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CAS No. : | 19812-93-2 | MDL No. : | MFCD00059625 |
Formula : | C13H9NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZRMIETZFPZGBEB-UHFFFAOYSA-N |
M.W : | 195.22 | Pubchem ID : | 140610 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 58.62 |
TPSA : | 44.02 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) : | -5.42 cm/s |
Log Po/w (iLOGP) : | 1.85 |
Log Po/w (XLOGP3) : | 2.92 |
Log Po/w (WLOGP) : | 2.93 |
Log Po/w (MLOGP) : | 2.34 |
Log Po/w (SILICOS-IT) : | 3.02 |
Consensus Log Po/w : | 2.61 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.42 |
Solubility : | 0.0749 mg/ml ; 0.000384 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.51 |
Solubility : | 0.0609 mg/ml ; 0.000312 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.43 |
Solubility : | 0.00727 mg/ml ; 0.0000372 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.7 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302+H312+H332-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 |
---|---|---|
85% | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 48 h; | General procedure: 4'-Hydroxybiphenyl-4-carbonitrile (1) (20.0 g, 0.1 mol), potassium carbonate (28.0 g, 0.2 mol) and DMF (600 mL) were placed in a 1000 mL flask and stirred. The corresponding alkylbromide (20.0 g for 1-bromohexane, 23.0 g for 1-bromo-octane, 0.12 mol) was added and the reaction mixture was heated at 120 °C for 48 h. The mixture was then cooled to room temperature and poured onto ice water (1000 mL) and left to stand overnight. The precipitated product was isolated by filtration and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 48 h; | General procedure: 4'-Hydroxybiphenyl-4-carbonitrile (1) (20.0 g, 0.1 mol), potassium carbonate (28.0 g, 0.2 mol) and DMF (600 mL) were placed in a 1000 mL flask and stirred. The corresponding alkylbromide (20.0 g for 1-bromohexane, 23.0 g for 1-bromo-octane, 0.12 mol) was added and the reaction mixture was heated at 120 °C for 48 h. The mixture was then cooled to room temperature and poured onto ice water (1000 mL) and left to stand overnight. The precipitated product was isolated by filtration and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate In acetone for 6.5 h; Reflux | To a solution of 4’-hydroxy-4-biphenylcarbonitrile (500 mg, 2.48 mmol) in acetone (50 mL) was added bromoethane (0.47 mL, 6.2 mmol) and K2CO3 (684 mg, 4.96 mmol). The resulting mixture was stirred at reflux for 6.5 h. The white solid was filtered off and the filtrate was concentrated in vacuo to give light yellow solid, which was purified by gravity chromatography with 20percent EtOAc/hexane to get white solid, which was further recrystallized from EtOAc to give 6 as white crystalline (386 mg, 70percent). 1H NMR (300 MHz, CDCl3) δ 7.68-7.59 (m, 4H), 7.54-7.48 (m, 2H), 7.07-6.96 (m, 2H), 4.07 (q, J = 6.9 Hz, 2H), 1.44 (t, J = 6.9 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3) δ 159.66, 145.28, 132.60, 131.30, 128.38, 127.10, 119.19, 115.11, 110.06, 63.66, 14.86 ppm. MS-ESI (m/z): calcd for C15H13NO, [M+H]+ 224.1; found 224.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide In methanol | 4'-hydroxy-3'-iodo [1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0° C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25percent Clorox.(TM)., 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53percent). MS (DCI) m/z 339[M+NH4+]+. |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide In methanol | EXAMPLE 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0° C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25percent Clorox.(TM)., 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53percent). MS (DCI) m/z 339[M+NH4+]+. |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide In methanol | Example 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0° C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25percent Clorox.(TM)., 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53percent). MS (DCI) m/z 339[M+NH4+]+; |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide In methanol | Example 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0° C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25percent Clorox.(TM)., 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53percent). MS (DCI) m/z 339[M+NH4+]+; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With sodium hydroxide; sodium iodide In methanol | EXAMPLE 169A 4'-hydroxy-3'-iodo-1,1'-biphenyl-4-carbonitrile 4'-Hydroxy-1,1'-biphenyl-4-carbonitrile (25.0 g, 128 mmol), purchased commercially, NaI (19.19 g, 128 mmol), and sodium hydroxide (5.12g, 128 mmol) were combined in methanol (500 mL) at 0° C. and treated with bleach (5.25percent, 181.0 g) dropwise over 1 hour. After stirring at 0° C. for 1 hour, the mixture was treated with 10percent aqueous sodium thiosulfate (250 mL). The mixture was adjusted to pH 6.8 with 10percent aqueous HCl and then the mixture was filtered. The filter cake was crystallized from hot CH2Cl2/hexane to provide the title compound (40percent yield). 1H-NMR (300 MHz, CDCl3) δ 5.40 (s, 1H), 7.10 (m, 1H), 7.50 (m, 1H), 7.60 (m, 2H), 7.77(m, 2H), 7.90 (m, 1H); MS (CDI) m/z 339 (M+NH4)+. |
40% | With sodium hydroxide; sodium iodide In methanol | EXAMPLE 169A 4'-hydroxy-3'-iodo-1,1'-biphenyl-4-carbonitrile 4'-Hydroxy-1,1'-biphenyl-4-carbonitrile (25.0 g, 128 mmol), purchased commercially, NaI (19.19 g, 128 mmol), and sodium hydroxide (5.12g, 128 mmol) were combined in methanol (500 mL) at 0° C. and treated with bleach (5.25percent, 181.0 g) dropwise over 1 hour. After stirring at 0° C. for 1 hour, the mixture was treated with 10percent aqueous sodium thiosulfate (250 mL). The mixture was adjusted to pH 6.8 with 10percent aqueous HCl and then the mixture was filtered. The filter cake was crystallized from hot CH2Cl2/hexane to provide the title compound (40percent yield). 1H-NMR (300 MHz, CDCl3) δ5.40 (s, 1H), 7.10 (m, 1H), 7.50 (m, 1H), 7.60 (m, 2H), 7.77(m, 2H), 7.90 (m, 1H); MS (CDI) m/z 339 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In acetone; for 6.5h;Reflux; | To a solution of 4’-hydroxy-4-biphenylcarbonitrile (500 mg, 2.48 mmol) in acetone (50 mL) was added bromoethane (0.47 mL, 6.2 mmol) and K2CO3 (684 mg, 4.96 mmol). The resulting mixture was stirred at reflux for 6.5 h. The white solid was filtered off and the filtrate was concentrated in vacuo to give light yellow solid, which was purified by gravity chromatography with 20% EtOAc/hexane to get white solid, which was further recrystallized from EtOAc to give 6 as white crystalline (386 mg, 70%). 1H NMR (300 MHz, CDCl3) δ 7.68-7.59 (m, 4H), 7.54-7.48 (m, 2H), 7.07-6.96 (m, 2H), 4.07 (q, J = 6.9 Hz, 2H), 1.44 (t, J = 6.9 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3) δ 159.66, 145.28, 132.60, 131.30, 128.38, 127.10, 119.19, 115.11, 110.06, 63.66, 14.86 ppm. MS-ESI (m/z): calcd for C15H13NO, [M+H]+ 224.1; found 224.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 85℃; | Compound [MA11-1] (50.00 g, 256 mmol) was added to a 2 L four-necked flask,<strong>[2009-83-8]6-chloro-1-hexanol</strong> (36.74 g,268 mmol), potassium carbonate (106.2 g, 768 mmol), potassium iodide (21.3 g, 128 mmol),DMF (500 g) was heated at 85C.Reaction tracing by HPLC,After confirming the end of the reaction,The reaction solution was poured into distilled water (3L).Filtration, washing with distilled water,Crude product was obtained.After that, the resulting crude product is washed with methanol and filtered.After drying under reduced pressure, 61.9 g of compound [MA11-2] was obtained (yield 82%). |
With potassium carbonate; In N,N-dimethyl-formamide; | The LC-3 mesogen was prepared via alkylation of 4'-hydroxybiphenyl-4-carbonitrile (Aldrich) with 6-chlorohexan-1-ol in DMF in the presence of K2CO3 and was purified by recrystallization from ethanol and 12 h maintaining at the residual pressure of 200 Pa at the temperature of the mesophase existence. The purity of the liquid crystalline solvents was judged from the constant temperature of nematic-isotropic transition (TNI) in the repeated purification cycles, the absence of layering into the nematic and the isotropic phases upon the phase transition, and the correspondence of the melting points to the reference values [28]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 48h; | 4.2. Typical procedure for the alkylation of 1 General procedure: 4'-Hydroxybiphenyl-4-carbonitrile (1) (20.0 g, 0.1 mol), potassium carbonate (28.0 g, 0.2 mol) and DMF (600 mL) were placed in a 1000 mL flask and stirred. The corresponding alkylbromide (20.0 g for 1-bromohexane, 23.0 g for 1-bromo-octane, 0.12 mol) was added and the reaction mixture was heated at 120 °C for 48 h. The mixture was then cooled to room temperature and poured onto ice water (1000 mL) and left to stand overnight. The precipitated product was isolated by filtration and crystallized from ethanol. |
72% | With sodium isopropylate In isopropyl alcohol for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In acetone for 24h; Heating; | |
92% | With potassium carbonate; potassium iodide In butanone | |
91% | With potassium carbonate In acetone at 64℃; for 24h; | 1 5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenol, 4.6 g (25.6 mmol) of 6-bromo-1-hexanol, 7.0 g (50 mmol) of potassium carbonate and 50 ml of acetone were added to a 100 ml round bottom flask equipped with a condenser to provide a mixture, followed by reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid was mixed with 70 ml of water, to which 50 ml of diethyl ether was added for extraction. The extraction was repeated three times. Anhydrous magnesium sulfate was added to a separated organic phase for drying and after filtration, the solvent was distilled off under reduced pressure to obtain a yellow solid. This solid was dissolved in 3 ml of ethyl acetate and purified by silica gel column chromatography (column: silica gel 60, 0.063-0.200 mm, made by Merck & Co., eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the resulting solution to obtain 6.9 g of a white solid. The solid was subjected to measurement of NMR with the results shown below. From the results, it was confirmed that the white solid was made of an intermediate compound (A1) shown in the following synthetic scheme (yield: 91%). 1H-NMR(DMSO-d6) δ: 1.26(m, 6H), 1.69(m, 2H), 3.37(t, 2H), 4.03(t, 2H), 7.06(d, 2H), 7.69(d, 2H), 7.85(m, 4H). |
91% | With potassium carbonate In acetone at 64℃; for 24h; | 1 [Synthesis Example 1]; Synthesis of polymerizable liquid crystal compound (E3); In a 100-mL pear-shaped flask fitted with a condenser, 4-cyano-4'-hydroxybiphenol (5.0 g, 25.6 mmol), 6-bromo-1-hexanol (4.6 g, 25.6 mmol), potassium carbonate (7.0 g, 50 mmol) and acetone (50 mL) were placed and combined into a mixture. The mixture was subjected to a reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain yellow wet solid. Subsequently, the solid and water (70 mL) were mixed. Diethyl ether (50 mL) was added, followed by extraction. The extraction was conducted three times. An organic layer was separated, to which anhydrous magnesium sulfate was added to dry the same. Subsequent to filtration, the solvent was distilled off under reduced pressure to obtain yellow solid. The solid was dissolved in ethyl acetate (3 mL), followed by purification by silica gel column chromatography (column: "Silica Gel 60," 0.063-0.200 mm, product of Merck & Co., Inc., eluent: hexane/ethyl acetate = 1/1). From the thus-obtained solution, the solvent was distilled off to obtain white solid (6.9 g). The results of a measurement of the solid by NMR are shown below. From the results, the white solid was confirmed to be an intermediate compound (A1) represented by the below-described synthesis scheme (yield: 91%). 1H-NMR(DMSO-d6) δ: 1.26(m,6H), 1.69(m,2H), 3.37(t,2H), 4.03(t,2H), 7.06(d,2H), 7.69(d,2H), 7.85(m,4H). |
91% | With potassium carbonate; potassium iodide In butanone at 80℃; for 48h; Inert atmosphere; | |
91% | With potassium carbonate In acetone at 64℃; for 24h; | 2.A2 Synthetic Example 2 Synthesis of polymerizable liquid crystal compound (E2) [Show Image] 5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenyl, 4.6 g (25.6 mmol) of 6-bromo-1-hexanol, 7.0 g (50 mmol) of potassium carbonate and 50 ml of acetone were added to a 100-ml round-bottomed flask equipped with a condenser tube to provide a mixture, followed by reaction under agitation at 64°C for 24 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid and 70 ml of water were mixed together, to which 50 ml of diethyl ether was added for extraction. The extraction was repeated three times. The separated organic phase was dried by addition of anhydrous magnesium sulfate and filtered, followed by distilling off the solvent under reduced pressure to obtain a yellow solid. This solid was dissolved in 3 ml of ethyl acetate and purified according to silica gel column chromatography (column: silica gel 60, 0.063 to 0.200 mm, made by Merck KGaA, eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the solution to obtain 6.9 g of a white solid. The results of NMR measurement of the solid are indicated below. From the results, it was confirmed that this white solid was an intermediate compound (A2) (yield: 91%) 1H-NMR (DMSO-d6) δ:1.26 (m, 6H), 1.69 (m, 2H), 3.37 (t, 2H), 4.03 (t, 2H), 7.06 (d, 2H), 7.69 (d, 2H), 7.85 (m, 4H). |
91% | With potassium carbonate In acetone at 64℃; for 24h; | 2 n a 100 ml eggplant flask equipped with a cooling tube,5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenol,4.6 g (25.6 mmol) of 6-bromo-1-hexanol,7.0 g (50 mmol) of potassium carbonate,And 50 ml of acetone were added to the mixture,The reaction was carried out with stirring at 64 DEG C for 24 hours.After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a wet solid of yellow color. Thereafter, this solidAnd water (70 ml) were mixed and extracted with 50 ml of diethyl ether. Extraction was carried out three times.The organic layer separated was dried over anhydrous magnesium sulfate,After filtration, the solvent was distilled off under reduced pressure to obtain a yellow solid.This solid was dissolved in 3 ml of ethyl acetate,Silica gel column chromatography (column: silica gel 60,0.063-0.200 mm,Eluent: hexane / ethyl acetate = 1/1).The solvent was distilled off from the obtained solution,6.9 g of a white solid was obtained.The result of measurement of this solid by NMR is shown below.From this result, it was confirmed that the white solid was the intermediate compound (A2) (yield: 91%). |
75% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 3.5h; Cooling with ice; Inert atmosphere; | |
68% | With potassium carbonate In acetone for 24h; Reflux; Inert atmosphere; | |
With potassium carbonate In N,N-dimethyl-formamide Heating; Yield given; | ||
With potassium carbonate In ethanol for 24h; Heating; | ||
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 4h; | ||
With potassium carbonate In butanone Heating; | ||
With potassium carbonate In acetone Heating; | ||
With potassium carbonate; potassium iodide In butanone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 48h; | General procedure: 4'-Hydroxybiphenyl-4-carbonitrile (1) (20.0 g, 0.1 mol), potassium carbonate (28.0 g, 0.2 mol) and DMF (600 mL) were placed in a 1000 mL flask and stirred. The corresponding alkylbromide (20.0 g for 1-bromohexane, 23.0 g for 1-bromo-octane, 0.12 mol) was added and the reaction mixture was heated at 120 C for 48 h. The mixture was then cooled to room temperature and poured onto ice water (1000 mL) and left to stand overnight. The precipitated product was isolated by filtration and crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; potassium iodide In butanone | |
93% | With potassium carbonate In butanone for 15h; Heating; | |
93% | With potassium carbonate In butanone for 15h; Heating / reflux; | 1; 2 EXAMPLE 1 This synthesis is representative for compounds of this general structure. Other end groups (X) using this synthetic route are: cyclopropyl, cyclopentyl, cycloheptyl, adamantyl and norboranyl (see Table 1). 4-CYANO-4 -(11-HYDROXYUNDECYLOXY) biphenyl (1) 4-cyano-4'-hydroxybiphenyl (8.22 g; 0.042 mol), 11-BROMO-1-UNDECANOL (10.00 g; 0.040 mol) and potassium carbonate (23.00 g; 0.170 mol) were heated under reflux in dry butanone (125 ml) for 15 h. The solids were removed by filtration and washed with acetone (2 x 50 ml). The combined solvents were removed in vacuo to give a white solid which was recrystallised from acetonitrile. Yield 14. 31 g (93%); 4-Cyano-4'-(11-hydroxyundecyloxy) biphenyl (2) 4-Cyano-4'-hydroxybiphenyl (8.22 g; 0. 042MOL), 1, 11-BROMO-1-UNDECANOL (10.0 g; 0.040 mol) and potassium carbonate (23.0 g; 0.170 mol) were heated under reflux in dry butanone (125 ml) for 15 h. The solids were removed by filtration and washed with acetone (2 x 50 ml). The combined solvents were removed in vacuo to give a white solid which was recrystallised from acetonitrile. Yield 14.31 g (93%) |
93% | With potassium carbonate In acetone for 20h; Reflux; | |
90% | With potassium carbonate; potassium iodide In acetone for 18h; Reflux; | |
89% | With potassium carbonate; potassium iodide In acetone for 12h; Reflux; | |
88% | With potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 120℃; for 20h; | |
82% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; | |
77% | With tetra-(n-butyl)ammonium iodide; potassium carbonate In butanone for 48h; Reflux; Inert atmosphere; | |
47% | With potassium carbonate In ethanol; water at 20 - 60℃; for 23h; Inert atmosphere; | Synthesis of 11-(4'-cyanophenyl-4"-phenoxy)undecanol Synthesis of 11-(4'-cyanophenyl-4"-phenoxy)undecanol In a 3-necked (500 mL) RB flask a mixture of 4-cyano-4'-hydroxybiphenyl (10.0 g, 0.05 mol) and K2CO3 (8.5 g, 0.06 mol) were dissolved in ethanol/water (128 mL/32 mL, 80%/20% (v/v)). A solution of 11-bromo-1-undecanol (14.2 g, 0.06 mol) in ethanol (100 mL) was added dropwise to it using a pressure equalizer at room temperature. After complete addition, solution was brought to an oil bath set at 60° C. After 23 h the solution was poured into 500 mL of ice-chilled distilled water and stirred for 1.5 h. The product was filtered out using a frit and recrystallized twice in ethanol (300 mL). Final yield=8.92 g (47%). 1H-NMR (CDCl3, 7.27 ppm): 1.31 (m, (CH2)6), 1.48 (m, -CH2CH2CH2OAr), 1.59 (m, -CH2CH2OH), 1.82 (m, -CH2CH2OAr), 3.65 (t, -CH2OH), 4.02 (t, -CH2OAr), 7.00 (d, 2 aromatic H ortho to -OCH2), 7.53 (d, 2 aromatic H meta to -OCH2), 7.67 (m, 4 aromatic H ortho and meta to -CN). |
With potassium carbonate In N,N-dimethyl-formamide Heating; Yield given; | ||
With potassium carbonate In butanone | ||
With potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide Heating; | ||
With potassium carbonate In butanone | ||
With potassium carbonate In butanone for 12h; Heating; | Alkylation of phenols with 11-bromo-1-undecanol General procedure: Correspondingphenol (10 mmol), 11-bromo-1-undecanol (3.0 g, 12.00 mmol), K2CO3(4.15 g,30.00 mmol) was heated with stirring in40 ml of methyl ethyl ketone 12 hours. The reaction mixture was evaporated to dryness under reduced pressure. Theresidue was suspended in water andfiltered solid product was washedwith water several times more,and then recrystallized from a suitable solvent.If a substance after adding waterto the residue after evaporation does not form a solid precipitate, theproduct was extracted with severalportions of chloroform, followed bywashing of the extract threetimes with water. Afterevaporation, the product was obtained and purified by hot extraction in modified Sokslett’s extractor with silica gel or flash chromatography. The product was dried in vacuo at 100 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium carbonate In acetone for 48h; Reflux; | Synthesis of 8-(4-cyano-4’-biphenyl) -1-octanoyl acrylate (CBOA). A stirred mixture of octane-1, 8-diol (15 g, 0.103 mol) and hydrogen bromide (45%) (19.54 ml, 0.154 mol) was refluxed for 48 h in 300 ml of toluene. After removing toluene by evaporation on a rotary evaporator at 60 °C, the crude product was purified by silica-gel column chromatography, using petroleum ether (PE)/ ethyl acetate (EA) (3:1 v/v) mixture as eluent. 16.94 g of 8-bromo-1-octanol was obtained as a liquid in yield 79%. 4-Hydroxyoctyloxy-4’-cyanobiphenyl was prepared by refluxing a phenolate solution for 48 h. The phenolate solution was obtained by adding 4.68 g 4-cyano-4’-hydroxybiphenyl and 6.62 gof anhydrous K2CO3 to a stirred solution of 4.18 g of 8-bromo-1-octanol dissolved in 30 ml of acetone. After the reaction was over, the reaction mixture was extracted with water and chloroform to remove the KBr by-product. The organic layer was separated, washed with water, and dried. The residue was purified by silica-gel column chromatography (chloroform). The resulting product was dried in vacuo. 3.60 g of 4-hydroxyoctyloxy-4’-cyanobiphenyl was obtained as a white solid in yield 56%. 4-hydroxyhexyloxy-4’-cyanobiphenyl (2.16 g) and triethylamine (1.2 ml) were dissolved in 50 ml dichloromethane at 0 °C. 8-(4-cyano-4’-biphenyl) -1-octanoylacrylate was obtained by acylation of the dissolved solution by slowly adding acryloyl chloride solution (0.7 ml) dissolved in 5 ml dichloromethane at 5 °C for 24 h. The reaction mixture was extracted with water and chloroform to remove triethylamine salt. The organic layer was separated, washed with water, and dried. The residue was purified by silica-gel column chromatography (chloroform). The resulting product was dried in vacuo. 1.67 g of 8-(4-cyano-4’-biphenyl)-1-octanoylacrylate was obtained as a white solid in yield 77%. |
With potassium carbonate; potassium iodide In ethanol; water Heating; | ||
With potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.2% | With sodium hydroxide In ethanol at 70 - 80℃; for 1h; | 5 4-Cyano-4'-acetic acid biphenyl (6.5g, 0.027mol) and sodium hydroxide solution (1N, 55ml) and 13ml of ethanol were added to a 200ml three-necked flask at room temperature, and heated to 70 ° C ~ 80 ° C reaction 1h, TLC detected no raw material points. The reaction solution was cooled to 0 ° C, hydrochloric acid (5%) was added dropwise, the pH of the system was adjusted to 5-6, the yellow solid was precipitated, stirred for 30 min, filtered, and washed with water until neutral, to obtain a yellowish solid, dried. 30 ml of ethyl acetate was dissolved at room temperature, 0.5 g of activated carbon was added, and the mixture was heated to 50 ° C for 1 hour, and the activated carbon was filtered, and the filtrate was passed through a column (silica gel 5 g), and concentrated to dryness to give a white solid 4.7 g (yield: 89.2%). |
With potassium hydroxide In isopropyl alcohol Heating; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With boron tribromide In dichloromethane at 20℃; Cooling with ice; | |
80% | With aluminium(III) iodide In acetonitrile for 5h; Heating; | |
67% | With iodine; aluminium In acetonitrile at 20℃; for 4h; Reflux; |
With boron tribromide In dichloromethane at -78 - 20℃; for 16h; | 4.4.2 Stage 4.2 Stage 4.2 (0253) (0254) 1.0 M 18 dichloromethane solution of 39 boron tribromide (48.78 ml, 48.78 mmol) is added dropwise to a solution of 37 4′-methoxy-biphenyl-4-carbonitrile (10.00 g, 47.79 mmol) in 50 ml dry dichloromethane at -78° C. The reaction mixture is allowed to reach ambient temperature and is stirred for 16 hours. The reaction mixture is cooled to 0° C. and quenched by adding 50 ml 19 water. The organic phase is separated from the aqueous phase, dried over magnesium sulphate and evaporated. Purification by column chromatography on silica gel dichloromethane:ethyl acetate (8:2 ratio) yields pure 40 4′-hydroxy-biphenyl-4-carbonitrile) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 3h; | |
83% | With potassium carbonate; butanone; potassium iodide for 24h; Heating; | |
69% | With potassium hydroxide In ethanol for 20h; Heating; |
68% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h; | General procedure: In a 100mL 3-necked flask, 4′-hydroxy-[1, 1′-biphenyl]-4-carbonitrile (1) (5.00g, 25.61mmol), 3-bromoprop-1-ene (2a) (3.72g, 30.74mmol), K2CO3 (7.43g, 53.79mmol), and N, N-dimethylformamide (DMF) (50mL) were added in turn. Following this, the reaction mixture was stirred for 12hat 60°C, and then poured into DCM. The organic layer was washed with water. After removing the solvent, the crude product obtained was purified through column chromatography (DCM/PE=1/3, v/v; where PE is petroleum ether, boiling range: 60-90°C) to give white crystals (5.08g, 84% yield). |
58% | With potassium hydroxide In tetrahydrofuran; water for 48h; Ambient temperature; | |
With potassium carbonate; potassium iodide In butanone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In acetonitrile at 85℃; for 20h; | 32 A mixture of 4'-cyano-4-hydroxybiphenyl (4.0 g, 20.5 mmol), MeCN (30 ml), ethyl 4- bromobutyrate (3.75 ml, 5.11 g, 26.2 mmol), and K2CO3 (3.86 g, 27.9 mmol) was stirred at 85 0C. After 20 h water (150 ml) was added, and the product was extracted with AcOEt. The combined extracts were washed with brine, dried over MgSO4, and concentrated, to yield 6.91 g (100%) of 4-(4'-cyanobiphenyl-4-yloxy)butyric acid ethyl ester as an oil. |
55% | With caesium carbonate In tetrahydrofuran; dichloromethane at 20℃; for 16h; | Synthesis of 4-[4-(4-Cyanophenyl)phenoxy]ethylbuterate [13] To a solution of 4-(4-cyanophenyl)phenol (1.01 g, 5.1 mmol) in 20 mL THF/2 mL DCM was added CsCO3 (4.0g, 12.3 mmol) Ethyl bromobuterate (0.89 mL, 6.1 mmol) was added dropwise to the suspension and the reaction stirred sixteen hours at RT. The solvent was removed in vacuo, and the residue partitioned between Et2O and pH 7 buffer. The aqueous phase was discarded and the organic phase dried with brine and over NaSO4 prior to removing the solvent in vacuo. The residue was recrystallized from EtOAc/hexane to yield 0.86g 13 (55% yield). 1H NMR (300 MHz CDCl3) 1.29, (t, 3H), 2.14 (t, J = 6.9 H, 2H, z), 2.53 (t, J=7.2 Hz, 2H), 4.07 (t, J=6 Hz, 2H), 4.16 (q, J=7.2 Hz, 2H), 6.99 (d, J=8.7, 2H), 7.53 (d, J=9 Hz, 2H), 7.618-7.705 (m, 4H) ppm. 13C NMR 14.2, 24.5, 30.7, 60.5, 66.7, 110.1, 115.0, 119.1, 127.1, 128.3, 131.5, 132.5, 145.2, 159.4, 173.1 ppm. |
With tetra-(n-butyl)ammonium iodide; potassium carbonate In butanone Heating; |
3.30 g | With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; | |
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.84% | With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 24h; | As it is shown in the following schemes 1, 4-cyano-4'-hydroxy-biphenyl (4-cyano-4'-hydroxybiphenyl, 4.105 g, 21.05 mmol) and ethyl 6-bromo-hexanoate (ethyl-6-bromohexanoate, 4.9 g, 21.96 mmol) and Anhydrous calcium carbonate (anhydrouspotassiumcarbonate,K2CO3,2.91g,21.05The mmol)RefinedN, N- dimethyl methane amide (N, N-dimethylmethanamide, is added to 30 mL).And refluxed at 90 for 24 hours.After the reaction, remove all the solvent,Ethyl acetate (ethyl acetate, EA) to melt and wash with distilled water.The organic layer is MgSO4Dried with.Recrystallized with ethanolThe filter then forward (yield: 67.84%, 4.81 g).We confirmed the 2-ethyl hexanoate acid ester of the (4-cyano-4'-by-phenoxy) prepared by NMR, the results 1[0121]The it exhibited.1H NMR (CDCl3): delta =1.18-1.21 (t; 3H), 2.45 (m; 2H), 1.63-1.64 (m; 2H), 1.74-1.76 (m; 2H) 2.25-2.29 (t;[0122]2H), 3.92-4.07 (t; 2H), 4.05-4.07 (t; 2H), 6.89-6.92 (d; 2H), 7.44-7.46 (d; 2H), 7.57-7.60 (d; 4H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium <i>tert</i>-butylate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; | |
