CN114315527A - Preparation method of resorcinol - Google Patents
Preparation method of resorcinol Download PDFInfo
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- CN114315527A CN114315527A CN202111642365.0A CN202111642365A CN114315527A CN 114315527 A CN114315527 A CN 114315527A CN 202111642365 A CN202111642365 A CN 202111642365A CN 114315527 A CN114315527 A CN 114315527A
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- resorcinol
- methoxyphenol
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- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 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
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- 230000009471 action Effects 0.000 claims abstract description 8
- 230000001335 demethylating effect Effects 0.000 claims abstract description 8
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 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 24
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 12
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
- 229940071870 hydroiodic acid Drugs 0.000 claims description 6
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 5
- 235000009518 sodium iodide Nutrition 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 claims description 3
- 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 compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 3
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 claims description 2
- CECABOMBVQNBEC-UHFFFAOYSA-K aluminium iodide Chemical compound I[Al](I)I CECABOMBVQNBEC-UHFFFAOYSA-K 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 238000001816 cooling Methods 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 14
- 238000005406 washing Methods 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 6
- 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
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 6
- 229940045803 cuprous chloride Drugs 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000010992 reflux Methods 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
- 230000008569 process Effects 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229940018563 3-aminophenol Drugs 0.000 description 3
- 238000005481 NMR spectroscopy Methods 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
- 239000000243 solution Substances 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
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229940040145 liniment Drugs 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
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 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
- 241000208340 Araliaceae Species 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
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- 239000012649 demethylating agent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- DCJGJEZFCWRDSY-UHFFFAOYSA-L disodium 1,3-dimethylpurin-7-ide-2,6-dione acetate Chemical compound [Na+].[Na+].CC([O-])=O.Cn1c2nc[n-]c2c(=O)n(C)c1=O DCJGJEZFCWRDSY-UHFFFAOYSA-L 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
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum 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
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
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Abstract
The invention discloses a preparation method of resorcinol, belonging to the technical field of medicine preparation, comprising the following two steps: (1) synthesizing m-methoxyphenol: m-substituted phenol is taken as a raw material, and nucleophilic substitution reaction is carried out under the action of a catalyst to generate m-methoxyphenol; (2) synthesizing resorcinol: under the action of demethylating reagent, m-methoxyphenol removes methyl to generate resorcinol. The catalyst in the step (1) is a mixture of a copper catalyst and an ester, wherein the ester can be coordinated with the copper catalyst. The preparation method is simple, mild in condition and beneficial to industrial production, and the finally obtained resorcinol is high in purity and yield.
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 raw material for pharmaceutical and chemical production, is widely used as a preservative and a medicament, and is also a raw material for preparing phenolic resin, fuels, adhesives and various reagents. When used as a medicament, the resorcinol preparations on the market at present are all external preparations, including compound resorcinol cream, compound ginseng resorcinol liniment, compound resorcinol theophyllol liniment and the like.
In industrial production, resorcinol is prepared by various methods, and the following methods are mainly used in common methods: firstly, the technology of the method is mature, and the method 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, not only can seriously corrode production equipment, but also can generate a large amount of three wastes, and has large environmental protection pressure; and secondly, the m-diisopropylbenzene oxidation method has the disadvantages of high technical difficulty, strict requirements on production equipment, complex process and difficult realization. Thirdly, m-phenylenediamine hydrolysis method hydrolyzes m-phenylenediamine to synthesize resorcinol, 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 above-described conventional production methods of several general types, there are other production methods. For example, in chinese patent application CN111592447A (resorcinol preparation method), m-aminophenol is used as a raw material, and 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. The diazotization reaction belongs to dangerous reaction, the process risk is large, a large amount of concentrated sulfuric acid is used in the reaction process, equipment is easy to corrode, and environmental pollution is easy to cause. For another example, in chinese patent application CN101372445A (resorcinol synthesis process), resorcinol is prepared by catalytic dehydrogenation using cyclohexane having-OH or ═ O substituent groups at positions 1 and 3 as raw material and water as solvent. The catalytic dehydrogenation step in the method adopts high-temperature palladium-carbon dehydrogenation reaction, so that the method has high danger, strict requirements on equipment and lower yield.
