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Glycerol is a versatile chemical commonly used in sample preparation and gel formation in polyacrylamide gel electrophoresis.
Synonyms: Trihydroxypropane; Glycerin; NSC 9230
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Selective Aster inhibitors distinguish vesicular and nonvesicular sterol transport mechanisms
Xiao, Xu ; Kim, Youngjae ; Romartinez-Alonso, Beatriz ; Sirvydis, Kristupas ; Ory, Daniel S. ; Schwabe, John W. R. , et al.
Abstract: The Aster proteins (encoded by the Gramd1a-c genes) contain a ligand-binding fold structurally similar to a START domain and mediate nonvesicular plasma membrane (PM) to endoplasmic reticulum (ER) cholesterol transport. In an effort to develop small mol. modulators of Asters, we identified 20α-hydroxycholesterol (HC) and U18666A as lead compounds Unfortunately, both 20α-HC and U18666A target other sterol homeostatic proteins, limiting their utility. 20α-HC inhibits sterol regulatory element-binding protein 2 (SREBP2) processing, and U18666A is an inhibitor of the vesicular trafficking protein Niemann-Pick C1 (NPC1). To develop potent and selective Aster inhibitors, we synthesized a series of compounds by modifying 20α-HC and U18666A. Among these, AI (Aster inhibitor)-1l, which has a longer side chain than 20α-HC, selectively bound to Aster-C. The crystal structure of Aster-C in complex with AI-1l suggests that sequence and flexibility differences in the loop that gates the binding cavity may account for the ligand specificity for Aster C. We further identified the U18666A analog AI-3d as a potent inhibitor of all three Aster proteins. AI-3d blocks the ability of Asters to bind and transfer cholesterol in vitro and in cells. Importantly, AI-3d also inhibits the movement of low-d. lipoprotein (LDL) cholesterol to the ER, although AI-3d does not block NPC1. This finding positions the nonvesicular Aster pathway downstream of NPC1-dependent vesicular transport in the movement of LDL cholesterol to the ER. Selective Aster inhibitors represent useful chem. tools to distinguish vesicular and nonvesicular sterol transport mechanisms in mammalian cells.
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Keywords: cholesterol ; lipid metabolism ; lipid transport
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CAS No. : | 56-81-5 |
Formula : | C3H8O3 |
M.W : | 92.09 |
SMILES Code : | OCC(O)CO |
Synonyms : |
Trihydroxypropane; Glycerin; NSC 9230
|
MDL No. : | MFCD00004722 |
InChI Key : | PEDCQBHIVMGVHV-UHFFFAOYSA-N |
Pubchem ID : | 753 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P264-P337+P313-P305+P351+P338 |
* 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 |
---|---|---|
56% | Stage #1: at 120℃; Stage #2: at 130℃; |
Step 1: A 100 mL flask was charged with 3,5-dibromoaniline (5.00 g, 19.9 mmol), sodium 3-nitrobenzenesulfonate (987 mg, 4.39 mmol), iron(ll)sulfate heptahydrate (63.2 mg, 0.658 mmol), and methanesulfonic acid (20 mL). A reflux condenser was added, and the reaction was heated in a 120 °C aluminum block.Glycerol (0.64 mL, 8.8 mmol) was added through the condenser, and the aluminum block temperature was then increased to 130 °C. Heating was continued overnight. After cooling to rt, the reaction mixture was diluted with DCM and water, cooled in an ice/water bath, and rendered alkaline by addition of a 50percent aqueous solution of NaOH. The resulting mixture was filtered over Celite® and extracted with DCM. The organicphase was dried over Na2SO4 and concentrated to a brown solid. Purification by chromatography (80 g Si gel, 0—40percent EtOAc in heptane gradient over 17 CV and then held at 40percent) afforded 5,7-dibromoquinoline as a tan solid (3.19 g, 56percent). 