Structure of 16355-00-3
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CAS No. : | 16355-00-3 |
Formula : | C8H10O2 |
M.W : | 138.16 |
SMILES Code : | O[C@H](C1=CC=CC=C1)CO |
MDL No. : | MFCD00064262 |
InChI Key : | PWMWNFMRSKOCEY-QMMMGPOBSA-N |
Pubchem ID : | 2724621 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 38.54 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.24 |
Solubility | 7.92 mg/ml ; 0.0573 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.78 |
Solubility | 22.7 mg/ml ; 0.164 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.67 |
Solubility | 2.95 mg/ml ; 0.0213 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.88 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.36 |
* 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 |
---|---|---|
92% | With potassium osmate dihydrate; potassium carbonate; (9S,9"S)-9,9"-[phthalazine-1,4-diylbis-(oxy)]bis[10,11-dihydro-6'-methoxycinchonane]; potassium hexacyanoferrate(III); In water; tert-butyl alcohol;Electrochemical reaction; Irradiation; Inert atmosphere; | General procedure: A flame-dried three-necked round-bottomed flask was chargedunder argon with 1 equiv of o-phenylenediamine (0.31 mmol,33.8 mg), 1.1 equiv of 3-nitrobenzaldehyde (0.34 mmol,52 mg), 20 mol % CAN (31 mg), and LiClO4 (0.1 M, 127 mg)in 12 mL of THF/MeOH 5:1. A RVC anode and a carbon rodcathode were inserted into the flask. A constant current of 8 mAwas supplied (either via a potentiostat or a photovoltaic cell)until 2.3 F/mol of charge had passed. After the electrolysis, thecontents of the flask were extracted with EtOAc, washed withbrine, and dried with MgSO4. The product was purified bycolumn chromatography (EtOAc/hexanes 1:1) to give the benzimidazoleproduct |
82% | With dihydrogen peroxide; In toluene; at 55℃; for 1.8h;Green chemistry; | Take a certain amount of styrene, followed by adding its mass is 0.3 times and 1.2 times the catalyst 40% hydrogen peroxide, reaction at 55 1.8h, to obtain a reaction mixture;The method of preparation of the catalyst was: S- take a certain amount of nicotine, which was added 2.25 times mass of bromooctadecane, 115 refluxed in toluene for 20 hours, the solvent evaporated under reduced pressure to give a yellow viscous chiral ionic liquids , was added dropwise with stirring a solution of phosphorous acid to a concentration of 6% by mass percentage of, 400r / min, the quality of phosphate acid solution stirring rate was 20 times the mass of S- nicotine, generating a particle diameter of 0.4mm shaped yellow precipitation, filtration and drying to obtain a catalyst;The toluene was used in an amount 12 times the mass of S- nicotine;2) a) step the reaction mixture was added to 18 times its mass of water at room temperature, filtered, and recovered the precipitate, the filtrate was added 8 times the mass of ethyl acetate, the extracts were collected, the solvent was evaporated under reduced pressure to give (R) - benzene white glycol base crude;3) Step 2) The crude product was dissolved in 0.2 times its mass, petroleum ether 75 , the cooling was recrystallized, filtered and dried to obtain (R) - phenyl glycol pure.Obtained by the method described above (R) - phenyl ethylene glycol in a yield of 82%, compared with the standard of enantiomeric excess (ee) of 100%. |
80% | With potassium osmate(VI); disodium hydrogenphosphate; dipotassium peroxodisulfate; methanesulfonamide; (9S,9"S)-9,9"-[phthalazine-1,4-diylbis-(oxy)]bis[10,11-dihydro-6'-methoxycinchonane]; potassium hexacyanoferrate(III); In water; tert-butyl alcohol; at 20℃; | General procedure: Water (5 mL/mmol substrate) was added to a solid mixture of K2S2O8 (1.5 equiv), Na2HPO4 (3 or 4 equiv), NaIO4 (0.2 equiv) or K3Fe(CN)6 (0.2 equiv), MeSO2NH2 (1 equiv) and K2OsO2(OH)4 (0.05 equiv) at room temperature, and the mixture was stirred for 5 min. (DHQD)2Phal (0.075 equiv), tert-BuOH (5 mL/mmol substrate), and the olefin (1 equiv) were then added sequentially, and the reaction was stirred at room temperature until olefin was consumed as judged by TLC. A solution of saturated aqueous Na2S2O3 was added, and the mixture was extracted with CH2Cl2 (3 x 5 mL/mmol substrate).The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure, and the crude product was purified by flash chromatography to provide the pure diol. |
