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CAS No. : | 95-71-6 | MDL No. : | MFCD00002345 |
Formula : | C7H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CNHDIAIOKMXOLK-UHFFFAOYSA-N |
M.W : | 124.14 | Pubchem ID : | 7253 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 35.45 |
TPSA : | 40.46 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -6.41 cm/s |
Log Po/w (iLOGP) : | 1.25 |
Log Po/w (XLOGP3) : | 0.91 |
Log Po/w (WLOGP) : | 1.41 |
Log Po/w (MLOGP) : | 1.15 |
Log Po/w (SILICOS-IT) : | 1.35 |
Consensus Log Po/w : | 1.21 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.68 |
Solubility : | 2.62 mg/ml ; 0.0211 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.35 |
Solubility : | 5.61 mg/ml ; 0.0452 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.59 |
Solubility : | 3.19 mg/ml ; 0.0257 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.7% | With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 120℃;Inert atmosphere; | 250ml of three bottles by adding 125mlN, N-dimethylformamide,Pass nitrogen into solvent deaeration,Then join2-methyl, 1,4-hydroquinone(10 g, 80.55 mmol) and potassium carbonate (33.5 g, 242.8 mmol)Nitrogen protection,Heated to 80 C to 120 C,To a solution of bromoethane (26. 3 g, 24 L 7 mmol)Reaction overnight. After completion of the reaction, the mixture was concentrated under reduced pressure,Get a brown solid,Adding methylene chloride to dissolve, washing with saturated brine three times,Concentration under reduced pressure to obtain crude 1,4-diethoxy-2-methyl-benzene(8. 8 g, yield 60. 7%) |
2-Methyl-benzene-1,4-diol (5, 10.0 g, 80.55 mmol) was dissolvedin dry N,N-dimethyl formamide. After addition of K2CO3(33.5 g, 242.8 mmol), the solution was heated under nitrogen at80 C for 10 min, bromoethane (26.3 g, 241.7 mmol) was addeddropwise to the solution over 30 min, followed by stirring at80 C for 12 h. Then the mixture was cooled to room temperatureand N,N-dimethylformamide was removed by distillation. The residuewas dissolved in dichloromethane and extracted with water(3 200 mL). The combined organic phases were dried withNa2SO4, and concentrated under reduced pressure to give the crudeproduct 6 8.8 g (yield 60.7%) without further purification. | ||
With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 120℃;Inert atmosphere; | 250 ml of a 3-necked flask was charged with 125 ml of N, N-dimethylformamide, and the solvent was deoxygenated by introducing nitrogen. Then, 2-methyl, 1,4-hydroquinone (10 g, 80.55 mmol) and potassium carbonate 33.5 (26.3 g, 24.17 mmol) was added dropwise and the reaction was allowed to proceed overnight at 0 & lt; 0 & gt; C under nitrogen. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to give a brown solid, which was dissolved in methylene chloride, washed three times with saturated brine and concentrated under reduced pressure to give the crude 1,4-diethoxy-2- Benzene (8. 8 g, yield 60.7%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon monoxide; hydrogen in Gegenwart von Octacarbonyldikobalt und CoCO3 in Benzol bei ca. 190grad/240 at; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With silica gel supported cerium(IV) ammonium nitrate-NaBrO3; In dichloromethane; water; at 40℃; for 2h; | General procedure: A solution of CAN (0.056 g, 0.102 mmoles) and sodium bromate (0.780 g, 5.17 mmoles) in H2O (3 mL) was added slowly to vigorously stirred anhydrous silica gel (5 g) that was contained in a 100 mLround-bottom flask containing a magnetic stirring bar and fitted with a rubber septum. After complete addition of the aqueous solution, stirring was continued until a free-flowing powder was obtained.CH2Cl2 (25 mL) was then added to the flask and a solution of hydroquinone 1A (220.23 mg, 2.0 mmol), in CH2Cl2 (5 mL) was added slowly to the stirred heterogeneous mixture. A condenser was attached to the flask and the reaction was heated to reflux. Disappearance of 1A was monitored by thin-layer chromatography (EtOAc-hexane, 1:4; panisaldehyde/sulfuric acid as staining agent). Upon complete disappearance of 1A (ca. 2 h), the reaction mixture was filtered through a sintered glass funnel, the solid residue was washed with additional CH2Cl2 (3 × 10 mL), and the washings were added to the filtrate. Removal of solvent from the organic solution under vacuum gave an orange solid. Radial chromatography of the crude product (EtOAc-hexane,1:9) gave 1,4-benzoquinone 2A (89 mg, 82%) as an orange solid. |
EXAMPLE 4 The procedure described in Example 3 is repeated using 2.5 g (0.02 mole) of methylhydroquinone as the aromatic diol reactant. The yield of methyl-p-benzoquinone obtained is 79%. | ||
EXAMPLE 4 In an experiment similar to Example 1 except that o-cresol is used in place of phenol, a good yield of methyl-p-benzoquinone is obtained which is hydrogenated to 1,4-dihydroxy-2-methylbenzene. |
In acetone; | EXAMPLE 14 The reaction was made under the same conditions as those in the procedure of EXAMPLE 1 except that the aromatic diol compound was 62g (0.5 mole) of methylhydroquinone and 250 ml of acetone was used as the solvent. No unreacted methylhydroquinone was detected and the yield of 2-methyl-p-benzoquinone was 99.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine; at 20℃; for 24h; | 5.1.2.1 2,5-Diacetoxytoluene (16) This compound was obtained in quantitative yield without the need for chromatographic purification; IR (film, cm-1); 1H NMR (CDCl3, 400 MHz, delta ppm); 13C NMR (CDCl3, 100 MHz, delta ppm) and HRMS data are consistent with that those reported previously. 16 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid; at 0℃; for 1h;Milling; | General procedure: <strong>[95-71-6]2-Methylbenzene-1,4-diol</strong> (12.4 g, 0.1 mol), ethyl 3-oxobutanoate or ethyl 2-chloro-3-oxobutanoate (0.12 mol), and H2SO4 (98%, 50 mL) were mixed in a 250 mL round bottom flask and stirred at 0 C for 1 h. Then the mixture was reacted at room temperature overnight. Reaction mixture was poured into crushed ice (500 mL) and stirred until it was cooled to room temperature. The solid product was collected by filtration and washed with water to yield 6-hydroxycoumarin 2. The residue was dried and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium dithionite In diethyl ether; dichloromethane; water at 20℃; | |
96% | With hydrogen In ethyl acetate for 4h; Ambient temperature; | |
90% | With 1,1,3,3-Tetramethyldisiloxane; iodine In dichloromethane for 0.5h; Heating; |
89% | With 2,5-dihydrotoluene; trifluoroacetic acid In toluene at 30℃; for 2h; | |
88% | With sodium disulfite In diethyl ether; water for 4h; Ambient temperature; | |
85% | With sodium azide In water; acetone at 20℃; | |
81% | With palladium 10% on activated carbon; ammonium formate In methanol for 0.166667h; Inert atmosphere; Reflux; | |
70% | With sodium dithionite; water In dichloromethane at 20℃; for 1h; | 4.4.3 Synthesis of Toluhydroquinone (5) To a solution of toluquinone (22, 61 mg, 0.5 mmol) in CH2Cl2 (0.5 mL) atroom temperature was added with a solution of Na2S2O4 (0.24 g, 1.5 mmol) inwater (1.5 mL). The resulting mixture was stirred vigorously at roomtemperature for 1 hour, added with water (2 mL), and extracted with ethylacetate (3×10 mL). The combined organic extracts were washed with brine,dried over anhydrous sodium sulfate, filtered, and concentrated. The residuewas purified by column chromatography over silica gel to affordtoluhydroquinone (5) as a yellow solid (43 mg); Yield: 70%; m.p. = 126-127 °C; 1H NMR (400 MHz, DMSO-d6): δ/ppm = 8.50 (s, 1H), 8.48 (s, 1H),6.55 (d, 1H, J = 8.5 Hz), 6.47 (s, 1H), 6.37 (dd, 1H, J = 8.4, 2.3 Hz), 2.03 (s,3H); 13C NMR (100 MHz, DMSO-d6): δ/ppm = 16.1, 112.6, 115.0, 117.1,124.3, 147.7, 149.5; IR (thin film): νmax = 3252, 2253, 1604, 1508, 1466, 1202,1022, 999, 774 cm-1. HRMS (ESI+): m/z calcd for C7H8O2Na [M+Na]+:147.0416; found: 147.0415. |
With 1,4-dihydronicotinamide adenine dinucleotide In water; acetonitrile at 30℃; pH=7.0; | ||
With Phenylhydroquinone In water at 22℃; effect of water properties (pH, composition) and water pretreatment; | ||
With water; sodium hydrogensulfite | ||
With sulfur dioxide; water | ||
With water; tin(ll) chloride bei Siedetemperatur; | ||
With hydrogenchloride; palladium on activated charcoal; carbon monoxide | ||
