CN112390736A - Preparation method of methyl sulfone compound - Google Patents

Preparation method of methyl sulfone compound Download PDF

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CN112390736A
CN112390736A CN202011433327.XA CN202011433327A CN112390736A CN 112390736 A CN112390736 A CN 112390736A CN 202011433327 A CN202011433327 A CN 202011433327A CN 112390736 A CN112390736 A CN 112390736A
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methylsulfone
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CN112390736B (en
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邓辰亮
辛艳花
张兴国
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Wenzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/34—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/76—Dibenzothiophenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Abstract

The invention discloses a synthetic method of a methyl sulfone compound, which comprises the following steps: taking an iodo compound as a substrate, adding a sulfite compound into the substrate, taking a 1, 4-dioxane solution as a solvent, heating under the protection of nitrogen and the action of a silicon reagent, a phase transfer catalyst and a palladium catalyst to prepare a crude product, purifying and purifying the crude product, filtering the crude product, and removing the solvent to obtain a residue; performing silica gel column chromatography on the residue, leaching by eluent, and collecting effluent; combining the effluent containing the product; and concentrating the combined effluent to remove the solvent, and finally performing vacuum drying to obtain the target product. The method has the advantages of simple process flow, easy purification of products, environment safety and high yield.

Description

Preparation method of methyl sulfone compound
Technical Field
The invention relates to a preparation method of a methyl sulfone compound.
Background
The sulfone is a key organic structural element in various bioactive molecules, medicaments and synthetic intermediates, and the sulfone compound has broad-spectrum bioactivity, such as insecticidal activity, sterilization, weeding activity, anti-tumor activity, anti-virus activity and the like. Therefore, the development of a high-efficiency green method for synthesizing the compound has important significance. A method for synthesizing corresponding methyl sulfone compounds by oxidizing sulfides is disclosed in Marjan Jerbe (Green chem., 2012, 143047), namely 75oAnd oxidizing the benzylsulfide with 30% aqueous hydrogen peroxide solution to synthesize the phenyl methyl sulfone.
Although the methyl sulfone compound can be prepared by the method, the method needs to add a strong oxidant, and the use of the strong oxidant not only causes the functional group compatibility to be deficient, but also causes serious damage to equipment and instruments, and is not beneficial to industrial popularization.
Disclosure of Invention
The purpose of the invention is as follows: in order to overcome the defects of the prior art, the invention provides a new sulfur dioxide source and a preparation method of a methyl sulfone compound, which is convenient for industrial popularization.
In order to achieve the purpose, the invention adopts the technical scheme that:
a preparation method of a methyl sulfone compound comprises the following steps: iodo compound is taken as a substrate, sulfite compound is added into the substrate, 1, 4-dioxane solution is taken as a solvent, and the reaction is carried out for 18 hours at 120 ℃ under the protection of nitrogen and the catalysis of a silicon reagent, a phase transfer catalyst and a palladium catalyst, wherein the chemical reaction formula is as follows:
Figure 219721DEST_PATH_IMAGE001
wherein R1 is one of 4-methoxyphenyl, 4-methylphenyl, 4-tert-butylphenyl, biphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 2-methoxyphenyl, 3, 5-dimethylphenyl, 3, 4-dimethoxyphenyl, 1-naphthyl, 2-thienyl, 4-benzothienyl, 2-fluorenyl, cyclohexyl and decyl, and R2 is one of methyl and ethyl.
Preferably, the amount of the sulfite-based compound is 10 equivalents.
Preferably, the palladium catalyst is bis (triphenylphosphine) palladium (II) dichloride.
Preferably, the molar percentage of the bis (triphenylphosphine) palladium (II) dichloride is 0.1 equivalent.
Preferably, the silicon reagent is 1,1,3, 3-tetramethyldisiloxane.
Preferably, the amount of the 1,1,3, 3-tetramethyldisiloxane is 1.5 equivalents.
Preferably, the phase transfer catalyst is tetrabutylammonium bromide.
Preferably, the amount of tetrabutylammonium bromide is 1 equivalent.
Preferably, the molar ratio of the substrate to the sulfite compound is 1: 10.
Preferably, the method also comprises the following purification steps: filtering and removing the solvent from the crude product to obtain a residue; performing silica gel column chromatography on the residue, leaching by eluent, and collecting effluent; combining the effluent containing the product; and concentrating the combined effluent to remove the solvent, and finally performing vacuum drying to obtain the target product.
