(dba)2, add 20mL anhydrous toluene, and react at 110°C for 24h under a nitrogen atmosphere. After the reaction is completed, it is diluted with water, extracted with ethyl acetate 3 times, and dried with anhydrous Na2SO4. The solvent was spin-dried under reduced pressure, and the crude product was subjected to silica gel column chromatography to obtain a white solid (eluent: petroleum ether/dichloromethane = 10:1). Product yield: 1.4g, yield rate: 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: 2,2'-bipyridyl-6-carbonitrile With sodium methylate In methanol for 0.5h; Reflux; Stage #2: (S,S)-1,2-diphenyl-1,2-diaminoethane In dichloromethane Reflux; Stage #3: p-toluenesulfonyl chloride With dmap In dichloromethane at 0 - 20℃; for 4h; | 2.1 (1) 6-((4S,5S)-4,5-diphenyl-1-tosyl-4,5-dihydro-1H-imidazol-2-yl)-2,2'-bipyridine preparation: a: Add 2,2'-bipyridine-6-carbonitrile (1.0g, 5.52mmol) and sodium methoxide (120mg, 2.21mmol) into a 50mL Shrek bottle, and then add 20mL of anhydrous methanol and reflux for 30min. After the reaction, add glacial acetic acid to adjust the pH to neutral. Then spin-dry the solvent and put it in a vacuum drying oven to obtain a white solid;b: Add the obtained white solid and (1S,2S)-1,2-diphenylethylenediamine (1.29g, 6.07mmol) into a 100mL round bottom flask, and then add 50mL of anhydrous dichloromethane for reflux reaction Overnight, after the reaction is complete, spin off the solvent, and separate by column chromatography (PE/EA=1/1) to obtain the intermediate;c: Add the intermediate (376.5mg, 1.0mmol) and DMAP (366.5mg, 3.0mmol) to a 50mL Shrek bottle,Then add 20mL of dichloromethane, cool the solution to 0°C, add p-toluenesulfonyl chloride (419.4mg, 2.2mmol), react the reactants at room temperature for 4h, then wash with saturated aqueous ammonium chloride Then, the aqueous phase was washed three times with dichloromethane, the organic phases were mixed, dried with anhydrous magnesium sulfate, filtered, concentrated, and separated by thin layer chromatography (PE/EA=1/1) to obtain the target compound. White solid; Yield: 0.45g, 91%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: (S,S)-1,2-diphenyl-1,2-diaminoethane With potassium carbonate In acetonitrile at 20℃; for 0.5h; Stage #2: 3,5-bis(trifluoromethyl)benzyl chloride With tetrabutylammomium bromide In acetonitrile at 20℃; for 12h; | 1 (1) Synthesis of chiral bis-secondary amine 3 Add the reaction solvent: acetonitrile (3.50L) to the 10L reaction kettle, then add chiral diphenylethylenediamine 1 (150.00g, 0.70mol, 1.00equiv.) and acid binding agent in sequence,The acid binding agent is preferably potassium carbonate (289.80 g, 1.58 mol, 3.00 equiv.).After stirring for 30 minutes at room temperature,Benzyl chloride 2 (397.90 g, 1.47 mol, 2.10 equiv.) was added dropwise to the reaction kettle, and then TBAB (23.32 g, 0.07 mol, 0.10 equiv.) was added and then stirred at room temperature for 12 hours. After TLC and HPLC were qualified, water (2.0L) was slowly added to the reaction kettle and stirred at room temperature for 1 hour. The lower aqueous phase was removed by liquid separation, and the upper organic phase was concentrated to obtain a pale yellow solid: chiral di-secondary amine 3 (471.60 g, yield 100%), which can be used directly in the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 2-bromoanisole With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 20℃; for 0.5h; Stage #2: (S,S)-1,2-diphenyl-1,2-diaminoethane In toluene at 120℃; for 12.1667h; | 1.b b) Under the protection of nitrogen, add Pd(dba)2 (0.271g, 0.5mmol) and rac-BINAP (0.352g, 0.6mmol) to the reaction flask, then add 25mL of dewatered toluene to dissolve, and stir at room temperature for 1h. Then, compound I-a-1 (0.793 g, 4.2 mmol) and sodium tert-butoxide (1.358 g, 14.1 mmol) were added to the reaction flask, and stirring was continued at room temperature for about 30 minutes. Then add (1S,2S)-1,2-diphenyl-1,2-ethylenediamine (1.000g, 4.7mmol) into the reaction flask, mix and stir for 10min, then heat to 120°C for reflux reaction for 12h .After the reaction is over, the reaction solution is cooled to room temperature, the reaction solution is filtered through a short section of silica gel column, washed with 20 mL of ethyl acetate, repeated 3 times, the filtrate is collected, and the crude product is obtained by rotary drying under reduced pressure.Finally, it was purified by column chromatography (petroleum ether/ethyl acetate=4/1) to obtain a yellow solid product I-a-21.083g with a yield of 81%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With toluene-4-sulfonic acid In toluene; acetonitrile at 120℃; for 10h; Inert atmosphere; | 3 Example 3 Synthesis of target compound LP4: Λ-fac-Ir-CHO (37.0 mg, 0.05 mmol) and(1S,2S)-1,2-diphenylethylenediamine (25.4 mg, 0.12 mmol)placed in a 50 mL three-necked flask,To this was added 45 mL of toluene and acetonitrile solvent with a volume ratio of 1:2.5,Stir to dissolve completely,Then add 15 mol% p-toluenesulfonic acid,The reaction was carried out under argon atmosphere at 120 °C for 10 h.After the reaction solution was cooled to room temperature,Under reduced pressure distillation to obtain orange-yellow solid,It was dissolved in dichloromethane and diffused with ether to give crystalline LP4, 46.5 mg, yield 93%. |
Tags: 29841-69-8 synthesis path| 29841-69-8 SDS| 29841-69-8 COA| 29841-69-8 purity| 29841-69-8 application| 29841-69-8 NMR| 29841-69-8 COA| 29841-69-8 structure
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