With sulphurous acid | ||
With nickel at 200℃; Hydrogenation; | ||
With chloro-trimethyl-silane; 1,1,3,3-Tetramethyldisiloxane; sodium iodide 1.) chlorotrimethylsilane, sodium iodide, acetonitrile, 5 min; 2.) 1,1,3,3-tetramethyldisiloxane, dichloromethane, reflux, 30 min; Yield given. Multistep reaction; | ||
With triethylamine In acetonitrile Irradiation; | ||
With sodium bromate; sulfuric acid; water at 25℃; | ||
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In dichloromethane at 25℃; for 0.5h; Inert atmosphere; | ||
With sodium dithionite; water | ||
With sulfur dioxide; water for 1h; | 3.2 3.2 Preparation of methylhydroquinone In a 300 mL three-necked flask, 140 g of water was added to the above-mentioned methylphenylhydrazine-water mixture and diluted with sulfur dioxide.Restore until the yellow crystal is completely dissolved. Stirring was continued for 1 h. After the reaction was clarified, it was extracted with ether (3 x 10 mL). Rotary evaporator decompression recovery of ether to obtain crude methyl hydrogen hydrazine, Methylhydroquinone crude product 2.2g plus deionized water 6.6g, sulfur dioxide aqueous solution 2.2g, sulfur dioxide to pH=2,Stir and heat. After being completely dissolved, add 0.5g of activated carbon to decolorize and heat-filter. The filtrate was cooled and crystallized, filtered, washed, dried, and dried under reduced pressure to obtain a six-oxafine product | |
With porous organic polymer (POP) supported Pd nanoparticle catalyst for 12h; Inert atmosphere; | ||
With sulfur dioxide In water for 1h; | 2.3 Preparation of methylhydroquinone (hexasin) Dilute the above-mentioned methyl benzoquinone-water mixture with 140 g of water in a 300 mL three-necked flask.Reduction is carried out with sulfur dioxide until the yellow crystals are completely dissolved.Stirring was continued for 1 h. After the reaction mixture was clarified, extracted with diethyl ether (3×10 mL).The ether was recovered under reduced pressure by rotary evaporator to give crude methylhydroquinone.The crude methylhydroquinone 2.2 g was added with 6.6 g of deionized water and 2.2 g of a sulfur dioxide aqueous solution, and sulfur dioxide was passed to pH = 2, and the mixture was heated by stirring. After total dissolution, 0.5 g of activated carbon was added for decolorization and filtered while hot. The filtrate is cooled and crystallized, filtered, washed with water, dried, and dried under reduced pressure to give a hexahydrate product, melting point 125-126 ° C. | |
With sulfur dioxide; water at 20℃; for 0.166667h; | 1-6 Example 1: Take a mass fraction of 8% o-methyl-p-benzoquinone aqueous suspension 300ml,Placed in a 500ml closed reactor,Turn on the stir,Control the stirring speed to 120 rpm,Introducing sulfur dioxide,Keep the sulfur dioxide pressure at 0.05 MPa,The temperature of the system rises after the reaction starts.Turn on the cooling water,Keep the reaction temperature at 20±2°C,During the reaction, the reaction solution was taken to analyze the content of o-methyl-p-benzoquinone.When no o-methyl p-benzoquinone is reached, the reaction time is 10 minutes.The reaction was stopped, and the reaction solution was extracted with extraction agent methyl isobutyl ketone 150 ml, 100 ml, 100 ml, 50 ml, 50 ml, 50 ml for 6 times.To obtain an o-methyl hydroquinone extract,Add 200 ml of water to the extract.The solvent was distilled off under reduced pressure to give an o-methyl hydroquinone aqueous solution.The o-methyl hydroquinone aqueous solution is decolorized, concentrated under reduced pressure,Cooling crystallization,Drying gives o-methyl hydroquinone products.Product quality: o-methyl hydroquinone content ≥ 99.8%, initial melting point ≥ 171.2 ° C, ash content ≤ 0.015%, heavy metal (in Pb) ≤ 0.0005%. | |
99.5 %Spectr. | With hydrogen In ethanol; toluene at 25℃; Flow reactor; | 1; 5-8 Example 1 Hydrogenation The apparatus of FIG. 1 was used.In FIG. 1, 1 is a hydrogen cylinder.2 is a flow controller. 3 is a container. 4 is a pump.5 is a column packed with a polysilane metal catalyst.The length of column 5 is 8 cm.This column 5 is packed with 8 g of polysilane palladium catalyst (Pd / γ-alumina (200 mesh), Pd: 0.1 mmol / g). The polysilane palladium catalyst has a phenyl group and a methyl group in the side chain.6 is a container.7 is a solution of the compound represented by the above general formula [I] filled in the container 3.8 is a solution of the compound represented by the above general formula [II] filled in the container 6.Hydrogenation was performed at 25 ° C. conditions.2-Methyl-1,4-benzoquinone (toluquinone)Is the solvent (toluene: ethanol = 3: 1)Dissolved inSaid toluquinoneThe concentration of is 0.05 mol / l.Hydrogen was supplied from cylinder 1 to column 5.The flow rate is 5.6 ml / min.Toluquinone solution 7 was supplied from vessel 3 to column 5.The flow rate is 0.2 ml / min.A hydrogenation reaction was performed at column 5.2-Methyl-1,4-benzoquinone was converted to 2-methyl-1,4-hydroquinone.The solution before flowing into the column (solution 7) and the solution after flowing into the column (solution 8) were analyzed by gas chromatograph. The results are shown in Table 1. The numerical value is (2-methyl-1,4-benzoquinone) + (2-methyl-1,4-hydroquinone) = 100%. BelowThe same is true for the table below.Table 12-Methyl-1,4-benzoquinone 2-Methyl-1,4-hydroquinoneSolution 7 99.5% 0.5%Solution 8 0.5% 99.5%There was no detection of substances other than toluene, ethanol, 2-methyl-1,4-benzoquinone and 2-methyl-1,4-hydroquinone.It was found that most of the 2-methyl-1,4-benzoquinone was converted to 2-methyl-1,4-hydroquinone.The solvent of solution 8 was distilled off.This was examined by 1 H-NMR. As a result, it was found that 99.5% was 2-methyl-1,4-hydroquinone. |
With hydrogen In tetrahydrofuran at 30℃; Flow reactor; | ||
23 g | With hydrogen at 100℃; | 1; 2; 3; 4; 5 In a 500 mL eggplant-shaped flask, 40.0 g of o-cresol, 8.0 g of 20% (w / w) catalyst Ti-Superoxide and 1% (w / w) benzyltriethylammonium chloride were added, and heated under strong mechanical stirring To 50-60 ° C, 320 mL of 30% hydrogen peroxide (99% conversion, 91% selectivity) was slowly added dropwise while maintaining the reaction system at 50-60 ° C. Cold after 1 hour of reactionAfter reaching room temperature, the catalyst was washed with 300 mL of toluene three times and the reaction solution was extracted.The recovered catalyst and hydrogen peroxide are recycled, and the combined organic phases are directly put into a closed container.4.5g of Raney nickel was added, and the reaction was carried out under a hydrogen pressure of 0.6 MPa and 100 ° C. for more than 10 hours. After the reaction is completed, the catalyst is removed, and it is allowed to stand for 5 minutes after heating under reflux.Decant the upper toluene solvent and crystallize to obtain an off-white solid.It was recrystallized from toluene to obtain 23.0 g of a white solid with a yield of 50%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine; In dichloromethane; at 0℃; for 0.5h; | To a well stirred solution of methyl hydroquinone (4) (3 gm, 24.19 mmol) in 50 ml DCM pyridine (6 mL, 75 mmol) was added and stirred about 15 minute then acetyl chloride was added to the reaction mixture dropwise at the ice cold condition and stirred about half an hour. Then the reaction mixture was quenched with distilled water and extracted with DCM (15 mL X 3). The organic fraction was washed with distilled water then the organic fraction was dried over anhydrous sodium sulphate. Solvent was evaporated to reduced pressure afforded the pure 2-methyl-1, 4-phenylene diacetate (5) (4.8 gm, 95%). Rf = 0.55 (Ethyl acetate/Petroleum ether = 3:7). 1H NMR (400 MHz, CDCl3) delta = 7.02-6.90 (m, 3H), 2.31 (s, 3H), 2.28 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3) delta = 169.3, 169.0, 147.9, 146.6, 131.4, 123.8, 122.5, 119.7, 21.0, 20.6, 16.2; HRMS (ESI) calc?d for C11H12O4 [M]+ : 208.0736, Found 208.0729. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; for 3h;Inert atmosphere; | 2-Bromo-5-methylcyclohexa-2,5-diene-1,4-dione (23). To a solution of toluquinol (1) (2.5 g, 20.14mmol,1.0 equiv.) in acetone (15 mL) was added K2CO3 (14 g, 100.70 mmol, 5.0 equiv.) and Me2SO4 (5.7 mL,60.41 mmol, 3.0 equiv.) and the reaction mixture was stirred for 3 h. After this time, the reactionmixture was diluted with water and the aqueous phase was extracted with Et2O. The organic phasewas washed with brine, dried over MgSO4, filtered, and the solvent removed under reduced pressureto obtain the corresponding dimethoxy derivative (~20 mmol), which was used in the next stepswithout purification. To a solution of the dimethoxy derivative obtained above (~20 mmol) and NaOAc(3.3 g, 40.28 mmol, 2.0 equiv.) in AcOH (20 mL) was added bromine (1.2 mL, 2.15 mmol, 1.1 equiv.)over 25 min and, after the addition, the reaction mixture was stirred for 1 h. Then, the reaction mixturewas quenched by a slow addition of a saturated aqueous NaHCO3 solution at 0 C. The aqueousphase was then extracted with EtOAc and the organic phase washed with brine, dried over MgSO4,ltered, and the solvent removed under reduced pressure to obtain the corresponding bromo derivative(~20 mmol), which was used in the next step without purication. The bromo derivative obtainedabove (~20 mmol) was dissolved in CH3CN (35 mL). Then, CAN (28 g, 50.34mmol, 2.5 equiv.) and H2O(20 mL) were added and the reaction mixture was stirred for 1 h at 25 C. After this time, the reactionmixture was diluted with water and the aqueous phase was extracted with Et2O twice. The combinedorganic phases were washed with brine, dried over MgSO4, filtered, and the solvent removed underreduced pressure. The residue was purified by flash column chromatography (silica gel, 1% EtOAc inhexanes) to obtain compound 23 (1.5 g, 37% over 3 steps) as an orange solid [13]: Rf = 0.45 (silica gel,20% EtOAc in hexanes); 1H NMR (400 MHz, CDCl3) delta 7.29 (s, 1 H), 7.26 (s, 2 H), 2.08 (d, J = 1.6 Hz,3 H); 13C NMR (100 MHz, CDCl3) delta 185.1, 179.5, 146.5, 138.1, 137.5, 132.6, 15.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water at 25℃; dependence on pH; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 91% 2: 9% | With methyllithium In tetrahydrofuran; diethyl ether at -78℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With zinc(II) chloride at 80 - 90℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 20℃; sowie bei 30grad und 40grad; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 4 A molecular sieve In methanol at 20℃; for 2h; | |
70% | for 0.00833333h; Molecular sieve; Microwave irradiation; neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; toluene-4-sulfonic acid; dicyclohexyl-carbodiimide In dichloromethane at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With toluene-4-sulfonic acid; In para-xylene; for 20h;Dean-Stark; Reflux; | A mixture of 4-hydroxybenzoic acid (111 g, 0.8 mol), 2-methylhydroquinone (50 g, 0.4 mol), p-toluenesulfonic acid monohydrate (7.7 g, 0.04 mol) and p-xylene (400 ml_) was heated to reflux using a Dean-Stark apparatus for 20 h. The reaction mixture was cooled to room temperature and the product was isolated by filtration, washed with methanol (400 ml_) and vacuum- dried at 40 C for 12 h to give the product as a white crystalline solid (136 g, 93%). |
85% | With toluene-4-sulfonic acid; In ortho-diethylbenzene; at 180℃; for 4h; | First, 4-hydroxybenzoic acid and 2-methylhydroquinone were heated at 180 C. for about 4 hours in diethylbenzene as a solvent at a mole ratio of 2:1 with a small amount of TsOH added thereto, while removing water. After the completion of the reaction, the reaction mixture was filtered to obtain a crude solid compound, which, in turn, was washed with water and with ether several times to obtain an ester compound as a white solid at a yield of 85%. |
With toluene-4-sulfonic acid; In xylenes; at 20℃; for 44h;Heating / reflux; | A mixture of 240.0 g 4-hydroxybenzoic acid, 100.2 g methylhydroquinone, 6 g p-toluenesulfonic acid, and 1500 mL xylenes in a flask equipped with a Dean-Stark trap, condenser and mechanical stirrer, was heated to reflux under a nitrogen atmosphere for a total of 26 h. Additional p- <n="26"/>toluenesulfonic acid (6.0 g portions) was added after 8 and 18 h after cooling the reaction mixture RT. The final reaction mixture was cooled to RT, the solids collected and washed with hexanes. The solids were slurried with hot acetone (600 mL) and cooled to RT, collected and dried to provide Compound 1. 1H NMR (DMSO-d6, 500 MHz) delta 2.16 (s, 3H), 6.93 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 7.13 (m, IH), 7.23 (m, 2H), 7.99 (d, J = 8.8 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 10.51 (s, 2H). |
With toluene-4-sulfonic acid; In xylene; at 20℃;Heating / reflux; | A mixture of 4-hydroxybenzoic acid (240.0 g), methylhydroquinone (100.2 g), pTSA (6 g), and xylenes (1.5 L) was heated to reflux under a nitrogen atmosphere for a total of 26 h in a flask equipped with a Dean-Stark trap, condenser and mechanical stirrer. Additional pTSA (6.0 g portions) was added after 8 and 18 h after cooling the reaction mixture RT. The final reaction mixture was cooled to RT, the solids collected and washed with hexanes. The solids were slurried with hot acetone (600 mL) and cooled to RT, collected and dried to provide Compound 25A: 1H NMR (DMSO-d6, 500 MHz) delta 2.16 (s, 3H), 6.93 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, <n="34"/>2H), 7.13 (m, IH), 7.23 (m, 2H), 7.99 (d, J = 8.8 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 10.51 (s, 2H). | |
With toluene-4-sulfonic acid; In xylenes; for 26h;Reflux; Inert atmosphere; Dean-Stark conditions; | Example 1; This example illustrates the formation of Compound 9, a liquid crystal monomer of one embodiment of the invention. A mixture of 240.0 g 4-hydroxybenzoic acid, 100.2 g methylhydroquinone, 6 g p-toluenesulfonic acid, and 1.5 L xylenes was heated to reflux under a nitrogen atmosphere for a total of 26 h in a flask equipped with a Dean-Stark trap, condenser and mechanical stirrer. Additional p-toluenesulfonic acid (6.0 g portions) was added after 8 and 18 h after cooling the reaction mixture RT. The final reaction mixture was cooled to RT, the solids collected and washed with hexanes. The solids were slurried with hot acetone (600 mL) and cooled to RT, collected and dried to provide Compound 7. 1H NMR (DMSO-d6, 500 MHz) delta 2.16 (s, 3H), 6.93 (d, J=8.8 Hz, 2H), 6.95 (d, J=8.8 Hz, 2H), 7.13 (m, 1H), 7.23 (m, 2H), 7.99 (d, J=8.8 Hz, 2H), 8.02 (d, J=8.8 Hz, 2H), 10.51 (s, 2H). | |
10.5 g | With toluene-4-sulfonic acid; In toluene; for 8h;Reflux; Dean-Stark; Inert atmosphere; | 11.1 g of p-hydroxybenzoic acid, 5.0 g of methylhydroquinone and 0.5 g of pTSA were added to 100 mL of toluene, and the mixture was heated and refluxed for 8 hours while stirring and removing water in the system using a Dean-Stark apparatus under a nitrogen atmosphere. The mixture was cooled and the precipitate was separated off by filtration. The obtained crystal was washed with acetone at 50 C. to obtain 10.5 g of a compound (cex-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.0%; 96% | With dihydrogen peroxide;Ti-superoxide; In water; acetic acid; at 50 - 60℃; for 1.25h;Heating / reflux;Product distribution / selectivity; | Preparation of 2-methyl-1, 4-benzoquinone A mixture of o-cresol (5 mmol) and Ti-superoxide catalyst (125 mg, 20% w/w) in acetic acid (5 ml) was heated with stirring at 50-60 C under inert atmosphere. To this reaction mixture was added aq. 30% H2O2 (20 mmol) drop wise over 15 min. and heated for 1 h. The catalyst was recovered by simple filtration and 2-methyl-1, 4-benzoquinone formed (96%) was separated by chromatographic purification.Table 1: Ti-superoxide (1) catalyzed oxidation of phenols to quinines and hydroquinones with aq. 30% H202 : a Ex. Substrate t/h Conversion ProductU Selectivity (%) c No. (%) Quinone HQd 1. Phenol 10 22 2 20e 91. 0 2. Phenol 8 66 5 6 92. 4 3. Phenol 7 65 3 60 92.3 4. Phenol 7 68 3.5 63g 92.7 5. Phenol 1 92 88 2.3 95.7 6. o-Cresol 1 99 96 3.0 97.0 7. 7n-Cresol 1 100 99 0.5 99.0 8. 2,6-Dimethylphenol 1 100 97 2.0 97.0 9. 2-'Butylphenol 1 99 97 0. 7 98.0 10. 2, 6-Dibutylphenol 3 70 65 2. 0 93.0 11.4-Chlorophenol 1 57 55-96.5 12.4-Bromophenol 1 61 60-98. 4 13. 4-Iodophenol 1 77 75-97.4 14.2, 4-Dichlorophenol 1 32 25 5. 0 78.1 (a) See examples for detailed experimental procedure; (b) determined by GC analysis of the crude product; (c) selectivity to hydroquinone ; (d) hydroquinone; (e) aq. 10% H202; (f) aq.50% H202; (g) 40% w/w catalyst. |
