Structure of 6609-56-9
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CAS No. : | 6609-56-9 |
Formula : | C8H7NO |
M.W : | 133.15 |
SMILES Code : | C1=CC=CC(=C1C#N)OC |
MDL No. : | MFCD00001783 |
InChI Key : | FSTPMFASNVISBU-UHFFFAOYSA-N |
Pubchem ID : | 81086 |
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 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.65 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.27 mg/ml ; 0.00955 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.85 |
Solubility | 1.87 mg/ml ; 0.014 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.58 |
Solubility | 0.353 mg/ml ; 0.00265 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 |
-6.01 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) |
1.21 |
* 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 |
---|---|---|
82% | With ammonia borane; In methanol; at 50℃; for 12h;Inert atmosphere; | Add PdNPore (2.7mg, 5mol%) catalyst into the mesoporous reactorAnd ammonia borane complex (30.86mg, 1mmol),Add methanol (3mL) under nitrogen,Add the substrate <strong>[6609-56-9]o-methoxybenzonitrile</strong> (58.5mg, 0.5mmol),Put it in an oil bath and react at 50 for 12h,After separation and purification by column chromatography (silica gel, 200-300 mesh; the developing solvent is ethyl acetate: methanol = 2:1),Obtained 55.9 mg of o-methoxybenzylamine with a yield of 82%. |
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; In isopropyl alcohol; at 200℃; under 75007.5 Torr; | General procedure: A solution (50 mL) containing the nitrile (5 mmol), and dichloro(p-cymene)ruthenium(II) dimer (0.05mmol) in 2-propanol (solution was sonicated until the catalyst was solubilized 10-50 min) was pumpedat 4 mL/min through the reactor coil heated at 200 C. The Phoenix backpressure regulator was set tomanual at 30%, which correlated to approximately 100 bar. A 10 mL fraction of the solution obtainedfrom the system in steady state was used to prepare the hydrochloric salt by method A or B dependingon substrate. Yields are reported as isolated hydrochloride salts, unless otherwise stated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium azide; at 80℃; for 4h; | General procedure: In a 25 mL round-bottomed flask, benzonitrile (1 mmol, 0.1 mL) and sodium azide (1.5 mmol, 0.097 g) were dissolved in PEG-400 (5 mL). Then, IR (80 mg) was added tothe reaction mixture and heated for 3 h at 80 C. The reactionprogress was monitored by TLC. After the completionof the reaction, i.e., disappearance of the nitrile spot on chromatogram,and observing a single spot of the formed tetrazoleat the bottom of the chromatogram, the reaction vesselwas cooled to room temperature. Then, IR nano-catalyst wascentrifuged and separated by filter paper. HCl (5 M, 15 mL)was added until the reaction mixture became strongly acidic(pH 3), to eliminate any unreacted nitrile and protonationof the ring tetrazole. Afterward, the reaction mixture wastreated with ethyl acetate (30 mL) and stirred vigorously for30 min. The resultant organic layer was extracted by n-hexane(3 × 50 mL). The solvent was dried by anhydrous CaCl2and evaporated by vacuum-rotary. A crude crystalline solid5-phenyl-1H-tetrazole was obtained. The prepared tetrazolewas recrystallized in hot ethanol to afford a pure product. Awhite crystalline solid 0.072 g (75%, mp: 214-215 C) wasobtained. The product was sufficiently pure, characterizedby FT-IR, 1H NMR, and 13C NMR, compared with reportedspectral data in the literature (Table 5, entry 1).5-phenyl-1H-Tetrazole (white solid); FTIR (KBr, cm-1):v 3205-2187 (N-H stretch.), 1615 (aromatic C=C stretch.),1562 (N-H bending.), 1491 (C=N stretch.), 1418 (C-Nstretch.), 1267 (N=N stretch.), 1165, 1069, and 986 (ringtetrazole and amine 2), 720, 715, and 691 (bending vibrations);1H NMR (400 MHz,DMSO, δ/ppm): 8.49 (2H, Ph),7.93 (2H, Ph),7.43 (1H, Ph); 13C NMR (100 MHz, DMSO,δ/ppm): 155.03 (NH-C=N), 131.51, 129.74, 127.04, 124.05. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97%Chromat. | With lithium diisobutylmorpholinoaluminum hydride; In tetrahydrofuran; hexane; at 0℃; for 0.5h; | General procedure: The following procedure for reduction of N,N-dimethylbenzamide with LDBMOA is representative. To a solution of N,N-dimethylbenzamide (0.149 g, 1.0 mmol) in THF (10.0 mL) containing naphthalene as an internal standard was added LDBMOA (2.4 mL, 0.5 M in THF-hexanes, 1.2 mmol) at 0 C. After 30 min, the reaction mixture was hydrolyzed with 1 N aq HCl (10 mL) and extracted with diethyl ether. The combined organic layers were dried over anhydrous magnesium sulfate, and filtered. After the removal of solvents in vacuum and purification of residue by column chromatography on silica gel gave benzaldehyde (0.103 g, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With lithium hexamethyldisilazane; In diethyl ether; at 0 - 20℃; for 48.0833 - 72.0833h; | At 00C anhydrous ether was introduced to flask under Ar, LiHMDS (94 ml, 93.9 mmol) was then introduced and stirred for 5 mins. <strong>[6609-56-9]2-methoxy-benzonitrile</strong> (5g, 37.6 mmol) was added and the mixture was stirred at room temperature for 2-3 days. Upon completion of the reaction solvent was removed and 200 mL cold 1N HCI was added and stirred. The aqueous layer was extracted with Et2O, then adjust the pH was adjusted by 6N NaOH to 13. Extraction with CH2CI2, dried over Na2SO4 and filtered. Upon concentration the above benzamidine compound was obtained in 91% yield. |
82% | With cobalt(II) chloride hexahydrate; oxygen; ethylenediamine; zinc; In neat (no solvent); at 120℃; under 3800.26 Torr; for 12h;Autoclave; | General procedure: The reaction was carried out in a 100-mL stainless steel autoclave. Phenylcyanide (0.10 g, 1.00 mmol) was added to a mixture of ethylenediamine (0.12 g, 2.00 mmol), CoCl26H2O (0.24 g, 1.00 mmol) and Zn (0.07 g, 1.00 mmol) and the vessel was placed in an autoclave. For some of the reactions that were carried out in solvent, 5 mL of solvent was also added. The autoclave was pressurized to 5.00 atm with O2. The mixture was stirred in a preheated oil bath at 120 C for 12 h. Then, the reaction mixture was cooled to room temperature and the product was purified by column chromatography on silica gel using n-hexane:CH2Cl2 (1:1) to give the benzamide(88 % yield). |
61% | With C12H24O16Ru3*2H2O; In water; at 110℃; for 4h;Schlenk technique; Inert atmosphere; Autoclave;Catalytic behavior; | General procedure: Hydration reactions were carried out in Schlenk tube under N2atmosphere. The reaction mixture was prepared dissolving 5 mg(6.5 lmol) of catalyst 2 in 3 mL of H2O. The mixture was degassedand 1.5 mmol of corresponding acetonitrile substrate was addedwith micropipette to stirred solution. The reaction was allowedfor heating at 110 C using oil bath or microwave-assisted heating.The isomerization reactions of allylic alcohols were conductedSchlenk tube under N2 atmosphere. The reaction mixture wasprepared dissolving 3 mg (3.9 lmol) of catalyst 2 in 2 mL ofappropriate solvent (DMF, EtOH or H2O). The mixture wasdegassed and 1 mmol of corresponding allylic alcohol substratewas added with micropipette to stirred solution. The reactionwas allowed for heating using oil bath.The reaction solutions were analyzed by regular sampling usingGC/FID (Hewlett Packard) equipped with Beta DEX 120(30 m 0.25 mm 0.25 lm) 30 m long column. The degrees ofconversion were calculated on the basis of the ratio of areas ofthe substrate material and the products determined from correspondingchromatograms. The optimization of chromatographicmethods and the calibration procedures for detection of productsas well as substrates were realized by injection of authenticcommercial samples. |
50% | With copper(l) iodide; caesium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In nitromethane; water; at 20 - 100℃; for 2h; | To a nitromethane (0.1 mL) solution of 4-methoxybenzonitrile (1f) (30 mg, 0.225 mmol) were addedH2O (1.0 mL), DBU (69 mg, 0.436 mmol), copper (I) iodide (9 mg, 0.0451 mmol), cesium (I)carbonate (37 mg, 0.113 mmol) at room temperature. The reaction mixture was heated at 100 C for2 h and then poured into water (50 mL). The organic layer was separated and the aqueous layer wasextracted with AcOEt. The combined organic layer was dried over MgSO4. The solvent wasremoved under reduced pressure. The residue was purified by preparative TLC on silica gel elutingwith AcOEt-n-hexane (1:1) to give 2-methoxybenzamide (2f)S5 (17 mg, 50%) as pale yellow powders.mp 123-125 C, |
92%Chromat. | General procedure: 0.6 mmol benzonitrile and 0.6 mmol DMSO were solved in 3 mL EtOH and pumped into inlet A, 50 μL 1 M NaOH (aq) solved in 1 mL EtOH and pumped into inlet B, 30% H2O2 (aq) was solved in 7 mL ethanol and pumped into inlet C (flow rate A: B: C = 1.54 μl/min:0.46 μl/min:0.3 μl/min for a 400s residence time). The whole system was maintained on 25 C. The flow system was equilibrated for 30 min, then the product stream was quenched and collected in a glass vessel with saturated aqueous NaHSO3 in it for 2 h. After being filtered, 5.0 ml of this solution was injected to the HPLC instrument for analysis. The conversion of the reaction was determined by relative area percentage of nitriles and corresponding amides. Conversion = Area (benzamide)/[Area (benzamide) + Area (benzonitrile)]. | |
