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CAS No. : | 1137-42-4 | MDL No. : | MFCD00002355 |
Formula : | C13H10O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NPFYZDNDJHZQKY-UHFFFAOYSA-N |
M.W : | 198.22 | Pubchem ID : | 14347 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 58.34 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.33 cm/s |
Log Po/w (iLOGP) : | 1.78 |
Log Po/w (XLOGP3) : | 3.07 |
Log Po/w (WLOGP) : | 2.62 |
Log Po/w (MLOGP) : | 2.34 |
Log Po/w (SILICOS-IT) : | 2.92 |
Consensus Log Po/w : | 2.55 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.46 |
Solubility : | 0.0682 mg/ml ; 0.000344 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.52 |
Solubility : | 0.0598 mg/ml ; 0.000302 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.29 |
Solubility : | 0.0101 mg/ml ; 0.0000511 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.25 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
8.32 g | With tetrabutylammomium bromide In acetone at 30 - 40℃; for 4.16667 h; | (1) In a 250 ml three-necked flask equipped with a magnetic stirrer, a thermometer, a dropping funnel, and a condenser, 70 ml of acetone and 8.65 g (0.0437 mol) of 4-hydroxybenzophenone were added.Then pretreated 36.33g (0.1453mol exchange capacity)The D201FC exchange resin was added to a three-necked flask and stirred for heating.0.1 g of tetrabutylammonium bromide was added to the system.The system was heated to 30-40 °C.At this temperature, 5 g (0.0291 mol) of diethylaminochloroethane hydrochloride was added to the system and the addition was completed within ten minutes.Stirring was continued with stirring, and the reaction was monitored by HPLC, and the reaction was completed after 4 hours.Filtration was carried out, and the filtrate was distilled under reduced pressure to give about 15 g of a yellow oil. (2) To the oil was added 30 ml of methanol to dissolve, then 3.6 g of concentrated hydrochloric acid was added, and finally 45 ml of diethyl ether was added, which was formed as a white solid, and the upper liquid was pale yellow.Filter and wash the filter cake with ether. The finally obtained white solid was dissolved in 20 ml of water, and then adjusted to pH = 8 to 11 with a 2N sodium hydroxide solution of about 30 ml. (3) Extracted three times with methyl tert-butyl ether, 50 ml each time, and the organic phase was combined, washed once with saturated brine, and dried over 15 g of anhydrous sodium sulfate.After suction filtration and rotary evaporation, 8.32 g of 4-[2-(N,N-diethylamino)ethoxy]benzophenone was obtained.The yield was 96.27percent based on diethylaminochloroethane hydrochloride and the purity was 99.08percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: With potassium hydroxide In diethylene glycol diethyl ether for 0.5 h; Stage #2: at 120℃; for 1 h; Stage #3: With hydrogenchloride In diethylene glycol diethyl ether; water |
I a) Ethylene glycol p-benzophenone ether; In a laboratory autoclave having a capacity of 2 L there were placed 520 g of diethylene glycol diethyl ether, 286 g of p-hydroxybenzophenone (>98 wt percent), and 0.8 g of powdered potassium hydroxide. A pressure test was then carried out for 30 minutes using dry nitrogen. Following pressure let-down to atmospheric pressure and heating of the reaction mixture under a blanket of nitrogen to 120° C., 95.4 g of ethylene oxide were continuously forced in to give a maximum internal pressure of 4 bar over a period of 1 h. On completion of gassing with ethylene oxide, the reaction mixture was allowed to react, until the pressure remained constant for at least 30 minutes. The reaction mixture was discharged from the autoclave in the hot state, neutralized with 5 wt percent strength aqueous hydrochloric acid, and poured into 2 L of ice water, and the reaction product was caused to crystallize by constant agitation. The resulting solid matter was filtered off in vacuo, washed with ice water and dried in vacuo (40° C., 10 mbar absolute). The resulting filtrate was concentrated in a rotary film evaporator to 20percent of its volume, the precipitated product filtered off in vacuo, washed with ice water and likewise dried in vacuo. The total yield was 82percent of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With potassium carbonate; sodium iodide In acetoneHeating / reflux | Step 1: {4-[(2-Hydroxyethyl)oxy]phenyl}(phenyl)methanone (5)To a solution of 4-hydroxybenzophenone (6.0 g, 29.7 mmol) in acetone (50 mL) were added K2CO3 (12.3 g, 89.0 mmol) and 2-chloroethanol (4.0 mL, 59.3 mmol), followed by addition of NaI (4.50 g, 29.7 mmol). The reaction mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. The white solid was filtered off and washed with acetone (100 mL). The filtrate was concentrated to a brown oil residue with some white solid. EtOAc (200 mL) was added, the white solid was filtered off and then washed with 50 mL of EtOAc. The filtrate was washed with 1 N NaOH, water, brine and dried over Na2SO4. Concentration afforded a pale yellow oil which was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 60percent EtOAc:hexanes to give 5 as a white solid (1.52 g, 21percent). 1H NMR (400 MHz, CDCl3): δ 4.00-4.05 (m, 2H), 4.15-4.20 (m, 2H), 6.98 (d, J=8.7 Hz, 2H), 7.45-7.50 (m, 2H), 7.55-7.60 (m, 1H), 7.75 (d, J=7.1 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium iodide In toluene at 60℃; for 1.5 h; Reflux | 4-hydroxybenzophenone (262 g, 1.32 mol)NaI (6.5 g, 0.043 mol),Ethylene carbonate (125 g, 1.42 mol) andToluene (10 mL) were added to a 2000 mL three-necked flask,Raise the temperature until the system is clear.Continue to raise the temperature to the reaction system was refluxed for 1.5h,After the TLC test reaction is completed, the heating is stopped,Cooled to 60 ° C.To the reaction system was added water and ethyl acetate,extraction,The organic phase was dried over anhydrous sodium sulfate,Concentrated to give 304 g of a pale yellow solid,Yield 95percent. |
94% | With sodium iodide In toluene at 99 - 176℃; for 0.5 h; | A mixture of ethylene carbonate (124.6 g; 1.07 eq.), sodium iodide (6.3 g; 0.03 eq.), 4-hydroxybenzophenone (262 g; 1 eq.) and toluene (8.1 g) was heated. At99°C a clear solution was obtained. The reaction mixture was heated with reflux condenser to 176°C over one hour, during which gas evolution occurred. After an additional 1/2 hour at 176°C, the reaction mixture was cooled to 122°C and toluene (350 g) and water (24 g) was added. The lower phase was cut and discarded. More water (14 g) was added and the lower phase was again cut and discarded. Water and toluene (95 g in total) was azeotropically removed, reaching a boiling point of 11 1 °C. More toluene (1 14 g) was added and the product was isolated by filtration at 8°C. In total, 302 g of 4-(2-hydroxyethoxy)benzophenone (94percent) was obtained after drying as white crystals (99.8 percent chromatographic purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.5% | With hydrogenchloride; aluminum (III) chloride In water at 30℃; for 0.333333h; | To sum up, the experiment of 4-hydroxybenzophenone (1000ml four-necked bottle), condenser + tail gas recovery, thermometer drip funnel (0.8194mol) anisole, keep it at room temperature and put 135g (1.0112mol) aluminum trichloride . After the dissolution is complete, 19 g (0.8469 mol) of benzoyl chloride is added dropwise. After dripping (about 1.5h), the temperature is raised to 55/50C for 2h, and then to reflux for 2h; after refluxing, it is reduced to 55°C, and then dripped into the mixed solution containing 600ml and 50gHCL. After dripping, stirring for 20 minutes, standing and separating the water, then centrifuging at 20C, the mother liquor is recovered and used, the filter cake is washed to neutrality, and the alcohol is recrystallized to obtain the intermediate 4-hydroxybenzophenone; the yield is 94.5%; Put 100g of 4-hydroxybenzophenone into a four-necked round-bottomed flask containing 400ml of acetone, add 1.5g of homemade CatAP with 63g of chloro-n-hexane under stirring, heat to 45/40C, and start adding NaOH solution dropwise. After dripping, the temperature is raised to reflux for 3h, then the temperature is reduced to 20C and centrifuged, the mother liquor is recovered and used, and the filter cake is recrystallized with alcohol |
66% | With ytterbium(III) triflate In carbon disulfide for 10h; Heating; | |
With carbon disulfide; aluminium trichloride Man zersetzt das Reaktionsprodukt mit Wasser und krystallisiert das 4-Methoxy-benzophenon aus Aether um, man erhitzt mit Salzsaeure auf 145grad bis 150grad; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris(6,6'-diamino-2,2'-bipyridine); 4,4-diphenyl-1,3,5,7,8-pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene; Br2Ni*3H2O; water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Glovebox; Irradiation; Inert atmosphere; | |
38% | With nickel(II) sulfate hexahydrate; 4,4'-Dimethoxy-2,2'-bipyridin; 8,9-bis((R)-2-acetoxypropyl)-7,10-dimethoxyperyleno[1,12-def][1,3]dioxepine-5,6,11,12-tetrayl tetraacetate; <SUP>18</SUP>O-labeled water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Schlenk technique; Irradiation; Inert atmosphere; | 2.6. Typical experimental procedure for the hydroxylation of arylhalides with water catalyzed by HARCP General procedure: In a 10 mL schlenk tube with magnetic stirring bar, aryl halide 1(0.2 mmol), HARCP (1.2 mol%), NiSO46H2O (10 mol%), 4,40-dimethoxy-2,20-bipyridine (10 mol%), DIPEA (1.5 equiv), H2O (40 equiv)were dissolved in the mix solvent (CH3CN: DMF = 1: 1, 2 mL). Thereaction mixtures were then irradiated with 23 W CFL (at approximately2 cm away from the light source) under nitrogen atmosphere.When the reaction finished, the reaction mixtures werequenched with water (5 mL) and extracted with ethyl acetate (3x10 mL). The organic phase was washed with brine (3x 30 mL), driedover Na2SO4 and then concentrated in vacuum. The resulting residuewas purified by silica gel column chromatography to afford thedesired product 5. |
With copper(II) oxide; sodium hydroxide at 200℃; for 3h; | 1 The 4-hydroxy-benzophenone synthetic method, comprising the following steps (1) the high-pressure reaction kettle with stirring in accordance with the mass ratio of 1 : 0.01: 0.005 : 2 the proportion of 4-chloro benzophenone, copper oxide, the quality of a phase-transfer catalyst and the concentration of 5% of sodium hydroxide solution, control the stirring speed is 40r/min, heating to 200 °C reaction 3 hours;(2) after the reaction by the high-pressure reactor is poured out of the material after cooling to room temperature, add quality as the total mass of the material after the reaction of 2 times that of the de-ionized water after diluting goes to the copper oxide pumping filtered, phase-transfer catalyst and the unreacted 4-chloro benzophenone, to obtain 4-hydroxy-benzophenone alkaline solution, wherein the copper oxide, the phase transfer catalyst and unreacted 4-chloro benzophenone can be recovered for the step (1);(3) in the 4-hydroxy-benzophenone alkaline solution by adding activated carbon, is heated to boiling, 5 min oil filtering off the active carbon, obtained after the decoloring 4-hydroxy-benzophenone alkaline solution, wherein the amount of activated carbon 4-hydroxy benzophenone the total weight of the alkaline solution of 1%;(4) after the decoloring 4-hydroxy-benzophenone alkaline solution dropping the mass concentration is 5% hydrochloric acid solution until the solution is pH 1, filtered and dried to obtain the 4-hydroxy-benzophenone. |
With copper(I) oxide; sodium hydroxide at 220℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In butanone at 65℃; for 7h; | 1 Examples; Example 1; Synthesis of 4-allyloxybenzophenone (1) Example 1 [0091] Synthesis of 4-allyloxybenzophenone (1) [0092] 4-hydroxybenzophenone (186.7 g, 940 mmol, Fluka Chemical) was dissolved in 2-butanone (700 mL, Fisher Scientific) in a 2L four-necked flask equipped with a mechanical stirrer, reflux condenser, addition funnel and internal temperature probe. K2CO3 (195 g, 1.41 mol, Aldrich Chemical) was added to the reactor, and the contents was placed under a slow N2 purge. Allyl bromide (123 mL, 1.41 mol, Aldrich Chemical) was charged to the addition funnel. The pot temperature was raised to 65° C., at which point the allyl bromide was added over the course of 30 minutes. The reaction was stirred for 6.5 h at 65° C. after the addition was completed. At this point no starting material was present as determined by GC analysis. [0093] The slurry was filtered, and the filtrate was extracted with 1% HClaq (500 mL). The organic layer was isolated, dried over MgSO4 anhyd., filtered, and solvent removed in vacuo to yield a pale yellow solid (1; 207 g, 92%). The product exhibited acceptable 1H & 13C NMR, FT-IR, GC and UV-Vis characteristics. |
90% | With potassium carbonate In acetone for 8h; Heating; | |
With sodium ethanolate |
With potassium carbonate; acetone | ||
With potassium carbonate | ||
With potassium hydroxide 1.) DMSO, 5 min, 2.) DMSO, RT, 3 h; Yield given. Multistep reaction; | ||
With potassium carbonate In acetone Inert atmosphere; Reflux; | ||
4.76 g | With potassium carbonate In tetrachloromethane at 60℃; for 24h; Inert atmosphere; | 1 4.9% g (50 mmol) of 4-hydroxybenzophenone,Potassium carbonate 3.46 g (25 mmol),80 ml of carbon tetrachloride was added to a 250 ml three-necked flask equipped with a magnetic stirrer and a thermometer.Passing nitrogen,Heat and stir.9.25 g (75 mmol) of 3-bromopropene,154 g (1 mol) of carbon tetrachloride was uniformly mixed in a constant pressure funnel.Then slowly add the mixture to the three-necked flask.Rinse to 60 ° C for 24 h,After the reaction,Filter to remove solid impurities,Washed,Dissolve the salt three times,After the solvent is removed by steaming,Recrystallization gave a white powder crystal, 4.76 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With potassium carbonate; sodium iodide; In acetone;Heating / reflux; | Step 1: {4-[(2-Hydroxyethyl)oxy]phenyl}(phenyl)methanone (5)To a solution of 4-hydroxybenzophenone (6.0 g, 29.7 mmol) in acetone (50 mL) were added K2CO3 (12.3 g, 89.0 mmol) and 2-chloroethanol (4.0 mL, 59.3 mmol), followed by addition of NaI (4.50 g, 29.7 mmol). The reaction mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. The white solid was filtered off and washed with acetone (100 mL). The filtrate was concentrated to a brown oil residue with some white solid. EtOAc (200 mL) was added, the white solid was filtered off and then washed with 50 mL of EtOAc. The filtrate was washed with 1 N NaOH, water, brine and dried over Na2SO4. Concentration afforded a pale yellow oil which was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 60% EtOAc:hexanes to give 5 as a white solid (1.52 g, 21%). 1H NMR (400 MHz, CDCl3): delta 4.00-4.05 (m, 2H), 4.15-4.20 (m, 2H), 6.98 (d, J=8.7 Hz, 2H), 7.45-7.50 (m, 2H), 7.55-7.60 (m, 1H), 7.75 (d, J=7.1 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H). |