With (DHQ)2PHAL; osmium(VIII) oxide; potassium carbonate; potassium hexacyanoferrate(III); In water; toluene; tert-butyl alcohol; at 0℃; for 24h; | EXAMPLE 1 To a mixture of K3Fe(CN)6, K2CO3 and (DHQ)2PHAL in t-BuOH-H2O (1:1) cooled to 0 C. was added OsO4 (0.1 M solution in toluene).After stirring for 5 minutes at 0 C., styrene was added in one portion.The reaction mixture was stirred at 0 C. for 24 h and then quenched with solid sodium sulfite.The stirring was continued for 1 h and the solution was extracted with ethyl acetate.The combined organic phase was washed with brine, dried (Na2SO4) and concentrated.Silica gel column chromatography of crude product using petroleum ether: EtOAc (3.5:1.5) as eluent gave (R)-phenylethylene glycol as a white solid. | |
93%Chromat. | With D-glucose; In aq. phosphate buffer; Hexadecane; at 30℃; for 8h;pH 8.0;Microbiological reaction; | General procedure: To research the potential for production of another enantiomer, substituted (R)-mandelic acid, we then tested another existing system to produce the key intermediates, substituted (R)-phenylethane-1,2-diols. The E. coli (P-StyA*StyB*StEH) was grown in 1 mL LB medium containing 50 mg/L kanamycin at 37 C. and then 2% inoculated into 25 mL M9-Glu-Y medium with 50 mg/L kanamycin. When OD600 reached 0.6, 0.5 mM IPTG was added to induce the expressing of enzymes. The cells continued to grow and expressed protein for 12 hours at 22 C. before they were harvested by centrifuge (5000 g, 5 mins). The cells were resuspended in 100 mM KPB buffer (pH=8.0) to 10 g cdw/L and used in a buffer:hexadecane two-phase system (2 mL:2 mL) for biotransformation of 20 mM different substituted styrenes. The reaction was conducted at 30 C. and 300 rpm in a 100-mL flask for 8 hours. A 100 uL aqueous sample was taken during the reaction and analyzed by reverse phase HPLC (Agilent poroshell 120 EC-C18 column, acetonitrile:water=60:40, flow rate 0.5 mL/min) to quantify the production of diols. The ee of the product diols was determined by chiral HPLC. As can be seen in Table 2, many of the (R)-diols can be produced in high ee (12 out of 16 achieved >85% ee) with good yields (>80%) from substituted styrenes by E. coli (P-StyA*StyB*StEH) cells. The recombinant biocatalyst E. coli (P-StyA*StyB*StEH) was proven to accept various substituted styrenes and yield (R)-diols, which are subjected to tandem biocatalytic oxidation to produce substituted (R)-mandelic acids. |
With potassium permanganate; N-benzyl-N,N,N-triethylammonium chloride; potassium hydroxide; In dichloromethane; at -40 - -25℃; for 15h;Autoclave; Large scale; | (1) 208.3 kg of styrene was charged into a 5000 L reactor, and 700 L of dichloromethane was added with stirring,And 18 kg of potassium hydroxide was added, 2.5 kg of benzyltriethylammonium chloride was added at a temperature of -40 C to _25 C,An aqueous solution of potassium permanganate (328 kg) was added in portions. After 15 h of reaction, the solid residue was removed by filtration.The reaction solution was concentrated to remove the solvent and the remaining very little amount of phenylene to give the crude (R) _l_phenyl-1,2-ethanone. | |
With AD mix-β; In water; tert-butyl alcohol; at 0℃; | General procedure: A round-bottomed flask, equipped with amagnetic stirrer, was chargedwith 5 mL of tert-butyl alcohol, 5 mL of water, and 1.4 g ofAD-mix-α or AD-mix-β. Stirring at rt produced two clear phases; the loweraqueous phase appears bright yellow. The mixture was cooled to 0 C whereuponsome of the dissolved salts precipitated.One mmol of olefin was addedat once, and the heterogeneous slurry was stirred vigorously at 0 C for 6-24 h(progress was monitored by TLC). While the mixture was stirred at 0 C, anhydroussodium sulfite (1.5 g) was addedand the mixture was allowed to warm to rt and further stirred for 30-60 min. EtOAc (10 mL) was added to the reactionmixture and after separation of the layers, the aqueous phase was furtherextracted with EtOAc (3x5 mL). The combined organic extracts were dried over anhydrousNa2SO4 and concentrated to afford the diol and theligand. This crude reaction