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CAS No. : | 18531-99-2 | MDL No. : | MFCD00004068 |
Formula : | C20H14O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PPTXVXKCQZKFBN-UHFFFAOYSA-N |
M.W : | 286.32 | Pubchem ID : | 11762 |
Synonyms : |
(S)-1,1'-Bi-2,2'-naphthol;S-(-)-2,2'-Dihydroxy-1,1'-binaphthyl;(S)-(-)-1,1'-Bi-2-naphthol
|
Num. heavy atoms : | 22 |
Num. arom. heavy atoms : | 20 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 90.94 |
TPSA : | 40.46 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.26 cm/s |
Log Po/w (iLOGP) : | 2.98 |
Log Po/w (XLOGP3) : | 5.34 |
Log Po/w (WLOGP) : | 5.07 |
Log Po/w (MLOGP) : | 4.02 |
Log Po/w (SILICOS-IT) : | 4.6 |
Consensus Log Po/w : | 4.4 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -5.59 |
Solubility : | 0.000743 mg/ml ; 0.00000259 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -5.94 |
Solubility : | 0.000327 mg/ml ; 0.00000114 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -7.11 |
Solubility : | 0.0000222 mg/ml ; 0.0000000776 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.97 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P301+P310+P330-P302+P352-P305+P351+P338 | UN#: | 2811 |
Hazard Statements: | H301-H315-H319 | Packing Group: | Ⅲ |
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 |
---|---|---|
100% | With triethylamine In dichloromethane at -78 - 20℃; for 2h; Inert atmosphere; | |
100% | With 2,6-dimethylpyridine; 4-dimethylaminopyridine In dichloromethane at -78 - 20℃; | |
100% | With pyridine In dichloromethane at 0 - 20℃; for 5h; Schlenk technique; |
100% | With 2,6-dimethylpyridine; 4-dimethylaminopyridine In dichloromethane at -78 - 20℃; for 16h; | |
99% | With pyridine In dichloromethane | |
99% | With 2,6-dimethylpyridine; 4-dimethylaminopyridine In dichloromethane at -20 - 20℃; | |
99% | With pyridine | |
99% | With 2,6-dimethylpyridine; 4-dimethylaminopyridine In dichloromethane at -30 - 20℃; | |
99% | With pyridine In dichloromethane at 0 - 20℃; for 29h; Inert atmosphere; | |
99% | With pyridine In dichloromethane at 0 - 20℃; for 1h; | 3.2.1. Synthesis of (S)-1,10-Binaphthalene-2,20-Bis(trifluoromethanesulfonate) (2) To a solution of (S)-1,10-bi-2-naphthol (2.86 g, 10.0 mmol) in CH2Cl2 (75 mL) was addedpyridine (3.16 g, 40.0 mmol), which was followed by a dropwise addition of a solutionof (CF3SO2)2O (6.78 g, 24.0 mmol) in CH2Cl2 (25 mL) at 0 C. After stirring the reactionmixture at room temperature for 1 h, an aqueous solution of 3N HCl was added and stirredfor 30 min. The mixture was neutralized by a saturated aqueous solution of NaHCO3,and the organic layer was separated and washed with water and brine. The organic layercontaining the product was dried over MgSO4 and concentrated under reduced pressure.Purification by flash chromatography on a silica gel afforded 2 (5.43 g, 99%; Figures S1and S2, In the Supplementary Materials) as a white powder. 1H NMR (399.8 MHz, CDCl3,RT): δ 7.26 (d, 3JHH = 9.1 Hz, 2H; C10H6), 7.41 (ddd, 3JHH = 7.0 Hz, 7.4 Hz, 4JHH = 1.2 Hz,2H; C10H6), 7.58 (ddd, 3JHH = 6.9 Hz, 7.2 Hz, 4JHH = 1.2 Hz, 2H; C10H6), 7.62 (d, 3JHH =9.2 Hz, 2H; C10H6), 8.00 (d, 3JHH = 8.3 Hz, 2H; C10H6), 8.14 (d, 3JHH = 9.2 Hz, 2H; C10H6).13C{1H} NMR (100.5 MHz, CDCl3, RT): δ 118.2 (q, 1JCF = 320 Hz, OSO2CF3), 119.4, 123.5,126.8, 127.4, 128.0, 128.4, 132.1, 132.4, 133.2, 145.5 (C10H6). 19F NMR (376.2 MHz, CDCl3,RT): d -74.5 (OSO2CF3). |
98% | With pyridine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; | |
98% | With pyridine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; Schlenk technique; | 2.1 General Procedure for the Preparation of Aryl Triflates (GP1) General procedure: Prepared according to a previously reported literature procedure.2 A solution of the corresponding diol (34.9 mmol, 1.00 equiv) and pyridine (104 mmol, 3.00 equiv) in CH2Cl2 (50 mL) was cooled to 0 °C in an ice bath, and trifluoromethanesulfonic anhydride (73.3 mmol, 2.1 equiv) was added dropwise. The ice bath was removed, and the reaction mixture stirred at room temperature for 3 h. CH2Cl2 (75 mL) and dest. H2O (25 mL) were added, and the phases were separated. The organic phase was subsequently washed with a sat. aq. solution of NH4Cl ( 25 mL) and brine (25 mL), dried over NaSO4, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography on silica gel afforded the desired bis-triflate. |
97% | With pyridine | |
97% | With pyridine In acetonitrile at 5 - 10℃; for 2h; | 1 Reference Example 1; (S)-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl Reference Example 1 (S)-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl To a solution of (S)-1,1'-bi-2-naphthol (26.2 g, 91 MmoL) in acetonitrile (130 ML) was added pyridine (19.5 g, 2.7 equivalents) at room temperature.. Then, trifluoromethanesulfonic anhydride (64.2 g, 2.5 equivalents) was added at 5°C, and the mixture was stirred at 5 to 10°C for 2 hrs.. water (100 ML) was added at 3°C, and ethyl acetate (130 ML) was added, and the mixture was stirred at room temperature for 30 min.. The reaction mixture was partitioned, and the organic layer was washed with water (50 ML) and concentrated under reduced pressure.. To the residue were added diisopropyl ether (150 ML) and activated carbon (0.25 g) and the mixture was stirred at 60°C for 30 min.. The activated carbon was filtered off and the filtrate was concentrated under reduced pressure.. The residue was recrystallized from heptane to give the title compound (48.9 g, white crystals).. yield 97%1H-NMR (300MHz, CDCl3, TMS) δ: 7.33 (d, 2H, J = 8.14 Hz), 7.34-7.46 (m, 2H), 7.57-7.63 (m, 2H), 7.68 (d, 2H, J = 9.09 Hz), 8.03 (d, 2H, J = 8.23 Hz), 8.16 (d, 2H, J = 9.08 Hz). |
97% | With pyridine In acetonitrile at 5 - 20℃; for 2h; | 1 (S)-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl Reference Example 1 (S)-2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl To a solution of (S)-1,1'-bi-2-naphthol (26.2 g, 91 mmol) in acetonitrile (130 mL) was added pyridine (19.5 g, 2.7 equivalents) at room temperature. Then, trifluoromethanesulfonic anhydride (64.2 g, 2.5 equivalents) was added at 5°C, and the mixture was stirred at 5°C to 10°C for 2 hours. After water (100 mL) was added at 3°C and then ethyl acetate (130 mL) was added, the mixture was stirred at room temperature for 30 minutes. The reaction solution was allowed to separate into layers. An organic layer was washed with water (50 mL) and then concentrated under reduced pressure. To the residue were added diisopropyl ether (150 mL) and active carbon (0.25 g), and the mixture was stirred at 60°C for 30 minutes. The active carbon was filtered off and the filtrate was concentrated under reduced pressure. The residue was recrystallized from heptane to obtain the title compound (48.9 g, white crystal). Yield 97%. 1H-NMR (300 MHz, CDCl3, TMS) δ: 7.33 (d, 2H, J = 8.14 Hz), 7.34-7.46 (m, 2H), 7.57-7.63 (m, 2H), 7.68 (d, 2H, J = 9.09 Hz), 8.03 (d, 2H, J = 8.23 Hz), 8.16 (d, 2H, J = 9.08 Hz). |
96% | With pyridine In dichloromethane at 0℃; for 6h; | |
90% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With pyridine In dichloromethane at 0℃; for 0.25h; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane | |
90% | With pyridine In dichloromethane at 0℃; for 0.25h; | |
89% | With pyridine In toluene at 10 - 25℃; for 20.5h; | |
87% | With pyridine In dichloromethane at 0 - 20℃; for 6h; Inert atmosphere; | |
83% | With potassium hydroxide In Carbon tetrachloride; water monomer for 0.5h; temp. below 10 deg C; | |
82% | With triethylamine In dichloromethane at 20℃; for 12h; Inert atmosphere; Reflux; | Preparation of (S)-2,2’-bis(trifluoromethanesulfonyloxy)-1,1’-binaphthalene (S)-[1,1'-binaphthalene]-2,2'-diol (2 g, 7 mmol) was placed in a 100 mL round flask under argon, anddry dichloromethane (35 mL) was added. Then, Et3N (4.4 mL, 31.5 mmol) was added, and thereaction mixture was cooled to 0 C. Then, trifluoromethanesulfonic anhydride (2.9 mL, 17.5mmol) was slowly added, and after the addition, the reaction mixture was allowed to warm toroom temperature and stirred for further 12 h. The reaction mixture was washed with water (3×5mL), and the organic layer was dried over anhydrous MgSO4, and the solvents were evaporatedin vacuo. The crude was subjected to chromatography (silica gel, hexane), yielding thecompound 10 as a white solid (3.15 g, 82%). [α]25D = +139 (c 1.0, CHCl3) [lit.:35 [α]20D = +145(c 1.0, CHCl3)]. mp 76-77 C (lit.:35 75-77 C). Rf = 0.15 (hexane). tr = 18.3 min. 1H NMR (300MHz, CDCl3): δ = 7.26 (2H, m, 2×ArH), 7.41 (2H, m, 2×ArH), 7.58 (2H, m, 2×ArH), 7.62 (2H,d, J 9.0 Hz, 2×ArH), 8.00 (2H, d, J 8.2 Hz, 2×ArH), 8.14 (2H, d, J 9.1 Hz, 2×ArH). 13C NMR(75 MHz, CDCl3): δ = 118.0 (q, JC-F = 320 Hz), 119.3, 126.7, 127.3, 128.0, 128.3, 132.0, 132.3,133.1, 145.3. IR (ATR): ν = 1510, 1422, 1218, 1136 cm-1. MS (EI): m/z 284 [M+ -2(SO2CF3),13%], 268 (100), 255 (13), 226 (12). |
82% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere; | (S)-BINOL(4.00 g, 14.0 mmol) was dissolved in CH2Cl2 (250 mL), thesolution was cooled to 0°C, and DIPEA (2.4 mL, 14.0 mmol) was addedfollowed by the dropwise addition of Tf2O (2.3 mL, 14 mmol). Thereaction mixture was stirred at r. t. overnight, after which time the solutionwas concentrated to half of its volume. The organic phase was washed with H2O(100 mL), aq 1 M HCl (100 mL), and brine (100 mL), and dried over Na2SO4.The residue was purified by silica gel column chromatography to afford productas pale yellow oil (4.811 g, 82%). Rf=0.43(petroleum ether/ethyl acetate, 5/1 v/v); [α]D20=-31 (c 0.5, CHCl3); 1HNMR (400 MHz, CDCl3) δ8.12(d, J=8 Hz, 1 H), 8.02(d, J=8 Hz, 1 H), 7.97(d, J=8 Hz, 1 H), 7.87(d, J=8 Hz, 1 H), 7.62-7.59(m, 2 H),7.44-7.43(m, 2 H), 7.37-7.28(m, 3 H), 7.00(d, J=8 Hz, 1 H), 4.91(s, 1 H); 19F NMR (376 MHz, CDCl3)δ -74.39; MS (ESI) m/z: ([M+H]+) Calcd for C21H14F3O4S419 Found 419; IR (KBr, neat): 3536, 1510, 1420, 1215, 1141, 951, 835, 812 cm-1. |
With triethylamine In dichloromethane at -78 - 20℃; | ||
With pyridine In dichloromethane at -78 - 20℃; | ||
With pyridine | ||
With pyridine In dichloromethane Inert atmosphere; | ||
With pyridine In dichloromethane at 20℃; for 2h; | ||
With pyridine In acetonitrile | ||