Preparation of Compound I; Synthesis of 3-(2-methylaziridin-l-yl)propionic acid 2-(4-benzoylphenoxy)ethyl ester (AZBP); To a 250 mL, one -neck, round bottom flask equipped with a magnetic stirrer were added sodium hydroxide (10.0 g, 0.250 mol) in a water (45 mL)/ethanol (20 mL) solution and 4-hydroxybenzophenone (Alfa Aesar, 50.0 g, 0.250 mol) and the mixture was heated to 55 0C. Chloroethanol (Aldrich, 20.3 g, 0.250 mol) in ethanol (25 mL) was then added dropwise to the reaction flask and the mixture heated to 75 0C for 8 hours then cooled to room temperature. The precipitate was collected by filtration, washed with water and recrystallized three times from ethanol/water to obtain 24.4 g of a white solid (4-(2- hydroxyethoxy)benzophenone). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium nitrate; potassium hydrogensulfate; silica gel In dichloromethane at 20℃; for 12h; | General procedure for the synthesis of 2a and 2b General procedure: To a solution of 4-hydroxybenzophenone or 4-hydroxyacetophenone (1.26 mmol) in dichloromethane(15 mL), potassium hydrogen sulfate (6.82 mmol), sodiumnitrate (7.32 mmol), and 0.875 g of wet silica 50% p/p wasadded. The slurry was was left under constant stirring atroom temperature until the completion of the reaction,checked by TLC (hexane/ethyl acetate, 8:2v/v). Then themixture was filtered through silica, the solid was washedwith dichloromethane and the solvent removed underreduced pressure. The products were then purified byrecrystallization. 4-hydroxy-3-nitrobenzophenone (2a) (Cohen et al. 1984)90% yield, yellow solid after recrystallization from water/methanol (1:1v/v); M.p. 105-107 °C; clogP = 3.12; IR(νmax cm-1): 3296, 3069, 1660, 1609, 1525, 1319. 1H NMR(300 MHz, CDCl3) δ: 7.28 (1H, d, H-5, 3J = 8.7 Hz),7.49-7.55 (2H, m, H-3′, H-5′), 7.64 (1H, tt, H-4′, 3J = 1.2Hz, 4J = 7.5 Hz), 7.74-7.78 (2H, m, H-2′, H-6′), 8.12 (1H,dd, H-6, 4J = 2.1 Hz, 3J = 8.7 Hz), 8.58 (1H, d, H-2, 4J =2.1 Hz). 13C NMR (75 MHz, CDCl3) δ: 193.2 (C, C-7),157.8 (C, C-4), 138.4 (CH, C-6, C, C-1′), 136.6 (C, C-3),132.9 (CH, C-4′), 129.8 (C, C-1), 129.6 (CH, C-2′, CH, C-6′), 128.6 (CH, C-3′, CH, C-5′), 127.8 (CH, C-2), 120.3(CH, C-5). pKa = 5.1. |
80% | With poly(ethylene glycol)-N2O4 In dichloromethane at 20℃; for 0.416667h; | |
78% | With ammonium nitrate; silica gel In chloroform; water for 11h; Reflux; |
70% | With NO+*18-crown-6*H(NO3)2- In acetone at 20℃; | |
With nitric acid at 0℃; | ||
With nitric acid; acetic anhydride; acetic acid at 50 - 60℃; | ||
With nitric acid; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.5% | Stage #1: 4-Hydroxybenzophenone With ethanol; sodium at 30℃; for 0.666667h; Inert atmosphere; Stage #2: 1,3-dibromo-propane at 60℃; | |
79% | Stage #1: 4-Hydroxybenzophenone With sodium n-propoxide In propan-1-ol at 20℃; for 0.0833333h; Stage #2: 1,3-dibromo-propane In propan-1-ol at 60℃; for 7h; Reflux; | General synthetic procedure for compounds 1a-1u General procedure: A solution of freshly prepared sodium 1-propanolate, proper substituted phenols were added and stirred in room temperature for 5 min. α,ω-dibromoalkanes were then added drop wisely in the time of 1 h. The reaction mixture was stirred in 60 °C for 3 h, and then refluxed for another 3 h. After cooling down to RT mixture was filtrated and evaporated. To a rough product, 100 ml of 10% NaOH was added and left overnight in cold. To a resulting white oil CH2Cl2 was added, mixed and layers were then separated. Organic layer was dried over sodium sulphate filtered and evaporated. Rough product was used for further reactions after purification. |
75% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; |
66.7% | With potassium carbonate In acetonitrile for 24h; Reflux; | |
66.7% | With potassium carbonate In acetonitrile for 24h; Reflux; | 1 Example 1 - 4-0-(3-bromopropyl)benzophenone la According to the general procedure for the halide alkylation of 4-hydroxybenzopheonone derived from Saettone et ai, International Journal of Cosmetic Sciences, 1988, 10, 99-109. 1,3- dibromopropane (60.5 mmol, 6.14 mL), potassium carbonate (30.2 mmol, 4.18 g) and 4- hydroxybenzophenone (15.1 mmol, 3.0 g) were stirred in acetonitrile (20 mL) under reflux for 24 hours to give a crude product of 4-0-(3-bromopropyl)benzophenone which was recrystallized in toluene/hexanes to yield compound la (3.22 g, 66.7% yield). Ci6Hi5Br02; off white powder, mp 54-66 °C; NMR (CDCI3, 400 MHz) δ 2.35 (m, -CH2, 2H), 3.62 (m, -CH2, 2H), 4.21 (m, - CH2, 2H), 6.95 (s, Ar, 2H), 7.55 (m, Ar, 2H), 7.60 (m, Ar, 1H), 7.75 (m, Ar, 2H), 7.80 (m, Ar, 2H) ppm; 13C NMR (CDCI3, 100 MHz) δ 195.52 (C5), 162.31 (C9), 138.24 (C4), 132.58 (C3), 129.74 (CI), 129.73 (C6), 128.21 (C2), 1 14.04 (C8), 65.53 (CIO), 32.14 (C12), 29.74 (Cl l) ppm. HRMS-DART (m/z): [M+J calcd. for Ci6Hi5Br02, 319.0334; found, 319.0329. |
With sodium hydride In N,N-dimethyl-formamide Ambient temperature; | ||
With potassium carbonate In butanone | ||
With potassium hydroxide In methanol; dimethyl sulfoxide | ||
2.78 g | Stage #1: 4-Hydroxybenzophenone With potassium carbonate; potassium iodide In acetone at 20℃; for 0.166667h; Stage #2: 1,3-dibromo-propane In acetone for 24h; Reflux; | 3.1.1. Procedure 1 To a solution of proper hydroxy benzophenone (0.01 mol) in acetone (60 mL), anhydrouspotassium carbonate (1.12 g, 0.008 mol) and catalytic amount of potassium iodidewere added. The reaction mixture was stirred for 10 min at room temperature, after which1,3-dibromopropane (12 g, 0.06 mol) was added. The reaction mixture was then heated atreflux for 24 h, after which the inorganic solids were filtered, and acetone was evaporated.Remaining oils were then purified by flash chromatography (system I).4-(3-Bromopropoxyphenyl)(phenyl)methanone (1). Synthesis from (4-hydroxyphenyl) (phenyl)methanone (1.98 g, 0.01 mol). Obtained 2.78 g of white quickly crystalizing oil. C16H15BrO2,MolecularWeight (MW) = 319.20, Yield = 87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.6% | With potassium carbonate In acetonitrile for 24h; Reflux; | |
91.6% | With potassium carbonate In acetonitrile for 24h; Reflux; | 3 Example 3 - 4-0-(4-bromobutyl)benzophenone 2a According to the general procedure for the halide alkylation of 4-hydroxybenzophenone derived from Saettone et al., International Journal of Cosmetic Sciences, 1988, 10, 99-109, 1,4- dibromobutane (50.4 mmol, 6.02 mL), potassium carbonate (25.3 mmol, 3.49 g) and 4- hydroxybenzophenone (12.6 mmol, 2.50 g) were stirred in acetonitrile (20 mL) under reflux for 24 hours to give a crude product of 4-0-(4-bromobutyl)benzophenone which was recrystallized in toluene/hexanes to yield compound 2a (3.846 g, 91.6% yield). CnHnBrC^; pale yellow powder; NMR (CDC13, 400 MHz) δ= 1.99 (m,-CH2-, 2H), 2.09 (m, -CH2-, 2H), 3.51 (m, -Br- CH2, 2H), 4.09 (m, -0-CH2, 2H), 6.95 (m, -Ax, 2H), 7.45 (m, -Ar, 2H), 7.55 (m, -Ar, 1H), 7.75 (m, -Ar, 2H), 7.85 (m, -Ar, 2H) ppm; I3C NMR (CDC13, 100 MHz) δ 195.52 (C5), 162.51 (C9), 138.27 (C4), 132.57 (C3), 131.90 (1), 129.72 (C6), 128.20 (2), 113.99 (8), 67.13 (CIO), 33.31 (C13), 29.36 (Cl l) 27.76 (C12) ppm. HRMS-DART (m/z): [M+] calcd. for C,7HI7Br02, 333.0490 found, 333.0486. |
82% | With potassium carbonate In acetone Reflux; Inert atmosphere; |
76% | Stage #1: 4-Hydroxybenzophenone With potassium carbonate In acetone at 25℃; for 1h; Stage #2: 1,4-dibromo-butane In acetone at 60℃; for 6h; | |
67% | With potassium carbonate In acetone for 8h; Reflux; | |
30.5% | With potassium carbonate In acetone Reflux; | |
With sodium hydride In N,N-dimethyl-formamide Ambient temperature; | ||
With sodium hydroxide In ethanol; pentane | 23 4-(4-Bromobutoxy)benzophenone EXAMPLE 23 4-(4-Bromobutoxy)benzophenone Combine 4-hydroxybenzophenone (14.11 g, 71.2 mmol) and aqueous 1M sodium hydroxide solution (70 mL). Add 1,4-dibromobutane (43.4 g, 200 mmol). Heat the reaction mixture to reflux. After 20.5 hours, cool to ambient temperature. Add pentane (100 mL) and again heat to reflux. After 0.5 hours, cool to ambient temperature to give a solid. Collect the solid by filtration. recrystallize the solid from ethanol to give the title compound: mp; 42°-43° C. | |
With potassium hydroxide In methanol; dimethyl sulfoxide | ||
With sodium hydroxide In ethanol | ||
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 85℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate In acetone Reflux; | 1.2 2. Preparation of compound 2 4-hydroxybenzophenone (2.52 mmol), 1,6-dibromohexane (7.56 mmol) and potassium carbonate (1.045 g) were dissolved in 15 mL of acetone solution. Heat to reflux overnight, cool to room temperature at the end of the reaction, and filter. The filtrate was distilled off under reduced pressure to remove the solvent, and the concentrate was separated by column chromatography to obtain the target compound 2 as a white solid with a yield of 82%. |
82% | With potassium carbonate In acetone Reflux; Inert atmosphere; | |
76% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; | I 4-[(6-Bromohexyl)oxy]benzophenone 4-[(6-Bromohexyl)oxy]benzophenone: [0088] 4-Hydroxy benzophenone (5.94 g, 30 mmol), 1,6 dibromohexane (8.05 g, 33 mmol), potassium carbonate (5.95 g, 45 mmol) and DMF (60 mL) were stirred at room temperature for 16 h under inert atmosphere. The reaction mixture was poured into ice water (300 mL) and extracted with ether (100 mL). The organic layer was collected and the solvent was removed by rotary evaporator. The crude product was purified on silica gel column by using 10:1 hexane ethylacetate mixture. Yield: 8.2 g (76%). 1H NMR (CDCl3): δ, 7.81 (d, 2H, J=8.4 Hz), 7.75 (d, 2H, J=7.8 Hz), 7.54 (t, 1H, 7.5 Hz), 7.47 (t, 2H, J=6.9 Hz), 6.93 (d, 2H, J=9.0 Hz), 4.06 (t, 2H, J=6.3 Hz), 3.43 (t, 2H, 6.6 Hz), 1.86 (m, 4H), 1.50 (m, 4H). 13C NMR (CDCl3): δ, 25.47, 28.10, 29.11, 32.86, 33.95, 68.2, 114.2, 128.37, 129.92, 129.94, 132.06, 132.78, 138.55, 162.9, 195.7. |
76% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; | 4-[(6-Bromohexyl)oxy]benzophenone 4-[(6-Bromohexyl)oxy]benzophenone 4-Hydroxy benzophenone (5.94 g, 30 mmol), 1,6 dibromohexane (8.05 g, 33 mmol), potassium carbonate (5.95 g, 45 mmol) and DMF (60 mL) were stirred at room temperature for 16 h under inert atmosphere. The reaction mixture was poured into ice water (300 mL) and extracted with ether (100 mL). The organic layer was collected and the solvent was removed by rotary evaporator. The crude product was purified on silica gel column by using 10:1 hexane ethylacetate mixture. Yield: 8.2 g (76%). 1H NMR (CDCl3): δ, 7.81 (d, 2H, J=8.4 Hz), 7.75 (d, 2H, J=7.8 Hz), 7.54 (t, 1H, 7.5 Hz), 7.47 (t, 2H, J=6.9 Hz), 6.93 (d, 2H, J=9.0 Hz), 4.06 (t, 2H, J=6.3 Hz), 3.43 (t, 2H, 6.6 Hz), 1.86 (m, 4H), 1.50 (m, 4H). 13C NMR (CDCl3): δ, 25.47, 28.10, 29.11, 32.86, 33.95, 68.2, 114.2, 128.37, 129.92, 129.94, 132.06, 132.78, 138.55, 162.9, 195.7. |
71% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere; | 1.1.1 Example 1.1: Synthesis of (4-((6-bromohexyl)oxy)phenyl)(phenyl)methanone (Compound 1). 4-Hydroxy benzophenone (5 g), 1,6-dibromohexane (4.3 mL), potassium carbonate (5.23 g) and dry DMF were stirred at room temperature under argon atmosphere for 18 hrs. The reaction mixture was poured into ice-water mixture (300 mL) and extracted with CHCI3. The organic layer was collected followed by removal of the solvent under reduced pressure. The crude product was purified on a silica gel column by using 20:1 hexane: ethyl acetate mixture. Solid white product (Compound 1) was obtained with 71% yield upon evaporation of the solvent under reduced pressure. Yield, 71%; 1H NMR (CDC13400MHZ) δ/ppm: 1.52-1.56 (t, -CftCH2CH2Br, 4H), 1.80-1.94 (m, -OCH2CH2CH2CH2-, 4H), 3.41-3.45 (t, -CH2CH2Br, 2H), 4.03-4.06 (t, -OCH2CH2-, 2H), 6.93-6.95 (d, Ar -H, 2H), 7.45-7.48 (m, Ar -H, 2H), 7.54-7.58 (m, Ar -H, 2H), 7.74- 7.75 (d, Ar -H, 1H), 7.76-7.82 (t, Ar -H, 2H). |
42.7% | With potassium carbonate In acetonitrile for 24h; Reflux; | |
42.7% | With potassium carbonate In acetonitrile for 24h; Reflux; | 4 Example 4 - 4-0-(6-bromohexyl)benzophenone 3a According to the general procedure for the halide alkylation of 4-hydroxybenzopheonone derived from Saettone et al., International Journal of Cosmetic Sciences, 1988, 10, 99-109, 1,6- dibromohexane (40.4 mmol, 6.21 mL), potassium carbonate (20.2 mmol, 2.79 g) and 4- hydroxybenzophenone (10.1 mmol, 2.00 g) were stirred in acetonitrile (20 mL) under reflux for 24 hours to give a crude product of 4-0-(6-bromohexyl)benzophenone which was recrystallized in toluene/hexanes to yield compound 3a (1.495 g, 42.7% yield). Cic>H2|Br02; white powder; NMR (CDCI3, 400 MHz) δ= 1.55 (m, -CH2-, 4H), 1.88 (m, -CH2-, 4H), 3.45 (m, -Br-CH2) 2H), 4.09 (m, -O-CH2, 2H), 6.95 (m, -Ar, 2H), 7.45 (m, -Ar, 2H), 7.55 (m, -Ar, 1H), 7.79 (m, -Ar, 4H) ppm; 13C NMR (CDCI3, 100 MHz) δ 195.52 (C5), 162.75 (C9), 138.22 (C4), 132.57 (C3), 129.98 (C7), 129.72 (CI), 128.18 (C2), 114.00 (C8), 67.99 (CIO), 33.78 (C15), 32.63 (C14), 28.94 (Cl l), 27.88 (C13), 25.25 (C12) ppm. HRMS-DART (m z): [M+] calcd. for C19H2iBr02, 361.0803; found, 361.0796. |
With sodium hydride In N,N-dimethyl-formamide Ambient temperature; | ||