mixture waspurified by silica gel column chromatography (100-200 mesh) elutingwith EtOAc/petroleum ether (1:1) to afford the pure1,2-diol in 80-98% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.2% | With water monomer; In aq. phosphate buffer; at 20℃; for 8h;pH 7.0; | General procedure: The scale-up enantioconvergent hydrolysis of 400 mM rac-SO in50 mL 30% (v/v) Tween-20/phosphate buffer was conducted using200 mg/mL wet cells of E. coli/sleh2 at 20 C within 8 h. During the hydrolytic process, aliquots of 50 L samples were drawn from hydrolyticsuspension periodically, and monitored by chiral GC until rac-SOwas almost completely hydrolyzed. Then, total hydrolytic solution wasextracted three times with equivoluminal ethyl acetate, and purified bysilica gel column chromatography, followed by recrystallization with nhexane,thus obtaining (R)-PED product with over 99% eep and highoverall yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ketoreductase; stereospecific carbonyl reductase 1; zinc(II) sulfate; In aq. phosphate buffer; at 30℃; for 8h;pH 7.0;Enzymatic reaction; | The biocatalytic deracemization of racemic (R,S)-PED was performed by the following methods: a reaction mixture (2.0 mL) containing 1gL-1 (R,S)-PED, 1 mM ZnSO4, and the purified enzymes of SCR1 and KRD. The reaction was performed at 30C and 200 rpm for 8 h. The analytical methods were carried out as described above. The reaction parameters, including activity ratio of SCR1 (20-100 U) to KRD (20-100 U), molar ratio of NADP+ (0.05-0.2 mM) to NADPH (0.05-0.2 mM), and substrate concentration (1-5 gL-1), were evaluated for the deracemization of (R,S)-PED to (R)-enantiomer. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diborane; In tetrahydrofuran; methanol; | EXAMPLE 1 Preparation of R-styrene oxide To a cold stirred solution of 300 g. of R-mandelic acid in 2000 ml. of tetrahydrofuran was added dropwise over two hours 3000 ml. of a 1 molar solution of diborane in tetrahydrofuran. The reaction mixture was stirred for twelve hours at 25 C. following complete addition, and then was cooled to 0 C. in an ice water bath. To the cold solution was added 600 ml. of methanol dropwise over thirty minutes, and the reaction mixture was then stirred for another three hours. Removal of the solvent by evaporation under reduced pressure provided 260 g. of the product as a solid. The solid was crystallized from diethyl ether to provide R-2-phenyl-2-hydroxyethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In the glove box, add the Mn-Cat.1 catalyst (3.8 mg, 0.005 mmol) and the substrate α-hydroxyacetophenone (136 mg, 1 mmol) into a 5 mL clear glass vial, then potassium carbonate (1.4 mg, 0.01 mmol) and absolute ethanol (3 mL) were added, and the mixture was stirred at room temperature for 5 min. Finally, the hydrogenation bottle was put into the autoclave, the hydrogen was replaced three times and then filled with 30 bar H2, and reacted at 50C for 16h. After the reaction is completed, the hydrogen is released carefully, the solvent is spin-dried under reduced pressure, and the hydrogenated product alcohol is purified by silica gel column, a colorless viscous liquid. The reaction is determined by HPLC, >99% conversion, 95% yield, 80% ee. | |
With hydrogen;dichloro[(R)-N-bis(3,4-difluorophenyl)phosphino-N-methyl-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine](triphenylphosphine)ruthenium; In ethanol; at 20℃; under 16274.9 Torr; for 6h;Conversion of starting material; | Complex 5A-j from Example 12 (2.8 mg; 0.0025 mmol; 0.005 equiv) and 2hydroxy-acetophenone (68 mg; 0.5 mmol) were placed in a reaction vessel, which was pressurized with argon and vented five times. Argon-degassed ethanol (5 mL) was added and the reaction mixture was pressurized with argon and vented five times and then pressurized to 20.7 barg (300 psig) with hydrogen and stirred at ambient temperature for 6 hours. The vessel was vented, then pressurized with argon and vented five times. Analysis of the reaction mixture by chiral GC indicated 11.2% conversion to (R)-1-phenyl-1,2-ethanediol with 77.6% ee according to chiral GC. Chiral GC [30 m×0.25 mm Cyclosil-B (J&W Scientific), 0.25 μm film thickness, 150 C. isothermal]: tR=12.94 min (2-hydroxy-acetophenone), tR 28.30 min [(S)-1-phenyl-1,2-ethanediol], tR=29.21 min [(R)-1-phenyl-1,2-ethanediol]. | |
