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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
2',5'-Dihydroxyacetophenone is a mixture of various isomers of adihydroxyacetophenone which is used as a flavoring agent.
Synonyms: DHAP; 2-Acetylhydroquinone; Quinacetophenone
4.5
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Batch number can be found on the product's label following the word 'Batch'.
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Search for reports by entering the product batch number.
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CAS No. : | 490-78-8 |
Formula : | C8H8O3 |
M.W : | 152.15 |
SMILES Code : | CC(C1=CC(O)=CC=C1O)=O |
Synonyms : |
DHAP; 2-Acetylhydroquinone; Quinacetophenone
|
MDL No. : | MFCD00002343 |
InChI Key : | WLDWSGZHNBANIO-UHFFFAOYSA-N |
Pubchem ID : | 10279 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
81.3% | With potassium iodide; In acetone; for 6h;Reflux; | 2 ', 5'-hydroxyacetophenone (7.60g, 0.05mol),Anhydrous potassium carbonate (8.00g, 0.06 mol),Potassium iodide (1.00g, 0.006mol),100mL of acetone is placed in a 250mL eggplant-shaped bottle.Stir at room temperature.Benzyl chloride (7.87 g, 0.06 mol) was diluted with 10 mL of acetone and dropped into the reaction solution at a constant rate. The addition was completed in about 10 minutes. The reaction was heated at reflux for 6 h and the reaction was monitored by TLC. After the reaction was completed, it was cooled to room temperature and the organic solvent was distilled off under reduced pressure to give yellow crystals.Recrystallization from 50 mL of ethanol gave 9.84 g of yellow crystals with a yield of 81.3%. |
81.3% | With potassium carbonate; potassium iodide; In acetone; for 6h;Reflux; | The 2',5'-dihydroxyacetophenone(7.60g, 0.05mol),Anhydrous potassium carbonate (8.00g, 0.06mol), potassium iodide (1.00g, 0.006mol),100 mL of acetone was placed in a 250 mL eggplant-shaped flask and stirred at room temperature.Benzyl chloride (7.87g, 0.06mol) was diluted with 10mL of acetone and dropped into the reaction solution at a constant rate.About 10 minutes after the completion of the drop. The reaction was heated at reflux for 6 h and the reaction was monitored by TLC.After the reaction was completed, it was cooled to room temperature and the organic solvent was distilled off under reduced pressure to give yellow crystals.Recrystallization from 50 mL of ethanol gave 9.84 g of yellow crystals with a yield of 81.3% |
80.7% | With potassium carbonate; In acetone; at 56 - 60℃; for 5h; | General procedure: In a 250 ml round-bottomed flask were placed 2?,4?-dihydroxyacetophenone or 2?,5?-dihydroxyacetophenone (0.10 mol), benzylchloride(0.105 mol), potassium iodide (0.01 mol), anhydrous potassium carbonate (1 mol) and 100 ml dry acetone. The mixture was refluxed for 5 h at 56-60 C in oil bath. After reaction was finished, the reaction liquid was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure to obtain the crude. The solid was recrystallized from 100 ml ethanol to obtain 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 18-crown-6 ether; potassium carbonate; potassium iodide; In toluene; at 115℃; for 14h; | The second alternate way consists in making at first the protection of the OH function with a benzylic group by involving the same conditions as for the previous O-alkylation reaction to furnish the acetophenone derivative (1-6) in a very good yield (95%). To form the product (1- 7), beforehand synthesized by the other methodology, acetophenone derivative (1-6) was submitted to VilsmeierHaack reaction using standard conditions (70%). Knoevenagel condensation of the resulting product (1-7) with diethyl malonate provided in an ultimate stage the expected diester (1-8) in high yield (94%). In view of these results (Scheme 2), we can notice that in priori both ways can be used to synthesize the intermediate (1-7) in an overall yield of 42% and 66%, respectively, from the dihydroxy-acetophenone (1-4) as the raw material; with however the second way more effective in term of yield. |
88.3% | With sodium hydrogencarbonate; In ethanol; at 0 - 10℃; for 3.33333h; | [0168] 152 g (1.0 mol) of 2,5-dihydroxy acetophenone was added to a 1L three-necked flask. 400 mL of absolute ethanol was added, stirred for dissolution. 92.4 g (1.1 mol) of sodium bicarbonate was added at room temperature and stirred for 5 minutes. The temperature of the reaction mixture was kept at 0-10 C. 180 g (1.05 mol) of benzyl bromide was added dropwise, and the addition was completed within 20 minutes. At this temperature, the reaction was continued with stirring for 3 hours, and thin layer detection showed that the raw material 2,5-dihydroxyacetophenone was reacted completely. The solvent was removed under reduced pressure. The residue was dissolved with 400 mL of dichloromethane, and washed with saturated citric acid aqueous solution 3 times (3150 mL). The the dichloromethane solution was dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was removed by filtration. Dichloromethane was removed from the solution under reduced pressure. The residue was dissolved in 300 mL of absolute ethanol which is cooled and crystallized to obtain 213.7 g of 2-hydroxy-5-benzyloxy acetophenone as a white solid with a yield of 88.3%. The chemical purity was 99.0% (HPLC). |
