CN115611790A - Preparation method of methylthio methyl phenyl ether - Google Patents
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- FHZZRIIWMOYGOA-UHFFFAOYSA-N methylsulfanylmethoxybenzene Chemical compound CSCOC1=CC=CC=C1 FHZZRIIWMOYGOA-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 59
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 13
- 150000002989 phenols Chemical class 0.000 claims abstract description 13
- 238000010992 reflux Methods 0.000 claims abstract description 12
- -1 methylthio methyl phenyl ether compound Chemical class 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- 239000012044 organic layer Substances 0.000 claims description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- 238000010898 silica gel chromatography Methods 0.000 claims description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000003513 alkali Substances 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- 238000010438 heat treatment Methods 0.000 description 8
- 239000008399 tap water Substances 0.000 description 7
- 235000020679 tap water Nutrition 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical class CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 2
- 231100000357 carcinogen Toxicity 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- RKSOPLXZQNSWAS-UHFFFAOYSA-N tert-butyl bromide Chemical compound CC(C)(C)Br RKSOPLXZQNSWAS-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FZTLLUYFWAOGGB-UHFFFAOYSA-N 1,4-dioxane dioxane Chemical compound C1COCCO1.C1COCCO1 FZTLLUYFWAOGGB-UHFFFAOYSA-N 0.000 description 1
- ZMOMCILMBYEGLD-UHFFFAOYSA-N 2-chloro-4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(Cl)=C1 ZMOMCILMBYEGLD-UHFFFAOYSA-N 0.000 description 1
- JDWWIEFMFPWBST-UHFFFAOYSA-N 4-hydroxy-2-methylbenzaldehyde Chemical compound CC1=CC(O)=CC=C1C=O JDWWIEFMFPWBST-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000005815 base catalysis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- NHOGGUYTANYCGQ-UHFFFAOYSA-N ethenoxybenzene Chemical compound C=COC1=CC=CC=C1 NHOGGUYTANYCGQ-UHFFFAOYSA-N 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/26—Separation; Purification; Stabilisation; Use of additives
- C07C319/28—Separation; Purification
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of methylthio methyl phenyl ether, which comprises the following steps: adding a phenolic compound and dimethyl sulfoxide (DMSO) into a container, and carrying out reflux reaction for 60min; separating and purifying after the reaction is finished to obtain the methylthio methyl phenyl ether compound. The synthesis method provided by the invention is simple to operate and high in yield; no alkali catalyst and solvent are needed to be added, the method is environment-friendly and green, and a new method is provided for preparing methylthio methyl phenyl ether.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of methylthio methyl phenyl ether.
Background
For recent decades, methylthiomethyl ethers have been used as protecting groups for primary, secondary and tertiary alcohols. Phenol derivatives are useful compounds for use as dyes, pigments and agrochemicals, and are versatile building blocks for many natural products, bioactive compounds and pharmaceuticals. The main process for converting phenol to methylthio methyl ether comprises: (a) Phenol with dimethyl sulfoxide and tert-butyl bromide in base K 2 CO 3 Reacting in the presence of a catalyst to produce methylthiomethylphenyl ether (Journal of the Chemical society. Perkin transformations 1, 1141-1144); (b) Phenol and K 2 CО 3 The reaction of the-DMSO-acetylene system produces methylthiomethylphenyl ether (Russian Journal of Organic Chemistry,50, 1199-1200). These processes have limitations in that the process (a) mainly obtains methylthiomethyl ortho-substituted phenol (formula 2 in FIG. 1), while the objective methylthiomethyl phenyl ether is obtained only in a relatively low yield, and the process (a) requires the use of a large excess of a halogenated hydrocarbon, i.e., t-butyl bromide, which has been found to be a carcinogen; the same problem exists with process (b), the main product being phenyl vinyl ether (formula 3 in FIG. 1), whereas the title compound methylthiomethyl phenyl ether is obtained in only 8% yield. In conclusion, the methods (a) and (b) for preparing methylthio methyl phenyl ether both need to use base catalysis, and are accompanied by byproducts with low yield.