With sodium hydroxide; tetrabutylammomium bromide In dichloromethane at 20℃; for 36h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; dimethyl sulfoxide; | EXAMPLE 11 2-(4-Benzoylphenoxy)-5-nitrobenzonitrile To a solution of 11.4 g (0.0575 moles) of 4-hydroxybenzophenone dissolved in 150 ml of DMSO was added 2.3 g (0.0575 moles) of NaOH. The mixture was heated to 60 C. and 10.0 g (0.0548 moles) of <strong>[16588-02-6]2-chloro-5-nitrobenzonitrile</strong> was added and the mixture heated at 75 C. for 3 hrs. The reaction mixture was cooled and poured into a solution of 100 ml of 2 N aqueous NaOH and 700 ml of water. The product was collected by filtration, washed well with water and dried to obtain 17.75 g of product (89.6% yield). Recrystallization from a mixture of ethanol and dimethylformamide and a second recrystallization from chloroform afforded purified 2-(4-benzoylphenoxy)-5-nitrobenzonitrile, mp 179.5-180.5 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.9% | With triethylamine; In dichloromethane; at 0 - 20℃; for 19h; | j00146j Sp,thesLc of 4-benzoylphen.vi inethacrylate: 4-benzoyiphenyi methacrylate was synthesized in an esterification reaction between 4-hvdroxybenzophenone and methacroyl chloride. 4-hydroxyhenzophenone, 3.5 g (0.0177 mol), was dissolved in 90 mL of dichioromethane. While stirring, 5 mL (0.0354 mol) of triethylamine was added. Under ice- bath cooling (0C to 4C), 1.73 niL (0.0177 mol) of methacroyl chloride was added drop wise to the solution. The mixture was allowed to stir in the ice-bath for 1 hr after which it was stirred at room temperature for the duration of 1 8 hrs, after which it was washed with water twice. The organic layer ‘vas dried with Na2SO4 and the solvent was removed under vacuum, The crude product was purified by column chromatography with dichioromethane as an eluent. 3.39 g, 719% yield.j00147j IH NMR (400 MHz, CDCI3), 8: 2.11 (s, 3H, a-methyl), 5.83 and 6.41 (d, 1H, CH2=), 7.27-7.91 (in, 9F1, phenyl) ppm. Figure 1 shows the NMR spectrum of the resulting benzophenone methacrylate. Schematic 1 below illustrates the synthesis of benzophenone methacrylate according to Example i |
In pyridine; | EXAMPLE 38 4-methacryloyloxybenzophenone Prepared from 6.0 g of 4-hydroxybenzophenone and 4.4 ml of methacryloyl chloride in 70 ml of pyridine. Recrystallized from ethyl acetate-ethanol-water; M.P.~69.5-70.5 C. Analysis Calcd. for C17 H14 O3: C, 76.68; H, 5.30. Found: C, 76.73; H, 5.35. | |
2.74 g | Example 3 - Comparative Synthesis of 4-acryloyloxy-benzophenone 1.3 g (16.25mmoii) of NaOH 50% water solution, were added to a solution of 3 g (15.21mmol) of 4-hydroxybenzophenone in 20 cc of methyl ethyl ketone. After 30 minutes under stirring, a solution of 1.59 g (15.21 mmol) of methacryloyl chloride in 5 ml_ of methyl ethyl ketone were added dropwise. After the addition the reaction mixture was stirred for 1 hour, filtered and the solvent was evaporated. The oil residue was purified by flash chromatography on silica gel (eluent CH2CI2) to obtain 2.74 g of a colourless liquid. LHNMR (CDC3) : δ (ppm) :2.10 (s,3H); 5.82 (s,lH); 6.40 (s,lH); 7.2-7.3 (m,2H); 7.45-7.55 (m,2H); 7.60-7.65 (m,lH); 7.75-7.85 (m,2H); 7.85-7.95 (m,2H) |
With triethylamine; In dichloromethane; water;Flow reactor; | General procedure: For EX-1, the following procedure was carried out using Microreactor B, described above, with the mixing device at ambient temperature. Syringe I contained 15 g BP, 22 g TEA, and 22 g water. Syringe II contained 3 g ACL and 20 g DCM. Each syringe was placed in a separate syringe pump and the pump speeds were controlled to deliver the blends at the flow rates indicated for EX-1 in Table 3 below. The two unused addition ports of the mixing device were sealed with plugs. The molar flow ratios of BP: ACL: TEA pumped to the mixing device were 1: 1.1 :2.9. Separation of aqueous phase and an organic phase was observed in the collection vessel. Analysis of the upper, aqueous phase by NMR indicated approximately 8 mol % of acrylic acid-TEA salt and approximately 92 mol % TEA -HQ salt. Analysis of the lower, organic phase by NMR indicated approximately 51 mol % 4- acryloxybenzophenone (ABP), approximately 0.01 mol % BP and approximately 42 mol % of the above mentioned TEA salts. Analysis of the organic layer by GC indicated 95% Composition of ABP and 2% of unreacted alcohol. After analysis, the organic layer was washed with water to remove salts and residual TEA. For EX-2 through EX-17, the same procedure was followed but with syringe contents and flow rates as indicated in Table 3. Blend compositions, flow rates, molar flow ratios of BP:ACL:TEA, and % Composition are provided in Table 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; tetra-(n-butyl)ammonium iodide; In N-methyl-acetamide; | EXAMPLE 127 4-[2-(4-Benzoylphenoxy)ethyl]-1H-imidazole 240 mg (60% in oil, 6 mmol) of sodium hydride are added to a solution of 2.34 g (12 mmol) of 4-hydroxybenzophenone in 10 ml of dimethylformamide. The mixture is stirred at room temperature for 1 hour under nitrogen. 200 mg (1.2 mmol) of <strong>[6429-10-3]4-(2-chloroethyl)-1H-imidazole hydrochloride</strong> and tetrabutylammonium iodide (catalytic amount) are then added. The mixture is heated at 100 C. for 2 days and the solvent is then evaporated under reduced pressure. Dilute hydrochloric acid is added to the oily residue and the excess hydroxybenzophenone is extracted with diethyl ether. The aqueous solution is basified with potassium carbonate and the product is extracted with diethyl ether. The title compound is converted to the dioxalate. Crystallization from an ethanol/diethyl ether (2/1) mixture gives a pure product, M.p.: 193-194 C. C18 H16 N2 O2.1.3C2 H2 O4 Elemental analysis: calculated: C 60.4 H 4.58 N 6.8 found: C 60.2 H 4.63 N 7.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With tetrabutylammomium bromide; potassium carbonate In water at 100℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.32 g | With tetrabutylammomium bromide; In acetone; at 30 - 40℃; for 4.16667h; | (1) In a 250 ml three-necked flask equipped with a magnetic stirrer, a thermometer, a dropping funnel, and a condenser, 70 ml of acetone and 8.65 g (0.0437 mol) of 4-hydroxybenzophenone were added.Then pretreated 36.33g (0.1453mol exchange capacity)The D201FC exchange resin was added to a three-necked flask and stirred for heating.0.1 g of tetrabutylammonium bromide was added to the system.The system was heated to 30-40 °C.At this temperature, 5 g (0.0291 mol) of diethylaminochloroethane hydrochloride was added to the system and the addition was completed within ten minutes.Stirring was continued with stirring, and the reaction was monitored by HPLC, and the reaction was completed after 4 hours.Filtration was carried out, and the filtrate was distilled under reduced pressure to give about 15 g of a yellow oil. (2) To the oil was added 30 ml of methanol to dissolve, then 3.6 g of concentrated hydrochloric acid was added, and finally 45 ml of diethyl ether was added, which was formed as a white solid, and the upper liquid was pale yellow.Filter and wash the filter cake with ether. The finally obtained white solid was dissolved in 20 ml of water, and then adjusted to pH = 8 to 11 with a 2N sodium hydroxide solution of about 30 ml. (3) Extracted three times with methyl tert-butyl ether, 50 ml each time, and the organic phase was combined, washed once with saturated brine, and dried over 15 g of anhydrous sodium sulfate.After suction filtration and rotary evaporation, 8.32 g of 4-[2-(N,N-diethylamino)ethoxy]benzophenone was obtained.The yield was 96.27percent based on diethylaminochloroethane hydrochloride and the purity was 99.08percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; | 2 [0112] The following two compounds A and B were made by reacting a phenolic functionality with ethyl bromoacetate, dissolved in dimethylformamide (DMF) with potassium carbonate. [0113] The procedure for preparing the ethyl ester derivative of 4- hydroxybenzophenone (compound A) was as follows: 12 grams (60.54 mmol) were suspended in 250 mL of DMF. 8 grams of potassium carbonate (1.1 equivalents) were added at room temperature. Next, 7.4 mL of ethyl bromoacetate (66.6 mmol, 1.1 equivalents) were added and allowed to react overnight. The work-up was performed by the addition of 200 mL of ethyl acetate and 500 mL of water. The aqueous phase was extracted after washing with 3x200 mL of ethyl acetate. The combined organic phases were then washed with 4x100 mL of water and 2x150 mL of saturated sodium chloride solution. After drying with magnesium sulfate and crystallization with chloroform, 17.0 grams (98% yield) of product were obtained. FIG. 6 shows the LC chromatogram for compound A. Compound A had a melting point of 84.4°C. |
94% | With potassium carbonate In acetone Inert atmosphere; Reflux; | Procedure for the Preparation of Esters 7-16 General procedure: The ethyl 2-bromo-2-methylpropanoate or ethylbromoacetate (1.72 mmol) was added to a solution of (4-[(E)-2-phenylvinyl]phenol) (2), (2E)-1-(4-hydroxyphenyl)-3-phenylprop-2-en-1-one (3), (2E)-3-(4-hydroxyphenyl)-1-phenylprop-2-en-1-one (4), N-(4-hydroxyphenyl)-N-phenylurea(5) or 4-hydroxyphenyl)(phenyl)methanone (6) (1.72mmol) and dry K2CO3 (6.19 mmol) dissolved in dry acetone(15 mL) under nitrogen atmosphere. After stirring for 18-20h at reflux, the reaction was filtered and the precipitate wasconcentrated under reduced pressure. The residue was solubilizedin chloroform (30 mL) and washed with NaOH 0.5 N(3 x 30 mL) and water (30 mL). The organic layer was driedover Na2SO4 and concentrated under reduced pressure. Thecrude residue was purified by column chromatography onsilica gel (eluent cyclohexane/ethyl acetate 9:1). |
90% | With potassium carbonate In acetone at 60℃; |
85% | With potassium carbonate In acetone for 6h; Heating; | |
80% | With potassium carbonate In acetone for 6h; Heating; | |
63% | With sodium In ethanol for 20h; Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With ammonium chloride In water at 100℃; for 24h; | |
98% | With trifluorormethanesulfonic acid; palladium diacetate; 2-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine In water at 60℃; for 5h; | General procedure for addition of arylboronic acids to nitrile General procedure: To a mixture of arylboronic acid (1.2 mmol), nitrile (1.0 mmol), Pd(OAc)2 (4 mol%)and L1 (4 mol%), H2O (1.2 mL) and triflic acid (0.4 mL) were added and stirred at 60 °Cunder air for desired time (TLC monitoring). Then the reaction mixture was neutralized withsaturated NaHCO3 solution and extracted with ether. The combined ether solution waswashed with brine, dried by Na2SO4 and concentrated. The residue was purified by flashcolumn chromatography on silica gel using petroleum ether/cetone or petroleum ether/DCMas eluent to give the desired product. |
91% | In nitromethane for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triphenylphosphine In chloroform | 1 Synthesis of Trifunctional Triazine Crosslinker EXAMPLE 1 Synthesis of Trifunctional Triazine Crosslinker 1.2 g (4 mmol) of triglycidyl isocyanurate (Aldrich Chemicals, Milwaukee, Wis.) and 2.4 g (12 mmol) of 4-hydroxybenzophenone (Aldrich Chemicals, Milwaukee, Wis.) were mixed in a 50-ml round bottom flask containing a magnetic stir bar. The flask was flushed with argon for 10 min and heated to 130° C. in an oil bath. Once the reaction mixture melted, 6 mg (0.02 mmol) of triphenylphosphine (Aldrich Chemicals, Milwaukee, Wis.) was added. The mixture was stirred for another 2 minutes under argon and cooled to room temperature. The reaction residue was dissolved in 30 ml chloroform, then washed with 4N NaOH (30 ml*3) and deionized water (30 ml*3). The organic layer was dried over magnesium sulfate and concentrated to dryness on the under reduced pressure. The product was purified by column chromatography (silica gel, 230-400 mesh, Whatman, Inc.) using ethyl acetate as eluent (Rf~4.5). The fractions containing the pure product were combined and concentrated under reduced pressure and a white powder was obtained after drying under vacuum (yield 70%). The crosslinker is soluble in most common solvents including chloroform, methylene chloride, acetone, ethyl acetate, isopropanol, etc. 1H NMR (CDCl3) confirmed the structure of the product. The peaks at d 7.78 ppm (m, 12H), 7.46 ppm (m, 9H), 6.98 ppm (m, 6H) were the typical signals from 4-subsituted benzophenone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 0 - 70℃;Inert atmosphere; | Into a 500 mL two-necked round-bottom flask were added 4-hydroxylbenzophenone (1.9 g,10 mmol), benzophenone (2.2 g, 12 mmol) and Zn powder (2.9 g, 44 mmol). The flask was evacuatedunder vacuum and flushed with dry N2 three times. Then 80 mL fresh dried THF was added. After all the solids were completely dissolved, the solution was cooled to 0 C and TiCl4 (2.4 mL, 22 mmol)was slowly injected into the flask. After refluxing at 70 C overnight, the mixture was cooled to roomtemperature and 80 mL dilute hydrochloric acid (1 molL1) was added to it, which was extracted withdichloromethane (3 80 mL). The collected organic layer was dried over anhydrous magnesium sulfate.After solvent evaporated, the crude product was purified by a silica gel column chromatography usingpetroleum ether (60-90 C)/ethyl acetate (40:1) as eluent. White crystal; yield 58% (2.4 g). 1H-NMR(400 MHz, CDCl3,delta): 7.16-7.09 (m, 8H), 7.07-7.01 (m, 9H), 6.91 (d, 1H), 6.58 (d, 1H), 4.78 (s, 1H). |
50% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 0℃; for 8.5h;Inert atmosphere; Reflux; | 4-(1,2,2-triphenylvinyl)phenol (TPP) was conveniently synthesized via a McMurry reaction in one step [43]. Zinc dust (2.18 g, 33.00 mmol), 4-hydroxy diphenyl ketone (1.65 g, 8.32 mmol), and benzophenone (1.50 g, 8.23 mmol) were added into a round-bottom flask in that order. The flask was then evacuated of air under vacuum and flushed with dry nitrogen several times. Anhydrous THF (80 mL) was then added into the flask, then the resultant mixture was cooled to 0 C and TiCl4 (1.88 mL, 16.50 mmol) was slowly added via syringe. The reaction proceeded at room temperature for half an hour, and then heated under refluxed for 8h K2CO3 solution (10% aq.) was employed to quench the reaction and the solution extracted with diethyl ether several times. The organic layer was combined and washed with brine twice. The mixture was dried with anhydrous sodium sulfate and then the solvent was removed. The resulting residue was subjected to column chromatography using dichloromethane/petroleum ether (v/v 4:1) to give the 4-(1,2,2-triphenylvinyl)phenol (1.40 g, 4.00 mmol, 50%, melting points: 225-226 C). 1H NMR (400 MHz, DMSO-d6) delta 9.36 (s, 1H), 7.10 (ddd, J=14.1Hz, 11.7Hz, 6.8Hz, 9H), 6.95 (dd, J=13.5Hz, 7.3Hz, 6H), 6.74 (d, J=7.6Hz, 2H), 6.50 (d, J=7.6Hz, 2H). |
47% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 0 - 70℃; for 25h;Inert atmosphere; | A 250 mL round bottom flask was charged with 4-hydroxybenzophenone (1.9 g, 10 mmol)Benzophenone (2.2 g, 12 mmol),Zn powder (2.9 g, 44 mmol).After evacuating nitrogen for three times,Add 80 mL of tetrahydrofuran.After cooling to 0 C,TiCl4 (4.2 g, 22 mmol) was slowly added,Then stir for 1 h.Then stirred at 70 C for 24 h,After cooling to room temperature,Add 80mL dilute hydrochloric acid (1mol / L),Adjusted to neutral,DCM extraction three times,The organic layer was collected,Dried over anhydrous magnesium sulfate,The solvent is dried to give the crude product,A volume ratio of 20: 1 petroleum ether and ethyl acetate mixture as eluent,SiO2 as the stationary phase,Column chromatography isolated white solid 0.8g,Yield 47%. |
47% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 0 - 70℃; for 25h;Inert atmosphere; | In a 250 ml round bottom flask is added 4 - hydroxy benzophenone (1.9g, 10mmol), benzophenone (2.2g, 12mmol), Zn powder (2.9g, 44mmol). After three rounds of pumping nitrogen exchange, add 80 ml tetrahydrofuran. Cooling to 0 C after, slowly adding TiCl4(4.2g, 22mmol), then stirring 1h. Then in the 70 C stirring 24h, after cooling to room temperature, add 80 ml dilute hydrochloric acid (1 mol/L), is adjusted to neutral, DCM extraction three times, collection of the organic layer, drying by anhydrous magnesium sulphate, turns on lathe does solvent to get the crude product, to the volume ratio of 20:1 mixture of petroleum ether and ethyl acetate as eluent, SiO2As stationary phase, column chromatography separation to obtain the white solid 0.8g, yield 47%. |
38% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 20℃; for 20h;Inert atmosphere; Reflux; | A 250 mL reaction vial was evacuated into a baking tube three times. Under argon protection, 150 mL of tetrahydrofuran and 2.76 g of activated zinc powder were added to the reaction vial.The reaction vial was then placed in an ice-water bath and stirred for half an hour; 0.24 mL of titanium tetrachloride was gradually added using a syringe within half an hour to obtain a dark brown reaction solution.After the reaction solution was returned to room temperature, the temperature was gradually raised and refluxed for 2 hours;After returning to room temperature again, 1.92 g of benzophenone and 2.10 g of 4-hydroxybenzophenone were added and refluxed for 20 h.The reaction was quenched with 100 mL of 10% aqueous potassium carbonate solution and the tetrahydrofuran was removed by rotary evaporation.The product was finally extracted with methylene chloride, dried and concentrated. Column chromatography yielded 4-(1,2,2-triphenylvinyl)phenol (yield 38%). |
A solution of 9.5146 g (48 mmol) of 4-hydroxybenzophenone, 7.288 g (40 mmol) of benzophenone and 11.44 g (0.176 mol) of zinc powder was added to a dry two-necked flask, evacuated and vented three times with nitrogen, Water tetrahydrofuran. The reaction system was cooled to 0 C, 9.6 ml (88 mmol) of titanium tetrachloride was slowly added, the reaction time was 1 hour, and then the reaction was carried out under reflux for 8 hours. After cooling to room temperature, 1 mol / l dilute hydrochloric acid was added to the two vials, and the mixture was extracted with methylene chloride. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography 1- (4-hydroxyphenyl) -1,2,2'-triphenyl ethylene as a white solid. | ||
12 mmol | With titanium tetrachloride; zinc; In tetrahydrofuran;Inert atmosphere; Reflux; | (1) under a nitrogen atmosphere, 0 C under the conditions of 44 mmol of TiCl4 was added dropwise to a solution of 88mmol of zinc powder in tetrahydrofuran suspension,And stirred at room temperature 0.5h; reflux 2.5h, cooled to 0 C, to prepare a mixed solution; (2) 24 mmol of benzophenone and 20 mmol of 4'-hydroxybenzophenone are dissolved in dry tetrahydrofuran,And added dropwise to the mixed solution obtained in step (1); reflux, TLC track the progress of the reaction;(3) until the reaction in step (2) was completed, the reaction was quenched with water, the aqueous layer was extracted three times with CH2Cl2; organic layer was taken and dried over anhydrous sodium sulfate, the column chromatography to give a white solid 12mmol; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With di-isopropyl azodicarboxylate; triphenylphosphine; In 1,4-dioxane; at 20 - 45℃; | 4-[2-(Adamantan-1-yl)ethoxy]benzophenone. In a round-bottom flask equipped with magnetic stirrer, room temperature water bath and dropping funnel 4-hydroxybenzophenone (1.98 g, 10 mmol), 1-adamantaneethanol (1.98 g, 11 mmol) and triphenylphosphine (3.15 g, 12 mmol) were dissolved in dry dioxane (50 mL). DIAD (2.46 ml, 12.5 mmol) was added dropwise within 20 min with stirring. The reaction mixture was heated to 40-45C until starting benzophenone is consumed according to TLC (CHCl3-MeOH 9:1), then cooled to room temperature; the precipitate formed was filtered off, washed successively with cold dioxane and MeOH and dried in vacuo. The solid was purified by column chromatography on silica gel (eluation with benzene). The appropriate fractions were combined and evaporated. The residue was triturated in petroleum ether to give the desired product (1.91 g, 53%), colorless crystals, mp 96C. Rf 0.17 (toluene), 0.57 (toluene-EtOAc, 9:1), 0.64 (toluene-EtOAc, 4:1). NMR (DMSO-d6): 7.74 (d, 2H, J = 8.7 Hz, ArH); 7.70-7.62 (m, 3H, ArH); 7.55 (m, 2H, ArH); 7.07 (d, 2H, J= 8.7 Hz, ArH); 4.14 (t, 2H, J= 7.2 Hz, OCH2); 1.93 (br. s, 3H, H-3,5,7 (adamantane)); 1.70-1.60 (m, 6H, H-4,6,10 (adamantane)); 1.58-1.50 (m, 8H, H-2,8,9 (adamantane), OCH2CH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate; In acetone; at 20℃; for 48h; | 4-[5-(tert-Butyloxycarbonyl)pentyloxy]benzophenone. To a solution of 4-hydroxybenzophenone (1.98 g, 10.0 mmol) in in dry acetone (80 mL) dry K 2CO3 (14 g, 0.1 mol) and <strong>[65868-63-5]ter<strong>[65868-63-5]t-butyl 6-bromohexanoate</strong></strong> (3.76 g, 15 mmol) were added, and the mixture was stirred for 48 h at ambient temperature, then filtered, and the solid was washed with acetone. The combined filtrate was evaporated, and the residue was dissolved in CHCl3 (100 mL), filtered, and evaporated. The residue was chromatographed on silica gel in 0?6% EtOAc in toluene to give desired product (3.10 g, 84%). NMR (DMSO-d6): 7.73 (d, 2H, J = 8.7 Hz, ArH); 7.70-7.62 (m, 3H, ArH); 7.54 (t, 2H, J = 7.6 Hz, ArH); 7.06 (d, 2H, J = 8.7 Hz, ArH); 4.07 (t, 2H, J = 6.4 Hz, OCH2); 2.21 (t, 2H, J = 7.4 Hz, COCH2); 1.74 (m, 2H), 1.56 (m, 2H), 1.42 (m, 2H) (OCH2CH2CH2CH2); 1.39 (s, 9H, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.0 g (53%) | With N2; potassium carbonate; In hexane; ethyl acetate; | A. [4-(3-Chloro-1-phenylpropoxy)phenyl]phenylmethanone To a 125 mL round-bottomed flask equipped with condenser and N2 inlet were added 3.78 g (16.15 mmol) <strong>[21763-00-8]3-chloro-1-bromo-1-phenylpropane</strong>, 3.52 g (17.76 mmol) 4-benzoylphenol, 4.46 g (32.3 mmol) potassium carbonate, and 27 mL methylisobutylketone. The reaction was refluxed 40 h, cooled, and poured into water. After extracting with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using ethyl acetate/hexane as eluant to afford 3.0 g (53%) of an oil. 'H-NMR (delta, CDCl3): 2.38 (AB, 2H), 3.73 (AB, 2H), 5.48 (dd, J=4,8, 1H), 6.92 (m, 2H), 7.2-7.8 (m, 12H). 13C-NMR (delta, CDCl3): 41.04, 41.13, 76.83, 115.28, 125.76, 126.53, 128.11, 128.41, 128.87, 129.61, 131.80, 133.54, 138.24, 139.96, 161.43, 195.34. |
3.0 g (53%) | With N2; potassium carbonate; In hexane; ethyl acetate; | A. [4-(3-Chloro-1-phenyl-propoxy)-phenyl]-phenyl-methanone: (Referring to Scheme 1) To a 125 mL round-bottomed flask equipped with condenser and N2 inlet were added 3.78 g (16.15 mmol) <strong>[21763-00-8]3-chloro-1-bromo-1-phenylpropane</strong>, 3.52 g (17.76 mmol) 4-benzoylphenol, 4.46 g (32.3 mmol) potassium carbonate, and 27 mL methylisobutylketone. The reaction was refluxed 40 hours (h), cooled, and poured into water. After extracting with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using ethyl acetate/hexane as eluant to afford 3.0 g (53%) of an oil. 1H-NMR (delta, CDCl3): 2.38 (AB, 2H), 3.73 (AB, 2H), 5.48 (dd, J=4,8, 1 H), 6.92 (m, 2H), 7.2-7.8 (m, 12H). 13C-NMR (delta, CDCl3): 41.04, 41.13, 76.83, 115.28, 125.76, 126.53, 128.11, 128.41, 128.87, 129.61, 131.80, 133.54, 138.24, 139.96, 161.43, 195.34. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | Stage #1: phosgene; 4-Hydroxybenzophenone With triethylamine In toluene at 20℃; for 3h; Stage #2: 1,4-diazabicyclo[3.2.2]nonane With polymer supported DMAP at 20 - 100℃; for 18h; | |
With dmap; ammonium hydroxide; triethylamine In PhCH3; chloroform | 27 1,4-Diaza-bicyclo[3.2.2]nonane-4-carboxylic acid 4-benzoyl-phenyl ester EXAMPLE 27 1,4-Diaza-bicyclo[3.2.2]nonane-4-carboxylic acid 4-benzoyl-phenyl ester Phosgene (1.22 mL, 2.3 mmol, 20% in PhCH3) was slowly added to a solution of 4-hydroxybenzophenone (440 mg, 2.2 mmol) and Et3N (280 μL, 4.0 mmol) in PhCH3 (10.0 mL) at RT. The mixture was stirred for a period of 3 h. Et3N (280 μL, 4.0 mmol), polymer supported DMAP (140 mg, 0.2 mmol) and 1,4-diaza-bicyclo[3.2.2]nonane (256 mg, 2.0 mmol) were added. The mixture was allowed to stir for 2 h. at RT and then was heated to 100° C. for 16 h. The reaction mixture was allowed to cool to RT, filtered and CHCl3 (40 mL) was added. The organics were washed with H2O (10 mL*2) and brine (10 mL) and then dried (Na2SO4), filtered and concentrated. The crude residue was purified by chromatography (Biotage 40M column) eluding with 5% MeOH in CHCl3 containing 20 drops of NH4OH per liter of eluent to afford 116 mg (15% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz, mixture of conformational isomers) δ7.83 (d, 2H, J=8.7 Hz), 7.78 (d, 2H, J=7.5 Hz), 7.57 (t, 1H, J=7.5 Hz), 7.47 (t, 2H, J=7.5 Hz), 7.26-7.22 (m, 2H), 4.48-4.47 (m, 1H, major), 4.41-4.40 (m, minor), 3.86 (t, J=5.8 Hz, minor), 3.78 (t, 2H, J=5.8 Hz), 3.20-3.02 (m, 6H), 2.14-2.08 (m, 2H), 1.83-1.73 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ195.9, 155.0, 154.9, 153.4, 152.6, 137.9, 134.7, 134.6, 132.6, 131.84, 131.81, 130.2, 128.5, 121.74, 121.72, 57.4, 57.1, 49.2, 49.1, 46.5, 46.4, 43.2, 42.9, 27.4, 26.6; MS (Cl) m/z 351.3 (M+H). The hydrochloride salt was prepared by dissolving the title compound in ethyl acetate and adding 3N HCl in ethyl acetate; m.p.=236.° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium iodide; In toluene; at 60℃; for 1.5h;Reflux; | 4-hydroxybenzophenone (262 g, 1.32 mol)NaI (6.5 g, 0.043 mol),Ethylene carbonate (125 g, 1.42 mol) andToluene (10 mL) were added to a 2000 mL three-necked flask,Raise the temperature until the system is clear.Continue to raise the temperature to the reaction system was refluxed for 1.5h,After the TLC test reaction is completed, the heating is stopped,Cooled to 60 C.To the reaction system was added water and ethyl acetate,extraction,The organic phase was dried over anhydrous sodium sulfate,Concentrated to give 304 g of a pale yellow solid,Yield 95%. |
94% | With sodium iodide; In toluene; at 99 - 176℃; for 0.5h;Product distribution / selectivity; | A mixture of ethylene carbonate (124.6 g; 1.07 eq.), sodium iodide (6.3 g; 0.03 eq.), 4-hydroxybenzophenone (262 g; 1 eq.) and toluene (8.1 g) was heated. At99C a clear solution was obtained. The reaction mixture was heated with reflux condenser to 176C over one hour, during which gas evolution occurred. After an additional ½ hour at 176C, the reaction mixture was cooled to 122C and toluene (350 g) and water (24 g) was added. The lower phase was cut and discarded. More water (14 g) was added and the lower phase was again cut and discarded. Water and toluene (95 g in total) was azeotropically removed, reaching a boiling point of 11 1 C. More toluene (1 14 g) was added and the product was isolated by filtration at 8C. In total, 302 g of 4-(2-hydroxyethoxy)benzophenone (94%) was obtained after drying as white crystals (99.8 % chromatographic purity). |
from 4-hydroxy-benzophenone and ethylene carbonate there is obtained 2-(p-benzoylphenoxy)-ethanol, m.p. 78-80 C.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.5 g (80%) | With potassium carbonate; In N-methyl-acetamide; | EXAMPLE 1 10 g of p-hydroxybenzophenone are dissolved in 100 ml of dimethylformamide. 8.3 g of <strong>[6329-26-6]2-chloroethylcarbamic acid ethyl ester</strong> and 13.8 g of potassium carbonate are added to the solution and the mixture is warmed to 100 C. and maintained there for 3 hours with stirring. The mixture is poured onto an ice/water bath. The resulting crystals are filtered and washed with water. The crystalline substance is dried at 40 C. in a vacuum drying oven. Recrystallization once from ether yields 12.5 g (80%) of 2-(p-benzoylphenoxy)ethylcarbamic acid ethyl ester, m.p.--84-86 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; In ethanol; water; | EXAMPLE 2 Sodium 2-hydroxy-3-(4-benzoylphenoxy)propane sulphonate A solution of sodium hydroxide (3.3g) in water (5 mls) was added to a solution of sodium 3-chloro-2-hydroxypropane sulphonate (14.73g) in water (30 mls) and the resultant solution added to a solution of 4-hydroxybenzophenone (9.9g) in ethanol (50 mls). After stirring under reflux for 18 hours, the pH of the pale yellow solution was brought to 4 via the addition of 4N. hydrochloric acid and after cooling in an ice bath for several hours the crude title compound was filtered and twice washed with ethanol (20 ml portions) and dried at 50C. giving a pale brown sandy solid (11.58g) of melting point equal to 320-323C. Recrystallisation with charcoaling from a mixture of ethanol (50 mls) and water (15 mls) followed by filtration, washing and drying gave sodium 2-hydroxy-3-(4-benzoylphenoxy) propane sulphonate (9.84g; yield = 55%) as a pale brown sandy solid of melting point equal to 316-318C. Analysis:- Calcd for C16H15NaO6S C 53.63; H 4.22; S 8.95; Na 6.42 Found: C 53.57; H 4.24; S 8.75; Na 6.69 An aqueous solution of this compound has an absorption maximum at 294 nm with an extinction coefficient (1%, 1cm) of 467. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In dichloromethane at 0 - 20℃; | General procedure for synthesis of aryl mesylates General procedure: To a solution of phenol substrate (1.0 eq, 10.0 mmol) and Et3N (1.5 eq, 15.0 mmol) in CH2Cl2 (0.5 g/mL) was added dropwise the solution of MsCl (1.2 eq, 12.0 mmol) in CH2Cl2 at 0 oC. The mixture was allowed to warm to RT and stirred for 4 h-12 h to detect for the reaction completion. The reaction solution was added to H2O (20 ml). The layers were separated and the aqueous layer was extracted with CH2Cl2 (10 mL× 2). The combined organic layers were washed with brine (20 mL), and dried over Na2SO4. After the solvent was evaporated, the product was purified by column chromatography over silica gel. |