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; | Synthesis of (S)-2'-(3,5-bis(trifluoromethyl)phenyl)-[1,1'-binaphthalen]-2-ol (6) Tf2O (1.18 mL, 10 mmol) was added dropwise into a solution of (S)-binaphthol (2.86 g, 10 mmol)and iPr2NEt (1.74 mL, 10 mmol) in CH2Cl2 (50 mL) at 0 °C under argon. The reaction mixture was stirred for 1 h at this temperature and then quenched with saturated NaHCO3. Extractive workup wasperformed with CH2Cl2, and the combined extracts were washed with brine and dried over anhydrous Na2SO4. The solvents was evaporation, then dried under vacuum, the crude product and NiCl2(dppe)(530 mg, 1 mmol) was dissolved into THF (40 mL) under argon. To this solution was added dropwise a1 M THF solution of 3,5-bis(trifluoromethyl)phenyl magnesium bromide (60 mL, 60 mmol) at 0 °C, and stirring was continued under reflux for overnight. The reaction was quenched with saturated NH4Cl carefully and extractive workup was conducted with EA. The organic extracts were washed with brineand dried over anhydrous Na2SO4. Removal of solvents and purification of the residual oil by column chromatography on silica gel afforded (S)-6 (1.59 g, 3.3 mmol, 33% yield) as yellow powder. This is a known compound.1 1H NMR (400 MHz, CDCl3, TMS): 8.10 (d, J = 8.4 Hz, 1H, ArH), 8.01 (d, J = 8.0 Hz, 1H, ArH), 7.77 (t, J = 9.2 Hz, 2H, ArH), 7.66 (d, J = 8.4 Hz, 1H, ArH), 7.59-7.53 (m, 4H, ArH), 7.45-7.37 (m, 2H, ArH), 7.28-7.19 (m, 2H, ArH), 7.12 (d, J = 9.2 Hz, 1H, ArH), 6.98 (d, J = 8.4 Hz, 1H, ArH), 4.81 (br, 1H, OH); 19F NMR (376 MHz, CDCl3, CFCl3): -63.107. | |
With triethylamine In dichloromethane at 0℃; Inert atmosphere; | ||
With pyridine In toluene at 25℃; for 3h; | 1 Example 1: S configuration 2'-(diarylphosphine)-[1,1'-binaphthyl]-2-carboxylic acid preparation condensation reaction: Add (S)-BINOL (1,1'-bi-2-naphthol) and trifluoromethanesulfonic anhydride in a molar ratio of 1:2.5 to the reaction flask,And add pyridine and toluene, react at 25°C for 3h, add saturated sodium bicarbonate after the reaction is over, extract, dry and remove solvent,Then column chromatography is performed with n-hexane and ethyl acetate to obtain the first intermediate, as shown in formula (V); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With bromine; In dichloromethane; at -78 - 20℃; for 0.25h; | (S)-BINOL (7.20 g, 25.0 mmol, 1.0 eq.) was suspended in CH2Cl2(250 ml) at -78C. A solution of Br2(3.9 ml, 34.0 mmol, 1.4 eq.)in CH2Cl2(40 ml) was added dropwise to the reaction (over20-30 min) and stirred further 15 min at -78C. The mixture wasthen let to reach r.t. and reacted until full conversion was observedby TLC (aprox. 3 h). A sat. aq. solution of Na2S2O3(50 ml) wasadded and the aqueous layer extracted with EtOAc (3 × 50 ml).The combined organic layers were dried over MgSO4, filtered andthe solvent was removed under reduced pressure. Recrystalliza-tion from CH2Cl2/pentane gave the title compound as a white solid(10.34 g, 23.3 mmol, 93%).1H-NMR (300 MHz, CDCl3) [ppm]: 8.03(d, J = 1.9 Hz, 2H), 7.87 (d, J = 9.0 Hz, 2H), 7.45-7.35 (m, m 4H), 6.94(d, J = 9.0 Hz, 2H), 5.00 (bs, 2H).13C-NMR (75 MHz, CDCl3) [ppm]:153.0, 131.9, 130.8, 130.7, 130.6, 130.4, 125.9, 119.0, 118.0, 110.7.The analytical data are in accordance with the literature. |
89% | With bromine; In dichloromethane; at -70 - 20℃;Product distribution / selectivity; | Example 1; Compound (1 ) is prepared according to reaction scheme 1 below.; Step 1 : S-(-)-6.6'-Dibromo-n ,1 'lbinaphthalenyl-2,2'-diol; Bromine (10.2 ml, 200.0 mmol) is added dropwise to a solution of S- (-)-1 ,1 '-bi-2-naphthol (30.0 g, 104.8 mmol) dissolved in dichloromethane (400 ml) at -700C under an atmosphere of nitrogen. The mixture is allowed to warm to room temperature, whereupon sodium bisulphite is added to destroy excess bromine. The solution is washed with brine, removed, dried over sodium sulphate and evaporated to dryness. The resulting crude product is recrystallised from a mixture of toluene and petrol to yield white crystals of the desired product. 1H NMR shows expected signals.; Example 5; Compound (5) is prepared as described below.; (S)-6,6'-Dibromo-1 ,1 '-binaphthalenyl-2.2'-diol:; (S)-1 , 1 '-Binaphthalenyl-2,2'-cliol (40.00 g, 139.70 mmol) is dissolved in DCM (400 ml) and stirred under nitrogen at -70 0C. Bromine (13.6 ml, EPO <DP n="49"/>265.4 mmol) is added very slowly, ensuring the temperature remained at 70 0C. on complete addition the reaction is allowed to slowly return to r.t. overnight. On completion the excess bromine is destroyed by addition of 50ml of 10% solution of sodium bisulphite. Two layers form and the organic is separated, washed with brine, dried (sodium sulphate) and excess solvents removed in vacuo. The resulting solid is recrystallised from toluene / petrol to yield a white solid, which is dried without heating (55.2 g, 124.3 mmol, 89%). M.p. 79 0C. 1H NMR and 13C NMR give expected signals. GCMS shows the (M/z) 444 ([M]+ . |
82% | In dichloromethane; at -75℃; for 3h; | Preparation 1; Preparation of (S)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphthyl. 7.7 g (26.9 mmol) of (S)-2,2'-dihydroxy-1,1'-binaphthyl are dissolved in 145 ml of dichloromethane. The solution is cooled to -75 C. and 3.66 ml of Br2 (71.7 mmol) are then added dropwise over 30 minutes with constant stirring. The solution is stirred for a further 2 and a half hours and then cooled to room temperature. After addition of 180 ml of sodium bisulfite (10% by mass), the organic phase is washed with saturated NaCl solution and dried over Na2SO4. After evaporating off the solvent, the solid obtained is recrystallized from a toluene/cyclohexane mixture at 80 C. to give 9.8 g (22 mmol, 82% yield) of expected product. The optical rotation as measured on a Perkin-Elmer-241 polarimeter (I=10 cm, 25 C., concentration c in g/dm3) is 124.3 at c=1.015 and 578 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With oxygen In Carbon tetrachloride at 20℃; for 144h; | |
With d-amphetamine; copper chloride (II) In methanol stereoselectivity of the coupling reaction with various optically active amines; variation of the temperature; | ||
With d-amphetamine; copper chloride (II) In methanol at 25℃; for 20h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
With air In toluene at 25℃; for 24h; Irradiation; | ||
With [N-5,6-benzosalicylidene-L-Val][VO]; oxygen In Carbon tetrachloride at 20℃; for 192h; | ||
With chloro-trimethyl-silane; oxygen In chloroform at 20℃; for 24h; | ||
With oxygen In Carbon tetrachloride at 40 - 45℃; for 168h; Title compound not separated from byproducts; | ||
With (R,S)-[3,3'-(O2C-CH(iBu)-N=CH)2-2,2'-(O)2-1,1'-binaph-V2O3]; oxygen In Carbon tetrachloride at 0℃; for 192h; Title compound not separated from byproducts; | ||
With Camellia sinensis; dihydrogen peroxide for 0.2h; | ||
With Cu2[(R,R,R,R)-C46H46N4O2](2+); oxygen In Carbon tetrachloride at 0℃; for 168h; | ||
With air In dichloromethane at 30℃; for 24h; | ||
With oxygen In Carbon tetrachloride at 20℃; for 120h; | ||
In Carbon tetrachloride at 0℃; | ||
With air In dichloromethane at 0℃; for 72h; Title compound not separated from byproducts.; | ||
With air In dichloromethane at 30℃; for 24h; | ||
With air; C120H96Fe2N4O6 In toluene at 60℃; for 72h; optical yield given as %ee; enantioselective reaction; | ||
With iron(III) trichloride hexahydrate; (S)-2-phenylglycine at 60℃; for 24h; Neat (no solvent); optical yield given as %ee; enantioselective reaction; | ||
Multi-step reaction with 3 steps 1: iron(III) trichloride hexahydrate 2: pyridine; dmap / toluene; dichloromethane / 0 - 20 °C 3: Arthrobacter sp. lipase / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / 25 °C / pH 7 / Resolution of racemate; Enzymatic reaction | ||
Multi-step reaction with 3 steps 1: iron(III) trichloride hexahydrate 2: pyridine; dmap / toluene; dichloromethane / 6 h / 0 - 20 °C 3: Arthrobacter sp. lipase / dimethyl sulfoxide; aq. phosphate buffer / 44 h / 25 °C / pH 7 / Resolution of racemate; Enzymatic reaction | ||
87 % ee | With oxygen In toluene at -10℃; for 34h; Overall yield = 87 %; Overall yield = 89 %Chromat.; enantioselective reaction; | |
85 % ee | With oxygen In toluene at -10℃; for 34h; Overall yield = 87 %; Overall yield = 88 %Chromat.; enantioselective reaction; | |
80 % ee | With C34H36N2O10V2; oxygen In water monomer at 50℃; for 24h; Overall yield = 91 %; enantioselective reaction; | 4.3. General procedure for coupling reactions of 2-naphthols 2using (Ra,S,S)-1 in water General procedure: A test tube was charged with a water (1 mL) heterogeneoussolution of coupling substrate 2 (0.2 mmol) under O2 (1 atm) atmosphere.Vanadium catalyst (Ra,S,S)-1 (0.01 mmol, 5 mol %) wasadded to the solution. The reaction mixture was stirred at 50 Cfor 2a, 2b, 2c, 2d, and 2f or 70 C for 2e, 2g, 2h, 2i, and 2j untilthe reaction had reached completion by monitoring with TLC analysis.The reaction mixture was then directly purified by silica gelcolumn chromatography eluting with ethyl acetate/hexane to givethe coupling product. |
88 % ee | With di-tert-butyl peroxide; C120H108FeO12P3 In 1,2-dichloro-ethane at 20℃; Overall yield = 86 %; enantioselective reaction; | |
22 % ee | With tert.-butylhydroperoxide; C42H66CoN4O2(1+)*Cl(1-); potassium hydroxide In decane; toluene at 25℃; for 4h; Inert atmosphere; Schlenk technique; Overall yield = 74 %; | Oxidative coupling of 2-naphthol (general procedure). General procedure: A 5.5 M solution of tert butyl hydroperoxide in decane (0.03 mL, 3•10-4mol) was added to a Schlenk flask (charged with a mixture of 2-naphthol (14 mg,125 mmol), catalyst (1.01 10-5 mol), and freshly ground solid KOH (3 mg, 5•10-5 mol) in toluene (1.25 mL) under a flow of argon at room temperature. The reaction mixture was vigorously stirred for 4 h. The product was isolated by preparative chromatography on silica gel adsorbent and petroleum ether-ethyl acetate (5 : 1) as eluent. Yield 74%, white solid. 1H NMR, δ 7.98 (d, 2 H, J = 8.9 Hz); 7.90 (d, 2 H, J = 7.9 Hz);7.43-7.35 (m, 4 H); 7.34-7.28 (m, 2 H); 7.17 (t, 2 H, J = 9.7 Hz); 5.03 (s, 2 H, OH). |
44 % ee | With C18H25N2O7V; oxygen; acetic acid In toluene at 25℃; for 18h; Inert atmosphere; Overall yield = 75 %; | |
68 % ee | With iron(II) trifluoromethanesulfonate; tert.-butylhydroperoxide; (S)-(6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(bis(3,5-dimethylphenyl)phosphine oxide) In nonane; nitromethane at 0℃; Overall yield = 98 percent; enantioselective reaction; | |
With C12H13NO4(2-)*Cu(2+)*H2O; oxygen; potassium iodide In ethanol; water monomer at 40℃; for 24h; Overall yield = 47 percent; Optical yield = 48 percent ee; enantioselective reaction; | General procedure for the oxidative coupling of 2-naphthol General procedure: The solid catalyst (5 mg, ca. 2 mol%), KI (0.01-1.0 mmol) and 2-naphthol (1.0 mmol) were dissolved in the appropriate solvent (4 mLfor 24-48 h runs, 6 mL for longer runs). The resulting solution wasstirred at either 25 or 40 °C in a glass vessel with a vented screw cap tomaintain a constant contact with air. Control catalytic runs without thecatalyst were alsoncarried out.The analysis of oxidation profiles was done by chiral HPLC, using aDaicel Chiralpak IA column and Borwin software. The detection wavelengthused was 254 nm. The eluent was n-heptane: 1-propanol(80:20). The flow rate used was 1.0 mL/min. The internal standard(1 mmol of acetophenone) was added to the reaction mixture beforenanlyis by HPLC. In the case precipitate was present, the reactionmixtures were homogenised with an appropriate organic solvent. | |