With formic acid; triethylamine;Cp*IrCl[(S,S)-MsDPEN]; at 50℃; for 24h;Product distribution / selectivity; | A formic acid-triethylamine mixture (molar ratio of HCOOH:Et3N:substrate=3.1:2.6:1) as the hydrogen source, 1.044 mg (1.6 μmol) of Cp*IrCl[(S,S)-MsDPEN] as the catalyst, and 1.089 g (8.0 mmol) of α-hydroxyphenone were introduced in a 20 mL Schlenk tube, and the mixture was subjected to argon substitution and maintained at 50 C. for 24 hr while stirring. HPLC analysis of the reactant confirmed that 1-phenyl-1,2-ethanediol with optical purity of 66% ee was produced in 12% yield. |
With potassium formate;(1,2,3,4,5-pentamethylcyclopentadienyl)IrCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine]; In water; toluene; at 50℃; for 24h;Product distribution / selectivity; | The reaction was performed under the same conditions as those in Example B-1, except that 1.165 mg (1.6 μmol) of Cp*IrCl[(R,R)-TsDPEN] was used as the catalyst. HPLC analysis of the reactant confirmed that 1-phenyl-1,2-ethanediol with optical purity of 28% ee was produced in 30% yield. Comparison with Example B-1 demonstrated that it is superior to have a methyl group as the substituent on the sulfonyl group. | |
With potassium formate;[(1,2,3,4,5-pentamethylcyclopentadienyl)IrCl((S,S)-N-(p-toluenesulfonyl)-1,2-cyclohexanediamine(1-))]; In water; toluene; at 50℃; for 24h;Product distribution / selectivity; | The reaction was performed under the same conditions as those in Example B-1, except that 1.008 mg (1.6 μmol) of Cp*IrCl[(S,S)-TsCYDN] was used as the catalyst. HPLC analysis of the reactant confirmed that 1-phenyl-1,2-ethanediol with optical purity of 68% ee was produced in 10% yield. Comparison with Example B-1 demonstrated the superiority of MsDPEN as the dimaine ligand. | |
With potassium formate;Cp*IrCl[(R,R)-(R)-CsDPEN]; In water; toluene; at 50℃; for 24h;Product distribution / selectivity; | The reaction was performed under the same conditions as those in Example B-1, except that 1.467 mg (1.6 μmol) of Cp*IrCl[(R,R)-(R)-CsDPEN] was used as the catalyst. HPLC analysis of the reactant confirmed that 1-phenyl-1,2-ethanediol with optical purity of 87% ee was produced in 40% yield, showing that the catalytic efficiency of the iridium complex having camphorsulfonyl DPEN as the ligand is insufficient for the asymmetric reduction of ketones having a functional group. | |
With hydrogen;Ru(trifluoromethanesulfonate)(N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine)(η6-cymene); In methanol; at 50℃; under 76005.1 Torr; for 16h;Product distribution / selectivity; | The hydrogenation reaction of α-hydroxyacetophenone was performed by the same method as in Example 30 except that the sulfonate catalyst was changed to Ru(OTf)[(S,S)-Tsdpen](p-cymene). As a result, 67% ee of optically active 1-phenyl-1,2-ethanediol was produced in a yield of only 3%. | |
With potassium phosphate; Candida parapsilosis aldo-keto reductase CPAR5; NADPH; at 30℃; for 8h;pH 6.5;Enzymatic reaction; | General procedure: Asymmetric reductions of various carbonyl compounds by the purified enzymes were carried out at 30C for 8h with mild shaking in a reaction mixture containing 0.1M potassium phosphate buffer (pH 6.5), 1gL-1 substrate, 10mM NADPH, and the purified enzyme of appropriate amount in a total volume of 2mL. In order to determine the absolute configuration of chiral alcohols, the reaction products were extracted with ethyl acetate or hexane and the organic layer was used for analysis. The optical purity of the reaction products were determined by chiral HPLC (HP 1100, Agilent, USA) equipped with Chiralcel OB-H column (4.6mm×250mm; Daicel Chemical Ind. Ltd., Japan) or chiral GC (7890A, Agilent, USA) equipped with FID detector and Chrompack Chirasil-Dex CB chiral capillary column (25m×0.25mm; Varian, USA) [21]. | |
