CN114315527B - Preparation method of resorcinol - Google Patents
Preparation method of resorcinol Download PDFInfo
- Publication number
- CN114315527B CN114315527B CN202111642365.0A CN202111642365A CN114315527B CN 114315527 B CN114315527 B CN 114315527B CN 202111642365 A CN202111642365 A CN 202111642365A CN 114315527 B CN114315527 B CN 114315527B
- Authority
- CN
- China
- Prior art keywords
- resorcinol
- methoxyphenol
- reaction
- catalyst
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052802 copper Inorganic materials 0.000 claims abstract description 10
- 239000010949 copper Substances 0.000 claims abstract description 10
- -1 m-substituted phenol Chemical class 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 230000009471 action Effects 0.000 claims abstract description 8
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- 230000001335 demethylating effect Effects 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 15
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 claims description 9
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 7
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 7
- 229940045803 cuprous chloride Drugs 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical group Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- 239000012649 demethylating agent Substances 0.000 claims description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 10
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 229940071870 hydroiodic acid Drugs 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229940018563 3-aminophenol Drugs 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 239000000865 liniment Substances 0.000 description 2
- 229940018564 m-phenylenediamine Drugs 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- UNEATYXSUBPPKP-UHFFFAOYSA-N 1,3-Diisopropylbenzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1 UNEATYXSUBPPKP-UHFFFAOYSA-N 0.000 description 1
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 description 1
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 1
- CECABOMBVQNBEC-UHFFFAOYSA-K aluminium iodide Chemical compound I[Al](I)I CECABOMBVQNBEC-UHFFFAOYSA-K 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- 239000005011 phenolic resin Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Abstract
The invention discloses a preparation method of resorcinol, which belongs to the technical field of medicine preparation and comprises the following two steps: (1) synthesizing m-methoxyphenol: taking m-substituted phenol as a raw material, and performing nucleophilic substitution reaction under the action of a catalyst to generate m-methoxyphenol; (2) Synthesis of resorcinol: under the action of demethylating reagent, m-methoxyphenol removes methyl to produce resorcinol. The catalyst in step (1) is a mixture of a copper catalyst and an ester, wherein the ester is capable of coordinating with the copper catalyst. The preparation method disclosed by the invention is simple, mild in condition, favorable for industrial production, and high in purity and yield of the finally obtained resorcinol.
Description
Technical Field
The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of resorcinol.
Background
Resorcinol is an important pharmaceutical and chemical production raw material, widely used as a preservative and a drug, and is also a raw material for preparing phenolic resin, fuel, adhesives and various reagents. When used as a medicament, the resorcinol preparations on the market at present are all external preparations, including compound resorcinol emulsifiable paste, compound ginseng resorcinol liniments, compound resorcinol tea phenol liniments and the like.
In industrial production, resorcinol is prepared by various methods, and the common methods mainly comprise the following main categories: firstly, the sulfonated alkali fusion method is mature in technology and is a traditional production process, but the method can be applied to a large amount of dangerous chemicals such as sulfur trioxide, sulfuric acid, sodium hydroxide and the like in the production process, so that production equipment can be severely corroded, a large amount of three wastes can be generated, and environmental protection pressure is high; secondly, the m-diisopropylbenzene oxidation method has the advantages of high technical difficulty, strict requirements on production equipment, complex process and difficult realization. Thirdly, m-phenylenediamine is hydrolyzed to synthesize resorcinol by a m-phenylenediamine hydrolysis method, which is the main process for producing resorcinol at present, but the method needs to be carried out at high temperature and high pressure, and has great potential safety hazard.
In addition to the conventional several general types of production methods described above, there are other methods of preparation. For example, in chinese patent application CN111592447a (resorcinol preparation method), m-aminophenol is used as a raw material, diazotization is performed under the action of concentrated sulfuric acid and sodium nitrite to obtain m-aminophenol diazonium salt, and then the m-aminophenol diazonium salt is hydrolyzed to obtain resorcinol. Diazotization reaction belongs to dangerous reaction, has large technological risk, uses a large amount of concentrated sulfuric acid in the reaction process, is easy to corrode equipment and is easy to cause environmental pollution. For another example, in chinese patent application CN101372445A (resorcinol synthesis process), resorcinol is prepared by catalytic dehydrogenation using cyclohexane having-OH or=o substituents at the 1,3 positions as a raw material and water as a solvent. The catalytic dehydrogenation step in the method adopts high Wen Batan dehydrogenation reaction, has high risk, strict requirements on equipment and lower yield.