1H NMR (400 MHz, CDCI3) O 7.53 (dd, 1 H), 7.96 (d, 1 H), 8.29 (d, 1 H), 8.50 (d, 1 H), 8.93 (dd, 1 H). LCMS (ESI) m/z: 285.9 [M+H] (95percent). LCMS data were acquired from the reactionmixture immediately prior to workup. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With sulfuric acid; sodium 3-nitrobenzenesulfonate In water at 120 - 130℃; for 1.5 h; | The raw materials 3,5-difluoroaniline G-1 (5.6 g, 27 mmol) and sodium 3-nitrobenzenesulfonate (7.2 g, 32 mmol) Was added to a mixed solution of concentrated sulfuric acid (15 mL) and water (6 mL) After heating to an internal temperature of 120 ° C, glycerol (7.4 g, 80 mmol) After the addition was completed, the temperature was raised to 130 ° C and reacted for 1.5h, then cooled. The reaction was poured into crushed ice, concentrated ammonia water to adjust the pH to 5 ~ 6, the precipitated solid was filtered off, washed with water, After drying, column chromatography gave 3.82 g of white solid compound G-2 in 58percent yield. A mixture of 6-bromo-7-methylquinoline (I-2) and 6-bromo-5-methylquinoline (J-1) was synthesized. Then separated by supercritical preparative chromatography (SFC), IC-H column, mobile phase: isopropanol / carbon dioxide = 18/82, detection wavelength: 254nm. The first fraction was collected as 6-bromo-7-methylquinoline (I-2) as a white solid, yield: 25percent. The second fraction was collected as a 6-bromo-5-methylquinoline (J-1) white solid in a yield of 20percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | Stage #1: With iron(III) sulfate; sulfuric acid In nitrobenzene for 3 h; Heating / reflux Stage #2: With water; sodium hydrogencarbonate In nitrobenzene |
Intermediate 4: 6-Bromo-7-methyl-quinoline; [0304] A mixture of 4-bromo-3-methylaniline (20 g, 107.5 mmol), ferric sulfate (6.6 g, 43.4 mmol), glycerol (40.8 g, 440 mmol), nitrobenzene (8.12 g, 66 mmol), and concentrated EPO <DP n="81"/>sulfuric acid (23 ml) was heated gently. After the first vigorous reaction, the mixture was boiled for 3h and then evaporated to remove the excess nitrobenzene. The solution was added a saturated aqueous solution of sodium bicarbonate until pH=7-8, then the solution was filtered and extracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The solid was purified by flash column chromatography to give a yellow solid, which was further washed with petroleum ether to give 7.5 g of 6-bromo-7-methyl-quinoline (31percent yield): 1H NMR (CDCl3): 2.60 (s, 3H), 7.36 (m, IH), 7.96 (s, IH), 8.04 (m, 2H), 8.89 (m, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: at 120℃; for 4 h; Stage #2: With water; sodium hydroxide In ethanol; ethyl acetate; nitrobenzene at 20℃; |
To a mixture of 5-bromo-2-(trifluoromethyl)aniline (3.0g, 12.6mmol), glycerol (4.64g, 50.0mmol), and ferrous sulfate (0.56 g, 2.0mmol) was added cone, sulfuric acid (2.2mL) dropwise. The reaction mixture was heated at 120 0C for 4hr. After cooled to RT, the reaction was diluted with ethyl acetate (15OmL), and 2N aq. NaOH was introduced to adjust pH about 13. The organic layer was separated and washed with brine and dried over Na2SO4 and evaporated to give the crude product, which was purified with flash column chromatography to give 5-bromo- 8-(trifluoromethyl)quinoline (1.2g, 48percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With methanesulfonic acid; ferrous sulfate hydrate; sodium 3-nitrobenzenesulfonate; at 120 - 135℃; for 16h; | Sodium nitrobenzene sulfonic acid (3.9 g, 17.3 mmol) and methanesulfonic acid (10 ml) were placed in a 100 ml three-necked flask and stirred. 