The invention has the beneficial effects that: the substrate, the palladium catalyst, the silicon reagent and the phase transfer catalyst adopted by the invention are common chemicals and have lower price. The preparation method of the methyl sulfone compound has the advantages of simple process flow and low toxicity, in addition, the preparation process is green and safe, the economic utilization rate of atoms is high, the method has wide substrate universality, and the problem of functional group compatibility in the synthesis of related compounds is successfully solved.
Detailed Description
Specific examples of the present invention are as follows.
The first embodiment is as follows: 117.0 mg (0.5 mmol) of p-iodoanisole, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane, 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube,then 2 mL of 1, 4-dioxane solution, 120oHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 78.1 mg of 4-methoxy methyl sulfone as a white solid with the yield of 84%.1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 2.98 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 163.6, 132.2, 129.4, 114.5, 55.7, 44.7。
The second embodiment is as follows: 102.0 mg (0.5 mmol) of iodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide were addedoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 63.4 mg of white solid, namely the phenylmethanesulfone with the yield of 81%.1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.6 Hz, 2H), 7.69 -7.65 (m, 1H), 7.61 - 7.56(m, 2H), 3.06 (s, 3H).13C NMR (125 MHz, CDCl3) δ 140.5, 133.7, 129.3, 127.3, 44.4。
The third concrete embodiment: 109.0 mg (0.5 mmol) of 4-iodotoluene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was addedoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 57.5 mg of 4-methyl phenyl sulfone as a white solid with the yield of 68%.1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 3.01 (s, 3H), 2.47 (s, 3H).13C NMR (125 MHz, CDCl3) δ 144.6, 137.7, 129.9, 127.3, 44.6, 21.6。
The fourth concrete embodiment: 140.1 mg (0.5 mmol) of 4-iodobiphenyl, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide were addedoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 84.8 mg of 4- (methylsulfonyl) -1, 1-biphenyl as a white solid with the yield of 73%.1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 7.6Hz, 2H), 7.46-7.37 (m, 3H), 3.09 (s, 3H).13C NMR (125MHz, CDCl3) δ 146.6, 139.1, 139.1, 129.1, 128.7, 128.0, 127.9, 127.4, 44.6。
The fifth concrete embodiment: 130.1 mg (0.5 mmol) of 4-tert-butyliodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120oHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 75.8 mg of 4-tert-butyl methyl sulfone as a white solid with the yield of 72%.1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 3.07 (s, 3H), 1.37 (s, 9H).13C NMR (125 MHz, CDCl3) δ 157.6, 137.6, 127.2, 126.3, 44.5, 35.2, 31.0。
The sixth specific embodiment: 111.0 mg (0.5 mmol) of p-fluoroiodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bistriphenylphosphine dioxidePalladium (II) chloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane, 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120oHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 60.5 mg of white solid 4-fluorobenzenesulfone with the yield of 70%.1H NMR (400 MHz, CDCl3) δ 8.13-7.66 (m, 2H), 7.29-7.25(m, 2H), 3.08 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.78 (d, J = 256.0 Hz), 136.70 (d, J = 3.0 Hz), 130.29 (d, J = 9.5 Hz), 116.68 (d, J = 22.5 Hz), 44.66。
The seventh specific embodiment: 119.2 mg (0.5 mmol) of p-chloroiodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was added to the reaction tubeoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 52.6 mg of 4-chlorobenzenesulfone as a white solid with the yield of 55%.1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 3.02 (s, 3H).13C NMR (125 MHz, CDCl3) δ 140.4, 139.0, 129.7, 128.9, 44.5。