Therefore, the development of a simple, green and efficient synthetic method of the methylthio methyl phenyl ether has certain significance.
Disclosure of Invention
The invention aims to provide a preparation method of methylthio methyl phenyl ether, which has simple operation and higher yield; no alkali catalyst and solvent are needed to be added, and the environment is protected.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for preparing methylthio methyl phenyl ether, the structure of which is shown in the following general formula 1:
wherein R is phenyl, substituted phenyl or naphthyl, and the specific preparation method is as follows:
adding a phenolic compound and dimethyl sulfoxide into a container, and carrying out reflux reaction for 60min; separating and purifying after the reaction is finished to obtain the methylthio methyl phenyl ether compound;
the phenolic compound has a structural formula as follows:
R-OH
wherein R is phenyl, substituted phenyl or naphthyl. The reaction is heated and boiled during reflux.
The preparation method of the methylthio methyl phenyl ether comprises the following steps: the addition amount of the phenolic compound and dimethyl sulfoxide n Phenolic compounds ：V Dimethyl sulfoxide =0.3mmol:1mL. According to the chemical property of dimethyl sulfoxide, the reaction is designed and the addition of dimethyl sulfoxide is controlled, so that the dimethyl sulfoxide not only serves as a reactant, but also has the function of a solvent.
The preparation method of the methylthio methyl phenyl ether comprises the following steps: the separation and purification process after the reaction is as follows: extracting a substance obtained after the reaction is finished by using ethyl acetate for 2-3 times, taking an organic layer, washing the organic layer by using water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; the obtained filtrate was concentrated under reduced pressure, and the concentrated residue was separated and purified by silica gel column chromatography to obtain methylthio methyl phenyl ether compounds.
The preparation method of the methylmercapto-methylphenyl ether comprises the following steps: the eluent of the silica gel column chromatography is petroleum ether/ethyl acetate, and the volume ratio is 20-40: 1.
compared with the prior art, the invention has the beneficial effects that:
the synthesis method is simple to operate, and the methylthio methyl phenyl ether can be prepared by directly heating and refluxing; the invention solves the problem of low yield of the existing preparation method, and the preparation yield is higher and reaches 47-72%; and an alkali catalyst is not needed, carcinogens are prevented from contacting in the preparation process, a solvent is not needed to be additionally used, the environment is protected, and a new method is provided for preparing the methylthio methyl phenyl ether.
In order to ensure that the preparation method of the methylthio methyl phenyl ether is scientific and reasonable, the inventor carries out corresponding research and screening through the following tests to finally determine the technical scheme of the invention.
1. Main instruments and reagents
INOVA 600MHz nuclear magnetic resonance tester (TMS internal standard), warian technologies, china ltd, usa;
dimethylsulfoxide DMSO, carbofuran reagent limited;
phenolic compounds, carbofuran reagents ltd;
thin layer chromatography silica gel plate, qingdao ocean chemical plant.
2. Reaction condition optimization
Phenol (0.3 mmol) and DMSO (1 mL) are used as reaction substrates, reaction temperature, reaction time and solvent types are selected as reaction factors to be considered, the influence of each reaction factor on yield is designed and considered, and the results are shown in Table 1. As can be seen from Table 1, phenol was best refluxed in DMSO for 60 min. The solvent is selected from N, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMA), 1,4-dioxane (1,4-dioxane), tetrahydrofuran (THF), dichloroethane (DCE), carbon tetrachloride (CCl) under the optimal reaction condition 4 ) Anhydrous ethanol (EtOH) was used as an object of the examination. As can be seen from Table 1, the reaction yield was low or even non-reactive after the addition of the solvent, and thus, no additional solvent was required for the reaction, and DMSO was both a reactant and a reaction solvent.
