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CAS No. : | 629-41-4 | MDL No. : | MFCD00002989 |
Formula : | C8H18O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OEIJHBUUFURJLI-UHFFFAOYSA-N |
M.W : | 146.23 | Pubchem ID : | 69420 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 42.89 |
TPSA : | 40.46 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.22 cm/s |
Log Po/w (iLOGP) : | 2.11 |
Log Po/w (XLOGP3) : | 1.37 |
Log Po/w (WLOGP) : | 1.31 |
Log Po/w (MLOGP) : | 1.29 |
Log Po/w (SILICOS-IT) : | 1.62 |
Consensus Log Po/w : | 1.54 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.15 |
Solubility : | 10.4 mg/ml ; 0.0712 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.82 |
Solubility : | 2.2 mg/ml ; 0.015 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.95 |
Solubility : | 1.66 mg/ml ; 0.0113 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.48 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P337+P313 | UN#: | N/A |
Hazard Statements: | H319 | 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 |
---|---|---|
82% | With dihydrogen peroxide; sodium hydroxide In water at 79.84℃; for 8 h; Schlenk technique | General procedure: All experiments to test the catalytic activity were performed in a Schlenk tube (50mL vol.) attached to a condenser. The catalytic activity was evaluated for HDO oxidation in basic aqueous media with H2O2 as oxidant to obtain HCA. In a typical reaction procedure, aliphatic diol (0.5mmol) and catalyst (25mg) were weighed and dispersed in deionized water (3.5mL) in a Schenk tube. 30percent H2O2 (0.75mL) and 0.5M NaOH (0.75mL) were added to the above mixture, and then the Schlenk tube was mounted on a preheated oil bath at 353K. The mixture was allowed to react for various time intervals with continuous magnetic stirring (500 rpm). After the reaction, a part of the resultant solution was diluted 20 times with an aqueous H2SO4 (10mM) solution, and the catalyst was filtered off using a 0.20μm filter (Milex®-LG). The obtained filtrate was analyzed by high performance liquid chromatography (HPLC, WATERS 600) using an Aminex HPX-87H column (Bio-Rad Laboratories, Inc.) attached to a refractive index detector. An aqueous 10mM H2SO4 solution (eluent) was run through the column (maintained at 323K) at a flow rate of 0.5mLmin−1. The conversion and yield(s) were determined with a calibration curve method using commercial products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With ammonia In tert-Amyl alcohol at 140℃; for 48 h; Autoclave | Example 3; Reaction of 1,8-octanediol; The reaction was carried out under the same conditions as in Example 1 using 10.0 mmol of 1,8-octanediol. Yield and conversion were determined by gas chromatography using commercially available reference compounds. Yield of linear primary diamine: 78percent, conversion of the linear diol: >99percent.; Example 1; Reaction of 1,19-nonadecanediol; 3.01 g (10.0 mmol) of 1,19-nonadecanediol and 151 mg (0.25 mol percent) of carbonylchloro[4,5-bis(diisopropylphosphinomethyl)acridine]hydridoruthenium(II) were dissolved under protective gas in 25 ml of 2-methyl-2-butanol and transferred to an autoclave provided with stirrer, heating and temperature measuring facility. 6 ml of liquid ammonia were subsequently introduced into the autoclave by means of a spindle press. The autoclave was closed and the contents stirred at 140° C. for 48 hours. This resulted in an increase in the internal pressure from 22 to 40 bar. After cooling, the contents of the reactor were filtered through kieselguhr, the filtrate was evaporated to dryness and the residue subjected to a bulb tube distillation. Yield of linear primary diamine: 2.02 g (68percent of theory; bp0.8 mbar=170-185° C.), conversion of the linear diol: >99percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen bromide In water; toluene for 8 h; Reflux | 16 g (110 mmol) of octane diol have been dissolved in 250 ml toluene. After addition of 15.5 ml of HBr (137 mmol, 1.25 eq., 48percent in water) the reaction mixture has been refluxed with a dean-stark receiver to remove the water from the reaction. After 8 hours the mixture was cooled to room temperature and was washed two times with distilled water and once with brine. After filtration over sodium sulfate and evaporation of the solvent the bromide was obtained in quantitative yield. In the NMR spectra, residual toluene was observed, which had no impact on the subsequent steps. D2o-c = 1.23 g/ml (lit: 1.22 g/ml) 13C NMR (CDC ; ppm): 62.95 (CH2OH), 34.04 (BrCH2CH2), 32.78/32.71 (BrCH2) and (CH2CH2OH), 29.23/28.73/28.09/25.65 (CH2) |
92% | With hydrogen bromide In toluene for 13.5 h; | 438 g (3 mol) of 1,8-octanediol was dissolved in 3 1 of toluene. 375 ml (3.3 mol) of aqueous 48percent HBr was then added. The medium was then heated to eliminate water that was present and water formed during the reaction by azeotropic distillation. After 13.5 h of contact, the medium was cooled and taken up with a saturated solution of NaHCO3. The organic phase was separated and washed with a saturated solution of NaCl. After drying over MgSO4, the medium was concentrated to yield a crude product of 672 g. [0057] The 8-bromooctanol was purified by distillation under reduced pressure, at 96° C. under P<1 mbar, m=575 g (92percent). [0058] Characterization [0059] TLC: Rf=0.8 (heptane/ether iso 8/2) [0060] 1H NMR (200 MHz, CDCl3): 3.65 (t, 2H, J=6.4 Hz); 3.43 (t, 2H, J=6.8 Hz); 1.87 (m, 2H); 1.36-1.69 (m, 10H). |
84.3% | With hydrogen bromide In water; toluene for 96 h; Reflux | The compound 2-1-1 (octanediol) (1.01 g, 6.91 mmol) was dissolved in 20 ml of toluene, and 40percent HBr (aq) (1.12 ml, 7.81 mmol) was added to the reaction system at room temperature, bath reflux.72h after TLC monitoring, there is still the remaining raw materials, add 40percent HBr (aq) (0.5ml, 3.49mmol), continue to return 24h.The system was cooled to room temperature, diluted with ether, saturated sodium bicarbonate solution, saturated sodium chloride solution, washed once, sodium sulfate dried about half an hour after the filter, steamed ether.The residue was purified by column chromatography on silica gel, eluting with petroleum ether: ethyl acetate = 6: 1 to give an oily product, 1.21 g, in 84.3percent yield. |
81% | With hydrogen bromide In toluene at 80 - 90℃; for 2 h; Large scale | A mixture of 1,8-octanediol(1.461kg, 10mol) and toluene (25L) were added to the reaction kettle, stirred and heated to 80-90 ° C,Fourteen drops of pale yellow HBr (1.9 Kg, 11mol) were added dropwise four times,The molar ratio of HBr was 10: 5: 3: 2,After the dropwise addition, the incubation was carried out for 2 hours.TLC monitoring, when the 1,8-dibromo octane content of 3percent when the reaction end point,Cooled to room temperature, stratified, respectively with 5percent NaOH, 10percent HC1, water,Saturated sodium bicarbonate solution in turn on the organic layer washed three times, to neutral, add Na2S04 dry overnight. The solvent was obtained by rotary evaporator to obtain 1.78 kg of 8-bromo-1-octanol, the product yield was 81percent, and the GC content was> 95percent. |
79% | With hydrogen bromide In water; toluene for 48 h; Reflux | A stirred mixture of octane-1, 8-diol (15 g, 0.103 mol) and hydrogen bromide (45percent) (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 79percent. 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 56percent. 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 77percent. |
68.7% | With hydrogen bromide In water; toluene at 0 - 80℃; for 6.33333 h; | Step-i:To the solution of compound-i (100 g, 0.76mo1) in toluene (1200 ml), aqueous 47percentHBr (600 ml) was added at 0 °C for 20 mm and the reaction mixture was heated to 80 °C for 6h. After consumption of the starting material (by TLC), the reaction mass was quenched with ice cold water (500m1) then the compound was extracted into EtOAc (2Xl000ml) and combined organic layer was dried over anhydrous Na2SO4 filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, eluting with 10-15percent EtOAc/Hexane to afford 2 (110 g, 68.7as yellow liquid.TLC: 20percent EtOAc/Hexane (RI: 0.5)1H NMR (500MHz, CDC13, ö in ppm): 8 3.62 (m, 211), 3.40 (m, 2H), 1.85-1.80 (m, 2H). 1.60-1.57 (m, 2H), 1.50-1.25 (m, 8H). |
65% | at 80℃; for 0.116667 h; Sealed tube; Microwave irradiation | In a vial (10 mL), a mixture of [bmim]HSO4 (0.283 g, 1.2mmol) and NaBr (0.154 g, 1.5 mmol)was taken and irradiated in microwave oven [160W in LGMS-194A (800 W)] for 1 min,followed by cooling period of 1 min. Alcohol (1 mmol) was added to vial, sealed properly andirradiated at 160W for 7 min with the mechanical shaking done after each 30 sec irradiationtime. The resulting mixture was allowed to cool, followed by extraction with diethyl ether (3 £10 mL) and worked up as before to get the product (2, 0.135 g, 65percent).IR (neat)/nmax cm21: 3390, 2928, 1670, 1310, 602. 1H NMR (CDCl3, 300MHz) d: 3.38 (t,2H, J 6.2 Hz, ZCH2OH), 3.20 (t, 2H, J 6.4 Hz, ZCH2Br), 1.93–1.88 (m, 4H, saturatedmethylene protons), 1.48–1.16 (m, 12H, saturated methylene protons). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogen bromide In toluene | EXAMPLE 1 Preparation of 8-bromooctan-1-ol In a 6 m3 kettle, 235 kg of octane-1,8-diol were stirred under reflux with 3 m3 of toluene and 440 kg of HBr (48percent strength) for 40 hours. The aqueous phase was then separated off. The toluene phase was thoroughly washed with 500 1 of water, then with 500 l of 10percent strength sodium carbonate solution and then again with 500 1 of water. A sample was concentrated and was found to contain 92percent of bromooctanol in addition to 1.9percent of dibromooctane and 2.0percent unconverted octanediol. After removal of the toluene by distillation in the reaction kettle and a Sambay distillation of the remaining residue, the yield was 254 kg (76percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium at 220℃; Erhitzen des Reaktionsprodukts mit Natrium unter 0.1-2 Torr auf 240grad; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With ammonia In tert-Amyl alcohol at 140℃; for 48h; Autoclave; | 3 Example 3; Reaction of 1,8-octanediol; The reaction was carried out under the same conditions as in Example 1 using 10.0 mmol of 1,8-octanediol. Yield and conversion were determined by gas chromatography using commercially available reference compounds. Yield of linear primary diamine: 78%, conversion of the linear diol: >99%.; Example 1; Reaction of 1,19-nonadecanediol; 3.01 g (10.0 mmol) of 1,19-nonadecanediol and 151 mg (0.25 mol %) of carbonylchloro[4,5-bis(diisopropylphosphinomethyl)acridine]hydridoruthenium(II) were dissolved under protective gas in 25 ml of 2-methyl-2-butanol and transferred to an autoclave provided with stirrer, heating and temperature measuring facility. 6 ml of liquid ammonia were subsequently introduced into the autoclave by means of a spindle press. The autoclave was closed and the contents stirred at 140° C. for 48 hours. This resulted in an increase in the internal pressure from 22 to 40 bar. After cooling, the contents of the reactor were filtered through kieselguhr, the filtrate was evaporated to dryness and the residue subjected to a bulb tube distillation. Yield of linear primary diamine: 2.02 g (68% of theory; bp0.8 mbar=170-185° C.), conversion of the linear diol: >99%. |
> 99 %Chromat. | With L-alanin; L-alanine dehydrogenase; ω-transaminase from Chromobacterium violaceum; alcohol dehydrogenase from Bacillus stearothermophilus; pyridoxal 5'-phosphate; NAD; ammonium chloride; sodium hydroxide In 1,2-dimethoxyethane; water at 20℃; for 20h; Enzymatic reaction; | |
With ammonia; nickel at 220 - 260℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen bromide In water; toluene for 8h; Reflux; | 1 Step 1 : Preparation of 8-bromo-octanol 16 g (110 mmol) of octane diol have been dissolved in 250 ml toluene. After addition of 15.5 ml of HBr (137 mmol, 1.25 eq., 48% in water) the reaction mixture has been refluxed with a dean-stark receiver to remove the water from the reaction. After 8 hours the mixture was cooled to room temperature and was washed two times with distilled water and once with brine. After filtration over sodium sulfate and evaporation of the solvent the bromide was obtained in quantitative yield. In the NMR spectra, residual toluene was observed, which had no impact on the subsequent steps. D2o-c = 1.23 g/ml (lit: 1.22 g/ml) 13C NMR (CDC ; ppm): 62.95 (CH2OH), 34.04 (BrCH2CH2), 32.78/32.71 (BrCH2) and (CH2CH2OH), 29.23/28.73/28.09/25.65 (CH2) |
100% | With hydrogen bromide In water; toluene for 8h; Reflux; | 1.1 Step 1 : Preparation of 8-bromo-octanol 16 g (110 mmol) of octane diol have been dissolved in 250 ml toluene. After addition of 15.5 ml of HBr (137 mmol, 1.25 eq., 48% in water) the reaction mixture has been refluxed with a dean-stark receiver to remove the water from the reaction. After 8 hours the mixture was cooled to room temperature and was washed two times with distilled water and once with brine. After filtration over sodium sulfate and evaporation of the solvent the bromide was obtained in quantitative yield. In the NMR spectra, residual toluene was observed, which had no impact on the subsequent steps. Dare = 1.23 g/ml (lit: 1.22 g/ml); 13C NMR (CDCI3; ppm): 62.95 (CH2OH), 34.04 (BrCH2CH2), 32.78/32.71 (BrCH2) and (CH2CH2OH), 29.23/28.73/28.09/25.65 (CH2) |
99% | With hydrogen bromide In toluene Heating; |
97.3% | With hydrogen bromide In cyclohexane at 75℃; for 60h; | |
96% | With hydrogen bromide | |
95% | With hydrogen bromide In toluene Heating; | |
95% | With hydrogen bromide In water; toluene for 21h; Heating; | |