With 5% Pd/CeO2; In water; at 140℃; for 18h; | Add 100mg Pd/CeO2 in 6g water (Pd load mass percentage: 5.0%,The mass percentage of the entire catalytic material in the mixture: 1.7%), 60 mg <strong>[6609-56-9]o-methoxybenzonitrile</strong> (mass percentage in the mixture: 1%), mixed uniformly; reacted at 140C for 18 hours,The conversion rate of <strong>[6609-56-9]o-methoxybenzonitrile</strong> is >99.0%,The corresponding selectivity of o-methoxybenzamide is >99.0% | |
With manganese(IV) oxide; iron(III) oxide; cobalt(II,III) oxide; In tert-Amyl alcohol; water; at 80℃; for 24h; | To 6 g of tert-amyl alcohol, 100 mg of ferric oxide, 100 mg of tricobalt tetraoxide and 100 mg of manganese dioxide (mass percentage in the mixture: 4.6%), 60 mg <strong>[6609-56-9]o-methoxybenzonitrile</strong> (mass percentage in the mixture: 0.91% ), 200uL water (mass percentage in the mixture: 3.0%), mix well; react at 80C for 24 hours, the conversion rate of <strong>[6609-56-9]o-methoxybenzonitrile</strong> is 89.5%, the corresponding selectivity of o-methoxybenzamide is 99.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydroxylamine; In ethanol; water; at 20 - 55℃; for 40h; | Hydroxylamine (Fluka 55458; 50% in water; 11.28 ml 187.76 mmol; 5 eq.) was added to a solution of 2-methoxybenzonitrile (Alrich 231231 ; 4.59 ml 37.55 mmol; 1 eq.) in EtOH (50 ml_) and the resulting mixture was stirred at room temperature for 16 hours then at 55C for 24 hours. The solvent was then evaporated and the resulting colourless oil was further dried under high vaccum to give a white solid. The latter was triturated in n-hexane, filtered and dried to afford the title compound (6.29 g, quantitative) as a white solid. HPLC (Method A) : Rt 0.96 min (purity 99.2%). |
73% | With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; for 6h;Reflux; | General procedure: To a stirred suspension of nitrile (30 mmol) and hydroxylaminehydrochloride (3.13 g, 45 mmol) in EtOH (50 mL) a NaHCO3 (3.78 g,45 mmol)was added. The reaction mixturewas stirred under refluxfor 6 h. After the reaction had completed, the reaction mixture wasconcentrated under reduced pressure, and the residue was dilutedwith cold water (80 mL). The resulting precipitate was filtered off,washed with cold water (20 mL) and dried in air at roomtemperature. |
63% | With hydroxylamine hydrochloride; potassium carbonate; In methanol; for 6h;Reflux; | General procedure: A 1.3 g of a solution of 4-chorobenzonitrile (16v, 9.69 mmol, 1 equivalent) was dissolved in 50 mL of methanol. To this 2 g of K2CO3 (14.53 mmol, 1.5 equiv) was added and mixed properly. The reaction mixture was cooled at 0 C, and 1.35 g of hydroxylamine hydrochloride (19.38 mmol, 2 equiv) was added in portion-wise. After completion of the addition, it was refluxed for 6 hr.Then evaporated the solvent and excess of water was added to afford the precipitate of the desired product which was filtered and dried. |
50% | With hydroxylamine hydrochloride; sodium carbonate; In water; at 20℃; | General procedure: Na2CO3 (3.61 g, 34 mmol) was dissolved in water (83 mL), and NH2OHxHCl (4.30 g, 61.4 mmol) was slowly added. After complete removing of CO2 appropriate nitrile (19 mmol) was added and mixture was stirred at room temperature for several days. Solvents were evaporated under reduced pressure to final volume of 50 mL. Obtained solution was extracted with ethylacetate (2 x 50 mL) and dried over Na2SO4. The solvent was removed at reduced pressure, to give the raw product that was finally purified by crystallization in ethyl acetate or by chromatography on SiO2, eluting with hexane/ethyl acetate (yields 20-50 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium hydroxide; hydroxyamino hydrochloride; In ethanol; at 20℃; for 12h;Heating / reflux; | Add potassium hydroxide (30.3 g, 225 mmol) to a solution of 2- methoxybenzonitrile (25.0 g, 187 mmol) and hydroxylamine hydrochloride (15.77 g, 225 mmol) in ethanol (500 mL) at room temperature under nitrogen and heat the mixture at reflux for 12 hours. Remove the solvent under reduced pressure, triturate the residue with ethyl acetate/hexanes (1: 9,300 mL) and collect by vacuum filtration to provide N hydroxy-2-methoxybenzamidine (24.0 g, 91%). |
