CN112939830A - Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone - Google Patents
Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone Download PDFInfo
- Publication number
- CN112939830A CN112939830A CN201911169533.1A CN201911169533A CN112939830A CN 112939830 A CN112939830 A CN 112939830A CN 201911169533 A CN201911169533 A CN 201911169533A CN 112939830 A CN112939830 A CN 112939830A
- Authority
- CN
- China
- Prior art keywords
- compound
- phenyl
- organic solvent
- nucleophilic reaction
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a nucleophilic reaction method of alkenyl thioether p-o-methylene benzoquinone, which comprises the steps of dissolving a 2- (hydroxy (phenyl) methyl) phenol compound and a vinyl thioether compound in an organic solvent, adding a p-toluenesulfonic acid catalyst, and stirring and reacting for 5-10h at 25-80 ℃; extracting the reacted reaction solution, combining organic layers, washing, drying, evaporating to remove the solvent, and performing silica gel column chromatography on the residue to obtain the product. The method has the advantages of mild reaction conditions, high efficiency, high reaction yield and easy separation and purification of products, and overcomes the defects of expensive catalyst and harsh conditions in the traditional method.
Description
Technical Field
The invention relates to a nucleophilic reaction method for catalyzing alkenyl thioether p-o-methylene benzoquinone by p-toluenesulfonic acid, belonging to the technical field of organic synthesis.
Background
The o-methylene benzoquinone compound is a very active and important intermediate and is widely applied to natural products and pharmaceutical chemistry. Because of the wide application of the o-methylene benzoquinone compound, the research on the preparation method of the o-methylene benzoquinone compound is always a focus of attention of organic synthesis experts. Such a reaction method requires neutralization to neutrality of the system after the reaction is completed, and the post-treatment operation is complicated.
The construction of carbon-sulfur bonds has wide application in the synthesis of many sulfur-containing natural products and drug molecules. Among them, the sulfur Michael addition reaction is a simple and efficient synthesis method for synthesizing sulfur-containing organic compounds. In recent years, chemists have promoted this type of reaction primarily by noble metals, such as [ LNi2(CH3CN)(THF)](ClO4)3,Ru(acetone)(R,R-BIPHOP-F)Cp][SbF6]And so on.
Therefore, the development of a new method for catalyzing the nucleophilic addition reaction of vinyl thioether to o-methylene benzoquinone by p-toluenesulfonic acid simply and efficiently has important significance.
Disclosure of Invention
The invention aims to provide a nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone, which has the advantages of mild condition, simple and convenient operation, less limitation on the substitution type of a functional group, and easy separation and purification of a product; has important significance for the methodology research of o-methylene benzoquinone.
The technical scheme adopted by the invention is as follows:
a nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone comprises the following steps:
(1) dissolving 2- (hydroxy (phenyl) methyl) phenol compounds and vinyl thioether compounds in an organic solvent, adding a p-toluenesulfonic acid catalyst, and stirring for reaction for 5-10h at 25-80 ℃; the structural formula of the 2- (hydroxy (phenyl) methyl) phenol compound is as follows:
in the formula R1And R2Same or different from H, C1-C5 alkyl, halogen X, -NO2Any one of-CN and-OR 4;
(2) extracting the reacted reaction solution, combining organic layers, washing, drying, evaporating to remove the solvent, and performing silica gel column chromatography on the residue to obtain the product.
In the above reaction method, the vinyl sulfide compound in step (1) is as follows:
in the formula R3Is selected from any one of phenyl, benzyl and C1-C10 alkyl.
The R4 is selected from any one of alkyl of H, C1-C5. The adding proportion of the 2- (hydroxyl (phenyl) methyl) phenol compound, the vinyl thioether compound, the p-toluenesulfonic acid catalyst and the organic solvent is 1: 1.5-3: 0.05-0.2: 2.5-10; mmol: mmol: ml. The preferable adding proportion of the 2- (hydroxyl (phenyl) methyl) phenol compound, the vinyl thioether compound, the p-toluenesulfonic acid catalyst and the organic solvent is 1: 2: 0.1: 5; mmol: mmol: ml. The organic solvent is one of DMF, DMSO, toluene, acetonitrile, dichloromethane, chloroform, 1, 2-dichloroethane, ethyl acetate or tetrahydrofuran; 1, 2-dichloroethane is preferred.