95% | With hydrogen bromide In toluene Reflux; | 1.1; 2.1; 3.1 (1) 8-bromooctyl alcohol synthesis 7.3 g (50 mmol) of 1,8-octanediol and 10.0 g of 40% hydrobromic acid (50 mmol) were placed in 150 ml of toluene.Heating and refluxing for 8-20 h, the reaction is completed, neutralized, washed with water, dried over anhydrous sodium sulfate and distilled to give 8-bromooctanol9.9 g, yield 95%. |
92% | With hydrogen bromide In toluene for 13.5h; | 1.1 EXAMPLE 1; 1. Step 1: Bromination 438 g (3 mol) of 1,8-octanediol was dissolved in 3 1 of toluene. 375 ml (3.3 mol) of aqueous 48% HBr was then added. The medium was then heated to eliminate water that was present and water formed during the reaction by azeotropic distillation. After 13.5 h of contact, the medium was cooled and taken up with a saturated solution of NaHCO3. The organic phase was separated and washed with a saturated solution of NaCl. After drying over MgSO4, the medium was concentrated to yield a crude product of 672 g. [0057] The 8-bromooctanol was purified by distillation under reduced pressure, at 96° C. under P<1 mbar, m=575 g (92%). [0058] Characterization [0059] TLC: Rf=0.8 (heptane/ether iso 8/2) [0060] 1H NMR (200 MHz, CDCl3): 3.65 (t, 2H, J=6.4 Hz); 3.43 (t, 2H, J=6.8 Hz); 1.87 (m, 2H); 1.36-1.69 (m, 10H). |
90% | With hydrogen bromide In water; toluene at 20 - 115℃; for 22h; | |
89% | With hydrogen bromide at 75℃; for 80h; | |
89% | ||
89% | With bromine; triphenylphosphine In N,N-dimethyl-formamide at 50℃; for 0.5h; | |
89% | With hydrogen bromide In water; toluene at 95 - 97℃; for 72h; | |
89% | With hydrogen bromide In water; toluene for 36h; Reflux; | |
88% | With hydrogen bromide In toluene for 5h; Heating; | |
86% | With hydrogen bromide In n-heptane Heating; | |
85% | With hydrogen bromide In benzene for 48h; Heating; | |
84.3% | With hydrogen bromide In water; toluene for 96h; Reflux; | 1 8-bromo-1-octanol (compound 2-2-1) The compound 2-1-1 (octanediol) (1.01 g, 6.91 mmol) was dissolved in 20 ml of toluene, and 40% HBr (aq) (1.12 ml, 7.81 mmol) was added to the reaction system at room temperature, bath reflux.72h after TLC monitoring, there is still the remaining raw materials, add 40% HBr (aq) (0.5ml, 3.49mmol), continue to return 24h.The system was cooled to room temperature, diluted with ether, saturated sodium bicarbonate solution, saturated sodium chloride solution, washed once, sodium sulfate dried about half an hour after the filter, steamed ether.The residue was purified by column chromatography on silica gel, eluting with petroleum ether: ethyl acetate = 6: 1 to give an oily product, 1.21 g, in 84.3% yield. |
83% | With hydrogen bromide In n-heptane at 75℃; for 24h; | |
83% | With hydrogen bromide | |
83% | With hydrogen bromide In toluene at 110℃; for 50h; | 1 8 - Synthesis of bromine propyl butyl-carbinol In a 2 L three-opening bottle into the 1, 8 - octandiol (250 g, 1.712 µM), toluene (1000 ml), 48% hydrogen bromide (231 ml, 2 . 054 µM, 1.2 eq), heating to 110 °C reflux 30 hours. Added 48% hydrogen bromide (84 ml, 0 . 753 µM, 0 . 44 eq), heating reflux for 20 hours, GC detection with a small amount of residues of raw materials. Cooling to the room temperature plus 500 ml petroleum ether dilution, liquid [...] bromic acid, organic phase are saturated sodium bicarbonate (400 ml × 2) and saturated brine (400 ml × 2) cleaning, dried with anhydrous sodium sulfate. Turns on lathe does 8 - bromine propyl butyl-carbinol 318 g, yield 83%, direct throws down the step. |
81% | With hydrogen bromide In toluene at 80 - 90℃; for 2h; Large scale; | 1.a 8-bromo-1-octanol A mixture of 1,8-octanediol(1.461kg, 10mol) and toluene (25L) were added to the reaction kettle, stirred and heated to 80-90 ° C,Fourteen drops of pale yellow HBr (1.9 Kg, 11mol) were added dropwise four times,The molar ratio of HBr was 10: 5: 3: 2,After the dropwise addition, the incubation was carried out for 2 hours.TLC monitoring, when the 1,8-dibromo octane content of 3% when the reaction end point,Cooled to room temperature, stratified, respectively with 5% NaOH, 10% HC1, water,Saturated sodium bicarbonate solution in turn on the organic layer washed three times, to neutral, add Na2S04 dry overnight. The solvent was obtained by rotary evaporator to obtain 1.78 kg of 8-bromo-1-octanol, the product yield was 81%, and the GC content was> 95%. |
80% | With hydrogen bromide In water; Petroleum ether for 9h; Heating; | |
79% | With hydrogen bromide In water; toluene 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%. |
78% | With hydrogen bromide In benzene for 18h; Heating; | |
78.7% | With tetrabutylammomium bromide; hydrogen bromide In water for 0.0833333h; Microwave irradiation; | |
76% | With hydrogen bromide In toluene | |
75% | ||
75% | With hydrogen bromide Heating; | |
75% | With hydrogen bromide In toluene for 13h; Heating; | |
75% | With hydrogen bromide In cyclohexane Heating; | |
74% | With hydrogen bromide In toluene Reflux; | |
73% | With hydrogen bromide In benzene for 18h; Heating; | |
72% | With hydrogen bromide In benzene for 18h; Heating; | |
70% | With hydrogen bromide In toluene for 6h; Heating; | |
68.7% | With hydrogen bromide In water; toluene at 0 - 80℃; for 6.33333h; | 2.1 Preparation of 8-bromo octan-i-ol (Compound-2) (SUT-MA1 102-086) Step-i:To the solution of compound-i (100 g, 0.76mo1) in toluene (1200 ml), aqueous 47%HBr (600 ml) was added at 0 °C for 20 mm and the reaction mixture was heated to 80 °C for 6h. After consumption of the starting material (by TLC), the reaction mass was quenched with ice cold water (500m1) then the compound was extracted into EtOAc (2Xl000ml) and combined organic layer was dried over anhydrous Na2SO4 filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, eluting with 10-15% EtOAc/Hexane to afford 2 (110 g, 68.7as yellow liquid.TLC: 20% EtOAc/Hexane (RI: 0.5)1H NMR (500MHz, CDC13, ö in ppm): 8 3.62 (m, 211), 3.40 (m, 2H), 1.85-1.80 (m, 2H). 1.60-1.57 (m, 2H), 1.50-1.25 (m, 8H). |
65% | With hydrogen bromide | |
65% | With 1-butyl-3-methylimidazolium hydrogen sulfate; sodium bromide at 80℃; for 0.116667h; Sealed tube; Microwave irradiation; | In a vial (10 mL), a mixture of [bmim]HSO4 (0.283 g, 1.2mmol) and NaBr (0.154 g, 1.5 mmol)was taken and irradiated in microwave oven [160W in LGMS-194A (800 W)] for 1 min,followed by cooling period of 1 min. Alcohol (1 mmol) was added to vial, sealed properly andirradiated at 160W for 7 min with the mechanical shaking done after each 30 sec irradiationtime. The resulting mixture was allowed to cool, followed by extraction with diethyl ether (3 £10 mL) and worked up as before to get the product (2, 0.135 g, 65%).IR (neat)/nmax cm21: 3390, 2928, 1670, 1310, 602. 1H NMR (CDCl3, 300MHz) d: 3.38 (t,2H, J 6.2 Hz, ZCH2OH), 3.20 (t, 2H, J 6.4 Hz, ZCH2Br), 1.93-1.88 (m, 4H, saturatedmethylene protons), 1.48-1.16 (m, 12H, saturated methylene protons). |
60% | With hydrogen bromide In water; toluene at 90 - 95℃; for 48h; | |
60% | With hydrogen bromide In benzene for 18h; Heating; | |
59% | With hydrogen bromide In benzene Heating; | |
56% | With hydrogen bromide | |
45% | With hydrogen bromide In toluene at 90℃; for 72h; | |
27.6% | With hydrogen bromide In cyclohexane; water at 90℃; for 5h; Inert atmosphere; | |
With hydrogen bromide | ||
With hydrogen bromide In water at 80℃; for 24h; | ||
With hydrogen bromide In cyclohexane at 80℃; for 120h; | ||
With hydrogen bromide In toluene for 6h; Heating; | ||
With carbon tetrabromide; triphenylphosphine In tetrahydrofuran for 20h; Ambient temperature; | ||
With hydrogen bromide | ||
With hydrogen bromide In toluene Heating; | ||
With hydrogen bromide In water for 60h; Heating; | ||
With hydrogen bromide In toluene for 18h; Heating; | ||
With hydrogen bromide In cyclohexane; water for 6h; Heating / reflux; | ||
With hydrogen bromide In cyclohexane; water for 6h; Reflux; | 1.a 25 g of octane-1,8-diol was boiled in 250 ml of cyclohexane with 22.6 ml of 47% aqueous hydrobromic acid for six hours in a water separator. The reaction mixture was then poured onto saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated, aqueous sodium chloride solution, dried on sodium sulfate, filtered and concentrated by evaporation in a vacuum. Column chromatography on silica gel with a mixture that consists of hexane/ethyl acetate yielded 21.6 g of the title compound as a yellowish oil. 1H-NMR (300 MHz, CDCl3): δ [ppm]=3.64 t (J=6.8 Hz, 2H, CH2OH); 3.41 t (J=6.8 Hz, 2H, CH2Br); 1.85 tt (J=7.3 Hz/6.8 Hz, 2H, CH2); 1.56 m (2H, CH2); 1.49-1.27 m (8H, CH2). | |
With hydrogen bromide In hexane; acetone; Petroleum ether Dean-Stark; Reflux; | ||
With hydrogen bromide In toluene for 75h; Reflux; | ||
With hydrogen bromide In water; toluene | ||
With hydrogen bromide In toluene at 120℃; for 16h; | 4.1.2. General Synthesis Procedure for Bromoalcohols 8a, 8b,and 8c. General procedure: To a stirred solution of diol 7 (300 mmol, 1.0 equiv)in toluene (600 mL) was added slowly 48% HBr (360 mmol,1.2 equiv) at RT. -e reaction mixture was reLuxed at 120°Cfor 16 h. After cooling to 0°C for 30 min, the organic layerwas separated and washed with saturated NaHCO3 solution.-e resulting aqueous layer was extracted with hexane(120 mL× 3). -e combined organic layer was washed withbrine (300 mL), dried over anhydrous MgSO4, :ltered, andconcentrated in vacuo to obtain the corresponding bromoalcohol8 as a light yellow oil. -e crude bromoalcohol 8was employed in the next step without further puri:cation.Bromoalcohols 8a, 8b, and 8c were synthesized independentlyaccording to the general procedure with 90%, 85%,and 91% yields, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydride In tetrahydrofuran | |
85% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.333333h; Stage #2: benzyl bromide In tetrahydrofuran at 25℃; for 3h; | |
84% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide; mineral oil at -10 - 20℃; for 1h; Inert atmosphere; Stage #2: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 6h; Inert atmosphere; | 4.8. 8-(Benzyloxy)octan-1-ol 15 To a suspension of sodium hydride (0.83 g, 20.6 mmol, 60% mineral dispersion) in DMF (30 mL) was slowly added a solution of octane-1,8-diol 14 (3.0 g, 18.7 mmol) in DMF (10 mL) at -10° C under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. Next, the reaction mixture was cooled to 0 C, and benzyl bromide (2.65 mL, 22.5 mmol) was added. The reaction mixture was again warmed to room temperature and stirred for an additional 6 h. After complete conversion, it was quenched with saturated aqueous NH4Cl solution (20 mL) at 0° C, and the resulting mixture was extracted with diethylether (2ϰ30 mL). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (30% EtOAc/hexanes) to give 15 (3.7 g, 84%) as a white solid. Mp 83-86° C. IR(neat): 3393, 2928, 2854, 1452, 1362, 1096, 1070, 772, 734,696, 610 cm-1; 1H NMR (500 MHz, CDCl3): δ 7.39-7.24 (m, 5H),4.50 (s, 2H), 3.63 (t, J = 6.7 Hz, 2H), 3.46 (t, J = 6.7 Hz, 2H), 1.77-1.68 (m, 2H), 1.65-1.51 (m, 5H), 1.41-1.22 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 138.6, 128.3, 127.6, 127.4, 72.8, 70.4, 62.9,32.7, 29.6, 29.3, 29.2, 26.0, 25.6; MS (ESI): m/z 259 [M+Na]+;HRMS (ESI): m/z calcd for C15H25O2 [M+H]+ 237.18491, found 237.18524. |
78% | With tetra-(n-butyl)ammonium iodide; mercury(II) oxide In dichloromethane at 20℃; for 20h; | |
61% | With silver(l) oxide In dichloromethane at 20℃; for 15h; | |
56% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 2h; Stage #2: benzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; | |
54% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran Stage #2: benzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide | |
54% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 10h; Inert atmosphere; | 4 Compound 29: To a stirred suspension of NaH (60% in oil, 82 g, 1.7096 mol) in 500mL anhydrous DMF, a solution of compound 28 (250 g, 1.7096 mol) in 1.5 L DMF was added slowly using a dropping funnel at 0 °C. The reaction mixture was stirred for 30 minutes, then benzyl bromide (208.86 mL, 1.7096 mol) was added slowly under an atmosphere of nitrogen. The reaction was then warmed to ambient temperature and stirred for 10 hours. The mixture wasthen quenched with crushed ice (~2 kg) and extracted with ethyl acetate (2 x 1 L). The organic layer was washed with water (1L) to remove unwanted DMF, dried over Na2S04 and evaporated to dryness in vacuo. The crude compound was purified on 60-120 silica gel, eluted with 0-5% MeOH in DCM to afford compound 29 (220 g, 54%) as a pale yellow liquid. 1H NMR (400 MHz, CDC13): δ = 7.33-7.24 (m, 5 H), 4.49 (s, 2 H), 3.63-3.60 (m, 2 H), 3.47-3.43 (m, 2 H), 1.63-1.51 (m, 4 H), 1.39-1.23 (m, 8 H). |
54% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 10h; Inert atmosphere; | 4; 7 Compound 29 To a stirred suspension ofNaH (60% in oil, 82 g, 1.7096 mol) in 500 mE anhydrous DMF, a solution of compound 28 (250 g, 1.7096 mol) in 1.5 L DMF was added slowly using a dropping funnel at 00 C. The reaction mixture was stirred for 30 minutes, then benzyl bromide (208.86 mE, 1.7096 mol) was added slowly under an atmosphere of nitrogen. The reaction was then warmed to ambient temperature and stirred for 10 hours. The mixture was then quenched with crushed ice (.-2 kg) and extracted with ethyl acetate (2x1 L). The organic layer was washed with water (IL) to remove unwanted DMF, dried over Na2504 and evaporated to dryness in vacuo. The crude compound was purified on 60-120 silica gel, eluted with 0-5% MeOH in DCM to afford compound 29 (220 g, 54%) as a pale yellow liquid. ‘H NMR (400 MHz, CDC13): &7.33-7.24 (m, 5H), 4.49 (s, 2H), 3.63- 3.60 (m, 2H), 3.47-3.43 (m, 2H), 1.63-1.51 (m, 4H), 1.39-1.23 (m, 8H). |