With dihydrogen peroxide;copper(II) hydroxide phosphate; In cyclohexane; water; at 66℃; for 2h;Product distribution / selectivity; | General procedure followed for the preparation of a mixture comprising benzoquinone and hydroquinone from ortho-cresol is set forth below. Hydrogen peroxide (30 weight percent) was added to a mixture of water, water-immiscible solvent, catalyst and ortho-cresol at a specific rate. The amount of water, water-immiscible solvent, catalyst, ortho-cresol, hydrogen peroxide (30 weight percent) and the reaction parameters including temperature and rate of hydrogen peroxide addition are set forth in Table II below. The conversion of ortho-cresol, peroxide efficiency and quantity of benzoquinone and hydroquinone are included in Table III. | |
With dihydrogen peroxide;copper(II) hydroxide phosphate; In n-heptane; water; at 73℃; for 2h;Product distribution / selectivity; | General procedure followed for the preparation of a mixture comprising benzoquinone and hydroquinone from ortho-cresol is set forth below. Hydrogen peroxide (30 weight percent) was added to a mixture of water, water-immiscible solvent, catalyst and ortho-cresol at a specific rate. The amount of water, water-immiscible solvent, catalyst, ortho-cresol, hydrogen peroxide (30 weight percent) and the reaction parameters including temperature and rate of hydrogen peroxide addition are set forth in Table II below. The conversion of ortho-cresol, peroxide efficiency and quantity of benzoquinone and hydroquinone are included in Table III. |
With dihydrogen peroxide;copper(II) hydroxide phosphate; In acetonitrile; at 73℃; for 1h;Product distribution / selectivity; | General procedure followed for the preparation of a mixture comprising benzoquinone and hydroquinone from ortho-cresol is set forth below. Hydrogen peroxide (30 weight percent) was added to a mixture of water, water-immiscible solvent, catalyst and ortho-cresol at a specific rate. The amount of water, water-immiscible solvent, catalyst, ortho-cresol, hydrogen peroxide (30 weight percent) and the reaction parameters including temperature and rate of hydrogen peroxide addition are set forth in Table II below. The conversion of ortho-cresol, peroxide efficiency and quantity of benzoquinone and hydroquinone are included in Table III. | |
With dihydrogen peroxide;copper(II) hydroxide phosphate; In decane; water; at 73℃; for 2.3h;Product distribution / selectivity; | General procedure followed for the preparation of a mixture comprising benzoquinone and hydroquinone from ortho-cresol is set forth below. Hydrogen peroxide (30 weight percent) was added to a mixture of water, water-immiscible solvent, catalyst and ortho-cresol at a specific rate. The amount of water, water-immiscible solvent, catalyst, ortho-cresol, hydrogen peroxide (30 weight percent) and the reaction parameters including temperature and rate of hydrogen peroxide addition are set forth in Table II below. The conversion of ortho-cresol, peroxide efficiency and quantity of benzoquinone and hydroquinone are included in Table III. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 99% 2: 0.5% | With dihydrogen peroxide In water; acetic acid for 1.25h; Heating / reflux; | 7 Preparation of 2-methyl-1, 4-benzoquinone A mixture of m-cresol (5 mmol) and Ti-superoxide catalyst (125 mg, 20% w/w) in acetic acid (5 ml) was heated with stirring at 50-60 C under inert atmosphere. To this reaction mixture was added aq. 30% H202 (20 mmol) drop wise over 15 min. and heated for 1 h. The catalyst was recovered by simple filtration and 2-methyl-1, 4-benzoquinone formed (99%) was separated by chromatographic purification.Table 1: Ti-superoxide (1) catalyzed oxidation of phenols to quinines and hydroquinones with aq. 30% H202 : a Ex. Substrate t/h Conversion ProductU Selectivity (%) c No. (%) Quinone HQd 1. Phenol 10 22 2 20e 91. 0 2. Phenol 8 66 5 6 92. 4 3. Phenol 7 65 3 60 92.3 4. Phenol 7 68 3.5 63g 92.7 5. Phenol 1 92 88 2.3 95.7 6. o-Cresol 1 99 96 3.0 97.0 7. 7n-Cresol 1 100 99 0.5 99.0 8. 2,6-Dimethylphenol 1 100 97 2.0 97.0 9. 2-'Butylphenol 1 99 97 0. 7 98.0 10. 2, 6-Dibutylphenol 3 70 65 2. 0 93.0 11.4-Chlorophenol 1 57 55-96.5 12.4-Bromophenol 1 61 60-98. 4 13. 4-Iodophenol 1 77 75-97.4 14.2, 4-Dichlorophenol 1 32 25 5. 0 78.1 (a) See examples for detailed experimental procedure; (b) determined by GC analysis of the crude product; (c) selectivity to hydroquinone ; (d) hydroquinone; (e) aq. 10% H202; (f) aq.50% H202; (g) 40% w/w catalyst. |
Yield | Reaction Conditions | Operation in experiment |
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Stage #1: With polyethylene glycol at 390 - 480℃; for 24.25h; Calcination; Stage #2: methanol; hydroquinone With water In 1,2-dimethoxyethane at 465 - 480℃; for 10 - 24h; Gas phase; | 1; 2-10 A dry mixture of 100 grams (gms) of magnesium carbonate, 2.5 gms of polyethylene glycol, 1 gram (gm) graphite, and 1000 ppm of copper nitrate was prepared. This mixture was pelletized and crushed to particles having a size of 800 - 1400 micrometers to provide the catalyst precursor system. Examples 2- 10: A glass reactor was loaded with 5 grams of the catalyst precursor system prepared in example 1. The catalyst was calcined in-situ for 22 hours at 390°C under a flow of nitrogen, at atmospheric pressure. After calcination, the temperature was increased to 480°C over a period of two hours under a nitrogen atmosphere. After 15 minutes, a feed mixture comprising hydroquinone, methanol (MeOH), monoglyme and water, was introduced at the flow rates indicated by the weighted hourly space velocity (WHSV) in Table 1. The molar ratio of hydroquinone to monoglyme to water was maintained at 1:2:3 and the carrier gas to hydroquinone molar ratio was maintained at 8:1. The temperature of the feed mixture and the molar ratio of methanol to hydroquinone were varied as indicated in Table 1. The alkylation was run for 24 hours under the above mentioned conditions during which methyl hydroquinone selectivity and dimethyl hydroquinone selectivity were monitored on HPLC. Samples for measuring conversion and selectivity were withdrawn as indicated by the time of sampling (TOS) data indicated in Table 1 below. 2-Methyl hydroquinone selectivity was calculated as follows: 2-MeHQ selectivity=(moles of 2- MeHQ formed/moles of HQ converted) *100 %. Table 1 Ex. HQ in moles MeOH/HQ Time of sampling WHSV Temp HQ 2-MeHQ 2,6-di Me HQ in hours in °C conversion selectivity in selectivity in in mole % mole% mole % 1 1 3 10 1.3 480 25 75 13 2 1 2 10 1 480 50 32 20 3 1 3 10 1.3 465 27 53 15 4 1 4 10 1.6 480 30 55 26 5 1 2 10 1.6 480 24 63 10 6¹ 1 3 10 1.3 480 38 44 17 7² 1 3 24 1.3 480 15 64 13 Hydrogen as the carrier gas ²5 moles of water per mole of hydroquinone. | |
Stage #1: Calcination; Stage #2: methanol; hydroquinone With water In 1,2-dimethoxyethane at 480℃; for 10h; Gas phase; | Comparative Example. A similar procedure was followed as in examples 2-10, except that the catalyst precursor contained only magnesium carbonate. Results are shown in Table 2. Table 2. Ex. HQ in MeOH/HQ Time of WHSV Temp HQ 2-MeHQ 2,6-di Me HQ moles sampling in °C conversi selectivity in selectivity in in hours on in mole% mole % mole % Comp 10 15 Ex. 1 1 3 1.3 480 34 49 15 |
Yield | Reaction Conditions | Operation in experiment |
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28% | 7 3-Benzyl-9-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one hydrochloride EXAMPLE 7 3-Benzyl-9-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one hydrochloride Prepared by the procedure of Example 1 from 3-methyl-4-hydroxyphenol and ethyl 1-benzyl-4-oxo-3-piperidinecarboxylate hydrochloride. The crude product was converted to the hydrochloride salt. Yield 28%; mp 283°-289° C. |
Yield | Reaction Conditions | Operation in experiment |
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With water at 20℃; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
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With water UV-irradiation; |
Yield | Reaction Conditions | Operation in experiment |