The eluent of the silica gel column chromatography in the step (2) is one or a combination of more of petroleum ether, normal hexane and cyclohexane; preferably petroleum ether.
The reaction formula of the method is as follows:
in the formula, R1And R2Same or different from H, C1-C5 alkyl, halogen X, -NO2Any one of, -CN and-OR 4. R4 is selected from any one of alkyl of H, C1-C5. R3Is selected from any one of phenyl, benzyl and C1-C10 alkyl.
The invention has the beneficial effects that:
(1) the method uses the 2- (hydroxy (phenyl) methyl) phenol compound and the vinyl thioether compound to generate the o-methylene benzoquinone in situ under the catalysis of the p-toluenesulfonic acid and perform nucleophilic addition reaction, has mild reaction conditions and high efficiency, and avoids the defects of expensive catalyst and harsh conditions in the traditional method.
(2) The method has the advantages of simple raw materials and reagents, simple operation, high reaction yield, high product yield of 82-95 percent, easy separation and purification of the product, important value for the methodology research of o-methylene benzoquinone, and important significance in the synthesis of sulfur-containing natural products and drug molecules.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The invention is further described with reference to specific examples.
Example 1:
in a 100mL round-bottom flask was placed 2.00g (10mmol) of Compound I-1, 2.72g (20mmol) of Compound II-1, 0.17g (1mmol) of solid p-toluenesulfonic acid, and finally 50mL of dry 1, 2-dichloroethane, the resulting mixture was addedStirred at 30 ℃ for 10 hours. The reaction mixture was cooled to room temperature, poured into ice water, extracted with 50mL × 3 dichloromethane, the organic phases combined and washed once with saturated brine, anhydrous Na2SO4Drying, concentrating to remove solvent to obtain crude product, and separating by column chromatography to obtain pure product of compound III-1. Oily liquid, 2.63g, yield 90%.1H NMR(400MHz,CDCl3)δ:7.45(d,J＝7.4Hz,2H),7.28(ddd,J＝16.7Hz,8.6Hz,3.6Hz,5H),7.20–7.05(m,5H),6.92–6.78(m,2H),6.39(s,1H),5.77(s,1H)；13C NMR(CDCl3,100MHz)δ:154.16,139.15,134.58,131.09,130.03,129.08,128.92,128.70,128.66,127.60,127.30,125.89,120.94,117.15,53.67；HRMS(ESI)calcd for C17H19OS[M+H]+293.0995,found 293.0997.
Example 2:
in a 100mL round bottom flask was added 2.14g (10mmol) of Compound I-2, 2.72g (20mmol) of Compound II-1, 0.34g (2mmol) of solid p-toluenesulfonic acid and finally 25mL of dry DMF and the resulting mixture was stirred at 30 ℃ for 3 h to completion. The reaction mixture was cooled to room temperature, poured into water, stirred, extracted with 50mL × 3 dichloromethane, the organic phases combined and washed once with saturated brine, anhydrous Na2SO4Drying, concentrating to remove solvent to obtain crude product, and separating by column chromatography to obtain pure product of compound III-2. Oily liquid, 2.69g, 88% yield.1HNMR(400MHz,CDCl3)δ7.39–7.27(m,4H),7.19–7.03(m,7H),6.87–6.77(m,2H),6.41(s,1H),5.73(s,1H),2.32(s,3H)；13C NMR(CDCl3,100MHz)δ:154.21,137.36,136.02,134.69,131.01,130.03,129.40,129.02,128.90,128.49,127.23,125.99,120.89,117.19,53.56,21.12；HRMS(ESI)calcd for C20H19OS[M+H]+307.1151,found 307.1150.