The eighth embodiment: 141.5 mg (0.5 mmol) of p-bromoiodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was addedoHeating for 18 hr, cooling after reaction, filtering, rotary evaporating the filtrate, removing solvent, performing silica gel column chromatography on the residue, eluting with petroleum ether, detecting by TLC, mixing the effluent containing the product, distilling with rotary evaporator to remove solvent, and vacuum drying to obtain white solid61.2 mg of 4-bromobenzenesulfone, yield 52%.1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 3.03 (s, 3H).13C NMR (125 MHz, CDCl3) δ 139.55, 132.69, 128.97, 44.49。
The specific embodiment is nine: 136.0 mg (0.5 mmol) of 4-iodotrifluorotoluene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bistriphenylphosphine palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mgoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 56.1 mg of 4-trifluoromethyl phenylsulfone as a white solid with the yield of 50%.1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 3.08 (s, 3H).13C NMR (125 MHz, CDCl3) δ143.97, 135.40 (q, J = 33.0 Hz), 128.08, 126.55 (q, J = 3.5 Hz), 124.17, 122.00, 119.83，44.26。
The specific embodiment ten: 117.0 mg (0.5 mmol) of 2-iodoanisole, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mgoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 41.0 mg of 2-methoxy methyl sulfone as a white solid with the yield of 44%.1H NMR (400 MHz, CDCl3) δ 7.87 (dd, J = 7.6, 1.6 Hz, 1H), 7.57-7.43 (m, 1H), 7.02 (t, J = 8.0 Hz, 2H), 3.92 (s, 3H), 3.14 (s, 3H).13C NMR (125 MHz, CDCl3) δ 160.11 , 141.74, 130.51, 120.16, 119.45, 111.85 , 55.74, 44.44。
Detailed description of the inventionExample eleven: 117.0 mg (0.5 mmol) of 3-iodoanisole, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mgoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 64.2 mg of 3-methoxy methyl sulfone as a white solid with the yield of 69%.1H NMR (400 MHz, CDCl3) δ 7.51-7.38 (m, 2H), 7.18 -7.09 (m, 1H), 3.84 (s, 3H), 3.03 (s, 3H).13C NMR (125 MHz, CDCl3) δ 160.09, 141.73, 130.51, 120.10, 119.41, 111.88, 55.73, 44.41。
The specific example twelve: 116.0 mg (0.5 mmol) of 5-iodo-m-xylene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mgoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 72.8 mg of 1, 3-dimethyl-5- (methylsulfonyl) benzene as a white solid with the yield of 79 percent.1H NMR (400 MHz, CDCl3) δ 7.68 (s, 1H), 7.64 (d, J = 7.8Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 3.01 (s, 3H), 2.33 (s, 6H). 13C NMR (125 MHz, CDCl3) δ 143.35, 138.18, 137.87, 130.44, 128.10, 124.82, 44.63, 19.99, 19.79。
The specific example thirteen: mg (0.5 mmol) of 3, 4-dimethoxyiodobenzene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was addedoC heating for 18 hours, reactingAfter cooling, filtration, rotary evaporation of the filtrate to remove the solvent, chromatography of the residue on silica gel column, washing with petroleum ether, detection by TLC, combination of the effluents containing the product, distillation by a rotary evaporator to remove the solvent, and vacuum drying to give 75.7 mg of 1, 2-dimethoxy-4- (methylsulfonyl) benzenediol as a white solid in 70% yield.1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 8.4 Hz, 1H), 7.30 (s, 1H), 6.92 (d, J = 8.4 Hz, 1H),3.82 (d, J = 4.8 Hz, 6H), 2.94 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 153.26, 149.20, 132.29, 121.32, 110.88, 109.54, 56.21, 44.71。
The specific embodiment fourteen: 127.0 mg (0.5 mmol) of 1-iodonaphthalene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide were addedoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 81.5 mg of 1- (methylsulfonyl) naphthalene as a white solid with the yield of 79%.1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 8.8 Hz, 1H), 8.30 (d, J = 7.4 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.74 -7.64 (m, 1H), 7.63 - 7.50 (m, 2H), 3.18 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 135.60, 135.20, 134.19, 129.60, 129.37, 128.78, 128.62, 127.05, 124.48, 123.88, 44.29。
The specific embodiment fifteen: 105.0 mg (0.5 mmol) of 2-iodothiophene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was addedoHeating for 18 hr, cooling after reaction, filtering, rotary evaporating the filtrate, removing solvent, performing silica gel column chromatography on the residue, eluting with petroleum ether, detecting by TLC, mixing the eluates, distilling with rotary evaporator to remove solvent, and vacuum evaporatingDrying afforded 43.8 mg of 2-methylsulfonylthiophene as a white solid in 54% yield.1H NMR (400 MHz, CDCl3) δ8.08 -7.46 (m, 2H), 7.14 (t, J = 4.4 Hz, 1H), 3.17 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 141.80, 133.70, 133.48, 127.93, 46.13。