60 % ee | With iron(II) perchlorate; (1R,2R)‐N1,N2‐di(quinolin‐8‐yl)cyclohexane‐1,2‐diamine; oxygen In chlorobenzene at 50℃; Schlenk technique; Molecular sieve; Overall yield = 84 percent; Overall yield = 60.6 mg; | 3.4. Iron-Catalyzed Asymmetric Oxidative Coupling Reaction of 2-Naphthols (S)-[1,1′-Binaphthalene]-2,2′-diol (2a) [47]: Fe(ClO4)2 (12.7 mg, 10 mol%; NOTE: perchlorate salt isa potential explosive [72] and should be handled with extreme caution) and L1 (9.2 mg, 5 mol%) weredissolved in anhydrous PhCl (5 mL) in a 25 mL Schlenk tube, and the mixture was stirred at roomtemperature for 30 min. Then, 2-naphthol (72.3 mg, 0.5 mmol, 1.0 equiv) and MS 4Å (152.7 mg) wereadded. The reaction mixture was quickly evacuated and refilled with oxygen (1 atm), and thisoperation was repeated for three cycles. Then the mixture was stirred at 50 °C under oxygen, asmonitored by TLC. The desired product was obtained (60.6 mg, 84% yield) as a pale yellow solid afterpurification by silica gel chromatography (PE to PE/EA = 10/1 to 5/1). 80:20 er (HPLC: Chiralpak ASH,hexane/propan-2-ol = 90/10, 0.5 mL/min, λ = 230 nm, tR (min): major = 24.9, minor = 38.9). 1H-NMR(400 MHz, Chloroform-d) δ 7.99 (d, J = 8.9 Hz, 2H), 7.90 (d, J = 7.9 Hz, 2H), 7.38 (td, J = 7.7, 1.6 Hz, 4H),7.31 (ddd, J = 8.2, 6.9, 1.4 Hz, 2H), 7.19-7.12 (m, 2H), 5.04 (s, 2H). |
84 % ee | With C66H58ClF4N2O3RuSi2 In toluene at 10℃; for 48h; Overall yield = 79 percent; Overall yield = 22.6 mg; enantioselective reaction; | |
83 % ee | With copper (I) iodide; oxygen; (R)-6-(((3,3'-bis(4-(tert-butyl)phenyl)-2'-hydroxy-[1,1'-binaphthalen]-2-yl)oxy)methyl)picolinic acid; Cs2CO3 In toluene at 20℃; for 72h; Overall yield = 73 percent; Overall yield = 20.9 mg; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; | |
100% | With potassium carbonate In acetone at 70℃; for 72h; Inert atmosphere; | (S)-2,2'-Dimethoxy-1,1'-binaphthalene (S4) The title compound was prepared following a literature procedure.3a,5A three-necked round-bottom flask was charged with commercially available,enantiopure (S)-[1,1'-binaphthalene]-2,2'-diol (26 g, 91 mmol, 1.0 equiv), acetone(750 mL), K2CO3 (40 g, 289 mmol, 3.2 equiv), and methyl iodide (22 ml, 50 g,350 mmol, 3.9 equiv). The reaction mixture was stirred at 70 °C for 72 h. Water (100 mL) wasadded and the formed precipitate was collected via a Büchner funnel. The title compound wasobtained as a colorless solid (29 g, 91 mmol, quantitative). The acquired NMR spectrum was inaccordance with the data reported by our group. |
99% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol; methyl iodide With potassium carbonate In acetone for 36h; Reflux; Stage #2: With water at 20℃; for 4h; |
99% | In acetone at 60℃; for 16h; Inert atmosphere; | |
98% | With potassium carbonate In acetone | |
98% | With potassium carbonate In acetone for 36h; Heating; | |
98% | With potassium carbonate In [(2)H6]acetone for 24h; Reflux; | |
98% | With potassium carbonate In acetone for 24h; Inert atmosphere; Reflux; | Synthesis of (S)-2,2'-dimethoxy-1,1'-binaphthalene(2). To a solution of (S)-1,1'-binaphthalene-2,2'-diol (1) (10 mmol) in acetone (5 mL) at room temperature under the atmosphere of N2 were added potassium carbonate (40 mmol) and methyl iodide (80 mmol), and the mixture was refluxed for 24 h. The solvent was evaporated under reduced pressure, the obtained crude product was cooled down to 25°C, diluted with water (50 mL), and the mixture was stirred for 2 h. The solid precipitate was filtered off, washed with water and hexane and dried to afford compound 2 as white powder, yield 98%. 1H NMR spectrum, δ, ppm: 3.77 s (6H, 2-OCH3), 7.10 d (2H, J =8.8 Hz, C3H and C3H), 7.21 t (2H, J = 7.6 Hz, C6H andC6H), 7.31 t (2H, J = 7.2 Hz, C7H and C7H), 7.46 d (2H,J = 9.2 Hz, C4H and C4H), 7.86 d (2H, J = 8.0 Hz, C5Hand C5H), 7.98 d (2H, J = 9.2 Hz, C8H and C8H). 13CNMR spectrum, δ, ppm: 57.2, 114.5, 119.7, 123.8, 125.3,126.5, 128.1, 129.6, 155.2. ITMS: m/z: 315.68 [M + H]+.C22H18O2. Calculated 314.38. |
96% | With potassium carbonate In acetone Heating; | |
95% | With potassium carbonate In acetone at 60℃; | |
91% | With potassium hydroxide In dimethyl sulfoxide at 70℃; for 16h; Inert atmosphere; | |
89.2% | With potassium carbonate In acetone for 36h; Reflux; Inert atmosphere; | |
86% | With potassium carbonate In acetone at 20℃; for 8h; Inert atmosphere; | |
With potassium carbonate In acetone for 36h; Heating; | ||
With potassium carbonate | ||
With sodium hydride | ||
With potassium carbonate In acetone at 20℃; | ||
With potassium carbonate In acetone for 24h; Inert atmosphere; Reflux; | 4.3.3. (S)-2,2'-Dimethoxy-l,l'-dinaphthyl A suspension of 25.0 g (8.7 mmol) (S)-2,2'-di-hydroxy-l,l'-dinaphthyl in 800 mL of acetone was heated and stirred with maximum rotation to give a homogeneous solution. To this solution stirred under N2 was added 40.0 g (29.0 mmol) K2CO3 and 60.0 g (0.42 mol) CH3I, and the mixture was refluxed for 24 h. An additional 20.0 g (0.14 mol) portion of CH3I was added, and the mixture was refluxed for an additional 12 h. The solvent was evaporated to leave a volume of 150 mL, which was cooled to 25 °C, and 900 mL water was added to the stirred suspension. The solid was collected, washed with water, and dried under vacuum to give crude product. The crude product was dissolved in 100 mL CH2Cl2 and heated. The solution was poured into 500 mL petroleum ether and appeared as a precipitate. The precipitate was filtered off and dried in vacuo to give desired product as a white powder that was used without further purification in the next reaction. Mp 224-225 °C (24.48 g, yield 89.2%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: (±)-1,1’-binaphthalene-2,2’-diol With copper chloride (I); (-)-sparteine In methanol; dichloromethane at 25℃; for 24h; Inert atmosphere; Darkness; Stage #2: With hydrogenchloride In methanol; dichloromethane; lithium hydroxide monohydrate optical yield given as %ee; enantioselective reaction; | |
87% | With (5aR,10bS)-2-mesityl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-2-ium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 24℃; for 10h; Molecular sieve; Inert atmosphere; Glovebox; enantioselective reaction; | |
76.9% | Stage #1: (±)-1,1’-binaphthalene-2,2’-diol With 3-propyl-4-((S)-1'-phenylethylamino)butanoic acid In methanol at 20 - 50℃; Resolution of racemate; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate | 15 Example 15: Separation of (S)-1 , 1 '-bi-2-naphthol from (RS)-1 ,1'-bi-2-naphthol via formation of binary/ternary co-crystal with 3-alkyl-4-(1'-phenylethylamino)butanoic acid. 3-alkyl-4-(1'-phenylethylamino)butanoic acid (0.385 moles) was dissolved in methanol (five volumes) and (RS)-1 ,1'-bi-2-naphthol (0.35 moles, i.e. 100 g) was added to it at room temperature. The mixture was stirred at 50 °C for 2 hour, during which time solid precipitate came out from the reaction mixture. Reaction mixture was allowed to cool to room temperature and filtered under reduced pressure to obtain solid co-crystal.Co-crystal was suspended in methanol (five volumes) and stirred at 50 °C for 2 h. After which reaction mixture was cooled to room temperature and filtered under reduced pressure to obtain pure solid co-crystal.Pure co-crystal was suspended in a biphasic mixture of ethyl acetate (2.5 volumes) and 1Λ/ hydrochloric acid (2.5 volumes) and stirred for 30 to 45 min to decompose the complex. Aqueous phase was washed with 2 volumes of ethyl acetate. Organic phases were mixed together and washed with brine, followed by drying over sodium sulfate. Solvent was evaporated under vacuum to obtain optically pure (S)-1 ,1'-bi-2-naphthol which was analyzed for ee on chiral chromatography.Chiral chromatographic conditions for (S)-1.1'-bi-2-naphtholRetention time for (S)-1, 1'-bi-2-naphthol : 17.77 minRetention time for (R)-1, 1'-bi-2-naphthol : 20.64 minInstrument HPLC using a Shimadzu LC 2010 system equipped Pump, Injector, UV detector and Recorder Column: Chiral Pak IA, 4.6mm x 250mm, 5μιη, column oven temperature 40 °C Detector. UV at 230 nm.Mobile phase: n-hexane (94) :n-butanol (5) : ethanol (1): trifluoroacetic acid (0.3 mL) Flow rate: 1 mL minInjection volume: 20 μΙ.Yield and enantiomeric excess of (S)-1 ,1'-bi-naphthol using various 3-alkyl-4-(1'- phenylethylamino)butanoic acids for co-crystal formation during resolution of (RS)-1 ,1 - bi-naphthol are tabulated below in table 4:Table 4* Data represented for antipode of (S)-1 ,1'-bi-naphthol. |
72% | With (R,R)-(+)-dimethoxy-N,N,N',N'-tetramethylsuccinamide (7) In hexane; benzene for 12h; Ambient temperature; | |
72% | Stage #1: (±)-1,1’-binaphthalene-2,2’-diol With (3R)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid; (3S)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid In methanol at 60℃; for 1h; Resolution of racemate; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate; ethyl acetate | |
30% | Stage #1: (±)-1,1’-binaphthalene-2,2’-diol With Orthoboric acid; (S)-1-(phenyl(pyrrolidin-1-yl)methyl)naphthalen-2-ol In acetonitrile at 25℃; for 6h; Resolution of racemate; Stage #2: With hydrogenchloride In tetrahydrofuran; diethyl ether; lithium hydroxide monohydrate Resolution of racemate; | |
Multi-step reaction with 2 steps 1: 1.697 g / DCC; DMAP / CH2Cl2 / 3 h / 20 °C 2: 93 percent / LiOH*H2O / methanol / 0.08 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 83.2 percent / Et3N / tetrahydrofuran 2: 9.3 g / aq. AcOH / 0.5 h / Heating | ||
Multi-step reaction with 2 steps 1: triethylamine; 4-dimethylaminopyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere; Resolution of racemate 2: potassium hydroxide / methanol; 1,4-dioxane / 20 °C | ||
Multi-step reaction with 2 steps 1: triethylamine / diethyl ether / 1.33 h 2: taurocholic acid sodium salt; sodium hydroxide / diethyl ether; aq. phosphate buffer / 72 h / 25 °C / pH 7.2 - 7.5 / Enzymatic reaction | ||
Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate 2: lithium hydroxide monohydrate; diethyl ether | ||
Multi-step reaction with 2 steps 1: (R)-(3,3'-bis(1-naphthyl)-1,1'-binaphthanele-2,2'-yl)phosphoric acid / dichloromethane / 20 °C 2: lithium hydroxide monohydrate / tetrahydrofuran / 24 h / 70 °C | ||