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89% | 2-Methylhydroquinone (30 g, 0.24 mol) was dissolved in a mixed solvent of dry THF (0.4 L) and pyridine (59 ml, 0.73 mol). Trimellitic anhydride chloride (104 g, 0.48 mol) was dissolved in anhydrous THF (0.3 L) and added dropwise to the methyl hydroquinone solution at 0 C with continuous stirring over 1 h, then subsequently reacted at room temperature for 12 h. The reaction mixture was filtered off to collect the white precipitate consisting of crude product and pyridine/hydrochloride salt as by-product. The precipitate was repeatedly washed with water and THF to remove the salt and subsequently dried at 160 C for 24 h in vacuum. Since the product undergoes partial hydrolysis toward anhydride ring opening on the procedure, the solid was suspended in dry toluene (600 mL), added with DMF (6 drops) and oxalyl chloride (49.5 g, 0.39 mol) and stirred at reflux for 8 h to ensure ring closure dehydration. The batch is cooled to room temperature, filtered and washed with dry toluene and dry THF and finally dried at 120 C in vacuum. The crude product obtained was finally recrystallized from a mixed solvent of 1 ,4-dioxane/TFIF (1/1 , v/v) then vacuum-dried again at 160 C for 24 h to yield the product as a white solid (102 g, 89 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; dicyclohexyl-carbodiimide In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
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66.6% | With Myceliophthora thermophila laccase In aq. phosphate buffer at 20℃; for 0.333333h; Green chemistry; Enzymatic reaction; | 2.3 Experimental procedures General procedure: For analytical experiments one thiol (1-5 mM) and one p-hydroquinone (1 mM) were incubated with laccase (activity 1 U) in a final volume of 4 ml of the respective buffer (sodium acetate buffer, pH 5 for Pycnoporus cinnabarinus and citrate phosphate buffer, pH 7 for Myceliophthora thermophila, both stored at 4°C and used at room temperature for reactions). Reaction mixtures were incubated with agitation at 200 rpm at room temperature in brown-glass-bottles. After incubation for 20 min, 2 h, or 24 h the mixture was analyzed by HPLC, LC-10AT VP system (Shimadzu, Germany) consisting of a FCV-10AL VP pump, SPD-M10A VP diode array detector, and a SCL-10A VP control unit controlled by Class-VP version 6.12 SP5. The separation of substances was achieved on a RP18 column at a flow rate of 1 mL min-1. The solvent system consisted of methanol (eluent A) and 0.1% phosphoric acid (eluent B), starting from an initial ration of 10% A and 90% B and reaching 100% methanol within 14min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Myceliophthora thermophila laccase In aq. phosphate buffer at 20℃; for 0.333333h; Green chemistry; Enzymatic reaction; | 2.3 Experimental procedures General procedure: For analytical experiments one thiol (1-5 mM) and one p-hydroquinone (1 mM) were incubated with laccase (activity 1 U) in a final volume of 4 ml of the respective buffer (sodium acetate buffer, pH 5 for Pycnoporus cinnabarinus and citrate phosphate buffer, pH 7 for Myceliophthora thermophila, both stored at 4°C and used at room temperature for reactions). Reaction mixtures were incubated with agitation at 200 rpm at room temperature in brown-glass-bottles. After incubation for 20 min, 2 h, or 24 h the mixture was analyzed by HPLC, LC-10AT VP system (Shimadzu, Germany) consisting of a FCV-10AL VP pump, SPD-M10A VP diode array detector, and a SCL-10A VP control unit controlled by Class-VP version 6.12 SP5. The separation of substances was achieved on a RP18 column at a flow rate of 1 mL min-1. The solvent system consisted of methanol (eluent A) and 0.1% phosphoric acid (eluent B), starting from an initial ration of 10% A and 90% B and reaching 100% methanol within 14min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Pycnoporus cinnabarinus laccase In aq. acetate buffer at 20℃; for 2h; Green chemistry; Enzymatic reaction; Overall yield = 18.8 %; Overall yield = 9.34 mg; | 2.3 Experimental procedures General procedure: For analytical experiments one thiol (1-5 mM) and one p-hydroquinone (1 mM) were incubated with laccase (activity 1 U) in a final volume of 4 ml of the respective buffer (sodium acetate buffer, pH 5 for Pycnoporus cinnabarinus and citrate phosphate buffer, pH 7 for Myceliophthora thermophila, both stored at 4°C and used at room temperature for reactions). Reaction mixtures were incubated with agitation at 200 rpm at room temperature in brown-glass-bottles. After incubation for 20 min, 2 h, or 24 h the mixture was analyzed by HPLC, LC-10AT VP system (Shimadzu, Germany) consisting of a FCV-10AL VP pump, SPD-M10A VP diode array detector, and a SCL-10A VP control unit controlled by Class-VP version 6.12 SP5. The separation of substances was achieved on a RP18 column at a flow rate of 1 mL min-1. The solvent system consisted of methanol (eluent A) and 0.1% phosphoric acid (eluent B), starting from an initial ration of 10% A and 90% B and reaching 100% methanol within 14min. |
Yield | Reaction Conditions | Operation in experiment |
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General procedure: Synthesis of Liquid Crystal Composition Compound (IV-1) (54 g, 204 mmol) and Compound (V-29) (6.8 g, 17.7 mmol) were mixed with ethyl acetate (50 mL), THF (45 mL) and diisopropylethylamine (41.8 mL). The obtained solution was added dropwise to an ethyl acetate solution of methanesulfonyl chloride (25.5 g, 223 mmol), slowly under cooling on ice. The feed ratio by mole of Compound (IV-1) and Compound (V-1) was 92:8. Next, the mixture was stirred for one hour under cooling on ice, an ethyl acetate solution of Compound (III-1) (13.5 g, 109 mmol) was added dropwise under cooling on ice, N-methylimidazole (0.5 g) was further added, and thereto triethylamine (33.7 mL) was slowly added dropwise under cooling on ice. The mixture was then stirred for two hours while keeping the reaction temperature at 20 C., water (140 mL) was added for extraction into an organic layer, and the organic layer was washed with a 2% aqueous hydrochloric acid solution and a 10% brine in this order. A portion of the organic layer was sampled and subjected to HPLC analysis, and production ratio of Compound (I-1) and Compound (II-53) was estimated based on the ratio of peak areas. The production ratio by mole was found to be 88:12. The obtained result was listed in Table 2 below. Next, the organic layer was filtered under suction, methanol/water was added to the filtrate so as to allow crystal to deposit, and the resultant crystal was collected by filtration, to thereby obtain a liquid crystal composition containing Compound (I-1) and Compound (II-53) (yield=60 g). The obtained liquid crystal composition was sampled and subjected to HPLC analysis, and compositional ratio of Compound (I-1) and Compound (II-53) was estimated based on the ratio of peak areas. The compositional ratio by mass was found to be 87:113. The obtained result was listed in Table 2 below. The liquid crystal composition was found to show a nematic-Iso phase transition temperature of 140 C. Note that the production ratio and the compositional ratio of Compound (I-1) and Compound (II-53) were estimated using standard curves determined based on the ratio of peak areas in HPLC analyses, using standard samples of separately synthesized Compound (I-1) and Compound (II-53). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With hydrogenchloride; dmap; diisopropyl-carbodiimide; In tetrahydrofuran; at 40℃; for 5h; | 2-methylhydroquinone 3.0 g (24.2 mmol), 4-[3-(acryloyloxy)butoxy]benzoic acid 14.7 g (55.6 mmol), 4-dimethylaminopyridine (DMAP) 0.18 g (1.5 mmol) ) And 0.14 g (1.4 mmol) of 35% hydrochloric acid were added to 39 mL of tetrahydrofuran (THF) and stirred, and 7.0 g (55.6 mmol) of N,N-diisopropylcarbodiimide (DIC) was added dropwise to the solution. After completion of dropping, the mixture was stirred at 40 C. for 5 hours to obtain a reaction solution. The reaction solution was filtered to remove insoluble matter. A part of the solvent of the filtrate from which the insoluble matter was removed was distilled off to obtain 15 mL of a solution. 60 mL of methanol was added dropwise to 15 mL of the obtained solution to crystallize the polymerizable liquid crystal compound, and then the mixture was stirred under cooling. The obtained precipitate (crystal) is collected by filtration, and the collected precipitate (crystal) is dried to give 2-methyl-1,4-phenylene=bis{4-[3-(acryloyloxy)butoxy]. Benzoate} was obtained with a yield of 94% (14.0 g, 22.8 mmol). The purity of the obtained 2-methyl-1,4-phenylene=bis{4-[3-(acryloyloxy)butoxy]benzoate} was 97.8%. In addition, the content of N,N-diisopropylurea as a by-product contained in the finally obtained 2-methyl-1,4-phenylene bis{4-[3-(acryloyloxy)butoxy]benzoate} , 0.01% by mass relative to the yield, which was sufficiently reduced. |