With silver tetrafluoroborate; diethoxymethylane; C26H29N3O2*Cl(1-)*Ir(1+)*C8H12; at 20℃; for 20h; | General procedure: A flask was charged with azolium salt L12 (0.02 mmol, 9.1 mg),Ag2O (0.01 mmol, 2.4 mg) and CH2Cl2(1 mL). After stirring the resulting mixture at room temperature for 2 h in the dark, CH2Cl2 was removed in vacuo. Then, a THF (1 mL) solution of [IrCl(cod)]2(0.01 mmol, 6.9 mg) was added to the reaction vessel. The resulting mixture was stirred at room temperature for an additional 4 h in the dark, filtered through a membrane filter, and evaporated to dry-ness in vacuo. Subsequently, to the resulting flask containing yellow solid of the unpurified IrCl(cod)(NHC) complex, a solution of AgBF4(0.025 mmol, 4.9 mg) in CPME (2 mL) was added, and then stirred at room temperature for 1 h. Finally, propiophenone (0.5 mmol,66 mg) and (EtO)2MeSiH (2.25 mmol, 294 mg) were added to the resulting CPME solution (see Appendix A. Supplementary data fordetails). After stirring at room temperature for 20 h under open-air conditions, K2CO3(2 mg) and MeOH (2 mL) were added. Then, the resulting mixture was stirred at room temperature for 2 h. Afterevaporation of the solvents, the residue obtained was purified bycolumn chromatography on silica gel (Et2O/n-hexane = 3:7) to give(S)-1-phenyl-1-propanol (61 mg, 91% isolated yield). The ee was measured by chiral GLC. | |
With C. parapsilosis strains containing exogenous gene scrII; In aq. phosphate buffer; at 35℃; for 45h;pH 6.0;Microbiological reaction; | methodsThe asymmetric reduction of 2-HAP to (S)-PED by C. parapsilosiswas conducted as described by Nie et al. [26] with some mod-ifications. After 36 h incubation, cells were collected at 6000 × gcentrifugation and washed twice with saline. For asymmetric reac-tion, 1 mL of the reaction mixture contained 0.2 M acetate (pH4.0-6.0) or 0.2 M phosphate buffer (pH 6.0-7.0), 2-HAP (1 g/L to30 g/L) and 10% (W/V) wet-cells of C. parapsilosis. The productswere extracted with ethyl acetate, and the optical purity andyield were determined by HPLC on a Chiralcel OB-H column (Dai-cel Chemical Ind, Ltd., Japan) as described previously [26]. Theoptical purity and yield were calculated basing on the followingequations | |
The N. corallina cells were incubated in 50 mL phosphate buffer (0.1 mol L-1, pH 7.00),30 min, at 28-30 C in an orbital shaker (150 rpm), and 2a or 2b was added to the whole cellsat a substrate:cells mass ratio of 1:100 for 2a and 1:400 for 2b, using 0.6 vol. % of N,N--dimethylformamide and shaken under the same conditions. The experiments were performedin triplicate at different final pH values of the culture media and times. The sample was centrifugedat 4500 rpm for 15 min and then extracted with ethyl acetate (4×15 mL), and the organiclayer was concentrated to dryness. The product was dissolved in 0.5 mL of HPLC grade2-propanol. The GC analysis was performed with a HP-5 column (30 m×0.33 mm, 0.25 μm)(Hewlett-Packard, Germany) at 80-200 C, with N2 as the carrier gas at 1.0 mL min-1. Theoven temperature was ramped from 80-200 C at 10 C min-1, held for 3 min, decreased to 80C at 25 C min-1 and held for 2 min. The retention times were tR(2a) = 4.90 min and tR(2b) == 5.79 min. Then, the analyse was realized by HPLC using a chiracel OB-H (25.0 cm×0.46cm, 0.5 μm) column (Daicel Chemical Industries, Tokyo, Japan). The mobile phase washexane:2-propanol (90:10), 0.5 mL min-1, λ = 220 nm, 24 C. For the reduction of 2a, theretention times were tR(R)-2b = 15.10 min, tR(S)-2b= 18.90 min and tR(2a) = 28.90 min. Forthe oxidation of 2b, the mobile phase was hexane:2-propanol (90:10), 0.8 mL min-1, λ = 260nm, 24 C. The retention times were tR(R)-2b = 9.04 min, tR(S)-2b = 11.38 min and tR(2a) == 17.12 min, The absolute configuration of 2b was assigned according to the literature.23 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.9% | With β-D-glucose; In aq. phosphate buffer; at 35℃; for 24h;pH 7.5;Enzymatic reaction;Kinetics; | The bioconversion mixture (2mL) consisted of 0.1M potassium phosphate buffer (pH 7.0), 6gL-1 2-HAP, 12gL-1 glucose, and 0.1g washed wet cells. The reactions were carried out at 35C for 36h with shaking at 200rpm. After the cells were removed by centrifugation, the supernatant was extracted with ethyl acetate., and the organic layer was filtered through a 0.22μm PVDF syringe filter (Troody Technology, Shanghai, China) for analysis. The optical purity and yield of (R)-PED were determined by HPLC (HP 1100, Agilent, USA) equipped with a Chiralcel OB-H column (4.6mm×250mm; Daicel Chemical Ind., Ltd., Japan) as described by Nie et al. [39]. |