Example 3:
in a 100mL round bottom flask was added 2.14g (10mmol) of Compound I-3, 2.04g (15mmol) of Compound II-1, 0.09g (0.5mmol) of solid p-toluenesulfonic acid and finally 50mL of dry DMSO and the resulting mixture was stirred vigorously at 35 ℃ for 5 h. The reaction mixture was cooled to room temperature, poured into water, stirred, extracted with 50mL × 3 dichloromethane, the organic phases combined and washed once with saturated brine, anhydrous Na2SO4Drying, concentrating, evaporating to remove solvent to obtain crude product, and purifying by column chromatography to obtain pure product of compound III-3. Oily liquid, 2.66g, yield 87%.1H NMR(400MHz,CDCl3)δ:7.62–7.52(m,1H),7.30–7.07(m,11H),6.85(dd,J＝7.4,5.4Hz,2H),6.27(s,1H),5.92(s,1H),2.37(s,3H)；13C NMR(CDCl3,100MHz)δ:154.11,137.28,136.34,135.53,130.70,130.07,129.95,128.96,128.92,128.72,127.58,126.89,126.43,125.81,121.03,116.88,49.69,19.39；HRMS(ESI)calcd for C20H19OS[M+H]+307.1151,found 307.1150.
Example 4:
a100 mL round bottom flask was charged with 2.48g (10mmol) of Compound I-4, 2.04g (15mmol) of Compound II-1, 0.17g (1mmol) of solid p-toluenesulfonic acid, and finally 50mL of 1, 2-dichloroethane, and the resulting mixture was stirred vigorously at 40 ℃ for 7 hours. The reaction mixture was cooled to room temperature, poured into water, stirred, extracted with 50mL × 3 dichloromethane, the organic phases combined and washed once with saturated brine, anhydrous Na2SO4Drying, concentrating to remove solvent to obtain an oily residue, and purifying by column chromatography to obtain pure compound III-4. Oily liquid, 2.77g, 85% yield.1H NMR(400MHz,CDCl3)δ:7.38(d,J＝8.4Hz,2H),7.27(dt,J＝10.5Hz,5.7Hz,4H),7.23–7.09(m,5H),6.89–6.78(m,2H),6.22(s,1H),5.75(s,1H)；13C NMR(CDCl3,100MHz)δ:153.85,137.97,134.34,133.31,131.14,130.02,129.79,129.20,129.00,128.76,127.44,125.73,121.10,117.05,52.65；HRMS(ESI)calcd for C19H16ClOS[M+H]+327.0605,found 327.0605.
Example 5:
in a 100mL round bottom flask was added 2.44g (10mmol) of Compound I-5, 2.72g (20mmol) of Compound II-1, 0.17g (1mmol) of solid p-toluenesulfonic acid, and finally 30mL of dry DMF, and the resulting mixture was stirred vigorously at 30 ℃ for 8 hours. The reaction mixture was cooled to room temperature, poured into water, stirred, extracted with 50mL × 3 dichloromethane, the organic phases combined and washed once with saturated brine, anhydrous Na2SO4Drying, concentrating to remove solvent to obtain an oily residue, and purifying by column chromatography to obtain pure compound III-5. Oily liquid, 2.56g, yield 86%.1H NMR(400MHz,CDCl3)δ:7.47(d,J＝7.4Hz,2H),7.33–7.22(m,4H),7.19–7.07(m,4H),6.79(t,J＝8.0Hz,1H),6.72(d,J＝8.0Hz,1H),6.03(s,1H),5.91(s,1H),4.17–3.95(m,2H),1.41(t,J＝7.0Hz,3H)；13C NMR(CDCl3,100MHz)δ:145.64,142.93,140.85,136.72,129.66,128.67(d,J＝2.7Hz),128.69,128.66,128.45,128.42,128.39,127.05,126.83,126.11,121.04,119.64,110.29,64.58,49.60,14.91；HRMS(ESI)calcd for C18H21OS[M+H]+285.1308,found285.1308.
