CN114044730B - Synthesis method of sulfoxide compound - Google Patents

Synthesis method of sulfoxide compound Download PDF

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CN114044730B
CN114044730B CN202111419804.1A CN202111419804A CN114044730B CN 114044730 B CN114044730 B CN 114044730B CN 202111419804 A CN202111419804 A CN 202111419804A CN 114044730 B CN114044730 B CN 114044730B
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sulfoxide
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CN114044730A (en
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吴劼
王雪枫
张俊
叶盛青
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Taizhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/04—Formation or introduction of functional groups containing sulfur of sulfonyl or sulfinyl groups
    • 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
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

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Abstract

The invention belongs to the technical field of organic chemistry, and particularly relates to a synthesis method of sulfoxide compounds. The synthesis method is characterized in that sulfinic acid or salts thereof, N '-carbonyl diimidazole and 4-alkyl Hantzsch ester react in an organic solvent under the condition of simplicity and mildness in the presence of a photocatalyst, an N-heterocyclic carbene catalyst and alkali, the sulfinic acid and the N, N' -carbonyl diimidazole firstly react to generate corresponding sulfinyl imidazole, then the sulfinyl imidazole is subjected to nucleophilic attack of the N-heterocyclic carbene, single-electron transfer is carried out under the photocatalysis, sulfinyl free radicals and alkyl free radicals are generated in the system, and then free radical coupling is carried out to generate the target sulfoxide compound. The method provides a new idea of synthesizing sulfoxide compounds without thiol and thioether compounds through oxidation reaction, constructs a series of sulfoxide compounds which are difficult to synthesize by a common method, and has good guiding significance and application prospect in the scientific research and industrial fields.

Description

Synthesis method of sulfoxide compound
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a synthesis method of sulfoxide compounds.
Background
Sulfoxide compounds have wide application in organic synthesis, pharmaceutical chemistry and agrochemistry. The traditional strategy for synthesizing sulfoxide compounds is greatly dependent on catalytic oxidation [(a)K.-J.Liu,Z.Wang,W.-M.He et al.Green Chem.,2021,23,496;(b)L.Zhao,H.Zhang and Y.Wang,J.Org.Chem.,2016,81,129;(c)R.-H.Wu,J.Wu,M.-X.Yu and L.-G.Zhu,RSC Adv.,2017,7,44259.], of thioether compounds, which is easy to generate sulfone byproducts and difficult to separate; however, the thioether compounds are usually prepared by using malodorous mercaptan and thiophenol compounds, so that the application development of the thioether compounds is greatly limited.
Disclosure of Invention
The invention aims to provide a simple, environment-friendly and efficient method for synthesizing sulfoxide compounds without a thiol/thioether oxidation path. The synthesis method of the invention uses sulfinic acid and the salt thereof as reaction raw materials, generates sulfinyl free radical under the co-catalysis of light and nitrogen heterocyclic carbene, and obtains sulfoxide compounds through one-step coupling. The sulfinic acid and the salt thereof have the advantages of wide sources and easy preparation, simultaneously do not pass through malodorous mercaptan and thioether compounds in the reaction process, do not generate sulfone byproducts, are simple in subsequent separation, and have wide application prospects.
The invention innovatively uses sulfinic acid and the salt thereof as synthons, and the sulfoxide compound is simply and efficiently generated with high selectivity. Sulfoxide groups exist in the molecules of the compounds, and the molecular structural general formula of the compounds is as follows:
the technical scheme adopted for solving the technical problems is as follows:
The synthesis method is characterized in that sulfinic acid compounds, N '-carbonyl diimidazole and 4-alkyl Hantzsch ester compounds react in an organic solvent under the existence of a photocatalyst, an N-heterocyclic carbene catalyst and alkali, the sulfinic acid compounds and the N, N' -carbonyl diimidazole firstly react to generate corresponding sulfinyl imidazole, then nucleophilic attack of the N-heterocyclic carbene is carried out, single electron transfer occurs under the photocatalysis, sulfinyl free radicals and alkyl free radicals are generated in a system, and then free radical coupling is carried out to generate the target sulfoxide compounds.