Disclosure of Invention
The present invention aims to provide a method for preparing resorcinol, which solves the problems mentioned in the background art.
In order to achieve the aim, the invention discloses a preparation method of resorcinol, which comprises the following steps:
(1) synthesizing m-methoxyphenol: m-substituted phenol is taken as a raw material, and nucleophilic substitution reaction is carried out under the action of a catalyst to generate m-methoxyphenol;
(2) synthesizing resorcinol: under the action of demethylating reagent, m-methoxyphenol removes methyl to generate 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 a 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 cuprous bromide, cuprous iodide or cupric acetate.
Further, the esters are selected from one or a mixture 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 be coordinated with the copper catalyst, so that the activity of the catalyst can be greatly improved, and the reaction can be promoted to be rapidly carried out.
Further, in the step (2), the demethylating reagent is selected from one or a mixture of more of aluminum trichloride, aluminum tribromide, aluminum triiodide, iodotrimethylsilane, hydroiodic acid and hydrobromic acid.
Further, in the 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 not less than 99.5%, and the yield is not less than 70%.
Compared with the prior art, the preparation method of the resorcinol has the following advantages:
(1) the preparation method of the resorcinol provided by the invention only comprises two steps, and is simple in process, mild in reaction condition, free of dangerous reaction and high in safety.
(2) The reaction conditions of the resorcinol preparation method are easy to control, and the corrosive strong acid and strong base compounds are not used, so that the requirements on production equipment are low.
(3) The resorcinol prepared by the preparation method of the resorcinol has high purity and high yield, and is beneficial to industrial production.
Description of the figures (since examples 1 to 6 are all different versions of the first step and examples 7 to 10 are all different versions of the second step, only the HPLC and hydrogen spectra of each of them are retained)
FIG. 1: high performance liquid chromatogram of the 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 chromatogram 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 solution of the present invention will be described in detail by the following specific examples.
A preparation method of resorcinol comprises the following steps:
(1) synthesizing m-methoxyphenol: m-substituted phenol is used as a raw material, cuprous chloride and methyl formate are used as catalysts, and m-bromophenol and sodium methoxide are subjected to nucleophilic substitution reaction to generate m-methoxyphenol;
(2) synthesizing resorcinol: under the action of hydroiodic acid, the m-methoxyphenol is demethylated to obtain the resorcinol.
For example, with m-bromophenol as a raw material, the reaction equation in the preparation process is as follows:
firstly, synthesizing m-methoxyphenol:
example 1
Adding 200ml of methanol into a reaction kettle, starting stirring, adding 37g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 30g of m-bromophenol, 3g of cuprous chloride and 10g of methyl formate. And after the addition is finished, heating and refluxing for reaction for 7-8 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 20.5g of brownish red oily matter, which is marked as S1, namely the M-methoxyphenol.
Detecting the purity of S1 by high performance liquid chromatography (general rule 0512), and detecting the purity of S1 by a chromatogram shown in figure 1: 98.72 percent.
Yield of S1: 95.3 percent.
Performing nuclear magnetic resonance hydrogen spectrum analysis on S1, wherein the spectrum is shown in figure 2: 1HNMR (400MHz, DMSO-d6) δ 7.79(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
Adding 200ml of methanol into a reaction kettle, starting stirring, adding 37g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 30g of m-bromophenol, 4g of cuprous bromide and 10g of methyl formate. And after the addition is finished, heating and refluxing for reaction for 7-8 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 19.7g of brownish red oily matter, which is marked as S2, namely the M-methoxyphenol.
Detecting the purity of S2 by high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of S2: 98.49 percent.
Yield: 91.6 percent.