0.2 g (0.8 mmol) of iron (II) sulfate hydrate, and 3-methoxyaniline (3.09 mL) were added dropwise and the mixture was heated to about 120 C.6.3 g of glycerol was added and the reaction was carried out at 135 C. for 16 hours. After completion of the reaction, 10Approximately 100 mL of M aqueous NaOH solution was added and extracted with ethyl acetate. The organic layer was collected, dried over anhydrous magnesium sulfate, and the solvent was removed and purified by column chromatography to obtain 4.2 g of RL-0107 (yield: about 48%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sulfuric acid; sodium 3-nitrobenzenesulfonate sulfuric acid; In water; at 140℃; | To the solution of concentrated sulfuric acid (18 mL) diluted with water (6 mL), was added <strong>[367-34-0]2,4,5-trifluoroaniline</strong> (3.68 g, 25 mmol), glycerol (4.60 g, 50 mmol) and sodium 3-nitrobenzenesulfonate (6.75 g, 30 mmol) in sequence. The resulting suspension was stirred at 140°C overnight. The reaction mixture was cooled to room temperature and added saturated NaHCC>3 aqueous solution to adjust pH to 7, extracted with dichloromethane (200 mL x 2). The combined organic layer was evaporated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 3/1) to give the desired product (3.5 g, 76percent) as a yellow solid. H NMR (400 MHz, CDC13) delta 8.99 (s, IH), 8.46- 8.44 (m, IH), 7.61-7.56 (m, IH), 7.38-7.31 (m, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
INTERMEDIATE 4 5-BROMO-8-FLUORO-2-METHOXYQUINOLINE25MRL DOB-00006Step A. 5-Bromo-8-fluoroquinolme5-Bromo-2-fluoroaniline (1.0 g, 5.3 mmol) was mixed with glycerol (2.0 raL, 27 mmoi), sodium 3 -nitrobenzene sulfonate (1.2 g, 5.3 mmol) and concentrated sulfuric acid (85 mL), then the mixture was heated to 14O0C for 2 hours. The inital suspension became a dark brown solution. The mixture was allowed to cool to room temperature. The solution was made basic with 5N NaOH (30 mL), then extracted with EtOAc. The combined organic phase was washed with water then saturated NaCl (aq), dried over MgSO4, filtered, then concentrated to afford the title compound as a white solid:. 1H NMR (500 MHz, CDCl3): delta 9.00 (d, J = 4.2 Hz, 110 H); 8.54 (d, J = 8.6 Hz, 1 H); 7.77 (dd, J = 8.3, 4.5 Hz, 1 H); 7.59 (dd, J - 8.6, 4.2 Hz, 1 H); 7.32 (dd, J - 9.9, 8.3 Hz, 1 H). LC4 1.81 min. (M+H) = 226. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With rabbit 3-hydroxyhexobarbital dehydrogenase (AKR1C29); NADPH; In aq. phosphate buffer; ethyl acetate; at 37℃; for 0.5h;pH 7.4;Enzymatic reaction;Catalytic behavior; Kinetics; | General procedure: The reaction was conducted at 37°C in a 2.0-mL reaction mixture, containing coenzyme (1-mM NADP+ or 0.1-mM NADPH), substrate (0.05?0.1mM), enzyme (0.1?0.3mg), and 0.1-M potassium phosphate, pH 7.4. The substrate and products were extracted into 4-mL ethyl acetate 30min after the reaction was started at 37°C. The products of oxidoreduction of steroids [25] and reduction of PGD2 [28], farnesal [29] and 4-oxo-2-nonenal [18] were analyzed by TLC, as described. The reduced products of TBE were identified by the HPLC methods [23]. The products of 3HB oxidation, 3OB reduction, 5beta-androstane-3alpha,17beta-diol oxidation and 5beta-androstan-3alpha-ol-17-one reduction were analyzed by the liquid chromatography?electrospray ionization-mass spectrometry (LC?ESI-MS) using a Hewlett-Packard HP 1100 Series LC/MSD system attached with a diode array detector and a column (Mightysil RP-18 GP 5mum, 4.6mm×250mm, Kanto Chemical Co., Tokyo, Japan). Separations were carried out at a flow rate of 0.5mL/min and 40°C using the following mobile phases: 25percent acetonitrile aqueous solution containing 0.1percent formic acid for 3OB and alpha/beta-3HBs, and 80percent acetonitrile aqueous solution containing 0.1percent formic acid for the two steroids. 3OB, alpha-3HB, beta-3HB, 5beta-androstan-3alpha-ol-17-one and 5beta-androstane-3alpha,17beta-diol were detected by monitoring their total ions (m/z 249.1, 251.1, 251.1, 289.4 and 291.4, respectively) in the negative ESI mode, and eluted at the retention times of 20.1, 17.6, 16.8, 14.9 and 12.7min, respectively. The detection limits of 3OB, alpha/beta-3HBs and the two steroids were 0.1, 0.1 and 1nmol, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