The specific embodiment is sixteen: 146.1 mg (0.5 mmol) of 2-iodofluorene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was added to the reaction tubeoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 94.8 mg of 2- (methylsulfonyl) -fluorene as a white solid with the yield of 78%.1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.80 -7.77 (m, 1H), 7.54 (d, J = 6.4 Hz, 1H), 7.43 -7.34 (m, 2H), 3.88 (s, 2H), 3.08 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 147.01, 144.27, 144.02, 139.63, 138.32, 128.60, 127.26, 126.42, 125.33, 124.06, 121.07, 120.29, 44.78, 36.89。
Specific example seventeen: 155 mg (0.5 mmol) of 4-iododibenzothiophene, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was added to the reaction tubeoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 43.8 mg of 4- (methylsulfonyl) dibenzothiophene as a white solid with the yield of 59%.1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 7.8 Hz, 1H), 8.14 (d, J = 7.4 Hz, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.55 -7.44 (m, 2H), 3.15 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 139.98, 138.02, 137.66, 134.07, 133.96, 127.99, 127.25, 126.51, 125.11, 124.92, 122.63, 121.91, 42.92。
The specific embodiment eighteen: 105.0 mg (0.5 mmol) of iodocyclohexane, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide were addedoC, heating for 18 hours, cooling after the reaction is finished, filtering, carrying out rotary evaporation on the filtrate to remove the solvent, carrying out silica gel column chromatography on the residue, carrying out leaching with petroleum ether, carrying out TLC detection, combining effluent containing the product, distilling by using a rotary evaporator to remove the solvent, and carrying out vacuum drying to obtain 65.0 mg of (methylsulfonyl) cyclohexane oil with the yield of 80%.1H NMR (400 MHz, CDCl3) δ 2.84-2.72 (m, 4H), 2.13 (d, J = 13.4 Hz, 2H), 1.87 (d, J = 13.4, 2H),, 1.72- 1.61 (m, 1H), 1.44 (q, J = 12.5 Hz, 2H), 1.34 -1.08 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 62.37, 37.22, 25.37, 25.00。
The specific examples are nineteen: 134.1 mg (0.5 mmol) of 1-iododecane, 550.3 mg (5 mmol) of dimethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 161.3 mg (0.5 mmol) of tetrabutylammonium bromide were added to a reaction tube, 120.5 mg (0.5 mmol) of tetrabutylammonium bromide was addedoHeating for 18 hours, cooling after the reaction is finished, filtering, performing rotary evaporation on the filtrate to remove the solvent, performing silica gel column chromatography on the residue, leaching with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 20.9 mg of 1- (methylsulfonyl) decane oily liquid with the yield of 19%.1H NMR (400 MHz, CDCl3) δ 3.07-2.98 (m, 2H), 2.91 (s, 3H), 1.92 - 1.79 (m, 2H), 1.48-1.43 (m,2H), 1.32-1.28 (m, 12H), 0.90 (t, J = 6.7 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 54.87, 40.41, 31.82, 29.43, 29.23, 29.21, 29.03, 28.39, 14.07。
In the first to nineteenth embodiments, the substrates are: 4-iodoanisole, iodobenzene, 4-iodotoluene, 4-iodobiphenyl, 4-tert-butyliodobenzene, p-fluoroiodobenzene, p-chloroiodobenzene, p-bromoiodobenzene, 4-iodotrifluorotoluene, 2-iodoanisole, 3, 4-dimethoxyiodobenzene, 5-iodometaxylene, 1-iodonaphthalene, 2-iodothiophene, 2-iodofluorene, 4-iododibenzothiophene, iodocyclohexane, 1-iododecane; wherein dimethyl sulfite is taken as a methyl sulfone source, and the amount of the dimethyl sulfite is 10 equivalents; bis (triphenylphosphine) palladium dichloride (II) is used as a catalyst, and the molar percentage content is 1 equivalent; tetrabutylammonium bromide is used as a phase transfer catalyst, and the amount of the tetrabutylammonium bromide is 1 equivalent; 1,1,3, 3-tetramethyldisiloxane is taken as an additive, the amount of the additive is 1.5 equivalents, and the molar ratio of the substrate to the bisulphite is 1: 10; under the condition of nitrogen, the reaction temperature is 120 ℃; the reaction time was 18 h.