Example 3
Adding 200ml of methanol into a reaction kettle, starting stirring, adding 37g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 30g of m-iodophenol, 4g of cuprous chloride and 10g of methyl formate. And after the addition is finished, heating and refluxing for reaction for 7-8 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 20.1g of brownish red oily matter, which is marked as S3, namely the M-methoxyphenol.
Detecting the purity of S3 by high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of S3: 97.27 percent.
Yield: 93.5 percent.
Example 4
Adding 50ml of methanol into a reaction kettle, starting stirring, adding 13g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 10g of m-bromophenol, 1g of cuprous chloride and 10g of methyl acetate. And after the addition is finished, heating and refluxing for reaction for 10-12 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 18.7g of brownish red oily matter, which is marked as S4, namely the M-methoxyphenol.
Detecting the purity of S4 by high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of S4: 95.24 percent.
Yield: 87.0 percent.
Example 5
Adding 50ml of methanol into a reaction kettle, starting stirring, adding 13g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 10g of m-bromophenol, 1g of cuprous chloride and 10g of ethyl formate. And after the addition is finished, heating and refluxing for reaction for 10-12 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 18.9g of brownish red oily matter, which is marked as S5, namely the M-methoxyphenol.
Detecting the purity of S5 by high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of S5: 95.88 percent.
Yield: 88.0 percent.
Example 6
Adding 50ml of methanol into a reaction kettle, starting stirring, adding 13g of sodium methoxide, cooling to 20-30 ℃, and sequentially adding 10g of m-bromophenol, 1g of cuprous chloride and 10g of ethyl acetate. And after the addition is finished, heating and refluxing for reaction for 10-12 h, cooling to room temperature after the reaction is finished, adding 2M dilute hydrochloric acid to adjust the pH value to 1-2, extracting for 2 times by using ethyl acetate, washing for 2 times by using saturated sodium chloride, drying by using anhydrous sodium sulfate of an organic phase, and concentrating to obtain 14.7g of brownish red oily matter, which is marked as S6, namely the M-methoxyphenol.
Detecting the purity of S6 by high performance liquid chromatography (general rule 0512), and finally detecting to obtain the purity of S6: 96.93 percent.
Yield: 82.3 percent.
Secondly, synthesis of resorcinol:
example 7
Adding 300ml of toluene into a reaction kettle, starting stirring, sequentially adding 38g of aluminum trichloride and 30g of m-methoxyphenol into a reaction bottle, and heating to 80-90 ℃ for reacting for 8-9 h. Cooling to room temperature after the reaction is finished, adding water into the reaction solution for quenching, separating liquid, adding toluene into the water phase for extraction once, and discarding the organic phase; adding ethyl acetate into the water phase, extracting for 2 times, combining organic phases, washing with the aqueous solution for 2 times, and concentrating under reduced pressure to obtain the resorcinol. Adding 150ml toluene, heating to 110 deg.C to dissolve, cooling to 0 deg.C, filtering, and washing with 20ml toluene to obtain 7.1g white crystal, which is recorded as L7, i.e. resorcinol.
The purity of L7 was checked by high performance liquid chromatography (general rule 0512), and the chromatogram was as shown in FIG. 3, and the final detection gave the purity of L7: 99.95 percent.
Yield: 80.3 percent.
The hydrogen nuclear magnetic resonance spectrum analysis is carried out on the L7, and the spectrum is shown in FIG. 4: 1HNMR (300MHz, DMSO-d6): delta 6.21-6.25 (m,3H),6.92-6.96(t,1H),9.19(s, 2H).
Example 8
Adding 80ml of water, 52g of sodium iodide and 30g of m-methoxyphenol into a reaction bottle in sequence, adding 150ml of concentrated hydrochloric acid, and heating to 100 ℃ for reaction for 15 hours. After the reaction is finished, cooling to room temperature, adding ethyl acetate to extract for 2 times, combining organic phases, washing the aqueous solution for 2 times, and concentrating under reduced pressure to obtain the resorcinol. Adding 150ml toluene, heating to 110 deg.C to dissolve, cooling to 0 deg.C, filtering, and washing with 20ml toluene to obtain 6.6g white crystal, which is recorded as L8, i.e. resorcinol.