Disclosure of Invention
The invention aims to provide a preparation method of resorcinol, which aims to solve the problems in the background art.
In order to achieve the above object, the present invention discloses a method for preparing resorcinol, comprising the steps of:
(1) Synthesizing m-methoxyphenol: taking m-substituted phenol as a raw material, and performing nucleophilic substitution reaction under the action of a catalyst to generate m-methoxyphenol;
(2) Synthesizing resorcinol: under the action of demethylating reagent, m-methoxyphenol removes methyl to produce resorcinol.
Further, in the step (1), the m-substituted phenol is selected from one of m-bromophenol, m-chlorophenol and m-iodophenol.
Further, in the step (1), the catalyst is a mixture of copper catalyst and esters, wherein the dosage ratio of the copper catalyst to the esters is 1:1-10.
Further, the copper catalyst is selected from one or a mixture of more of cuprous bromide, cuprous iodide and cupric acetate.
Further, the esters are selected from one or a mixture of more of methyl acetate, ethyl formate or ethyl acetate.
In the invention, the ester compound and the copper catalyst are selected for composite use, and the ester compound can coordinate with the copper catalyst, so that the catalyst activity can be greatly improved, and the reaction can be promoted to be rapidly carried out.
Further, in the step (2), the demethylating agent is selected from one or a mixture of several of aluminum trichloride, aluminum tribromide, aluminum triiodide, trimethyliodosilane, hydroiodic acid or hydrobromic acid.
Further, in step (2), the demethylating agent is hydroiodic acid.
Further, in the step (2), sodium iodide is added into the reaction system to generate hydroiodic acid in situ as a demethylating reagent.
Furthermore, the purity of the resorcinol obtained by the preparation method is larger than or equal to 99.5%, and the yield is larger than or equal to 70%.
Compared with the prior art, the preparation method of resorcinol has the following advantages:
(1) The preparation method of resorcinol only comprises two steps, and has the advantages of simple process, mild reaction conditions, no dangerous reaction and high safety.
(2) The reaction condition of the preparation method of resorcinol is easy to control, no corrosion-prone strong acid and alkali compound is used, and the requirement on production equipment is low.
(3) The resorcinol obtained by the preparation method of resorcinol has high purity and high yield, and is beneficial to industrial production.
Description of the drawings (since examples 1-6 are all first-step variants and examples 7-10 are all second-step variants, only one of the HPLC and hydrogen patterns of each is retained)
Fig. 1: high performance liquid chromatography of purity of product S1 in example 1.
Fig. 2: nuclear magnetic resonance hydrogen spectrum of the product S1 in example 1.
Fig. 3: high performance liquid chromatography of the purity of product L7 in example 7.
Fig. 4: nuclear magnetic resonance hydrogen spectrum of the product L7 in example 7.
Detailed Description
The technical scheme of the invention is explained in detail by specific examples.
A method for preparing resorcinol, comprising the steps of:
(1) Synthesizing m-methoxyphenol: taking m-substituted phenol as a raw material, and cuprous chloride and methyl formate as catalysts, and enabling m-bromophenol and sodium methoxide to undergo nucleophilic substitution reaction to generate m-methoxyphenol;
(2) Synthesizing resorcinol: and (3) removing methyl from the m-methoxyphenol under the action of hydroiodic acid to obtain resorcinol.
For example, m-bromophenol is used as a raw material, and the reaction equation in the preparation process is as follows:
First, synthesizing m-methoxyphenol:
Example 1
200Ml of methanol is added into a reaction kettle, stirring is started, 37g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 30g of m-bromophenol, 3g of cuprous chloride and 10g of methyl formate are sequentially added. After the addition, heating and refluxing for 7 to 8 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 20.5g of brownish red oily matter, and marking the brownish red oily matter as S1, namely M-methoxyphenol.
Detecting the purity of S1 by adopting a high performance liquid chromatography (general rule 0512), wherein a chromatogram is shown in fig. 1, and finally detecting to obtain the purity of S1: 98.72%.
Yield of S1: 95.3%.