97% | With cobalt(II) acetate; C31H31N2OP; In tetrahydrofuran; at 25℃; for 1h;Inert atmosphere; | Under a nitrogen atmosphere at 25C, cobalt acetate (0.01mmol), PNNtBu ligand (0.01mmol), α-hydroxyacetophenone (R is phenyl) (2mmol), tetrahydrofuran ( THF) (1 mL), polymethylhydrosiloxane (PMHS) (2.1 mmol), the reaction mixture was stirred for 1 hour, and then column chromatography was separated to obtain the product 1,2-diol. |
80% | With Kurthia gibsonii SC0312; In aq. phosphate buffer; at 35℃; | In a typical experiment, PB (100 mM, pH 7.5, 4 mL) containing 20mM HAP, 30mM glycerine, 30 mg/mL wet cells and a DES (4 %, v/v)was incubated at 35 C and 180 rpm. Aliquots were withdrawn at regularintervals to monitor the initial reaction rate, enantiomeric excess(ee) and yield of (R)-PED. The initial reaction rate was based on thegenerated amount of PED after catalytic reaction for 30 min. The productyield was defined as the ratio of the generated amount of (R)-PEDto the theoretical amount. The ee of (R)-PED was calculated based onthe following equation. where CS and CR were the concentrations of (S)-PED and (R)-PED, respectively. |
48% | EXAMPLE 17 2-Hydroxyacetophenone (1.0 g, 7.3 mmol) was asymetrically reduced, with cooling in an ice-water bath in accordance with the procedure described in Example 2, giving 0.8 g of (R)-(-)-phenyl-1,2-ethanediol, having a specific rotation [α]D21 of -22.1 (cl. 02, acetone). The synthesis yield was 80% and the optical yield was 48% e.e (see Reference 13). | |
48% | EXAMPLE 17 2-Hydroxyacetophenone (1.0 g, 7.3 mmol) was asymetrically reduced, with cooling in an ice-water bath in accordance with the procedure described in Example 2, giving 0.8 g of (R)-(-)-phenyl-1,2-ethanediol, having a specific rotation [α] [21/D ] of -22.1 (cl. 02, acetone). The synthesis yield was 80% and the optical yield was 48% e.e (see Reference 13). | |
With potassium phosphate; Candida parapsilosis aldo-keto reductase CPAR4; at 30℃; for 8h;pH 6.5;Enzymatic reaction; | General procedure: Asymmetric reductions of various carbonyl compounds by the purified enzymes were carried out at 30C for 8h with mild shaking in a reaction mixture containing 0.1M potassium phosphate buffer (pH 6.5), 1gL-1 substrate, 10mM NADPH, and the purified enzyme of appropriate amount in a total volume of 2mL. In order to determine the absolute configuration of chiral alcohols, the reaction products were extracted with ethyl acetate or hexane and the organic layer was used for analysis. The optical purity of the reaction products were determined by chiral HPLC (HP 1100, Agilent, USA) equipped with Chiralcel OB-H column (4.6mm×250mm; Daicel Chemical Ind. Ltd., Japan) or chiral GC (7890A, Agilent, USA) equipped with FID detector and Chrompack Chirasil-Dex CB chiral capillary column (25m×0.25mm; Varian, USA) [21]. | |
With hydrogen; In n-heptane; acetic acid; toluene; at 30℃; under 37503.8 Torr; for 24h;Autoclave; | General procedure: The enantioselective hydrogenation of 1,1-dimethoxyacetone 1a was used as a representative: The autoclave was charged with the above-prepared chiral Pt nanoparticle catalyst (32 mg, containing 3.56×10-3 mmol of Pt), CILPEG-CD (12 mg), glacial acetic acid (1.6 g), toluene (1.0 g), n-heptane (0.3 g) and cyclohexane (50 mg, internal standard). The mixture was stirred for 30 min at 30 C, and then 1,1-dimethoxyacetone 1a (42 mg, 1a/Pt=100:1) was added. The reactor was flushed three times with 2.0 MPa H2 and stirred under required hydrogen pressure at an appointed temperature for a designated time. After reaction, the autoclave was cooled in an ice-water bath and then depressurized. The lower chiral Pt nanoparticle catalyst phase was easily separated from the upper organic phase containing products by simple phase separation and directly reused in next catalytic cycle. The upper phase was directly analyzed by chiral GC and 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With pyridine; at 0 - 20℃;Inert atmosphere; | To a stirred solution of (i?)