48% | With potassium <i>tert</i>-butylate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 16h; | Synthesis of 3-[4-(4-Cyanophenyl)phenoxy]propionic acid [12] To a solution of 3.30g 4-cyano-4’-hydroxybiphenyl (16.9 mmol) in 75mL of THF and 10mL DMF was added potassium tert-butoxide (2.4g, 20mmol). Neat β-propiolactone (1.30mL, 18.6 mmol) was added dropwise over five minutes. The resulting suspension was stirred 16 h at RT and reduced in volume in vacuo. The residue was resuspended in 50mL of EtOAc and extracted twice with 40mL 5% sodium bicarbonate with 5% NaCl. The aqueous phases were combined and acidified to approximately pH 2. A white precipitate formed ad was collected by filtration and dried to constant weight to give 3-[4-(4-cyanophenyl)phenoxy)propionic acid (1.98g, 48% yield) as a beige powder. 1H NMR (300 MHz DMSO) δ 12.35 (broad s, 1H), 7.84 (s, 4H), 7.68 (s, 2H), 7.05 (d, J=6.6 Hz, 2H), 4.22 (broad s, 2H), 2.71 (broad s, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 72h; | 5-(4’-Cyano-biphenyl-4-yloxy)-pentanoic acid methyl ester [14] To a suspension in dry DMF (10 mL) of 4’-hydroxy-4-biphenylcarbonitrile (0.976 g, 5.0 mmol) and Cs2CO3 (1.95 g, 6.0 mmol) was added methyl 5-bromovalerate (1.17 g, 6.0 mmol), and the reaction mixture was stirred for 72 h at ambient temperature. The reaction mixture was diluted with Et2O (50 mL) and extracted with pH 7 buffer (50 mL). The organic layer was washed with brine (2 × 50 mL), dried over Na2SO4, filtered and then concentrated in vacuo to afford 14 as white solid (1.6 g, >95%). 1HNMR (300 MHz, CDCl3) δ 7.71-7.62 (c, 4H), 7.53 (d, J= 8.8 Hz, 2H), 6.98 (d, J= 9.1 Hz, 2H), 4.03 (t, J= 5.8 Hz, 2H), 3.68 (s, 3H), 2.42 (t, J= 7.1 Hz, 2H), 1.89-1.80 (m, 4H) ppm |
1.49 g | With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With sodium carbonate at 65 - 70℃; for 10h; Stage #2: With tetrabutylammomium bromide In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #3: 1,2-Epoxy-3-bromopropane In N,N-dimethyl-formamide at 70 - 80℃; for 7h; | 4 Example 4: Synthesis of 4'-cyanobiphenyl glycidyl ether 1, according to the synthesis route shown in the figure, first prepared intermediate 4'-cyanophenol sodium 97.5 g (0.5 mol) of 4'-cyano-p-biphenol and 42.4 g (0.4 mol) of sodium carbonate were respectively charged into a 100 ml single-necked round bottom flask equipped with a reflux condenser, and the mixture was heated to 65-70 ° C with stirring to react for 10 hours. Cool to room temperature, take the upper liquid for the second reaction. 2. Prepare 4'-cyanobiphenyl glycidyl ether by the synthetic route as shown in the figure A 250 ml three-necked flask equipped with a reflux condenser and a constant pressure dropping funnel was charged with the crude product solution of sodium 4'-cyano-p-diphenyloxide which was the intermediate of the previous step reaction, 50.0 ml of N, N-dimethylformamide and 48.3 g (0.3 mol%) of tetrabutylammonium bromide and stirred at room temperature for 30 minutes. Take 82.2g (0.6mol) of epibromohydrin through a constant pressure dropping funnel was added dropwise to a stirred three-necked flask. After the addition was completed, the temperature was raised to 70-80 ° C and reacted for 7 hours. Cooled to room temperature, a small amount of solid at the bottom, the product was suction filtered, liquid separation (organic layer), anhydrous sodium sulfate overnight, suction filtration, distillation under reduced pressure to distill off the solvent and unreacted raw materials, the final biphenyl glycidol Ether 112.1g, yield: 89.3%. |
With potassium carbonate In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
81% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 0.5h; | |
71% | With potassium carbonate In acetone at 70℃; for 12h; Inert atmosphere; |
64% | With potassium carbonate In acetone at 60℃; for 12h; | 3 Example 3 31 mmol of p-cyanobiphenol, 58 mmol of 1,4-dibromobutane and 35 mmol of potassium carbonate were placed in acetone and heated under reflux at 60 ° C for 12 h.Acetone was removed, chloroform and water were added to the mixture, the mixture was allowed to stand still, the chloroform in the organic phase was removed,Recrystallization from ethyl acetate and petroleum ether (8:15 by volume) afforded the intermediate.The yield of intermediate was 64% with a purity of 97% |
64% | With sodium n-propoxide Reflux; | 4.1.1 Synthesis of starting bromides (1a - 1d) General procedure: Compounds were obtained by O-alkylation of commercially available 4′-hydroxy-4-biphenylcarbonitrile (CAS19812-93-2; 10mmol, 1.95g) with a proper α,ω-dibromoalkane (10mmol) in a freshly prepared sodium 1-propanolate (10mmol Na in 15mL 1-propanol) as described previously [45]. The mixture was refluxed for 5-7h. The product was filtered off, washed with water and 2% NaOH and used without further purification. |
59% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium carbonate In acetone for 0.5h; Reflux; Schlenk technique; Stage #2: 1,4-dibromo-butane In acetone at 56℃; for 16h; Schlenk technique; | 1.S1 S1, synthetic compound f: Into a 100mL Schlenk bottle,Add cyanobiphenol (2.00g, 10.25mmol), anhydrous potassium carbonate (2.83g, 20.50mmol), replace the gas 3 times, add 30mL of acetone, and reflux for 0.5h.Add 1,4-dibromobutane (3.32g, 15.38mmol), stir at 56°C for 16h, then stop heating and cooling.It was quenched by adding 100 mL of water, and extracted three times with ethyl acetate for separation, the organic phase was dried over anhydrous Na2SO4 and concentrated.The crude product was separated and purified with petroleum ether/ethyl acetate=10:1 (V/V) as the eluent to obtain white solid compound f (2.00 g, 6.05 mmol, yield 59%). |
With caesium carbonate; potassium iodide In butanone | ||
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate | ||
With 18-crown-6 ether; potassium carbonate In acetone at 60℃; for 72h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With caesium carbonate In N,N-dimethyl-formamide for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In propan-2-one at 50℃; for 48h; Inert atmosphere; | |
91% | With potassium carbonate In N,N-dimethyl-formamide for 6h; Reflux; | |
90% | With potassium carbonate; potassium iodide In butanone for 24h; Reflux; |
86% | With potassium carbonate In propan-2-one at 60℃; for 24h; | |
86% | With potassium carbonate; potassium iodide In propan-2-one for 24h; Inert atmosphere; Reflux; | 1 Preparation of 4 '- (6-bromohexyloxy) -biphenyl-4-carbonitrile (1) In a 250 mL three-necked flask,Cyanobiphenol (5.0 g, 25.6 mmol) was added in turn,1,6-dibromohexane (31.0 g, 128.0 mmol)Potassium carbonate (17.7 g, 128.0 mmol) andPotassium iodide (127 mg, 0.8 mmol)In 200 mL of acetone solution,Vacuum nitrogen protection, reflux reaction 24hThe mixture was cooled to room temperature and the reaction was adjusted to pH 7 with dilute HCl. The acetone was distilled off and then extracted with CH2Cl2 (3 x 20 mL).The extract was washed with water (3 x 20 mL), dried over anhydrous magnesium sulfate, column separated (PE),To give 8.2 g of the colorless transparent solid (yield: 86.0%). |
86% | With potassium carbonate; potassium iodide In propan-2-one at 80℃; for 8h; | 2 2.2.2. Synthesis of 4-(hexyloxybromide)-4′-cyanobiphenyl To a mixture of 4-(4-hydroxyphenyl) benzonitrile, dibromohexane, K2CO3 and KI in acetone heat to 80 °C,the mixture was stirred for 8 h. The reaction solvent was precipitated into ice water, and was filtered and washed repeatedly with deionized water. The crude products were purified by column chromatography on silica gel using CH2Cl2 as eluents to give a white powder. 1H NMR (δ, ppm, CDCl3): 7.87-7.81 (dd, 4H, pH-H), 7.70-7.67 (d, 2H, pH-H), 7.05-7.03 (d, 2H, pH-H), 4.02-3.99 (m, 2H, -CH2-), 3.54-3.51 (m, 2H, -CH2-), 1.83-1.80 (m, 2H, -CH2-), 1.74-1.71 (m, 2H, -CH2-), 1.45-1.43 (m, 4H, -CH2-). Mass Spectrometry (MS) (m/z) [M] Calcd for C19H20BrNO, 357.07; [M + H] found 358, yield: 86%. |
81% | With potassium carbonate; potassium iodide In butanone Heating; | |
81% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
80% | With Cs2CO3 In 1-methyl-pyrrolidin-2-one for 0.0166667h; microwave irradiation; | |
79% | With potassium carbonate; potassium iodide In butanone for 24h; Reflux; Inert atmosphere; | |
75% | With potassium carbonate In propan-2-one at 70℃; for 12h; Inert atmosphere; | |
70% | With potassium carbonate In butanone Reflux; | |
70% | With 18-crown-6 ether; potassium carbonate In propan-2-one at 60℃; for 72h; Inert atmosphere; | |
66% | Stage #1: 4-hydroxy-4′-cyanobiphenyl With potassium carbonate In propan-2-one for 0.5h; Reflux; Schlenk technique; Stage #2: 1 ,6-dibromohexane In propan-2-one at 56℃; for 16h; Schlenk technique; | 2.S1 S1, synthetic compound h: To a 100mL Schlenk bottle, add cyanobiphenol (2.00g, 10.25mmol), anhydrous potassium carbonate (2.83g, 20.50mmol), replace the gas 3 times, add 30mL acetone, and reflux for 0.5h.1,6-Dibromohexane (3.72g, 15.38mmol) was added dropwise, after stirring at 56°C for 16 hours, the heating and cooling were stopped, 100 mL of water was added to quench, and after three extractions with ethyl acetate for separation,The organic phase was dried with anhydrous Na2SO4 and concentrated. The crude product was separated and purified with petroleum ether/ethyl acetate=10:1 (V/V) as the eluent to obtain a white solid compound h (2.42 g, 6.765 mmol, 66% yield). |
63.9% | With potassium carbonate In propan-2-one at 60℃; for 12h; | 1 Example 1 31 mmol of cyanobiphenol, 58 mmol of 1,6-dibromohexane and 35 mmol of potassium carbonate were placed in acetone and heated under reflux at 60 ° C for 12 h to remove acetone. Chloroform and water were added to the mixture,The mixture was allowed to stand still, the chloroform in the organic phase was removed, and the residue was recrystallized from ethyl acetate and petroleum ether (8:15 by volume) to obtain an intermediate.The yield of intermediate was 63.9% with a purity of 96% |
62% | With potassium carbonate In propan-2-one at 56℃; for 18h; | |
54% | With potassium carbonate In DMF (N,N-dimethyl-formamide) at 100℃; for 5h; | 1.1-1 40 g of 4- (4-hydroxyphenyl) benzonitrile, 42 g of potassium carbonate, and 250 g of 1,6- dibromohexane were mixed. The resultant mixture was then caused to react in dimethylformamide at 100°C for 5 hours. After cooled, the resultant was poured into 1 L of water and extracted with chloroform. The resultant was purified by silica gel column chromatography, and then recrystallized from chloroform/hexane, to give the target compound (yielded amount 39 g, and yield 54%). |
53% | With sodium n-propanolate Reflux; | 4.1.1 Synthesis of starting bromides (1a - 1d) General procedure: Compounds were obtained by O-alkylation of commercially available 4′-hydroxy-4-biphenylcarbonitrile (CAS19812-93-2; 10mmol, 1.95g) with a proper α,ω-dibromoalkane (10mmol) in a freshly prepared sodium 1-propanolate (10mmol Na in 15mL 1-propanol) as described previously [45]. The mixture was refluxed for 5-7h. The product was filtered off, washed with water and 2% NaOH and used without further purification. |
41% | With potassium carbonate In propan-2-one for 24h; Inert atmosphere; Reflux; | |
With Cs2CO3; potassium iodide In butanone | ||
With potassium carbonate In ether-dichloromethane; propan-2-one | 1 1a - Formation of 4'-(6-bromohexyloxy)-4-cyanobiphenyl 1a - Formation of 4'-(6-bromohexyloxy)-4-cyanobiphenyl A mixture of 4'-hydroxy-4-cyanobiphenyl (7.8 g, 40 mmol), potassium carbonate (8.3 g, 60 mmol), 1,6-dibromohexane (29.8 g, 120 mmol), and acetone (80 mL) was heated to reflux for 6 hours under a nitrogen atmosphere. The acetone was concentrated and the residue dissolved in ether-dichloromethane (4:1,400 mL). The solution was filtered through glass fiber. The filtrate was washed with water and brine, dried over magnesium sulfate, and concentrated. Excess 1,6-dibromohexane was removed by Kugelrohr distillation up to 75°C at 0.1 mm Hg. The material remaining in the pot was recrystallized from ethanol (100 mL), filtered while hot, and cooled in the freezer to give crystals of the bromide (9.6 g, 67 %): mp 65.5-66°C, mesophase at 63°C in cooling; NMR (CDC13) 7.55(s, 4H), 7.49(d, 2H), 6.82(d, 2H), 3.91(t, 2H), 2.0-1.3(m, 8H); IR (CH2C12) 2222, 1602 cm-1. | |
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate | ||
With potassium carbonate In cyclohexanone at 70℃; for 10h; | ||
With potassium carbonate In propan-2-one | ||
With potassium carbonate In butanone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide; In methanol; | 4'-hydroxy-3'-iodo [1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0 C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25% Clorox, 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53%). MS (DCI) m/z 339[M+NH4+]+. |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide; In methanol; | EXAMPLE 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0 C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25% Clorox, 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53%). MS (DCI) m/z 339[M+NH4+]+. |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide; In methanol; | Example 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0 C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25% Clorox, 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53%). MS (DCI) m/z 339[M+NH4+]+; |
53% | With sodium hydroxide; sodium hypochlorite; sodium iodide; In methanol; | Example 1A 4'-hydroxy-3'-iodo[1,1'-biphenyl]-4-carbonitrile To a solution of 4-hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol), sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) in methanol (90 mL) at 0 C. was added an aqueous solution of sodium hypochlorite (47 mL of 5.25% Clorox, 2.29 g, 30.8 mmol) over 45 minutes. The mixture was stirred cold for 1 hour, warmed to ambient temperature and diluted with sodium thiosulfate solution (10 mL), water (80 mL) and adjusted to a pH of 7 by addition of sodium dihydrogen phosphate. The mixture was extracted with dichloromethane (2*90 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give a white powder. The solid was crystallized from dichloroethane/hexane and chromatographed on silica with dichloromethane to give the titled compound (5.19 g, 53%). MS (DCI) m/z 339[M+NH4+]+; |