The specific embodiment twenty: 117.0 mg (0.5 mmol) of p-iodoanisole, 691.0 mg (5 mmol) of diethyl sulfite, 35.1 mg (0.05 mmol) of bis (triphenylphosphine) palladium (II) dichloride, 100.7 mg (0.75 mmol) of 1,1,3, 3-tetramethyldisiloxane and 150.8 mg (0.5 mmol) of tetrabutylammonium acetate were added to a reaction tube, 120.5 mg ofoHeating for 18 hours, cooling after the reaction is finished, filtering, carrying out rotary evaporation on the filtrate to remove the solvent, carrying out silica gel column chromatography on the residue, eluting with petroleum ether, detecting by TLC, combining effluent containing the product, distilling by a rotary evaporator to remove the solvent, and carrying out vacuum drying to obtain 8.1 mg of 1- (ethylsulfonyl) -4-methoxybenzene as a white solid with the yield of 8%.1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H), 3.07 (q, J = 7.4 Hz, 2H), 1.24 (t, J = 7.4 Hz, 3H).13C NMR (125 MHz, CDCl3) δ 163.72, 130.34,130.08, 114.43, 55.69, 50.85, 7.57。
In the above specific example twenty, the substrates are: p-iodoanisole; adding diethyl sulfite into a substrate in an amount of 10 equivalents; bis (triphenylphosphine) palladium dichloride (II) is used as a catalyst, and the molar percentage content is 1 equivalent; tetrabutylammonium acetate is used as a phase transfer catalyst, and the amount of the tetrabutylammonium acetate is 1 equivalent; 1,1,3, 3-tetramethyldisiloxane is taken as an additive, the amount of the additive is 1.5 equivalents, and the molar ratio of the substrate to the diethyl sulfite is 1: 10; under the condition of nitrogen, the reaction temperature is 120 ℃; the reaction time was 18 h.
In all the embodiments, a series of aryl methyl sulfone and alkyl methyl sulfone compounds are synthesized by selecting iodo compounds containing different substituents to react with sulfite compounds, and the method has certain substrate universality and operation simplicity.
Because the methyl sulfone source adopted by the invention is dimethyl sulfite, no intermediate product needs to be separated in the reaction process, the target product can be directly synthesized in one step, the process is simplified, the environmental pollution is reduced, and the yield of sulfone compounds is effectively improved.

Claims (10)

1. A preparation method of a methyl sulfone compound comprises the following steps: iodo compound is taken as a substrate, sulfite compound is added into the substrate, 1, 4-dioxane solution is taken as a solvent, under the protection of nitrogen, and the reaction is carried out for 18 hours at 120 ℃ under the catalysis of silicon reagent, phase transfer catalyst and palladium catalyst to obtain a crude product, wherein the chemical reaction formula is as follows:
Figure 545884DEST_PATH_IMAGE001
wherein R is1Is one of 4-methoxyphenyl, 4-methylphenyl, 4-tert-butylphenyl, biphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 2-methoxyphenyl, 3, 5-dimethylphenyl, 3, 4-dimethoxyphenyl, 1-naphthyl, 2-thienyl, 4-benzothienyl, 2-fluorenyl, cyclohexyl and 1-decyl; r2Is one of methyl and ethyl.
2. The method for preparing a methylsulfone compound according to claim 1, wherein: the amount of the sulfite compound is 10 equivalents.
3. The method for preparing a methylsulfone compound according to claim 1, wherein: the palladium catalyst is bis (triphenylphosphine) palladium dichloride (II).
4. The method for preparing a methylsulfone compound according to claim 3, wherein: the molar percentage of bis (triphenylphosphine) palladium (II) dichloride was 0.1 equivalents.
5. The method for preparing a methylsulfone compound according to claim 1, wherein: the silicon reagent is 1,1,3, 3-tetramethyldisiloxane.
6. The method for preparing a methylsulfone compound according to claim 5, wherein: the amount of the 1,1,3, 3-tetramethyldisiloxane was 1.5 equivalents.
7. The method for preparing a methylsulfone compound according to claim 1, wherein: the phase transfer catalyst is tetrabutylammonium bromide.
8. The method for preparing a methylsulfone compound according to claim 7, wherein: the amount of tetrabutylammonium bromide is 1 equivalent.
9. The method for preparing a methylsulfone compound according to claim 1, wherein: the molar ratio of the substrate to the sulfite compound is 1: 10.
10. The method for preparing a methylsulfone compound according to claim 1, wherein: also comprises the purification and purification steps: filtering and removing the solvent from the crude product to obtain a residue; performing silica gel column chromatography on the residue, leaching by eluent, and collecting effluent; combining the effluent containing the product; and concentrating the combined effluent to remove the solvent, and finally performing vacuum drying to obtain the target product.
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