platinum on carbon; In water; for 3h;Direct aqueous phase reforming; | Direct aqueous phase reforming (APR) experiments were conducted in 100-ml stirred reactors with draft-tube gas-induction impeller (Parr Series 4590). Reaction tests for direct bio-based feedstock aqueous phase reforming (APR) entailed filling the reactor with 60-grams of solvent (deionized water, or a mixture of DI water and isopropanol (IPA), and 3-3.5 grams of bio-based feedstock comprising biomass (bagasse, or pine sawdust)). One (1) gram of acetic acid was optionally charged to facilitate biomass hydrolysis.[0098] Bagasse was milled via a 1-mm grate. Dry, debarked Loblolly pine was ground via blender (Thomas Scientific of Swedesboro, NJ) and sieved to less than 30 mesh. Dry solids fraction was determined by vacuum drying at 80 °C to 82 °C. One gram of aqueous phase reforming catalyst (reduced 5percent Pt/C catalyst at 50percent moisture, or powdered 1.9percent Pt/A1203) was charged to the reactor, which was charged with 4200 kPa of hydrogen or nitrogen. To minimize degradation of hydrolysate to heavy ends, each reactor was typically heated with a staged temperature sequence of one hour at, 160 °C, 190 °C, 225 °C, and finally 250 °C, before leaving overnight at the final setpoint.[0099] Comparison tests were also conducted with glucose or sorbitol fed directly to the reaction in place of biomass, to simulate and quantify conversion of model hydrolysate to APR intermediates. Glucose is one of the sugars readily leached from biomass in hot water, while sorbitol is readily formed via hydrogenation of glucose, where platinum or other catalysts capable of hydrogenation are present.[00100] A batch reaction time of 20 hours under these conditions corresponds to a weight hourly space velocity (g-feed/g-catalyst/h) of about 3, for a comparable continuous flow reactor. A 0.5-micron sintered metal filter attached to a dip tube allowed liquid samples to be taken throughout the course of reaction, without loss of biomass or catalyst. Samples were analyzed by an HPLC method based on combined size and ion exclusionchromatography, to determine unreacted sorbitol, and amount of C3 and smaller polyols formed: glycerol (Gly), ethylene glycol (EG), and 1,2-propylene glycol (PG). Additional GC analysis via a moderate polarity DB-5 column were conducted to assess formation of C6 and lighter oxygenates (e.g., ketones, aldehydes, alcohols), as well as alkane and alkene products. A separate GC equipped with thermal conductivity and flame ionization (FID) detectors for refinery gas analysis, were used for detection of H2, C02, and light alkanes C1-C5. GC-mass spec was used to characterize select APR reaction product mixtures. Examples 1-3[00101] Batch APR reactions with sugar cane bagasse as biomass feed, and with a comparison of 25percent sorbitol as feed, were performed as described above. 