Example 1 Compound (IV-1) (21 g, 80 mmol) and Compound (V-1) (1.3 g, 8.9 mmol) were mixed with ethyl acetate (24 mL), tetrahydrofuran (22 mL) and triethylamine (13 mL). The obtained solution was slowly added dropwise to an ethyl acetate solution of methanesulfonyl chloride (10 g, 89 mmol) under cooling on ice. Feed ratio by mole of Compound (IV-1) and Compound (V-1) was 90:10. Next, the mixture was stirred for one hour under cooling on ice, an ethyl acetate solution of Compound (III-1) was added dropwise under cooling on ice, and then triethylamine (14 mL) was slowly added dropwise under cooling on ice. The mixture was then stirred for two hours while keeping the reaction temperature at 20 C., water (60 g) was added for extraction into an organic layer, and the organic layer was washed with a 2% aqueous hydrochloric acid solution and a 10% brine in this order. A portion of the organic layer was sampled and subjected to HPLC analysis, and production ratio of Compound (I-1) and Compound (II-1) was estimated based on the ratio of peak areas. The production ratio by mole was found to be 82:18. The obtained result was listed in Table 1 below. Next, the organic layer was filtered under suction, methanol/water was added to the filtrate so as to allow crystal to deposit, and the resultant crystal was collected by filtration, to thereby obtain a liquid crystal composition containing Compound (I-1) and Compound (II-1) (yield=21.6 g). The obtained liquid crystal composition was sampled and subjected to HPLC analysis, and compositional ratio of Compound (I-1) and Compound (II-1) was estimated based on the ratio of peak areas. The compositional ratio by mass was found to be 89:11. The obtained result was listed in Table 1 below. The liquid crystal composition was found to show a nematic-Iso phase transition temperature of 115 C. Note that the production ratio and the compositional ratio of Compound (I-1) and Compound (II-1) were estimated using standard curves determined based on the ratio of peak areas in HPLC analyses, using standard samples of separately synthesized Compound (I-1) and Compound (II-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.3g | With dmap; triethylamine; In tetrahydrofuran; for 1h;Cooling with ice; | Stirrer, was added methanesulfonyl chloride 5.00 g (43.6 mmol) and tetrahydrofuran 10mL the reactor having a thermometer and two dropping device. Ice-cold while each by dropping a tetrahydrofuran solution 30mL of formula tetrahydrofuran solution 60mL and triethylamine 5.25g of (I-3-1) represented by the compound 12.9g (44.1 mmol) of (51.9 mmol) from device (equation (solution of the compound represented by I-3-1)) :( triethylamine solution) = 2: were added dropwise simultaneously with one of the drip rate.After stirring for 1 hour while cooling with ice, it was added 4-dimethylaminopyridine 2.64 g (21.6 mmol) and 2- (4-hydroxyphenyl) ethanol 2.69 g (19.4 mmol).With ice-cooling was added dropwise triethylamine 5.25g (51.9 mmol).After stirring for 7 hours, the solvent was distilled off and treated added for liquid separation dichloromethane and 5% hydrochloric acid.After the organic layer was washed with brine neutralization, and purified by column chromatography (silica gel) and reprecipitated (dichloromethane / methanol) to give the compound 12.2g of formula (I-3).82% yield, had a purity of 99.63%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1-methyl-1H-imidazole; triethylamine; In tetrahydrofuran; ethyl acetate; at 23℃; for 3h; | To the solution obtained as the upper layer, 440 ml of ethyl acetate, 222 ml of THF (tetrahydrofuran), 45.6 g (0.367 mol) of methylhydroquinone and 5 ml (63.6 mmol) of N-methylimidazole were sequentially added. While keeping the internal temperature at 20 C. or less, 160 ml (1.15 mol) of triethylamine was added dropwise, and the mixture was stirred at 23 C. for 3 hours. 1000 ml of water and 80 g of common salt were added to the reaction solution and transferred to a separatory funnel to remove the aqueous layer. Methanol (1400 ml) was added to the organic layer, and the resulting crystals were separated by filtration and dried to obtain 203 g (yield 90%) of a compound C as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
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92% | With toluene-4-sulfonic acid; In water; at 40℃; for 1h;Green chemistry; | General procedure: A mixture of hydroquinones 1 (0.5 mmol), TsOH.H2O (2 mol%) and benzhydryl alcohols 2(0.6 mmol) in H2O (2 mL) was heated at 40 C for 1h. After it was cooled, the reactionmixture was poured into water and extracted with EtOAc. The organic layer was dried overanhyd. Na2SO4, and concentrated in a rotatory evaporator. The residue was purified by silicagel column chromatography (step gradient with 10-20% ethyl acetate in hexanes as theeluent) to afford the desired products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With toluene-4-sulfonic acid; In water; at 40℃; for 1h;Green chemistry; | General procedure: A mixture of hydroquinones 1 (0.5 mmol), TsOH.H2O (2 mol%) and benzhydryl alcohols 2(0.6 mmol) in H2O (2 mL) was heated at 40 C for 1h. After it was cooled, the reactionmixture was poured into water and extracted with EtOAc. The organic layer was dried overanhyd. Na2SO4, and concentrated in a rotatory evaporator. The residue was purified by silicagel column chromatography (step gradient with 10-20% ethyl acetate in hexanes as theeluent) to afford the desired products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid; In water; at 40℃; for 1h;Green chemistry; | General procedure: A mixture of hydroquinones 1 (0.5 mmol), TsOH.H2O (2 mol%) and benzhydryl alcohols 2(0.6 mmol) in H2O (2 mL) was heated at 40 C for 1h. After it was cooled, the reactionmixture was poured into water and extracted with EtOAc. The organic layer was dried overanhyd. Na2SO4, and concentrated in a rotatory evaporator. The residue was purified by silicagel column chromatography (step gradient with 10-20% ethyl acetate in hexanes as theeluent) to afford the desired products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid; In water; at 40℃; for 1h;Green chemistry; | General procedure: A mixture of hydroquinones 1 (0.5 mmol), TsOH.H2O (2 mol%) and benzhydryl alcohols 2(0.6 mmol) in H2O (2 mL) was heated at 40 C for 1h. After it was cooled, the reactionmixture was poured into water and extracted with EtOAc. The organic layer was dried overanhyd. Na2SO4, and concentrated in a rotatory evaporator. The residue was purified by silicagel column chromatography (step gradient with 10-20% ethyl acetate in hexanes as theeluent) to afford the desired products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With toluene-4-sulfonic acid; In water; at 40℃; for 1h;Green chemistry; | General procedure: A mixture of hydroquinones 1 (0.5 mmol), TsOH.H2O (2 molpercent) and benzhydryl alcohols 2(0.6 mmol) in H2O (2 mL) was heated at 40 °C for 1h. After it was cooled, the reactionmixture was poured into water and extracted with EtOAc. The organic layer was dried overanhyd. Na2SO4, and concentrated in a rotatory evaporator. The residue was purified by silicagel column chromatography (step gradient with 10?20percent ethyl acetate in hexanes as theeluent) to afford the desired products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-methylbenzene-1,4-diol With 3,4-dihydro-2<i>H</i>-pyran; iron(III) sulphate monohydrate In diethyl ether at 20℃; Inert atmosphere; Stage #2: trans-4-<trans-4-Pentylcyclohexyl>cyclohexyl-1-carboxylic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane Inert atmosphere; Stage #3: 2.4-dihydroxybenzophenone; 4-(8-(tetrahydro-2H-pyran-2-yloxy)octyloxy)benzoic acid Overall yield = 160 g; Further stages; | 2.2 To a reaction flask containing 2-methylhydroquinone (189 g) and ferric sulfate hydrate (12.18 g) was added 1 L of diethyl ether. Dihydropyran (160.08 g) was added dropwise. The resulting solution was stirred overnight at room temperature under nitrogen. After filtration, sodium hydroxide (67.5 g) in water (750 mL) was added to the filtrate and the aqueous phase was acidified by addition of dry ice cubes over two days. The formed precipitate was collected by filtration, washed with deionized water and dried in a vacuum oven to yield a brown solid (160 g). NMR showed that the product had a structure consistent with 2,3-methyl-4-((tetrahydro-2H-pyran-2-yl)oxy)phenol. Step 2 (0247) The procedures of Example 1 were followed, with the exception that an equimolar amount of 2,3-methyl-4-((tetrahydro-2H-pyran-2-yl)oxy)phenol was used in place of 4-((tetrahydro-2H-pyran-2-yl)oxy)phenol in step 7. The crude product was recrystallized in dichloromethane to yield a pale brown solid. NMR showed that the product had a structure consistent with 4-((4-((8-(4-benzoyl-3-hydroxyphenoxy)octyl)oxy)benzoyl)oxy)-2-methylphenyl 4′-pentyl-[trans,trans-1,1′-bi(cyclohexane)]-4-carboxylate, as represented by the following formula. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Under a nitrogen atmosphere, 0.8 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 1.8 g of the compound represented by the formula (D-2 R-7) in 10 mL of tetrahydrofuran and 0.8 g of diisopropylethylamine were added dropwise, followed by stirring at -5 ° C. for 1 hour.8 mL of a tetrahydrofuran solution of 1.6 g of a compound represented by the formula (D-2 R-3), 0.8 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added,And the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water and extracted with dichloromethane. Purification by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol) gave 2.3 g of a compound represented by the formula (D-2R). Purity 95.186percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-4-1)15.2 g of the compound represented by the formula (C-4-2), 0.8 g of phosphoric acid,150 mL of mesitylene was added,And heated under reflux for 20 hours while removing water.After cooling, the solid was filtered and dispersed and washed with water. And dried to obtain 21.8 g of a compound represented by the formula (C-4). Under a nitrogen atmosphere,2.0 g of the compound represented by the formula (C-4) produced in Example 1-7,4.0 g of the compound represented by formula (D-2-1)0.1 g of 4-dimethylaminopyridine,40 mL of dichloromethane was added.2.1 g of diisopropylcarbodiimide was added dropwise while cooling with ice, and the mixture was stirred at room temperature for 10 hours.The precipitate was removed by filtration, and the filtrate was washed successively with 1percent hydrochloric acid, water and brine.After recrystallization (dichloromethane / methanol), purification was carried out by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol) to obtain 4.6 g of the compound represented by the formula (D-2) .The obtained compound had a purity of 98.644percent (impurity content represented by formula (C-4) of 0.006percent, impurity content represented by formula (F1-2) and formula (F2-2) 0.120percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Under a nitrogen atmosphere,To the reaction vessel, 1.0 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 2.0 g of the compound represented by the formula (D-2R-1) in 10 mL of tetrahydrofuran and 1.3 g of diisopropylethylamine were added dropwise, followed by stirring at -5 ° C. for 1 hour.4 mL of a tetrahydrofuran solution of 0.8 g of a compound represented by the formula (D-2 R-2), 1.3 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added, and the mixture was stirred at room temperature for 2 hours.The reaction solution was poured into 5percent hydrochloric acid and extracted with ethyl acetate.Purification by column chromatography (silica gel, ethyl acetate) gave 2.1 g of a compound represented by the formula (D-2 R-3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-acetoxybenzoyl chloride; 2-methylbenzene-1,4-diol With pyridine In dichloromethane at 20℃; for 5h; Inert atmosphere; Cooling with ice; Stage #2: With methanol; sodium hydroxide In water at 20℃; for 8h; Stage #3: 4-[(4-propenoyloxy)butyloxy]benzoic acid Further stages; | 2-11 (Example 2-11) Preparation of the compound represented by the formula (D-10B) 15.1 g of a compound represented by the formula (C-2B-3)Methanol 150 mL,Water 50 mL,17 mL of 25% aqueous sodium hydroxide solution was added,And the mixture was stirred at room temperature for 8 hours.The reaction solution was poured into 5% hydrochloric acid and extracted with ethyl acetate.By distilling off the solvent and drying, 11.8 g of a compound represented by the formula (C-2B) was obtained. In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2A-1)11.1 g of the compound represented by the formula (C-2A-2)p-toluenesulfonic acid monohydrate3.1 g,200 mL of xylene was added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol.And dried to obtain 18.1 g of a compound represented by the formula (C-2A). Under a nitrogen atmosphere,To the reaction vessel, 1.0 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 2.0 g of the compound represented by the formula (D-10A-1) in 10 mL of tetrahydrofuran and 1.3 g of diisopropylethylamine were added dropwise and stirred at -5 ° C. for 1 hour.9 mL of a tetrahydrofuran solution of 1.8 g of the compound represented by the formula (C-2A) produced in Example 1-2,1.3 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added,And the mixture was stirred at room temperature for 2 hours.The reaction solution was poured into water and extracted with dichloromethane.Purification was carried out by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol)4.5 g of a compound represented by the formula (D-10A) was obtained.The obtained multi-compound has a purity of 99.431% (impurity content represented by formula (C-2A) of 0.002%, impurity content represented by formula (F1-10) and formula (F2-10) 0.012%). In Example 2-10, the compound represented by the formula (C-2A) was added to the compound represented by the formula (C-2B) produced in Example 1-3,By the same method except that the compound represented by the formula (D-10A-1) was replaced with the compound represented by the formula (D-10B-1)To prepare a compound represented by formula (D-10B).The obtained compound had a purity of 99.211% (impurity content represented by formula (C-2B) of 0.004%, impurity content represented by formula (F1-10) and formula (F2-10) 0.030%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-methylbenzene-1,4-diol; p-(benzyloxy)benzoic acid With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene for 30h; Dean-Stark; Reflux; Stage #2: With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50℃; for 5h; Autoclave; Stage #3: 4-[(4-propenoyloxy)butyloxy]benzoic acid Further stages; | 2-12 (Example 2-12) Preparation of a compound represented by the formula (D-10C) In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2C-1)18.4 g of the compound represented by the formula (C-2C-2)3.1 g of p-toluenesulfonic acid monohydrate and 200 mL of xylene were added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol. And dried to obtain 25.6 g of a compound represented by the formula (C-2C-3). In an autoclave, 25.6 g of the compound represented by the formula (C-2C-3)Tetrahydrofuran 300 mL,Ethanol 150 mL,0.3 g of 5% palladium carbon was added,And the mixture was heated and stirred for 5 hours at 50 ° C. under a hydrogen pressure of 0.5 MPa.After removal of palladium carbon, the solvent was distilled off and dried,To obtain 17.8 g of a compound represented by the formula (C-2C). In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2A-1)11.1 g of the compound represented by the formula (C-2A-2)p-toluenesulfonic acid monohydrate3.1 g,200 mL of xylene was added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol.And dried to obtain 18.1 g of a compound represented by the formula (C-2A). Under a nitrogen