With triethylamine In dichloromethane | ||
With triethylamine In dichloromethane |
With triethylamine In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: 4-Hydroxybenzophenone With sodium methylate In N,N-dimethyl acetamide for 0.5h; Stage #2: bromoacetic acid methyl ester In N,N-dimethyl acetamide at 40℃; for 1h; | 2 137 g (0.69 mol) 4-hydroxybenzophenone was dissolved in 650 mL dimethyl acetamide. 166 mL of a 5.4 molar solution of sodium methanolate in methanol was added. The reaction mixture was stirred for 30 minutes. 126.7 g (0.83 mol) bromoacetic acid methyl ester was added drop wise at 40°C. The reaction was allowed to continue for 1 hour at 40°C. The reaction mixture was allowed to cool down to room temperature and poured into 1 L ice/water, containing 20 mL acetic acid. The intermediate benzophenone ester precipitated from the medium, was isolated by filtration, washed with water and dried. 181 g (97 %) of the intermediate ester was isolated (m.p. 100-102°C). |
56% | With potassium carbonate In N,N-dimethyl-formamide at 65℃; | 1.6. General method for O-alkylation yielding compounds 5a-q General procedure: To a solution of 5a-q (1.0 eq.) in DMF (0.2 M) was added K2CO3 (2.0 equiv.) and 2-methylbromoacetate (2.0 equiv.). The mixture was stirred at 65 °C for 24 h, after which it was cooled to room temperature and the mixture was separated between ethyl acetate and water. The organic layer was washed with water (3 times), brine, dried over MgSO4, and concentrated. This gave the desired O-alkylated products (5a-q) as one spot on TLC (1 EtOAc/4 Pet. ether) and used as crude material in the next reaction or purified as specified in the individual examples. 1.6.1. Methyl 2-(4-benzoylphenoxy)acetate (5a).[20] Recrystallized from EtOAc/Pet. ether. White solids 1.52 g, yield = 56%. 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.48 (t, J = 8.0 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 4.73 (s, 2H), 3.83 (s, 3H) ppm. |
50% | With sodium methylate In methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With cesiumhydroxide monohydrate; t-BuBrettPhos; C44H62NO5PPdS; water In 1,4-dioxane at 20℃; for 18h; Inert atmosphere; | |
95% | With cesiumhydroxide monohydrate; bis[(trimethylsilyl)methyl](1,5-cyclooctadiene)palladium(II); 2-((di-adamantan-1-yl)phosphaneyl)-1-(2,6-diisopropylphenyl)-1H-imidazole In tetrahydrofuran at 24℃; for 20h; Inert atmosphere; | |
91% | Stage #1: (4-bromophenyl)(phenyl)methanone With potassium hydroxide; tris-(dibenzylideneacetone)dipalladium(0); 2-((di-adamantan-1-yl)phosphaneyl)-1-(2,6-diisopropylphenyl)-1H-imidazole In 1,4-dioxane; water at 100℃; for 20h; Inert atmosphere; Stage #2: With hydrogenchloride In 1,4-dioxane; water at 20℃; Inert atmosphere; |
90% | With tris(6,6'-diamino-2,2'-bipyridine); 4,4-diphenyl-1,3,5,7,8-pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene; Br2Ni*3H2O; water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Glovebox; Irradiation; Inert atmosphere; | |
85% | With nickel(II) sulfate hexahydrate; 4,4'-Dimethoxy-2,2'-bipyridin; water; 8,9-bis((R)-2-acetoxypropyl)-7,10-dimethoxyperyleno[1,12-def][1,3]dioxepine-5,6,11,12-tetrayl tetraacetate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Schlenk technique; Irradiation; Inert atmosphere; | 2.6. Typical experimental procedure for the hydroxylation of arylhalides with water catalyzed by HARCP General procedure: In a 10 mL schlenk tube with magnetic stirring bar, aryl halide 1(0.2 mmol), HARCP (1.2 mol%), NiSO46H2O (10 mol%), 4,40-dimethoxy-2,20-bipyridine (10 mol%), DIPEA (1.5 equiv), H2O (40 equiv)were dissolved in the mix solvent (CH3CN: DMF = 1: 1, 2 mL). Thereaction mixtures were then irradiated with 23 W CFL (at approximately2 cm away from the light source) under nitrogen atmosphere.When the reaction finished, the reaction mixtures werequenched with water (5 mL) and extracted with ethyl acetate (3x10 mL). The organic phase was washed with brine (3x 30 mL), driedover Na2SO4 and then concentrated in vacuum. The resulting residuewas purified by silica gel column chromatography to afford thedesired product 5. |
82% | With bis(η3-allyl-μ-chloropalladium(II)); p-methylbenzaldehyde oxime; caesium carbonate; tert-butyl XPhos In tetrahydrofuran at 75℃; for 3h; Inert atmosphere; | |
81% | With 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole; tris-(dibenzylideneacetone)dipalladium(0); cesiumhydroxide monohydrate In tetrahydrofuran at 65℃; Inert atmosphere; Glovebox; Sealed tube; | |
66 %Spectr. | With 1-methylpyrrol-2-carboxaldoxime; potassium <i>tert</i>-butylate In dimethyl sulfoxide at 30℃; for 16h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 4-Hydroxybenzophenone With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 20h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | 2 Example 2: (4-Benzyloxy-phenyl)-phenyl-methanone (I); [00194] The standard procedure for the benzylation of phenols is exemplified by the synthesis of (4-Benzyloxy-phenyl)-phenyl-methanone (1).[00195] NaH (60% in mineral oil, 1.2 g, 30 mmol) was added to an ice-cooled solution of (4-hydroxy-phenyl)-phenyl-methanone (5 g, 25.2 mmol) in DMF (25 mL). The resulting mixture was stirred for 20 minutes at room temperature (r.t). Benzyl bromide (6.1 mL, 50 mmol) was added at 0 0C. The reaction temperature was raised to r.t. after Ih and thereafter stirred for additional 2h. Water (20 mL) was added and the aqueous phase was extracted with dichloromethane (2 x 30 mL). The combined organic phase was concentrated and purified by flash chromatography (eluent: 100% dichloromethane). Yield: 7.0 g, 96% of 1. 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 7.2 Hz, 2H), 7.58-7.52 (m, IH), 7.50-7.32 (m, 7H), 7.03 (d, J = 8.4 Hz, 2H), 5.17 (s, 2H). |
96% | Stage #1: 4-Hydroxybenzophenone With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.333333h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | 23 NaH (60% in mineral oil, 1.2 g, 30 mmol) was added to an ice-cooled solution of (4-hydroxy-phenyl)-phenyl-methanone (5 g, 25.2 mmol) in DMF (25 mL). Stirred for 20 minutes at room temperature. Benzyl bromide (6.1 ml, 50 mmol) was added at 00C. The reaction temperature was raised to room temperature after Ih. Stirred 2 h. Water (20 mL) was added and aqueous phase was extracted dichloromethane (2 x 30 mL). The combined organic phase was concentrated and purified by flash chromatography (eluent: dichloromethane). 1H nmr revealed the product was pure. Yield: 7.0 g, 96%[00243] 1H NMR (400 MHz, CDCl3): 7.83 (d, 2H, J = 8.4 Hz), 7.77 (d, 2H, J = 7.2 Hz), 7.58-7.52 (m, IH), 7.50-7.32 (m, 6H), 7.03 (d, J = 8.4 Hz), 5.17 (s, 2H). |
80% | With tetrabutylammomium bromide; potassium hydroxide at 50℃; for 0.666667h; Inert atmosphere; | IV Comparative Example IV 4-Hydroxybenzophenone (5.9 g, 30 mmol), potassium hydroxide (2.49 g, 44 mmol) under a nitrogen atmosphere.TBAB (1.482 g, 4.6 mmol), benzyl bromide (2.4 mL, 37.2 mmol) was added to a 250 mL round bottom flask.The reaction was carried out at 50 ° C for 40 minutes. The reaction was completely cooled to room temperature, and an appropriate amount of dilute hydrochloric acid solution (2 mol/L) was added.Until no bubbles are formed, extract and concentrate the organic phase with chloroform.The crude product is obtained and purified by chromatography to obtain a pure product with a yield of 80%.The structure was characterized by 1H-NMR and 13C-NMR to confirm that the product was a compound of Comparative Example IV. |
With potassium carbonate; potassium iodide In acetone for 3h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | I a) Ethylene glycol p-benzophenone ether; In a laboratory autoclave having a capacity of 2 L there were placed 520 g of diethylene glycol diethyl ether, 286 g of p-hydroxybenzophenone (>98 wt %), and 0.8 g of powdered potassium hydroxide. A pressure test was then carried out for 30 minutes using dry nitrogen. Following pressure let-down to atmospheric pressure and heating of the reaction mixture under a blanket of nitrogen to 120 C., 95.4 g of ethylene oxide were continuously forced in to give a maximum internal pressure of 4 bar over a period of 1 h. On completion of gassing with ethylene oxide, the reaction mixture was allowed to react, until the pressure remained constant for at least 30 minutes. The reaction mixture was discharged from the autoclave in the hot state, neutralized with 5 wt % strength aqueous hydrochloric acid, and poured into 2 L of ice water, and the reaction product was caused to crystallize by constant agitation. The resulting solid matter was filtered off in vacuo, washed with ice water and dried in vacuo (40 C., 10 mbar absolute). The resulting filtrate was concentrated in a rotary film evaporator to 20% of its volume, the precipitated product filtered off in vacuo, washed with ice water and likewise dried in vacuo. The total yield was 82% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; for 24.0h;Reflux; | Synthesis of BP-4; [0146] Synthesis of Acrylic acid 4-[3-(4-benzoyl-phenoxy)-2-hydroxy- propoxy]butyl ester: A reaction mixture containing 4-hydroxybenzophenone (14.9 g, 75 mmol), acetonitrile (40 mL), potassium carbonate (7.8 g, 56,3 mmol) and 4- hydroxybutylacrylate glycidylether (7,5 g, 37,5 mmol) was heated to reflux. The mixture was allowed to stir at reflux temperature for 24 hours. The mixture was cooled to room temperature and filtered to remove the undissolved potassium carbonate. The filtrate was evaporated under reduced pressure, The residua. oil was diluted with ethyl acetate (250 ml) and extracted with a mixture of an aqueous solution of sodium hydroxide (1 N) and distilled water (4/1). The organic layer was separated, dried over MgSO4, filtered and evaporated to provide 15.1 g of a yellow oil. The product was purified on a SVP D40 Merck Np Column using dichloromethane / n-hexane (50/50) as eluent, to afford 5.5 g of a yellow oil. | |
With sodium hydroxide; potassium carbonate; In hexane; dichloromethane; water; acetonitrile; | Synthesis of BP-7 Synthesis of acrylic acid 4-[3-(4-benzoyl-phenoxy)-2-hydroxy-propoxy]butyl ester: A reaction mixture containing 4-hydroxybenzophenone (14.9 g, 75 mmol), acetonitrile (40 mL), potassium carbonate (7.8 g, 56.25 mmol) and 4-hydroxybutylacrylate glycidylether (7.5 g, 37.5 mmol) was heated to reflux. The mixture was allowed to stir at reflux temperature for 24 hours. The mixture was cooled to room temperature and filtered to remove the undissolved potassium carbonate. The filtrate was evaporated under reduced pressure. The residual oil was diluted with ethyl acetate (250 ml) and extracted with a mixture of an aqueous solution of sodium hydroxide (1N) and distilled water (4/1). The organic layer was separated, dried over MgSO4, filtered and evaporated to provide 15.1 g of a yellow oil. The product was purified on a SVP D40 Merck Np Column using dichloromethane/n-hexane (50/50) as eluent, to afford 5.5 g of a yellow oil. | |
5.5 g | With potassium carbonate; In acetonitrile; for 24.0h;Reflux; | Synthesis of acrylic acid 4-[3-(4-benzoyl-phenoxy)-2-hydroxy-propoxy]butyl ester A reaction mixture containing 4-hydroxybenzophenone (14.9 g, 75 mmol), acetonitrile (40 mL), potassium carbonate (7.8 g, 56.25 mmol) and 4-hydroxybutylacrylate glycidylether (7.5 g, 37.5 mmol) was heated to reflux. The mixture was allowed to stir at reflux temperature for 24 hours. The mixture was cooled to room temperature and filtered to remove the undissolved potassium carbonate. The filtrate was evaporated under reduced pressure. The residual oil was diluted with ethyl acetate (250 ml) and extracted with a mixture of an aqueous solution of sodium hydroxide (1N) and distilled water (4/1). The organic layer was separated, dried over MgSO4, filtered and evaporated to provide 15.1 g of a yellow oil. The product was purified on a SVP D40 Merck Np Column using dichloromethane/n-hexane (50/50) as eluent, to afford 5.5 g of a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | at 130℃; for 0.0333333h; Inert atmosphere; | 1 1.2 g (4 mmol) of triglycidyl isocyanurate (Aldrich Chemicals,Milwaukee, WI) and 2.4 g (12 mmol) of 4-hydroxybenzophenone (Aldrich Chemicals, Milwaukee, WI) were mixed in a 50-ml round bottom flask containing a magnetic stir bar. The flask was flushed with argon for 10 min and heated to 130 0C in an oil bath. Once the reaction mixture melted, 6 mg (0.02 mmol) of triphenylphosphine (Aldrich Chemicals, Milwaukee, WI) was added. The mixture was stirred for another 2 minutes under argon and cooled to room temperature. The reaction residue was dissolved in 30 ml chloroform, then washed with 4N NaOH (30 ml x 3) and deionized water (30 ml x 3). The organic layer was dried over magnesium sulfate and concentrated to dryness on the under reduced pressure. The product was purified by column chromatography (silica gel, 230- 400 mesh, Whatman, Inc.) using ethyl acetate as eluent (Rf- 4.5). The fractions containing the pure product were combined and concentrated under reduced pressure and a white powder was obtained after drying under vacuum (yield 70 %).[0270] The crosslinker is soluble in most common solvents including chloroform, methylene chloride, acetone, ethyl acetate, isopropanol, etc. 1H NMR (CDCl3) confirmed the structure of the product. The peaks at d 7.78 ppm (m, 12H), 7.46 ppm (m, 9H), 6.98 ppm (m, 6H) were the typical signals from 4- subsituted benzophenone. The peak at d 4.35 ppm (m, 6H) was assigned to the protons of methylene connected to phenoxy group. The peak at d 4.13 ppm (m, 9H) was a combination of 6 protons of 3 methylene groups connected to nitrogen atom and 3 protons from 3 methine groups. The peak at d 3.00 ppm (s, 3H) corresponded to hydroxyl groups. |