Multi-step reaction with 2 steps 1: (S)-3,3’-bis(2,4,6-triisopropylphenyl)-1,1’-binaphthyl-2,2’-diyl hydrogenphosphate / 1,2-dichloro-ethane / 40 °C 2: lithium hydroxide monohydrate / tetrahydrofuran / 24 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydride In tetrahydrofuran | |
100% | With sodium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
100% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether at 0 - 20℃; Inert atmosphere; |
100% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 20℃; for 2.5h; Inert atmosphere; | |
100% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 20℃; for 3h; | |
99% | With sodium hydride In tetrahydrofuran at 0℃; | |
98% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at -0.15℃; for 0.416667h; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide at -0.15℃; for 0.5h; | |
98% | With sodium hydride In tetrahydrofuran at 20℃; for 12h; | |
98% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; | |
98% | In tetrahydrofuran at 0℃; | |
98% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0 - 10℃; for 1h; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 10℃; for 1h; | 1.1 Example 1Preparation of (S)-3,3'-difluoro-l ,l '-binaphthyl-2,2'-diol (3)Synthesis of (S)-2,2'-bis(methoxymethoxy)-l,l'-binaphthyl (4)A solution of (R)-l,l'-binaphthyl-2,2'-diol (30 g, 0.10 mol) in THF (200 ml) is added to a stirred slurry of 60wt NaH (10.48 g, 0.26 mol) in THF (100 mL) at 0-10°C. The mixture is stirred 1 hour and treated with chloro(methoxy)methane (MOMCl) (20.25 g, 0.25 mol) while maintaining the temperature below 10°C. The resultant mixture is stirred for 1 hour at 0-5°C then treated with water (100 mL) to quench the reaction. The organic phase is collected and the aqueous phase extracted with EtOAc (2 x 250 mL). The combined organics layers are washed with water (200 mL) and concentrated. The resultant pale yellow solid is then slurried in 10: 1 (vol/vol) hexane/EtOAc. The solids are collected by filtration and dried under reduced pressure to provide 4 as a white solid. Yield: 38.5g, 98%. |
98% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 20℃; for 0.5h; | 1.1 Synthesis of Compound 2 Under nitrogen protection,At 0 ° C, 2 g of NaH (3 eq) was added to a 250 mL three-necked flask,Vacuum for nitrogen,100 mL of solvent tetrahydrofuran was added,5g(S) -dinaphthol(17.5 mmol) was dissolved in tetrahydrofuran and slowly added to the system,0 ° C for 0.5 hour,3 mL (2.3 eq) of chloromethyl methyl ether was added,At 0 for half an hour,Stirred at room temperature,TLC was detected until the reaction was complete.After the reaction is complete,The system down to 0 ,Slowly drop the H2O to hydrolyze excess NaH, separate the organic phase,The aqueous phase was extracted twice with ethyl acetate,The organic phases were combined, washed once with saturated brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. The residue was recrystallized from methanol to give the product as a white solid, 6.4 g in 98% yield. |
97% | With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; | |
96% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 4h; Further stages.; | |
96% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 1.5h; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide for 0.5h; Further stages.; | |
96% | With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; | |
96% | With sodium hydride Inert atmosphere; | |
96% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 10℃; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 15 - 20℃; for 16h; | |
96% | With sodium hydride | |
95% | With sodium hydride | |
95% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1h; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; for 4h; | |
95% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 4h; | 2 2-(methoxymethoxy)-1-(2-(methoxymethoxy)naphthalen-1-yl)naphthalene 4 4.2 Synthesis of 2-(methoxymethoxy)-1-(2-(methoxymethoxy)naphthalen-1-yl)naphthalene 4 Stirred suspension of sodium hydride (60% suspension in mineral oil, 1.18 g, 29.5 mmol) in dimethylformamide (DMF) (20 ml) was added to a solution of (S)-BINOL (1.2 g, 4.2 mmol) in DMF at 0 °C. After stirring the reaction mixture for 10 min at 0 °C, methoxy methyl chloride (1.25 ml, 16.65 mmol) was added and the reaction mixture was allowed to stir at 0 °C for 1 h. The reaction was continued at room temperature for 3 h. The reaction mixture was quenched with water and extracted with diethyl ether (60 ml). The extracted organic layer was washed with saturated NaHCO3 solution, brine, and dried over magnesium sulfate. The title compound, with diethyl ether as the solvent, was allowed to recrystallize at room temperature. Colorless crystals of the title compound appeared with 95% isolated yield. Rf = 0.39 (hexane/ethyl acetate 3:1); [α]D25 = +98 (c 1, THF). 1H NMR (400 MHz, CDCl3). δ 8.03-8.00 (d, J = 12 Hz, 2H), 7.95-7.93 (d, J = 8 Hz, 2H), 7.67-7.94 (d, J = 12H, 2H), 7.43-7.39 (m, 2H), 7.31-7.24 (m, 4H), 5.16-5.14 (d, J = 8 Hz, 2H), 5.05-5.03 (d, J = 8 Hz, 2H), 3.2 (s, 6H); 13C NMR (400 MHz, CDCl3) δ 152.7, 134.1, 129.9, 129.4, 127.9, 126.3, 125.6, 124.1, 121.3, 117.3, 95.2, 55.8. |
95% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran Stage #2: chloromethyl methyl ether at 20℃; for 12h; | |
95% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 20℃; for 2.5h; | |
94% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; for 4h; | |
94% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0 - 5℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 0 - 5℃; for 1h; Inert atmosphere; | |
92% | With sodium hydride In N,N-dimethyl-formamide for 1h; | |
92% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; | |
92% | With sodium hydride In N,N-dimethyl-formamide for 1h; | |
90% | With sodium hydride In diethyl ether; N,N-dimethyl-formamide 1.) r.t., 15 min, 2.) 0.5 h; | |
90% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 10℃; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 20℃; for 4h; | |
90% | With sodium hydride In tetrahydrofuran at 0℃; Inert atmosphere; | |
90% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran Inert atmosphere; | |
90.3% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.25h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 0 - 20℃; for 3h; | |
85% | With sodium hydride In tetrahydrofuran at 0 - 20℃; | |
83% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide at 0 - 20℃; for 3.08333h; | |
80% | With sodium hydride In N,N-dimethyl-formamide | |
80% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; | |
65% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 23℃; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran; acetic acid methyl ester; mineral oil at 23℃; for 5h; Inert atmosphere; | |
With sodium hydride Ambient temperature; | ||
With sodium hydride | ||
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 3.83333h; | ||
With sodium hydride In tetrahydrofuran; mineral oil Inert atmosphere; | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride Stage #2: chloromethyl methyl ether | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran for 1h; Stage #2: chloromethyl methyl ether In tetrahydrofuran for 12h; | 16 Example 16; Preparation of (S)-3,3'-Dimethyl-2,2'-dihydroxy-1,1'-dinaphthyl To 18.3 g of sodium hydride was added 50 g (0.175 mol) of (S)-2,2'-dihydroxy-1,1'-dinaphthyl and stirred under nitrogen in 1.0 L of dry tetrahydrofuran (THF). After 1 hour, 116 g of chloromethyl methyl ether was added to the heavy precipitate and the resulting mixture was stirred for about 12 hours and then filtered through a pad of celite. The filtrate was shaken with 500 ml of water and 1 L of methylene chloride. An aqueous layer formed and was extracted two times more with methylene chloride. The combined organic layers were washed with water saturated with potassium bicarbonate. The organic layer was dried and filtered through a squat column of alumina and the column filtrate was evaporated until crystals appeared. The crude product was purified on a silica gel column by elution with a methylene chloride/hexane solution. About 41 g of (S)-2,2'-20 bis(methoxymethoxy)-1,1'-dinaphthyl, m.p 93-94° C., 0.11 mol was collected. [00086] Next, 171 ml of 1.6 N butyllithium in hexane was added to a mixture of 41 g of the above bisacetal in 1 L of tetrahydrofuran and stirred under nitrogen at 0° C. for 45 minutes. The reaction mixture was then allowed to warm to 25° C. and 25.8 ml of dimethyl sulfate was added to the suspension and the mixture was stirred for 12 hours. About 30 ml of water saturated with sodium carbonate was added and the solvent was evaporated under reduced pressure at 50° C. [00087] The residue, in 300 ml of methylene chloride, was washed twice with water. An additional 300 ml of methylene chloride, 300 ml of methanol, and 25 ml of concentrated hydrochloric acid was added to the organic solution. The solution was stirred for 3 hours, and the solvent was evaporated. The yellow product was recrystallized from methylene chloride-hexane and was purified on a silica gel column (methylene chloride, hexane 1:1) to give 29.5 g (86%) of (S)-3-3'-dimethyl-2,2'-dihydroxy-1,1'-dinaphthyl, m.p. 204-206° C.; 1HNMR:2.2(s.6H), 7.1(d.2H), 7.3(m.2H), 7.4(m.2H), 7.8(m.4H). This example is comparable to Example 1 except that the starting compound was an (S) enantiomer. Thus, an (S) isomer was formed. | |
With sodium hydride | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; for 4h; Inert atmosphere; | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran Stage #2: chloromethyl methyl ether | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 0 - 20℃; | ||
With sodium hydride In tetrahydrofuran Inert atmosphere; | ||
With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 5h; Inert atmosphere; | 4 This example provides the synthesis of the sensor 1 described in Example 1, in particular: 0 ° C, under nitrogen protection, to a chloromethyl methyl ether protected (S) -BINOL tetrahydrofuran solution (12 mmol, THF 120 mL) Lithium solution (14.4 mmol) was added and stirred at room temperature for 5 hours.The anhydrous acetone was added to the reaction system and allowed to warm to room temperature overnight.The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic phases were combined and the organic phase was dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure. The residue was separated by column chromatography (eluent ethyl acetate / N-hexane, v / v = 1: 20-1: 5) to give methyl ether protected intermediates.The intermediate was dissolved in tetrahydrofuran and stirred in 10 mL of concentrated hydrochloric acid at room temperature to give a BINOL-derived C1 symmetric fluorescence sensor.Yield 48%. | |
