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CAS No. : | 623-03-0 |
Formula : | C7H4ClN |
Linear Structure Formula : | ClC6H4(CN) |
M.W : | 137.57 |
SMILES Code : | ClC1=CC=C(C=C1)C#N |
MDL No. : | MFCD00001813 |
InChI Key : | GJNGXPDXRVXSEH-UHFFFAOYSA-N |
Pubchem ID : | 12163 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H332-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.17 |
TPSA ? Topological Polar Surface Area: Calculated from | 23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.79 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 2.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.46 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.2 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.74 |
Solubility | 0.249 mg/ml ; 0.00181 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.61 |
Solubility | 0.335 mg/ml ; 0.00243 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.07 |
Solubility | 0.117 mg/ml ; 0.000853 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 | -5.39 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) | 1.38 |
* 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 |
---|---|---|
EXAMPLE 8 Reaction of potassium phenate with para-chlorobenzonitrile, in order to prepare para-phenoxybenzonitrile having the formula: STR22 in the presence of tris-(3,6,9-trioxadecyl)-amine in o-dichlorobenzene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With di-tert-butyl{2′-isopropoxy-[1,1′-binaphthalen]-2-yl}phosphane; tripotassium phosphate tribasic; Palladium(0) bis(dibenzylideneacetone); In toluene; at 110℃; for 18h;Inert atmosphere;Catalytic behavior; | General procedure: An oven-dried Schlenk tube was evacuated and backfilled with nitrogen. The Schlenk tube was charged with Pd(bda)2 (11.5 mg,0.02 mmol), L1 (13.7 mg, 0.03 mmol), K3PO4 (424.5 mg, 2 mmol), and toluene (1.0 mL). After stirring for 15 min, the solution of arylhalide (1.0 mmol) and phenol (1.2 mmol) in toluene (1.5 mL) was added. The septum was replaced with an inside reflux condenser, and then the reaction mixture was stirred for 18 h at 110 C. Then,the reaction mixture was cooled to room temperature and quenched with water (5 mL). After separating the organic phase, the aqueous phase was extracted with ethyl acetate (3 mL3), and the combined organic phase was dried over anhydrous Na2SO4. The solvent was concentrated under reduced pressure, and then the crude material was purified by column chromatography on silica gel |
92% | With copper (I) iodide; potassium carbonate; dimethylbiguanide; In acetonitrile; at 20 - 60℃; for 10.1667h; | General procedure: To a 25 mL flask containing a mixture of CuI (19.2 mg,0.1 mmol), metformin (0.1 mmol), phenol (1.0 mmol), and K2CO3(2 mmol, 276 mg) in CH3CN (5 mL) was added an aryl halide(1.1 mmol). The mixture was stirred for 10 min at room temperature, and then heated to 60∘C for the appropriate amount of time(see Table 4). The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product. |
81% | With copper(II) oxide; potassium hydroxide; In N,N-dimethyl acetamide; at 27℃; for 20h;Inert atmosphere; Sealed tube; | General procedure: A magnetic stirring bar, nanocrystalline CuO (10 mg, 3 mol %), KOH (112 mg, 2 mmol) and phenol/substituted phenol/ thiophenol (1.2 mmol) were added into an oven-dried flask (25 mL). The flask was sealed with a septum, followed by three cycles of evacuation and filling with dry nitrogen. Then aryl halide (1 mmol) and N,N-dimethyl acetamide (DMAc) (4 mL) were injected through a syringe. The flask was sealed and stirred under nitrogen until the completion of the reaction (as monitored by TLC or GC). The catalyst was recovered from the reaction mixture and washed several times with ethyl acetate. The catalyst-free reaction mixture was quenched with brine solution and the product was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 80/20) to afford the product with high purity. |
40% | With sodium hydroxide; In neat (no solvent); at 90℃; for 13h;Green chemistry; | General procedure: A round bottom glass tube was charged by phenol (1mmol,0.094g), iodobenzene (1mmol, 0.203g), NaOH (3mmol,0.12g), and Fe3O4AMCA-MIL53(Al)-NH2-CoII NPs(VI)(1.08mol%, 0.04g). The reaction mixture was stirred at 90C under solvent free conditions. Thin layer chromatography(TLC) or gas chromatography (GC) were used to monitor the progress of the reaction. After completion of the reaction (6h), the reaction mixture was quenched by additionof 2mL ethyl acetate. The nanostructured catalyst was separated using an external magnetic field, washed with ethanol and water before drying in an oven at 50C overnight for the next run use. The obtained crude product was purified by thin layer chromatography using n-hexane/ethyl acetate(50:1) to aford the pure diphenyl ether (0.161g, 95% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
159 mg (89%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | EXAMPLE 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound. |