Preferably, the structure of the sulfoxide compound is as follows:
wherein R 1 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted heterocyclic group, or a C1-C14 alkyl group, and R 2 is a primary alkyl group, a secondary alkyl group, or a tertiary alkyl group; wherein, the substituent is at least one of electron withdrawing group and electron donating group, the electron withdrawing group is at least one of fluoro, chloro, bromo, acyl, ester, cyano and trifluoromethyl, the electron donating group is at least one of iodo, C1-C14 alkyl, C1-C14 alkoxy and amino, the heterocycle is a multi-membered ring compound containing at least one hetero element, the hetero element is at least one of N, O, S, and the multi-membered ring is a four-membered ring to fourteen-membered ring; more preferably, the heterocycle is pyridine, thiophene, pyrimidine, furan, or a (pyridine, thiophene, pyrimidine, furan) fused ring derivative thereof.
Preferably, the reaction formula of the synthesis method is as follows:
Wherein R is an ester group or a cyano group, R 1 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted heterocyclic group, or a C1-C14 alkyl group, and R 2 is a primary alkyl group, a secondary alkyl group, or a tertiary alkyl group; wherein, the substituent is at least one of electron-withdrawing group and electron-donating group, the electron-withdrawing group is at least one of fluoro, chloro, bromo, acyl, ester, cyano and trifluoromethyl, the electron-donating group is at least one of iodo, C1-C14 alkyl, C1-C14 alkoxy and amino, the heterocycle is a multi-ring compound containing at least one hetero element, the hetero element is at least one of N, O, S, and the multi-ring is a four-membered to fourteen-membered ring; more preferably, the heterocycle is pyridine, thiophene, pyrimidine, furan, or a (pyridine, thiophene, pyrimidine, furan) fused ring derivative thereof.
Preferably, when the sulfinic acid compound is unstable, the corresponding salt can be replaced by the sulfinic acid compound, and the salt is preferably sodium salt or lithium salt, and when the sulfinic acid compound is replaced by the corresponding salt, the acid is added into the reaction system to convert the corresponding salt of the sulfinic acid compound into the sulfinic acid compound for reaction.
Preferably, the dosage of each material is 1.0 equivalent of 4-alkyl Hantzsch ester compound, and the dosage of sulfinic acid compound and N, N' -carbonyl diimidazole is 1.2-2.5 equivalents; the dosage of the photocatalyst is 0.005-0.02 equivalent; the dosage of the N-heterocyclic carbene catalyst is 0.05-0.2 equivalent; the amount of the alkali is 0.05-0.4 equivalent; namely, the feeding amount of each material is calculated as the mole ratio to be 4-alkyl Hantzsch ester compound: sulfinic acid compounds: n, N' -carbonyldiimidazole: and (3) a photocatalyst: azacyclo-carbene catalyst: the base was 1.0: (1.2-2.5): (1.2-2.5): (0.005-0.02): (0.05-0.2): (0.05-0.4).
Preferably, the reaction temperature is room temperature, and the room temperature is 15-40 ℃.
Preferably, the organic solvent is at least one of acetonitrile, dichloromethane, dichloroethane and chloroform, more preferably dichloromethane.
Preferably, the R group in the 4-alkyl Hantzsch ester compound used is selected from COOMe, COOEt, COO t Bu and CN, and is preferably COOEt when R 2 is a primary alkyl group or a secondary alkyl group, and is preferably CN when R 2 is a tertiary alkyl group.
Preferably, the photocatalyst is at least one of Ir(ppy)3、Ir[dF(CF3)ppy]2(bpy)PF6、Ir[dF(CF3)ppy]2(dtbbpy)PF6、4CzIPN, more preferably Ir [ dF (CF 3)ppy]2(bpy)PF6 or 4 CzIPN).
Preferably, the N-alkyl derivative salt of imidazole, triazole, thiazole, oxazole is at least one of imidazole, triazole, thiazole, oxazole, imidazole iodide, 1, 4-dimethyl-1, 2, 4-triazolium iodide, 1, 3-bis-mesitylene-1H-imidazole-3-ium tetrafluoroborate, 1, 3-di-tert-butyl-1H-imidazole-3-ium tetrafluoroborate, 2-phenyl-5, 6-dihydro-8H- [1,2,4] triazolo [3,4-c ] [1,4] oxazine-2-ium tetrafluoroborate, 3-ethylbenzo [ d ] thiazol-3-ium bromide; more preferably 1, 3-di-tert-butyl-1H-imidazol-3-ium tetrafluoroborate, CAS 263163-17-3.
Preferably, the base is at least one of carbonate, phosphate and acetate of sodium, potassium and cesium (alkali metal), and more preferably cesium carbonate.