Example 6:
in a 100mL round bottom flask was added 2.00g (10mmol) of Compound I-1, 1.76g (20mmol) of Compound II-2, 0.17g (1mmol) of solid p-toluenesulfonic acid and finally 50mL of dry 1, 2-dichloroethane and the resulting mixture stirred at 60 ℃ for 10 h. The reaction mixture was cooled to room temperature, poured into water and stirredStirring, extracting with 50mL × 3 dichloromethane, combining the organic extracts, washing with saturated brine, anhydrous Na2SO4Drying, concentrating to remove solvent to obtain crude product, and purifying by column chromatography to obtain pure product of compound III-6. Oily liquid, 2.15g, 88% yield.1HNMR(400MHz,CDCl3)δ:7.40(d,J＝7.4Hz,2H),7.35–7.14(m,5H),7.05(dd,J＝7.6Hz,1.2Hz,1H),6.91(dd,J＝8.0Hz,0.7Hz,1H),6.88–6.78(m,1H),5.39(s,1H),2.52–2.39(m,2H),1.23(t,J＝7.4Hz,3H)；13C NMR(CDCl3,100MHz)δ:155.15,139.31,130.17,129.21,128.39,128.67,128.53,128.51,127.55,125.16,120.76,117.60,50.47,26.36,14.19；HRMS(ESI)calcd for C15H23OS[M+H]+251.1464,found251.1464.
The present invention has been described in detail with reference to the specific embodiments, but the scope of the present invention is not limited thereto.
Claims (9)
1. A nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone is characterized by comprising the following steps:
(1) dissolving 2- (hydroxy (phenyl) methyl) phenol compounds and vinyl thioether compounds in an organic solvent, adding a p-toluenesulfonic acid catalyst, and stirring for reaction for 5-10h at 25-80 ℃; the structural formula of the 2- (hydroxy (phenyl) methyl) phenol compound is as follows:
in the formula R1And R2Same or different from H, C1-C5 alkyl, halogen X, -NO2Any one of-CN and-OR 4;
(2) extracting the reacted reaction solution, combining organic layers, washing, drying, evaporating to remove the solvent, and performing silica gel column chromatography on the residue to obtain the product.
2. The method of claim 1, wherein the vinyl sulfide compound of step (1) has a structure formula of
R3Is selected from any one of phenyl, benzyl and C1-C10 alkyl.
3. The method of claim 1, wherein R4 is selected from H, C1-C5 alkyl.
4. The nucleophilic reaction method for alkenylthio-p-o-methylenebenzoquinone according to claim 1, wherein the 2- (hydroxy (phenyl) methyl) phenol compound, the vinyl sulfide compound, the p-toluenesulfonic acid catalyst and the organic solvent are added in a ratio of 1: 1.5-3: 0.05-0.2: 2.5-10; mmol: mmol: ml.
5. The nucleophilic reaction method for alkenylthio-p-o-methylenebenzoquinone according to claim 4, wherein the 2- (hydroxy (phenyl) methyl) phenol compound, the vinyl sulfide compound, the p-toluenesulfonic acid catalyst and the organic solvent are added in a ratio of 1: 2: 0.1: 5; mmol: mmol: ml.
6. The nucleophilic reaction method for an alkenyl thioether p-o-methylenequinone according to claim 1, wherein the organic solvent is one of DMF, DMSO, toluene, acetonitrile, dichloromethane, chloroform, 1, 2-dichloroethane, ethyl acetate, or tetrahydrofuran.
7. The method as claimed in claim 6, wherein the organic solvent is 1, 2-dichloroethane.
8. The method for nucleophilic reaction of alkenyl thioether to o-methylene benzoquinone according to claim 1, wherein the eluent from the silica gel column chromatography in step (2) is one or more of petroleum ether, n-hexane and cyclohexane.