70% | Stage #1: teroxirone; 4-Hydroxybenzophenone With triphenylphosphine at 130℃; Inert atmosphere; Stage #2: With triphenylphosphine for 0.0333333h; Inert atmosphere; | 1 EXAMPLE 1 Synthesis of Trifunctional Triazine Crosslinker 1.2 g (4 mmol) of triglycidyl isocyanurate (Aldrich Chemicals, Milwaukee, Wis.) and 2.4 g (12 mmol) of 4-hydroxybenzophenone (Aldrich Chemicals, Milwaukee, Wis.) were mixed in a 50-ml round bottom flask containing a magnetic stir bar. The flask was flushed with argon for 10 min and heated to 130° C. in an oil bath. Once the reaction mixture melted, 6 mg (0.02 mmol) of triphenylphosphine (Aldrich Chemicals, Milwaukee, Wis.) was added. The mixture was stirred for another 2 minutes under argon and cooled to room temperature. The reaction residue was dissolved in 30 ml chloroform, then washed with 4N NaOH (30 ml*3) and deionized water (30 ml*3). The organic layer was dried over magnesium sulfate and concentrated to dryness on the under reduced pressure. The product was purified by column chromatography (silica gel, 230-400 mesh, Whatman, Inc.) using ethyl acetate as eluent (Rf~4.5). The fractions containing the pure product were combined and concentrated under reduced pressure and a white powder was obtained after drying under vacuum (yield 70%). The crosslinker is soluble in most common solvents including chloroform, methylene chloride, acetone, ethyl acetate, isopropanol, etc. 1H NMR (CDCl3) confirmed the structure of the product. The peaks at d 7.78 ppm (m, 12H), 7.46 ppm (m, 9H), 6.98 ppm (m, 6H) were the typical signals from 4-subsituted benzophenone. The peak at d 4.35 ppm (m, 6H) was assigned to the protons of methylene connected to phenoxy group. The peak at d 4.13 ppm (m, 9H) was a combination of 6 protons of 3 methylene groups connected to nitrogen atom and 3 protons from 3 methine groups. The peak at d 3.00 ppm (s, 3H) corresponded to hydroxyl groups. |
70% | With triphenylphosphine at 130℃; for 0.0333333h; Inert atmosphere; | 1 Synthesis of trifunctional triazine crosslinker. A triazine crosslinker was synthesized as follows. 1.2 g (4 mmol) of triglycidyl isocyanurate (Aldrich Chemicals, Milwaukee, WI) and 2.4 g (12 mmol) of 4- hydroxybenzophenone (Aldrich Chemicals, Milwaukee, WI) were mixed in a 50-ml round bottom flask containing a magnetic stir bar. The flask was flushed with argon for 10 min and heated to 130 °C in an oil bath. Once the reaction mixture melted, 6 mg (0.02 mmol) of triphenylphosphine (Aldrich Chemicals, Milwaukee, WI) was added. The mixture was stirred for another 2 minutes under argon and cooled to room temperature. The reaction residue was dissolved in 30 ml chloroform, then washed with 4N NaOH (30 ml x 3) and deionized water (30 ml x 3). The organic layer was dried over magnesium sulfate and concentrated to dryness under reduced pressure. The product was purified by column chromatography (silica gel, 230-400 mesh, Whatman, Inc.) using ethyl acetate as eluent (Rf ~ 4.5). The fractions containing the pure product were combined and concentrated under reduced pressure and a white powder was obtained after drying under vacuum (yield 70 %). NMR (CDCI3) confirmed the structure of the product. The peaks at d 7.78 ppm (m, 12H), 7.46 ppm (m, 9H), 6.98 ppm (m, 6H) were the typical signals from 4-subsituted benzophenone. The peak at d 4.35 ppm (m, 6H) was assigned to the protons of methylene connected to phenoxy group. The peak at d 4.13 ppm (m, 9H) was a combination of 6 protons of 3 methylene groups connected to nitrogen atom and 3 protons from 3 methine groups. The peak at d 3.00 ppm (s, 3H) corresponded to hydroxyl groups. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.4% | With 2,4-dimethyl-6-tert-butylphenol; sulfuric acid; 4-methoxy-phenol; at 90℃; for 6h;Air introduction; | Example 1; Apparatus: 4 l four-neck round-bottomed flask with mechanical stirrer, reflux condenser, Pt100 temperature sensor, air introduction tube, Anschutz attachment, dropping funnel, electrically heated oil bathBatch:3.5 mol of 4-hydroxybenzophenone, 99.7%: 695.9 g3.85 mol of methacrylic anhydride (stabilized with 2000 ppm of 2,4-dimethyl-6-tert-butylphenol): 618.4 g0.020 mol of concentred sulphuric acid: 1.99 g1864 mg of hydroquinone monomethyl ether932 mg of 2,4-dimethyl-6-tert-butylphenolNeutralization of the catalyst acid with 1.8 g of sodium hydroxide in solution in 10 g of waterEsterification of the excess methacrylic anhydride with 22.4 g of methanol Theoretical yield: 930.0 gProcedure:The batch was weighed out completely and then heated to 90 C. with stirring and introduction of air. Reaction time at 90 C.: 6 h. It was then cooled to about 60 C. and the sodium hydroxide in solution in water, for neutralizing the sulphuric acid catalyst, and also the methanol, for esterifying the unreacted methacrylic anhydride, were added. This was followed by stirring at 60 C. for 1 h, after which the batch was poured as thin jet, with stirring (metallic paddle stirrer, stirring motor), into 3 l of water. The mixture was stirred for 0.5 h and the precipitate was then isolated by suction on a glass filter frit, washed with twice 2 l of water, and subsequently subjected to preliminary drying with air on the suction filter. The solid was subsequently dried in air.Yield: 924.6 g (99.4% of theory)Analyses: water content: 0.08%hydroquinone monomethyl ether: 6 ppm2,4-dimethyl-6-tert-butylphenol: 174 ppmGas chromatography:0.047% methyl methacrylate0.013% methacrylic acid0.637% 4-hydroxybenzophenone97.56% 4-(methacryloyloxy)benzophenonePt-Co colour number as 20% strength solution in acetone: 150 |
99.7% | With sulfuric acid; In methanol; at 90℃; for 2h;Large scale; | Apparatus: 2 I four-necked round-bottom flask with mechanical stirrer, reflux condenser, Pt100 temperature sensor, air inlet tube and electrically heated oil bath. (0138) Mixture: (0139) 1.51 mol of 4-hydroxybenzophenone, 99.7%: 300 g (0140) 1.70 mol of MAAH (purity 98.59% (GC), methacrylic acetic anhydride 0.40%, (0141) acetic anhydride not detected; (0142) stabilized with 2070 ppm of 2,4-dimethyl-6-tert-butylphenol): 262.8 g 1.80 mol of MMA: 180 g (0143) 0.0087 mol of concentrated sulfuric acid: 0.846 g (0144) Total stabilizer content at start of reaction: 1813 ppm based on 4-hydroxybenzophenone. Neutralization of the catalyst acid with 1.8 g of aqueous sodium hydroxide solution dissolved in 10 g of water (0145) Esterification of the excess methacrylic anhydride with 22.4 g of methanol Theoretical yield: 1354 g (0146) Procedure: (0147) The mixture was weighed out in full and then heated to 90C with stirring and introduction of air. The reaction time at 90C is 2 h. Cooling was then carried out, down to approximately 60C, and the sodium hydroxide dissolved in water for neutralization of the catalyst sulfuric acid, and also the methanol for esterification of the unreacted methacrylic anhydride, were added. Stirring was subsequently carried out for 1 h at 60C, and then 600 g of methyl methacrylate were added to the mixture with stirring. The resulting solution was cooled to room temperature with stirring, and filtered. The solution of 4-(methacryloyloxy)benzophenone in methyl methacrylate has the following composition, determined by gas chromatography (figures in wt%): (0148) 57.9% methyl methacrylate (0149) 10.0% methacrylic acid (0150) 0.28% 4-hydroxybenzophenone (0151) 0.32% 4-(acetoxy)benzophenone (0152) 29.8% 4-(methacryloyloxy)benzophenone (0153) The water content is 0.08%, the stabilizer content is 53 ppm of 2,4-dimethyl-6-tert-butylphenol. The Pt-Co colour index is 152 APHA. (0154) Direct comparison with example 1 shows that the starting concentration of methacrylic acetic anhydride in the methacrylic anhydride is critical for the amount of 4-(acetoxy)benzophenone found in the product. (0155) Yield: 1350 g (99.7% of theory) |
With tempol; 2,4-dimethyl-6-tert-butylphenol; 4-methoxy-phenol; magnesium bromide; at 90℃; for 6h; | 3.35 g (0.017 mol) of 4-hydroxybenzophenone and 3.65 g (0.024 mol) of methacrylic anhydride, stabilized with 2000 ppm of 2.4-dimethyl-6-tert-butylphenol and 1000 ppm of hydroquinone monomethyl ether and 10 ppm of 4-hydroxy-2.2.6.6-tetramethylpiperidinooxyl (ppm based on the total mass of anhydride and alcohol) were combined. The obtained mixture was gently heated in the absence of any catalyst and a clear stock solution was obtained. General Procedure for Example 128-137:7.0 g samples of the stock solution were placed in a 15 ml_ pressure tube with a Teflon plug and a magnetic agitator. To this solution, 0.1 mol% (unless indicated otherwise), based on the tert- butanol, of the first catalyst were added and the pressure tube was tightly closed. Subsequently, the pressure tubes were placed for 6 h in an oil bath at 90 C with an integrated magnetic stirrer and stirred.A sample without any catalyst (Reference Example 128) in the oil bath at 90 C served as a reference sample. After 6 hours, the conversion and the product yield were determined by gas chromatography (area-%).The results of Examples 128-137 are summarised in Table 8 below: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 2; Apparatus: 4 l four-neck round-bottomed flask with mechanical stirrer, reflux condenser, Pt100 temperature sensor, air introduction tube, Anschütz attachment, dropping funnel, electrically heated oil bathBatch:1.5 mol of 4-hydroxybenzophenone: 303 g1.65 mol of methacrylic anhydride (stabilized with 2000 ppm of 2,4-dimethyl-6-tert-butylphenol): 262 g0.0087 mol of concentred sulphuric acid: 0.84 g798 mg of hydroquinone monomethyl ether399 mg of 2,4-dimethyl-6-tert-butylphenolProcedure:The batch was weighed out completely and then heated to 90 C. with stirring and introduction of air. Reaction time at 90 C.: 6 h. It was then cooled to about 60 C. and the sodium hydroxide in solution in water, for neutralizing the sulphuric acid catalyst, and also the methanol, for esterifying the unreacted methacrylic anhydride, were added. The batch was subsequently stirred at 60 C. for 1 h and then admixed with 1566 g of methyl methacrylate, with stirring. The resulting solution was cooled to room temperature with stirring, and filtered. The solution of the 4-(methacryloyloxy)benzophenone in methyl methacrylate has the following composition as determined by gas chromatography:56.016% methyl methacrylate6.954% methacrylic acid2.399% 4-hydroxybenzophenone32.717% 4-(methacryloyloxy)benzophenone.The water content is 0.27%; the stabilizer content is 113 ppm of 2,4-dimethyl-6-tert-butylphenol and 4 ppm of hydroquinone monomethyl ether. The Pt-Co colour number is 169. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 24h; | 4-hydroxy benzophenone (9.9 g, 50 mmol), 2-bro-moethanol (7.5 g, 60 mmol) and potassium carbonate (10 g, 75 mmol) were added to N,N-dimethylformamide (DMF, 150 mE), and stirred at 90 C. for one day. A solvent was distilled off, and dichioromethane was added. The mixture extracted with water and saturated saline solution, and dried. A solvent was distilled off to obtain a pale yellow powder (crude yield 12 g). This compound was used in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | General procedure: A solution of phenol (5 mmol) was added to a solution of sodium (114 mg, 5 mmol) in absolute EtOH (5 mL) at room temperature. After stirring for 30 min, a solution of suitable ethyl or isobutyl ester (5-bromovalerate, 5-bromo-2,2-dimethylpentanoic acid ethyl ester or <strong>[109232-37-3]5-chloro-2,2-dimethylpentanoic acid isobutyl ester</strong>) (5 mmol) in absolute EtOH (5 mL) was added and the solution was stirred at reflux for 10-15 h. The solvent was removed under reduced pressure and the residue was dissolved into CH2Cl2 or ethyl acetate (25 mL) and washed with NaOH 2 N (3 × 25 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to yield the crude product that was purified by column chromatography to give the ester 9-14, 16 or 25-31. Ester 15 was obtained with the same procedure, but under milder conditions: K2CO3 (1.1 g, 8.38 mmol) was added to a solution of N-(4-hydroxyphenyl)-N'-phenylurea (531 mg, 2.33 mmol) in acetone (10 mL) at room temperature. After stirring for 30 min, a solution of ethyl 5-bromovalerate (488 mg, 2.33 mmol, 0.37 mL) in acetone (10 mL) was added. After 30 h the solvent was removed under reduced pressure and the residue was treated as above to give the compound 15. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: 4-Hydroxybenzophenone With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 0.5h; Inert atmosphere; Stage #2: 1-bromo-6-hexanol In N,N-dimethyl-formamide at 100℃; for 4h; Inert atmosphere; | |
91% | With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 4.5h; | 4-(6-Hydroxyhexyloxy)benzophenone (3q) A solution of 4- hydroxybenzophenone s3 (200 mg, 1.01 mmol) and 2.0 g of K2CO3 (101.0 mg, 0.731 mmol) in DMF (3 mL) was stirred at 100 °C for 30 min. A solution of 6-bromo-hexanol si (200.0 mg, 1.10 mmol) in 2 mL of DMF was then added dropwise. After addition, the reaction mixture was stirred at 100 °C for 4 h. Then it was cooled, poured into water, and extracted with CH2C12. The extract was dried over Na2S04, concentrated to yield the crude product, which was purified by column chromatography (10:1→ 2:1 Hexanes-Ethyl Acetate) to afford s4 (298.7 mg, 91%) as a white amorphous solid: 1H NMR (400 MHz, CDC13, δΗ) 7.75 - 7.69 (m, 2H), 7.68 - 7.63 (m, 2H), 7.46 (t, J= 8.3 Hz, 1H), 7.37 (t, J- 7.5 Hz, 2H), 6.86 (d, J= 5.8 Hz, 2H), 3.93 (t, J= 6.5 Hz, 2H), 3.64 - 3.47 (m, 2H), 3.04 (s, 1H), 1.82 - 1.64 (m, 2H), 1.62 - 1.22 (m, 6H); 13C NMR (100 MHz, CDC13, δΗ) 195.84, 163.06, 161.45, 138.38, 132.75, 132.10, 129.86, 128.36, 114.21, 68.32, 62.60, 32.76, 29.24, 26.01, 25.75. ESI-MS: 299.2 (M+H4), 321.2 (M+Na+). |