53% | With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 4h; | |
53% | With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 16h; | |
52% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 4h; Stage #2: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 17h; | |
48% | Stage #1: 1,8-Octanediol With 18-crown-6 ether; sodium hydride In tetrahydrofuran for 0.166667h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran for 4h; Reflux; | Diethyl 10-(8-(benzyloxy)octyloxy)decylphosphonate 1,8-octanediol (5.0 g, 34.2 mmol) and 18-crown-6 (spatula tip) were added to anhydrous tetrahydrofuran under inert atmosphere. Sodium hydride (820 mg, 34.2 mmol) was added and the solution stirred for 10 minutes. Benzyl bromide(4.1 mL, 34.2mmol) was then added and the reaction stirred at reflux for 4 hours and then overnight at room temperature. A white precipitate formed and this was filtered off. The filtrate was concentrated under reduced pressure. Column chromatography (stationary phase: silica, mobile phase: 1 : 1 hexanes: ethyl acetate) was used to isolate the desired product (Rf = 0.40, 1 : lhexanes: ethyl acetate) as a yellow oil (3.914 g, 48 % yield). 1H NMR is consistent with 8-(benzyloxy)octan-l-ol. 8-(benzyloxy)octan-l-ol (1.15 g, 4.86 mmol) was added to anhydrous dimethylformamide in a round bottom flask under inert atmosphere. Sodium hydride (175 mg, 7.3 mmol) was added and the solution allowed to stir for 30 minutes. 1,10- dibromodecane (11.7 g, 38.9 mmol) was then added and the reaction stirred at 90 0C for 4 hours and then cooled to room temperature. The solvent was removed under reduced pressure. Column chromatography (stationary phase: silica, mobile phase: hexanes with increasing amounts of ethyl acetate) was used to isolate the desired product (Rf = 0.65, 9: 1 hexanes: ethyl acetate) as a viscous oil. The resulting oil contained some desired product (((8-(10-bromodecyloxy)octyloxy)methyl)benzene, as evidenced by H NMR), though impure (tic), and used in the next reaction without further purification.((8-(10-bromodecyloxy)octyloxy)methyl)benzene (900 mg, 2.0 mmol) was combined with triethylphosphite (5 mL, 30 mmol) and the reaction mixture stirred at 135 0C for 2 days. Excess triethylphosphite and other side products were removed under vacuum (approximately 0.1 torr) and with heating at 80 0C for 5 hours to yield a viscous oil (760 mg, 74 % yield). 1H NMR (400.14 MHz, CD2Cl2) δ 7.35 - 7.29 (m, 4H), 7.29 - 7.21 (m), 4.46 (2H), 4.13 - 3.92 (m, 4H), 3.45 (t, J= 6.60 Hz, 2H), 3.35 (t, J= 6.66 Hz, 4H), 1.73 - 1.62 (m, 2H), 1.62 - 1.41 (m, 8H), 1.41 - 1.18 (m, 26H). 13C(1H) NMR (100.62 MHz, CD2Cl2) δ 139.4, 128.6 (2C), 127.9 (2C), 127.7, 73.02, 71.13 (2C), 70.87, 61.61 (d, J= 6.4 Hz, 2C), 30.94 (d, J= 16.8 Hz), 30.17 (2C), 30.14, 29.91, 29.84, 29.81 (2C), 29.72, 29.45, 26.57, 26.53 (2C), 25.87 (d, J = 140.3 Hz), 22.76 (d, J= 5.2 Hz), 16.65 (d, J= 5.9 Hz, 2C). 31P(1H) NMR (161.97 MHz, CD2Cl2): δ 32.94. Analysis calculated (found) %: C 67.94 (67.08), H 10.42 (10.50). MS (ESI, m/z): 513 (M+, 100%). Exact mass calculated (found) for [M+H]+, m/z): 513.3703 (513.3674). |
With sodium hydride | ||
With sodium hydride 1.) THF, 60 deg C, 1 h; 2.) 60-70 deg C, 5 h; Yield given. Multistep reaction; | ||
In N,N-dimethyl-formamide | ||
5.9 g | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 6h; Cooling with ice; | 12 Intermediate 12a: 8-(benzyloxy)octan-1-ol In a round bottom flask, 1 ,8-octanediol (10 g, 68.4 mmol) was dissolved in anhydrous DMF (300 ml) and anhydrous THF (100 ml_). The solution was cooled in an ice-water bath, and NaH (60% dispersion in mineral oil) (2.462 g, 61.5 mmol) was added portion wise. Benzyl bromide (12.87 g, 75 mmol) was then added. The reaction was slowly warmed to ambient temperature. After 6 h, the reaction was diluted with 150 ml_ H20 and then extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHC03 solution, dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified on silica gel using ethyl acetate /heptane as eluent to provide 5.9 g of the expected product. 1H NMR (400MHz, CDCI3) δ = 7.42 - 7.19 (m, 5H), 4.51 (s, 2H), 3.70 - 3.57 (m, 2H), 3.47 (t, J=6.7 Hz, 2H), 1.73 - 1.43 (m, 4H), 1.43- 1.30 (m, 8H). |
Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere; | ||
With sodium hydride In tetrahydrofuran at 20℃; | ||
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; | 1 C10aaMe-acid-2-TG (Int-151): Intermediate C10aaMe-acid-2-TG (Int-151) was prepared from octane-1,8-diol as shown in Scheme 39, using methods described above. 1H NMR (400 MHz, CDCl3) d 5.28 (m, 1H), 4.34 (dd, J = 11.8, 4.2 Hz, 2H), 4.18 (dd, J = 11.8, 6.1 Hz, 2H), 2.36 (dt, J = 17.1, 7.5 Hz, 4H), 1.65 - 1.51 (m, 8H), 1.29 (s, 58H), 1.19 (s, 6H), 0.91 (t, J = 6.5 Hz, 6H); 13C NMR (101 MHz, CDCl3) d 179.57 (1C), 177.49 (1C), 173.33 (2C), 68.94 (1C), 62.16 (1C), 42.40 (1C), 40.63 (1C), 34.24 (2C), 31.96 (2C), 30.06-29.15 (26C), 25.07 (1C), 24.89 (2C), 24.81 (1C), 24.65 (1C), 22.73 (2C), 14.16 (2C); MS (ESI, -ve) m/z: 780.08 (M-1); MS (ESI, +ve) m/z: 799.16 (M+18). | |
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; | ||
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; | 1 [00568] C10ααMe-acid-2-TG (Int-151): [00569] Intermediate C10ααMe-acid-2-TG (Int-151) was prepared from octane-1,8-diol as shown in Scheme 40, using methods described above. 1H NMR (400 MHz, CDCl3) δ 5.28 (m, 1H), 4.34 (dd, J = 11.8, 4.2 Hz, 2H), 4.18 (dd, J = 11.8, 6.1 Hz, 2H), 2.36 (dt, J = 17.1, 7.5 Hz, 4H), 1.65 - 1.51 (m, 8H), 1.29 (s, 58H), 1.19 (s, 6H), 0.91 (t, J = 6.5 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 179.57 (1C), 177.49 (1C), 173.33 (2C), 68.94 (1C), 62.16 (1C), 42.40 (1C), 40.63 (1C), 34.24 (2C), 31.96 (2C), 30.06-29.15 (26C), 25.07 (1C), 24.89 (2C), 24.81 (1C), 24.65 (1C), 22.73 (2C), 14.16 (2C); MS (ESI, -ve) m/z: 780.08 (M-1); MS (ESI, +ve) m/z: 799.16 (M+18). | |
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; | 1 [00568] C10ααMe-acid-2-TG (Int-151): [00569] Intermediate C10ααMe-acid-2-TG (Int-151) was prepared from octane-1,8-diol as shown in Scheme 40, using methods described above. 1H NMR (400 MHz, CDCl3) δ 5.28 (m, 1H), 4.34 (dd, J = 11.8, 4.2 Hz, 2H), 4.18 (dd, J = 11.8, 6.1 Hz, 2H), 2.36 (dt, J = 17.1, 7.5 Hz, 4H), 1.65 - 1.51 (m, 8H), 1.29 (s, 58H), 1.19 (s, 6H), 0.91 (t, J = 6.5 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 179.57 (1C), 177.49 (1C), 173.33 (2C), 68.94 (1C), 62.16 (1C), 42.40 (1C), 40.63 (1C), 34.24 (2C), 31.96 (2C), 30.06-29.15 (26C), 25.07 (1C), 24.89 (2C), 24.81 (1C), 24.65 (1C), 22.73 (2C), 14.16 (2C); MS (ESI, -ve) m/z: 780.08 (M-1); MS (ESI, +ve) m/z: 799.16 (M+18). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Dowex 50X2 In toluene at 30℃; for 5h; | |
98% | With Dowex50WX2 In toluene at 30℃; for 5h; | |
98% | With Dowex 50x2 In toluene at 30℃; for 5h; | S-((tetrahydro-2H-pyran-2-yl)oxy)octan- 1 -ol (4): Compound 4 was synthesized following a reported protocol (Babu, K. V.; Sharma, G. V. M. Tetrahedron Asyni. 2008. 19 (5), 577-583). |
86% | With tetrachlorosilane In dichloromethane at 20℃; for 0.5h; | |
85% | With iodine In dichloromethane for 3.5h; | |
82% | With toluene-4-sulfonic acid In dichloromethane at 0℃; for 1h; | |
82% | With sodium hydrogen sulfate In hexane; water; dimethyl sulfoxide at 40℃; for 16h; | 1 Synthesis of 8-((tetrahydro-2H-pyran-2-yl)oxy)octan-1 -ol (2) A mixture of 1 ,8-octanediol (1 ) (1 .46 g, 10 mmol), aqueous 5 M NaHS04(2 ml_), 5:95 (vol/vol) dihydropyran-hexane (57.6 mL) and DMSO (2 ml.) was stirred at 40 °C for 16h. The reaction mixture was washed with H20 and extracted 3 times with hexane. The organic layer was separated from the aqueous layer, dried with brine and Na2S04and concentrated under reduced pressure. Purification was done with flash chromatography (40% ethyl acetate/hexane) to give a clear oil of 2 (82%).1H NMR (400 MHz, CDCI3) d 4.56 (d, J = 4.1 Hz, 1 H), 3.94 - 3.80 (m, 1 H), 3.80 - 3.68 (m, 1 H), 3.63 (t, J = 6.2 Hz, 2H), 3.49 (dd, J = 10.9, 4.7 Hz, 1 H), 3.38 (dt, J = 9.5, 6.7 Hz, 1 H), 1.90 - 1 .76 (m, 1 H), 1.76 - 1.45 (m, 10H), 1.33 (m, 8H).13C NMR (100 MHz, CDCI3) d 98.86, 67.64, 63.02, 62.35, 32.75, 30.77, 29.70, 29.39, 29.32, 26.14, 25.66, 25.49, 19.68. |
75% | With copper dichloride In dichloromethane Ambient temperature; | |
75% | In dichloromethane at 20℃; for 0.333333h; | |
74% | With sodium hydrogen sulfate In hexane; water at 40℃; for 16h; | General procedure for the synthesis of monotetrahydropyranyl acetals 2a-d General procedure: A mixture of 1,n-diols 1a-d (1.0 mmol), DHP-hexane 3% (v/v) (1.96 mmol) and aqueous 5 M NaHSO4 (01 mL) was prepared. To 1,10-decanediol 1c and 1,12-dodecanediol 1d, 0.2 mL of DMSO were also added to the mixture at the beginning of the reaction. This mixture was stirred at 40 °C for 16 h and then extracted with hexane (3 × 20 mL). The combined organic phases were dried (Na2SO4), filtered and then evaporated under reduced pressure. The residue obtained was chromatographed using silica gel using hexane/EtOAc (8:2) to yield pure Compounds 2a-d. |
62% | With pyridinium p-toluenesulfonate In tetrahydrofuran for 12h; Ambient temperature; | |
60% | With toluene-4-sulfonic acid In dichloromethane for 0.5h; | |
56% | With pyridinium p-toluenesulfonate In tetrahydrofuran; dichloromethane at 20℃; for 32h; | |
54% | With pyridinium p-toluenesulfonate In chloroform at 20℃; for 18h; Inert atmosphere; | 2; 2.a General procedure: DHP (3.46 ml, 37.9 mmol) and a catalytic amount of PPTS were added to a solution of 1,8-octanediol (Compound 7, 5.85 g, 40.0 mmol) in CHCl3 (100 ml) in a stream of argon at room temperature, and the mixture was stirred for 16 hours. The reaction solution was stirred for 5 minutes after addition of H2O. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed with a saturated aqueous NaHCO3 solution then with a saturated aqueous NaCl solution, and was dried over Na2SO4. After evaporation of the solvent, the residue was purified by column chromatography on silica gel (Hexane:EtOAc = 3:1 to 2:1) to yield the corresponding THP ether (4.95 g, 54%). |
54% | With pyridinium p-toluenesulfonate In chloroform at 20℃; for 16h; Inert atmosphere; | 2 To a solution of 1,8-octanediol (compound 7, 5.85 g, 40.0 mmol) in CHCl3 (100 ml), DHP (3.46 ml, 37.9 mmol) and a catalytic amount of PPTS were added at room temperature under an argon stream and then stirred for 16 hours. After the reaction mixture was diluted with H2O and stirred for 5 minutes, the organic layer was separated and collected, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with aqueous solutions of sat. NaHCO3 and sat. NaCl, and then dried over Na2SO4. After the solvent was distilled off, the residue was purified by silica gel column chromatography (hexane:EtOAc = 3:1 → 2:1) to give the corresponding THP ether (4.95 g, 54%). |
50% | With pyridinium p-toluenesulfonate In tetrahydrofuran; chloroform-d1 at 20℃; Inert atmosphere; | |
49% | With aluminum(III) sulfate In octane at 78℃; | |
43% | at 25℃; for 6h; | |
41% | With hydrogenchloride In 1,2-dimethoxyethane for 2h; Ambient temperature; | |
39% | With pyridinium p-toluenesulfonate In dichloromethane | 1; 6 A new series of tris-malonate tethers that possess an open structure and bear alkyl groups as spacers were tested. The synthesis of one such tether that worked well with C60 is described in FIG. 6. PPTS: Pyridinium toluene-4-sulfonate. The intermediates of the synthesis of FIG. 6 were purified by flash column chromatography as follows, and were fully characterized by 13C-, 1H-NMR and mass spectrometry (FAB-MS). 1: SiO2, Hexane/EtOAc=1/1, Colorless oil. 2: SiO2, Hexane/EtOAc=7/3, Colorless oil. 3: SiO2, Hexane/EtOAc=3/2, Colorless oil. 4: SiO2, Hexane/EtOAc=1/1, Colorless oil. The yield of the first step of the synthesis was 39% because the bis-protected diol was also formed. The reason is that 1,8-octane-diol was not well soluble in CH2Cl2 and consequently, the mono-protected diol (soluble in CH2Cl2) was subjected to a rapid second reaction. We expect the use of larger amounts of solvent will improve the yield of the first step of the synthesis. Yields about 85% have been reported for similar diols according to the experimental procedure we followed. For details see: H. M. S. Kumar, B. V. S. Reddy, E. J. Reddy, J. S. Yadav, Chemistry Letters, 1999, 857-858. |
34% | In various solvent(s) for 3h; | |
With toluene-4-sulfonic acid In diethyl ether for 5h; Heating; | ||
With hydrogen cation | ||
With Montmorillonite K10 In dichloromethane | ||
With toluene-4-sulfonic acid | ||
With toluene-4-sulfonic acid In tetrahydrofuran | ||
With hydrogenchloride; sodium hydrogencarbonate In dichloromethane | 4 Example 4 Example 4 The following example describes the synthesis of (E,Z)-8,10-pentadecadien-1-ol acetate. 8-[(Tetrahydro-2H-pyran-2-yl)oxy]-1-octanol. 1,8-Octanediol (16.8 g) (115 mmol) and 4.83 g of dihydropyran (57.5 mmol) in 1400 ml of dichloromethane containing 5 drops of concentrated HCl were stirred for 2 hours. Then 10 g of NaHCO3 were stirred in and the solution was filtered. Dichloromethane was removed with a rotary evaporator, and the resulting residue was triturated with pentane; the undissolved solid was 1,8-octanediol. The solid was filtered from the pentane solution, and the pentane was removed with a rotary evaporator to give 13.2 g (99.8%) of crude product oil. | |
96 %Chromat. | With polystyrene-supported GaCl3 In dichloromethane at 20℃; for 1.25h; | |
With sodium hydrogen sulfate In hexane; dimethyl sulfoxide at 40℃; for 16h; | ||