9. The method as claimed in claim 8, wherein the eluent from the silica gel column chromatography in step (2) is petroleum ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911169533.1A CN112939830B (en) | 2019-11-26 | 2019-11-26 | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911169533.1A CN112939830B (en) | 2019-11-26 | 2019-11-26 | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112939830A true CN112939830A (en) | 2021-06-11 |
| CN112939830B CN112939830B (en) | 2022-09-16 |
Family
ID=76224865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911169533.1A Active CN112939830B (en) | 2019-11-26 | 2019-11-26 | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112939830B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106588721A (en) * | 2016-10-27 | 2017-04-26 | 同济大学 | Vinyl thioether compound and preparation method thereof |
| CN109096162A (en) * | 2018-08-29 | 2018-12-28 | 山东省科学院新材料研究所 | A kind of nucleophilic addition method of the scandium catalysis mercaptan to o-quinone methides |
-
2019
- 2019-11-26 CN CN201911169533.1A patent/CN112939830B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106588721A (en) * | 2016-10-27 | 2017-04-26 | 同济大学 | Vinyl thioether compound and preparation method thereof |
| CN109096162A (en) * | 2018-08-29 | 2018-12-28 | 山东省科学院新材料研究所 | A kind of nucleophilic addition method of the scandium catalysis mercaptan to o-quinone methides |
Non-Patent Citations (1)
| Title |
|---|
| GUO, WENGANG，ET AL: "Formal Asymmetric Catalytic Thiolation with a Bifunctional Catalyst at a Water-Oil Interface: Synthesis of Benzyl Thiols", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112939830B (en) | 2022-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112608296B (en) | Synthesis method of Brazilane natural product Brazilane | |
| CN109651210B (en) | Preparation method of 3-sulfonyl-1, 2-dihydronaphthalene compound | |
| CN110437128B (en) | Synthetic method of 3-thioether-based isoindolinone compound | |
| CN109096162B (en) | Sc-catalyzed nucleophilic addition reaction method of mercaptan to o-methylenebenzoquinone | |
| CN110437129B (en) | Simple method for synthesizing 3-ether-based isoindolinone compound | |
| CN112142694A (en) | Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof | |
| EP2914574B1 (en) | New process | |
| CN112707795B (en) | Preparation method of Icetexane type abietane diterpene | |
| CN107032972B (en) | Preparation method of Diels-Alder product with 2' -hydroxychalcone structure | |
| CN112939830B (en) | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone | |
| CN107715909B (en) | Pentaerythritol-supported proline catalyst and preparation method and application thereof | |
| CN109134351B (en) | Synthesis method of S-3- (4-aminophenyl) piperidine | |
| CN109265385B (en) | Synthesis process of chiral catalyst | |
| CN110734354B (en) | Method for preparing biaryl compound from alcohol compound | |
| CN111018928B (en) | Synthetic method and application of gastrodin hemihydrate | |
| CN110467558B (en) | Reaction method for synthesizing 3-aminoisoindolinone under catalysis of nickel | |
| CN102464626B (en) | Method for preparing 5-(4-(N,N-diphenyl-amino) phenmethylene)-3-(2-phenethyl)-2,4-oxazolidinedione | |
| CN105622493B (en) | Method for synthesizing fully-substituted pyridine compound through cascade reaction of enaminone and aldehyde | |
| CN110467613B (en) | Reaction method for alkylation of imide cation intramolecular amide by nickel catalysis | |
| CN115536494B (en) | Synthesis method of 1- (4-bromophenyl) -1, 4-butanediol | |
| CN111747874B (en) | Ericoxib intermediate and preparation method and application thereof | |
| CN115322106B (en) | Synthesis method of trans-3-azido-1-methylcyclobutanol and trans-3-amino-1-methylcyclobutanol | |
| CN110586195B (en) | Chiral catalyst and preparation method and application thereof | |
| CN102586356B (en) | Method for synthesizing quinoline heterocycle derivatives by way of enzyme catalysis | |
| CN102432466B (en) | Preparation method of aliskiren intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221221 Address after: Room 3115, No. 135, Ward Avenue, Ping'an Street, Changqing District, Jinan, Shandong 250000 Patentee after: Shandong Jiqing Technology Service Co.,Ltd. Address before: 250014 No. 19, ASTRI Road, Lixia District, Shandong, Ji'nan Patentee before: NEW MATERIAL INSTITUTE OF SHANDONG ACADEMY OF SCIENCES |