With hydroxyamino hydrochloride; Sodium hydrogenocarbonate; In methanol; at 20 - 80℃; for 48h; | General procedure: General Method A for the synthesis of hydroxyamidines (A-4)To a solution of nitrile-derivative (1.0 eq.) in MeOH (0.5 M), hydroxylamine HCI (1.1 to 3.0 eq.)and NaHCO3 (1.1 to 3.0 eq.) was added at rt. The resulting suspension was stirred at a giventemperature and time (see Table 5). The mixture was concentrated in vacuo, then EtOAc wasadded to the remaining residue and the org. layer was washed with brine (lx), dried (MgSO4), filtered and concentrated to yield hydroxyamidine A-4. Listed in Table 5 below are hydroxylamidines of type A-4, prepared from either commercially available nitrile-derivates or synthesized according to described methods. | |
2.8 g | With hydroxyamino hydrochloride; triethylamine; In ethanol; lithium hydroxide monohydrate; at 70℃; for 15h; | To a stirred solution of 2-methoxybenzonitrile (2.0 g, 15.0 mmol, 1 .83 mL) in ethanol (20 mL) were added hydroxylamine hydrochloride (2.09 g, 30.0 mmol), triethylamine (3.04 g, 30.0 mmol, 4.16 mL), and water (2 mL), then the mixture was heated to 70 00 for 1 5h. The mixture was cooled and quenched with water (20 mL), extracted with dichloromethane (30 mL x 3), and the combined organicphases were washed with water (20 mL), saturated aqueous sodium chloride solution (20 mL), dried overanhydrous sodium sulfate, filtered, and concentrated to give N-hydroxy-2-methoxybenzimidamide (2.80 g)as a light green solid, which was used in next step directly. 1H NMR (400 MHz, Methanol-d4) O 7.47 -7.30 (m, 2H), 7.06 (d, J8.4 Hz, 1H), 6.95 (t, J7.5 Hz, 1H), 3.86 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 7; N-[4-Hydroxy-2-[2-(methyloxy)phenyl]-6-oxo-1-(phenylmethyl)-1,6-dihydro-5-pyrimidinyl]carbonyl}glycine; 7a) 6-Hydroxy-2-[2-(methyloxy)phenyl]-3-(phenylmethyl)-4(3H)-pyrimidinone; A 1 M solution of dimethylaluminium chloride in hexane (5.50 mL, 5.50 mmol) was added dropwise to a stirred solution of benzylamine (0.536 g, 5.00 mmol) in toluene (20 mL) under nitrogen. After stirring at ambient temperature for 20 min, 2-methoxybenzonitrile (1.33 g, 10.0 mmol) was added and the mixture refluxed for 18 h under nitrogen. After cooling, 1 M aqueous sodium hydroxide (40 mL) was added and the mixture concentrated under reduced pressure to remove the organic solvents, then extracted with ether. The extracts were dried (K2CO3, Na2SO4) and evaporated under reduced pressure to leave the crude amidine (1.12 g). A mixture of the crude amidine (0.268 g), diethyl malonate (0.359 g, 2.24 mmol), sodium methoxide in methanol (0.513 mL of a 4.37 M solution, 2.24 mmol) and 2-methoxyethanol (5 mL) was refluxed under nitrogen for 18 h, then cooled and diluted with water (20 mL). 6 M aqueous hydrochloric acid (2 mL) was added, the mixture stirred 0.5 h, and the precipitate filtered, washed with water and dried to give the title compound (0.283 g, 76%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.64 (s, 3 H) 4.69 (d, J=15.41 Hz, 1 H) 5.13 (d, J=15.66 Hz, 1 H) 5.47 (s, 1 H) 6.79-6.87 (m, 2 H) 6.95 (t, J=7.45 Hz, 1 H) 7.11 (d, J=8.34 Hz, 1 H) 7.14-7.23 (m, 4 H) 7.42-7.50 (m, 1 H) 11.63 (br. s., 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With pyridine; diammonium sulfide; triethylamine; In water; at 0 - 55℃; | To a stirred solution of 2-methoxy benzo nitrile (130 g, 977 mmol) in pyridine (1200 mL) at 0oC was added ammonium sulfide solution (650 mL, 5 vol), followed by triethyl amine (150 mL, 1075 mmol). Then the reaction mixture was stirred at 55 oC for 12h. The reaction was monitored by TLC (30 % Ethyl acetate/Hexane). After completion of the reaction, diluted with cold water (4.0 L), solid was filtered, dried over vacuum to afford 2- methoxybenzothioamide (145 g, yield: 89%) as a yellow solid.1H NMR (400 MHz, DMSO- d6) δ 9.94 br(s, 1H), 9.30 (brs, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.94 (t, J = 7.2 Hz, 1H), 3.79 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; | General procedure: A solution containing K4[Fe(CN)6] (0.2 mmol), aryl halide (1.0 mmol), Na2CO3 (1.5 mmol), Pd(at)CS-biguanidine (50 mg,0.7 mol%), and DMF (3 ml) was mixed under stirring at 120 C for the specified time. TLC was used to follow the reaction. At the end of the reaction, the obtained solution was cooled to ambient temperature and centrifuged, and the residue was rinsed using ethyl acetate (3 10 ml). Water phase containing ethyl acetate (30 mL) was mixed with the organic phase to extract the ethyl acetate from the water. The organic phase was dried over Na2SO4. The products were resulted by evaporating the organic solvent. If more purification was needed, the products were passed through a short silica gel column using the eluent of n-hexane. All the products are known substances and were compared with authentic specimens. |