20 g | With Dowex 50WX8 Hydrogen form In dichloromethane; toluene at 25℃; for 16h; | Step 3. 8-((tetrahydro-2H-pyran-2-yl)oxy)octan-l-ol To a stirred solution of octane- 1 ,8-diol (20 g, 137.9 mol, 1.0 eq.) in Toluene/DCM (4:1) (500 mL) at 25°C was added DHP (13.4 mL, 157.2 mmol, 1.14 eq.) and Dowex 50WX8 Hydrogen form (5 g). The reaction was stirred at 25°C for 16 hours and monitored by TLC. The reaction mixture was quenched with ice water (50 mL) and extracted with EtOAc (3 x 200 mL). The total organic layer was dried over anhydrous NazSCL and concentrated under reduced pressure to obtain the crude, which was purified by silica gel chromatography (60-120 mesh) using gradient elution with 10% EtO Ac/hexane to afford 8 -((tetrahydro-2H-pyran-2-yl)oxy)octan- 1 - ol (20 g) as a colorless liquid. -NMR (400 MHz, CDC13): δ 4.59-4.55 (m, 1H), 3.90-3.83 (m, 1H), 3.76-3.69 (m, 1H), 3.66-3.60 (m, 2H), 3.53-3.46 (m, 1H), 3.41- 3.34 (m, 1H), 1.88-1.78 (m, 1H), 1.75-1.69 (m, 1H), 1.63-1.48 (m, 8H), 1.39-1.29 (m, 8H). |
20 g | With Dowex 50WX8 Hydrogen form In dichloromethane; toluene at 25℃; for 16h; | Step 3. 8-((tetrahydro-2H-pyran-2-yl)oxy)octan-l-ol To a stirred solution of octane- 1 ,8-diol (20 g, 137.9 mol, 1.0 eq.) in Toluene/DCM (4:1) (500 mL) at 25°C was added DHP (13.4 mL, 157.2 mmol, 1.14 eq.) and Dowex 50WX8 Hydrogen form (5 g). The reaction was stirred at 25°C for 16 hours and monitored by TLC. The reaction mixture was quenched with ice water (50 mL) and extracted with EtOAc (3 x 200 mL). The total organic layer was dried over anhydrous NazSCL and concentrated under reduced pressure to obtain the crude, which was purified by silica gel chromatography (60-120 mesh) using gradient elution with 10% EtO Ac/hexane to afford 8 -((tetrahydro-2H-pyran-2-yl)oxy)octan- 1 - ol (20 g) as a colorless liquid. -NMR (400 MHz, CDC13): δ 4.59-4.55 (m, 1H), 3.90-3.83 (m, 1H), 3.76-3.69 (m, 1H), 3.66-3.60 (m, 2H), 3.53-3.46 (m, 1H), 3.41- 3.34 (m, 1H), 1.88-1.78 (m, 1H), 1.75-1.69 (m, 1H), 1.63-1.48 (m, 8H), 1.39-1.29 (m, 8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With zirconium tetrachloride bis(tetrahydrofuran) complex; hydrogen; C24H20B(1-)*C36H55ClIrN2P2(1+); sodium hydride; butan-1-ol In toluene at 180 - 190℃; for 28h; | |
23% | With potassium hydroxide; samarium diiodide In tetrahydrofuran; water for 0.01h; Ambient temperature; | |
94.8 %Chromat. | With cobalt(II) oxide; hydrogen In 1,4-dioxane at 189.84℃; for 10h; Autoclave; | 2.3 Catalytic evaluation and product analysis General procedure: The hydrogenation of carboxylic acids or other substrates was performed in a high-pressure stainless-steel autoclave (Xinyuan Chemical Machinery, Series CJK, 300 mL) with a maximum stirring rate of 1500 r/min. In a typical experiment, 0.2 g of catalyst (or without catalyst for the control experiment), 3 mmol of the substrate, and 100 mL alkane solvent (n-hexane, n-heptane, i-octane, or n-dodecane) were well mixed in the autoclave and purged with pure nitrogen at room temperature. The gas supply and discharge were carried out manually through needle valves. The autoclave was rapidly heated to the desired temperature and hydrogen was introduced at 2 MPa to initiate the reaction. The reaction pressure was kept at 2 MPa with a small negative deviation (∼0.2 MPa) owing to the consumption of hydrogen. Samples of the liquid phase were continuously taken through a sampling tube with a filter at certain intervals. The stirring rate was kept at 750 r/min during the reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium hydroxide In xylene at 100℃; for 3h; | |
68.1% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at -5℃; for 1h; Stage #2: benzyl chloride In N,N-dimethyl-formamide at 20℃; for 8h; | 1 Preparation of Compound H: Sodium hydride (5.47 g, 136.77 mmol) was added to a 500 mL round bottom flask.And adding 50mL of N,N-dimethylformamide, stirring in an ice salt bath (-5 ° C),150 mL of a solution of 1,8-octanediol (20 g, 136.77 mmol) in N,N-dimethylformamide was added dropwise to a round bottom flask, and stirred at this temperature for 1 h;Add benzyl chloride (15.74 mL, 136.77 mmol),The reaction was carried out for 8 h at room temperature, and the reaction was completely confirmed by TLC.The reaction was quenched with saturated ammonium chloride and the aqueous phase was extracted with diethyl ether.The organic phases were combined and washed with saturated aqueous NaCI.The solvent was dried and the column was passed (the eluent was PE/EA = 10/1) to give 22.0 g of Compound H.The yield was 68.1%. |
53% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: benzyl chloride In N,N-dimethyl-formamide at 0 - 20℃; | 1.DS At 0 °C, a solution of octane-l,8-diol (100 g, 0.684 mol) in 100 mL DMF was slowly added into a suspension of NaH (27.35 g, 0.684 mol) in 700 mL DMF. After stirring for 30 min, a solution of benzyl chloride (78.7 mL, 0.684 moles) in 200 mL DMF was slowly added. After addition, the reaction mixture was warmed up to room temperature and stirred overnight. TLC showed starting material was almost consumed. The reaction mixture was poured onto ice, and then extracted by EtOAc (2 X). The combined organic layers were washed with water and brine, and then dried over sodium sulfate. After filtration and concentration, the crude was purified by flash column chromatography (SiC^: 0 to 60% EtOAc/hexanes) to provide the product as a colorless oil (85.83 g, 53%). |
With sodium 1.) xylene, 130 deg C, 2.) xylene, reflux, 15 min; Yield given. Multistep reaction; | ||
Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 50℃; for 10h; Stage #2: benzyl chloride In N,N-dimethyl-formamide at 20℃; | ||
12.19 g | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Cooling with ice; Stage #2: benzyl chloride In 1,2-dimethoxyethane; N,N-dimethyl-formamide | 3 8-(Benzyloxy)octan-1-ol A 60% dispersion of sodium hydride in mineral oil (5.38 g, 134 mmol) was washed with hexanes to remove the oil. While cooling with an ice bath, a mixture of 1,8-octanediol (24.49 g, 168 mmol) in 300 mL of DMF was added slowly. The mixture was allowed to warm to room temperature. After 1 hr, a mixture of benzyl chloride (7.70 mL, 66.7 mmol) in 30 mL of DME was added dropwise. After 2 hr, additional benzyl chloride (1.00 mL, 8.7 mmol) was added, and the mixture was stirred overnight. Then, 2 mL of concentrated NH4OH was added. After 1 hr, the volatile components were evaporated. The residue was taken up in Et20 and thrice washed with 1M HC1 and once with brine. The organic phase was dried over anhydrous MgS04 and evaporated onto silica gel. SPE, washing with 5% EA/Hex and then eluting with 20% EA/Hex gave 12.19 g of the product as a colorless oil. (Eluting with EA gave 12.19 g of recovered 1,8-octanediol after recrystallization from EA/Hex.) R 0.55 (20% EA/Hex). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With pyridine; dmap In N,N-dimethyl-formamide for 2h; Ambient temperature; | |
53% | With dmap; triethylamine In dichloromethane at 0 - 20℃; | 2-Hydroxyethyl Dodecanoate (13a) General procedure: Ethanediol (1.1 mL, 20.00 mmol), Et3N (5.10 g, 50.0 mmol) and DMAP (122 mg, 1.0 mmol) were dissolved in 200 mL anhydrous CH2Cl2. The C11H23COCl (2.18 g, 10.00 mmol) was added dropwise at 0 °C. The mixture was warmed up to room temperature and kept stirring overnight then washed with 1 N HCl solution, water, saturated aqueous solution of NaHCO3and brine, successively. The organic phase was dried overNa2SO4, filtered, and then concentrated. The crude mixture was purified by column chromatography (petroleum ether-EtOAc 30 : 1) on silica gel to afford 13a as a colorless oil (1.51 g, 62%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: 1,8-Octanediol With 1H-imidazole In dichloromethane at 0℃; for 0.25h; Stage #2: tert-butyldimethylsilyl chloride In dichloromethane at 0 - 20℃; for 1h; | 8-((tert-Butyldimethylsilyl)oxy)octan-1-ol (22) Imidazole (7.6 g, 112 mmol) was added to a solution of 1,8-octanediol (15.0 g, 102 mmol) in CH2Cl2 (200 mL) at 0 °C. The solution was stirred for 15 min before adding TBSCl (23.1g, 154 mmol) at 0 °C and allowed to warm to rt. After 1 h, the reaction mixture was diluted with cold water (200 mL), the aqueous layer extracted with CH2Cl2 (2 × 150 mL) and dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure afforded a colorless oil that was purified by silica gel (60-120 mesh) column chromatography to afford 22 as colorless oil (26.1 g, 100.6 mmol, 98%); Rf = 0.5 (20%, EtOAc-hexane).IR max: 3345, 2929, 2856, 1466, 1387, 1252, 1096, 773, 662 cm-1.1H NMR (400 MHz, CDCl3): δ 3.56 (dt, J=2.8, 6.7 Hz, 4H), 1.55-1.41 (m, 1H), 1.34-1.21 (m, 12H), 0.85 (s, 9H), 0.01 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ 63.22, 62.67, 32.73, 32.62, 29.34, 29.31, 25.88, 25.64, 18.26, -5.36 ppm.MS(ESI): m/z 261 [M+H]+.HRMS(ESI) m/z calculated for C14H32O2Si 261.2244, found 261.2242. |
72% | With dmap; triethylamine In dichloromethane Ambient temperature; | |
67% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran at 20℃; for 2h; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran at 20℃; |
66% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 2h; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran; mineral oil at 20℃; | |
65.2% | With 1H-imidazole In dichloromethane at 20℃; Cooling with ice; | |
62% | With triethylamine In dichloromethane at 20℃; Inert atmosphere; | |
61% | With sodium hydride In tetrahydrofuran Inert atmosphere; | |
51% | With dmap; triethylamine In methanol at 0℃; for 1h; Inert atmosphere; | 4.1.7. 8-[(tert-Butyldimethylsilyl)oxy]octan-1-ol (11) To a solution of 1,8-octadiol (10.0 g, 68.4 mmol) in MeOH(340 mL) were added Et3N (47.8 mL, 342 mmol), TBSCl (9.79 g,65.0 mmol) and DMAP (0.418 g, 3.42 mmol) and the mixture wasstirred at 0 °C under nitrogen atmosphere. After stirring for 1 h, thereaction mixture was added to CHCl3 (600 mL) washed with saturatedaqueous NaHCO3 (900 mL), saturated aqueous NH4Cl(900 mL, x2) and brine (900 mL). The organic layer was dried with Na2SO4, filtered and concentrated in vacuo. The crude product waspurified by column chromatography on silica gel (hexane/EtOAc 15/1 to 5/1) to afford 11 (9.06 g, 51%) as a colorless oil.IR (Diamond Prism) ν (cm-1): 3349, 2931, 2858, 1471, 1387,1362,1255, 1099, 1059, 837, 775, 665; 1H NMR (500 MHz, CDCl3) δ (ppm):3.63 (t, J 6.6 Hz, 2H), 3.59 (t, J 6.6 Hz, 2H), 1.58-1.46 (complexm, 4H), 1.35-1.30 (complex m, 8H), 0.88 (s, 9H), 0.04 (s, 6H); 13CNMR (125 MHz, CDCl3) δ (ppm): 63.3, 62.9, 32.8, 32.7, 29.4 (2C),25.9 (3C), 25.69, 25.66, 18.3, 5.3 (2C); HRMS (FAB, NBA) m/z:261.2250 [M+H]+, calcd for C14H33O2Si: 261.2242. |
48% | With dmap; triethylamine In dichloromethane for 6h; | |
48.4% | With 1H-imidazole In N,N-dimethyl-formamide for 15h; | |
46% | With sodium hydride In tetrahydrofuran | |
19% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 17h; | |
With sodium hydride In tetrahydrofuran | ||
With sodium hydride 1.) THF, room temperature, 20 h, 2.) 4 h; Yield given; Multistep reaction; | ||
With 1H-imidazole | ||
In dichloromethane for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 1,8-Octanediol With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #2: propargyl bromide In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; | 4 (4) Preparation of intermediate 5a A 100 mL round bottom flask was charged with 3 g of octane-1,8-diol, 20 mL of anhydrous THF, and 1.3 g of potassium tert-butoxide. The reaction solution was stirred at room temperature under argon for 15 minutes, and 1.2 g of 3-bromopropyne was added dropwise.The reaction solution was stirred under an argon atmosphere at room temperature for 12 hours.The solvent was spin-dried, and the reaction was quenched by adding 30 mL of a saturated sodium chloride aqueous solution. The pH was adjusted to 3-5 with 1M HCl. The mixture was extracted three times with 30 mL x 3 dichloromethane. The organic phases were combined and dried over anhydrous sodium sulfate ,The solvent was spin-dried and separated and purified using a 200-300 mesh silica gel column. The mobile phase was petroleum ether: ethyl acetate = 3: 1 to obtain intermediate 5a with a yield of 55%. |
55% | Stage #1: 1,8-Octanediol With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #2: propargyl bromide In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; | (4) Preparation of intermediate 5a In a 100 mL round bottom flask, 3 g octane-1,8-diol, 20 mL anhydrous THF and 1.3 g potassium tert-butoxide were added.The reaction solution was kept stirring for 15 minutes under argon protection at room temperature, and 1.2 g of 3-bromopropyne was added dropwise.The reaction solution was kept stirred for 12 hours under argon protection at room temperature.Rotate the solvent to dryness, add 30mL saturated sodium chloride aqueous solution to quench the reaction, adjust the pH to 3-5 with 1M HCl, extract the mixture three times with 30mL×3 dichloromethane, combine the organic phases, and dry with anhydrous sodium sulfate , Spin-dry the solvent, use 200-300 mesh silica gel chromatographic column for separation and purification, the mobile phase is petroleum ether: ethyl acetate = 3:1, that is, intermediate 5a is obtained with a yield of 55%. |
20% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: propargyl bromide In tetrahydrofuran at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9% | With triethylamine In tetrahydrofuran; toluene for 14h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With C24H33IrN4O3; water; sodium hydroxide for 18h; Reflux; | |
91% | With sodium bromate; sodium hydrogensulfite In acetonitrile for 2h; Heating; | |
86% | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48h; |
86% | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 20℃; for 48h; Schlenk technique; | 16 Example 15: Synthesis of cyclohex-3-ene-1-carboxylic acid General procedure: Other operations Reference Example 1 was carried out using cyclohexane-3-ene-1-methanol (114.7 mg, 98% purity,1.0 mmol) for 48 hours to give cyclohex-3-ene-1-carboxylic acid 102.5 mg, 81%) (petroleum ether: ethyl acetate= 5: 1).In the oxygen atmosphere (oxygen balloon)Fe (NO3) 3 · 9H2O (40.4 mg, 0.10 mmol),2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO, 15.5 mg, 0.10 mmol)KCl (7.5 mg, 0.10 mmol),Dodecanol (189.0 mg, 98% purity, 1.0 mmol) and1,2-dichloroethane (DCE, 4 mL)Was added to a 50 mL Schlenk tube.Stir at room temperature for 12 h, TLC monitoring until completion of the reaction.The reaction solution was filtered through a short column of silica gel, eluted with ether (75 mL) and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1)The corresponding dodecanoic acid (199.2 mg, 100%) was obtained. |
62% | With potassium permanganate; acetic acid In water at 75℃; for 5.16667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dmap; triethylamine In dichloromethane at 20℃; for 24h; | |
60% | With triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere; | 2.2 General synthetic procedure for Series 2 compounds (TPM-G6 - TPM-G10) General procedure: Synthetic procedure for TPM-G6 is described below as a representative example.The same procedure was used for the synthesis of the remaining compounds (TPMG7 - TPM-G10) at similar molar scales. Trityl chloride (697 mg, 2.50 mmol) dissolved in 4 mL of DCM was added to a stirred solution of 1,6-hexanediol (300 mg,2.50 mmol) in DCM at room temperature in a 50 mL round bottom flask undernitrogen atmosphere. Triethylamine (253 mg, 2.50 mmol) diluted in 2 mL of DCMwas added dropwise to the reaction mixture and stirring continued for 24 h at roomtemperature. The reaction mixture was taken in ~30 mL DCM and washed threetimes with water. The organic extract was dried over anhydrous sodium sulfate andconcentrated by rotary evaporation. The crude product was purified by columnchromatography over silica gel 60-120 mesh using petroleum ether/ethyl acetate(9:1) as the eluent to give compound TPM-G6. |
55% | In pyridine; dichloromethane Ambient temperature; |
With pyridine In N,N-dimethyl-formamide at 20℃; for 1h; | ||
With dmap; triethylamine In dichloromethane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | 2.11 4.2.11. 1,8-Bis(benzyloxy)octane (11) Sodium hydride (0.44 g, 10.94 mmol) was added to a solution of octane diol (0.50 g, 3.42 mmol) in dry DMF (12 mL) at 0 °C and stirred for 15 min. Benzyl bromide (1.09 mL, 9.23 mmol) was added drop-wise to the reaction mixture in cold condition and stirring continued for 3 h at rt. The solvents were evaporated under reduced pressure and the residue worked up with ethyl acetate followed by drying over anhyd sodium sulfate. Purification of the crude product by column chromatography (eluent: 8% ethyl acetate/light petroleum) afforded 11 (1.08 g, 97%) as a colorless oil. Found: C, 80.89; H, 9.14. C22H30O2 requires C, 80.94; H, 9.26%; Rf (5% ethyl acetate/light petroleum) 0.28; 1H NMR (CDCl3, 200 MHz): δ 7.12-7.41 (m, 10H, ArH), 4.48 (s, 4H, PhCH2), 3.44 (t, 4H, J=6.5 Hz, 2×OCH2), 1.50-1.70 (m, 4H, 2×CH2), 1.30 (br s, 8H, 4×CH2) ppm; 13C NMR (CDCl3, 50.3 MHz): δ 138.8, 128.4, 127.7, 127.6, 72.9, 70.6, 29.9, 29.5, 26.2 ppm. |
Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran at 60℃; for 0.5h; Stage #2: benzyl bromide In tetrahydrofuran at 60℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With pyridine In chloroform at 0℃; | |
56% | With sodium hydroxide In tetrahydrofuran; water at 0℃; Inert atmosphere; | |
53% | With pyridine at 20℃; |
46% | With dmap; triethylamine In dichloromethane at 20℃; for 24h; | |
43% | With pyridine In dichloromethane at 20℃; | 7 Toluene-4-sulfonic acid 8-hydroxy-octyl ester (Reagent 7) To a mixture of HO(CH2)8OH (1.8 g, 12 mmol) and pyridine (0.91 g, 10 mmol) in CH2Cl2 (20 mL) was added dropwise a solution of TsCl (1.9 g, 10 mmol) in CH2Cl2 (10 mL). The mixture was stirred at rt overnight, and washed with 1.0 M hydrochloride (10 mL*2) and dried over Na2SO4. After the solvent was removed under reduced pressure, the residue was purified by chromatography on silica gel (eluted with petroleum ether:ethyl acetate=4:1) to give reagent 7 as a colorless oil (1.3 g, 43% yield). |
20% | With pyridine In dichloromethane at 20℃; for 16h; | 1 Step 1-8-Hydroxyoctyl 4-methylbenzenesulfonate To a mixture of octane-1,8-diol (23.5 g, 160 mmol, CAS629-41-4) and pyridine (10.1 g, 128 mmol) in DCM (360 mL) was added a solution of TsCl (24.5 g, 128 mmol) in DCM (240 mL) dropwise. The mixture was then stirred at rt for 16 hours. On completion, the mixture was washed with 1N HCl (2×50 mL). The organic layer was dried with Na2SO4, filtered and concentrated in vacuo to give a residue. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=3:1) to give the title compound (10.0 g, 20% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 4.02 (t, J=6.4 Hz, 2H), 3.63 (t, J=6.4 Hz, 2H), 2.45 (s, 3H), 1.69-1.60 (m, 2H), 1.56-1.53 (m, 2H), 1.36-1.23 (m, 8H); LC-MS (ESI+) m/z 323.0 (M+Na)+. |
With dmap; triethylamine In dichloromethane | ||
With triethylamine In tetrahydrofuran at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: C12H13O2(CH3)3(O)(OO) With sodium tetrahydroborate; amberlyst-15 In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 1,8-Octanediol In dichloromethane at 20℃; for 32h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With HY-Zeolite In chloroform for 3.5h; Heating; | |
89% | With sulfuric acid In toluene at 75℃; for 15h; | |
68% | With sulfuric acid In water; pentane for 12h; Reflux; | 1 first step Octane-1,8-diol (2.0 g), concentrated sulfuric acid (4 ml), acetic acid (25 ml), water (200 ml)Was placed in a continuous extractor. The mixture was heated to reflux with pentane (200 ml) for 12 hours. The pentane layer is washed with a saturated aqueous solution of sodium bicarbonate, followed by a saturated saline solution.Washed with. After drying over magnesium sulfate and filtering, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 8-hydroxyoctyl acetate (1.7 g, 68%). |
46% | With sulfuric acid In water; toluene for 36h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 1H-imidazole In dichloromethane | |
71% | With 1H-imidazole In dichloromethane at 20℃; Inert atmosphere; | |
67% | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h; |
58% | With 1H-imidazole In tetrahydrofuran at 20℃; for 9h; | |
51.9% | With 1H-imidazole In dichloromethane at 20℃; for 24h; | 10 8-((tert-Butyldiphenylsilyl)oxy)octane-1-ol 14 Tert-butyldiphenylchlorosilane (17.50 ml, 68.39 mmol, 1 eq.) was added to a solution of 1,8-octanediol (10.0 g, 68.39 mmol) and imidazole (5.59 g, 82.06 mmol, 1.2 eq.) in DCM (250 ml), and the reaction mixture was stirred for 24 h at rt. The solution was poured into a 1000 ml separatory flask, diluted with water (400 ml) and brine (100 ml), and the product was extracted with DCM (2 x 100 ml). The combined organic phase was washed with brine (100 ml), dried over anhydrous sodium sulphate, filtered through an S2 frit, and the solvents were evaporated in an RVE. The crude product was purified by silica gel column chromatography using a linear gradient of ethyl acetate in cyclohexane (0-30 %). Alcohol 14 (13.65 g, 51.9 %; Rf 0.35 in mobile phase CE20, detection with KMnO4) was obtained as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.08 (s, 9H), 1.31-1.41 (m, 8H), 1.55-1.62 (m, 4H), 3.64-3.70 (m, 4H), 7.38-7.47 (m, 6H), 7.69-7.71 (m, 4H) ppm.13C NMR (101 MHz, CDCl3): δ = 19.24, 25.68, 25.72, 26.89, 29.33, 29.38, 32.56, 32.79, 63.09, 63.99, 127.57, 129.48, 134.19, 135.58 ppm. IR (CCl4): νmax/cm- 1 = 3072 m (20a); 3053 m (20b); 2529 s, sh (tBu, νas CH3); 2898 s, sh (tBu, νs CH3); 1590, 1568 (8a, 8b); 1487 m (19a); 1463 m, 1473 s (tBu, δas CH3); 1428 s (19b); 1390 m, 1362 m (tBu, δs CH3); 1189 m; 1112 vs, 1094 vs (νas Si-Ph); 1030 m (18a); 1008 m (δ Ph-Si); 939 m (r CH3); 701 vs (νs COSi); 688 m (4); 622 m (6b); 614 s (6a); 505 s (16b); 489 m (δ Si-Ph); 2932 vs (νas CH2); 2858 vs (νs CH2); 3636 m, 3341 m, br (νs OH); 1057 m (νs C-OH). HRMS (ESI): m/z calculated for C24H36O2NaSi [M + Na]+ 407.23768; found 407.23742. |
37% | Stage #1: 1,8-Octanediol With 1H-imidazole In dichloromethane at 20℃; for 0.583333h; Stage #2: tert-butylchlorodiphenylsilane In dichloromethane at 20℃; for 0.166667h; | |
37% | With 1H-imidazole In dichloromethane at 20℃; for 12h; | |
With 1H-imidazole In tetrahydrofuran for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 26% | With 4-methylmorpholine N-oxide In dimethyl sulfoxide at 20℃; for 65.5h; | 1.2 2. Step 2: Oxidation in Aldehyde 708 g (5.87, 3 eq) of anhydrous N-methylmorpholine N-oxide was dissolved under N2 in 3 l of DMSO. 410 g (1.96 mol) of 8-bromooctanol dissolved in 1 l of DMSO was then added over 30 minutes. The medium became clear. N-methylmorpholine ammonium bromide precipitated. After 65 h of agitation at ambient temperature, the salt was filtered and the medium was taken up with 4 l of a saturated solution of NaCl. After extraction with 4×1 l of ethyl acetate and drying, 320 g of crude product, constituted of 74% of aldehyde (yield=83%) and 26% of 1,8-octanediol. [0063] Characterization [0064] TLC: Rf=0.6 (heptane/ethyl acetate 8/2) [0065] 1H NMR (400 MHz, CDCl3): 9.74 (t, 1H, J=1.7 Hz); 3.61 (t, 2H, J=6.6 Hz); 2.41 (dt, 2H, J=1.7 and 7.3 Hz); 1.51-1.65 (m, 4H); 1.24-1.37 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
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at 230℃; for 1 - 2h; | 18 To the a clean dry reaction flask equipped with heating, thermometer, agitation, vacuum and an ability to remove water is added the specified number of grams of the specified chain capper (examples 1-8). Next add the specified number of grams of the specified diol (example 9-11). Next add 0.1% by weight, based upon the total weight of the capper and diol of ZnO. Mix well and heat to 230° C. The reaction will begin at about 170° C. The heating should be rapid, most commonly with 1-2 hours. The reaction progress is monitored by water generated and a drop in hydroxyl value. When the hydroxyl value approaches theoretical, the reaction is cooled and the product filtered at 100° C. The product is used without additional purification. The compounds of example 12-20 are highly lubricious and oxidatively stable. They provide an outstanding feel on the skin as prepared, when diluted in solvent, when formulated into lotions, and emulsions. |
Yield | Reaction Conditions | Operation in experiment |
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46% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0℃; Stage #2: alpha-bromo-3,4-difluorotoluene In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil for 4h; | 1.1 Example 1; (R)-3-[8-(3,4-Difluoro-benzyloxy)-octanoylamino]-4-dimethylamino-butyric acid; Step 1: A solution of 1,8-octanediol (300 mg, 2.05 mmol) in tetrahydrofuran/N,N-dimethylformamide 2:1 (3 mL) was added dropwise at 0° C. to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.3 mmol) in N,N-dimethylformamide (1.5 mL), then after 2 h 3,4-difluorobenzyl bromide (445 mg, 2.15 mmol) was added. After 4 h the reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2, heptane-ethyl acetate gradient) afforded 8-(3,4-difluoro-benzyloxy)-octan-1-ol (258 mg, 46%). Colorless oil, m/e=273.3 ([M+H]+). |
46% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0℃; Stage #2: alpha-bromo-3,4-difluorotoluene In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil for 4h; | 1.1 Intermediate 1; (R)-3-[8-(3,4-Difluoro-benzyloxy)-octanoylamino]-4-dimethylamino-butyric acid; Step 1: A solution of 1,8-octanediol (300 mg, 2.05 mmol) in tetrahydrofuran/N,N-dimethylformamide 2:1 (3 mL) was added dropwise at 0° C. to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.3 mmol) in N,N-dimethylformamide (1.5 mL), then after 2 h 3,4-difluorobenzyl bromide (445 mg, 2.15 mmol) was added. After 4 h the reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2, heptane-ethyl acetate gradient) afforded 8-(3,4-difluoro-benzyloxy)-octan-1-ol (258 mg, 46%). Colorless oil, m/e=273.3 ([M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With Pt-Sn/γ-Al2O3 In o-xylene at 145℃; for 24h; Inert atmosphere; | A general procedure for the direct synthesis of diamines 3 from the N-alkylation of amines 2 with diols 1: General procedure: Under nitrogen atmosphere, to a 15-mL Pyrex glass screw-cap tube were added diol 1 (1.0 mmol), amine 2 (2.0 mmol), Pt-Sn/γ-Al2O3 catalyst (200 mg, 0.5 mol % Pt), and o-xylene (5 mL). The resultant mixture was stirred in the sealed tube at 145 °C for 24 h. After cooled to ambient temperature, the catalyst was removed by centrifugation and washed with CH2Cl2 (3 × 5 mL). The combined supernatant was condensed under reduced pressure and subjected to purification by silica gel column chromatography (eluent: petroleum ether (60-90 °C)/EtOAc = 20:1, v/v), affording diamine 3. The known compounds were identified by comparison of their NMR features with the reported data or of their GC traces with those of the authentic samples. The spectroscopic features of these known compounds are in good agreement with those reported in the literatures. All the new products were characterized by NMR and HRMS techniques. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLES 'TMPTMA' refers to trimethylolpropane trimethacrylate; 'MHP' refers to 6-methacryloxyhexyl phosphate, prepared as described in ; 'MDP' refers to 10-methacryloxydecyl phosphate, prepared as described in ; 'MOP' refers to 8-methacryloxyoctyl phosphate, prepared from 1,8-octanediol using the method essentially as described for the preparation of MHP and MDP in ; 'HEMA' refers to 2-hydroxyethyl methacrylate; '1,3-BDDM' refers to 1,3-butanediol dimethacrylate; 'MA' refers to methacrylic acid; 'TEGDMA' refers to triethyleneglycol dimethacrylate; '2-TMSEM' refers to 2-(trimethoxysiloxy)ethyl methacrylate (obtained from Polysciences Inc., Warrington, PA; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.3% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 24h; | 224c 2-(8-hydroxyoctyloxy)-6-nitrobenzonitrile To a solution of 1,8-octanediol (3.87 mmol, 566 mg) in THF (dry, 10 mL) was added 2,6-dinitrobenzonitrile (1.29 mmol, 250 mg) and DBU (1.30 mmol, 194 L). The reaction mixture was stirred for 24 hours at room temperature an evaporated. The oily residue was triturated with 10% citric acid/water and solid NaCl added. The precipitate was collected, washed with water, dried in vacuo and purified on silica gel (40% to 100% EtOAc in hexanes) to give the desired product (235 mg, 62.3%) as a pinkish solid. MS 293 (MH+). |