The purity of L8 was checked by high performance liquid chromatography (general rule 0512) to obtain the final purity of L8: 99.87 percent.
Yield: 74.6 percent.
Example 9
Adding 80ml of water, 52g of sodium iodide and 30g of m-methoxyphenol into a reaction bottle in sequence, adding 200ml of hydrobromic acid, heating to 100 ℃ and reacting for 15 hours. After the reaction is finished, cooling to room temperature, adding ethyl acetate to extract for 2 times, combining organic phases, washing the aqueous solution for 2 times, and concentrating under reduced pressure to obtain the resorcinol. Adding 150ml toluene, heating to 110 deg.C to dissolve, cooling to 0 deg.C, filtering, and washing with 20ml toluene to obtain 5.8g white crystal, which is recorded as L9, i.e. resorcinol.
The purity of L9 was checked by high performance liquid chromatography (general rule 0512) to obtain the final purity of L9: 99.91 percent.
Yield: 75.8 percent.
Example 10
Adding 300ml of toluene into a reaction kettle, starting stirring, sequentially adding 30g of m-methoxyphenol and 50g of iodotrimethylsilane into a reaction bottle, heating to 80-90 ℃, and reacting for 8-9 h. Cooling to room temperature after the reaction is finished, adding water into the reaction solution for quenching, separating liquid, adding toluene into the water phase for extraction once, and discarding the organic phase; adding ethyl acetate into the water phase, extracting for 2 times, combining organic phases, washing with the aqueous solution for 2 times, and concentrating under reduced pressure to obtain the resorcinol. Adding 150ml toluene, heating to 110 deg.C to dissolve, cooling to 0 deg.C, filtering, and washing with 20ml toluene to obtain 4.3g white crystal, which is recorded as L10, i.e. resorcinol.
The purity of L10 was checked by high performance liquid chromatography (general rule 0512) to obtain the final purity of L10: 99.88 percent.
Yield: 71.3 percent.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like made within the design concept of the present invention should be included in the scope of the present invention.
Claims (9)
1. A preparation method of resorcinol is characterized in that: the method comprises the following steps:
(1) synthesizing m-methoxyphenol: m-substituted phenol is taken as a raw material, and nucleophilic substitution reaction is carried out under the action of a catalyst to generate m-methoxyphenol;
(2) synthesizing resorcinol: under the action of demethylating reagent, m-methoxyphenol removes methyl to generate resorcinol.
2. The method of claim 1, wherein: in the step (1), the m-substituted phenol is selected from one of m-bromophenol, m-chlorophenol and m-iodophenol.
3. The method of claim 1, wherein: in the step (1), the catalyst is a mixture of a copper catalyst and esters, wherein the dosage ratio of the copper catalyst to the esters is 1: 1-10.
4. The method for producing resorcinol according to claim 3, wherein: the copper catalyst is selected from one or a mixture of more of cuprous bromide, cuprous iodide or copper acetate.
5. The method for producing resorcinol according to claim 3, wherein: the esters are selected from one or a mixture of methyl acetate, ethyl formate or ethyl acetate.
6. The method of claim 1, wherein: in the step (2), the demethylating reagent is selected from one or a mixture of more of aluminum trichloride, aluminum tribromide, aluminum triiodide, trimethyliodosilane, hydriodic acid and hydrobromic acid.
7. The method of claim 6, wherein: in the step (2), the demethylating reagent is hydroiodic acid.
8. The method of claim 7, wherein: in the step (2), sodium iodide is added into the reaction system to generate hydroiodic acid in situ as a demethylating reagent.
9. The method of claim 1, wherein: the purity of the resorcinol obtained by the preparation method is not less than 99.5%, and the yield is not less than 70%.
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