With N-iodo-succinimide; sulfuric acid; In water; acetic acid; at 20 - 30℃; for 1.0h; | 4'-Hydroxy-1,1'-biphenyl-4-carbonitrile (2.15 kg, 10.90 mol), purchased from Takeda Chemical Industries, Tokyo, Japan, and N-iodosuccinimide (2.4 kg, 97% pure, 10.36 mmol) were combined in acetic acid (17.2 L) at room temperature under nitrogen.The suspension was treated with sulfuric acid (290 ML) slowly maintaining the temperature below 27 C. The reaction was stirred at room temperature and the reaction progress was monitored by HPLC. The reaction mixture was treated with distilled water (35 L) while maintaining the temperature below 30 C. After stirring at room temperature for 1 hour, the solid was filtered and the filter cake was washed with distilled water (32 L) to afford a solid.The solid was dried under reduced pressure at 60 C. for 48 hours to provide the title compound. MS (ESI-) (M-H)-320; 1H-NMR (DMSO-d6) delta10.75 (1H, s), 8.05 (1H, d, J=2.3 Hz), 7.83 (2H, m), 7.80 (2H, m), 7.62 (1H, dd, J=6.1, 8.5 Hz), 7.00 (1H, d, J=8.5 Hz); 13C-NMR (DMSO-d6) delta156.84, 142.55, 136.63, 132.27, 130.52, 127.91, 126.36, 118.54, 114.96, 108.89, 85.32. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate In N,N-dimethyl-formamide at 160℃; for 5h; | |
93% | With potassium carbonate In acetone at 56℃; | |
84% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h; | In a 100mL 3-necked flask, 4′-hydroxy-[1, 1′-biphenyl]-4-carbonitrile (1) (5.00g, 25.61mmol), 3-bromoprop-1-ene (2a) (3.72g, 30.74mmol), K2CO3 (7.43g, 53.79mmol), and N, N-dimethylformamide (DMF) (50mL) were added in turn. Following this, the reaction mixture was stirred for 12hat 60°C, and then poured into DCM. The organic layer was washed with water. After removing the solvent, the crude product obtained was purified through column chromatography (DCM/PE=1/3, v/v; where PE is petroleum ether, boiling range: 60-90°C) to give white crystals (5.08g, 84% yield). 1H NMR (400MHz, CDCl3, TMS): δ (ppm) 7.68 (d, J=8.8Hz, 2H, phenyl-H), 7.62 (d, J=8.9Hz, 2H, phenyl-H), 7.52 (d, J=9.1Hz, 2H, phenyl-H), 7.00 (d, J=9.0Hz, 2H, phenyl-H), 6.10-6.02 (m, 1H, CH2=CH), 5.44 (d, J=17.3Hz, 1H, CH2=CH), 5.31 (d, J=11.1Hz, 1H, CH2=CH), 4.58 (dt, J=5.4, 1.6Hz, 2H, OCH2). 13C NMR (100MHz, CDCl3, TMS) δ (ppm) 159.25, 145.19, 132.97, 132.57, 131.65, 128.35, 127.12, 119.09, 117.94, 115.37, 110.16, 68.92. GC-MS (EI, m/z) calcd. for (C16H13NO): 235.1. Found: 235.2 (M+, 100%), 220.1 (12%), 194.1 (65%), 166.1 (47%), 140.1 (29%). IR (KBr, pellet, cm-1): 3108, 2898, 2223, 1606, 1495, 1245, 1174, 826, 530. |
80% | With potassium hydroxide In isopropyl alcohol for 5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate In acetone at 64℃; for 48h; | 3 9.8 g (50.0 mmol) of 4-cyano-4'-hydroxybiphenol, 7.0 g (50.0 mmol) of 3-bromo-1-propanol, 13.8 g (100 mmol) of potassium carbonate and 150 ml of acetone were added to a 500 ml round bottom flask equipped with a condenser to provide a mixture, followed by reaction at 64°C for 48 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid was mixed with 140 ml of water, to which 100 ml of diethyl ether was added for extraction. The extraction was repeated three times. Anhydrous magnesium sulfate was added to the separated organic phase for drying and the solvent was distilled off under reduced pressure after filtration to obtain a yellow solid. This solid was purified by recrystallization with a mixed solvent of hexane/ethyl acetate = 2/1 to obtain 8.7 g of a white solid. This solid was subjected to measurement of NMR with the results shown below. From the results, it was confirmed that the white solid was made of an intermediate compound (A2) (yield: 70%). 1H-NMR(CDCl3) δ: 2.09(m, 2H), 3.90(t, 2H), 4.20(t, 2H), 6.99(d, 2H), 7.52(d, 2H), 7.66(m, 4H). |
70% | With potassium carbonate In acetone at 64℃; for 48h; | 3 [Synthesis Example 3]; Synthesis of polymerizable liquid crystal compound (E1); [Show Image] In a 500-mL pear-shaped flask fitted with a condenser, 4-cyano-4'-hydroxybiphenol (9.8 g, 50.0 mmol), 3-bromo-1-propanol (7.0 g, 50.0 mmol), potassium carbonate (13.8 g, 100 mmol) and acetone (150 mL) were placed and combined into a mixture. The mixture was subjected to a reaction at 64°C for 48 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain yellow wet solid. Subsequently, the solid and water (140 mL) were mixed. Diethyl ether (100 mL) was added, followed by extraction. The extraction was conducted three times. An organic layer was separated, to which anhydrous magnesium sulfate was added to dry the same. Subsequent to filtration, the solvent was distilled off under reduced pressure to obtain yellow solid. Using a 2/1 mixed solvent of hexane and ethyl acetate, the solid was purified by recrystallization to obtain white solid (8.7 g). The results of a measurement of the solid by NMR are shown below. From the results, the white solid was confirmed to be the intermediate compound (A2) (yield: 70%). 1H-NMR(CDCl3 δ: 2.09(m,2H), 3.90(t,2H), 4.20(t,2H), 6.99(d,2H), 7.52(d,2H), 7.66(m,4H). |
70% | With potassium carbonate In acetone at 64℃; for 48h; | 1.A1 Synthetic Example 1 Synthesis of polymerizable liquid crystal compound (E1) [Show Image] 9.8 g (50.0 mmol) of 4-cyano-4'-hydroxybiphenyl, 7.0 g (50.0 mmol) of 3-bromo-1-propanol, 13. 8 g of potassium carbonate (100 mmol) and 150 ml of acetone were added to a 500-ml round-bottomed flask equipped with a condenser tube to provide a mixture, followed by reaction under agitation at 64°C for 48 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid and 140 ml of water were mixed together, to which 100 ml of diethyl ether was added for extraction. The extraction was repeated three times. The separated organic phase was dried by addition of anhydrous magnesium sulfate and filtered, followed by distilling off the solvent under reduced pressure to obtain a yellow solid. This solid was purified by re-crystallization from a mixed solvent of hexane/ethyl acetate = 2/1 to obtain 8.7 g of a white solid. The results of NMR measurement of the solid are indicated below. From the results, it was confirmed that this white solid was an intermediate compound (A1) (yield: 70%) 1H-NMR (CDCl3) δ:2.09 (m, 2H), 3.90 (t, 2H), 4.20 (t, 2H), 6.99 (d, 2H), 7.52 (d, 2H), 7.66 (m, 4H). |
70% | With potassium carbonate In acetone at 64℃; for 48h; | 1 The cooled tube was attached to the flask 500ml eggplant, 4-cyano-4'-hydroxybiphenyl phenol 9.8g (50.0mmol), 3- bromo-1-propanol7.0g (50.0mmol), potassium carbonate 13.8g (100mmol), and to the mixture was added to 150ml of acetone and stirred for 48 hours at 64 andHe reacted. After the reaction, the solvent was distilled off under reduced pressure, to give a wet yellow solid. Then, the highMixing the material with 140ml water and extracted in diethyl ether was added to 100ml to it. Extraction is carried out three times. The organic fractionLayer the solvent was evaporated under reduced pressure after dried over anhydrous magnesium sulfate, filtered and the yellow solid obtainedAll. This solid by using a mixed solvent of hexane / ethyl acetate = 2/1, purified by recrystallization, and obtain a white solid 8.7gIt was. It shows a result measured by the solid NMR below. From this result, it was confirmed that the white solid is the intermediate compound (A1) (yield: 70%). |
With potassium carbonate In butanone Heating; | ||
2 g (28%) | With potassium hydroxide In methanol; ethanol; water; toluene | 1 4-Cyano-4'-(3-hydroxypropoxy)biphenyl EXAMPLE 1 4-Cyano-4'-(3-hydroxypropoxy)biphenyl 3-Bromo-1-propanol (5.6 g, 0.04 mol) and 4-cyano-4'-hydroxybiphenyl (6.0 g, 0.02 mol) were dissolved in ethanol (300 ml) and agitated at room temperature. To this solution was gradually dropwise added a solution of KOH (10 g) dissolved in water (20 ml), over 30 minutes, followed by stirring for 40 hours, distilling off about 200 ml of ethanol under reduced pressure, adding water (500 ml) to deposit solids, adding toluene (300 ml) to the mixture system, filtering off insoluble matter, washing the toluene solution twice with 2N-NaOH, then three times with water, drying over anhydrous sodium sulfate, distilling off toluene, and recrystallizing the resulting crystals from methanol to obtain 4-cyano-4'-(3-hydroxypropoxy)biphenyl. Yield: 2 g (28%). C-N: 109.0°-110.7° C. N-I: 113.6° C. |
With potassium carbonate In acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In acetonitrile at 82℃; for 17h; | 3 4'-Cyanobiphenyl-4-yloxy)hexadecanoic acid methyl ester: A mixture of 16-bromohexadecanoic acid methyl ester (4.86 g, 13.9 mmol), MeCN (20 ml), 4-cyano-4'-hydroxybiphenyl (3.16 g, 16.2 mmol), and K2CO3 (2.45 g, 17.7 mmol) was stirred at 82 0C. After 17 h satd aquous NaHCO3 (150 ml) was added, and the product was filtered, washed with water, and recrystallized from boiling MeCN (approx 80 ml). Filtration and drying under reduced pressure yielded 5.40 g (84%) of (4'-cyanobiphenyl-4- yloxy)hexadecanoic acid methyl ester colorless needles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium hydroxide In ethanol; water at 120℃; for 24h; | |
With sulfuric acid; acetic acid | ||
With sulfuric acid In 1,2-dimethoxyethane Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2,6-di-tert-butyl-4-methyl-phenol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-(dimethylamino)pyridinium tosylate In dichloromethane for 3h; | |
With dicyclohexyl-carbodiimide In dichloromethane | 5 [Reference Example 5 (synthesis of acrylic compound 5)]; In accordance with Scheme 5 below, an acrylic compound 5 was synthesized. [Show Image] | |
With dmap; 2,6-di-tert-butyl-4-methyl-phenol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h; | 1 Reference Example 1 In accordance with Scheme 7 below, acrylic compounds (wherein m = 1) and (wherein m = 3) having no oxetanyl group (acrylic compounds 7 and 8)were synthesized. The 1H-NMR spectrum of each the acrylic compounds 7 and 8 is shown in Fig. 7 and 8. |
5.78 g | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 24h; Inert atmosphere; | |
62% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h; | General procedure: In a 100mL 3-necked flask, 4′-hydroxy-[1, 1′-biphenyl]-4-carbonitrile (1) (5.00g, 25.61mmol), 3-bromoprop-1-ene (2a) (3.72g, 30.74mmol), K2CO3 (7.43g, 53.79mmol), and N, N-dimethylformamide (DMF) (50mL) were added in turn. Following this, the reaction mixture was stirred for 12hat 60°C, and then poured into DCM. The organic layer was washed with water. After removing the solvent, the crude product obtained was purified through column chromatography (DCM/PE=1/3, v/v; where PE is petroleum ether, boiling range: 60-90°C) to give white crystals (5.08g, 84% yield). |
60% | With potassium hydroxide In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; | PART A -- Preparation of 4-[2-(2-ethoxyethoxy)ethoxy]-4'-cyanobiphenyl . To 0.975 g (five millimoles) of 4-hydroxy-4'-cyanobiphenyl dissolved with 1.08 g (5.5 millimoles) of 1-bromo 2-(2-ethoxyethoxy)ethane in 25 ml. of acetonitrile, 1.4 g (ten millimoles) of finely ground potassium carbonate were added. The reaction mixture was refluxed overnight. Thin layer chromatographic analysis indicated total conversion. The reaction mixture was cooled and filtered and the product was washed with acetonitrile and evaporated to a white solid. The product was recrystallized from isopropanol and dried in vacuo to two grams (93% yield) of a compound having the following formula structure: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate In acetone at 20℃; for 23h; | 6.1 [0114] Example 6: Synthesis of N-[3 -BROMO-4 -(LH-TETRAAZOL-5-YLMETHOXY)-1, 1 - biphenyl-4-yl] METHYL}-2-BUTYL-N-METHYL-1-BENZOFURAN-3-CARBOXAMIDE.; [0115] Step 1 : 4 -METHOXY-1, 1'-biphenyl-4-carbonitrile. A mixture of 4'-hydroxy- 1, 1 -BIPHENYL-4-CARBONITRILE (L. Olg, 5. 18 mmol), iodomethane (484 L, 7.77 mmol) and potassium carbonate (2.15g, 15.53 mmol) in 25 mL of acetone was stirred under nitrogen at room temperature for 23 h. The acetone was removed under reduced pressure and the residue partitioned between methylene chloride and water. The organic layer was separated, dried (MGS04) and the solvent removed under reduced pressure to give 996 mg of a light tan solid. Recrystallization of the solid from isopropyl alcohol gave 4 -METHOXY-1, 1'-biphenyl-4- CARBONITRILE (735 mg, 68%) as a light tan solid, mp 99-102°C. Elemental Analysis for CI4HNNOCALC D : C, 80.36 ; H, 5.30 ; N, 6.69. Found: C, 78.98 ; H, 5. 10 ; N, 6.25. |
65% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium <i>tert</i>-butylate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: methyl iodide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 16h; | 4-methoxy-4-cyano-1-1-biphenyl [5] To a solution of 1.25g 1-1-biphenyyl-4-cyano-4-hydroxyl in 3.8mL DMF and 28mL THF was added 7.0mL of 1M potassium tertbutoxide in THF. The solution was stirred for five minutes at RT. 0.4mL Iodomethane was added dropowise and the mixture stirred 16 h at room temperature. The mixure was purified using 60% EtOAc/40% hexane. Fractions containing the compound were dried in vacuo and recrystallized from EtOAc/Hexane. 0.85g product was obtained (65% yield). 1HNMR (300mHz, CDCl3) δ 7.83, (d, J=7.2 Hz, 2H) 7.84 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H) 7.05 (d, J=8.4Hz, 2H), 3.78 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With sodium hydroxide; sodium iodide; In methanol; | EXAMPLE 169A 4'-hydroxy-3'-iodo-1,1'-biphenyl-4-carbonitrile 4'-Hydroxy-1,1'-biphenyl-4-carbonitrile (25.0 g, 128 mmol), purchased commercially, NaI (19.19 g, 128 mmol), and sodium hydroxide (5.12g, 128 mmol) were combined in methanol (500 mL) at 0 C. and treated with bleach (5.25%, 181.0 g) dropwise over 1 hour. After stirring at 0 C. for 1 hour, the mixture was treated with 10% aqueous sodium thiosulfate (250 mL). The mixture was adjusted to pH 6.8 with 10% aqueous HCl and then the mixture was filtered. The filter cake was crystallized from hot CH2Cl2/hexane to provide the title compound (40% yield). 1H-NMR (300 MHz, CDCl3) delta 5.40 (s, 1H), 7.10 (m, 1H), 7.50 (m, 1H), 7.60 (m, 2H), 7.77(m, 2H), 7.90 (m, 1H); MS (CDI) m/z 339 (M+NH4)+. |