88% | With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Catalytic behavior; | General procedure: A solution containing K4[Fe(CN)6] (0.17 mmol), aryl halide (1.0mmol), Na2CO3 (1.5 mmol), Fe3O4PMDP/Pd (45 mg, 1.5 mol%),and DMF (3 mL) was mixed under stirring at 120 C for the specifiedtime. TLC was used to follow the reaction. At the end of thereaction, the obtained solution was cooled to ambient temperatureand filtered, and the residue was rinsed using ethyl acetate (3 10mL) to isolate the catalyst using a suitable magnet. Water phasecontaining ethyl acetate (30 mL) was mixed with the organic phaseto extreact the ethyl acetate from the water. The organic phase wasdried over Na2SO4. The products were resulted by evaporating theorganic solvent. If more purification was needed, the productswere passed through a short silica gel column using the eluent ofn-hexane. All the products are known substances and were comparedwith authentic specimens |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-Bromosuccinimide; iodine; In acetonitrile; for 12h;Darkness; | General procedure: To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 molpercent, 0.02 mmol) and CH3CN (1.0 mL),was added para-chloroanisole 1a (0.2 mmol). After being stirred at room temperature for 12 h in dark, the reaction was quenched by saturated aq. solution of Na2S2O3 (2 mL). The resulting mixture was extracted by ethyl acetate (3 5 mL). The combined organic extracts were washed by brine (10 mL), dried over Na2SO4 and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and the residuewas purified by flash chromatography on a silica gel column with petroleum ether/dichloromethane (5:1) as the eluent to give 4.3.1. 2-Bromo-4-chloroanisole (2a) |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile Br2 (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile Bromine (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Heating; | Example 37 5-Bromo-2-(methyloxy)benzonitrile Bromine (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to the solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile <n="134"/>Br2 (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonium hydroxide; copper(l) chloride; at 120℃; for 24h; | The reactants used were o-methoxybenzyl alcohol (i.e., R1 in the formula (I) was ortho OCH3) 1.0 mmol(138.2 mg), experimental procedure and procedure with Example 1, aqueous ammonia (1.7 mol / L) 5.0 mL,The amount of catalyst used in cuprous chloride was 8 mol% (7.9 mg)TEMPO is used in an amount of 8 mol% (12.5 mg)The reaction temperature was 120 and the reaction time was 24h. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 10: 1) to give the target product as 123.9 mgYield 93%. |
90% | With ammonium hydroxide; copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; N-Phenylalanin; sodium hydroxide; In methanol; at 60℃; for 24h;Cooling with ice; | General procedure: Reactants used were p-methylbenzyl alcohol (122.03g, 1000mmol, i.e., of formula (I) wherein R is methyl, n = 1, m = 0 , X = C),cuprous iodide (9.50 g of , 50mmol), N- phenylglycine (7.51g, 50mmol), TEMPO ( 7.80g, 50mmol),sodium hydroxide (4.00g, 100mmol), aqueous ammonia (300mL, 25 ~ 28%) ,ethanol, 800mL, in an ice bath under the condition, with oxygen round bottom flask is evacuated of air ventilation 3 times, and then the system was stirred at 25 , 24h, after completion of the reaction, the reaction solution was cooled to room temperature, rotary evaporated to remove the solvent, the residue was washed with water filtered and dried The product was 107.64g, yield 92%. he reaction was used for the o-methoxybenzyl alcohol (138.02g, 1000mmol, i.e., of formula (I) wherein R is 2-methoxy n = 1, m = 0 , X = C),the same experimental methods and procedures Example 2, except that: copper iodide (9.50g, 50mmol), N- phenylalanine (8.26g, 50mmol), TEMPO ( 7.80g, 50mmol),sodium hydroxide (4.00g, 100mmol ), ammonia (300mL, 25 ~ 28%) ,methanol 800mL, stirred at 60 for 24h, to give the final product 119.71g, yield 90%. |