Preferably, the organic solvent is used in an amount of 0.5-3mL per 0.2mmol of the 4-alkyl Hantzsch ester compound. More preferably 3mL of methylene chloride is used per 0.2mmol of 4-alkyl Hantzsch ester compound.
Preferably, the illumination condition is visible light irradiation, and the visible light comprises white light and blue light.
Preferably, the reaction time of the reaction is 4 to 20 hours, more preferably 4 to 12 hours.
Preferably, the specific steps of the synthesis method are as follows:
under inert atmosphere, adding a photocatalyst, a 4-alkyl Hantzsch ester compound, an N-heterocyclic carbene catalyst, alkali, a sulfinic acid compound or corresponding salt thereof and N, N' -carbonyl diimidazole into a dried reaction tube, so that the system is in an anhydrous and anaerobic condition, adding an organic solvent, and placing the reaction tube under an illumination condition for reaction to obtain the sulfoxide compound.
Preferably, the inert atmosphere is a nitrogen atmosphere or an argon atmosphere.
Preferably, after the reaction is completed, the sulfoxide compound is obtained through post-treatment; the post-treatment is as follows: concentrating the reaction liquid under reduced pressure, and performing column chromatography separation by using the mixed liquid of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfoxide compound.
The structure of the compound prepared by the invention is characterized and confirmed by 1H NMR、13 C NMR, HRMS and other methods.
Compared with the prior art, the invention has the beneficial effects that: the invention is characterized in that sulfinic acid, N '-carbonyl diimidazole and 4-alkyl Hantzsch ester react in an organic solvent under the condition of simplicity and mildness in the presence of a photocatalyst, an N-heterocyclic carbene catalyst and alkali, the sulfinic acid and the N, N' -carbonyl diimidazole firstly react to generate corresponding sulfinyl imidazole, then the N-heterocyclic carbene nucleophilic attack is carried out, single electron transfer is carried out under the photocatalysis, sulfinyl free radicals and alkyl free radicals are generated in the system, and then free radical coupling is carried out to generate the target sulfoxide compound. The method provides a new idea for synthesizing sulfoxide compounds without thiol and thioether compounds through oxidation reaction, builds a series of sulfoxide compounds which are difficult to synthesize by a common method, and has good guiding significance and application prospect in the scientific research and industrial fields.
Detailed Description
The technical scheme of the invention is further specifically described by the following specific examples. In the invention, the room temperature is 15-40 ℃.
Example 1
At room temperature, 0.002mmol Ir (dF) (CF 3)ppy]2(bpy)PF6, 0.2mmol Hantzsch ester diethyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dica rboxylate、0.04mmol 1,3- di-tert-butyl-1H-imidazole-3-onium tetrafluoroborate, 0.04mmol cesium carbonate, 0.4mmol p-toluene sulfinic acid and 0.4mmol N, N' -carbonyl diimidazole) was added into a dry test tube reaction tube, and placed in a high-purity argon atmosphere to allow the system to be in anhydrous and anaerobic condition, 3mL methylene chloride was added, and the mixture was placed in a blue light irradiation reactor and stirred until complete reaction was completed, the reaction time was 12H.
Structural characterization of compound example 1:
1H NMR(400MHz,Chloroform-d)δ7.88(dd,J＝5.4,3.1Hz,2H),7.76(dd,J＝5.5,3.1Hz,2H),7.60(d,J＝8.1Hz,2H),7.33(d,J＝8.0Hz,2H),4.85(d,J＝12.5Hz,1H),4.68(d,J＝12.5Hz,1H),2.42(s,3H).13C NMR(101MHz,Chloroform-d)δ166.76,142.69,138.56,134.68,131.74,130.32,124.63,124.01,60.37,21.67.HRMS(ESI)calc.for C16H13NNaO3S+(M+Na+):322.0508,found:322.0519.
Example 2
After monitoring the complete reaction by TLC, the reaction solution was concentrated under reduced pressure, and column chromatography was performed using a mixture of petroleum ether and ethyl acetate as a mobile phase, to give the corresponding 1- (((Benzyloxy) methyl) sulfinyl) -4-methylbenzene example 2 in 97% yield, with 0.03mmol of Ir [ dF (CF 3)ppy]2(bpy)PF6, 0.2mmolHantzsch ester diethyl 4- ((benzyloxy) methyl) -2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, 0.03mmol of 1, 3-di-tert-butyl-1H-imidazol-3-ium tetrafluoroborate, 0.03mmol of cesium carbonate, 0.4mmol of p-toluene sulfinic acid, and 0.4mmol of N, N' -carbonyldiimidazole, placed in a dry test tube at room temperature, purged in high-purity nitrogen, so that the system was kept in anhydrous and oxygen-free condition, 1mL of dichloromethane was added, placed in a blue light irradiation reactor, and stirred until the reaction was completed.