40% | With sodium hydroxide; sodium iodide; In methanol; | EXAMPLE 169A 4'-hydroxy-3'-iodo-1,1'-biphenyl-4-carbonitrile 4'-Hydroxy-1,1'-biphenyl-4-carbonitrile (25.0 g, 128 mmol), purchased commercially, NaI (19.19 g, 128 mmol), and sodium hydroxide (5.12g, 128 mmol) were combined in methanol (500 mL) at 0 C. and treated with bleach (5.25%, 181.0 g) dropwise over 1 hour. After stirring at 0 C. for 1 hour, the mixture was treated with 10% aqueous sodium thiosulfate (250 mL). The mixture was adjusted to pH 6.8 with 10% aqueous HCl and then the mixture was filtered. The filter cake was crystallized from hot CH2Cl2/hexane to provide the title compound (40% yield). 1H-NMR (300 MHz, CDCl3) delta5.40 (s, 1H), 7.10 (m, 1H), 7.50 (m, 1H), 7.60 (m, 2H), 7.77(m, 2H), 7.90 (m, 1H); MS (CDI) m/z 339 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With pyridine; hydrogenchloride; | EXAMPLE 4 Preparation of 4-cyano-4'-hydroxybiphenyl 1 g of p-(4-methoxyphenyl)benzonitrile and 3 g of pyridium chloride are introduced under nitrogen into a 50 ml two-necked flask. The mixture is heated at 200 C. for 6 hours then it is left to cool down. 5 ml of pyridine and 5 ml of 1 N hydrochloric acid are poured in at 110 C. The reaction mixture is extracted with chloroform at ambient temperature. The organic phases are collected and washed with water, (2*30 ml), dried over anhydrous magnesium sulphate and concentrated under vacuum. After recrystallization from an ethyl acetate/heptane mixture, the sought product is obtained (yield: 50%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
594 mg (52%) | With diethylazodicarboxylate | 1.5 Synthesis of Alkoxycyanobiphenyls. 4'-(cis-9, cis-12-Octadecadienyloxy)-4-cyanobiphenyl (w372). To a suspension of 4'-hydroxy-4-biphenylcarbonitrile (500 mg, 2.56 mmol), alcohol 26c (681 mg, 2.56 mmol), and TPP (1.008 g, 3.84 mmol) in 25 ml anhydrous ether was added DEAD (669 mg, 3.84 mmol) via syringe with stirring and under argon. The reaction mixture was stirred overnight under argon at 25° C. The crude product was purified via flash chromatography over silica gel with elutions of 98/2 and 95/5 (v/v) (Hex/EtOAc), respectively. Evaporation of solvent yielded 594 mg (52%) of a white liquid crystal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
765 mg (67%) | With diethylazodicarboxylate | 1.5 Synthesis of Alkoxycyanobiphenyls. 4'-(cis-9-Octadecenyloxy)-4-cyanobiphenyl (W396). To a suspension of 4'-hydroxy-4-biphenylcarbonitrile (500 mg, 2.56 mmol), alcohol 26b (686 mg, 2.56 mmol), and TPP (840 mg, 3.20 mmol) in 25 ml anhydrous ether was added DEAD (557 mg, 3.20 mmol) via syringe with stirring and under argon. The reaction mixture was stirred overnight under argon 25° C. The crude product was purified via flash chromatography over silica gel with elutions of 98/2, 95/5, and 90/10 (v/v) (Hex/EtOAc), respectively. Evaporation of solvent yielded 765 mg (67%) of a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | 8a Preparation of the phenolic ligand[0087] Under an atmosphere of nitrogen, 4-bromophenol (5.30 g, 3.08x10'2 mol), A- CN-1 -phenyl boronic acid (4.986 g, 3.39x10'2 mol), KF (5.91 g, 1.02x10"1 mol), Pd2(dba)3 (0.141 g, 1.54x10'4 mol) were mixed in THF (100 ml_). After a few minutes of stirring a THF (1OmL) solution of P(1Bu)3 (0.062 g, 3.08x10'4 mol). The resulting mixture was stirred at room temperature for 48 hours. Dilution of this solution with 200 mL of Et2O followed by filtration through a silica plug and evaporation of the volatiles yielded a dark brown thick oil. Upon addition of hexane to this oil, a light brown powder formed, which was further purified by column chromatography (1 :5 EtOAc/hexane) to give a white powder. Yield = 3.3 g (55%). The 1H NMR (in CD2CI2) spectrum of phenol 8a is shown below. | |
General procedure: A reaction mixture of (4-cyanophenyl)boronic acid 5 (150 mg,1.02 mmol, 1.0 equiv.), 4-bromo-2-chloro-6-methylphenol 6s (271 mg,1.22 mmol, 1.2 equiv.) and potassium carbonate (353 mg, 2.55 mmol,2.5 equiv.) in PEG400/H20 (4 mL/4 mL) was stirred at room temperaturefor 15 min, and then PdCl2 (1.8 mg, 0.01 mmol, 0.01 equiv.) wasadded to it. Stirring was continued for an additional 15 h until completeconsumption of starting material as judged by TLC. Then the reactionmixture was poured into water (20 mL) and extracted with ethyl acetate(10 mL * 4). The organic layers were washed with brine, dried overanhydrous Na2SO4, filtered and condensed. The residue was then purifiedvia flash chromatography on silica gel, eluting with EtOAc/petroleumethe to 7s as white solid in 54% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pyridine; benzene; | EXAMPLE 9 Preparation of 4'-cyano-4-biphenylyl n-pentyl carbonate 0.976 G. of 4'-cyano-4-hydroxy-biphenyl are dissolved in 10 ml. of absolute pyridine and reacted with 0.90 g. of <strong>[638-41-5]chloroformic acid n-pentyl ester</strong> as in Example 1. The 1.5 g. of yellow, partially crystallized oil obtained according to the procedure described in Example 1 is dissolved in benzene and chromatographed on 90 g. of silica gel. Benzene elutes 1.479 g. of colorless crystals which are recrystallized from ether-hexane up to constant melting point and clearing point. The pure 4'-cyano-4-biphenylyl n-pentyl carbonate obtained melts at 50.1-51.0 and has a clearing point of 61.1. UV (EtOH): epsilon270 = 26,800. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With hydrogenchloride; iron(III) chloride;copper(I) chloride; In N-methyl-acetamide; | PART C Preparation of 4-cyano-4'-hydroxybiphenyl A reaction mixture of 23.3 parts of <strong>[29558-77-8]4-bromo-4'-hydroxybiphenyl</strong>, 11.2 parts of cuprous chloride and 60 parts by volume of dimethylformamide was charged to a vessel equipped with a magnetic stirrer and a reflux condenser with a drying tube. The mixture was refluxed for 24 hours and poured over 500 parts of an aqueous solution containing 50 parts by volume of concentrated hydrochloric acid and 50 parts of ferric chloride. The mixture was stirred at about 60C. for 2 hours, cooled to room temperature and extracted three times with 300 parts by volume portions of ether. The combined ether extracts were washed three times with 500 parts of water, dried over anhydrous sodium sulfate and the solvent evaporated. The product was recyrstallized from 200 parts by volume of a 2:1:1 mixture of acetone-hexane-chloroform. Ten parts (51 percent yield) of 4-cyano-4'-hydroxybiphenyl were obtained having a melting point of 193-195C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.5% | With potassium carbonate In acetone at 65℃; for 12h; | 2 Example 2 31 mmol of p-cyanobiphenol, 58 mmol of 1,5-dibromopentane and 35 mmol of potassium carbonate were placed in acetone and heated under reflux for 12 h at 65 ° C.Acetone was removed, chloroform and water were added to the mixture, the mixture was allowed to stand still, the chloroform in the organic phase was removed,Recrystallization from ethyl acetate and petroleum ether (8:15 by volume) afforded the intermediate.The yield of the intermediate was 70%, the purity was 96.5% |
83% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
75% | With potassium carbonate In N,N-dimethyl-formamide for 0.0333333h; Microwave irradiation; |
68.2% | With potassium carbonate In acetone for 24h; Reflux; | |
65% | With potassium carbonate In N,N-dimethyl-formamide for 0.0333333h; Microwave irradiation; | |
64% | With sodium n-propoxide Reflux; | 4.1.1 Synthesis of starting bromides (1a - 1d) General procedure: Compounds were obtained by O-alkylation of commercially available 4′-hydroxy-4-biphenylcarbonitrile (CAS19812-93-2; 10mmol, 1.95g) with a proper α,ω-dibromoalkane (10mmol) in a freshly prepared sodium 1-propanolate (10mmol Na in 15mL 1-propanol) as described previously [45]. The mixture was refluxed for 5-7h. The product was filtered off, washed with water and 2% NaOH and used without further purification. |
1 1e - Formation of 4'-(5-bromopentyloxy)-4-cyanobiphenyl 1e - Formation of 4'-(5-bromopentyloxy)-4-cyanobiphenyl Treatment of 4'-hydroxy-4-cyanobiphenyl with 1,5-dibromopentane as described above gave crystals of the bromide. | ||
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate; potassium iodide In butanone for 24h; Reflux; | |
80% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
76% | With potassium carbonate; potassium iodide In butanone for 24h; Reflux; Inert atmosphere; |
75% | With potassium carbonate In butanone for 72h; Molecular sieve; Inert atmosphere; Reflux; | Compound 1b was obtained following the reaction of 4-hydroxybiphenyl-40-carbonitrile (3.4 g, 17.43 mmol) and excess of thecorresponding 1,8-dibromoctane (8 ml, 49.18 mmol) in the presenceof K2CO3 (8 g, 58 mmol) and molecular sieves (3 g) in butanone(150 ml). The resulting mixture was heated under reflux forthree days under inert atmosphere (nitrogen) and the progress ofreaction being monitored by TLC. After 72 h, the insoluble compoundswere filtered off and the solvent removed on a rotary evaporator.The product obtained was washed with methanol andpurified on a silica gel column using dichloromethane as eluant.The product was isolated as white solid.1b. 1H NMR (500 MHz, CDCl3): 7.70-7.63 (m, 4H), 7.53 (d,J = 8.7 Hz, 2H), 6.99 (d, J = 8.7 Hz, 2H), 4.01 (t, J = 6.5 Hz, 2H),3.41 (t, J = 6.8 Hz, 2H), 1.95 - 1.74 (m, 4H), 1.53 - 1.30 (m, 8H).13C NMR (126 MHz, CDCl3): 159.76, 145.27, 132.55, 131.28,128.32, 127.06, 119.10, 115.07, 110.04, 68.07, 33.96, 32.75, 29.15,28.66, 28.07, 25.93. Yield 75%. |
69% | 1 1b - Formation of 4'-(8-bromooctyloxy)-4-cyanobiphenyl 1b - Formation of 4'-(8-bromooctyloxy)-4-cyanobiphenyl Treatment of 4'-hydroxy-4-cyanobiphenyl with 1,8-dibromooctane as described above gave crystals of the bromide (10.9 g, 69 %): mp 79-80°C; NMR (CDCl3) 7.55(s, 4H), 7.50(d, 2H), 6.85(d, 2H), 3.9(t, 2H), 3.35(t. 2H), 1.9-1.3(m, 12H). | |
68% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium carbonate In acetone for 0.5h; Reflux; Schlenk technique; Stage #2: 1,8-dibromooctane In acetone at 56℃; for 16h; Schlenk technique; | 3.S1 S1, synthetic compound j: To a 100mL Schlenk bottle, add cyanobiphenol (2.00g, 10.25mmol) and anhydrous potassium carbonate (2.83g, 20.50mmol), replace the gas 3 times, add 30mL of acetone, reflux for 0.5h, then add 1, 8 -Dibromooctane (4.15g, 15.38mmol), stirred at 56°C for 16h, then stopped heating and cooling, quenched by adding 100mL water, and extracted three times with ethyl acetate for separation, the organic phase was dried with anhydrous Na2SO4 and concentrated. The crude product was separated and purified with petroleum ether/ethyl acetate=10:1 (V/V) as the eluent to obtain white solid compound j (2.68 g, 6.97 mmol, 68% yield). |
51% | With potassium carbonate In cyclohexanone at 70℃; for 10h; | |
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate | ||
With potassium carbonate In acetone for 19h; Inert atmosphere; Reflux; | ||
With 18-crown-6 ether; potassium carbonate In acetone at 60℃; for 72h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
49% | With 18-crown-6 ether; potassium carbonate In acetonitrile for 12h; Reflux; | |
With potassium carbonate In N,N-dimethyl-formamide |
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate | ||
With potassium carbonate In cyclohexanone at 70℃; for 10h; | ||
Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium carbonate In acetone for 1h; Reflux; Stage #2: 1,7-dibromoheptane In acetone at 20℃; for 20h; Reflux; | 1.1.1 Stage 1.1 4-Cyano-4′-hydroxybiphenyl (20.0 g, 102.45 mmol) is added into a flask containing 300 mL acetone. Then potassium carbonate (29.74 g, 215.15 mmol) is added. The mixture is heated to gentle reflux for one hour before being cooled to ambient temperature (also called room temperature), which is 20° C. in this application, unless explicitly specified otherwise. Then it is added dropwise to a flask containing 1,7-dibromoheptane (100 mL, 593.04 mmol). After the addition is completed, the flask is heated to gentle reflux for 20 hours. The reaction mixture is cooled to room temperature and the solid material is separated by filtration in vacuo. The filter pad is washed with acetone (100 mL). The filtrate is concentrated in vacuo before a portion of petroleum ether 40-60° C. (50 mL) is added. The solid formed is separated by filtration in vacuo and purified by column chromatography over silica gel, eluted with 10% ethyl acetate in petroleum ether 40-60° C. The pure product is obtained as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In acetone at 60℃; for 24h; | |
80% | With potassium carbonate In acetone at 135℃; for 24h; | |
With potassium carbonate In N,N-dimethyl-formamide |
With potassium carbonate In butanone for 48h; Reflux; | ||
With potassium carbonate In acetone for 19h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In butanone Reflux; | |
72% | With potassium carbonate; potassium iodide In butanone for 12h; Reflux; | |
70% | With potassium carbonate In butanone Reflux; |
57% | With sodium n-propoxide Reflux; | 4.1.1 Synthesis of starting bromides (1a - 1d) General procedure: Compounds were obtained by O-alkylation of commercially available 4′-hydroxy-4-biphenylcarbonitrile (CAS19812-93-2; 10mmol, 1.95g) with a proper α,ω-dibromoalkane (10mmol) in a freshly prepared sodium 1-propanolate (10mmol Na in 15mL 1-propanol) as described previously [45]. The mixture was refluxed for 5-7h. The product was filtered off, washed with water and 2% NaOH and used without further purification. |
56% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With sodium n-propoxide at 20℃; for 0.0833333h; Stage #2: 1,3-dibromo-propane at 60℃; for 6h; | 1.1. General synthetic procedure for compounds 1a-1k General procedure: A solution of freshly prepared sodium 1-propanolate, proper substituted phenols were addedand stirred in room temperature for 5 min. 1,3-dibromopropane was then added drop wisely inthe time of 1 h. The reaction mixture was stirred in 60 °C for 3 h, and then refluxed for another3 h. After cooling down to RT mixture was filtrated and evaporated. To a rough product, 100ml of 10% NaOH was added and left overnight in cold. To a resulting white oil CH2Cl2 wasadded, mixed and layers were then separated. Organic layer was dried over sodium sulphatefiltered and evaporated. Rough product was used for further reactions after purification. |