74.7% | With ammonium hydroxide; manganese sesquioxide; oxygen; at 130℃; under 11251.1 Torr; for 30h;Autoclave; | General procedure: The ammoxidation of alcohols and hydration of nitrileswere performed in a high-pressure steel autoclave reactorequipped with a PTFE bottle, magnetic stirrer (900 rpm), andan explosion-proof pressure sensor. For the ammoxidation ofalcohols, the as-prepared catalyst, aqueous ammonia(28%-30% NH3), and alcohols were added into a certainamount of t-amyl alcohol solvent in the reactor, then the autoclavewas sealed and purged with oxygen for two times to excludethe inside air. For the hydration of nitrile, the as-preparedcatalyst, nitrile, and water were added into a certain amount oft-amyl alcohol solvent in the reactor, then the autoclave wassealed and purged with N2 for two times to exclude the insideair. After that, the reactor was quickly heated to the desiredtemperature (the reaction temperature was measured by athermocouple in the autoclave) in an oil bath. After a desiredreaction time, the reactor was placed in an ice bath to quenchthe reaction. After separation of the solid catalyst by centrifugation,the liquid was analyzed with a Shimadzu GC-2014 gaschromatograph equipped with a flame ionization detector(FID) and an Agilent HP-6890 gas chromatograph-mass spectrometer,with ethylbenzene, bromobenzene, hexadecane, orbiphenyl used as internal standards. The gas-phase products,such as CO and CO2, were analyzed with a Fu Li-9790 gaschromatograph equipped with a thermal conductivity detector(TCD). Notably, no CO and CO2 signals were observed in TCDand total carbon balances were always >90.0% in this work.Safety Note: The high-pressure oxygen has been extensivelyused in the aerobic oxidations [21,22], and the reaction systemsin this work were out of the explosion limits of the reactants.For example, the explosion limit of benzyl alcohol is1.3%-13.0% in oxygen, and the concentration of benzyl alcoholin the gaseous phase in this work is in a 0-0.4% region, whichis out of the explosion limits. Furthermore, the fire and staticelectricity are not allowed to access the internal reactor forsafety reasons. In the kinetics study, the average reaction rateswere calculated from the moles of substrate converted pergram of catalyst in one hour (mmol gcat-1 h-1), with the conversionof substrate controlled to be lower than 20.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Catalytic behavior; | General procedure: A solution containing K4[Fe(CN)6] (0.17 mmol), aryl halide (1.0mmol), Na2CO3 (1.5 mmol), Fe3O4PMDP/Pd (45 mg, 1.5 mol%),and DMF (3 mL) was mixed under stirring at 120 C for the specifiedtime. TLC was used to follow the reaction. At the end of thereaction, the obtained solution was cooled to ambient temperatureand filtered, and the residue was rinsed using ethyl acetate (3 10mL) to isolate the catalyst using a suitable magnet. Water phasecontaining ethyl acetate (30 mL) was mixed with the organic phaseto extreact the ethyl acetate from the water. The organic phase wasdried over Na2SO4. The products were resulted by evaporating theorganic solvent. If more purification was needed, the productswere passed through a short silica gel column using the eluent ofn-hexane. All the products are known substances and were comparedwith authentic specimens |
92% | With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; | General procedure: A solution containing K4[Fe(CN)6] (0.2 mmol), aryl halide (1.0 mmol), Na2CO3 (1.5 mmol), Pd(at)CS-biguanidine (50 mg,0.7 mol%), and DMF (3 ml) was mixed under stirring at 120 C for the specified time. TLC was used to follow the reaction. At the end of the reaction, the obtained solution was cooled to ambient temperature and centrifuged, and the residue was rinsed using ethyl acetate (3 10 ml). Water phase containing ethyl acetate (30 mL) was mixed with the organic phase to extract the ethyl acetate from the water. The organic phase was dried over Na2SO4. The products were resulted by evaporating the organic solvent. If more purification was needed, the products were passed through a short silica gel column using the eluent of n-hexane. All the products are known substances and were compared with authentic specimens. |