1.7percent acetic acid was added to simulate catalysis of hydrolysis by recycle acid. Products formed from this concentration of acetic acid were subtracted from total product formation, to calculate the net production of liquid fuels from bagasse. This result shown in Table 1 shows the critical importance of concerted APR reaction with hydrolysis of biomass. In the absence of concerted aqueous phase reforming, the hydrolysate undergoes irreversible degradation (presumably to heavy ends), and cannot be reverted to liquid fuels upon subsequent APR and condensation. Converted reaction may be effected by direct inclusion of APR catalyst in the hydrolysis reactor, or via a pump around loop to recirculate liquid between a biomass contactor, and an APR catalytic reactor. Table 1: Direct APR of Biomass |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.4% | To a stirred solution of <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (AS) (10 g, 51.2 mmol) in glycerol(120 mL) were added sulfamix (17.3 g, 76.8 mmol), FeSO4.7H20 (2.9 g, 10.7 mmol) followedby boric acid (5.06 g, 81.9 mmol) at RT. The reaction mixture was cooled to 0 C;Conc.H2S04 (35 mL) was added to the reaction mixture and heated at 145 C for 3 h. Afterconsumption of the starting material (by TLC), the reaction was quenched with cold water and neutralized with NaHCO3. The aqueous layer was extracted with CH2C12 (3 x 500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The obtained crude material waspurified by silica gel column chromatography eluting with 30% EtOAc/hexane to afford AT(mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol, 34%) as syrup.To a stirred solution of AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol) in EtOAc(20 mL) was added m-CPBA (7.4 g, 43 mmol) at 0 C and the reaction mixture was stirred atRT for 12 h. After consumption of the starting material (by TLC), the reaction mixture wasconcentrated under reduced pressure. The crude material was purified by silica gel columnchromatography eluting with 10% MeOH/CH2C12 to afford AU (mixture of 5,6- and 6,7-regio isomers) (2 g, 8.06 mmol, 47.6%) as yellow solid.To a stirred solution of AU (mixture of 5,6- and 6,7-regio isomers) (5.0 g, 20.1 mmol) in ACN (50 mL) was added Et3N (7.1 g, 70.3 mmol) followed by TMSCN (6.9 g, 70.3 mmol) at 0 Cunder an inert atmosphere. The reaction mixture was stirred at RT for 14 h. The volatiles were evaporated under reduced pressure and the crude material was purified by silica gel column chromatography eluting with 8% EtOAc/Hexane to afford AV (6,7-isomer) (2.0 g, 7.75 mmol, 38.4%) as a brown solid. | |
To a stirred solution of <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (AS) (10 g, 51.2 mmol) in glycerol (120 mL) were added sulfamix (17.3 g, 76.8 mmol), FeS04.7H20 (2.9 g, 10.7 mmol) followed by boric acid (5.06 g, 81.9 mmol) at RT. The reaction mixture was cooled to 0 C; Conc.H2S04 (35 mL) was added to the reaction mixture and heated at 145 C for 3 h. After consumption of the starting material (by TLC), the reaction was quenched with cold water and neutralized with NaHC03. The aqueous layer was extracted with CH2CI2 (3 x 500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2S04> filtered and concentrated in vacuo. The obtained crude material was purified by silica gel column chromatography eluting with 30% EtOAc/hexane to afford AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol, 34%) as syrup.To a stirred solution of AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol) in EtOAc (20 mL) was added m-CPBA (7.4 g, 43 mmol) at 0 C and the reaction mixture was stirred at RT for 12 h. After consumption of the starting material (by TLC), the reaction mixture was concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 10% MeOH/CH2Ci2 to afford AU (mixture of 5,6- and 6,7-regio isomers) (2 g, 8.06 mmol, 47.6%) as yellow solid.To a stirred solution of AU (mixture of 5,6- and 6,7-regio isomers) (5.0 g, 20.1 mmol) in ACN (50 mL) was added Et3N (7.1 g, 70.3 mmol) followed by TMSCN (6.9 g, 70.3 mmol) at 0 C under an inert atmosphere. The reaction