With sodium hydride In tetrahydrofuran | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran at 20℃; for 4.5h; Inert atmosphere; | ||
With sodium hydride In N,N-dimethyl-formamide | ||
Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 0 - 20℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In acetonitrile at 0 - 20℃; for 5h; | |
98% | With triethylamine In acetonitrile at 0 - 20℃; for 4.5h; | |
97% | With triethylamine In acetonitrile at 0℃; |
97% | With triethylamine In acetonitrile at 25℃; for 4h; | |
97% | With triethylamine In acetonitrile at 0 - 20℃; for 5h; | 1; 1 SYNTHESIS EXAMPLE 1; [0133] Synthesis of (S)-2-hydroxy-2'-pivaloyloxy-1,1'-binaphthyl; Reaction scheme (1) A 5.726 g (20.0 mmol) portion of (S)-2,2'-dihydroxy-1,1'-binaphthalene having an optical purity of 99% ee or more and 8.4 ml (60.0 nmol) of triethylamine were dissolved in 60 ml of acetonitrile, and 2.435 g (20.2 mmol) of pivaloyl chloride was added dropwise thereto at 0° C. spending 1 hour. Thereafter, the mixture was stirred at room temperature for 4 hours. After adding 150 ml of diethyl ether to the reaction mixture, the organic layer was washed twice with 30 ml of 1 N hydrochloric acid aqueous solution, twice with 30 ml of saturated NaHCO3 aqueous solution and twice with 30 ml of saturated brine and then dried with magnesium sulfate, subsequently evaporating the solvent. By purifying the resulting residue by a silica gel column chromatography (hexane/ethyl acetate=6/1), 7.16 g of the title compound was obtained as a white solid with a yield of 97%. [0135] Its physical property values are as follows. [0136] [α]25D -56.8 (C=0.51, THF) [0137] 1H-NMR (CDCl3) δ (ppm) 0.78 (s, 9H), 5.13 (s, 1H), 7.06 (d, J=8.4 Hz, 1H), 7.23-7.39 (m, 6H), 7.51 (t, J=5.8 Hz, 1H), 7.82 (d, J=7.6 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H) [0138] 13C-NMR (CDCl3) δ (ppm) 26.51, 38.79, 114.18, 118.16, 121.74, 122.91, 123.43, 124.49, 125.54, 126.12, 126.56, 127.36, 127.81, 128.23, 128.94, 130.18, 130.62, 132.11, 133.40, 133.53, 148.22, 151.65, 177.67 [0139] Anal. calcd for C25H22O3: C, 81.06; H, 5.99. Found: C, 80.88; H, 6.11. |
96% | With triethylamine In acetonitrile at 0 - 20℃; | |
94% | With triethylamine In acetonitrile at 0℃; Inert atmosphere; | |
50% | With pyridine | |
With triethylamine In acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With Adams’s catalyst; hydrogen In glacial acetic acid at 20℃; for 72h; | (aS)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthalene-2,2′-diol19 The product was obtained by a modified version of the reported procedure.9 A mixture of (aS)-[1,1′-binaphthalene]-2,2′-diol (5.328 g,18.6 mmol) and PtO2 (0.48 g, 2.1 mmol, 0.11 equiv) in AcOH (160 mL) was placed in a 500 mL flask under H2 (balloon, 1 atm) and the mixture was stirred for 3 d at r.t. The mixture was then filtered through Celite, which was washed with CHCl3 (270 mL). The organic phase was washed successively with H2O (100 mL) and sat. aq NaHCO3 (100 mL) then dried (MgSO4), filtered, and evaporated to give a white solid; yield: 5.59 g (quant); mp 161 °C; [α]D25 -47 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.06 (d, J = 8.6 Hz, 2 H), 6.82 (d, J = 8.6Hz, 2 H), 4.53 (s, 2 H), 2.74 (t, J = 6.4 Hz, 4 H), 2.23-2.34 (m, 2 H), 2.21-2.10 (m, 2 H), 1.79-1.61 (m, 8 H). |
99% | With bis[chlorido(η2,η2-cycloocta-1,5-diene)rhodium(I)]; air; hydrogen In isopropanol at 20℃; for 16h; Molecular sieve; | |
98% | With palladium on activated charcoal; hydrogen Inert atmosphere; |
95% | With 5% Pd(II)/C(eggshell); hydrogen In ethanol at 70℃; for 7h; Autoclave; | |
95% | With 5%-palladium/activated carbon; hydrogen In ethanol at 70℃; for 7h; Inert atmosphere; | |
92% | With hydrogen; glacial acetic acid at 20℃; for 72h; | |
With Pd/C; hydrogen In ethanol at 70℃; | ||
With 10% palladium on carbon; hydrogen | ||
With hydrogen; Pearlman’s catalyst at 60℃; for 72h; | ||
100 %Chromat. | With 5% rhodium-on-charcoal; hydrogen In ethanol at 50℃; for 2h; | |
With palladium on activated charcoal; hydrogen In ethanol | ||
With palladium on activated charcoal; hydrogen Inert atmosphere; Schlenk technique; | ||
With 5%-palladium/activated carbon; hydrogen In ethanol at 75 - 80℃; for 8h; Autoclave; Sealed tube; Inert atmosphere; | 15 Example 15 In a 100 mL autoclave, 5 g of (S) -BINOL,1.5 g of 5% Pd / C (50% wet), 30mL ethanol, Sealed autoclave, Vacuum, Nitrogen was replaced once, Hydrogen replacement 3 times, Adjust the pressure to 80atm, The temperature was raised to 75 ~ 80 deg C, Incubated for 8 hours, The autoclave was cooled to room temperature, filter, The filtrate was concentrated to dryness, To obtain a viscous spares | |
With Pd/C; hydrogen In ethanol Inert atmosphere; | ||
Multi-step reaction with 2 steps 1: phosphorus trichloride / 2 h / 85 °C / Inert atmosphere 2: hydrogen; palladium(0) / ethanol | ||
With 50% palladium on charcoal; hydrogen In ethanol at 100℃; for 5.5h; | ||
With Adams’s catalyst; hydrogen |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.6% | In cyclohexane; toluene; at 3 - 52℃; for 1.25 - 1.75h; | EXAMPLE 5; Preparation of (S)-<strong>[117976-89-3]rabeprazole</strong>-(S)-(-)-BINOL complex; To a mixture of toluene (100 ml) and cyclohexane (150 ml) in a round bottom flask was added <strong>[117976-89-3]rabeprazole</strong> (10 g, 0.0278 mole), and gently warmed to 48-52 0C for 30-45 minutes. The reaction mass was cooled to 25-30 0C and further cooled to 3-8 0C, stirred for 45-60 minutes to isolate a solid product, which was washed with cold cyclohexane- toluene (1:1 v/v). The product was dried at 35-40 0C under reduced pressure. Yield: 55.6% e.e.: 99.8% optical purity: 99.9% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 8h; | Demonstration of chemospecificity on initial coupling step, preparation of (34a): In the preparation of (33a) [from (Sax)-Binol (1.00 g, 3.52 mmol) the presence of intermediate (34a) could be detected (Rf 0.45, CH2CI2). After 8 h quantitative yields were realised (1.55 g, 3.52 mmol, 100 %). M.p. 61 °C. [α]D25 -46 (c = 1.00, CHCI3). Compound (2) could be crystallised as colourless plates of a toluene solvate, C27H20O4S • CH3C6H5: calcd. C 76.7, H 5.3; found C 76.7, H 5.3 %. 1H NMR (400.1 MHz, CDCl3) of the toluene mono-solvate compound: δ = 8.10 (d, J = 9.0 Hz, 1 H, 4'-H), 8.0 (d, J = 8.2 Hz, 1 H, 5'-H), 7.9 (d, J = 9.0 Hz, 1 H, 4-H), 7.8 (d, J = 8.2 Hz, 1 H, 5-H), 7.7 (d, J = 9.0 Hz, 1 H, 3'-H), 7.5 (app. t, J = 7.1 Hz, 1 H, 7 or T or 6 or 6'-H), 7.37 (app. t, J = 7.0 Hz, 1 H, 7 or 7' or 6 or 6'-H), 7.3-7.1 (m, 11 H, Ar), 6.9 (d, J = 8.3 Hz, 2 H, Ts-m), 6.8 (d, J = 8.5 Hz, 1 H, 8 or 8'-H), 5.16 (s, 1 H, OH), 2.4 (s, 3H, Me toluene), 2.3 (s, 3H, Me (2)). 13C NMR (100.6 MHz, CDCI3) of pure, toluene freed (34a): δ = 151.6, 146.4, 144.7, 133.4 (2C), 132.7, 132.5, 130.9, 130.4, 129.3(2C), 128.8, 128.3, 127.8, 127.6, 127.5 (2 C), 126.7, 126.6, 126.2, 124.6, 123.8, 123.3, 121.7, 118.1 , 113.7, 21.6 (CH3 Ts). |
With dmap; triethylamine In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | Synthesis of Compound 27; 27(9; l-Bromo-2,2-dimethylpropane (220 mul, 1.75 mmol) was added to a mixture of l,l'-binaphth-2,2'-diol (500 mg, 1.75 mmol), potassium carbonate (LOOg, 7.27 mmol) and dimethylformamide (10 ml). The mixture was stirred at 80C for 7 days, and then cooled down and acidified with diluted hydrochloric acid. The mixture was diluted with water and extracted with ether. The crude product was purified by flash chromatography with 1-4% ethyl acetate:petrol as eluent to give the product 27(i) as a viscous oil (80 mg, 13%).1H NMR (500 MHz, CDCl3) delta 0.57, s, 9H; 3.57, m, 2H; 4.94, s, IH; 7.05, d, IH, / = 8.5 Hz; 7.17, m, IH; 7.26, m, 2H; 7.35, m, 4H; 7.81, d, J= 8 Hz, IH; 7.85, d, J = 9 Hz, 2H; 7.95, d, J = 9.5 Hz, IH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine; In n-heptane; toluene; at 70℃; for 0.5h;Product distribution / selectivity; | 10.0 g of <strong>[73590-58-6]omeprazole</strong> (29.0 mmol) and 12.4 g of (S)-(-)-[1 ,1'-binaphthalen]- 2,2'-diol (43.4 mmol) were suspended in 96 ml of toluene, 24 ml of heptane and 2 ml of triethylamine. It was heated at 70 0C for 30 min. It was cooled at 0-5 0C, the suspending solid was filtered and dried in vacuo at 40 0C. S-<strong>[73590-58-6]omeprazole</strong>*(S)-[1 ,1'-binaphthalen]-2,2'-diol inclusion complex with 1 :1 stoichiometric ratio was obtained with a 94% yield (corrected by HPLC) and a 97% e.e. (according to HPLC). 1 H-RMN (400 MHz, CDCI3): delta 11.9 (1 H, wide signal), 7.96 (1 H, s), 7.86 (2H, d, J=8.9 Hz), 7.82 (2H, d, J=8.0 Hz), 7.51 (1 H, wide signal), 7.32 (4H, m), 7.25 (2H, t, J=8.0 Hz), 7.14 (2H, d, J=8.3 Hz), 6.89 (1 H, d, J=8.5 Hz), 6.79 (1 H, wide signal), 4.70 (1 H, d, J=13.6 Hz), 4.63 (1 H, d, J=13.6 Hz), 3.80 (3H, s), 3.67 (3H, s), 2.17 (6H, s). |
89% | With triethylamine; In toluene; at 70℃; for 0.5h;Product distribution / selectivity; | 10.0 g of <strong>[73590-58-6]omeprazole</strong> (29.0 mmol) and 12.4 g of (S)-(-)-[1 ,1'-Binaphthalen]- 2,2'-diol (43.4 mmol) were suspended in 80 ml of toluene and 2 ml of triethylamine. It was heated at 70 0C for 30 min. It was cooled at 0-5 0C, the suspending solid was filtered and dried in vacuo at 40 0C. S-<strong>[73590-58-6]omeprazole</strong>*(S)- [1 ,1'-Binaphthalen]-2,2'-diol inclusion complex with 1 :1 stoichiometric ratio was obtained with a 89% yield corrected by HPLC and a 97% e.e. according to HPLC. 1H-RMN (400 MHz, CDCI3): delta 11.9 (1 H, wide signal), 7.96 (1 H, s), 7.86 (2H, d, J=8.9 Hz), 7.82 (2H, d, J=8.0 Hz), 7.51 (1 H, wide signal), 7.32 (4H, m), 7.25 (2H, t, J=8.0 Hz), 7.14 (2H, d, J=8.3 Hz), 6.89 (1 H, d, J=8.5 Hz), 6.79 (1 H, wide signal), 4.70 (1 H, d, J=13.6 Hz), 4.63 (1 H, d, J=13.6 Hz), 3.80 (3H, s), 3.67 (3H, s), 2.17 (6H, s). |
89% | With ammonia; In water; isopropyl alcohol; at 50 - 60℃;Product distribution / selectivity; | 99.6 g of (S)-(-)-binol (0.35 mol) was dissolved in a mixture of 1200 ml of isopropanol and 200 ml of water at 60 C , and 10 ml of 28% ammonia (0.15 mol) and 200.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (0.58 mol) were added thereto while maintaining the temperature at 50-55 C . 600 ml of water was slowly added to the resulting solution and after the complete dissolution of the contents was achieved, 0.2 g of the inclusion complex of es<strong>[73590-58-6]omeprazole</strong> and (S)-(- )-binol was added as a seed thereto. The resulting solution was slowly cooled to room temperature and stirred for 6 hrs, and further cooled to 5-10 C and stirred for 4 hrs. The precipitated solids were filtered, washed sequentially with a mixture of 160 ml of isopropanol and 40 ml of water and with 200 ml of n-hexane, and dried at 40 C to obtain 163.1 g of the white-yellow title compound (yield: 89%). The proton nuclear magnetic resonance (1H-NMR) and infrared ray (IR) spectra of the product were identical to those obtained in Example 1. Mp.: 157-159 C .Specific linear luminosity: [alpha]D 20 = -145.9 (c=1, THF).Optical purity: 96.8% ee (chiral HPLC). |
