Structure of 120121-01-9
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CAS No. : | 120121-01-9 |
Formula : | C8H9ClO |
M.W : | 156.61 |
SMILES Code : | C[C@@H](O)C1=CC=CC(Cl)=C1 |
MDL No. : | MFCD09863670 |
InChI Key : | QYUQVBHGBPRDKN-ZCFIWIBFSA-N |
Pubchem ID : | 6950742 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.72 |
Solubility | 0.298 mg/ml ; 0.00191 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.5 |
Solubility | 0.498 mg/ml ; 0.00318 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.86 |
Solubility | 0.216 mg/ml ; 0.00138 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 |
Yes |
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) |
Yes |
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 |
-5.53 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 |
2.0 |
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) |
1.55 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With [(2-(benzoimidazol-2-yl)-6-(3,5-dimethylpyrazol-1-yl)pyridine)RuCl2(PPh3)]; potassium tert-butylate; acetone; In methanol; at 56℃; under 750.075 Torr; for 0.166667h;Inert atmosphere;Catalytic behavior; | General procedure: The catalyst solutionwas prepared by dissolving complex 3(36.1 mg,0.05mmol) in methanol (5.0 mL).Under a nitrogen atmosphere, the mixture of an alcohol substrate (2.0 mmol) and1.0 mL of the catalyst solution (0.01mmol) in 20mL acetone was stirred at 56 Cfor 10 minutes. tBuOK(22.4mg, 0.2 mmol)was then added to initiate the reaction.At the stated time, 0.1 mL of the reaction mixture was sampled and immediately diluted with 0.5 mL acetone pre-cooled-to-0 C for GC or NMR analysis. After the reaction was complete, the reaction mixture was condensed under reduced pressure and subject to purification by flash silica gel column chromatography to afford the corresponding ketone product, which was identified by comparison with the authentic sample through NMR and GC analysis. |
93.3% | With tert.-butylhydroperoxide; at 60℃; for 18h; | General procedure: In a typical process, into a 5-ml two-necked round-bottomflask equipped with a magnetic stirrer were addedRu(pbbp)(pydic) (0.002 mmol) and alcohol (2 mmol)successively at room temperature. The mixture washeated to 60 C under stirring, and then TBHP (70%aqueous solution) was slowly dropped in 0.5 h. Thereaction was monitored by GC equipped with a SE 54column (30 m 9 0.5 lm). After reaction, the product waspurified by column chromatography over silica gel (eluent:n-hexane/ethyl acetate) and characterized by 1HNMR. |
93% | General procedure: Firstly, GO (0.01 g) was added into water (3 mL) and the mixturecould generate the stable colloidal suspensions under a mild ultrasonictreatment. Afterwards, the alcohol (2 mmol) and (NH4)5H5[H2(WO4)6](0.03 mmol, M=1602) were added. The mixture was stirred for 15 min atroom temperature. Subsequently, hydrogen peroxide (30 wt%, 8 mmol)was added dropwise and the mixture was heated to 70C until thereaction was fully completed (monitored by TLC). After the reactioncompleted, GO could be readily separated from the mixtures bycentrifugation, and then ethyl acetate was added to the mixture to extract organic constituents. Finally, the organic extracts were concentratedunder reduced pressure and purified by column chromatography. |
89% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium acetate; (S)-3-phenyl-2-(phenylamino)propionic acid; copper(ll) bromide; In water; for 12h;Reflux; Schlenk technique; | General procedure: A mixture of 1-phenethyl alcohol (1.0 mmol), N-(phenyl)phenylalanine(0.0241 g, 0.1 mmol), CuBr2 (0.0223 g, 0.1 mmol),NaOAc (0.1640 g, 2.0 mmol), TEMPO (0.0156 g, 0.1 mmol), andH2O (3.0 mL) were placed into a 100 mL Schlenk tube, whichwas vigorously stirred in air under reflux for 12 h. After thereaction, the product was extracted with CH2Cl2 (3 × 2.0 mL).The combined organic phase was washed with H2O (3.0 mL) anddried over anhydrous MgSO4. After concentration undervacuum, the residue was purified by column chromatography toafford acetophenone.Isolated yield: 0.1080 g (90%). |