-l-phenylethane-l ,2-diol (0.5 g, 3.6 mmol, 1.0 eq.) in anhydrous pyridine (2 mL) under a nitrogen atmosphere at 0 C was added 4-methylbenzene-l- sulfonyl chloride (0.76 g, 4.0 mmol, 1.1 eq.) portion wise over 20 minutes maintaining the temperature at 0 C. The reaction was allowed to warm to room temperature and stirred overnight. Brine was added and the mixture extracted with dichloromethane (x 2). The combined organic layers were washed with 1 M hydrochloric acid (x 2) and water and the solvent removed in vacuo to afford (i?)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate as a white solid (0.817 g, 78% yield). NMR (400 MHz, DMSO) 7.76 (2H, d, J=8.3 Hz), 7.49 (2H, d, J=7.8 Hz), 7.37 - 7.32 (5H, m), 5.81 (1H, d, J=4.6 Hz), 4.81 (1H, dd, J=4.9, 11.3 Hz), 4.07 - 4.04 (1H, m), 2.47 (3H, s). |
70% | With di(n-butyl)tin oxide; triethylamine; In dichloromethane; at 20℃; | General procedure: To a solution of the appropriate alcohol (10mmol) in dry CH2Cl2 (20ml) was added Bu2SnO (0.2mmol) followed by the addition of pTsCl e (10mmol) and TEA (10mmol). The reaction mixture was kept under vigorous stirring at rt for 1-6h. The reaction mixture was quenched by adding water. The solution was extracted with dichloromethane and then combined organic phase were washed with a saturated aqueous solution of brine and dried over anhydrous Na2SO4. The solvent removing in vacuo give a residue that was crystallized or chromatographed to afford the desired compounds (1-5). 4.2.1 (R)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate (1) Waxy solid (70%); mp 67-68 C; = - 50.1 (c 1.0, CHCl3). IR (CHCl3) 3220, 3020, 1595, 1451, 1355 cm-1. 1H NMR (CHCl3) δ 7.77 (d, 2H), 7.35-7.26 (m, 7H), 4.98 (dd, J = 8.4, 3.4 Hz, 1H), 4.15 (dd, J = 10.4, 3.4 Hz, 1H), 4.04 (dd, J = 8.4, 10.4 Hz, 1H), 2.45 (s, 3H). |
With pyridine; In dichloromethane; at -15℃; for 25h; | To a mixture of (R)-phenylethylene glycol, dry pyridine in dry dichloromethane cooled at -15 C. was added portion wise p-toluenesulfonyl chloride over a period of 1 h.The reaction was stirred at -15 C. for 24 h and quenched by adding water.The solution was extracted with dichloromethane and then combined organic phase was washed with aqueous CuSO4, dried (Na2SO4) and concentrated.Silica gel column chromatography of crude product using petroleum ether: EtOAc (4:1) as eluent gave monotosyl compound as a white solid. |
With pyridine; In dichloromethane; at 0℃; | To a stirred solution of diol (1.0 eq) in DCM(10 mL) was added pyridine (10.0 eq) at 0 C followed by p-toluenesulfonyl chloride (2.0 eq) and the reactionmixture was stirred for 3-4 h at 0 C. After completion of the reaction (TLC),reaction mixture was treated with 10% HCl at 0 C, and extracted with EtOAc(3x20 mL) The combined organic layers were pooled and washed with water (2x20mL) and brine (1x20 mL), dried over anhydrous Na2SO4,filtered, and concentrated. The concentrate was purified by silica gelchromatography (100-200 mesh) using EtOAc/petroleum ether (2:3) to furnish thedesired monotosylated product (75-90% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In methanol; at 20℃; for 4h; | General procedure: In order to determine the enantiomeric excesses in the cases of styrene derivatives as starting materials, the pure product was dissolved in MeOH (0.1 M). Addition of K2CO3 (1.5 equiv) was followed by stirring at r.t. for 4 h. MeOH was removed under reduced pressure after acidification with aq 1 M HCl. Extraction of the aqueous layer with CH2Cl2 (3 ×), drying the combined organic layers over Na2SO4, and evaporation of the solvent yielded the corresponding diol, which was submitted to HPLC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With Aspergillus niger epoxide hydrolases; In aq. phosphate buffer; dimethyl sulfoxide; at 25℃; for 4h;pH 7.0;Enzymatic reaction;Kinetics; | General procedure: Asymmetric hydrolysis of (R/S)-SO, (R/S)-PO and (R/S)-ECH were examined in a batch type reactor (1.1 cm × 5 cm). To 1.5 mL of 100 mM phosphate buffer (pH = 7.0 for the free and EHIL; pH = 6.5 for EHIF and EHIE), 100 L of the free EH solution (1 mg mL-1) or 30 mg of each immobilized EH was loaded and the mixture kept at 25 C for 2 min. The reaction was initiated by the addition 0.4 mL of each racemic epoxide solution (0.5 M in DMSO). A