89% | With ethylamine; In ethanol; water; at 20 - 55℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
87.3% | With phenol; In toluene; at 20 - 30℃;seeded with esomeprazole-BINOL;Product distribution / selectivity; | EXAMPLE 2Preparation of Es<strong>[73590-58-6]omeprazole</strong>-BINOL Inclusion ComplexBINOL (6.22 g; 21.72 mmol) and phenol (4.09 g; 43.46 mmol) were added to toluene (70 ml) at 20-30 C. Omeprazole (10 g; 28.95 mmol) was added to the reaction mixture and seeded with es<strong>[73590-58-6]omeprazole</strong>-BINOL inclusion complex. Thereafter, the reaction mass was stirred for 2 h to crystallize the product. Then, hexane (35 ml) was added to the reaction mass and stirred for 15 h at 20-30 C. for complete crystallization of title compound, which was filtered, washed with toluene-hexane mixture and dried to obtain white solid of es<strong>[73590-58-6]omeprazole</strong>-BINOL inclusion complex. |
86% | With ammonia; In water; acetone; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
85% | With triethylamine; In ethanol; water; at 20 - 60℃; for 12h;Product distribution / selectivity; | 25.0 g of (S)-(-)-binol (87.3 mmol) was dissolved in a mixture of 400 ml of ethanol and 100 ml of water at 60 C, and 5.0 ml of triethylamine (35.9 mmol) and 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol) were dissolved thereto while maintaining the temperature at 50-55 C . Then, the resulting solution was slowly cooled to room temperature and stirred at that temperature for 12 hrs. The precipitated solids were filtered, washed sequentially with a mixture of 85 ml of ethanol and 15 ml of water and with 100 ml of n-hexane, and dried at 40 C to obtain 38.9 g of the white-yellow title compound (yield: 85%). M.p.: 158-160 C .Specific linear luminosity: [alpha]D20 = -146.2 (c=1, THF).Optical purity: 98.7% ee (chiral HPLC).1H-NMR (CDCl3, ppm): delta 2.24 (s, 6H), 3.73 (s, 3H), 3.87 (s, 3H), 4.65 (d, 1H), 4.78 (d, 2H), 5.50 (br. s, 2H), 6.96 (br. s, 2H), 7.18 (d, 2H), 7.40-7.28 (m, 8H), 7.70 (br. s, 1H), 7.90 (d, 2H), 7.98 (d, 2H), 8.16 (s, 1H), 11.60 (bs, 1H).IR (KBr, cm-1): 3057, 1619, 1595, 1576, 1471, 1462, 1401, 1380, 1271, 1205, 1146, 1073, 1028, 815, 570, 506, 422. |
85% | With ammonia; In water; butan-1-ol; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
85% | In cyclohexane; toluene; at 0 - 55℃; for 1.5 - 1.75h; | EXAMPLE 1; Preparation of (S)-<strong>[73590-58-6]omeprazole</strong>-(S)-(-)-BINOL complex; Omeprazole (100 g, 0.2898 mole) was added to a mixture of toluene (1600 ml) and cyclohexane (400 ml) in a round bottom flask kept at 25-30 0C. (S)-(-)-BINOL (124.3 g, 0.4346 mole) was added and the content warmed to about 50-55 0C with stirring for 30-45 minutes. The content of the flask was allowed to attain the ambient temperature and then cooled to 0-5 0C with Stirling for about an hour. The (S)-<strong>[73590-58-6]omeprazole</strong>-(S)-(-)-BINOL complex crystallizes out, filtered and washed with a mixture of cyclohexane/toluene (1 :4, v/v) pre-cooled to 0-5 0C. The (S)-<strong>[73590-58-6]omeprazole</strong>-(S)-(-)-BINOL complex was dried at 35- 40 0C under reduced pressure. The e.e. of (S)-<strong>[73590-58-6]omeprazole</strong> in the complex was found to be99.5%. Yield: 85 %.The IR spectrum of the complex is given in Fig. 3. The powder X-ray diffraction pattern is given in Fig. 4 |
83% | With ammonia; In methanol; water; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
81% | With ammonia; In water; acetonitrile; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
80 - 92% | With ammonia; In ethanol; water; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
40% | With ammonia; In 1,4-dioxane; water; at 50 - 60℃;Product distribution / selectivity; | Examples 3 to 14The procedure of Example 1 or 2 was repeated employing 50.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> (144.8 mmol), 500 ml of a reaction solvent and the other specifics shown in Table I5 to obtain various compounds, whose yields and optical purities are listed in Table 1.Table 1 |
25% | In n-heptane; toluene; at 85℃; for 0.5h;Product distribution / selectivity; | 20.0 g of <strong>[73590-58-6]omeprazole</strong> (57.9 mmol) and 25.0 g of (S)-(-)-[1 ,1'-binaphthalen]- 2,2'-diol (86.8 mmol) were suspended in 600 ml of toluene and 150 ml of heptane. It was heated at 85 0C for 30 min. It was cooled at 0-5 0C, the suspending solid was filtered and dried in vacuo at 40 0C. S-<strong>[73590-58-6]omeprazole</strong>*(S)- [1 ,1'-Binaphthalen]-2,2'-diol inclusion complex with 1 :1 stoichiometric ratio was obtained with a 25% yield corrected by HPLC and a 94% e.e. according to HPLC. |
In hexane; benzene; at 0 - 110℃; for 12h;Product distribution / selectivity; | Preparation of inclusion complex of es<strong>[73590-58-6]omeprazole</strong> and (S)-(-)-binol (formula (I)) in accordance with the method disclosed in [J. Deng et al., Tetrahedron: Asymmetry, 11, 1729-1732, 2000] and [H. Cotton et al., Tetrahedron: Asymmetry, 11, 3819-3825, 2000](S)-(-)-binol and 10.0 g of the racemic form of <strong>[73590-58-6]omeprazole</strong> were dissolved in a mixture of 288 ml of benzene and 72 ml of n-hexane at 110 C . The (S)-(-)-binol was used in the amount of 0.6 mole equivalents based on <strong>[73590-58-6]omeprazole</strong>. Then, the resulting solution was slowly cooled to 0 C and stirred for 12 hrs. The precipitated solids were filtered, and washed with a mixture of benzene and hexane to obtain the title compound.Color of the product: yellow.Optical purity: 20.0 %ee (chiral HPLC). | |
94%Chromat. | With triethylamine; In n-heptane; toluene; at 70℃; for 0.5h;Product distribution / selectivity; | Example 1 Preparation of the S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1'-binaphthalen]-2,2'-diol inclusion complex in toluene/heptane with triethylamine 10.0 g of <strong>[73590-58-6]omeprazole</strong> (29.0 mmol) and 12.4 g of (S)-(-)-[1,1'-binaphthalen]-2,2'-diol (43.4 mmol) were suspended in 96 ml of toluene, 24 ml of heptane and 2 ml of triethylamine. It was heated at 70 C. for 30 min. It was cooled at 0-5 C., the suspending solid was filtered and dried in vacuo at 40 C. S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1'-binaphthalen]-2,2'-diol inclusion complex with 1:1 stoichiometric ratio was obtained with a 94% yield (corrected by HPLC) and a 97% e.e. (according to HPLC). 1H-RMN (400 MHz, CDCl3): delta 11.9 (1H, wide signal), 7.96 (1H, s), 7.86 (2H, d, J=8.9 Hz), 7.82 (2H, d, J=8.0 Hz), 7.51 (1H, wide signal), 7.32 (4H, m), 7.25 (2H, t, J=8.0 Hz), 7.14 (2H, d, J=8.3 Hz), 6.89 (1H, d, J=8.5 Hz), 6.79 (1H, wide signal), 4.70 (1H, d, J=13.6 Hz), 4.63 (1H, d, J=13.6 Hz), 3.80 (3H, s), 3.67 (3H, s), 2.17 (6H, s). |
89%Chromat. | With triethylamine; In toluene; at 70℃; for 0.5h;Product distribution / selectivity; | Example 2Preparation of the Inclusion Complex S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1-Binaphthalen]-2,2'-diol in toluene with triethylamine10.0 g of <strong>[73590-58-6]omeprazole</strong> (29.0 mmol) and 12.4 g of (S)-(-)-[1,1'-Binaphthalen]-2,2'-diol (43.4 mmol) were suspended in 80 ml of toluene and 2 ml of triethylamine. It was heated at 70 C. for 30 min. It was cooled at 0-5 C., the suspending solid was filtered and dried in vacuo at 40 C. S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1'-Binaphthalen]-2,2'-diol inclusion complex with 1:1 stoichiometric ratio was obtained with a 89% yield corrected by HPLC and a 97% e.e. according to HPLC. 1H-RMN (400 MHz, CDCl3): delta 11.9 (1H, wide signal), 7.96 (1H, s), 7.86 (2H, d, J=8.9 Hz), 7.82 (2H, d, J=8.0 Hz), 7.51 (1H, wide signal), 7.32 (4H, m), 7.25 (2H, t, J=8.0 Hz), 7.14 (2H, d, J=8.3 Hz), 6.89 (1H, d, J=8.5 Hz), 6.79 (1H, wide signal), 4.70 (1H, d, J=13.6 Hz), 4.63 (1H, d, J=13.6 Hz), 3.80 (3H, s), 3.67 (3H, s), 2.17 (6H, s). |
25%Chromat. | In n-heptane; toluene; at 85℃; for 0.5h;Product distribution / selectivity; | Comparative Example 2Preparation of the inclusion complex S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1'-binaphthalen]-2,2'-diol in toluene/heptane without amine20.0 g of <strong>[73590-58-6]omeprazole</strong> (57.9 mmol) and 25.0 g of (S)-(-)-[1,1'-binaphthalen]-2,2'-diol (86.8 mmol) were suspended in 600 ml of toluene and 150 ml of heptane. It was heated at 85 C. for 30 min. It was cooled at 0-5 C., the suspending solid was filtered and dried in vacuo at 40 C. S-<strong>[73590-58-6]omeprazole</strong>.(S)-[1,1'-Binaphthalen]-2,2'-diol inclusion complex with 1:1 stoichiometric ratio was obtained with a 25% yield corrected by HPLC and a 94% e.e. according to HPLC. |
In dichloromethane; toluene; at 20℃; for 4.25h; | Preparation of es<strong>[73590-58-6]omeprazole</strong>-S-BINOLS-l ,l '-bi-2-naphthol (364.5 gm) was added to a solution of <strong>[73590-58-6]omeprazole</strong> (405 gm) as obtained in example 1 in methylene chloride (1000 ml) at room temperature and stirred for 15 minutes. To the reaction mixture was added toluene (6000 ml) and maintained for 4 hours at room temperature. The solid obtained was collected by filtration and dried to obtain 310 gm of es<strong>[73590-58-6]omeprazole</strong>-S-BINOL. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 4 A molecular sieve In dichloromethane at 18 - 25℃; for 1h; | 1.d Under a nitrogen atmosphere, (5)-(-)-l,l'-bi(2-naphthol) (500 mg, 1.74 mmol), titanium tetraisopropoxide (500 μL, 1.69 mmol) and powdered 4A molecular sieves (500 mg) were suspended in dichloromethane (25 mL) and stirred for one hour at room temperature. The solids were filtered off, and the filtrate concentrated in vacuo to provide (£)-(-)- l,l'-bi-(2- naphthyloxy)(diisopropoxy)titanium (980 mg, 126% yield) as a dark red powder which was used in subsequent reactions without further purification. |
100% | In dichloromethane at 20℃; for 1h; Molecular sieve; | Under a nitrogen atmosphere, (>.?)-(-)- l,l'-bi(2-naphthol) (500 mg, 1.74 mmol), titanium tetraisopropoxide (500 μL, 1.69 mmol) and powdered 4A molecular sieves (500 mg) were suspended in dichloromethane (25 mL) and stirred for one hour at room temperature. The solids were filtered off, and the filtrate concentrated in vacuo to provide (ιS)-(-)-l,l'-bi-(2- naphthyloxy)(diisopropoxy)titanium (980 mg, 126% yield) as a dark red powder which was used in subsequent reactions without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In acetone for 16h; Reflux; Inert atmosphere; | |