With potassium carbonate In N,N-dimethyl-formamide | ||
With potassium carbonate In butanone for 48h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 72h; Inert atmosphere; | |
80% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 3h; | |
71% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran Inert atmosphere; |
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In dimethyl sulfoxide at 57℃; for 22h; | 2.a 4'-(2-(Benzoylthio)ethoxy)[1 ,1 '-biphenyl]-4-carbonithle (3).; 4'-Hydroxy[1 ,1 '- biphenyl]-4-carbonitrile (5.1 g, 0.025 mol), 2-chloroethyl-p-toluenesulfonate (1 , 9.2 g, 0.039 mol), and potassium carbonate (5.3 g, 0.038 mol) were stirred at 57 °C in 100 ml_ dimethyl sulfoxide (DMSO) for 22 hrs, resulting in quantitative conversion to 2 (verified by NMR analysis). Potassium chloride (2.1 g, 0.028 mol) was added to the reaction mixture, which was stirred 3 hrs at 85 °C to convert the excess 1 into dichloroethane. The reaction mixture was poured into a 1 L separatory funnel containing 300 ml_ water and extracted with 200 ml_ of 2-butanone (MEK). The aqueous phase was extracted with another 300 ml_ MEK, and the organic extracts were combined and washed 3 times with 300 ml_ water. Finally, solvent and dichloroethane were evaporated under reduced pressure at 80 °C to give 2 (6.4 g, 0.025 mol, 100% yield) as a brown-orange syrup which solidifies upon cooling. To the previous product in 100 ml_ N,N-dimethylformamide (DMF) in a 250 ml_ RBF were added thiobenzoic acid (7.3 g, 0.050 mol) and potassium bicarbonate (6.8 g, 0.068 mol), and the mixture was stirred at r.t. until CO2 effervescence ceased, then at 45 °C for 4 hrs. The reaction mixture was transferred to a 1 L separatory funnel containing 250 ml_ water, extracted with 400 ml_ ethyl acetate, and the organic phase was washed twice with 250 ml_ water before solvent removal under reduced pressure. The crude product was purified by dissolving in 300 ml_ ethanol at 9O°C (under slight pressure), and allowing to recrystallize by slowly cooling to r.t., then by letting stand overnight at 4° C. Filtration of the crystals and removal of solvent under reduced pressure gave analytically pure 3 as ultra-fine, pale brown needles (7.9 g, 0.022 mol, 88% overall yield in 2 steps). 1H NMR: δ = 8.02-7.96 (m, 2 aromatic H ortho to COS), 7.72-7.43 (m, 3 aromatic H meta and para to COS, 4 aromatic H ortho and meta to CN, and 2 aromatic H meta to OCH2), 7.05 (d, 2 aromatic H ortho to OCH2, J = 8.7 Hz), 4.25 (t, OCH2, J = 6.6 Hz), 3.50 (t, SCH2, J = 6.6 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium phosphate In dimethyl sulfoxide at 110℃; for 12h; | 2.c 4'-(2-(2-(Benzoylthio)ethoxy)ethoxy) [1 ,1 '-biphenyl]-4-carbonithle (6). 4'- Hydroxy[1 ,1 '-biphenyl]-4-carbonithle (4.9 g, 0.024 mol), 2-(2-chloroethoxy)ethanol (12.7 g, 0.101 mol) and potassium phosphate thbasic (K3PO4.xH2O, 22 g at ~ 25 %wt water, 0.078 mol) were stirred at 110 °C in 150 ml_ DMSO for 12 hrs, resulting in quantitative conversion to 4 (verified by NMR analysis). The reaction mixture was poured into a 1 L separatory funnel containing 200 ml_ chloroform and washed 5 times with 400 ml_ water to remove all of the chloroalcohol. The resultant organic phase was dried with MgSO4, filtered, and the solvent was removed under reduced pressure at 60 °C to afford analytically pure 4 (6.5 g, 0.023 mol, 96% yield) as a pale yellow-orange syrup which solidifies upon cooling. To this product in 100 ml_ DCM at 0 °C were added p-toluenesulfonyl chloride (22.2 g, 0.115 mol) and pyridine (7.2 g, 0.091 mol), after which the reaction vessel was allowed warm up to and left to stir at r.t. for 24 hrs. The reaction mixture was transferred to a 500 ml_ separatory funnel, washed twice with 150 ml_ water + 25 ml_ pyridine, and again with 150 ml_ water and 40 ml_ 36%wt aq. HCI (discarding the aqueous phase after each wash). The organic phase was again dried with MgSO4, filtered, and the solvent was removed under reduced pressure at 40 °C to yield analytically pure 5 (9.5 g, 0.022 mol, 95% yield), which was finally reacted to generate 6 as follows. To 1.96 g (4.5 mmol) of the said product in 40 ml_ DMF were added thiobenzoic acid (0.69 g, 4.7 mmol, 1.05 equiv.) and potassium bicarbonate (1.O g, 10 mmol), and the mixture was stirred at r.t. until CO2 effervescence ceased, then at 40 °C for 12 hrs. The reaction mixture was transferred to a 500 ml_ separatory funnel containing 200 ml_ water, extracted with 100 ml_ ethyl acetate, and the organic phase was washed three additional times with 200 ml_ water, dried with MgSO4, and gravity filtered before solvent removal at 80 °C under reduced pressure to give analytically pure 6 as an orange syrup which crystallizes upon cooling (1.80 g, 4.5 mmol, 91 % overall yield in 3 steps). 1H NMR: δ = 8.00-7.93 (m, 2 aromatic H ortho to COS), 7.72-7.39 (m, 3 aromatic H meta and para to COS, 4 aromatic H ortho and meta to CN, and 2 aromatic H meta to OCH2), 7.02 (d, 2 aromatic H ortho to OCH2, J = 8.7 Hz), 4.19 (t, ArOCH2, J = 4.8 Hz), 3.90 (t, ArOCH2CH2, J = 4.8 Hz), 3.79 (t, SCH2CH2, J = 6.5 Hz), 3.33 (t, SCH2CH2 , J = 6.5 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With dicyclohexyl-carbodiimide In dichloromethane at 20℃; | 3 Synthesis of polymerizable liquid crystal compound (Z3) 0.6 g (2.0 mmol) of the compound (Z1) obtained in Example 1, 0.4 g (2.0 mmol) of 4-cyano-4'-hydroxybiphenol, 0.008 g of DMAP and a small amount of BHT were suspended in 10 ml of methylene chloride under stirring at room temperature, to which a solution of 0.5 g (2.5 mmol) of DCC dissolved in 5 ml of methylene chloride was added, followed by stirring overnight. The precipitated DCC urea was separated by filtration and the resulting filtrate was successively washed each twice with 50 ml of 0.5N-HCl, 50 ml of a saturated sodium hydrogen carbonate aqueous solution and 50 ml of a saturated saline solution and dried over magnesium sulfate, after which the solvent was distilled off, followed by purification through recrystallization with ethanol to obtain 0.6 g of the intended polymerizable liquid crystal compound (Z3) (yield; 62%). 1H-NMR(CDCl3) δ: 1.56(m, 4H), 1.75(m, 2H), 1.85(m, 2H), 2.62(m, 1H), 3.10(m, 1H), 4.05(t, 2H), 4.54(m, 1H), 5.63(d, 1H), 6.24(d, 1H), 6.97(d, 2H), 7.35(d, 2H), 7.71(m, 6H), 8.15(d, 2H). It will be noted that the results of observation of the polymerizable liquid crystal compound (Z3) revealed that phase transition into a nematic phase occurred at 149°C upon temperature rise. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate In acetone at 64℃; for 24h; | 5.1 [Example 5]; Synthesis of compound (Z5); (1) Synthesis of compound (P5); [Show Image] In a 100-mL pear-shaped flask fitted with a condenser, 4-cyano-4'-hydroxybiphenol (4.7 g, 24 mmol), 2-(4-bromobutyl)-1,3-dioxolane (5.0 g, 24 mmol), potassium carbonate (6.6 g, 48 mmol) and acetone (100 mL) were placed and combined into a mixture. The mixture was subjected to a reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain yellow wet solid. The solid was dissolved in ethyl acetate (6 mL), followed by purification by silica gel column chromatography (column: "Silica Gel 60", 0.063-0.200 mm, product of Merck & Co., Inc., eluent: hexane/ethyl acetate = 2/1). From the thus-obtained solution, the solvent was distilled off to obtain white solid (7.5 g). The results of a measurement of the solid by NMR are shown below. From the results, the white solid was confirmed to be the intermediate compound (P5) shown in the above-described synthesis scheme (yield: 97%). 1H-NMR(CDCl3)δ: 1.63(m,2H), 1.73(m,2H), 1.87(m,2H), 3.86(t,2H), 3.99(m,4H), 4.91(t,1H), 7.00(d,2H), 7.51(d,2H), 7.68(m,4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 18h; | 29 4'-Hydroxy-4-biphenyl carbonitrile (329 mg, 1.68 mmol) and potassium carbonate (317 mg, 2.30 mmol) were added to a stirred solution of 1-(4-fluoro-benzoyl)-3-iodomethyl-pyrrolidine-3-carboxylic acid ethyl ester (620 mg, 1.53 mmol) (see Preparation 12) in dimethylformamide (7 mL). The reaction mixture was heated at 80° C. for 18 hours then partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was washed with water (2000 mL), dried over magnesium sulfate then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluding with 3:1->1:1 heptane:EtOAc to afford the title compound as a white solid (517 mg, 71%). The enantiomers were separated using a Chiralpak IB 55:45 heptane:IPA. Peak 1 Yield 140 mg, 96.7% ee (first eluding peak at 11.8 mins) Peak 2 Yield 132 mg, 98.8% ee (second eluding peak at 15.4 mins) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate In dimethyl sulfoxide at 80℃; for 18h; | 28a 4'-hydroxy-4-biphenyl carbonitrile (107.0 g, 549 mmol) and potassium carbonate (94.9 g, 687 mmol) were added to a stirred solution of 1-(4-methoxy-benzoyl)-3-(toluene-4-sulfonyloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester (211.3 g, 457.8 mmol) (see Preparation 11) in dimethylsulphoxide (422 mL). The reaction mixture was heated at 80° C. for 18 hours then partitioned between ethyl acetate (2000 mL) and water (2000 mL). The organic layer was washed with water (2000 mL) then separated and concentrated under reduced pressure to afford the title compound as an orange oil (207.7 g, 93%). (>99.5% e.e.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With potassium carbonate In cyclohexanone at 120℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In tetrahydrofuran at 20℃; for 12h; | 2.4. Synthesis of monomer 4-biphenyl-4-carbonitrilemethylmethacrylate (LC) 4-Hybdroxybiphenyl-4-Carbonitrile (9.36 g, 0.048 mol) wasdissolved in a mixture of TEA (5.34 g, 0.053 mol) and dry THF(100 mL). A solution of methacryloyl chloride (5.01 g, 0.048 mol) in50 mL THF was added dropwise to the obtained mixture. Afterstirring for 12 h at RT, the white solid which was removed by filtration and the solution was evaporated at reduced pressure.White crystals could be got after recrystallizing the residue in 96%ethanol. 1H NMR (400 MHz, CDCl3, δ): 7.72 (d, J 8 Hz, 2H; Ar H),7.66 (d, J 8 Hz, 2H; Ar H), 7.22 (d, J 8 Hz, 2H; Ar H), 6.38 (s, 1H,CH2), 5.79 (s, 1H, CH2), 2.07 (s, 3H, CH3). |
91.1% | With triethylamine In dichloromethane at 20℃; for 5h; | 2.4 Synthesis of probe 1 To a stirred solution of dye 2 (48.8mg, 0.25mmol) and triethylamine (10 μL) in 5mL dry dichloromethane was added methacryloyl chloride (83mg, 0.80mmol). The resulting reaction mixture was allowed to stir at room temperature for 5h and subsequently quenched with 20mL of water. The resulting solution was extracted twice with 15mL dichloromethane. After drying the mixture over anhydrous Na2SO4, the drying agent was removed by filtration and the solvent was removed by distillation. The obtained residue was purified by flash chromatography on silica gel (CH2Cl2 as eluent) to yield probe 1 (59.9mg, 91.1%). 1H NMR (600MHz, DMSO) δ 7.94 (d, J=8.5Hz, 2H), 7.91 (d, J=8.4Hz, 2H), 7.83 (d, J=8.6Hz, 2H), 7.33 (d, J=8.6Hz, 2H), 6.32 (s, 1H), 5.93 (s, 1H), 2.03 (s, 3H). 13C NMR (150MHz, DMSO) δ 165.68, 151.58, 144.22, 136.35, 135.67, 133.36, 128.80, 128.46, 128.04, 123.05, 119.32, 110.56, 18.53. HRMS (EI) m/z calcd for [C17H13NO2 + H]+: 264.1025, Found: 264.1017. |
88% | With triethylamine at 0℃; Inert atmosphere; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 1-chloro-3-(2-tetrahydropyranyloxy)propane; 4-Cyano-4'-hydroxybiphenyl With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 100℃; for 5h; Stage #2: With pyridinium p-toluenesulfonate In ethanol at 60℃; for 1h; | 4.1 (1) 2-(3-Chloropropoxy)tetrahydro-2H-pyran (11 g), potassium carbonate (11 g), and potassium iodide (4.4 g) were added to a DMF (0.10 L) solution of 4'-hydroxybiphenyl-4-carbonitrile (10 g), and the mixture was stirred for 5 hours at 100°C. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. Then, the organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered out, and the solvent was distilled off under reduced pressure. PPTS (1.3 g) was added to an ethanol (0.10 L) solution of the resulting residue, and the mixture was stirred for 1 hour at 60°C. The solvent was distilled off under reduced pressure, and the resulting residue was purified by OH type silica gel chromatography (gradient elution with hexane/ethyl acetate = 80/20 → 20/80) to obtain 4'-(3-hydroxypropoxy)biphenyl-4-carbonitrile (white solid) (12 g, 88%). MS (ESI/APCI Dual): 434 (M+H)+, 456 (M+Na)+, 432 (M-H)- 1H NMR (600 MHz, CHLOROFORM-d) δ ppm 2.09 (2 H, quin, J=6.0 Hz), 3.87 - 3.91 (2 H, m), 4.19 (2 H, t, J=6.0 Hz), 7.00 - 7.03 (2 H, m), 7.52 - 7.55 (2 H, m), 7.63 - 7.65 (2 H, m), 7.68 - 7.70 (2 H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With triethylamine; magnesium chloride In acetonitrile for 6h; Reflux; | |
55% | With triethylamine; magnesium chloride In acetonitrile for 6h; Reflux; | |
52% | With triethylamine; magnesium chloride In acetone at 70℃; for 8h; Inert atmosphere; | 1.a Example 1. Synthesis of fluorescent probe molecules (a) Under a nitrogen atmosphere, 3.1 g (16 mmol) of 4-cyanobiphenol was dissolved in 50 ml of acetonitrile, and 2.8 g (24 mmol) of anhydrous MgCl2 and 8.2 ml (60 mmol) were added thereto. Anhydrous triethylamine was added, and finally 6.1 g (220 mmol) of dry paraformaldehyde was added and reacted at 70 ° C for 8 hours. After the reaction is completed, the solution is acidified with a large amount of dilute hydrochloric acid, dichloromethane Extraction and separation on a silica gel column gave a white solid product II 1.8 g, yield 52%. |