S1 is subjected to nuclear magnetic resonance hydrogen spectrum analysis, and the spectrum is shown in figure 2 ：1HNMR(400MHz,DMSO-d6)δ7.79(d,J＝7.4Hz,1H),7.63–7.53(m,2H),7.49–7.45(m,3H),7.44–7.37(m,3H),7.36–7.28(m,7H),5.17(s,2H),5.02(s,2H),1.26(d,J＝7.2Hz,3H).
Example 2
200Ml of methanol is added into a reaction kettle, stirring is started, 37g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 30g of m-bromophenol, 4g of cuprous bromide and 10g of methyl formate are sequentially added. After the addition, heating and refluxing for 7 to 8 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 19.7g of brownish red oily matter, and marking the brownish red oily matter as S2, namely M-methoxyphenol.
And detecting the purity of the S2 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the S2: 98.49%.
Yield: 91.6%.
Example 3
200Ml of methanol is added into a reaction kettle, stirring is started, 37g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 30g of m-iodophenol, 4g of cuprous chloride and 10g of methyl formate are sequentially added. After the addition, heating and refluxing for 7 to 8 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 20.1g of brownish red oily matter, and marking the brownish red oily matter as S3, namely M-methoxyphenol.
And detecting the purity of the S3 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the S3: 97.27%.
Yield: 93.5%.
Example 4
50Ml of methanol is added into a reaction kettle, stirring is started, 13g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 10g of m-bromophenol, 1g of cuprous chloride and 10g of methyl acetate are sequentially added. After the addition, heating and refluxing for reaction for 10 to 12 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 18.7g of brownish red oily matter, and marking the brownish red oily matter as S4, namely M-methoxyphenol.
And detecting the purity of the S4 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the S4: 95.24%.
Yield: 87.0%.
Example 5
50Ml of methanol is added into a reaction kettle, stirring is started, 13g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 10g of m-bromophenol, 1g of cuprous chloride and 10g of ethyl formate are sequentially added. After the addition, heating and refluxing for reaction for 10 to 12 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 18.9g of brownish red oily matter, and marking the brownish red oily matter as S5, namely M-methoxyphenol.
And detecting the purity of the S5 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the S5: 95.88%.
Yield: 88.0%.
Example 6
50Ml of methanol is added into a reaction kettle, stirring is started, 13g of sodium methoxide is added, the temperature is reduced to 20-30 ℃, and 10g of m-bromophenol, 1g of cuprous chloride and 10g of ethyl acetate are sequentially added. After the addition, heating and refluxing for reaction for 10 to 12 hours, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1 to 2, extracting with ethyl acetate for 2 times, washing with saturated sodium chloride water for 2 times, drying an organic phase with anhydrous sodium sulfate, concentrating to obtain 14.7g of brownish red oily matter, and marking the brownish red oily matter as S6, namely M-methoxyphenol.
And detecting the purity of the S6 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the S6: 96.93%.
Yield: 82.3%.
Second, resorcinol is synthesized:
Example 7
300Ml of toluene is added into a reaction kettle, stirring is started, 38g of aluminum trichloride and 30g of m-methoxyphenol are sequentially added into a reaction bottle, and the temperature is raised to 80-90 ℃ for reaction for 8-9 h. Cooling to room temperature after the reaction is finished, adding water into the reaction solution for quenching, separating the solution, adding toluene into the water phase for extraction once, and discarding an organic phase; ethyl acetate is added to the water phase for extraction for 2 times, the organic phases are combined, the water solution is washed for 2 times, and resorcinol is obtained after decompression concentration. 150ml of toluene was added, heated to 110℃for dissolution, cooled to 0℃and filtered, and 7.1g of white crystals, designated L7, were obtained by washing with 20ml of toluene.
Detecting the purity of L7 by adopting a high performance liquid chromatography (general rule 0512), wherein a chromatogram is shown in fig. 3, and finally detecting to obtain the purity of L7: 99.95%.
Yield: 80.3%.
The nuclear magnetic resonance hydrogen spectrum analysis is carried out on L7, and the spectrogram is shown in figure 4: 1HNMR (300 MHz, DMSO-d 6): delta = 6.21-6.25 (m, 3H), 6.92-6.96 (t, 1H), 9.19 (s, 2H).