75% | With triethylamine; In N,N-dimethyl-formamide; for 12h;Reflux; | Cyanation: in a typical procedure, a mixture of aryl iodide (0.5 mmol),K4[Fe(CN)6] (0.35 mmol), catalyst Pd-ZnFe2O4 (10 mg), triethylamine(0.6 mmol) and DMF (3 ml) was added in a round bottom flask and stirredunder reflux at 120 C under atmospheric conditions. The progress of thereaction was monitored by GC. After the reaction was over, the catalyst wasremoved using external magnet and the solution was quenched by water. Thissolution was extracted thrice with ethyl acetate and washed with brinerepeatedly. The organic layer was dried in anhydrous sodium sulphate andthen removed by rotary evaporation to produce the pure product, which wasfurther purified using silica gel column chromatography (hexane/EtOAc:90:10). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | General procedure: n-Butyllithium (1.67 M solution in hexane, 2.9 mL, 4.8 mmol) was added dropwise into a solution of 1,3-dimethoxybenzene (0.55 g, 4.0 mmol) in THF (5 mL) at 0 C and the mixture was stirred for 2 h at the same temperature. Then, DMF (0.34 mL, 4.4 mmol) was added to the mixture and the obtained mixture was stirred at 0 C. After 2 h at the same temperature, aq NH3 (8 mL, 120 mmol) and I2 (1.12 g, 4.4 mmol) were added and stirred for 2 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (15 mL) and was extracted with Et2O (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide 2,6-dimethoxybenzonitrile in over 80% purity. The product was purified by a short column chromatography on silica gel (Hexane/EtOAc=3:1) to give pure 2,6-dimethoxybenzonitrile in 91% yield as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 5 Step 1 To a reaction vessel where the atmosphere was replaced with argon, N-methyl-4-chloropiperidine (15 g), magnesium (3.3 g) and THF (50 mL) were added and the resultant mixture was heated under reflux using an oil bath. Once an exothermic reaction was observed, the oil bath was removed, and vigorous stirring was continued until the exothermic reaction was completely terminated. After the reaction system was brought to room temperature (over a period of about one hour), 2-methoxybenzonitrile (100 g) was added and the resultant mixture was heated overnight under reflux. After the reaction system was cooled to 0C using an ice bath, 10 ml of water was gradually added and subsequently 12N hydrochloric acid solution (100 mL) was gradually added to the mixture. Then, the reaction solvent was removed under reduced pressure. The reaction mixture was thoroughly stirred with the addition of a solution prepared by mixing water (50 mL) and sodium hydroxide (50 g), and the reaction solvent was again removed under reduced pressure. With the addition of ethyl acetate (50 mL), the reaction mixture was sufficiently stirred, and thereafter the target ethyl acetate solution was separated by repeating the procedure for decantation 10 times. The whole ethyl acetate solution thus obtained was concentrated to obtain the desired compound as a crude product. The product was purified by silica gel chromatography, thereby obtaining 4 g of the desired compound. Step 2 In a reaction vessel where the atmosphere was replaced with argon, the compound (1.2 g) obtained in the Step 1 of Example 5 was added to a Grignard reagent in THF (50 mL), the Grignard reagent being prepared by vigorously stirring 2-bromothiophene and magnesium (1 g). The resultant mixture was stirred for 3 hours. Water (10 ml) was gradually added and subsequently 12N hydrochloric acid solution (50 mL) was gradually added to the reaction mixture. Then, the reaction solvent was removed under reduced pressure. The reaction mixture was thoroughly stirred with the addition of a solution prepared by mixing water (50 mL) and sodium hydroxide (50 g), and the reaction solvent was again removed under reduced pressure. With the addition of ethyl acetate (50 mL), the reaction mixture was sufficiently stirred, and thereafter the ethyl acetate solution was separated by repeating the procedure for decantation 10 times. The whole ethyl acetate solution thus obtained was concentrated to obtain the desired compound. Step 3 The compound obtained in the Step 2 of Example 4 was dissolved in a solution previously obtained by mixing concentrated sulfuric acid (8 mL) and methanol (20 mL), and the resultant mixture was heated to 50C for 3 hours. The concentrated sulfuric acid solution was brought to room temperature, and then gradually added to a solution prepared by mixing water (20 mL) and sodium hydroxide (20 g) and cooled using an ice bath. The mixture was extracted with two 150 mL portions of ethyl acetate, and thereafter the resultant solution was concentrated to obtain the desired compound as a crude product. Further, the product was purified by silica gel chromatography, thereby obtaining 1 g of the compound shown in Table. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | General procedure: A pressure tube equipped with a magnetic stir bar wascharged with Pd(OAc)2 (4.5mg, 0.02mmol), XPhos-SO3Na(20.9 mg, 0.04 mmol), K4[Fe(CN)6]·3H2O (105.6 mg,0.25mmol), K2CO3(35mg, 0.25mmol) and PEG-400(1.0mL). The reaction tube was evacuated and backfilledwith argon (this sequence was carried out three times) andthen aryl chloride (1.0mmol, if liquid) and water (1.0mL)were added by syringe (aryl chlorides that were solids atroom temperature were added with the palladium catalystand ligand). The reaction tube was sealed and the reactionmixture was stirred for 12h at the indicated temperature.After being cooled to room temperature, the mixture wasextracted with cyclohexane (3 × 10mL). The combinedcyclohexane phase was concentrated under reduced pressure,and the residue was purified by flash column chromatographyon silica gel (light petroleum ether-ethyl acetate)to afford the desired aryl nitrile 2.The residue of the extraction was heated to 50C invacuo for 30min to remove the residual cyclohexane, andthen subjected to a second cycle of the cyanation reactionby charging with the same substrates (aryl chloride,K4[Fe(CN)6]·3H2O and K2CO3)under the same conditionswithout further addition of Pd(OAc)2 and Xphos-SO3Na. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(1) 2-Methoxybenzonitrile (6 g) was dissolved in diethyl ether (140 ml), a 3 M solution of methylmagnesium bromide in diethyl ether (45 ml) was added to the solution, and the resulting mixture was stirred at room temperature for 1 hour. Titanium tetraisopropoxide (13.1 ml) was added to the reaction mixture, and the resulting mixture was stirred for 4 hours under reflux by heating. 10% Aqueous sodium hydroxide (160 ml) and ethyl acetate (160 ml) were added to the reaction mixture, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through Celite, and then the layers of the filtrate were separated. The aqueous layer was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia = 40:1:0.1 to 10:1:0.1) to obtain a dimethylamine compound (2.76 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42%Chromat. | General procedure: In an oven dried 25 ml two-necked round-bottom flask equipped with a condenser was placed a mixture of aryl halide (1 mmol), [Rh(cod)Cl]2 (0.05 mmol, 5 mol %), and Xantphos (0.1 mmol, 10 mol %) in 10 ml/mol formamide at room temperature and stirred for 2-3 min. Then POCl3 (2 mmol) was added to the reaction mixture which was then heated in an oil bath at 135-140 C for 24 h with continuous stirring under nitrogen atmosphere. After 24 h the reaction mixture was cooled to room temperature and poured into 40 ml saturated solution of NaHCO3. The product was extracted into ethyl acetate (3 × 15 ml). After drying over anhydrous Na2SO4, the combined ethyl acetate layer was concentrated by rotary evaporation. All the prepared compounds were characterized by GC-MS (Shimadzu QP 2010). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77%Chromat. | General procedure: In an oven dried 25 ml two-necked round-bottom flask equipped with a condenser was placed a mixture of aryl halide (1 mmol), [Rh(cod)Cl]2 (0.05 mmol, 5 mol %), and Xantphos (0.1 mmol, 10 mol %) in 10 ml/mol formamide at room temperature and stirred for 2-3 min. Then POCl3 (2 mmol) was added to the reaction mixture which was then heated in an oil bath at 135-140 C for 24 h with continuous stirring under nitrogen atmosphere. After 24 h the reaction mixture was cooled to room temperature and poured into 40 ml saturated solution of NaHCO3. The product was extracted into ethyl acetate (3 × 15 ml). After drying over anhydrous Na2SO4, the combined ethyl acetate layer was concentrated by rotary evaporation. All the prepared compounds were characterized by GC-MS (Shimadzu QP 2010). |
Tags: 6609-56-9 synthesis path| 6609-56-9 SDS| 6609-56-9 COA| 6609-56-9 purity| 6609-56-9 application| 6609-56-9 NMR| 6609-56-9 COA| 6609-56-9 structure
A624082 [53078-69-6]
2-Methoxy-4-methylbenzonitrile
Similarity: 1.00
A127069 [3556-60-3]
3-Methoxy-4-methylbenzonitrile
Similarity: 0.97
A624082 [53078-69-6]
2-Methoxy-4-methylbenzonitrile
Similarity: 1.00
A127069 [3556-60-3]
3-Methoxy-4-methylbenzonitrile
Similarity: 0.97
A624082 [53078-69-6]
2-Methoxy-4-methylbenzonitrile
Similarity: 1.00
A127069 [3556-60-3]
3-Methoxy-4-methylbenzonitrile
Similarity: 0.97
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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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The concentration of the dissolution solution you need to prepare is mg/mL