50% | With triethylamine; magnesium chloride In acetonitrile at 70℃; for 8h; Inert atmosphere; | 1.a Example 1, the combination of probe I (A) in a nitrogen atmosphere,6.24 g (about 32 mmol) of cyanobiphenyl acid and 4.56 g (about 48 mmol) of anhydrous MgCl2 were addedThree round bottomed flask,After the addition of 16.32 mL (about 122 mml) of triethylamine,Then, 80 mL of anhydrous acetonitrile was added as a solvent, and finally 12.3 g (about 440 mmol) of dry paraformaldehyde was added.The mixture was heated to 70 ° C for 8 hours.After completion of the reaction, the mixture was cooled to room temperature and then quenched with a small amount of water. And then add a large amount of 6M hydrochloric acid for acidification.The crude product was extracted with CH2C12 (3 * 50 mL)The organic layer was dried with anhydrous MgS04,Column chromatography to give whiteCompound III3.5 g, the yield is about 50% |
50% | With triethylamine; magnesium chloride In acetonitrile at 70℃; for 5h; Inert atmosphere; | 1.a nitrogen protection,Take 6 · 24g (about 32mmol)ofCyanobiphenyl acidwith4 56 g (about 48 mmol) of anhydrous MgCl2,80 mL of anhydrous acetonitrile was added followed by 16.32 mL (ca. 122 mmol) of triethylamine and 12.3 g (about 440 mmol) of paraformaldehyde (excess).The mixture was heated at 70 ° C for 5 hours. After completion of the reaction, it was quenched with water and acidified with 6M hydrochloric acid.The crude product was extracted with CH2C12, separated, and the solvent was removed under reduced pressure. The product was isolated by column chromatography. 3.5 g of white solid III,The yield is about 50%. |
50% | With triethylamine; magnesium chloride In acetonitrile at 70℃; for 8h; Inert atmosphere; | 1 Example 1,III synthesis Under nitrogen protection, 6.24 g ofCyanobiphenol,4.56 g of anhydrous magnesium chloride, 16.32 mL of triethylamine was dissolved in 80 mL of anhydrous acetonitrile, followed by the addition of excess dry paraformaldehyde (12.3 g)The mixture was refluxed at 70 ° C for 8 hours and the reaction was cooled to room temperature,Then quenched with a small amount of water, acidified with 6M hydrochloric acid,The crude product was extracted three times with CH2Cl2,The extract was dried over anhydrous MgSO4, filtered and the solvent was removed in vacuo,Purification by column chromatography gave white solid III 3.5 g,The yield is about 50%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 10 - 40℃; for 29h; Inert atmosphere; | 1.1 Step 1: Method for Synthesizing (S)-4-cyano-4′-(6-methyl-n-octyl-1-oxy)biphenyl (abbreviation: S-PP-O8CN) Into a 200-mL three-necked flask were put 1.3 g (6.4 mmol) of 4-cyano-4′-hydroxybiphenyl and 1.7 g (6.4 mmol) of triphenylphosphine. The mixture was degassed while being stirred under reduced pressure, and the air in the flask was replaced with nitrogen. To this mixture were added 0.76 g (5.3 mmol) of (S)-6-methyl-1-octanol and 46 mL of tetrahydrofuran (THF). To this mixture was added 2.9 mL (6.4 mmol) of a toluene solution of diethyl azodicarboxylate (2.2 mol/L) in a nitrogen atmosphere at 10° C. or lower, and the mixture was stirred at room temperature for 24 hours. The obtained mixture was stirred at 40° C. for five hours. The obtained mixture was diluted with about 50 mL of diethyl ether, and washed with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer of the resulting mixture was subjected to extraction with diethyl ether. The extracted solution and the organic layer were combined, and the mixture was dried with magnesium sulfate. (0156) This mixture was separated by gravity filtration, and the obtained filtrate was concentrated to give a white oily substance. This oily substance was purified by silica gel column chromatography (developing solvent: hexane and ethyl acetate (hexane:ethyl acetate=5:1)). The obtained fraction was concentrated and subjected to vacuum drying to give a colorless oily substance. This oily substance was purified by high performance liquid column chromatography (developing solvent: chloroform). The obtained fraction was concentrated to give 0.86 g of a white solid of (S)-4-cyano-4′-(6-methyl-n-octyl-1-oxy)biphenyl, which was a target substance, in a yield of 51%. A reaction scheme of Step 1 described above is shown in (E1-1).; This compound was identified as (S)-4-cyano-4′-(6-methyl-n-octyl-1-oxy)biphenyl (abbreviation: S-PP-O8CN), which was a target substance, by nuclear magnetic resonance (NMR). (0159) 1H NMR data of the obtained substance, S-PP-O8CN, are as follows. (0160) 1H NMR (CDC3, 300 MHz): δ (ppm)=0.84-0.89 (m, 6H), 1.09-1.46 (m, 9H), 1.77-1.86 (m, 2H), 4.01 (t, 2H), 6.99 (d, 2H), 7.52 (d, 2H), 7.62-7.70 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 1h; Stage #2: nonaethyleneglycol mono(p-toluenesulfonyl) ether In tetrahydrofuran; mineral oil at 20℃; for 24h; | 1 Nonaethylene glycol mono (4'-cyano-4-biphenyl) ether (9ci) 7ci (199 mg, 1.02 mmol) was dissolved in THF (2.0 mL). This sodium hydride (mineral oil suspension, purity 60%, 49 mg, 1.23 mmol) was stirred at room temperature for 1 hour added. The stuff 5 (203 mg, 0.36 mmol) was added THF (2.0 mL) solution of was stirred at room temperature for 24 hours. The reaction solution was diluted with ethyl acetate (10 mL), water (10 mL), and the washed successively with saturated brine (10 mL). This was filtered and dried over anhydrous sodium sulfate, and concentrated in an evaporator. The obtained residue was purified by silica gel column chromatography (silica gel:. 6 g, developing solvent: ethyl acetate - methanol mixed solvent pair 0 → 45 versus 2 →. 8 versus 1 → 2: 1) was separated and purified by, 9ci (165 mg, 0.28 mmol, 78% yield) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In pentan-3-one at 110℃; for 24h; | 2 Specifically, first, Compound (C) 2.60g (3.89mmol), 4- cyano-4'-hydroxybiphenyl 0.76 g, (3.89 mmol), potassium carbonate 0.57 g (4.11 mmol), and put the 3-pentanone 50mL in 200mL eggplant flask, for 24 hours at 110 ° C, was reflux. After completion of the reaction was transferred to stand by separatory funnel to room temperature. There, the water was separated into aqueous and organic phases by addition of cyclopentyl methyl ether and brine. Then, after it allowed to stand for 30 minutes over anhydrous magnesium sulfate the organic phase, subjected to pleat folding filtered and filtrate was concentrated with an evaporator to give a solid. The obtained solid after purification by silica gel column chromatography with chloroform and recrystallized from ethanol to give compound (2) 2.19g (2.84mmol). The obtained compound (2) is a colorless powder, whose melting point is 126-128 ° C, the yield was 73.0%. Further, the infrared spectrophotometer and a nuclear magnetic resonance device were identified compound (2). The results are shown in the following. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate In pentan-3-one at 110℃; for 24h; | 4 Synthesis of compound (1-4) Specifically, first, the compound (H) 0.59g (0.97mmol), 4- cyano-4'-hydroxybiphenyl 0.19 g (0.97 mmol), potassium carbonate 0.20 g (1.45 mmol), and put the 3-pentanone 50mL in 200mL eggplant flask, it was carried out for 24 hours under reflux at 110 ° C. After completion of the reaction was transferred to stand by separatory funnel to room temperature. There, the water was separated into aqueous and organic phases by addition of cyclopentyl methyl ether and brine. Then, after it allowed to stand for 30 minutes over anhydrous magnesium sulfate the organic phase, subjected to pleat folding filtered to obtain a filtrate was concentrated with an evaporator solid. The resulting solid was purified by silica gel column chromatography with chloroform to give the compound (1-4) 0.52g (0.72mmol). The resulting compound (1-4) is a white powder, the melting point is 124-125 ° C, the yield was 74%. In addition, by infrared spectrophotometer and a nuclear magnetic resonance apparatus, they were identified compound (1-4). The results are shown in the following. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With potassium carbonate In pentan-3-one at 110℃; for 24h; | 11 Synthesis of compound (7) Specifically, first, Compound (I) 0.60g (0.85mmol), 4- cyano-4'-hydroxybiphenyl 0.17 g (0.85 mmol), potassium carbonate 0.21 g (1.52 mmol), and 3-pentanone 50mL placed in a 200mL eggplant flask, was carried out under reflux for 1 day at 110 ° C. After completion of the reaction was transferred to stand by separatory funnel to room temperature. There, the water was separated into aqueous and organic phases by addition of cyclopentyl methyl ether and brine. Then, after it allowed to stand for 30 minutes over anhydrous magnesium sulfate the organic phase, subjected to pleat folding filtered to obtain a filtrate was concentrated with an evaporator solid. The resulting solid was purified by silica gel column chromatography with chloroform to give the compound (7) 0.40g (0.48mmol). The obtained compound (7) is a white powder, the melting point is 162-163 ° C, the yield was 57%. Further, the infrared spectrophotometer and a nuclear magnetic resonance device were identified compound (7). The results are shown in the following. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.6% | With potassium carbonate In acetone at 65℃; for 48h; | 1 Synthesis of compound (1-6) Specifically, first, Compound (B) 1.8g (2.38mmol), 4- cyano-4'-hydroxybiphenyl 0.59 g (2.40 mmol), potassium carbonate 0.53 g (3.89 mmol), and put the acetone 50mL in the eggplant flask, it was carried out under reflux for 2 days at 65 ° C. After completion of the reaction was transferred to stand by separatory funnel to room temperature. There, the water was separated into aqueous and organic phases by addition of cyclopentyl methyl ether and brine. Then, after it allowed to stand for 30 minutes over anhydrous magnesium sulfate the organic phase, subjected to pleat folding filtered to obtain a filtrate was concentrated with an evaporator solid. The resulting solid was purified by silica gel column chromatography with chloroform to give the compound (1-6) 1.49g (1.99mmol). The resulting compound (1-6) is a colorless powder, whose melting point is 108-110C ° C, the yield was 83.6%. Further, the infrared spectrophotometer and a nuclear magnetic resonance device were identified compound (1-6). The results are shown in the following. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis Example 3 <strong>[1852-04-6]Undecanedioic acid</strong> 4?-cyano-biphenyl-3-yl ester 4?-cyano-biphenyl-4-yl)ester (0393) (0394) Step 3.1 (0395) <strong>[1852-04-6]Undecanedioic acid</strong> (9.971 g, (46.103 mmol), Dicyclohexylcarbodiimide (DCC) (9.512 g, 46.103 mmol) and Dimethylaminopyridine (DMAP) (5.632 g, 46.103 mmol) are suspended in chilled DCM (140 mL) in a 250 mL round bottom flask. 4?-cyanobiphenol (9.000 g, 46.103 mmol) is added over a time span of 30 minutes and the reaction mixture is stirred at room temperature for 16 h. Once the first phenol has completely reacted the product from step 2.1 of Synthesis Example 2, 3?-cyanobiphenol (9.000 g, 46.103 mmol) and another equivalent of DCC (9.512 g, 46.103 mmol) are added to the reaction mixture. The reaction mixture is once more stirred at room temperature for 16 h. After completion of the reaction reaction mixture is filtered and the filtrate is reduced in vacuo. The crude product is purified using flash chromatography in DCM. The pure product is obtained and its structure confirmed by NMR. (0396) Phase sequence: K 73.0 X 93.0 Y 107.0 I; T*(N,I)=79.0 C.; e/K=1.81 V-1. (0397) (Remarks: T*(N,I) and e/K extrapolated from 10% in host mixture H-0 with 2% of R-5011, phases X and Y to be determined.) | ||
<strong>[1852-04-6]Undecanedioic acid</strong> (9.971 g (46.103 mmol), dicyclohexylcarbodiimide (DCC) (9.512 g, 46.103 mmol) and dimethylaminopyridine (DMAP) (5.632 g, 46.103 mmol) are suspended in chilled DCM in a 250 mL round bottom flask 4'-cyanobiphenyl-4-ol (9.000 g, 46.103 mmol) is added over a period of 30 minutes and the reaction mixture is stirred for 16 hours at room temperature.The first phenol is used in the synthesis example After completely reacting with the product from step 2.1 of 4'-cyanobiphenyl-3-ol (9.000 g, 46.103 mmol) and an additional 1 equivalent of DCC (9.512 g, 46.103 mmol) were added to the reaction mixture The reaction mixture is stirred for another 16 hours at room temperature After completion of the reaction the reaction mixture is filtered and the filtrate is reduced in vacuo The crude product is purified by flash chromatography in DCM Pure product is obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; | 2.1. A general synthetic procedure for compound (3a) General procedure: A mixture of 7-trifluorocoumarin-3-carboxylic acid 1a (0.1 g,4.0 mol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride)(EDC.HCl) (0.1 g, 5.0 mol) and catalytic amount of N, Ndimethylaminopyridine(DMAP) were taken in dry dichloromethane.To this reaction mixture, 4-hydroxybiphenyl-4'-carbonitrile2a (0.76 g, 4.0 mol) was added, stirred at room temperaturefor 3h and the progress of the reaction was monitored by TLC usingdichloromethane as mobile phase. After the completion of the reaction,the reaction mass was diluted with water and extractedwith dichloromethane (2 25 mL). The organic layer was washedwith saturated brine solution and was dried over anhydrous sodium sulphate. The crude product (3a) thus obtained was purifiedby column chromatography by using dichloromethane aseluent fallowed by recrystallization by ethanol. The yield was obtained96% as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With acetic acid for 10h; Reflux; | |