Example 8
80Ml of water, 52g of sodium iodide and 30g of m-methoxyphenol are added into a reaction kettle, 150ml of concentrated hydrochloric acid is added into the reaction kettle, and the temperature is raised to 100 ℃ for reaction for 15 hours. Cooling to room temperature after the reaction is finished, adding ethyl acetate, extracting for 2 times, combining organic phases, washing for 2 times by aqueous solution, and concentrating under reduced pressure to obtain resorcinol. 150ml of toluene was added, heated to 110℃for dissolution, cooled to 0℃and filtered, and washed with 20ml of toluene to give 6.6g of white crystals, designated L8, as resorcinol.
And detecting the purity of the L8 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the L8: 99.87%.
Yield: 74.6%.
Example 9
80Ml of water, 52g of sodium iodide and 30g of m-methoxyphenol are added into a reaction kettle in sequence, 200ml of hydrobromic acid is added, and the temperature is raised to 100 ℃ for reaction for 15 hours. Cooling to room temperature after the reaction is finished, adding ethyl acetate, extracting for 2 times, combining organic phases, washing for 2 times by aqueous solution, and concentrating under reduced pressure to obtain resorcinol. 150ml of toluene was added, heated to 110℃for dissolution, cooled to 0℃and filtered, and washed with 20ml of toluene to give 5.8g of white crystals, designated L9, which was resorcinol.
And detecting the purity of the L9 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the L9: 99.91%.
Yield: 75.8%.
Example 10
300Ml of toluene is added into a reaction kettle, stirring is started, 30g of m-methoxyphenol and 50g of trimethyliodosilane are sequentially added into a reaction bottle, and the temperature is raised to 80-90 ℃ for reaction for 8-9 h. Cooling to room temperature after the reaction is finished, adding water into the reaction solution for quenching, separating the solution, adding toluene into the water phase for extraction once, and discarding an organic phase; ethyl acetate is added to the water phase for extraction for 2 times, the organic phases are combined, the water solution is washed for 2 times, and resorcinol is obtained after decompression concentration. 150ml of toluene was added, heated to 110℃for dissolution, cooled to 0℃and filtered, and washed with 20ml of toluene to give 4.3g of white crystals, designated L10, which was resorcinol.
And detecting the purity of the L10 by adopting a high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of the L10: 99.88%.
Yield: 71.3%.
The above embodiments are only preferred embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements, etc. within the design concept of the present invention should be included in the scope of the present invention.
Claims (2)
1. A preparation method of resorcinol is characterized in that: the method comprises the following steps:
(1) Synthesizing m-methoxyphenol: taking m-substituted phenol as a raw material, and performing nucleophilic substitution reaction under the action of a catalyst to generate m-methoxyphenol;
(2) Synthesizing resorcinol: under the action of a demethylating reagent, methyl is removed from m-methoxyphenol to generate resorcinol;
Wherein in step (1), the m-substituted phenol is selected from m-bromophenol; the catalyst is a mixture of copper catalyst and esters, wherein the copper catalyst is selected from cuprous bromide or cuprous chloride; wherein the dosage ratio of the copper catalyst to the esters is 1:1-10;
in the step (2), the demethylating agent is aluminum trichloride.
2. The method for producing resorcinol according to claim 1, wherein: the esters are selected from one or a mixture of more of methyl acetate, ethyl formate and ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111642365.0A CN114315527B (en) | 2021-12-29 | Preparation method of resorcinol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111642365.0A CN114315527B (en) | 2021-12-29 | Preparation method of resorcinol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114315527A CN114315527A (en) | 2022-04-12 |
| CN114315527B true CN114315527B (en) | 2024-06-11 |
Family
ID=