62.3% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran; ethyl acetate | 224.c 2-(8-hydroxyoctyloxy)-6-nitrobenzonitrile Example 224c 2-(8-hydroxyoctyloxy)-6-nitrobenzonitrile To a solution of 1,8-octanediol (3.87 mmol, 566 mg) in THF (dry, 10 mL) was added 2,6-dinitrobenzonitrile (1.29 mmol, 250 mg) and DBU (1.30 mmol, 194 μL). The reaction mixture was stirred for 24 hours at room temperature an evaporated. The oily residue was triturated with 10% citric acid/water and solid NaCl added. The precipitate was collected, washed with water, dried in vacuo and purified on silica gel (40% to 100% EtOAc in hexanes) to give the desired product (235 mg, 62.3%) as a pinkish solid. MS 293 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; dimethyl sulfoxide; paraffin oil at 0℃; for 1h; Inert atmosphere; Stage #2: p-methoxybenzyl chloride With N,N,N-tributyl-1-butanaminium iodide In tetrahydrofuran; dimethyl sulfoxide; paraffin oil at 0 - 20℃; for 3h; Inert atmosphere; | |
78% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran; dimethyl sulfoxide; mineral oil at 0℃; for 1h; Stage #2: p-methoxybenzyl chloride With N,N,N-tributyl-1-butanaminium iodide In tetrahydrofuran; dimethyl sulfoxide; mineral oil at 0 - 20℃; for 18h; | |
69% | With silver(I) oxide In dichloromethane at 20℃; Inert atmosphere; |
63% | Stage #1: 1,8-Octanediol With N,N,N-tributyl-1-butanaminium iodide; sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: p-methoxybenzyl chloride In tetrahydrofuran at 60℃; Inert atmosphere; | General procedure for PMB protection of diol or alkynyl alcohol (for compounds 18, 1938 and PMBO(CH2)2C≡CH and PMBO(CH2)3C≡CH General procedure: Diol or alkynyl alcohol (1.2 equiv.) was added portionwise to a suspension of sodium hydride (60% in mineral oil, 1.2 equiv. and TBAI (0.1 equiv. in dry THF (conc. of diol ca 0.5 M) at 0°C under argon. The mixture was warmed up to r.t. with stirring. PMBCl (1.0 equiv.) was added at r.t. and the reaction mixture was heated at 60°C overnight. Once cooled to r.t. and quenched with water, the two layers ofthe mixture were separated and aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine and dried over anhydrous MgSO4 . The solvent was removed in rotary evaporator and the residue was purified by column chromatography (silica gel, pet. ether/EtOAc4/1) to give the product. |
58% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Cooling with ice; Stage #2: p-methoxybenzyl chloride In N,N-dimethyl-formamide for 2.5h; Cooling with ice; | 4.1.1 The oil attached to 63 wt % sodium hydride (1.14 g, 30.1 mmol, 1.00 eq.) was washed three times with hexane and removed. Subsequently, thereto were added dry DMF (30.0 mL) and 1,8-octanediol (4.40 g, 30.1 mmol, 1.00 eq.) at 0 degrees. The mixture was allowed to react for 5 minutes with ice-cooling, and then thereto was dropwise added a solution of PMBCl (4.08 mL, 30.1 mmol, 1.00 eq.) in dry DMF (20.0 mL) over 1 hour. The reaction mixture was allowed to react for further 1.5 hours and then poured into an aqueous ammonium chloride solution with ice-cooling, and the organic phase was extracted with ethyl acetate. The resulting organic phase was washed with 1 M hydrochloric acid, saturated sodium bicarbonate, and a saturated salt solution. The washed organic phase was dried over magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=75:25) to obtain 8-((4-methoxybenzyl)oxy)octa-1-nol as shown below (4.66 g, 17.5 mmol, 58%).Furthermore, the analysis results of the obtained compound were as follows.1H NMR (400 MHz, CDCl3): δ 7.26 (d, 2H, aromatic, J=9.2 Hz), 6.88 (d, 2H, aromatic, J=9.2 Hz), 4.43 (br-s, 2H, 4-MeOBn), 3.80 (s, 3H, Me), 3.63 (t, 2H, H-h, Jg,h=6.8 Hz), 3.43 (t, 2H, H-a, Ja,b=6.8 Hz), 1.52-1.63 (m, 4H, H-b, H-g), 1.27-1.39 (m, 8H, H-c, H-d, H-e, H-f); 13C NMR (100 MHz, CDCl3): δ 129.2, 113.7, 72.5, 70.1, 63.0, 55.3, 32.7, 29.7, 29.4, 29.3, 26.1, 25.6; FT-IR (neat): 2874, 1598, 1355, 1177, 1098, 923, 664, 555 (cm-1); HRMS (ESI-TOF) Calcd for C24H39N2O7 [M+Na]+ 467.2758. found 467.2757. |
With N,N,N-tributyl-1-butanaminium iodide; sodium hydride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: p-methoxybenzyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | 2.12 4.2.12. 1,8-Bis(4-methoxybenzyloxy)octane (12) Sodium hydride (0.44 g, 10.94 mmol) was added to a solution of octane-1,8-diol (0.50 g, 3.42 mmol) in dry DMF (12 mL) at 0 °C and stirred for 15 min. PMBCl (1.25 mL, 9.23 mmol) was added drop-wise to the reaction mixture (0-5 °C) and stirred for 3 h at rt. The reaction mixture was concentrated under reduced pressure and the residue worked up with ethyl acetate followed by drying over anhyd sodium sulfate. Purification of the crude product by column chromatography (eluent: 12% ethyl acetate/light petroleum) afforded 12 as a colorless oil (1.12 g, 89%), which turned into solid. Found: C, 74.20; H, 9.04. C24H34O4 requires C, 74.58; H, 8.87%; Rf (10% ethyl acetate/light petroleum) 0.30; mp=31.7-33.3 °C; 1H NMR (CDCl3, 200 MHz): δ 7.20-7.32 (m, 4H, ArH), 6.82-6.93 (m, 4H, ArH), 4.43 (s, 4H, PhCH2), 3.80 (s, 6H, 2×OCH3), 3.42 (t, 4H, J=6.7 Hz, 2×OCH2), 1.50-1.67 (m, 4H, 2×CH2), 1.29 (br s, 8H, 4×CH2) ppm; 13C NMR (CDCl3, 50.3 MHz): δ 159.1, 130.8, 129.3, 113.8, 72.5, 70.2, 55.3, 29.8, 29.5, 26.2 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 1,8-Octanediol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: 1-bromomethyl-4-bromobenzene In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | 2.13 4.2.13. 1,8-Bis(4-bromobenzyloxy)octane (13) Sodium hydride (0.66 g, 16.40 mmol) was added to a solution of octane-1,8-diol (1.00 g, 6.84 mmol) in dry DMF (20 mL) at 0 °C and stirred for 15 min. p-Bromobenzyl bromide (3.4 g, 13.68 mmol) was added to the reaction mixture (0-5 °C) and stirring continued for 3 h at rt. The reaction mixture was concentrated under reduced pressure and the residue worked up with ethyl acetate followed by drying over anhyd sodium sulfate. Purification of the crude product by column chromatography (eluent: 16% ethyl acetate/light petroleum) afforded 13 (3.08 g, 93%) as a colorless solid. Found: C, 54.59; H, 5.77. C22H28Br2O2 requires C, 54.56; H, 5.83%; Rf (10% ethyl acetate/light petroleum) 0.48; mp=44-46.5 °C; 1H NMR (CDCl3, 200 MHz): δ 7.41-7.52 (m, 4H, ArH), 7.17-7.25 (m, 4H, ArH), 4.44 (s, 4H, PhCH2), 3.44 (t, 4H, J=6.6 Hz, 2×OCH2), 1.52-1.67 (m, 4H, 2×CH2), 1.20-1.42 (m, 8H, 4×CH2) ppm; 13C NMR (CDCl3, 50.3 MHz): δ 137.8, 131.5, 129.2, 121.3, 72.1, 70.6, 29.7, 29.4, 26.1 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With Pd(OH)2/C In methanol for 5h; Reflux; | 4.3. General procedure for the cleavage of ethers (conditions A-G) General procedure: The required ether was dissolved in alcohol (methanol or 2-propanol or tert-butanol) and refluxed after the addition of Pd(OH)2/C (20 wt %, 0.35-1.05 g/mmol of the substrate). The reaction mixture was filtered through a short bed of Celite, and Celite washed with a suitable solvent (ethyl acetate, methanol, DCM, water). The filtrate was concentrated and the products were isolated by column chromatography over silica gel (100-200 mesh for compounds 1, 11, 23, 24 and 230-400 mesh for others). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With Pd(OH)2/C In isopropyl alcohol for 1.5h; Reflux; | 4.3. General procedure for the cleavage of ethers (conditions A-G) General procedure: The required ether was dissolved in alcohol (methanol or 2-propanol or tert-butanol) and refluxed after the addition of Pd(OH)2/C (20 wt %, 0.35-1.05 g/mmol of the substrate). The reaction mixture was filtered through a short bed of Celite, and Celite washed with a suitable solvent (ethyl acetate, methanol, DCM, water). The filtrate was concentrated and the products were isolated by column chromatography over silica gel (100-200 mesh for compounds 1, 11, 23, 24 and 230-400 mesh for others). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 1h;Inert atmosphere; | General procedure: Appropriate diol (1 equiv), 1-bromomethyl pyrene (2.2 equiv), and 3 ml ([diol]=50 mM) anhydrous DMF were placed in a round-bottomed flask under N2. NaH (3.0 equiv) was added to the solution at room temperature. The reaction mixture was stirred for 1 h at this constant temperature. Following completion, the reaction was quenched with H2O. The solution was diluted with water, and extracted using DCM. The organic layer was filtered through Na2SO4 and evaporated to dryness. The resulting residue was purified over silica gel (1:5, EtOAc/Hexane) to yield the desired product. |
31% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 1h;Inert atmosphere; | Octane-1,8-diol (99 mg, 0.68 mmol) (1 eq.)And 1-(bromomethyl)pyrene (440 mg, 1.49 mmol) (2.2 eq.),3 mL ([diol] = 50 mM) in anhydrous dimethylformamide in (DMF)To room temperature in the presence and condition of N2 and NaH (3 eq.), It was added to the round bottom flask. The mixed solution in the flask was stirred at room temperature for 1 hour.After that,Then quenched and diluted with distilled water was added to the solution.next, The organics were extracted by the addition of methyl-dichloro (DCM) to the mixed solution,The resulting organic layer was again distilled under reduced pressure to reotgo so that solution filtered through a filter containing sodium sulfate (Na2SO4).The resultant was purified by silica gel column chromatography (EtOAc: Hexane = 1: 5 (volume ratio)) of the solid state compound containing pyrene dimer increasing the purity of the resultant using,To give the 120 mg at a yield of 31%. |
Yield | Reaction Conditions | Operation in experiment |
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75% | With 10-camphorsufonic acid In dichloromethane at 20℃; for 24h; Inert atmosphere; | 4.2 General procedure for the catalytic azlactone ring opening in the presence of nucleophiles General procedure: In a flamed screw cap vial and under nitrogen atmosphere, 0.2 mmol of azlactone was added. After, CH2Cl2 was cannulated at the concentration of 0.2 M in azlactone. To this solution, 0.02 mmol (10.0 mol %) of (+/-)-camphorsulfonic acid was added followed by 0.21 mmol of nucleophile. The reaction mixture was kept at room temperature and under nitrogen atmosphere for 24 h. The reaction mixture was then diluted in CH2Cl2 (10 mL) and washed with saturated solution of sodium bicarbonate (5 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. After, the crude reaction mixture was purified through silica gel chromatography by using ethyl acetate/hexanes as solvents (up to 25% ethyl acetate/hexanes). The purified products were then fully characterized by the conventional elemental analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 1,8-Octanediol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: p-Methoxybenzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 0 - 20℃; for 1h; | 8-(4-methoxybenzyloxy)octan-1-ol (5) To a solution of 1,8-octanediol (2.0 g, 13.0 mmol) in dry THF (20 mL) was added NaH (60%, 0.328 g, 13mmol) at 0 °C, the reaction mixture was stirred for 30 min at same temperature. Then p-methoxybenzyl bromide (2.47 g, 12.0 mmol) was added slowly at 0 °C followed by TBAI (cat.), stirred at rt for 1 h. After completion of the reaction, the mixture was quenched with cold water at 0 °C and the two layers were separated, the aqueous phase was extracted with EtOAc (3 × 20mL). The combined organic layers were washed with water and brine, dried over anh. Na2SO4 and concentrated under vacuo. The residue was purified by silica gel column chromatography using Hexanes/EtOAc (7:3) as eluent to furnish the mono-PMB protected alcohol 5 (2.9 g, 80%) ascolorless oil. IR (neat): 3419, 2930, 2855, 1612, 1512, 1247, 1035. 1H-NMR(CDCl3, 300 MHz):δ 7.26 (d, J = 8.3 Hz, 2H), 6.87 (d, J= 8.1 Hz, 2H), 4.42 (s, 2H), 3.80 (s, 3H), 3.62 (t, J = 6.6 Hz, 2H), 3.42 (t, J= 6.4 Hz, 2H), 1.66-1.47 (m, 4H), 1.31 (s, 8H). 