TABLE 1 Effect of various reaction factors on yield
Optimized reaction conditions are adopted to prepare methylthio methyl phenyl ether with different substituents, which are detailed in examples.
Drawings
FIG. 1 shows the structure of the main product obtained by the reaction of two phenols which have not been subjected to the preparation process of the present invention, to convert into methylthiomethyl ether, wherein 2-methylthiomethyl group is ortho-substituted phenol; 3-phenyl vinyl ether.
Detailed Description
Example 1: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of phenol and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; the obtained filtrate was concentrated under reduced pressure, and the concentrated residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate volume ratio 40: 1) to obtain methylthiomethylphenyl ether derivative 1a; the yield was 62%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 a) obtained by the preparation of (1 a) (( 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ7.35–7.33(dd,J＝8.7,7.3Hz,2H),7.05–7.03(tt,J＝7.3,1.1Hz,1H),7.01–6.99(dd,J＝8.7,1.1Hz,2H),5.18(s,2H),2.29(s,3H) 13 C NMR(151MHz,CDCl 3 )δ157.06,129.49,121.78,115.98,72.38,14.62.
example 2: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of p-methylphenol and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by using silica gel column chromatography (petroleum ether: ethyl acetate volume ratio is 40; the yield was 69%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 b) obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ7.13–7.12(d,J＝8.2Hz,2H),6.89–6.88(d,J＝8.6Hz,2H),5.15(s,1H),2.32(s,3H),2.27(s,3H). 13 C NMR(151MHz,CDCl 3 )δ154.82,131.21,129.95,116.01,72.65,20.55,14.55.
example 3: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of p-4-phenylphenol and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by using silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 30); the yield was 72%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 c) obtained 1 H NMR and 13 c NMR) the data detected were: 1 H NMR(600MHz,CDCl 3 )δ7.58–7.56(td,J＝7.0,1.8Hz,4H),7.46–7.43(t,J＝7.7Hz,2H),7.35–7.32(m,1H),7.07–7.05(d,J＝8.7Hz,2H),5.22(s,2H),2.31(s,3H). 13 C NMR(151MHz,CDCl 3 )δ156.51,140.70,134.90,128.74,128.19,126.83,116.22,72.46,14.63.
example 4: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of 2-hydroxynaphthalene and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by using silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 30); the yield was 70%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 d) obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ7.81–7.79(dd,J＝8.6,2.4Hz,2H),7.78–7.76(dd,J＝8.3,1.1Hz,1H),7.49–7.46(ddd,J＝8.2,6.8,1.3Hz,1H),7.40–7.37(ddd,J＝8.1,6.8,1.2Hz,1H),7.25–7.25(d,J＝2.5Hz,1H),7.22–7.21(dd,J＝8.9,2.5Hz,1H),5.29(s,2H),2.32(s,3H). 13 C NMR(151MHz,CDCl 3 )δ154.95,134.25,129.60,129.41,127.66,126.98,126.47,124.08,119.12,109.03,72.44,14.76.
example 5: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of 4-hydroxy-2-methylbenzaldehyde and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by using silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 20); the yield was 65%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 e) obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ10.15(s,1H),7.79–7.78(d,J＝8.5Hz,1H),6.92–6.90(dd,J＝8.6,2.5Hz,1H),6.82–6.81(d,J＝1.6Hz,1H),5.22(s,2H),2.68(s,3H),2.29(s,3H). 13 C NMR(151MHz,CDCl 3 )δ191.23,161.07,143.23,134.52,128.58,118.63,113.06,72.19,19.90,14.69.
example 6: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of 3-hydroxybenzaldehyde and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by using silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 20); the yield was 62%.