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62230743A (en) * | 1986-03-31 | 1987-10-09 | Eisai Co Ltd | Production of 1-alkoxy-2-methylnaphthalene |
| US6132740A (en) * | 1997-09-23 | 2000-10-17 | Pfizer Inc. | Resorcinol derivatives |
| FR2971783A1 (en) * | 2011-02-17 | 2012-08-24 | Rhodia Operations | PROCESS FOR HYDROXYLATION OF PHENOLS AND PHENOL ETHERS |
| CN108069831A (en) * | 2018-01-25 | 2018-05-25 | 上海恩氟佳科技有限公司 | A kind of method for synthesizing 2,3- dimethyl -4- fluorophenols |
| CN108821930A (en) * | 2018-05-31 | 2018-11-16 | 荆楚理工学院 | A kind of ehter bond cleavage method of phenyl alkyl ether |
| CN112645799A (en) * | 2020-12-09 | 2021-04-13 | 山东兴强化工产业技术研究院有限公司 | Resorcinol post-treatment process |
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62230743A (en) * | 1986-03-31 | 1987-10-09 | Eisai Co Ltd | Production of 1-alkoxy-2-methylnaphthalene |
| US6132740A (en) * | 1997-09-23 | 2000-10-17 | Pfizer Inc. | Resorcinol derivatives |
| FR2971783A1 (en) * | 2011-02-17 | 2012-08-24 | Rhodia Operations | PROCESS FOR HYDROXYLATION OF PHENOLS AND PHENOL ETHERS |
| CN108069831A (en) * | 2018-01-25 | 2018-05-25 | 上海恩氟佳科技有限公司 | A kind of method for synthesizing 2,3- dimethyl -4- fluorophenols |
| CN108821930A (en) * | 2018-05-31 | 2018-11-16 | 荆楚理工学院 | A kind of ehter bond cleavage method of phenyl alkyl ether |
| CN112645799A (en) * | 2020-12-09 | 2021-04-13 | 山东兴强化工产业技术研究院有限公司 | Resorcinol post-treatment process |
Non-Patent Citations (5)
| Title |
|---|
| 3-二氨基苯酚的合成;王华等;《浙江化工》;第46卷(第3期);第41-43页 * |
| Cleavage of Catechol Monoalkyl Ethers by Aluminum Triiodide-Dimethyl Sulfoxide;Dayong Sang et a.;《Synthesis》;第A-I页 * |
| Expedient Synthesis of Hydroxytyrosol and its Esters;Paolo Bovicelli et al.;《Synthetic Communications》;第37卷;第4245-4252页 * |
| Matthew Lukeman et al..Photogeneration of 1,5-naphthoquinone methides via excited-state (formal) intramolecular proton transfer (ESIPT) and photodehydration of 1- naphthol derivatives in aqueous solution.《Can. J. Chem》.2004,第82卷第240-253页. * |
| 上海第一医学院主编.《药物合成反应》.化学工业出版社,1982,第477-478页. * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103724261B (en) | A kind of industrialized process for preparing of hydroxychloroquine sulfate quinoline | |
| CN108069831B (en) | Method for synthesizing 2, 3-dimethyl-4-fluorophenol | |
| CN113233962B (en) | Method for continuously producing 2, 6-dihydroxytoluene | |
| CN106188116A (en) | A kind of method of synthesizing pyrazole 4 boric acid pinacol ester | |
| CN111533663B (en) | Method for synthesizing mesalazine | |
| EP4169906A1 (en) | Method for synthesis of roxadustat and intermediate thereof, and intermediate thereof | |
| CN105669429A (en) | Preparation method of rhodium octanoate dimer | |
| CN103664923B (en) | The preparation method of Nifuratel | |
| CN114315527B (en) | Preparation method of resorcinol | |
| CN102199073A (en) | Method for preparing 4,4'-dihydroxydiphenylmethane | |
| CN107686440A (en) | A kind of preparation method of m-trifluoromethyl phenol | |
| CN101580460B (en) | Synthesis method of 3, 4-dihydroxy phenylethanol | |
| CN114315527A (en) | Preparation method of resorcinol | |
| CN105541712B (en) | The preparation method of Solifenacin intermediate | |
| CN101659650B (en) | Method of preparing piperonal in one kettle way | |
| CN113861034A (en) | Preparation method of 2-fluoro-3-nitrobenzoic acid | |
| CN114409524A (en) | Preparation method of 2, 6-dichlorophenylacetic acid | |
| CN107129466B (en) | Synthesis method of 4-chloro-3-methoxy-2-methylpyridine-N-oxide | |
| CN109060473B (en) | Preparation method of ambroxol hydrochloride impurity reference substance | |
| CN106748671B (en) | Method for synthesizing 2-alkoxy-4-methylphenol from 2-bromo-4-methylphenol | |
| CN112645799B (en) | Resorcinol post-treatment process | |
| US20220235010A1 (en) | Synthesis method for 1-methyl-1h-indazole-6-carboxylic acid | |
| CN107987115B (en) | Utilize the method for Promestriene organic waste residues recycling estradiol | |
| CN117603038A (en) | Preparation method of 3-hydroxy-2-methylbenzoic acid | |
| CN112574007B (en) | Novel cyclohexylimine ionic liquid and method for catalyzing synthesis of butyl citrate and bisphenol F |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant |