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Chemical Structure| 636-46-4 Chemical Structure| 636-46-4
Chemical Structure| 636-46-4

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Synonyms: 4-Hydroxyisophthalic acid

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Product Details of Salicylic acid impurity B

CAS No. :636-46-4
Formula : C8H6O5
M.W : 182.13
SMILES Code : OC(=O)C1=CC(C(O)=O)=C(O)C=C1
Synonyms :
4-Hydroxyisophthalic acid
MDL No. :MFCD00010391
InChI Key :BCEQKAQCUWUNML-UHFFFAOYSA-N
Pubchem ID :12490

Safety of Salicylic acid impurity B

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313

Application In Synthesis of Salicylic acid impurity B

* 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.

  • Downstream synthetic route of [ 636-46-4 ]

[ 636-46-4 ] Synthesis Path-Downstream   1~7

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YieldReaction ConditionsOperation in experiment
92% With thionyl chloride; at 0 - 20℃; for 6.5h;Reflux; Thionyl chloride (15 mL, 206 mmol) was added dropwise to a solution of 4-hydroxyisophthalic acid(5 g, 27.5 mmol, commercially available from, for example, Sigma Aldrich) in MeOH (50 mL) at 0 °Cunder nitrogen. The resulting solution was stirred at rt for 30 mm before heating gently to reflux for6 h. The reaction was allowed to cool. Upon cooling, a precipitate formed which was collected byfiltration to afford dimethyl 4-hydroxyisophthalate (5.32 g, 25.3 mmol, 92percent yield) as a white solid.LCMS (Formic): Retention time 1.02, poor ionisation1H NMR (DMSO-d6, 400 MHz): O (ppm) 11.01 (5, 1H), 8.36 (d, J=2.4 Hz, 1H), 8.04 (dd, J=8.6,2.4 Hz, 1H), 7.10 (d, J=8.6 Hz, 1H), 3.91 (5, 3H), 3.83 (5, 3H)
86% With thionyl chloride; for 3h;Reflux; 20 g (109.9 mmol) of 4-hydroxyisophthalic acid was added to 330 mL of anhydrous methanol. With stirring at room temperature, 130 g (1099 mmol) of thionyl chloride was slowly added dropwise to the above solution and it was dripped within 40 minutes. After dripping, warm up to a slow reflux of the solution. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 3:1) and the reaction was complete after 3 hours. After cooling to room temperature, a white solid precipitated. The solid was filtered and the cake was washed with plenty of water and dried in vacuo. The resulting solid was dissolved in 120 mL of ethyl acetate, and the ethyl acetate solution was washed with 90 mL of saturated sodium bicarbonate solution, 70 mL of distilled water, and 70 mL of saturated saline, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give 15 g of a white solid. The rate is 86%).
With sulfuric acid; for 22h;Heating / reflux; a) 4-Hydroxyisophthalic acid dimethyl ester To a solution of 4-hydroxyisophthalic acid (16.0 g) in methanol (150 mL) was added conc. sulfuric acid (5 mL), and the mixture was heated for 22 hours under reflux. Then, the reaction solution was allowed to stand for cooling down to room temperature, diluted with water (150 mL), and added with sodium bicarbonate (15 g). The resulting precipitate was filtered, washed successively with water/methanol (1:1, v/v) (150 mL) and water, and dried to give the title compound (17.45 g).
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YieldReaction ConditionsOperation in experiment
32.88 g With water; sodium hydroxide; at 100℃; for 2h; 100.00 g of the waste residue of wintergreen oil was dissolved in 300 ml of methanol, water bath stirring while hot filtration, the filtrate was allowed to settle to precipitate a solid. The filter cake was collected by filtration and dried to collect 30.56 g of crude <strong>[5985-24-0]4-hydroxyisophthalic acid dimethyl ester</strong>, take 17.00gNaOH solid with water as the solvent preparation 30percent NaOH solution, the crude <strong>[5985-24-0]dimethyl 4-hydroxyisophthalate</strong> was dissolved in the aqueous NaOH solution and refluxed in a water bath at 100 ° C for 2 hours. After cooling to room temperature, the filtrate was collected by filtration, decolorized by the addition of 3.00 g of activated charcoal, and refluxed at 100 ° C for 1 hour in a water bath. The filter cake was collected by filtration and dried to obtain 32.88 g of 4-hydroxyisophthalic acid. The reaction mixture was filtered and washed with water.
  • 7
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YieldReaction ConditionsOperation in experiment
With sulfuric acid; In methanol; EXAMPLE 64 4-Ethoxy-N'1, N"3-bis-(3-methoxy-benzyl)-isophthalamide Into a flask was placed 4-hydroxy-isophthalic acid (25.46 g) and 200 mL of methanol. Concentrated sulfuric acid (20 mL) was slowly added. The mixture was refluxed for 48 hours; upon cooling a copious white precipitate formed, which was collected by filtration. The white solid obtained was washed with water, then dried under vacuum at 50° C. to yield 26.65 g of 4-hydroxy-isophthalic acid dimethyl ester.
In methanol; i 4-Hydroxy-1,3-benzenedioic acid, dimethyl ester A mixture of 4-hydroxyisophthalic acid (25 g) and trimethylsily chloride (100 ml) in methanol (200 ml) was heated at reflux for 4 hours. The mixture was evaporated and partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic phase was dried (MgSO4) and evaporated. Yield 25.67 g. Used directly in the next step.
 

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