atmosphere,To the reaction vessel, 1.0 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 2.0 g of the compound represented by the formula (D-10A-1) in 10 mL of tetrahydrofuran and 1.3 g of diisopropylethylamine were added dropwise and stirred at -5 ° C. for 1 hour.9 mL of a tetrahydrofuran solution of 1.8 g of the compound represented by the formula (C-2A) produced in Example 1-2,1.3 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added,And the mixture was stirred at room temperature for 2 hours.The reaction solution was poured into water and extracted with dichloromethane.Purification was carried out by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol)4.5 g of a compound represented by the formula (D-10A) was obtained.The obtained multi-compound has a purity of 99.431% (impurity content represented by formula (C-2A) of 0.002%, impurity content represented by formula (F1-10) and formula (F2-10) 0.012%). In Example 2-10, the compound represented by the formula (C-2A) was added to the compound represented by the formula (C-2C) produced in Example 1-4,By the same method except that the compound represented by the formula (D-10A-1) was replaced by the compound represented by the formula (D-10C-1)To prepare a compound represented by the formula (D-10C).The obtained compound had a purity of 98.735% (impurity content represented by formula (C-2C) 0.005%, impurity content represented by formula (F1-10) and formula (F2-10) 0.054%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-acetoxybenzoyl chloride; 2-methylbenzene-1,4-diol With pyridine In dichloromethane at 20℃; for 5h; Inert atmosphere; Cooling with ice; Stage #2: With methanol; sodium hydroxide In water at 20℃; for 8h; Overall yield = 11.8 g; | 1-3 Under a nitrogen atmosphere, 10.0 g of a compound represented by the formula (C-2B-2)50 mL of thionyl chloride was added and the mixture was heated and stirred at 60 ° C. for 5 hours.Thionyl chloride was distilled off to obtain an acid chloride of the compound represented by the formula (C-2B-2).Under a nitrogen atmosphere, 6.9 g of the compound represented by the formula (C-2B-1), 60 mL of dichloromethane and 5.3 g of pyridine were added to the reaction vessel.A solution of the acid chloride of the compound represented by the formula (C-2B-2) dissolved in 20 mL of dichloromethane was added dropwise while cooling with ice, and the mixture was stirred at room temperature for 5 hours.The reaction solution was washed with 5% hydrochloric acid, water and brine.By distilling off the solvent and drying, 15.1 g of a compound represented by the formula (C-2B-3) was obtained. 15.1 g of a compound represented by the formula (C-2B-3)Methanol 150 mL,Water 50 mL,17 mL of 25% aqueous sodium hydroxide solution was added,And the mixture was stirred at room temperature for 8 hours.The reaction solution was poured into 5% hydrochloric acid and extracted with ethyl acetate.By distilling off the solvent and drying, 11.8 g of a compound represented by the formula (C-2B) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine In dichloromethane at 20℃; for 5h; Inert atmosphere; Cooling with ice; Overall yield = 15.1 g; | 1-3 (Example 1-3) Preparation of a compound represented by the formula (C-2B) Under a nitrogen atmosphere, 10.0 g of a compound represented by the formula (C-2B-2)50 mL of thionyl chloride was added and the mixture was heated and stirred at 60 ° C. for 5 hours.Thionyl chloride was distilled off to obtain an acid chloride of the compound represented by the formula (C-2B-2).Under a nitrogen atmosphere, 6.9 g of the compound represented by the formula (C-2B-1), 60 mL of dichloromethane and 5.3 g of pyridine were added to the reaction vessel.A solution of the acid chloride of the compound represented by the formula (C-2B-2) dissolved in 20 mL of dichloromethane was added dropwise while cooling with ice, and the mixture was stirred at room temperature for 5 hours.The reaction solution was washed with 5% hydrochloric acid, water and brine.By distilling off the solvent and drying, 15.1 g of a compound represented by the formula (C-2B-3) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-methylbenzene-1,4-diol; p-(benzyloxy)benzoic acid With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene for 30h; Dean-Stark; Reflux; Stage #2: With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50℃; for 5h; Autoclave; Overall yield = 17.8 g; | 1-4 In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2C-1)18.4 g of the compound represented by the formula (C-2C-2)3.1 g of p-toluenesulfonic acid monohydrate and 200 mL of xylene were added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol. And dried to obtain 25.6 g of a compound represented by the formula (C-2C-3). In an autoclave, 25.6 g of the compound represented by the formula (C-2C-3)Tetrahydrofuran 300 mL,Ethanol 150 mL,0.3 g of 5% palladium carbon was added,And the mixture was heated and stirred for 5 hours at 50 ° C. under a hydrogen pressure of 0.5 MPa.After removal of palladium carbon, the solvent was distilled off and dried,To obtain 17.8 g of a compound represented by the formula (C-2C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.1 g | Stage #1: 2-methylbenzene-1,4-diol; 4-methallyloxy-benzoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; Inert atmosphere; Stage #2: With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 16h; Inert atmosphere; | 5.2 2nd stage Under nitrogen atmospherein, DCC (33.8 g) while cooling to a mixture of compound [H7] (30.0 g), methylhydroquinone (9.5 g), DMAP (3.8 g), dichloromethane (300 mL),Was added and stirred at room temperature for 16 hours. The precipitated insolubles are removed by vacuum filtration, water is added to the filtrate, and the organic layer is separated,The resulting organic layer is washed sequentially with 2N hydrochloric acid and water,It was dried over anhydrous magnesium sulfate. The residue obtained by evaporation of the solvent under reduced pressure is subjected to column chromatography (silica gel, eluent:Purification by a mixed solvent of toluene and ethyl acetate (volume ratio: toluene / ethyl acetate = 16/1) gave colorless crystals (33.4 g). Then, under a nitrogen atmosphere, a solution of this crystal (33.4 g) in dichloromethane (330 mL) was added while cooling and 41.3 g of m-chloroperbenzoic acid was added and stirred at room temperature for 16 hours. The precipitated insolubles were removed by filtration under reduced pressure, and the filtrate was washed successively with 10% sodium bisulfite, 3% aqueous sodium hydroxide solution and water, and dried over anhydrous magnesium sulfate. The residue obtained by evaporating the solvent under reduced pressure is purified by column chromatography (silica gel, eluent: dichloromethane), and recrystallization (dichloromethane-methanol mixed solvent (volume ratio: dichloromethane / methanol = 1/10)). The residue was purified to give colorless crystalline compound (1-1-29) (21.1 g) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.2 g | With potassium carbonate; In N,N-dimethyl-formamide; at 150℃; for 7h; | In a 100 mL three-necked flask, 1.0 g (8.1 mmol) of methylhydroquinone and <strong>[13290-74-9]2-chloro-5-nitrotoluene</strong>.2.9 g (16.9 mmol) and potassium carbonate 1.5 g(10.6 mmol), 20 mL of DMF and a stirring magnet are charged and then heated,The reaction was carried out for 7 hours while maintaining the reaction temperature of 150C.After completion of the reaction, the mixture was cooled and 100 mL of distilled water was added.The precipitated solid is filtered,After washing and drying, a crude product of 1,4-bis(2-methyl-4-nitrophenoxy)-2-methylbenzene was obtained.This is dissolved in acetonitrile, heated, watered, cooled, filtered,Purified by washing and drying2.2 g of 1,4-bis(2-methyl-4-nitrophenoxy)-2-methylbenzene was obtained.The purity measured by HPLC is 99.9. The 1H-NMR spectrum chart of the compound produced in Example 1 is shown in FIG. 1, and the 13C-NMR spectrum chart is shown in FIG. The results of IR and GC-MS are as follows. |
Tags: 95-71-6 synthesis path| 95-71-6 SDS| 95-71-6 COA| 95-71-6 purity| 95-71-6 application| 95-71-6 NMR| 95-71-6 COA| 95-71-6 structure
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