Structural characterization of compound example 2:
1H NMR(400MHz,Chloroform-d)δ7.52(d,J＝8.1Hz,2H),7.38–7.30(m,7H),4.92–4.83(m,2H),4.51–4.41(m,2H),2.41(s,3H).13C NMR(101MHz,Chloroform-d)δ142.03,137.86,136.44,130.14,128.72,128.45,128.26,124.61,91.49,74.96,21.58.HRMS(ESI)calc.for C15H16NaO2S+(M+Na+):283.0763,found:283.0774.
Example 3
After adding 0.004mmol Ir (dF (CF 3)ppy]2(bpy)PF6, 0.2mmolHantzsch ester diethyl 2,6-dimethyl-4- (5-methylhex-4-en-2-yl) -1,4-dihydropyridine-3,5-dicarboxylate, 0.04mmol 1, 3-di-tert-butyl-1H-imidazole-3-onium tetrafluoroborate, 0.04mmol cesium carbonate, 0.5mmol p-toluene sulfinic acid and 0.4mmol N, N' -carbonyldiimidazole) into a dry test tube reaction tube at room temperature, placing the mixture in a high-purity argon medium for ventilation, adding 2.5mL of dichloromethane after the system is in an anhydrous and anaerobic condition, placing the mixture in a blue light illumination reaction device for stirring until the complete reaction, concentrating the reaction solution under reduced pressure after the complete reaction is monitored by TLC, and carrying out column chromatography separation by adopting a mixed solution of petroleum ether and ethyl acetate as a mobile phase, thus obtaining the corresponding 1-Methyl-4- ((5-methylhex-4-en-2-yl) sulfinyl) n3.81% yield.
Structural characterization of compound example 3:
1H NMR(400MHz,Chloroform-d)δ7.48(d,J＝8.0Hz,2H),7.44(d,J＝8.1Hz,2H),7.29(d,J＝7.4Hz,4H),5.14(t,J＝7.2Hz,1H),5.07(t,J＝7.3Hz,1H),2.71(dtd,J＝12.1,6.7,2.5Hz,1H),2.55(td,J＝14.0,7.3Hz,2H),2.40(s,6H),2.38–2.32(m,1H),2.12(td,J＝13.9,7.8Hz,2H),1.71(s,3H),1.68(s,3H),1.59(s,3H),1.55(s,3H),1.07(d,J＝6.9Hz,3H),1.02(d,J＝6.6Hz,3H).13C NMR(101MHz,Chloroform-d)δ141.60,141.12,138.99,138.47,135.21,135.11,129.70,125.41,124.82,120.05,119.63,60.10,60.03,29.45,27.58,25.93,21.54,21.50,18.06,18.01,12.61,10.52.HRMS(ESI)calc.for C14O20NaOS+(M+Na+):259.1127,found:259.1130.
example 4
To a dry test tube reaction tube were added 0.04mmol of 4CzIPN, 0.4mmol of Hantzsch ester 4- (adamantan-1-yl) -2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile, 0.04mmol of 1, 3-di-t-butyl-1H-imidazol-3-ium tetrafluoroborate, 0.05mmol of cesium carbonate, 0.8mmol of p-toluene sulfinic acid and 0.7 mmole of N, N' -carbonyldiimidazole at room temperature, and the mixture was placed in a high-purity argon atmosphere for air exchange, 4mL of methylene chloride was added after the system was placed in an anhydrous and anaerobic condition, and the mixture was placed in a blue light irradiation reactor and stirred until the reaction was completed. After TLC monitoring the complete reaction, the reaction solution was concentrated under reduced pressure, and column chromatography was performed using a mixed solution of petroleum ether and ethyl acetate as a mobile phase, to obtain the corresponding 1- (p-Tolylsulfinyl) adamantane example 4. The yield was 53%.
Structural characterization of compound example 4:
1H NMR(400MHz,Chloroform-d)δ7.42(d,J＝8.0Hz,2H),7.29(d,J＝8.0Hz,2H),2.42(s,3H),2.10(s,3H),1.75–1.67(m,9H),1.60(d,J＝12.0Hz,3H).13C NMR(101MHz,Chloroform-d)δ141.54,135.23,129.17,126.53,57.56,36.35,35.04,28.95,21.61.HRMS(ESI)calc.for C17H22NaOS+(M+Na+):297.1284,found:297.1292.