13C-NMR (CDCl3, 75 MHz: δ 159.0, 130.6,129.2, 113.7, 72.5, 70.1, 62.7, 55.2, 32.7, 29.7, 29.3, 26.1, 25.6. ESI-MS: m/z 289 [M+Na]+. HRMS (ESI): calc. 267.1954 C16H27O3,found 267.1955 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; at 100℃; under 75.0075 Torr; for 6h; | Intermediate 52a: 8-hydroxyoctyl decanoate In a round bottom flask, octane-1 ,8-diol (21.90 g, 150 mmol), ethyl decanoate (10 g, 49.9 mmol) and tosic acid trihydrate (0.4 g, 2.103 mmol) were mixed. The flask was placed on a rotary evaporator under reduced pressure (100 mbar) and rotated slowly in a 100 C oil bath to form a clear melt. After 6h, the pressure was reduced to 10 mbar and reaction was held for 15 minutes. The reaction was then diluted with 150 mL heptane and was stirred until octane-diol began to solidify. The reaction was placed in an ice bath and stirred 10 minutes, then filtered. The residue was washed with an additional 150 mL heptane, and the combined filtrates were transferred to a sepratory funnel. The heptane layer was washed with 3 x 150 mL water, then the combined water washes were back extracted with 100 mL heptane. The combined heptane extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the desired product (contaminated with bis-acylated product), which was utilized without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10.7%; 62.1% | With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; | To a suspension of 1-(bromomethyl)pyrene (500 mg, 1.69 mmol) and 1,8-octandiol (160 mg, 1.09 mmol in dry DMF (10 mL) were sodium hydride (180 mg, 4.50 mmol) added at 0 C. The reaction mixture was then stirred for 4 h at room temperature. The reaction mixture was quenched with cold water and the organic layer was extracted with dichloromethane. After the solvent was removed under reduced pressure, the residue was subjected to flash chromatography (EtOAc/hexane = 1/6) to afford 3 (244 mg, 0.68 mmol, 62.1% yield) and the known 4 (68 mg, 0.12 mmol, 10.7% yield) as yellow solids: mp 48.2-50.1 C; 1H NMR (400 MHz, Chloroform-d) delta 8.38 (d, J = 9.3 Hz, 1H), 8.23-8.11 (m, 4H), 8.05-7.98 (m, 4H), 5.25 (s, 1H), 5.21 (s, 2H), 3.60 (t, J = 6.6 Hz, 2H), 3.56 (t, J= 6.5 Hz, 2H), 1.69-1.19 (m, 12H); 13C NMR (100 MHz, CDCl3) delta 131.92, 131.37, 131.32, 130.96, 129.45, 127.69, 127.55, 127.43, 127.02, 126.01, 125.27, 125.26, 125.05, 124.87, 124.59, 123.65, 71.60, 70.61, 63.05, 32.84, 29.94, 29.47, 26.27, 25.77; FAB: m/z [M]+ calcd for C25H28O2: 360.2089; found: 360.2091. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With toluene-4-sulfonic acid In 1,4-dioxane at 160℃; for 0.833333h; | 2 4.1.2. Tetramethylene-1,4-diyl-bis-(3,4,5-trihydroxybenzoate) (8) General procedure: Gallic acid 1 (3.3 mmol, 566 mg), 1,4-butanediol (1.1 mmol, 100 mg) and a catalytic amount of p-toluensulfonic acid were dissolved in dioxane (5 mL) in a distillation system. The mixture was heated at 160 °C distilling the solvent which is continuously refilled until the reaction was completed. The reaction mixture was allowed to reach room temperature and then was cooled by a water-ice bath to give a precipitate that was filtered and washed with gently quantities of diethyl ether to give 305 mg (70%) of 8 as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 10h; | 5 4.1.2. Synthesis of compound 17 General procedure: To a solution of compound 16 (0.9 g, 5 mmol) in 50 mL driedDCM, 1.2 mL 1,4-butanediol, PyBOP (3.1 g, 6 mmol) and triethylamine(1.6 mL, 6.5 mmol) were added and the mixture was stirred at room temperature for 10 h. DCM was removed and the residuewas extracted with EtOAc (3 50 mL) and washed twice with water and brine. The organic portion was dried by anhydrou sNa2SO4. The crude product was obtained by removing EtOAc andpurified by silica chromatography column (P:E = 3:1) to get the product. 4.1.2.5 5(6)-((8-hydroxyoctyloxy)carbonyl)benzo[c][1,2,5]oxadiazole 1-oxide (17e) Weak yellow solid, yield: 75%. 1H NMR (600 MHz, CDCl3) δ 8.01 (s, 1H), 7.67 (s, 1H), 7.38 (s, 1H), 4.43 (t, J = 6.5 Hz, 2H), 3.71 (t, J = 6.4 Hz, 2H), 1.84-1.70 (m, 2H), 1.61 (dd, J = 13.2, 6.6 Hz, 2H), 1.42-1.37 (m, 2H), 1.31 (dd, J = 17.1, 8.1 Hz, 4H). 13C NMR (151 MHz, CDCl3) δ 164.2, 145.3, 134.9, 133.5, 128.1, 127.9, 125.6, 66.5, 62.8, 32.7, 29.2, 29.1, 28.5, 25.8, 25.6. ESI-MS m/z 309.3 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 10h; | 5 4.1.2. Synthesis of compound 17 General procedure: To a solution of compound 16 (0.9 g, 5 mmol) in 50 mL driedDCM, 1.2 mL 1,4-butanediol, PyBOP (3.1 g, 6 mmol) and triethylamine(1.6 mL, 6.5 mmol) were added and the mixture was stirred at room temperature for 10 h. DCM was removed and the residuewas extracted with EtOAc (3 50 mL) and washed twice with water and brine. The organic portion was dried by anhydrou sNa2SO4. The crude product was obtained by removing EtOAc andpurified by silica chromatography column (P:E = 3:1) to get the product. 4.1.6.5 4(7)-((8-hydroxyoctyloxy)carbonyl)benzo[c][1,2,5]oxadiazole 1-oxide (22e) Weak yellow solid, yield: 77%. 1H NMR (600 MHz, CDCl3) δ 8.07 (dd, J = 7.9, 1.6 Hz, 1H), 7.94 (dd, J = 8.1, 1.5 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 4.40 (t, J = 6.7 Hz, 2H), 3.63 (t, J = 6.6 Hz, 2H), 1.84-1.76 (m, 2H), 1.56 (dd, J = 13.8, 6.8 Hz, 2H), 1.48-1.42 (m, 2H), 1.39 (dd, J = 16.8, 8.3 Hz, 4H). 13C NMR (151 MHz, CDCl3) δ 164.2, 145.3, 134.9, 133.5, 128.1, 127.9, 125.6, 66.5, 62.8, 32.7, 29.2, 29.1, 28.5, 25.8, 25.6. ESI-MS m/z 309.3 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With N,N-dimethylamino-pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane | 37.1 (1) (1) Synthesis of 8-hydroxyoctyl methacrylate First, 219 g of 1,8-octanediol (1.5 mol, produced by Wako Pure Chem. Ind., Ltd.), 96 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.5 mol, produced by TOYOBO Co., Ltd.), 12 g of N,N-dimethylaminopyridine (produced by Wako Pure Chem. Ind., Ltd.) were dissolved in 2L of dichloromethane, 43 g of methacrylic acid (0.5 mol, produced by Wako Pure Chem. Ind., Ltd.) was added dropwise, and stirred at room temperature for 12 hours. Solvent was distilled off under reducer pressure by using rotary evaporator, purified by silica-gel column chromatography using mixed solution with 3/2 by volume ratio of hexane/ethyl acetate as elution solvent to obtain 72 g of colorless oily 8-hydroxyoctyl methacrylate (yield, 68%). |
68% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; | 37.1 Synthesis of Dye Monomer M-23 (1) Synthesis of 8-hydroxyoctyl methacrylate First, 219 g of 1,8-octanediol (1.5 mol, produced by Wako Pure Chem. Ind., Ltd.), 96 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.5 mol, produced by TOYOBO Co., Ltd.), 12 g of N,N-dimethylaminopyridine (produced by Wako Pure Chem. Ind., Ltd.) were dissolved in 2 L of dichloromethane, 43 g of methacrylic acid (0.5 mol, produced by Wako Pure Chem. Ind., Ltd.) was added dropwise, and stirred at room temperature for 12 hours. Solvent was distilled off under reducer pressure by using rotary evaporator, purified by silica-gel column chromatography using mixed solution with 3/2 by volume ratio of hexane/ethyl acetate as elution solvent to obtain 72 g of colorless oily 8-hydroxyoctyl methacrylate (yield, 68%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With iodine In acetonitrile at 120℃; for 0.0666667h; Microwave irradiation; chemoselective reaction; | 4. 2. Typical Procedure for Iodinationof Alcohol General procedure: To a suspension of polymer-bound triphenylphosphine (1.2 mmol) in anhydrous acetonitrile (10 mL) were added iodine (1 mmol) and 1,6-hexanediol diol (1mmol). The reaction mixture was irradiated in microwave reactor at 120 °C for 3 min. The reaction mixture was filtered over a filter paper and washed with chloroform.The filtrate was extracted with aqueous sodium thiosulfate solution and dried with anhydrous sodium sulfate.The reafter, solvent was removed under reduced pressure to obtain 6-iodohexan-1-ol (30) in 93% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 1,8-Octanediol With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: DMTr-L-Prolinol In acetonitrile at 20℃; for 24h; Inert atmosphere; | (1) DMTr-Urethane-L-Prolinol (Compound 4) (1) DMTr-Urethane-L-Prolinol (Compound 4)1,8-octanediol (9.0 g, 62 mmol) was dissolved in 90 ml of THF, and this solution was placed under argon. On the other hand, carbonyldiimidazole (2.0 g, 12 mmol) was dissolved in 10 ml of THF. The latter THF solution was added to the former THF solution, and this was stirred for 1 hour at room temperature. This reaction solution was washed with water until a spot of the 1,8-octanediol no longer was observed in TLC. Further, an organic layer collected after the washing was washed with saturated saline and dried with anhydrous sodium sulfate. The organic layer was filtered, and the filtrate obtained was vacuum concentrated. The residual substance obtained was applied to silica gel column chromatography (the eluent: CH2C12:CH3OH=95:5). Thus, a purified title compound was obtained. In this compound, one end of the 1 ,8-octanediol was activated with carbonyldiimidazole (2.3 g, yield: 77%).0.9 g of the compound was dissolved in 10 ml of acetonitrile, and this solution was placed under argon. On the other hand, DMTr-L-prolinol (Compound 3) (1.9 g, 4.8 mmol) was dissolved in 20 ml of acetonitrile. The latter acetonitrile solution was added to the former acetonitrile solution, and this was stirred for 24 hours at room temperature. Then, this reaction solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated saline. An organic layer was collected and dried with anhydrous sodium sulfate. The organic layer was filtered, and the filtrate obtained was vacuum concentrated. The residual substance obtained was applied to silica gel column chromatography (the eluent: dichloromethane:acetone=9:1, containing 0.1% pyridine). Thus, purified Compound 4 (prolinol-urethaneamidite) was obtained (1.5 g, yield: 65%). The result of NMR analysis with respect to this compound is shown below.‘H-NMR(CDC13): ö7.40-7.14 (9H, m,Ar-H), 6.82 (4H, d, J=8.6 Hz, Ar--H), 4.24-3.94 (2H, m, COOCH2), 3.78 (s, 6H, OCH3), 3.72-2.96 (7H, m, alkyl, H-2, H-5, H-6), 2.10-1.30 (16H, m, alkyl, H-3, H-4);FAI3-MS: 576 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dihydrogen peroxide; sodium hydroxide; In water; at 79.84℃; for 8h;Schlenk technique; | General procedure: All experiments to test the catalytic activity were performed in a Schlenk tube (50mL vol.) attached to a condenser. The catalytic activity was evaluated for HDO oxidation in basic aqueous media with H2O2 as oxidant to obtain HCA. In a typical reaction procedure, aliphatic diol (0.5mmol) and catalyst (25mg) were weighed and dispersed in deionized water (3.5mL) in a Schenk tube. 30% H2O2 (0.75mL) and 0.5M NaOH (0.75mL) were added to the above mixture, and then the Schlenk tube was mounted on a preheated oil bath at 353K. The mixture was allowed to react for various time intervals with continuous magnetic stirring (500 rpm). After the reaction, a part of the resultant solution was diluted 20 times with an aqueous H2SO4 (10mM) solution, and the catalyst was filtered off using a 0.20mum filter (Milex-LG). The obtained filtrate was analyzed by high performance liquid chromatography (HPLC, WATERS 600) using an Aminex HPX-87H column (Bio-Rad Laboratories, Inc.) attached to a refractive index detector. An aqueous 10mM H2SO4 solution (eluent) was run through the column (maintained at 323K) at a flow rate of 0.5mLmin-1. The conversion and yield(s) were determined with a calibration curve method using commercial products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In tetrahydrofuran; dichloromethane for 72h; | 1 A solution of octan-1,8-diol (9.8 g) in methylene chloride (100 mL) and tetrahydrofuran (60 mL) was treated with 2-ethylhexanoyl chloride (10 g). Triethylamine (15 mL) was slowly added and the solution stirred for three days. The reaction mixture was filtered and the filtrate washed with brine (2x). The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed.The crude product was filtered through silica gel (20 g) using methylene chloride, yielding 15.8 g of crude product. | |
With triethylamine In tetrahydrofuran; dichloromethane for 72h; | 5 EXAMPLE 5 (0629) SYNTHESIS OF COMPOUND I-1 Compound I-1 was prepared according to method B as follows: (0631) A solution of octan-1,8-diol (9.8 g) in methylene chloride (100 mL) and tetrahydrofuran (60 mL) was treated with 2-ethylhexanoyl chloride (10 g). Triethylamine (15 mL) was slowly added and the solution stirred for three days. The reaction mixture was filtered and the filtrate washed with brine (2×). The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The crude product was filtered through silica gel (20 g) using methylene chloride, yielding 15.8 g of crude product. The resultant oil was dissolved in methylene chloride (100 mL) and treated with pyridinum chlorochromate (13 g) for two hours. Diethyl ether (400 mL) as added and the supernatant filtered through a silica gel bed. The solvent was removed from the filtrate and resultant oil passed down a silica gel (77 g) column using a ethyl acetate/hexane (0-6%) gradient.8-O-(2′-ethylhexanoyloxy)octanal (6.7 g) was recovered as an oil. (0632) A solution of 8-O-(2′-ethylhexanoyloxy)octanal (6.7 g), acetic acid (25 drops) and 2-N,N-dimethylaminoethylamine (0.54 g) in methylene chloride (40 mL) was treated with sodium triacetoxyborohydride (1.5 g) overnight. The solution was washed with aqueous sodium hydrogen carbonate, followed by brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel (75 g) column using a methanol/methylene chloride (0-10%) gradient, followed by a second column (20 g), to yield compound I-1 (1 g) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; triethylamine In dichloromethane at 25℃; for 10h; | 4 Preparation of octanediol monomethyl furozanate as shown in Formula (2) 5.85 g of octanediol, 5.56 mL of triethylamine and 0.24 g of 4-dimethylaminopyridine were dissolved in 100 mL of dichloromethane, 3.77 g of monomethyl methanyl chloride was added, reacted at 25 ° C for 10 h, and then 50 mL And the mixture was washed three times to obtain an organic phase which was dried over anhydrous magnesium sulfate and distilled to remove methylene chloride to give the octanediol monomethyl furoate represented by the formula (2) in a yield of 92% |