mixture was stirred at RT for 14 h. The volatiles were evaporated under reduced pressure and the crude material was purified by silica gel column chromatography eluting with 8% EtOAc/Hexane to afford AV (6,7-isomer) (2.0 g, 7.75 mmol, 38.4%) as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid; at 0 - 145℃; | To a stirred solution of <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (AS) (10 g, 51.2 mmol) in glycerol (120 mL) were added sulfamix (17.3 g, 76.8 mmol), FeS04.7H20 (2.9 g, 10.7 mmol) followed by boric acid (5.06 g, 81.9 mmol) at RT. The reaction mixture was cooled to 0 C; Conc.H2S04 (35 mL) was added to the reaction mixture and heated at 145 C for 3 h. After consumption of the starting material (by TLC), the reaction was quenched with cold water and neutralized with NaHC03. The aqueous layer was extracted with CH2CI2 (3 x 500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2S04> filtered and concentrated in vacuo. The obtained crude material was purified by silica gel column chromatography eluting with 30% EtOAc/hexane to afford AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol, 34%) as syrup. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a stirred solution of <strong>[445-13-6]3-chloro-4-(trifluoromethyl)aniline</strong> (AS) (10 g, 51.2 mmol) in glycerol (120 mL) were added sulfamix (17.3 g, 76.8 mmol), FeS04.7H20 (2.9 g, 10.7 mmol) followed by boric acid (5.06 g, 81.9 mmol) at RT. The reaction mixture was cooled to 0 C; Conc.H2S04 (35 mL) was added to the reaction mixture and heated at 145 C for 3 h. After consumption of the starting material (by TLC), the reaction was quenched with cold water and neutralized with NaHC03. The aqueous layer was extracted with CH2CI2 (3 x 500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2S04> filtered and concentrated in vacuo. The obtained crude material was purified by silica gel column chromatography eluting with 30% EtOAc/hexane to afford AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol, 34%) as syrup.To a stirred solution of AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol) in EtOAc (20 mL) was added m-CPBA (7.4 g, 43 mmol) at 0 C and the reaction mixture was stirred at RT for 12 h. After consumption of the starting material (by TLC), the reaction mixture was concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 10% MeOH/CH2Ci2 to afford AU (mixture of 5,6- and 6,7-regio isomers) (2 g, 8.06 mmol, 47.6%) as yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | Step 1 : 4.0g (0.02 mol) of 3-Bromo-5-methoxy-aniline, 4.6 g (0.05 mol) of glycerol, 2.46g (0.02 mol) of nitrobenzene and 12 ml of 75% sulfuric acid were stirred for 3 h at 150C. After this dark solution was poured onto 100 g of crushed ice, 100 ml of ethylacetate (EtOAc) and 30 ml of 30% solution of NaOH. After 1 hour brown solid was filtered off and the organic layer was separated. After filtering through Si02 and evaporation of solvent 7-bromo-5- methoxy-quinoline and 5-bromo-7-methoxy-quinoline were separated as mixture approximately 60:40 (total 3.5g, 74%) This mixture was separated to individual 7-bromo-5- methoxy-quinoline and 5-bromo-7-methoxy-quinoline with column chromatography on silica-gel with benzene-EtOAc (3: 1) as eluent. Yield of pure 7-bromo-5-methoxy-quinoline was 950 mg (27% from mixture). | |