75.6% | With potassium carbonate; In 4-methyl-2-pentanone; at 60℃; for 20h; | 1-[2-hydroxy-5-(phenylmethoxy)-phenyl]-ethanone: 20 kg (131.4 mol) 2-acetyl-hydroquinone 6a are dissolved in 150 l methylisobutylketone and combined with 19.98 kg (144.6 mol) potassium carbonate. At 60 C., 22.48 kg (131.5 mol) benzyl bromide are added. The reaction mixture is stirred for 20 hours at 60 C. The reaction mixture is cooled to 25 C. and the solid is filtered off. The filtrate is washed twice with a solution of 0.96 kg (11.8 mol) sodium hydroxide solution (50%) and 60 l water at 25 C. The methylisobutylketone is largely distilled off in vacuo, and the residue is dissolved in 80 l methanol at 60 C. The solution is cooled to 0 C. and stirred for 1 hour at this temperature to complete the crystallisation. Yield (5a): 24.07 kg (75.6%), chemical purity according to HPLC: 99.2%. |
75.6% | With potassium carbonate; In 4-methyl-2-pentanone; at 60℃; for 20h;Industry scale; | 1-[2-hydroxy-5-(phenylmethoxy)-phenyl]-ethanone: 20 kg (131.4 mol) 2-acetyl-hydroquinone 6a are dissolved in 150 L methylisobutylketone and combined with 19.98 kg (144.6 mol) potassium carbonate. At 60 C., 22.48 kg (131.5 mol) benzyl bromide are added. The reaction mixture is stirred for 20 hours at 60 C. The reaction mixture is cooled to 25 C. and the solid is filtered off. The filtrate is washed twice with a solution of 0.96 kg (11.8 mol) sodium hydroxide solution (50%) and 60 L water at 25 C. The methylisobutylketone is substantially distilled off in vacuo, and the residue is dissolved in 80 L methanol at 60 C. The solution is cooled to 0 C. and stirred for 1 hour at this temperature to complete the crystallisation.Yield (5a): 24.07 kg (75.6%), chemical purity according to HPLC: 99.2%. |
8 g (82%) | With potassium carbonate; In acetone; | EXAMPLE 9 Stage A: 5-Benzyloxy-2-hydroxyacetophenone A mixture of 2,5-dihydroxyacetophenone (6.10 g = 40 mM), benzyl bromide (5 ml = 42 mM) and anhydrous potassium carbonate (5,6 g = 40 mM in anhydrous acetone (120 ml)) is heated under reflux for 5 hours. Then, the mixture is concentrated under reduced pressure, the residue is taken up with 1N HCl (120 ml) and extracted with ethyl ether. The combined extracts are washed with water and with a saturated ammonium sulfate solution, anhydrated (Na2SO4) and concentrated to give a crude solid compound that is then purified by flash-chromatography (4:1, n-hexane: ethyl acetate as the eluent) to give 8 g (82%) of a yellow solid, m.p. 63-65C. |
49 g | With potassium carbonate; In acetone; for 16h;Reflux; | 1000 ml three-neck bottle , the compound 1 - 4 (44 g, 290 mmol), potassium carbonate (44 g, 319 mmol) dissolved in acetone (750 ml), heated to 60 C, continue adding benzyl bromide (57.7 g, 304.5 mmol), reflux reaction 16 h. Cooling the reaction liquid to room temperature, the solid in filtering system, concentrated, continue adding ethyl acetate (400 ml), sequentially for cold aqueous solution of sodium hydroxide (1 M, 50 ml), water (200 ml) and saturated salt water (200 ml).The organic phase drying, filtering, concentrated and methanol recrystallization to obtain a yellow solid product 49 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In sodium hydroxide; hexane; ethyl acetate; acetone; | PREPARATION 1 5-Benzyloxy-2-hydroxyacetophenone To 2,5-dihydroxyacetophenone (30 g, 0.197 mol) dissolved in 600 ml acetone was added benzyl bromide (24.64 ml, 1.05 equiv) and K2 CO3 (68.0 g, 0.492 mol). The mixture was heated at reflux under N2 for 2 days, then cooled to room temperature, filtered and stripped of solvent in vacuo. The residue was taken up in 500 ml ethyl acetate, washed 3* with ice cold IN NaOH, 2* with H2 O and 2* with brine, dried (Na2 SO4), stripped to solids, and chromatographed on silica gel using 9:1 hexane:ethyl acetate as eluant to yield 35 g of purified title product. A portion was recrystallized as needles from hexane; mp 68-70 C.; Anal. C 74.37, H 5.69, calcd. C 74.36, H 5.82, 1 H-NMR (300 MHz, CDCl3) delta (ppm) 2.6 (s, 3H), 5.05 (s, 2 H), 6.9 (d, 1H), 7.1-7.45 (m, 7H), 11.85 (s, 1H). |
Tags: 2,5-Dihydroxyacetophenone | DHAP | Aryls | Ketones | Fluorinated Building Blocks | Organic Building Blocks | 490-78-8
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