88% | With 2,6-dimethylpyridine; 9-azabicyclo<3.3.1>nonane-N-oxyl; sodium perchlorate; In acetonitrile; for 8.66h;Inert atmosphere; Electrochemical reaction; | General procedure: The preparative electrolysis experiments were conducted with in an undivided cell containing0.1 M NaClO4-CH3CN solution (15 mL), alcohol substrate (1.0 mmol), ABNO (0.1 mmol),and 2,6-lutidine (1.0 mmol) at a constant current of 10.0 mA with moderate magnetic stirring for8.5 h in the atmosphere. Two square platinum sheets were employed as the anode and cathode,respectively. The electrolytic reaction was monitored by gas chromatography (GC) on a GC-2010system (Shimadzu, Kyoto, Japan) equipped with a SH-Rtx-Was polar column and a flame ionizationdetector (FID). Both the injector and detector were maintained at 220 C, the carrier gas is nitrogen,and the flow rate is 1.2 mL/min. The initial oven temperature of 100 C was held for 2 min andthen ramped up at 15 C per min to 220 C. This final temperature was held for 8 min. After thereaction was finished, the resulting mixture was concentrated in a rotary evaporator (Heidolph,Schwabach, Germany) and purified by column chromatography on silica gel using petroleum andethyl acetate 15:1) as eluent to afford the products. The products were confirmed by GC-MS, 1H-NMR,and 13C-NMR. NMR spectroscopy was carried out on a Bruker Avance III spectrometer (Bruker,Faellanden, Switzerland). The GC-MS analysis was measured on Thermo Trace ISQ instrument (ThermoFisher Nicolet,Waltham, MA, USA) with TG 5MS capillary column.Acetophenone (colorless oil, yield 80%): |
With tert.-butylhydroperoxide; Ru[2-(2-pyridymethylimino)ethylbenzimidazole]pyridinedicarboxylate; In neat (no solvent); at 40℃; for 4h; | General procedure: In a typical process, into a 5ml two-necked, round-bottom flask equipped with a magnetic stirrer and a thermometer were added the ruthenium complex [Ru(pymieb)(pydic)] (0.002mmol) and the substrate alcohol (2mmol) successively. The mixture was heated to 40C under stirring. Then t-butyl hydroperoxide (TBHP) was added dropwise to the mixture and the temperature was kept at 40C until completion of the reaction. The reaction samples were analyzed on a Shandong Lunan Ruihong Gas Chromatograph (SP-6800A) equipped with a FID detector and a SE 30 column (30m×0.5mm). The conditions used in gas chromatography were temperature of the detector 280C, column temperature 130-220C (varying with alcohols), pressure of the carrier gas 0.05-0.07MPa (varying with alcohols). | |
With manganese(IV) oxide; silica gel; In acetonitrile; at 70℃; for 8h;Molecular sieve; | General procedure: The above secondary alcohol was dissolved in acetonitrile (30mL). Molecular sieve (1.5g), silica gel (1.5g) and activated MnO2 (3.5g, 40mmol) were added, and the mixture was stirred at 70C for 8h. upon completion of the oxidation, the resulting suspension was filtered through diatomite, and the filtrate was concentrated by rotary evaporation. Purification of the residue by column chromatography (petroleum ethrt/EtOAc, 15:1) afforded ketone 13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 0 - 20℃; for 3.16667h;Inert atmosphere; | General procedure: To a solution of aldehyde 11 (4mmol) in THF (12mL) at 0C under nitrogen, was dropwise added methylmagnesium bromide (1.0M in THF, 5mmol). After stirring for 10min the reaction mixture was allowed to warm to room temperature and was stirred for 3h. Upon completion, the reaction was quenched with saturated NH4Cl solution and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and evaporated under reduced pressure. The crude residue was used directly. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With lithium aluminium tetrahydride; In diethyl ether; at -78℃; for 2.5h; | General procedure: A solution of LiAlH4 in diethyl ether (1 M, 6 mL, 6 mmol) was added dropwise to the cooled (dry ice/acetone bath) solution of the respective carbonyl compound (20 mmol for ketones, 10 mmol for esters, 7.5 mmol for carboxylic acids) in diethyl ether (20 mL), and the mixture was stirred at -78 C for an additional 30 min. The flask was immersed in an ice/water bath, the mixture was stirred for an additional 2 h, and a saturated aqueous NH4Cl solution was added dropwise under vigorous stirring (careful - foam) until the H2 gas evolution ceased. The mixture was stirred for an additional 15 min, filtered with suction through a pad of Celite, the filter cake was washed with diethyl ether (3 × 50 mL), and the combined filtrates were concentrated under reduced pressure to give the target alcohol. |
95% | With isopropyl alcohol; sodium hydroxide; for 1.5h;Inert atmosphere; Schlenk technique; Reflux; | General procedure: Under nitrogen atmosphere, a mixture of ketone (2 mmol), catalyst 4 (0.008 mmol), and 2-propanol (17.6 mL) was stirred at 82C. After 5 min, 2.4 mL of 0.1 M NaOH (0.24 mmol) solution in 2-propanol was introduced to initiate the reaction, and the reaction mixture was stirred at refluxing temperature. At the specified time, 0.1 mL of the reaction mixture was filtered through a short pad of celite to remove the complex catalyst, and immediately diluted with 0.2 mL of 2-propanol. The filtrate was used for GC analysis. After the reaction was finished, the mixture was condensed under reduced pressure and subject to flash silica gel column chromatography to afford the alcohol product (detected under 254 nm UV light or by alkaline potassium permanganate solution; eluent: petroleum ether (60-90 C)/ethyl acetate = 10:1 or petroleum ether (30-60 C)/dichloromethane= 1:1, v/v). The alcohol products were identified by comparison with the authentic sample through NMR and GC analyses. |
92% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); hydrogen; In tert-Amyl alcohol; at 30℃; under 760.051 Torr; for 12h;Green chemistry; | General procedure: To an oven-dried 5 mL round-bottom flask were added ketone (1 mmol), cat. 7 (2.7 mg, 0.5 mol %) and tert-amyl alcohol (1 mL). Next, vacuum was applied to the flask followed by filling with H2 gas and keeping the flask attached to a balloon filled with H2 gas. The mixture was heated at 30 C for 12 h. After completion of the reaction, the solvent was removed by evaporation under reduced pressure. The alcohols were isolated and purified by filtering a hexanes/ethyl acetate (5:1) solution of the crude product through a pad of silica gel, and then removing the solvent under reduced pressure. The conversion and purity of the alcohol products was assessed using NMR spectroscopy. |
98%Chromat. | General procedure: Under a nitrogen atmosphere, a mixture of ketone (2 mmol),catalyst 3 (0.01 mmol), and 2-propanol (18 mL) was stirred at 82 C for 10 min. Then, iPrOK solution in 2-propanol (2.0 mL,0.1 mol/L, 0.2 mmol) was introduced to initiate the reaction.The reaction mixture was stirred at reflux. After the statedtime, 0.1 mL of the reaction mixture was sampled and immediatelydiluted with 0.5 mL of 2-propanol precooled to 0 C, andfiltered through a short pad of celite to quench the reaction byremoving the complex catalyst. The resultant filtrate was usedfor GC analysis. After the reaction was finished, the mixture wascondensed under reduced pressure and subjected to flash silicagel column chromatography to afford the alcohol product. The alcohol products were identified by comparison with authenticsamples using NMR and GC analyses. | |
>= 99%Chromat. | With Ru(3-(2-(diphenylphosphino)benzylideneamino)-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-one)2Cl2; sodium hydroxide; In isopropyl alcohol; at 82℃; for 24h;Schlenk technique; Inert atmosphere;Catalytic behavior; | General procedure: A mixture of the Ru(II) complex (0.004 mmol), 2-propanol(3 mL), NaOH (0.1 mmol) and the substrate (2 mmol,substrate:catalyst/500:1) was introduced into a Schlenktube under an argon atmosphere. The resulting solution washeated at 82 C for 24 h. The solution was cooled downand then concentrated to dryness under reduced pressure.The residue was purified by flash chromatography (ethylacetate:hexane/1:10). The products were analyzed by GC. |