950 mg | With sulfuric acid; In water; nitrobenzene; at 150℃; for 3h; | 4.1.2. Synthesis of 5-hydroxy-7-bromo-quinoline from Scheme 2[0119]The title compound can be purchased by Shanghai Haoyuan Chemexpress Co., Ltd. CHINA or synthesized via known <strong>[16618-68-1]3-bromo-5-methoxyaniline</strong> (Liedholm, Brita. Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry (1984), B38(10), 877-84 or Hodgson, H. H.; Wignall, J. S Journal of the Chemical Society (1926)) in two steps. 3-Bromo-5-methoxy-aniline, 4.6 g (0.05 mol) of glycerol, 2.46 g (0.02 mol) of nitrobenzene and 12 ml of 75% sulfuric acid were stirred for 3 h at 150??? C. After this dark solution was poured onto 100 g of crushed ice, 100 ml of ethylacetate (EtOAc) and 30 ml of 30% solution of NaOH. After 1 hour brown solid was filtered off and the organic layer was separated. After filtering through SiO2 and evaporation of solvent 7-bromo-5-methoxy-quinoline and 5-bromo-7-methoxy-quinoline were separated as mixture approximately 60:40 (total 3.5 g, 74%) This mixture was separated to individual 7-bromo-5-methoxy-quinoline and 5-bromo-7-methoxy-quinoline with column chromatography on silica-gel with benzene-EtOAc (3:1) as eluent. Yield of pure 7-bromo-5-methoxy-quinoline was 950 mg (27% from mixture). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 375℃; under 760.051 Torr; for 6h;Inert atmosphere; Flow reactor; | The dehydrocyclization activities of Zn?Cr?Ocatalysts calcined at different temperatures were performedat 375°C and atmospheric pressure in a fixedbedvertical quartz reactor (i.d = 8 mm, length =450 mm) placed in a two zone furnace operated in adown flow mode. In the first zone maintained at300°C the reaction mixture was preheated whereas inthe second zone containing the catalyst bed the reactortemperature was set at 375°C. Temperatures in theboth zones were monitored by a temperature controller-cum-programmer using a K-type thermocouple.Glycerol (Fluka) and EDA (SDFCL, India) wereused. Nitrogen (IOLAR-I grade, BOC, India) wasused as a carrier gas. The catalytic activities were measured using ?18/+23 sieved (BSS) particles. The carbonmass balance was done based on the inlet and outletconcentration of the organic moiety. Prior to thereaction, the calcined catalyst (about 0.2 g) wasreduced in a flow of 5percent H2 and 95percent Ar (30 mL min?1)at 400°C for 5 h. The catalytic activities were measuredunder strict kinetic control. An aqueous glycerol solution(20 wtpercent in H2O) was used with a glycerol to EDAmole ratio of 1 :1 , at a flow rate of 5 mL h?1 (10 mmolglycerol + 10 mmol EDA + 200 mmol H2O), alongwith N2 as a carrier gas at a flow rate of 1800 mL h?1.The feed mixture mole ratio is glycerol : EDA : H2O :N2= 1 : 1 : 20 : 8. The product mixture was analyzed bygas chromatograph (Shimadzu, GC-17A) via a flameionization detector (FID) using a ZB-5 capillary columnat a ramping rate of 10°C min?1 from 60 to280°C. The mass balance for all the measurements was>95percent. The samples were analyzed by GC-MS(QP5050A Shimadzu) using a ZB-5 capillary columnwith EI mode. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid; sodium 3-nitrobenzenesulfonate; In water; at 50 - 135℃;Cooling with ice; Reflux; | Ice bath under conditions of 250 mLOf the three bottles by adding concentrated H2SO441 g (22 mL),Stir by addingSodium nitrobenzene sulfonate17.5 g (78 mmol),Boric acid2.4 g (39 mmol),FeSO4 · 7H2O 1.4 g (5 mmol)Glycerol 12.5 mL,2-amino-6-methylpyridine (4.3 g, 40 mmol)Mixed evenly after adding 22.5mL 50 warm water,in135 ° CUnder reflux2-3h,After cooling; with 50percent NaOH solution transferred to alkaline, filter,The aqueous solution was extracted three times with chloroform and the organic layer was dried over anhydrous MgSO4,The solvent was removed by rotary distillation to give the crude product which was recrystallized from cyclohexane to give 2-methylnaphthyridine,Ie probe reagent;The concentrated sulfuric acid concentration is 95-98percent; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The intermediate 3a-d (1.0 mmol) was dissolved in dichloromethane (10.0 mL), which