95% | With potassium carbonate In acetone Reflux; | |
95% | With potassium carbonate In acetone at 60℃; for 16h; |
78% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 24h; | General procedure for synthesis of acetylenic enone core General procedure: A mixture of the corresponding phenol (1.0 equiv.), propargyl bromide (1.25 equiv.) and anhydrous potassium carbonate (3.0 equiv.) in dry DMF (15 mL) was stirred at 60 oC for 24 h. The reaction mixture was then allowed to cool to room temperature and poured into ice water. The resulting precipitate was filtered, washed thoroughly with water and dissolved in CHCl3 (150 mL). The organic layer was washed with water (2 x 100 mL) and brine (1 × 150 mL), dried (Na2SO4) and evaporated to give the crude dendron, which was purified by column chromatography (SiO2). |
75% | With potassium carbonate In N,N-dimethyl-formamide Inert atmosphere; | General procedure for the synthesis of bispropargyloxy compound by O-alkylation (procedure B) General procedure: A mixture of 1.0 equiv. of the dihydroxyl compound and 2.2 equiv. of propargyl bromide with potassium carbonate (3.0 equiv.) in anhydrous DMF (5 mL) was stirred at 60 °C for 48 h under nitrogen. The reaction mixture was allowed to cool to rt and poured into ice water (500 mL) and extracted with CHCl3 (2*100 mL) and the combined organic layer was washed with water (2*50 mL) brine (50 mL) and dried over anhydrous Na2SO4. The crude product obtained after the removal of the solvent, was subjected to column chromatography over SiO2 using hexane:CHCl3 (1:2) as the eluent to give the corresponding bispropargyloxy compound. |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 48h; | ||
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In acetone Reflux; | ||
In acetone for 16h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 95% 2: 3% | Stage #1: 1,1'-bi-2-naphthol With copper(l) chloride; (-)-sparteine In methanol; dichloromethane at 25℃; for 24h; Inert atmosphere; Darkness; Stage #2: With sodium hydrogencarbonate In methanol; dichloromethane; water optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With pyridinium p-toluenesulfonate In dichloromethane at 23℃; for 16h; | 3.2. (S)-2,2'-Bis(1-ethoxyethoxy)-1,1'-binaphthyl (6) PPTS (219 mg, 0.871 mmol, 0.1 equiv) and EVE (1.88 g, 26.2 mmol, 3 equiv) were added to a suspension of (S)-BINOL (2.50 g, 8.70 mmol, 1 equiv) in 15 ml CH2Cl2. The resulting light brown mixture was stirred for 16 h at 23 °C. After evaporation of all volatile materials, the crude product was purified by flash chromatography (SiO2, hexane/EA 5:1, Rf=0.44) to furnish compound 6 (3.54 g, 8.22 mmol, 94%) as pale yellow oil. The 1H and the 13C{1H} NMR spectra showed double signal sets due to three diastereoisomers. 1H NMR (CDCl3, 500 MHz): δ=0.96 (t, J=7.0 Hz, 6H), 1.05-1.09 (m, 12H), 1.19-1.23 (m, 6H), 3.13-3.21 (m, 2H), 3.24-3.32 (m, 2H), 3.39-3.52 (m, 4H), 5.11 (q, J=5.2 Hz, 2H), 5.21 (q, J=5.2 Hz, 2H), 7.10-7.25 (m, 2×4H), 7.32-7.37 (m, 4H), 7.57-7.60 (m, 2×2H), 7.87 (d, J=8.1 Hz, 2×2H), 7.92 (d, J=9.0 Hz, 2×2H) ppm. 13C{1H} NMR (CDCl3, 125 MHz): δ=15.02 (2×CH3), 15.16 (2×CH3), 20.12 (CH3), 20.18 (CH3), 20.21 (CH3), 20.24 (CH3), 60.97 (CH2), 61.00 (CH2), 61.02 (CH2), 61.28 (CH2), 100.38 (CH), 100.53 (CH), 100.77 (CH), 100.85 (CH), 119.26 (CH), 119.45 (CH), 119.77 (CH) 119.85 (CH), 122.16 (C), 122.34 (C), 122.43 (C), 122.54 (C), 123.99 (2×CH), 124.05 (2×CH), 125.67 (CH), 125.70 (CH), 125.74 (CH), 125.77 (CH), 126.11 (CH), 126.12 (CH), 126.15 (CH), 126.18 (CH), 127.79 (4×CH), 129.10 (2×CH), 129.13 (2×CH), 129.83 (CH), 129.93 (CH), 129.96 (CH), 130.01 (CH), 134.07 (C), 134.10 (C), 134.17 (C), 134.23 (C), 152.56 (C-O), 152.61 (C-O), 152.69 (2×C-O) ppm. IR (ATR): inlMMLBox 2978 (m), 2934 (m), 1623 (m), 1594 (m), 1507 (m), 1381 (m), 1329 (m), 1226 (s), 1120 (s), 1074 (s), 977 (s), 946 (s), 865 (s), 809 (s), 751 (s) cm-1. MS (ESI, positive mode), m/z (%): 437 (100) [M+Li+], 453 (15) [M+Na+]. [α]D20 -11.1 (c 1.0, CHCl3). C28H30O4 (430.54): calcd C 78.11%, H 7.02%; found C 78.12%, H 7.13%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 70℃; for 12h; Inert atmosphere; | 4 Example 4 S type binaphthol (1.144g, 4mmol),Dibromoethanol (0.86 mL, 12.13 mmol) and triphenylphosphine (3.147 g, 12 mmol) were placed in a 50 mL reactor; 30 mL of dry tetrahydrofuran was added under nitrogen protection;DIAD (2.37mL, 11.96mmol) was added and the reaction temperature was raised to 70°C for 12h; then the solvent was removed; column chromatography was performed using n-hexane/dichloromethane (80/20) as the mobile phase to obtain a white solid,It is denoted as compound 4 with a yield of 80%. |
65% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With triphenylphosphine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #2: 2-bromoethanol With diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; Inert atmosphere; | 4.2.1. Synthesis of racemic (R,S)-8 General procedure: To a solution of binaphthol (3.46 g, 12 mmol) and PPh3 (9.5 g, 36.22 mmol) in THF (75 mL) at room temperature (rt) and under Ar is added dropwise during 2 h a mixture of 2-bromoethanol (2.56 mL, 36.04 mmol) and DEAD (azodicarboxylic acid diethyl ester, 40% solution in toluene, 16.5 mL, 36.3 mmol). After stirring overnight and solvent removal, the pale yellow oil is purified by chromatography on silica gel (CH2Cl2/petrol ether, 1:3). Recrystallisation from CH2Cl2/hexane at 5 °C gives (R,S)-8 as white needles (3.3 g, 57%). |
63% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran for 10h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | General procedure: In the air environment,Add 1a (0.2mmol), 2e (0.3mmol) to the reaction tube,Potassium carbonate (0.3 mmol),Potassium iodide (0.02 mmol) and dimethyl sulfoxide (2 ml) as reaction solvents,After adding a rubber stopper to the reaction tube,Into an oil bath preheated to 50C, stir for 24 hours.Thin layer chromatography (TLC) spots determine the end of the reaction when the TLC plate shows the reaction material 1aAfter completely disappearing, lift the reaction tube from the oil bath.Potassium hydroxide (2.0 mmol) was directly added to the reaction tube, and the mixture was placed in an oil bath preheated to 150 C. and stirred for 4 hours. After the reaction was completed, the reaction tube was cooled to room temperature.The reaction was quenched by the addition of 5 ml of water and then extracted and dried with ethyl acetate.The target product 3a was isolated by column chromatography.This type of invention simplifies the traditional cumbersome synthesis steps, is simple and easy to operate.Product yield 72%; yellow solid; 99% ee |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tert.-butylnitrite In tetrahydrofuran at 20℃; for 12h; | 6-7 Example 6: The target product in this embodiment is This is achieved by the following steps: 1 mmol (S) -1,1'-binaphthol was added to the reaction flask and dissolved in 5 mL of tetrahydrofuran.422 uL of tert-butyl nitrite was added, stirred at room temperature for 12 hours, and after the reaction was completed,The organic solvent was removed by a rotary evaporator, and the product was subjected to column chromatography to obtain the product nitrobisnaphthol. The reaction yield was 92%. |
72% | With nitric acid; acetic acid at 20℃; for 16h; | Preparation of (S)-/(R)-6,6'-dinitro[1,1'-dinaphthyl]-2,2'-diphenol [(S)-3/(R)-3] (S)-/(R)-BINOL (5.72 g, 20 mmol) was dissolved in acetic acid (25 mL) and dichloromethane (25 mL).A mixed solution of nitric acid (2.58 g, 40.1 mmol) and acetic acid (2 mL) was gradually added dropwise to the above solution. Reaction at room temperatureAfter stirring for 16 hours, the reaction mixture was poured into ice water (1000 mL), filtered, and washed with methanol and chloroform to give a green solid. (1) (S)-11 (5.4 g, yield 72%); (2) (R)-11 (4.4 g, yield 59%). |
With nitric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: diethyl chlorophosphate In tetrahydrofuran; mineral oil at 20℃; for 0.5h; | Synthesis of (S)-1,10-binaphthyl-2,2'-bis(diethylphosphate) 3 21 To a solution of (S)-BINOL (1.0g, 3.5mmol) in THF (10mL) was added NaH (60% in oil, 0.3g, 7.5 mmol) at 0°C. The mixture was stirred for 30 min, then diethyl chlorophosphate (1.1mL, 7.6 mmol) was added, and stirring was continued for 30 min at room temperature. The reaction was quenched with aqueous saturated NH4Cl and the mixture was extracted with ethyl acetate. The organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=1/1) to provide the diethylphosphate 3 as a colorless solid (1.95g, quant.); [α]D20 -5.1 (c 0.85, CHCl3); 1H NMR (500MHz, CDC13): δ=0.85 (t,J=6.3Hz, 6H), 1.06 (t, J=6.3Hz, 6H), 3.46-3.52 (m, 4H), 3.67-3.79 (m, 4H), 7.27-7.33 (m, 4H), 7.42-7.45 (m, 2H), 7.79 (d,J=9.2Hz, 2H), 7.90 (d, J=8.0Hz, 2H), 7.97 (d, J=9.2Hz, 2H); 13C NMR (125MHz, CDC13): δ=15.5, 15.7, 64.0, 64.3, 119.1, 121.5, 125.3, 126.1, 126.9, 127.8, 129.9, 130.7, 133.5, 146.7; IR (CHCl3): 3061, 2931, 2911, 1624, 1593, 1508, 1475, 1394, 1361, 1265, 1165, 1066, 1011, 868, 854, 816cm-1; HRMS (ESI) calcd for C28H32O8P2Na m/z 581.1465 [M+Na]+, found 581.1481. |