Example 5
After adding 0.004mmol Ir dF (CF 3)ppy]2(bpy)PF6, 0.2mmol Hantzsch ester diethyl 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, 0.04mmol 1, 3-di-tert-butyl-1H-imidazol-3-ium tetrafluoroborate, 0.04mmol cesium carbonate, 0.5mmol sodium p-iodobenzene sulfinate and 0.5mmol N, N' -carbonyldiimidazole in a dry test tube at room temperature, placing in a high-purity argon medium for ventilation, so that the system is in an anhydrous and anaerobic condition, adding 4mL of dichloromethane and 0.5mmol trifluoromethanesulfonic acid, placing in a blue light illumination reaction device for stirring until the complete reaction, concentrating the reaction liquid under reduced pressure after TLC monitoring, and separating by column chromatography by adopting a mixed liquid of petroleum ether and ethyl acetate as a mobile phase, thus obtaining the corresponding 1- (Cyclohexylsulfinyl) -4-iodobenzene example 5 with the yield of 89%.
Structural characterization of compound example 5:
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝8.2Hz,2H),7.31(d,J＝8.2Hz,2H),2.53(ddt,J＝11.7,8.3,3.4Hz,1H),1.88–1.81(m,3H),1.76(d,J＝13.0Hz,1H),1.65(d,J＝10.0Hz,1H),1.47–1.35(m,2H),1.27–1.15(m,3H).13C NMR(101MHz,Chloroform-d)δ142.01,138.12,126.71,97.42,63.34,26.38,25.74,25.52,25.44,23.95.HRMS(ESI)calc.for C12H15INaOS+(M+Na+):356.9780,found:356.9791.
Example 6
To a dry test tube reaction tube were added 0.006mmol 4CzIPN, 0.4mmol Hantzsch ester diethyl 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, 0.06mmol 1, 3-di-t-butyl-1H-imidazol-3-ium tetrafluoroborate, 0.06mmol cesium carbonate, 0.8mmol thiophene-2-sulfinic acid and 0.8mmol N, N' -carbonyldiimidazole at room temperature, and the mixture was placed in a high-purity argon atmosphere for air exchange, 4mL methylene chloride was added after the system was in an anhydrous and anaerobic condition, and the mixture was placed in a blue light irradiation reactor and stirred until the reaction was completed. After TLC monitoring the complete reaction, the reaction solution was concentrated under reduced pressure, and column chromatography was performed using a mixed solution of petroleum ether and ethyl acetate as a mobile phase, to obtain the corresponding 2- (Cyclohexylsulfinyl) thiophene example 6. The yield was 56%.
Structural characterization of compound example 6:
1H NMR(400MHz,Chloroform-d)δ7.68–7.62(m,1H),7.45–7.41(m,1H),7.12(dd,J＝4.8,3.8Hz,1H),2.82(ddt,J＝11.2,7.4,3.8Hz,1H),2.21–2.16(m,1H),1.95–1.89(m,1H),1.83–1.78(m,1H),1.69–1.66(m,2H),1.54–1.46(m,1H),1.33–1.23(m,4H).13C NMR(101MHz,Chloroform-d)δ135.95,131.10,130.43,127.33,64.96,25.97,25.63,25.42,25.28.HRMS(ESI)calc.for C10H14NaOS2 +(M+Na+):237.0378,found:237.0388.
example 7
To a dry test tube reaction tube were added 0.004mmol of 4CzIPN, 0.2mmol of Hantzsch ester diethyl-4-cyclohexyl-2, 6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, 0.04mmol of 1, 3-di-tert-butyl-1H-imidazol-3-ium tetrafluoroborate, 0.04mmol of cesium carbonate and 0.4mmol of N, N' -carbonyldiimidazole at room temperature, and the mixture was placed in a high-purity argon atmosphere for aeration, and after the system was placed in an anhydrous and anaerobic condition, a solution of 0.4mmol of p-trifluoromethylbenzene sulfinic acid in 4mL of dichloromethane was added and the mixture was placed in a blue light irradiation reactor and stirred until the reaction was completed. After TLC monitoring the complete reaction, the reaction solution was concentrated under reduced pressure, and column chromatography was performed using a mixed solution of petroleum ether and ethyl acetate as a mobile phase, to obtain the corresponding 1- (Cyclohexylsulfinyl) -4-trifluoromethylbenzene example 7. The yield was 40%.