has been dried through refluxing, under nitrogen atmosphere. Then, DMAP (1.5 mmol), EDCI (1.25mmol) were added to it in order. Then, ethylene glycol (0.5 mmol), glycerin (0.3 mmol), ribose (0.25 mmol) or xylose (0.25 mmol) was added. After stirring for 24 h at room temperature, the mixture was poured into water and washed with 1 mol/L HCl. The CH2Cl2 layer was concentrated, and the residue was purified using flash chromatography (ethyl acetate: Petroleum ether, 1:100-1:20) to obtain 4-6a, 4-7c or 4-7d. Compound 6-7a, 4-7b, 6d were used directly in the next step without purification and structural characterization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With toluene-4-sulfonic acid; hydroquinone; In diethylene glycol dimethyl ether; at 140℃; for 10h;Inert atmosphere; | 152 g (1.05 mol) of <strong>[51792-34-8]3,4-dimethoxythiophene</strong>, 775 g (8.42 mol) of glycerin, 19.9 g (0.105 mol) of p-toluenesulfonic acid monohydrate, 11.5 g (0.105 mol ) of Hydroquinone and 3.68 L of diglyme were added to a reactor, and then the inside of the reaction system was sufficiently purged with argon gas. The oxygen concentration in the reaction vessel gas atmosphere was 0.3 vol percent. Thereafter, the mixture was heated to 140 ° C and stirred for 10 hours. After cooling to room temperature, the reaction solution was analyzed by gas chromatography and the formation rate of the target product (2) was 75percent and the formation rate of the by-product (4) was 0.5percent (molar ratio 99.3 : 0.7). 1.68 L of a 10percent sodium hydroxide aqueous solution was added and the mixture was allowed to stand for 12 hours. The solvent was distilled off and extracted three times with a toluene / saturated aqueous sodium chloride solution. The toluene layer was concentrated and dried and dissolved in 3.7 L of a mixed solvent of toluene / ethyl acetate = 4/1, and the insoluble matter was filtered off. The solvent was distilled off and dissolved in 220 g of toluene, then 220 g of hexane was further added, and the mixture was allowed to stand at about 10 ° C for 2 hours. The obtained crystals were filtered, then washed with hexane and dried under vacuum to obtain 100 g of the desired product (2) as a white precipitate (yield: 55percent). By gas chromatography, 0.5percent of the by-product (4) was contaminated, and the purity of the target product (2) was 99.5percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sulfuric acid; sodium 3-nitrobenzenesulfonate sulfuric acid; at 130℃; | To the solution of concentrated sulfuric acid (30 mL) diluted with water (20 mL), was added pyridin-4-amine (3.76 g, 40.0 mmol), glycerol (12.52 g, 136 mmol) and sodium 3-nitrobenzenesulfonate (19.8 g, 88.0 mmol) in sequence. The resulting suspension was stirred at 130°C overnight. The reaction mixture was cooled to roomtemperature and added saturated NaOH aqueous solution to adjust pH to 10, extracted with dichloromethane (200 mL x 2). The combined organic layer was evaporated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 1/1) to give the desired product (900 mg, 69percent) as a white solid. H NMR (400 MHz, CDC13) delta 9.30 (s,lH), 9.12 (s,lH), 8.78 (d, / = 5.2 Hz, 1H), 8.32 (d, / = 8.0 Hz, 1H), 7.94 (d, / = 5.2 Hz, 1H), 7.62-7.48 (m, 1H). |
Tags: Glycerol | Trihydroxypropane | Aliphatic Chain Hydrocarbons | Alcohols | 56-81-5
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P390 | Absorb spillage to prevent material damage. |
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Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
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Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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