With potassium isopropoxide; In isopropyl alcohol; at 82℃; for 0.0833333h;Inert atmosphere; Green chemistry; | Under a nitrogen atmosphere, trinuclear ruthenium NNN complex 1 (2.5 mumol) was dissolved in 20.0 mL of isopropanol to prepare a catalyst solution.A mixture of the substrate acetophenone (2.0 mmol), 2 mL of the catalyst solution and 17.6 mL of isopropanol was stirred at 82 C for 5 minutes under a nitrogen atmosphere.Then 0.4 mL of iPrOK in isopropanol solution (0.05 M) was added to the reaction system.Extract 0.1 mL of the reaction solution within the specified time.Immediately diluted with 0.5 mL of isopropanol for gas chromatography analysis.Under the conditions described, acetophenone is reduced almost quantitatively to the corresponding alcohol product, indicating that the complex of the present invention can be used as a potential ketone reduction catalyst. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine; phosphorus tribromide; In dichloromethane; at -75 - -25℃; | Example 1: l-(l-Bromoethyl)-3-chlorobenzene Int-1 Step 1: l-(l-Bromoethyl)-3-chlorobenzene Int-1 To a solution of m-chlorophenylmethylcarbinol (0.50 g, 3.2 mmol) and pyridine (0.052 mL, 0.64 mmol) in DCM (10 mL) at -75C was added phosphorus tribromide (0.30 mL, 3.2 mmol) dropwise. The mixture was stirred for 10 min and left to stand in a -25C freezer overnight. The mixture was then placed in an ice bath and 3 mL water was added slowly. The mixture was partitioned into DCM and water. The organic layer was washed successively with water, 1M NaHC03 and brine, dried over Na2S04, filtered, and then concentrated to give l-(l-bromoethyl)-3-chlorobenzene (700 mg, 100%). H NMR (CDC13) delta 7.43 (s, 1H), 7.33 - 7.29 (m, 1H), 7.28 - 7.24 (m, 2H), 5.13 (q, J= 6.9 Hz, 1H), 2.03 (d, J= 6.9 Hz, 3H). |
57.1% | With phosphorus tribromide; In diethyl ether; at 0 - 20℃; | Example 44A1 -(1 -bromoethyl)-3-chlorobenzeneTo a solution of l-(3-chlorophenyl)ethanol (0.2 g, 1.28 mmol) in diethyl ether (10 mL) at 0 C was added tribromophosphine (0.38 g, 1.41 mmol). The mixture was warmed to room tmeperature and stirred overnight, then diluted with ether (10 mL). After quenching with water (10 mL), the organic phase was separated, dried over Na2S04, filtered and concentrated. The residue was purified by column chromatography on silica gel and eluted with petroleum ether to give the title compound as an oil (0.16 g, yield 57.1%). |
57.1% | With phosphorus tribromide; In diethyl ether; at 0 - 20℃; | Example 44A 1-(1-bromoethyl)-3-chlorobenzene To a solution of 1-(3-chlorophenyl)ethanol (0.2 g, 1.28 mmol) in diethyl ether (10 mL) at 0 C. was added tribromophosphine (0.38 g, 1.41 mmol). The mixture was warmed to room temperature and stirred overnight, then diluted with ether (10 mL). After quenching with water (10 mL), the organic phase was separated, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel and eluted with petroleum ether to give the title compound as an oil (0.16 g, yield 57.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With C45H32I4O6; 1,1,1,3,3,3-hexamethyl-disilazane; In dichloromethane; at -30℃; for 2h; | The racemic alcohol (1s) at -30 C1.0 mmol as a catalyst was dissolved in 5 ml dichloromethane (wherein, R I andn is 2; and pharmaceutically acceptable salts thereof) compound of the formula(2) the addition of 0.01 mol% of potassium and fluoro one equivalent offluoride, a carboxylic acid group and the ion exchange resin 80 mg silylatingagent of formula (5), including (in the formula, R is methyl) wasadded to 0.7 equivalents, and then the mixture was stirred for 1 hour. Filteringthe mixture was concentrated and then to recover the potassium fluoride and theion exchange resin. The residue was purified by flash chromatography (acetone /hexane / triethylamine = 1: 5: 0.025) to give the chiral alcohol; to give the(2s, 46% yield 97% ee, (S) -form). |