Nuclear magnetic resonance of methylthio methyl phenyl ether derivative (1 f) obtained by the preparation of (1 f) (( 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ10.01(s,1H),7.55–7.53(dt,J＝7.5,1.3Hz,1H),7.51–7.48(t,J＝7.8Hz,1H),7.48–7.47(dd,J＝2.7,1.4Hz,1H),7.26–7.25(ddd,J＝8.1,2.6,1.2Hz,1H),5.23(s,2H),2.28(s,3H). 13 C NMR(151MHz,CDCl 3 )δ191.90,157.57,137.76,130.17,124.18,122.91,114.83,72.51,14.59.
example 7: a preparation method of methylthio methyl phenyl ether comprises the following steps:
adding 0.3mmol of 2-chloro-4-hydroxybenzaldehyde and 1mL of DMSO into a 5mL round-bottom flask, and heating and refluxing for reaction for 60min; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using tap water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; the obtained filtrate was concentrated under reduced pressure, and the concentrated residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate volume ratio: 20: 1) to obtain 1g of a methylthiomethylphenyl ether derivative; the yield was 47%.
Nuclear magnetic resonance of methylthiomethylphenyl ether derivative (1 g) obtained by the preparation of (1 g) 1 HNMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ10.37–10.37(d,J＝0.8Hz,1H),7.94–7.92(d,J＝8.7Hz,1H),7.02–7.02(d,J＝2.4Hz,1H),6.97–6.95(ddd,J＝8.7,2.4,0.9Hz,1H),5.22(s,2H),2.29(s,3H). 13 C NMR(151MHz,CDCl 3 )δ188.58,162.04,139.53,130.94,126.65,117.09,114.96,72.72,14.70.
the structures of the methylthiomethyl ether derivatives 1a to 1g obtained in examples 1 to 7 correspond by number to the following:
Claims (4)
1. a preparation method of methylthio methyl phenyl ether, wherein the methylthio methyl phenyl ether has a structure shown in a general formula 1:
wherein R is phenyl, substituted phenyl and naphthyl, and the preparation method is characterized in that:
adding a phenolic compound and dimethyl sulfoxide into a container, and carrying out reflux reaction for 60min; separating and purifying after the reaction is finished to obtain the methylthio methyl phenyl ether compound;
the phenolic compound has a structural formula as follows:
R-OH
wherein R is phenyl, substituted phenyl or naphthyl.
2. The process for producing methylthiomethylphenyl ether according to claim 1, wherein: the addition amount of the phenolic compound and dimethyl sulfoxide n Phenolic compounds ：V Dimethyl sulfoxide ＝0.3mmol：1mL。
3. The process for producing methylthiomethylphenyl ether according to claim 1, wherein: the separation and purification process after the reaction is as follows: extracting a substance obtained after the reaction is finished by using ethyl acetate for 2-3 times, taking an organic layer, washing the organic layer by using water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; the obtained filtrate was concentrated under reduced pressure, and the concentrated residue was separated and purified by silica gel column chromatography to obtain a methylthiomethylphenyl ether compound.
4. The process for producing methylthiomethylphenyl ether according to claim 3, wherein: the silica gel column chromatography eluent is petroleum ether/ethyl acetate, and the volume ratio is 20-40: 1.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040116475A1 (en) * | 2002-12-02 | 2004-06-17 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| CN106083539A (en) * | 2016-06-15 | 2016-11-09 | 郑州泰基鸿诺医药股份有限公司 | A kind of single fluorine methoxyl group or the synthetic method of single fluorine deuterated methoxyl group compounds |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040116475A1 (en) * | 2002-12-02 | 2004-06-17 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| CN106083539A (en) * | 2016-06-15 | 2016-11-09 | 郑州泰基鸿诺医药股份有限公司 | A kind of single fluorine methoxyl group or the synthetic method of single fluorine deuterated methoxyl group compounds |
Non-Patent Citations (1)
| Title |
|---|
| GUZEI, ILIA A.等: "Interesting Reactivity in the Thermolysis and Photolysis of 2, 3-Diphenyl-1-naphthol", J CHEM CRYSTALLOGR, pages 399 * |
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