71% | With trifluoroacetic acid for 4h; Reflux; | 1 Synthesis of 3'-formyl-4'-hydroxy-4-cyanobiphenyl According to the literature (A cyanobiphenylcontaining fluorescence "turn on" sensor for Al3+ion in CH3CN-water, Onder Alici, et al, "Sensors and Actuators B: Chemical", Volume 208, pages 159-163) reported method for synthesis: 4'-hydroxy-4-bibenzonitrile (0.5g, 2.56mmol) and hexamethylenetetramine (HMTA, 2.15g, 15.36mmol) was refluxed in a solution of trifluoroacetic acid (40mL) for 4h. After completion, the reaction mixture was cooled to room temperature and 1.0M HCl (100 mL) was added, the resulting mixture was extracted with dichloromethane (100 mL), the organic layer was washed 3 times with water and once with saturated brine, and then dried over magnesium sulfate. After filtration, the solvent was removed to obtain 3'-formyl-4'-hydroxy-4-bibenzonitrile (40.59 mg, 71%) as a yellow solid. |
46.2% | In trifluoroacetic acid at 80℃; for 5h; | 3′-Formyl-4′-hydroxy-[1,1′-biphenyl]-4-carbonitrile (Compound 2). The procedure was performed according to the reported literatures[5,49]. A solution of 4′-Hydroxy-4-biphenylcarbonitrile (0.5 g,2.56 mmol) and HMTA (1.8 g, 12.84 mmol) in TFA (20 mL) was heatedat 80 °C for 5 h. Upon completion, the reaction mixture was cooled toroom temperature and added 80 mL HCl (1.2 M). Then the mixed solution was extracted with dichloromethane (3 × 30 mL). The organiclayers were combined, washed with water and saturated brine once,dried over sodium sulfate, and then evaporated to generate crude solid.The crude product was purified by flash chromatography (silica gel) togive the desired product as a white solid. (Eluents: Petro ether/ ethylacetate, v/v = 1:1), Yield: 0.26 g, 46.2%. mp 137-139 °C; 1H NMR(DMSO-d6, 400 MHz) δ = 11.05 (s, 1H), 10.33 (s, 1H), 8.03 (d,J = 2.5 Hz, 1H), 7.96 (dd, J1 = 8.7 Hz, J2 = 2.6 Hz, 1H), 7.92 (q,J = 8.7 Hz, 4H), 7.15 (d, J = 8.7 Hz, 1H). 13C NMR (DMSO-d6,100 MHz) δ = 191.1, 161.2, 143.4, 134.8, 132.9, 129.4, 127.4, 126.9,122.7, 118.9, 118.2, 109.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd. forC14H10NO2, 227.0712; found, 227.0714. |
With trifluoroacetic acid | ||
With trifluoroacetic acid at 120℃; for 8h; | 3.S2 Preparation of 3-formyl-4-hydroxybiphenyl cyanide 1.5 g of p-cyanobiphenol and 6.45 g of hexamethylene tetramine were dissolved in 80 mL of trifluoroacetic acid and refluxed in a round bottom flask at 120 ° C for 8 h. After the reaction, The reaction solution was cooled to room temperature, Acidified by addition of 1.0 M HCl (100 mL) Then extracted with dichloromethane. The organic layer was collected and washed three times with water and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed under reduced pressure to give 3-formyl-4-hydroxybiphenyl cyanide. | |
With trifluoroacetic acid at 100℃; for 4h; | 1.2 S2. Preparation of 3-formyl-4-hydroxydiphenyl cyanide: 0.39 g (2 mmol) p-cyanodiphenolUsed with 1.41g (10mmol) Urotropine30 mL of trifluoroacetic acid is completely dissolved and placed in a round bottom flask.Heat in a 100°C oil bath and stir at reflux for 4 h.After the reaction is complete, the system is cooled to room temperature.100 mL of 1.0 M dilute HCl was added to the system for acidification.The product was then extracted with dichloromethane and the dichloromethane phase was collected and washed three times with distilled water.After drying over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to give 3-formyl-4-hydroxydiphenyl cyanide. | |
With trifluoroacetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: heptanedioic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Stage #2: 4-Cyano-4'-hydroxybiphenyl In dichloromethane at 20℃; for 16h; | 4.4.3 Stage 4.3 Stage 4.3 (0255) (0256) 42 Heptanedioic acid (5.00 g, 31.22 mmol), 16 dicyclohexylcarbodiimide (6.44 g, 31.22 mmol) and 17 dimethylaminopyridine (381.16 mg, 3.12 mmol) are charged to a flask containing 18 dichloromethane (50 ml) at ambient temperature. The mixture is stirred for 30 min, then 40 4′-hydroxy-biphenyl-4-carbonitrile (6.09 g, 31.22 mmol) is added and stirred at ambient temperature for 16 hours. 19 Water (20 ml) is added, the organic phase is separated, dried over magnesium sulphate and evaporated. Purification by column chromatography on silica gel dichloromethane:ethyl acetate (6:4) yields 43 heptanedioic acid mono-(4′-cyano-biphenyl-4-yl) ester |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | This embodiment is for the diamine monomer, diamine monomer of the chemical name is 4, 6 - diamino - 2 - cyano biphenyl pyrimidine, structural formula is:The diamine monomer is obtained through the following steps:A, synthesis of 1 - bromo - 6 - (4 - cyano biphenyl - 4 '- oxygen) hexane: to the provided with a magneton, thermometer and condenser is sequentially added in three-mouth flask 4 - cyano - 4' - dihydroxybiphenyl (4.0132g, 20 . 5mmol), 1, 6 - two hexyl bromides (40.8135g, 169 . 1mmol), anhydrous potassium carbonate (7.1723g, 50 . 9mmol), a catalytic amount of potassium iodide and 140 ml acetone, under the protection of nitrogen and stirred to back flow. The acetone turns on lathe does, adding the ethyl acetate to re-dissolved, filtering, the filtrate is rotary evaporated most of the solvent, then adding an appropriate amount of petroleum ether, produce a large amount of precipitation, filtering and collecting, vacuum drying, the crude product is recrystallized in ethanol;Second, synthetic containing cyano biphenyl structure diamine: to join with magneton flask in the 4, 6 - diamino - 2 - mercapto-pyrimidine (1.4218g, 10mmol), the 40 ml methanol dissolved in 42 ml 0 . 25M in the sodium hydroxide solution, stirring at room temperature for 2 hours to obtain mercapto sodium salt, after the reaction is complete, vacuum distillation, vacuum drying overnight, the dry mercapto sodium salt is dissolved in 60 ml of N, N - dimethyl formamide (DMF) in the, adding step one of the obtained 1 - bromo - 6 - (4 - cyano biphenyl - 4' - oxygen) hexane (3.9271g, 11mmol), stirring at the room temperature 18h. The reaction is complete after the ethyl acetate extract, then the anhydrous magnesium sulfate drying overnight, filtering, and steaming and to remove the solvent, the obtained crude product is further purified with silica gel column chromatography separation, finally containing cyano biphenyl diamine monomer structure, its nuclear magnetism hydrogen spectrum characterization see Figure 1.This embodiment in the steps of a synthesis of 1 - bromo - 6 - (4 - cyano biphenyl - 4' - oxygen) hexane is a white solid, yield can reach 85%; this embodiment for the diamine monomer containing cyano biphenyl aromatic diamine monomer structure, white solid, yield is 91%, is a very good synthetic polyimide material, diamine monomer of the infrared spectrogram see Figure 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With triethylamine In tetrahydrofuran at 0℃; for 4h; | 1 2.2.1. Synthesis of (4′-cyanobiphenyl-4-oxy) acrylate (M0ACB) To a mixture of 4-hydroxy-4′-cyanobiphenyl and triethylamine inTHF, cooled to 0 °C, was added dropwise acryloyl chloride. The solventwas stirred for 4 h. The reaction solvent was precipitated into ice water,and was filtered and washed repeatedly with deionized water. The resultingsolid was dried to obtain products as a white solid. 1H NMR (δ,ppm, CDCl3):7.74-7.66 (dd, 4H, pH-H), 7.60 (d, 2H, pH-H), 7.36 (d,2H, pH-H), 6.66-6.62 (m, 1H, =CH2), 6.32-6.38 (m, 1H, =CH-),6.07-6.04 (m, 1H, =CH2). Mass Spectrometry (MS) (m/z) [M] Calcd forC16H11NO2, 249.08; [M+H] found 250, yield: 98%. |
96.91% | With triethylamine In tetrahydrofuran at 0℃; for 4h; | 2.2.1. Synthesis of (4′-cyanobiphenyl-4-oxy) acrylate (M0ACB) 4-Hydroxy-4′-cyanobiphenyl (10.0 g, 51.2 mmol), triethylamine(20.0 g, 76.9 mmol) were dissolved in 200 mL THF which was cooled to0 °C. Acroleyl chloride was dripped into the reaction bottle. The mixturewas stirred for 4 h. After the completion of the reaction, the reactionmixture was then poured into a large amount of deionized water. Theprecipitate was purified by filtration. The resulting solid was dried toobtain products as a white solid. H NMR (δ, ppm, CDCl3):7.74-7.66 (dd,4H, pH-H), 7.62 (d, 2H, pH-H), 7.34(d, 2H, pH-H), 6.65-6.61(m, 1H,=CH2), 6.31-6.37(m, 1H, =CH-), 6.05-6.03(m, 1H, =CH2). MassSpectrometry (MS) (m/z) [M] Calcd for C16H11NO2, 249.08; [M+H]found 250. Yield: 96.91%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With fluorosulfonyl fluoride; triethylamine In dichloromethane at 20℃; | 4.1. Procedure for the synthesis of aryl fluorosulfates (1-37) General procedure: In a 50 mL three-necked flask equipped with a stirring bar, phenol(2 mmol, 1.0 equiv) and Et3N (1.2 equiv) were dissolved in 10 mLCH2Cl2. SO2F2 was introduced by bubbling through the solution. Thereaction was monitored by TLC. After 4-12 h at room temperature beforeconcentrating under vacuum. The crude product was purified bysilica gel chromatography by gradient elution with 5-20% EtOAc/Petroleum ether to give pure product (1-37). |
With fluorosulfonyl fluoride; triethylamine In ethanol; water at 25℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 12h; Stage #2: 3-(3-chloroquinoxalin-2-yl)propionic acid ethyl ester In N,N-dimethyl-formamide Reflux; | 30 Process for preparing ethyl 3-(3-((4'-cyano-[1,1'-diphenyl]-4-yl)oxy)quinoxalin-2-yl)propanoate (code XQH-1 -89) 4'-Hydroxy-[1,1'-diphenyl]-4-carbonitrile (0.31 g, 2.5 mmol)And potassium carbonate (0.39 g, 2.5 mmol) was dissolved in DMF,Reflow at 85 ° C for 12 hours,Further ethyl ethyl 3-(3-chloroquinoxalin-2-yl)propanoate (0.59 g,2.23mmol), continue the reflux reaction until TLC monitoring the raw materials have no remaining,The reaction was quenched by the addition of ice water and extracted three times with ethyl acetate (3×15 ml).Separated and purified by column chromatography, PE/EA=40:1 (v:v),A white solid target of 0.453 g was obtained in a yield of 48%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 4-Cyano-4'-hydroxybiphenyl With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 12h; Stage #2: ethyl 3-(3,7-dichloroquinoxalin-2-yl)propanoate In N,N-dimethyl-formamide Reflux; | 34 Preparation of ethyl 3-(7-chloro-3-((4'-cyano-[1,1'-diphenyl]-4-yl)oxy)quinoxalin-2-yl)propanoate ( Code name XQH-2-45s) 4'-Hydroxy-[1,1'-diphenyl]-4-carbonitrile (0.31 g, 2.5 mmol)And potassium carbonate (0.39 g, 2.5 mmol) was dissolved in DMF,Reflow at 85 ° C for 12 hours,Additional ethyl 3-(3,7-dichloroquinoxalin-2-yl)propanoate (0.667 g, 2.23 mmol),Continue the reflux reaction until the TLC monitoring material has no residue, add ice water to quench the reaction,Ethyl acetate extraction three times (3 × 15ml), separation and purification by column chromatography,PE/EA = 40:1 (v: v), obtained as a white solid object, 0.562 g, yield 55%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | General procedure: To a stirred solution ofPhenols (45-2) (1.0 eq) in THF (5.0 mL) was added Sodiumhydride (60% dispersion in mineral oil) (2.0 eq) and the reaction mixture was stirred at roomtemperature for 15 minutes. Then to the solution was added <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (1-2)15 (1.0 eq) and the reaction was continued at room temperature for 3 hours. The reaction mixture wasdiluted with ethyl acetate, washed with water, brine solution and the organic fraction was driedover anhydrous sodium sulfate. It was then evaporated under reduced pressure. Crude mass waspurified by column chromatography (silica, gradient) to afford the analogs. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h; | General procedure: In a 100mL 3-necked flask, 4′-hydroxy-[1, 1′-biphenyl]-4-carbonitrile (1) (5.00g, 25.61mmol), 3-bromoprop-1-ene (2a) (3.72g, 30.74mmol), K2CO3 (7.43g, 53.79mmol), and N, N-dimethylformamide (DMF) (50mL) were added in turn. Following this, the reaction mixture was stirred for 12hat 60°C, and then poured into DCM. The organic layer was washed with water. After removing the solvent, the crude product obtained was purified through column chromatography (DCM/PE=1/3, v/v; where PE is petroleum ether, boiling range: 60-90°C) to give white crystals (5.08g, 84% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; | 1.4 (4) Synthesis of TPPP-NO2 To a 50 mL single-necked flask, 25 mL of N, N-dimethylformamide, 0.527 g (0.5 mmol) of Compound C were sequentially added,0.293 g (1.5 mmol) of 4'-hydroxybiphenyl-4-carbonitrile, 0.207 g (1.5 mmol) of anhydrous potassium carbonate.The reaction was stirred at 80 ° C. for 12 h. After the reaction was completed, 50 mL of deionized water was added.Then, the mixture was extracted with 30 mL of dichloromethane, and the extraction was repeated three times.The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phases were spin-dried to obtain a crude product. The crude product was separated by column chromatography to obtain 0.468 g of the product TPPP-NO2 with a yield of 73%. |
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 70℃; for 3h;Inert atmosphere; | BPN-OH (58.6 mg, 0.30 mmol), 2-(4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (128.2 mg, 0.6 mmol), KI (8 mg) and K2CO3(82.9 mg, 0.6 mmol) were dissolved in a solution ofDMF (7mL). The resultingmixture was stirred at 70 C under argon atmospherefor 3 h. The reactionmixturewas poured in 15mL water andextracted with dichloromethane three times (8 mL × 3). The organiclayerswere collected and dried over anhydrous sodium sulfate. The solventwasremoved under vacuumand the residue was purified by silicagel column chromatography (eluent: dichloromethane) to afford probeBPN-TOB (yield 73%). 1H NMR (600 MHz, DMSO-d6) delta 7.88 (d, J =8.3 Hz, 2H), 7.84 (d, J = 8.2 Hz, 2H), 7.75-7.67 (m, 4H), 7.48 (d, J =7.6 Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 5.23 (s, 2H), 1.29 (s, 12H). 13CNMR (150 MHz, DMSO-d6) delta 159.33, 144.66, 140.81, 135.07, 133.26,131.18, 128.33, 127.37, 127.26, 119.47, 116.00, 109.66, 84.16, 69.55,25.15. HRMS (EI) m/z calcd for [C26H26BNO3 + Na]+: 434.1903,Found: 434.1898. |
Tags: 19812-93-2 synthesis path| 19812-93-2 SDS| 19812-93-2 COA| 19812-93-2 purity| 19812-93-2 application| 19812-93-2 NMR| 19812-93-2 COA| 19812-93-2 structure
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P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
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 |
Sorry,this product has been discontinued.
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