Stage #1: 4-Hydroxybenzophenone With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 0.5h; Stage #2: 1-bromo-6-hexanol In N,N-dimethyl-formamide at 100℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; water;Flow reactor; | General procedure: For EX-1, the following procedure was carried out using Microreactor B, described above, with the mixing device at ambient temperature. Syringe I contained 15 g BP, 22 g TEA, and 22 g water. Syringe II contained 3 g ACL and 20 g DCM. Each syringe was placed in a separate syringe pump and the pump speeds were controlled to deliver the blends at the flow rates indicated for EX-1 in Table 3 below. The two unused addition ports of the mixing device were sealed with plugs. The molar flow ratios of BP: ACL: TEA pumped to the mixing device were 1: 1.1 :2.9. Separation of aqueous phase and an organic phase was observed in the collection vessel. Analysis of the upper, aqueous phase by NMR indicated approximately 8 mol percent of acrylic acid-TEA salt and approximately 92 mol percent TEA -HQ salt. Analysis of the lower, organic phase by NMR indicated approximately 51 mol percent 4- acryloxybenzophenone (ABP), approximately 0.01 mol percent BP and approximately 42 mol percent of the above mentioned TEA salts. Analysis of the organic layer by GC indicated 95percent Composition of ABP and 2percent of unreacted alcohol. After analysis, the organic layer was washed with water to remove salts and residual TEA. For EX-2 through EX-17, the same procedure was followed but with syringe contents and flow rates as indicated in Table 3. Blend compositions, flow rates, molar flow ratios of BP:ACL:TEA, and percent Composition are provided in Table 3. | |
With triethylamine; sodium hydroxide; In water; ethyl acetate; | For EX-1, the following procedure was carried out using the microreactor described above, with the mixing device at ambient temperature. Container I contained 100 g BP, 50 g TEA, 20 G NaOH, and 147 g water. Container II contained 40 g ACl and 80 g EtOAc. Each container was connected to a pump and the pump speeds were controlled to deliver the mixtures in the containers at the following rates: Container I; 14 mL/min, or 0.022 mol/min of BP; Container II: 7 mL/min, or 0.028 mol/min of ACl. The two unused addition ports of the mixing device were sealed with plugs. The molar flow ratios of BP:NaOH:TEA:ACl pumped to the mixing device were approximately 1 : 1 : 1 : 1.24. Separation of aqueous phase and an organic phase was observed in the collection vessel. The organic phase was observed to have a hazy appearance. The aqueous layer was removed from the collection vessel. Results of analysis of the organic layer by GC and NMR are presented in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at -78℃; Inert atmosphere; Reflux; | |
85% | With pyridine; titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at 75℃; for 12h; Inert atmosphere; | |
84.9% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Reflux; |
74.8% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran for 12h; Inert atmosphere; Reflux; | |
74.5% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at 70℃; for 24h; Inert atmosphere; Cooling with ice; | 1.1 (1) Preparation of TPE-2OH Dissolve 4-hydroxybenzophenone (1.98 g, 1 mmol) in 100 mL of anhydrous tetrahydrofuran, add zinc powder (3.45 g, 0.5 mmol), evacuate and introduce nitrogen for replacement The whole reaction process was carried out under nitrogen atmosphere for three times, and then TiCl4 (2.8 mL) was slowly added dropwise under ice-water bath conditions. After stirring for 30 min, the entire vacuum state of the device was moved to an oil bath at 70 The reaction was refluxed at for 24 hours, and then the reaction was cooled to room temperature, and K2CO3 aqueous solution (20 mL, 10%) was added under vigorous stirring to quench the reaction. The organic phase was separated by extraction with CH2Cl2, and the combined organic phase was dried with anhydrous Na2SO4. The organic layer was rotary evaporated, and the obtained crude product was purified by a silica gel column. The volume ratio of the eluent ethyl acetate to petroleum ether was 1:8, and the product was vacuum dried to obtain the product with a yield of 74.5%. |
56% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at 85℃; for 18h; | |
56% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran for 4h; Reflux; | |
54% | Stage #1: 4-Hydroxybenzophenone With zinc powder In tetrahydrofuran for 0.25h; Cooling with ice; Stage #2: With titanium(IV) tetrachloride In tetrahydrofuran at 0℃; for 25h; Reflux; Inert atmosphere; | 4 2.4 Synthesis of 1,2-bis(4-hydroxyphenyl)-1,2-diphenylethene 3 A mixture of 4-hydroxybenzophenone (7.93 g, 0.04 mmol), Zn dust (15.7 g, 0.24 mmol) and 150 mL dry THF was added to a 250 mL round-bottom flask and stirred vigorously for 15 min in an ice water bath. After degasification, titanium tetrachloride (13.2 mL, 0.12 mmol) was added dropwise into above solution and stirred at 0 °C for one hour. Then the mixture was refluxed under argon atmosphere and quenched after 24 h with 10% K2CO3 aqueous solution. The precipitate was removed and the crude product was extracted with CH2Cl2 (200 * 3 mL), dried, evaporated, and purified by silica-gel column chromatography (300-400 mesh, eluent petroleum ether/ethyl acetate 2:1). White solid in 54% yield. 1H NMR (600 MHz, CDCl3), δ (TMS, ppm): 7.12-6.97 (m, 10H), 6.87 (m, 4H), 6.55 (m, 4H). |
54% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran Reflux; | |
53% | Stage #1: 4-Hydroxybenzophenone With zinc powder In tetrahydrofuran at 0℃; for 0.25h; Stage #2: With titanium(IV) tetrachloride In tetrahydrofuran for 25h; Cooling with ice; Reflux; Inert atmosphere; | 2.2. Synthesis of TPE-2OH To a solution of 4-hydroxybenzophenone (3.97 g, 0.02 mol) in dryTHF (80 mL) was added Zn dust (7.85 g, 0.12 mol). The mixture wasstirred vigorously for a quarter of an hour to cool to 0 °C. Into the abovemixture was dropwise added titanium tetrachloride (6.6 mL, 0.06 mol)and stirred in an ice water bath for 1 h. Then it was gradually heated toreflux under argon atmosphere for 24 h. The reaction was allowed to becooled to room temperature and quenched with 10% K2CO3 aqueoussolution and the newly formed precipitate was removed. The residuewas extracted three times with 100 mL CH2Cl2, dried, filtered. After allof the solvent CH2Cl2 has been evaporated under reduced pressure, the target product was further purified by silica-gel column chromatography(300-400 mesh, eluent ethyl acetate/petroleum ether 1:2 vol).White solid in 53% yield. 1H NMR (600 MHz, CDCl3), δ (TMS, ppm):7.13-6.98 (m, 10H), 6.91-6.85 (m, 4H), 6.59-6.54 (m, 4H). 13C NMR(150 MHz, CDCl3), δ (TMS, ppm): 154.03, 144.28, 144.17, 139.82,139.80, 136.79, 136.71, 132.87, 132.85, 131.51, 131.50, 127.82,127.72, 126.38, 114.79, 114.71. MS(ESI) m/z: [M-H]- calcd C26H20O2363.1391, found 363.1387. |
51.6% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at -78 - 85℃; for 24h; Inert atmosphere; | 1.1 Example 1: N1,N1'-((((1,2-diphenylethylene-1,2-)bis(4,1-phenylene))bis(oxy))bis(4,1-ylidene (Phenyl)) bis(N1-(4-methoxy)benzene-1,4-diamine) preparation The first step reaction: add 24g of 4-hydroxybenzophenone, 15.7g zinc powder, 500mL tetrahydrofuran and then cooled to -78, Under stirring and nitrogen protection, slowly add 23g of titanium tetrachloride dropwise, After returning to room temperature, it was heated to 85°C and reacted for 24 hours. After the mixture was cooled to room temperature, 500mL, 10wt% potassium carbonate solution quenches the reaction, After filtration, the organic layer was collected. The aqueous layer of the filtrate was extracted three times with ethyl acetate. After the organic phases were combined and dried over magnesium sulfate overnight, After the ethyl acetate and tetrahydrofuran were distilled off, a solid crude product was obtained. The crude product was recrystallized from methanol, After filtration and drying, 12.4 g of white crystals of 1,2-bis(4-hydroxybenzene)-1,2-stilbene were obtained, with a yield of 51.6%. |
46% | With pyridine; titanium(IV) tetrachloride; zinc powder In tetrahydrofuran | |
20% | With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at 0℃; Inert atmosphere; Reflux; | |
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran Reflux; | ||
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran for 4h; Inert atmosphere; Reflux; | ||
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran | ||
With titanium(IV) tetrachloride; zinc powder | ||
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran at -30 - 90℃; for 13h; | 1.1 1. Synthesis of tetrastyrene derivatives Add 4-hydroxybenzophenone (0.2mol, 40.0g) and zinc powder (0.4mol, 25.9g) to a 1000mL four-neck flaskRepeatedly pump oxygen-nitrogen three times in a closed conditionAdd another 600 mL of refined THF,Slowly add titanium tetrachloride (0.3mol, 32.75mL) while stirring at -30 ° C. After the dropwise addition is complete, stir at room temperature for 1h.Then, the reaction was stirred under reflux at 90 ° C for 12 hours.After cooling, pour into 2L beaker,While stirring, add 10% potassium carbonate solution dropwise until the layers are separated.Filtered, the filtrate was three times with dichloromethane,The organic phase was dried over anhydrous magnesium sulfate for 4 h, and then filtered, and the filtrate was spin-dried to obtain a crude product.The crude product was dried and recrystallized with a toluene: petroleum ether = 4: 1 (v: v) mixed solvent.The product was obtained as a pale yellow solid. | |
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran | ||
With titanium(IV) tetrachloride; zinc powder In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Dissolve 4-hydroxybenzophenone in anhydrous THF and treat it with equimolar quantity of sodium hydride at 0 C for 2h. Stir and warm the suspension to 50 C and treat it with an equimolar quantity of 3-Bromomethyl-3-hydroxymethyloxetane (readily prepared in one step by method described in US5489700 or Tet. Lett. 2011, 52, p. 565 - 567 from commercially available 2,2-bis-(bromomethyl)propane-l,3-diol). Stir overnight at 50 C, filter the reaction mixture, evaporate the filtrate to dryness and purify the residue by column chromatography to provide (4-[3-(hydroxymethyl)oxetan-3-yl]methoxy}phenyl)(phenyl)methanone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.8% | With potassium carbonate; In acetonitrile; for 24h;Reflux; | According to the general procedure for the halide alkylation of 4-hydroxybenzopheonone, 1- bromo-6-chlorohexane (13.9 mmol, 2.77 mL), potassium carbonate (25.2 mmol, 3.49 g) and 4- hydroxybenzophenone (12.6 mmol, 2.50 g) were stirred in acetonitrile (20.0 mL) under reflux for 24 hours to give a crude product of 4-<9-(6-chlorohexyl)benzophenone which was recrystallized in toluene/hexanes to yield compound 3b (3.07 g, 76.8percent yield). C|9H2]C102; off white powder, mp 64-67°C; NMR (CDC13, 400 MHz) 5= 1.55 (m,-CH2-, 4H), 1.85 (m, -CH2- , 4Eta), 3.51 (m, -C1-CH2, 2Eta), 4.06 (m, -0-CH2, 2Eta), 6.95 (m, -Ax, 2Eta), 7.49 (m, -Ar, 2H),7.52 (m, -Ar, 1H), 7.77 (m, -Ar, 4H) ppm; l3C NMR (CDCI3, 100 MHz) delta 195.54 (C5), 162.74 (C9), 138.34 (C4), 132.57 (C3), 129.72 (CI), 128.18 (C2), 114.00 (C8), 67.99 (CIO), 30.32 (C15), 30.20 (C14), 28.92 (CI 1), 25.02 (C13) ppm. HRMS-DART (m/z): [M+] calcd. for C19H2|C102, 317.1308; found, 317.131 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium phosphate; 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); 4-methyl-N-phenyl-N-tosylbenzenesulfonamide In 1,4-dioxane at 110℃; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃;Cooling with ice; Inert atmosphere; | General procedure: A solution of diisopropylazodicarboxylate (DIAD, 10 mmol) in anhydrous THF (20 mL) was added dropwise to an ice-bath cooled mixture of ethyl or methyl phenyllactate (10 mmol), the suitable phenol (10 mmol) and PPh3 (10 mmol) in anhydrous THF (50 mL). The reaction mixture was stirred overnight, under N2 atmosphere, at room temperature. The organic solvent was evaporated in vacuo, and a mixture of Et2O and n-hexane (40 mL, 1:1) was added to the residue. The resulting precipitate was filtered off, and the filtrate was evaporated to dryness. The residue was chromatographed on a silica gel column using the suitable eluent affording the desired compounds in 33-79% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In [(2)H6]acetone; | Example 1 Synthesis of {4-[3-hydroxy-2(hydroxymethyl)propoxy]phenyl}(phenyl)methanone 4-Hydroxybenzophenone is treated with equimolar quantity of sodium hydride in dry dimethylformamide at 0 C. under an inert atmosphere. After stirring at ambient temperature for 2 hours, a bright yellow clear solution is obtained. To this solution is added equimolar quantity of (2,2-dimethyl-1,3-dioxan-5-yl)methyl methanesulfonate (its synthesis in two steps from commercially available <strong>[4704-94-3]2-hydroxymethyl-1,3-propanediol</strong> is described in European Patent EP2103611). After stirring at ambient temperature for 16 hours, the reaction mixture is diluted with water and extracted with dichloromethane. The organic phase is evaporated to dryness and the crude product is purified by column chromatography. This provide the intermediate {4-[(2,2-dimethyl-1,3-dioxan-5-yl)methoxy]phenyl}(phenyl)methanone. This intermediate is then dissolved in acetone, excess of 1M hydrochloric acid is added and the reaction mixture is stirred for 2 hours at room temperature. The reaction mixture is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography to provide the desired {4-[3-hydroxy-2-(hydroxymethyl)propoxy]phenyl}(phenyl)methanone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 1,4-diaza-bicyclo[2.2.2]octane In tetrahydrofuran for 12h; Reflux; Sealed tube; | 4-Benzoylphenyl diisopropylcarbamate (26). A mixture of (4-hydroxyphenyl)(phenyl)methanone (2.0 g, 10 mmol), was treated withdiisopropylcarbamic chloride (2.5 g, 15 mmol) and DABCO (2.2 g, 20 mmol) wererefluxed in THF (50 mL) for 12 h. The solvent was removed in vacuo. The purificationS7by flash column chromatography on silica gel (hexane/EtOAc = 10/1) gave the productas a white solid (26, 3.1 g, 97%). Rf = 0.32 (hexane/EtOAc = 5/1), White solid. Mp70 °C.1H NMR (CDCl3, 400 MHz): 1.32 (bs, 6H), 1.35 (bs, 6H), 4.00 (bs, 1H), 4.11 (bs, 1H),7.24-7.26 (m, 2H), 7.48 (t, J = 5.2 Hz, 2H), 7.59 (t, J = 4.8 Hz, 1H), 7.79-7.86 (m, 4H).13C NMR (CDCl3, 100 MHz): 20.3, 21.4, 46.2, 46.9, 121.5, 128.1, 129.8, 131.4, 132.2,134.0, 137.5, 152.8, 154.7, 195.6.HRMS (EI): Calcd for C20H23NO3 325.1678, Found 325.1679. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; butanone; | Synthesis of 4-acryloyloxy-benzophenone 1.3 g (16.25 mmoli) of NaOH 50percent water solution, were added to a solution of 3 g (15.21 mmol) of 4-hydroxybenzophenone in 20 cc of methyl ethyl ketone. After 30 minutes under stirring, a solution of 1.59 g (15.21 mmol) of methacryloyl chloride in 5 mL of methyl ethyl ketone were added dropwise. After the addition the reaction mixture was stirred for 1 hour, filtered and the solvent was evaporated. The oil residue was purified by flash chromatography on silica gel (eluent CH2Cl2) to obtain 2.74 g of a colourless liquid. 1HNMR (CDCl3): delta (ppm): 2.10 (s, 3H); 5.82 (s, 1H); 6.40 (s, 1H); 7.2-7.3 (m, 2H); 7.45-7.55 (m, 2H); 7.60-7.65 (m, 1H); 7.75-7.85 (m, 2H); 7.85-7.95 (m, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.2% | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 24h;Inert atmosphere; | To a stirred solution of 4-hydroxybenzophenone (198.2 mg, 1.0 mmol) in DMF (3 mL) at 0 C under nitrogen was added potassium carbonate (207 mg, 1.5 mmol) followed by methyl-5-chloromethyl-2-furoate (175 mg, 1.0 mmol). The reaction was allowed to warm to room temperature and the mixture was stirred at room temperature for 24 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous phase wasextracted twice with ethyl acetate and the combined organic phases were washed with10% aqueous K2C03 solution, water, brine, dried over MgSO4, filtered and the solvent removed in vacuo to yield the title compound (330 mg, 98.2%) as a yellow oil.?H NMR (400 MHz, CDC13): oe 7.84-7.74 (m, 3 H), 7.59-7.55 (m, 3 H), 7.49-7.45 (m, 1 H), 7.18-7.17 (m, 1 H), 7.03-7.01 (m, 2 H), 6.57-6.56 (m, 1 H), 5.14 (s, 2 H), 3.91(s, 3 H). LCMS (Method 2): [M-OH+] = 337 at 4.05 mm. |
98.2% | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 24h;Inert atmosphere; | To a stirred solution of 4-hydroxybenzophenone (198.2 mg, 1.0 mmol) in DMF (3 mL) at 0 C. under nitrogen was added potassium carbonate (207 mg, 1.5 mmol) followed by methyl-5-chloromethyl-2-furoate (175 mg, 1.0 mmol). The reaction was allowed to warm to room temperature and the mixture was stirred at room temperature for 24 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous phase was extracted twice with ethyl acetate and the combined organic phases were washed with 10% aqueous K2CO3 solution, water, brine, dried over MgSO4, filtered and the solvent removed in vacuo to yield the title compound (330 mg, 98.2%) as a yellow oil. [0387] 1H NMR (400 MHz, CDCl3): delta 7.84-7.74 (m, 3H), 7.59-7.55 (m, 3H), 7.49-7.45 (m, 1H), 7.18-7.17 (m, 1H), 7.03-7.01 (m, 2H), 6.57-6.56 (m, 1H), 5.14 (s, 2H), 3.91 (s, 3H). LCMS (Method 2): [M-OH+]=337 at 4.05 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With oxygen; cobalt(II) diacetate tetrahydrate; sodium hydroxide; In ethylene glycol; at 100℃; under 760.051 Torr; for 12h; | General procedure: A mixture of substrate 1 (2.0 mmol), Co(OAc)24H2O (40 mg, 0.16 mmol) andNaOH (160 mg, 4.0 mmol) in EG (9.0 ml) was stirred with molecular oxygen(1 atm) being bubbled, under 100 C for specified time. After completion ofreaction, diluted hydrochloric acid (15 ml, 2 %) and chloroform (15 ml) weresuccessively added to the reaction mixture. The organic layer was separated, and theaqueous phase was extracted with chloroform (15 ml 9 2). The combined organicphase was dried over anhydrous sodium sulfate and concentrated to give a residue,which was purified by column chromatography on silica gel (eluents: petroleumether:ethyl acetate = 10:1) providing the desired products 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1320.4 g | With methacryloyl anhydride; 2,4-dimethyl-6-tert-butylphenol; sodium methylate; In methanol; at 60 - 90℃; for 6h; | Example 1Sodium Methacrylate Catalyst Generated in situ10045] Apparatus: 2 1 four-necked round-bottom flask with mechanical stirring, reflux condenser, air inlet, PtiOO temperature sensor, oil bath.10046] Batch: 1.5 mol (297.9 g) of 4-hydroxybenzophe- none, 1.65 mol (270.3 g) of MAAH, 0.0087 mol (1.6 g) of NM3O solution, 399 mg of 2,4-dimethyl-6-tert-butylphenol (Topanol A);10047] Preparation of a 30% strength solution of 4-(meth- acryloyloxy)benzophenone in MMA: Addition of a total of 772 g of MMA10048] Theoretical yield of 4-(methacryloyloxy)benzo- phenone: 399 g10049] Procedure: 4-Hydroxybenzophenone was weighed out, and 126 g of the subsequently required MMA were added; a readily stirrable composition was formed. Then IVL&AH, Topanol A stabilizer and NM3O catalyst were added, air was introduced, and the batch was heated to 90 C. The course of the reaction was monitored by gas chromatography (a sample (approximately 1.5 ml) taken, diluted with approximately 5 ml of acetone, and filtered). After a total of 5 h at 90 C., the batch was cooled to 60 C., 30 g of methanol were added for conversion of the remaining MAAH, and the batch was stirred 60 C. for 1 h. The remainder of the MMA (646 g) was then added to the batch, to produce a 30% strength solution. After cooling with accompanying stirring, filtering took place through a pressure filter with Seitz Ti000 filter layer (014 cm). Yield:1320.4 g |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 0.166667h; | |
97% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 0.166667h; | 4 Example 3. General Procedure for the Synthesis of Aryl Fluorosulfates and Sulfamoyl Fluorides General procedure: To a 2-dram vial equipped with a magnetic stir bar, the phenol or amine substrate (0.4 mmol) and AFSI (134 mg, 0.48 mmol, 1.2 equiv.), was added tetrahydrofuran (2 mL). 1,8-Diazabicyclo[5.4.0]undec-7-ene (132 μL, 0.88 mmol, 2.2 equiv.) was added to the mixture over a period of 30 seconds. The reaction mixture was stirred at room temperature for 10 minutes and then diluted with ethyl acetate or ether and washed with either 0.5 N KHSO4 or 0.5 N HCl (2×) and brine (1×). The combined organic fraction was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography. |
96% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 2h; |
67% | With fluorosulfonyl fluoride; triethylamine In 1,4-dioxane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; water;Flow reactor; | General procedure: EX-22 was carried out using Microreactor B. For EX-22, syringe I contained 15 g BP, 33 g TEA, and 33 g water. Syringe II contained 4.2 g 3CPC and 20 g DCM. Each syringe was placed in a separate syringe pump and the pump speeds were controlled to deliver the blends at the flow rates indicated for EX-22 in Table 8 below. The two unused addition ports of the mixing device were sealed with plugs. Separation of aqueous phase and an organic phase was observed in the collection vessel. Analysis of the upper, aqueous phase by NMR indicated approximately 8 mol percent of acrylic acid-TEA salt and approximately 92 mol percent TEA-HC1 salt. Analysis of the lower, organic phase by NMR indicated approximately 51 mol percent ABP, approximately 0.01 mol percent BP and approximately 42 mol percent of the above mentioned TEA salts. Analysis by GC indicated the organic layer was 98percent ABP and 2percent unreacted alcohol. After analysis, the organic layer was washed with water to remove salts and residual TEA. For EX-23 through EX-26, the same procedure was followed as described for EX-22, except that flow rates were as indicated in Table 8. Blend compositions, flow rates, and percent Composition are provided in Table 8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 19% 2: 10% | With Co(difluoroboryl-dimethylglyoxime)<SUB>2</SUB>(CH<SUB>3</SUB>CN)<SUB>2</SUB>; water monomer; 3-cyano-1-methylquinolinium cation In acetonitrile at 20℃; for 5h; Inert atmosphere; Irradiation; Green chemistry; | 30 Example 30 Using 1-methyl-3-cyanoquinoline salt as photosensitizer, Cobalt oxime complex 2 as cobalt catalyst, 5mL acetonitrile2.69 mg (1 × 10 -2 mmol) of photosensitizer and 2.80 mg (6 × 10 -3 mmol) of cobalt catalyst were charged, the atmosphere was replaced with Ar atmosphere, and then 0.2 mmol of benzophenone(R1 is COC6H5, R2, R3, R4 are independently H) and 2 mmol H2O. Room temperature, high pressure mercury lamp irradiation 5h. After completion of the reaction, H2 production was detected by GC (TCD), benzene conversion by GC (FID) was detected, and then column separation was performed. Nuclear magnetic resonance spectrometry and mass spectrometry identified products 2-hydroxybenzophenone,3-hydroxybenzophenone and 4-hydroxybenzophenone. The conversion of benzophenone was 34%, the yields of 2-hydroxybenzophenone, 3-hydroxybenzophenone and 4-hydroxybenzophenone were 19%, 4% and 10%, The yield of H2 is 34%. |
With tert.-butylnitrite; water monomer; oxygen; 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 20℃; for 16h; Irradiation; Overall yield = 65 percent; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In acetone; at 55℃; for 20h; | Bromoethane (3.2 g, 30 mmol) and 4-hydroxybenzophenone (4.95 g, 25 mmol) were added to a three-necked flask,After adding 300mL of acetone,Additional potassium carbonate (4.1 g, 30 mmol)Then the temperature was raised to 55 C and stirring was continued for 20h.After the reaction was stopped cooling to room temperature,filter,The filtrate was collected,Rotary evaporation of the solvent gave the crude product,A volume ratio of 50: 1 petroleum ether and ethyl acetate mixture as eluent,SiO2 as the stationary phase,Purification by column chromatography to give 4-n-hexyloxybenzophenone 4.9g,Yield 86%. |
70% | With potassium carbonate; In acetone; for 12h;Reflux; Inert atmosphere; | 4-Hydroxybenzophenone (4.9 g, 25 mmol), anhydrous potassium carbonate (6.9 g, 50 mmol), bromoethane (2.23 mL, 30 mmol) was added to a 250 mL two-necked flask.An appropriate amount of acetone solvent was added and refluxed for 12 hours under a nitrogen atmosphere.The reaction was completely cooled to room temperature, and an appropriate amount of dilute hydrochloric acid solution (2 mol/L) was added until no bubbles were formed.The organic phase is extracted with chloroform and combined to obtain a crude product which is purified by chromatography to obtain a pure product.The yield was 70%, and the structure was characterized by 1H-NMR and 13C-NMR to confirm that the product was a compound of Comparative Example I. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 0 - 70℃; for 36.5h;Inert atmosphere; | A 250 mL round bottom flask was charged with 4-hydroxybenzophenone (1.9 g, 10 mmol)<strong>[27982-06-5]4-ethoxybenzophenone</strong> (2.7 g, 12 mmol),Zn powder (3.9 g, 50 mmol).After evacuating nitrogen for three times,Add 80 mL of tetrahydrofuran.After cooling to 0 C,TiCl4 (5.7 g, 25 mmol) was slowly added,Then stirred for 0.5 h.Then stirred at 70 C for 36 h,After cooling to room temperature,Add 80mL dilute hydrochloric acid (1mol / L),Adjusted to neutral,DCM extraction three times,The organic layer was collected,Dried over anhydrous magnesium sulfate,The solvent is dried to give the crude product,A volume ratio of 50: 1 petroleum ether and ethyl acetate mixture as eluent,SiO2 as the stationary phase,Column chromatography isolated white solid 0.8g,Yield 41%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With titanium tetrachloride; zinc In tetrahydrofuran at 0 - 65℃; for 36.8h; Inert atmosphere; | 2.1 (1) intermediate 4 - (1 - phenyl - 2, 2 - dimethyl phenyl vinyl) phenol synthesis. In a 250 ml round bottom flask is added 4 - hydroxy benzophenone (1.9g, 10mmol), 4, 4' - dimethyl benzophenone (3.2g, 15mmol), Zn powder (3.9g, 60mmol). After three rounds of pumping nitrogen exchange, add 80 ml tetrahydrofuran. Cooling to 0 °C after, slowly adding TiCl4(5.7g, 30mmol), then stirring 0.8h. Then in the 65 °C stirring 36h, after cooling to room temperature, add 80 ml dilute hydrochloric acid (1 mol/L), is adjusted to neutral, DCM extraction three times, collection of the organic layer, drying by anhydrous magnesium sulphate, turns on lathe does solvent to get the crude product, to the volume ratio of 40:1 mixture of petroleum ether and ethyl acetate as eluent, SiO2As stationary phase, column chromatography separation to obtain the white solid 0.62g, yield 32%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrabutylammomium bromide; potassium carbonate In dichloromethane for 6h; Reflux; | 3.1. General Procedure for the Synthesis of Compounds1-18 General procedure: Synthesis of benzophenone ester and sulfonates was carriedout by refluxing 4-hydroxy benzophenone with differentlysubstituted acyl halides, sulfonyl chlorides in the presenceof base potassium carbonate (K2CO3) in the presence oftetra-butyl ammonium bromide (TBAB) as catalyst. Reactionwas completed in 6 h which was confirmed through thinlayer chromatography (TLC) analysis. Completion of reactionwas followed by filtration and then the filtrate wascooled to room temperature, resulting in precipitation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 2: bis(η3-allyl-μ-chloropalladium(II)); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine / toluene / 16 h / 100 °C / Sealed tube; Inert atmosphere 3: toluene / 0.5 h / 45 °C |
Tags: 1137-42-4 synthesis path| 1137-42-4 SDS| 1137-42-4 COA| 1137-42-4 purity| 1137-42-4 application| 1137-42-4 NMR| 1137-42-4 COA| 1137-42-4 structure
[ 2657-25-2 ]
1-(4-Hydroxyphenyl)-3-phenylprop-2-en-1-one
Similarity: 0.97
[ 10425-11-3 ]
(3,4-Dihydroxyphenyl)(phenyl)methanone
Similarity: 0.95
[ 605-32-3 ]
2-Hydroxyanthracene-9,10-dione
Similarity: 0.95
[ 875-59-2 ]
1-(4-Hydroxy-2-methylphenyl)ethanone
Similarity: 0.95
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Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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