46% | With potassium fluoride; C46H34I4O6; 1,1,1,3,3,3-hexamethyl-disilazane; In dichloromethane; at -30℃; | At -30C, racemic alcohol (1s) 1.0 mmol was dissolved in 5 ml dichloromethane, the compound of formula 2(wherein, R is I and n is 2; and pharmaceutically acceptable salts) 0.01 mol% as a catalyst and the addition of 0.7 eq., of silylating agent formula (5) (in the formula, R4 is methyl)and 1 equivalent of potassium fluoride and 80 mg of carboxylic acid group ion exchange resin was added and stirred for 1 hour. The mixture was filtered then concentrated to recover potassium fluoride and the ion exchange resin. The residue was purified by flash chromatography (acetone /hexane / triethylamine = 1: 5: 0.025) to give the chiral alcohol (2s, 46% yield 97% ee, (S)-form). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With potassium fluoride; C46H34I4O6; 1,1,1,3,3,3-hexamethyl-disilazane; In dichloromethane; at -30℃; | At -30C, racemic alcohol (1s) 1.0 mmol was dissolved in 5 ml dichloromethane, the compound of formula 1(wherein, R is I and n is 2; and pharmaceutically acceptable salts) 0.01 mol% as a catalyst and the addition of 0.7 eq., of silylating agent formula (5) (in the formula, R4 is methyl)and 1 equivalent of potassium fluoride and 80 mg of carboxylic acid group ion exchange resin was added and stirred for 1 hour. The mixture was filtered then concentrated to recover potassium fluoride and the ion exchange resin. The residue was purified by flash chromatography (acetone /hexane / triethylamine = 1: 5: 0.025) to give the chiral alcohol (2s, 49% yield 96% ee, (R)-form). |
49% | With C45H32I4O6; 1,1,1,3,3,3-hexamethyl-disilazane; In dichloromethane; at -30℃; for 2h; | -30 C in the racemic alcohol (1s)1.0 mmol were dissolved in 5 ml of dichloromethane and then the catalyst as acompound of formula (I) (wherein, R is I and n is 2; and pharmaceuticallyacceptable salts thereof) is added and the 0.01 mol% of potassium fluoro oneequivalent of fluoride, a carboxylic acid group and the ion exchange resin 80mg silylating agent of formula (5), including (in the formula, R ismethyl) was added to 0.7 equivalents, and then the mixture was stirred for 1hour. Filtering the mixture was concentrated and then to recover the potassiumfluoride and the ion exchange resin. The residue was purified by flashchromatography (acetone / hexane / triethylamine = 1: 5: 0.025) to give thechiral alcohol; to give the (2s, 49% yield 96% ee, (R) -form). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Racemic secondary alcohols (0.25 mmol), catalyst (1.5 mol% of substrate), and KBr (0.02 mmol, 0.0024 g) were added to H2O(1.5 mL). The mixture was stirred for 10 min at room temperature, and then PhI(OAc)2 (0.175 mmol, 0.056 g) was added in four equal parts. The reaction progress was monitored by gas chromatography (GC). After achieving the desired oxidation level, the reaction mixture was heated to 40 ?C. The catalyst was precipitated out of the reaction system, washed with diethyl ether(3× 5 mL), dried in a vacuum, and finally recharged with fresh substrate, additive, and oxidant for the next catalytic cycle. The supernatants separated from the reaction system were extractedwith ether three times. The collected organic phase was driedover sodium sulfate and concentrated in a vacuum. The resultantmixture was purified by column chromatography on silica gel athe stationary phase (petroleum ether/ethyl acetate, 90/10). Enantioselectivitywas determined by a Agilent Technologies 6890NGC system equipped with a 19091G-B213 chiral capillary column(30 m×0.32 mm×0.25 m) with an FID. |
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