Structural characterization of compound example 7:
1H NMR(400MHz,Chloroform-d)δ7.78(d,J＝8.3Hz,2H),7.71(d,J＝8.3Hz,2H),2.58(tt,J＝11.9,3.6Hz,1H),1.96–1.83(m,3H),1.70–1.66(m,2H),1.51–1.41(m,2H),1.30–1.19(m,3H).13C NMR(101MHz,Chloroform-d)δ146.56(d,JF＝1.4Hz),133.03(q,J＝32.7Hz),126.02(q,J＝3.7Hz),125.53,123.71(q,J＝272.7Hz),63.40,26.57,25.78,25.46,25.43,23.65.19F NMR(376MHz,Chloroform-d)δ-62.79.
Example 8
Based on example 1, the solvent was replaced with acetonitrile, and the yield of sulfoxide compound example 1 was 89%.
Example 9
Based on example 1, the base was replaced by sodium acetate and the sulfoxide compound example 1 was obtained in a yield of 81%.
Example 10
Based on example 1, the substitution of the N-heterocyclic carbene catalyst with 1, 3-dimethyliodinated imidazole gave a yield of 78% for example 1 of the sulfoxide compound.
It will be appreciated by persons skilled in the art that the above examples are provided for illustration of the invention only as a preferred embodiment thereof and not as a definition of the limits of the invention in any way, and that changes and modifications of the above-described embodiments will fall within the scope of the appended claims without departing from the true spirit of the invention as defined by the claims.

Claims (5)

1. The synthesis method is characterized in that in an organic solvent, sulfinic acid compounds, N' -carbonyl diimidazole and 4-alkyl Hantzsch ester compounds react under the existence of a photocatalyst, an N-heterocyclic carbene catalyst and alkali to generate target sulfoxide compounds; wherein:
the photocatalyst is at least one of Ir(ppy)3、Ir[dF(CF3)ppy]2(bpy)PF6、Ir[dF(CF3)ppy]2(dtbbpy)PF6、4CzIPN;
the N-heterocyclic carbene catalyst is at least one of N-alkyl derivative salts of imidazole, triazole, thiazole and oxazole;
the alkali is at least one of carbonate, phosphate and acetate of sodium, potassium and cesium;
The reaction formula of the synthesis method is as follows:
Wherein R is an ester group or a cyano group, R 1 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted heterocyclic group, or a C1-C14 alkyl group, and R 2 is a primary alkyl group, a secondary alkyl group, or a tertiary alkyl group; wherein the substituent is at least one of electron withdrawing group and electron donating group, the electron withdrawing group is at least one of fluoro, chloro, bromo, acyl, ester, cyano and trifluoromethyl, the electron donating group is at least one of iodo, C1-C14 alkyl, C1-C14 alkoxy and amino, the heterocycle is a multi-membered ring compound containing at least one hetero element, the hetero element is at least one of N, O, S, and the multi-membered ring is a four-membered ring to fourteen-membered ring.
2. The method for synthesizing sulfoxide compound according to claim 1, wherein the organic solvent is at least one of acetonitrile, dichloromethane, dichloroethane and chloroform.
3. The method for synthesizing sulfoxide compounds according to claim 1, wherein the organic solvent is used in an amount of 0.5-3mL per 0.2mmol of 4-alkyl Hantzsch ester compound.
4. The method for synthesizing sulfoxide compounds according to claim 1, wherein the amount of each material is 4-alkyl Hantzsch ester compound in terms of molar ratio: sulfinic acid compounds: n, N' -carbonyldiimidazole: and (3) a photocatalyst: azacyclo-carbene catalyst: the base was 1.0: (1.2-2.5): (1.2-2.5): (0.005-0.02): (0.05-0.2): (0.05-0.4).
5. The method for synthesizing sulfoxide compounds according to claim 1, wherein the specific steps of the method are as follows: under inert atmosphere, adding a photocatalyst, a 4-alkyl Hantzsch ester compound, an N-heterocyclic carbene catalyst, alkali, a sulfinic acid compound or corresponding salt thereof and N, N' -carbonyl diimidazole into a dried reaction tube, so that the system is in an anhydrous and anaerobic condition, adding an organic solvent, and placing the reaction tube under an illumination condition for reaction to obtain the sulfoxide compound.
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