hundred microliters of aliquots withdrawn at different time intervals (15, 30,60, 90, 120, 180 and 240 min) were mixed with 400 L of diethylether and analyzed by a Shodex ORpak CDC-453 HQ chiral HPLC column (4.6 mm × 150 mm) according to Yildirim et al. [23]. The enantiomers of styrene oxide and their vicinal diols were detected at 220 nm. The enantiomers of propylene oxide, epichlorohydrin and their vicinal diols were detected using a refractive index detector (Shimadzu RID-10A). The optical configurations of remaining epoxides and formed diols were identified by comparing the retention time of these compounds with their optically active standard forms. The enantiomeric excess (ee) values of formed vicinal diol and remaining epoxide were calculated from the equations: eeepoxide=([S-R]epoxide)/([S+R]epoxide) and eediol=([R-S]diol)/([R+S]diol) The enantiomeric ratio values (E) of free and immobilized EHs were calculated from the equation proposed by Chen et al. [27]. E=(Vmax(R)/Km(R))/(Vmax(S)/Km(S)) where Vmax(R) and Km(R) values are maximum velocity and Michealis-Menten constant of free and immobilized EH preparations toward (R)-enantiomer of epoxide and Vmax(S) and Km(S) are corresponding values toward (S)-enantiomer of epoxide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.3%; 67.9% | Racemic styrene oxide was resolved to (S) -styrene oxide and (R)- styrene glycol using [(S, S)-CO (SALEN) ACCORDING] to the following reaction scheme: (S, S)-Co (salen) p-nitroberv-oic acid | |
48% | With Aspergillus niger epoxide hydrolases immobilized onto modified Eupergit C; In aq. phosphate buffer; dimethyl sulfoxide; at 25℃; for 4h;pH 6.5;Enzymatic reaction;Kinetics; | General procedure: Asymmetric hydrolysis of (R/S)-SO, (R/S)-PO and (R/S)-ECH were examined in a batch type reactor (1.1 cm × 5 cm). To 1.5 mL of 100 mM phosphate buffer (pH = 7.0 for the free and EHIL; pH = 6.5 for EHIF and EHIE), 100 L of the free EH solution (1 mg mL-1) or 30 mg of each immobilized EH was loaded and the mixture kept at 25 C for 2 min. The reaction was initiated by the addition 0.4 mL of each racemic epoxide solution (0.5 M in DMSO). A hundred microliters of aliquots withdrawn at different time intervals (15, 30,60, 90, 120, 180 and 240 min) were mixed with 400 L of diethylether and analyzed by a Shodex ORpak CDC-453 HQ chiral HPLC column (4.6 mm × 150 mm) according to Yildirim et al. [23]. The enantiomers of styrene oxide and their vicinal diols were detected at 220 nm. The enantiomers of propylene oxide, epichlorohydrin and their vicinal diols were detected using a refractive index detector (Shimadzu RID-10A). The optical configurations of remaining epoxides and formed diols were identified by comparing the retention time of these compounds with their optically active standard forms. The enantiomeric excess (ee) values of formed vicinal diol and remaining epoxide were calculated from the equations: eeepoxide=([S-R]epoxide)/([S+R]epoxide) and eediol=([R-S]diol)/([R+S]diol) The enantiomeric ratio values (E) of free and immobilized EHs were calculated from the equation proposed by Chen et al. [27]. E=(Vmax(R)/Km(R))/(Vmax(S)/Km(S)) where Vmax(R) and Km(R) values are maximum velocity and Michealis-Menten constant of free and immobilized EH preparations toward (R)-enantiomer of epoxide and Vmax(S) and Km(S) are corresponding values toward (S)-enantiomer of epoxide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hexane; isopropyl alcohol; at 35℃;Resolution of racemate;Product distribution / selectivity; | 1HNMR (400 MHz, CD3COCD3) δ 3.53 (dd, J=2 Hz, 4 Hz, 1H, CHHOH), 3.64 (dd, J=2 Hz, 10 Hz, 1H, CHHOH), 4.04 (br, H, OH), 4.43 (br, 1H, OH), 4.73 (dd, J=4 Hz, 10 Hz, 1H, CHOH), 7.21-7.40 (m, 5H, aromatic H); HPLC (CHIRALCEL OB; solvent, hexane/2-propanol=98/2; flow rate, 1.0 ml/min; temperature, 35 C.; UV wavelength, 220 nm); tR of both optical isomers of 1-phenyl-1,2-ethanediol, 26.0 minutes and 36.2 minutes. In the reaction, the optical isomer detected at 26.0 minutes was a main component, but R and S isomers were not identified. |
A363247 [52340-78-0]
(1R,2R)-1,2-Diphenylethane-1,2-diol
Similarity: 0.97
A363247 [52340-78-0]
(1R,2R)-1,2-Diphenylethane-1,2-diol
Similarity: 0.97