159 mg (89%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | Example 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With caesium carbonate; In dimethyl sulfoxide; at 120℃; for 24h;Sealed tube; | General procedure: A 5 mL reaction tube was charged with Phen-MCM-41-CuBr (36 mg, 0.025 mmol), amidine 4 (0.75 mmol), nitrile 2 (0.5 mmol), Cs2CO3 (489 mg, 1.5 mmol), and DMSO (1.5 mL) under an air atmosphere. The reaction tube was sealed and placed in an oil bath at r.t. The reaction mixture was stirred at 120 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with EtOAc (10 mL) and filtered. The supported copper catalyst was washed with water (2 5 mL) and acetone (2 5 mL), and reused in the next run. The filtrate was washed with 5percent aqueous NaHCO3 and brine. The organic layer was dried over Mg-SO4 and concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (hexane/EtOAc, 3:2) to provide the desired product 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.2% | With bis(triphenylphosphine)nickel(II) chloride; zinc(II) chloride; In tetrahydrofuran; at 10 - 15℃; for 7h;Inert atmosphere; | In another four 1L reaction flask, a nitrogen atmosphere, followed by adding 219.54g of tetrahydrofuran,73.18g (0.532mol) of chlorobenzonitrile, 0.73g (0.00532mol) zinc chloride, 0.35g (0.000532mol)Bis (triphenylphosphine) nickel chloride, open mixing, cooling to 10 ~ 15 the reaction system, and a solution ofMagnesium iodide, 4-bromophenyl Grignard reagent to produce a system, maintaining the temperature 10 ~ 15 , dropping time3 hours, the dropwise addition, heat 4h, sample detection reaction, dilute hydrochloric acid was added dropwise to the reaction mixture,The reaction was quenched by stirring 10min, allowed to stand, stratification, the organic layer was washed with 5% sodium chloride solution, was allowed to standThe layers were separated and the organic layer was added activated carbon, warmed to reflux, filtered hot and the filtrate was concentrated under reduced pressure off tetrahydrofuranNom to not far, down to 20 ~ 25 , to give a white flaky solid, as 4'-bromo-4-cyanobiphenyl,The solid was weighed 132.1g, a yield of 96.2% (in terms of chlorobenzene nitrile), purity (GC) ≥99.0%. |
96.2% | With bis(triphenylphosphine)nickel(II) chloride; zinc(II) chloride; In tetrahydrofuran; at 10 - 15℃; for 7h;Inert atmosphere; | In another 1L four-neck reaction flask, under nitrogen protection, 219.54g tetrahydrofuran, 73.18g (0.532mol) p-chlorobenzoic acid, 0.73g (0.00532mol) zinc chloride, 0.35g (0.000532mol) double (three Phenylphosphine) nickel chloride, start stirring, reduce the reaction system to 10 ~ 15 C, add the 4-bromophenyl magnesium iodide Grignard reagent produced in step 1 to the system, keep the temperature 10 ~ 15 C, drop Adding time is 3 hours, adding dropwise, keeping for 4h, sampling and testing reaction is completed, dilute hydrochloric acid is added dropwise to the reaction solution, quenching reaction, stirring for 10min, standing, layering, organic layer with 5% sodium chloride solution Washing, standingLayering, the organic layer is added with activated carbon, heated to reflux, filtered while hot, and the filtrate is concentrated under reduced pressure to remove tetrahydrofuran until it is lowered.Warm to 20 ~ 25 C, to obtain a white flake solid, 4'-bromo-4-cyanobiphenyl, solid weighing 132.1g, yield 96.2% (based on p-chlorobenzoic acid), purity (GC) ≥99.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
412 mg | To a solution of sodium methoxide in dry methanol (0.5M; 4 ml.) was added 4- chlorobenzonitrile (1 .38 g, 10 mmol). The resulting suspension was stirred at room temperature under argon for 2.5h. A solution of <strong>[20605-41-8]methoxyacetic acid hydrazide</strong> (1 .04 g, 10 mmol) in dry methanol (10 ml.) was added to the mixture, resulting in a clear solution, which was heated to reflux for 3h and then stirred at room temperature overnight. The mixture was concentrated under reduced pressure and purified by flash column chromatography eluting with 20percent to 60percent ethyl acetate in petroleum ether to afford 3-(4-chlorophenyl)-5- methoxymethyl-1 H-1 ,2,4-triazole as a white solid (412 mg, 1.84 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.1% | With hydrogenchloride; zinc(II) chloride; In water; 1,2-dichloro-ethane; at 90℃; for 7h;Reflux; | The specific steps of the preparation method of 4-chloro-4'-hydroxybenzophenone of this embodiment include:Dichloroethane 550ml was added to the reactor.Phenol 120g,P-chlorophenyl nitrile 146g,Anhydrous zinc chloride 22g and Dowex 50W resin Dow Chemicals 7g,Stirring, temperature control at 90 °C continuous flow of dry hydrogen chloride gas, the gap during the detection of material reaction conditions, until the complete reaction of chlorobenzene,After cooling to room temperature, 450 ml of a 30percent aqueous solution of hydrochloric acid was added and the mixture was heated to reflux for 7 hours.After the intermediates are hydrolyzed, the mixture is cooled to room temperature, and the layers are separated and washed with water. Dichloroethane is recovered from the organic layer. The residue is dissolved in 200 ml of a 15percent aqueous solution of sodium hydroxide, decolorized with activated charcoal 8 g, acidified and extracted. Filter and dry to obtain a pale yellow solid4-chloro-4'-hydroxybenzophenone,The content was 99.2percent, and the yield was 88.1percent. |
88.2% | Dichloroethane 600ml, phenol 120g, p-chlorobenzonitrile 146g, were added to the reactor. 25 g of anhydrous zinc chloride and 8 g of Amberlyst 15 resin produced by Dow Chemical, Stirring, temperature control at 90°C, continuous introduction of dry hydrogen chloride gas, During the ventilation process, the material in the gap is tested for reaction until complete reaction to chlorobenzonitrile. Cool to room temperature and add 500ml of a 30percent strength aqueous solution of hydrochloric acid and heat up to reflux. Reaction 5h, until the intermediate is hydrolyzed, then cooled to room temperature, layered, washed with water, Dichloroethane is recovered in the organic layer, The residue was dissolved in 250 ml of a 15percent aqueous sodium hydroxide solution. Decolorization with activated charcoal 8g, acid precipitation, suction filtration, Drying to give a pale yellow solid is 4-chloro-4'-hydroxybenzophenone. The content was 99.2percent and the yield was 88.2percent. |
Tags: 623-03-0 synthesis path| 623-03-0 SDS| 623-03-0 COA| 623-03-0 purity| 623-03-0 application| 623-03-0 NMR| 623-03-0 COA| 623-03-0 structure
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H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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