With 1,4-diaza-bicyclo[2.2.2]octane; triethylamine In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 4-(dimethylamino)pyridinium tosylate; diisopropyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere; | 2 Synthesis of bis-N-boc-0-benzyl(l-serine)-l,8-octanyl diester (M2) [00103] N-boc-O-benzyl-l-serine (15 gm, 50.79 mmol), 1,8-octanediol (3.09 gm, 21.16 mmol) and DPTS (1.06 gm, 4.23 mmol) were dissolved in 30 ml of anhydrous DCM under N2. The reaction flask was then immersed in an ice bath and DIC (7.62 ml, 48.67 mmol) was quickly injected into the flask under N2 at 0 °C. The reaction was left stirring overnight under inert atmosphere while the temperature gradually increased to room temperature. The reaction solution was filtered to remove the urea crystals and concentrated under vacuum. The oily product was dissolved in CHC13 and washed with 5% HCl solution twice and once with DI water, dried over anhydrous Na2S04, filtered and concentrated in vacuo. A light yellow colored oil (13.38 gm, yield = 89%) was obtained by silica gel column chromatography with hexane/ethyl acetate (2.65/1, v/v) as eluents. NMR (300 MHz, DMSO-d6, δ) : 1.20 (s, 4H, CH2), 1.37 (s, 22H, CH3), 1.50 (m, 4H, CH2), 3.53-3.77 (m, 4H, CH2), 3.85- 4.13 (m, 4H, CH2), 4.24 (dd, J = 5.55 Hz, 12.80 Hz, 2H; CH), 4.46 (s, 4H, CH2), 7.09 (d, J = 7.92Hz, 2H; CH), 7.19-7.40 (m, 12H, Ar H) . See FIG. 19. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sulfuric acid In toluene at 75℃; for 20h; | 3.8. 8-Hydroxyoctyl Isobutyrate 15 To a solution of octane-1,8-diol (7.3 g, 50 mmol) and isobutyric acid (4.2 g, 48 mmol) in toluene (100 mL), four drops of concentrated sulfuric acid were added, and the reaction mixture was warmed to 75 °C for 20 h. The reaction mixture was diluted using ethyl acetate (200 mL) and washed withwater, NaHCO3, and brine, then dried over MgSO4. The solvent was evaporated, and the residue was purified through column chromatography to give compound 15 (8.8 g, 85%) as a colorless oil. 1H NMR (500 MHz, CDCl3) 4.04 (t, J = 6.7 Hz, 2H), 3.62 (t, J = 6.6 Hz, 2H), 2.55-2.49 (m, 1H), 2.03 (s, 1H),1.62-1.52 (m, 4H), 1.32 (s, 8H), 1.15 (d, J = 7.0 Hz, 6H); 13C-NMR (125 MHz, CDCl3) 177.26, 64.31,62.93, 34.02, 32.70, 29.24, 29.15, 28.59, 25.79, 25.62, 18.97. |
47.9% | With sulfuric acid In toluene at 120℃; for 14h; | Synthesis of Compound 10 Experimental procedure: Take a 250 mL single-mouth round bottom flask.Isobutyric acid (4.2 g, 0.96 eq) was added sequentially.1,8-octanediol (7.3g, 1.0eq),Toluene (100mL),Concentrated H2SO4 (0.15mL),Concentrated H2SO4 was slowly added dropwise.Then start heating back,The oil bath temperature is 120°C and the reaction is 14h.The reaction solution is a colorless liquid.Post-reaction treatment: The reaction solution was concentrated under reduced pressure to remove toluene, and the concentrate was transferred to 50 mL of ice water, washed with saturated Na 2 CO 3 solution to neutral, extracted with ethyl acetate (10.0 mL×3), dried over anhydrous MgSO 4 , filtered and concentrated.Column chromatography afforded 5.1 g of a colorless oil, yield: 47.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With [2-(2-aminophenyl)phenyl]methylsulfonyloxypalladium dicyclohexyl-[3,6-dimethoxy-2-(2,4,6-triisopropylphenyl)phenyl]phosphane; caesium carbonate In toluene at 80℃; for 18h; Inert atmosphere; | Intermediate 147a: 8-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)octan-1-ol Intermediate 147a: 8-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)octan-1-ol RockPhos Pd G3 (25.8 mg, 0.03 mmol) was added in one portion to a degassed mixture of octane-1,8-diol (540 mg, 3.69 mmol), (1R,3R)-1-(4-bromo-2,6-difluorophenyl)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (300 mg, 0.62 mmol) and cesium carbonate (701 mg, 2.15 mmol) in toluene (7.5 mL) at 20° C. under nitrogen. The resulting mixture was stirred at 80° C. for 18 hours. The reaction was allowed to cool to RT and diluted with EtOAc (50 mL) and water (15 mL). The organic layer was collected and washed with saturated brine solution, dried over MgSO4, filtered and evaporated to afford crude product as an orange gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in heptane to afford the title compound (219 mg, 69%) as a yellow oil; 1H NMR (400 MHz, CDCl3, 30° C.) 1.10 (3H, d), 1.15-1.49 (15H, m), 1.52-1.62 (2H, m), 1.76 (2H, p), 2.39 (1H, dd), 2.60 (1H, ddd), 2.86 (1H, dd), 3.05-3.14 (1H, m), 3.58-3.73 (3H, m), 3.90 (2H, t), 5.18 (1H, s), 6.34-6.43 (2H, m), 7.04-7.13 (2H, m), 7.17-7.23 (1H, m), 7.43 (1H, s), 7.47-7.53 (1H, m); m/z: ES+ [M+H]+ 517.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With rhodium(II) acetate In dichloromethane at 20℃; for 21h; Inert atmosphere; | Intermediate 12a: Ethyl 2-((8-hydroxyoctyl)oxy)acetate Intermediate 12a: Ethyl 2-((8-hydroxyoctyl)oxy)acetate Ethyl 2-diazoacetate (0.846 mL, 6.84 mmol) was added slowly to a suspension of octane-1,8-diol (10 g, 68.39 mmol) and diacetoxyrhodium (0.030 g, 0.07 mmol) in DCM (5 mL) at 20° C. over a period of 3 hours under nitrogen. The resulting suspension was stirred at 20° C. for 18 hours. The reaction mixture was filtered and the filtrate was then diluted with EtOAc (75 mL), and washed sequentially with water (4*75 mL) and saturated brine (50 mL). The organic layer was dried with MgSO4, filtered and evaporated to afford crude product. The crude material was suspended in 1:1 heptane: diethyl ether (10 mL) and filtered. The filtrate was evaporated to afford the title compound (1.100 g, 69%) as a yellow liquid; 1H NMR (400 MHz, CDCl3) 1.22-1.41 (12H, m), 1.60 (4H, m), 3.52 (2H, m), 3.64 (2H, t), 4.05 (2H, s), 4.22 (2H, q). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; N,N,N,N,-tetramethylethylenediamine; oxygen In acetonitrile at 20℃; for 30h; | 1-6 Example 2 Add 10 g (0.068 mol) of 1,8-octanediol to a 100 mL single-mouth bottle.0.3 g of composite catalyst (tetramethylethylenediamine, cuprous iodide and Tempo,In a molar ratio of 1:1:1) and 40 mL of dry acetonitrile, the reaction mixture was stirred with air at room temperature, and the reaction was examined by TLC. After the reaction for 30 hours, the reaction was completed.The composite catalyst is removed by filtration (can be recycled and reused), and after the obtained filtrate is removed from the solvent,The liquid 8-hydroxyoctanal was obtained in an amount of 9.5 g, the yield was 97.0%, and the purity in the gas phase analysis was 98.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10 parts of the compound represented by (I-1-a) and 45 parts of acetonitrile were mixed and stirred at 23 C. for 30 minutes. To the obtained mixture, 15.36 parts of a compound represented by the formula (I-1-b) was added, and the mixture was further stirred at 60 C. for 2 hours. To the obtained reaction mixture, 37.76 parts of the compound represented by the formula (I-5-c) was added, and the mixture was further stirred at 60 C. for 2 hours, and then cooled to 23 C. To the obtained reaction mixture, 100 parts of chloroform and 50 parts of 5% oxalic acid aqueous solution were added and stirred at 23 C. for 30 minutes, followed by liquid separation to take out an organic layer. To the obtained organic layer, 50 parts of ion exchange water was added and stirred at 23 C. for 30 minutes, followed by liquid separation to take out the organic layer. This washing operation was repeated 5 times. The obtained organic layer was concentrated, and the concentrated residue was purified using a column (silica gel 60N (spherical, neutral) 100-210 mum; manufactured by Kanto Chemical Co., Inc., developing solvent: n-heptane / ethyl acetate = 1/1). By fractionation, 14.48 parts of a compound represented by the formula (I-5-d) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; | 4.8. General Synthetic Procedure for 9g-9i General procedure: A mixture of cinnamic acid (6.30 mmol), EDCI (7.50 mmol), DMAP (0.60 mmol), and anhydrous dichloromethane (20 mL) was stirred to dissolve, then alkane-diol (3 mmol) was added and stirred at room temperature for 12 h. The mixture solution was filtered under reduced pressure. After that, the residue was washed with dichloromethane and water successively, subsequently, purified by preparative TLC eluted with petroleum ether/ethyl acetate = 5:1 to give pale white solid. 4.8.1. Octane-1,8-Diyl (2E,2′E)-Bis(3-Phenylacrylate) (9g)Pale white solid, yield 35%, m.p. 61.1-62.5 °C;1H-NMR (300 MHz, CDCl3)δ: 7.68 (d,J= 16 Hz, 2H), 7.58-7.46 (m, 4H), 7.43-7.30 (m, 6H), 6.45 (d,J= 16 Hz, 2H), 4.21 (t,J= 6.7 Hz, 4H), 1.77-1.68 (m, 4H), 1.46-1.40 (m, 8H).13C-NMR (101 MHz, CDCl3)δ: 167.22, 144.72, 134.62, 130.35, 129.01, 128.19, 118.43, 64.79, 29.31, 28.85, 26.05. HRMS (ESI)m/z:407.2223 [M + H]+, calcd. for [C26H31O4]+407.2222. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With hafnium tetrakis(trifluoromethanesulfonate) In toluene at 110℃; for 16h; stereoselective reaction; | General procedure synthesis of macrodiolides. General procedure: Dienedicarboxylic acid (0.2mmol, 1.0 equiv.) and diol (0.2mmol, 1.0 equiv.) were dissolved in toluene (40mL, 5mM). Then Hf(OTf)4 (0.015g, 0.02mmol, 0.1equiv.) was added to the solution and the reaction mixture heated to 110°C for 16-18h. After cooling to room temperature, silica gel (~0.7g) was added and the slurry was concentrated under reduced pressure and purified by column chromatography (elution with petroleum ether/EtOAc (15/1)) to afford the desired product as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With hafnium tetrakis(trifluoromethanesulfonate) In toluene at 110℃; for 16h; stereoselective reaction; | General procedure synthesis of macrodiolides. General procedure: Dienedicarboxylic acid (0.2mmol, 1.0 equiv.) and diol (0.2mmol, 1.0 equiv.) were dissolved in toluene (40mL, 5mM). Then Hf(OTf)4 (0.015g, 0.02mmol, 0.1equiv.) was added to the solution and the reaction mixture heated to 110°C for 16-18h. After cooling to room temperature, silica gel (~0.7g) was added and the slurry was concentrated under reduced pressure and purified by column chromatography (elution with petroleum ether/EtOAc (15/1)) to afford the desired product as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With hafnium tetrakis(trifluoromethanesulfonate) In toluene at 110℃; for 16h; stereoselective reaction; | General procedure synthesis of macrodiolides. General procedure: Dienedicarboxylic acid (0.2mmol, 1.0 equiv.) and diol (0.2mmol, 1.0 equiv.) were dissolved in toluene (40mL, 5mM). Then Hf(OTf)4 (0.015g, 0.02mmol, 0.1equiv.) was added to the solution and the reaction mixture heated to 110°C for 16-18h. After cooling to room temperature, silica gel (~0.7g) was added and the slurry was concentrated under reduced pressure and purified by column chromatography (elution with petroleum ether/EtOAc (15/1)) to afford the desired product as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In dichloromethane; water at 20℃; | 1.1.1 1.1 Preparation of ROS-AD 1-1C8 Add 1,8-octanediol (585.2g, 4.0mmol), triethylamine (485.6mg, 4.8mmol) and DCM (8.0mL) in the reaction flask, and slowly dropwise add TsCl (762.2mg, 4.0mmol) DCM (8.0mL) solution,Stir at room temperature until the reaction is complete. After adding water, the liquids were separated, and then the aqueous phase was extracted with DCM,The organic phase was dried and filtered, and the solvent was distilled off under reduced pressure. The residue was separated by silica gel column chromatography to obtain a colorless oily liquid ROS-AD 1-1C8 (895.3 mg, 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With ZrCl4-Mg(ClO4)2 composite In neat (no solvent) at 20℃; for 0.166667h; | Typical experimental procedure for the onepotsynthesis of benzyl acetate General procedure: A mixture of 4-methoxy benzyl alcohol (1b, 1 mmol),acetic acid (3 mmol), 2 mol% ZrCl4-Mg(ClO4)2 catalyst was stirred at room temperature for the time specified inTable 5. After completion of reaction (monitored by TLC),the solid or liquid product was filtered and washed with25 ml diethyl ether and water. The organic layer wassuccessively washed with saturated NaHCO3 solution. Theorganic layer was dried over anhydrous sodium sulfateand evaporated of the solvent under reduced pressure toprovide a residue which was passed through a short padof silica gel (60-120 mesh) using hexane as eluent to providethe analytically pure acylated product (please seeAppendix S1).Note that as we know that esterification is a reversiblereaction, to avoid this reversible we used every time activatedmolecular sieves as dehydrating agent/waterabsorbing agent. We have not mentioned it in our actualexperimental procedure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With D-glucose; magnesium(II) chloride In aq. phosphate buffer at 30℃; for 24h; Microbiological reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84 %Chromat. 2: 7 %Chromat. 3: 7 %Chromat. | With hydrogen In lithium hydroxide monohydrate at 110℃; for 12h; Autoclave; | 4 Examples 2 to 5 General procedure: 1 mmol of the substrate as described in the table below, 100 mg of Catalyst (1) [Pt that is 2 mol % of the substrate, Mo that is 0.5 mol % of the substrate (in terms of metal)], and 3 mL of water were charged in an autoclave having a Teflon (trade name) inner cylinder and reacted at 110° C. for a number of hours as described in the table below under the condition of hydrogen pressure of 5 MPa to produce reaction products. The conversion ratio (conv. [%]) of the substrate was measured using HPLC, and the yield of each one of the reaction products was measured using a gas chromatograph mass spectrometer (GC-MS). |
Tags: 629-41-4 synthesis path| 629-41-4 SDS| 629-41-4 COA| 629-41-4 purity| 629-41-4 application| 629-41-4 NMR| 629-41-4 COA| 629-41-4 structure
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