88% | Stage #1: (S)-[1,1']-binaphthalenyl-2,2'-diol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Sealed tube; Stage #2: diethyl chlorophosphate In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Sealed tube; | Synthesis of Bisphosphates 13 and 15 with Diethyl Chlorophosphate (12); General Procedure General procedure: Under an argon atmosphere, to a solution of 1or 3(1 equiv) in anhydrous THF (0.3 M), NaH (2.5 equiv) was added at 0 °C and the mixture was stirred at this temperature for 30 min before the addition of 12(2.1 equiv). The mixture was stirred at r.t. for an additional 30 min,then hydrolyzed with H2O and extracted with CH2Cl2. The organic phase was washed with an aqueous 1N HCl solution and with H2O, then dried over anhydrous MgSO4. The solvent was removed undervacuum and the residue was purified by column chromatography onsilica gel using a mixture of petroleum ether/EtOAc as eluent. Compound 13 [α]D20-2.2 (c= 1.2, CHCl3) [cf. [α]D20-5.1 (c= 0.85, CHCl3)].18 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine; caesium carbonate In acetone at 40℃; for 4h; Inert atmosphere; | Procedure for the synthesis of (S,S,S)-TBP. Procedure for the synthesis of (S,S,S)-TBP. In a round-bottom flask were introduced (S)-binol (9.45 g, 33 mmol), hexachlorocyclotriphosphazene (2 g, 10 mmol) and cesium carbonate (21.97 g, 70 mmol). The flask was purged three times with nitrogen and acetone was added. The reaction mixture was stirred for 4 h at 40 °C. A precipitate was formed during formation of the desired product. Solid was filtered and washed three times with water and acetone. The resulting powder was grinded in a fine powder and suspended in water. After 1 h stirring, the solid was filtered, washed three times with water and acetone and dried under reduced pressure. TBP was obtained as a white powder (94% yield). RMN 1H (CDCl3, 400 MHz): δ (ppm)=7.84 (m, 12H); 7.53 (d, 6H, J=8,8 Hz); 7.41 (m, 12H); 7.27 (m, 6H); RMN 13C (CDCl3, 100 MHz): δ (ppm)=147,40 (6C); 132.26 (6C); 131.58 (6C); 130.85 (6C); 128.38 (6C); 127.25 (6C); 126.16 (6C); 125.22 (6C); 121.85 (6C); 121.58 (6C); RMN 31P (CDCl3, 160 MHz): δ (ppm)=27.48 (3P); HRMS (TOF ES+) [M+H]+: calculated for C60H37N3O6P3: 988.1895; found: 988.1901; [α]D 72° (c=0.5 in CHCl3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium hydroxide In 1,4-dioxane; methanol at 20℃; | 2 General method for the hydrolysis of binaphthol derivative esters General procedure: To a solution of binaphthol derivative ester in methanol and 1,4-dioxane (1:1 ratio) was added potassium hydroxide. The reaction mixture was stirred at room temperature for 3h and then acidified with 2M hydrochloric acid and extracted three times with ethyl acetate. The combined organic layer was washed with saturated sodium hydrogen carbonate solution, water and brine then dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by preparative thin layer chromatography (silica gel, ethyl acetate:hexane=20:80 as an eluent) to give 7,7′-disubstituted 1,1′-bi-2-naphthols. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere; | |
71% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
65% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; Cooling with ice; | 1 Synthesis of compound S-1 Under ice bath, (S)-Binaphthol (4.29g, 15mmol) and DIEA (4.07g, 31.5mmol) were dissolved in THF, and MOMBr (bromomethyl methyl ether, 2.06g, 16.5mmol) was added dropwise In THF (10 mL) solution, the addition was completed within 20 minutes; then heated to room temperature and stirred overnight. Acetic acid (0.90 g, 15 mmol) was added to react with excess DIEA. Water and ethyl acetate were added for extraction, the organic layer was separated, washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Separation by silica gel column chromatography (eluent: petroleum ether and ethyl acetate volume ratio = 10:1) to obtain 3.22 g of compound S-1, a white solid, with a yield of 65%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; at 50℃; for 0.5h;Inert atmosphere; | General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 muL, 0.02 mmol), pinacol (0.10 M, 200 muL,0.02mmol) and 5c (0.25M, 80 muL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 muL) was added undera positive pressure of argon. The reaction was stirred at 50°C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 muL, 5.0 mumol)was added under a positive pressure of argon and thereaction stirred at 23°C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 muL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 muL, 0.20 mmol), diethyl malonate (30 muL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 mumol)were added sequentially. The reaction was stirred at 23°Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 muL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0percent isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; at 50℃; for 0.5h;Inert atmosphere; | General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 muL, 0.02 mmol), pinacol (0.10 M, 200 muL,0.02mmol) and 5c (0.25M, 80 muL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 muL) was added undera positive pressure of argon. The reaction was stirred at 50°C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 muL, 5.0 mumol)was added under a positive pressure of argon and thereaction stirred at 23°C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 muL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 muL, 0.20 mmol), diethyl malonate (30 muL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 mumol)were added sequentially. The reaction was stirred at 23°Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 muL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0percent isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform at 50℃; for 0.5h; Inert atmosphere; | 3.1.1. General procedure for assembly of ligandsand evaluation in the allylic substitution of rac-7 General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 μL, 0.02 mmol), pinacol (0.10 M, 200 μL,0.02mmol) and 5c (0.25M, 80 μL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 μL) was added undera positive pressure of argon. The reaction was stirred at 50°C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 μL, 5.0 μmol)was added under a positive pressure of argon and thereaction stirred at 23°C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 μL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 μL, 0.20 mmol), diethyl malonate (30 μL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 μmol)were added sequentially. The reaction was stirred at 23°Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 μL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0% isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; at 50℃; for 0.5h;Inert atmosphere; | General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 muL, 0.02 mmol), pinacol (0.10 M, 200 muL,0.02mmol) and 5c (0.25M, 80 muL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 muL) was added undera positive pressure of argon. The reaction was stirred at 50C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 muL, 5.0 mumol)was added under a positive pressure of argon and thereaction stirred at 23C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 muL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 muL, 0.20 mmol), diethyl malonate (30 muL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 mumol)were added sequentially. The reaction was stirred at 23Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 muL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0% isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform at 50℃; for 0.5h; Inert atmosphere; | 3.1.1. General procedure for assembly of ligandsand evaluation in the allylic substitution of rac-7 General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 μL, 0.02 mmol), pinacol (0.10 M, 200 μL,0.02mmol) and 5c (0.25M, 80 μL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 μL) was added undera positive pressure of argon. The reaction was stirred at 50°C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 μL, 5.0 μmol)was added under a positive pressure of argon and thereaction stirred at 23°C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 μL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 μL, 0.20 mmol), diethyl malonate (30 μL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 μmol)were added sequentially. The reaction was stirred at 23°Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 μL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0% isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; at 50℃; for 0.5h;Inert atmosphere; | General procedure: A 0.5-dram vial equipped with a magnetic stirring bar wascharged with stock solutions of 2-formylphenylboronicacid (0.10 M, 200 μL, 0.02 mmol), pinacol (0.10 M, 200 μL,0.02mmol) and 5c (0.25M, 80 μL, 0.02mmol). The solventswere removed in vacuo. CHCl3 (50 μL) was added undera positive pressure of argon. The reaction was stirred at 50C for 30 min. The volatiles were then removed under highvacuum. [Pd(allyl)Cl]2 (0.13 M in CHCl3, 40 μL, 5.0 μmol)was added under a positive pressure of argon and thereaction stirred at 23C for 15 min. Allyl acetate rac-7(0.01 M in CHCl3, 10 μL, 0.10 mmol), bis(trimethylsilyl)acetamide (49 μL, 0.20 mmol), diethyl malonate (30 μL,0.20 mmol) and potassium acetate (0.50 mg, 5.0 μmol)were added sequentially. The reaction was stirred at 23Cfor 24 hours. The crude reaction mixture was then filteredthrough a short plug of Celite and rinsed three times withCH2Cl2. An aliquot of the reaction mixture (5.0 μL) wasused for conversion and ee analyses using HPLC. HPLCconditions: Chiralpak IA column, 2.0% isopropanol/hexanes,0.5 mL/min, 254 nm, tr: 22.9 and 29.2min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; Sealed tube; | Synthesis of Monophosphates 6, 8, 9, and 11 with Diphenyl Phosphoryl Chloride (10); General Procedure General procedure: Under an argon atmosphere, to a solution of 1-4 (1 equiv) and Et3N (3 equiv) in anhydrous CH2Cl2 (0.15 M), 10 (3 equiv) was added dropwise at 0 °C. The mixture was stirred at r.t. overnight, then hydrolyzed with H2O and extracted with CH2Cl2. The organic phase was washed with an aqueous 1N HCl solution and with H2O, then dried over anhydrous MgSO4. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel using a mixture of petroleum ether/EtOAc as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; Sealed tube; | Synthesis of Monophosphates 6, 8, and 9 from Phenyl Dichlorophosphate (5); General Procedure General procedure: Under an argon atmosphere, to a solution of 1, 3, or 4(1 equiv) and Et3N (3 equiv) in anhydrous CH2Cl2 (0.15 M), 5 (1.2 equiv) was added dropwise at 0 °C. The mixture was stirred at r.t. overnight, then hydrolyzed with H2O and extracted with CH2Cl2. The organic phase was washed with an aqueous 1N HCl solution and with H2O, then dried over anhydrous MgSO4. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel using a mixture of petroleum ether/EtOAc as eluent. X-ray single quality crystals of compounds 8 and 9 were grown by slow diffusion of pentane in CH2Cl2 solution. |
63% | With triethylamine In dichloromethane at 23℃; for 18h; | (S)-Phenyl 1,1′-Binaphthyl-2,2′-diylphosphate (8). Toa stirred solution of phenyl dichlorophosphate (0.16 mL, 1.1mmol, 95%, 1.1 equiv) and (S)-BINOL (0.28 g, 1.0 mmol, 1.0equiv) in anhydrous dichloromethane (10 mL) was addedtriethylamine (0.3 mL, 2.2 mmol, 2.2 equiv), and the mixturewas stirred for 18 h at room temperature (23 °C). The reactionmixture was filtered and washed with 0.1 N HCl and asaturated solution of NaHCO3 yielding 0.27 g (63%) ofproduct: 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.1 Hz,1H), 8.04 (d, J = 9.6 Hz, 1H), 8.01-7.97 (m, 2H), 7.67 (d, J =8.7 Hz, 1H), 7.56-7.50 (m, 2H), 7.48 (d, J = 8.7 Hz, 1H),7.46-7.29 (m, 8H), 7.27-7.21 (m, 1H); 31P NMR (160 MHz,CDCl3) δ -3.44 (s); HRMS (ESI+) m/z [M + H]+ calcd forC26H18O4P 425.0943, found 425.0931. |
A840497[ 602-09-5 ]
[1,1'-Binaphthalene]-2,2'-diol
Reason: Racemic-enantiomer
A290939[ 18531-94-7 ]
(R)-[1,1'-Binaphthalene]-2,2'-diol
Reason: Optical isomers
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