CN101597226B - Method for synthesizing 6-hydroxyl-1-anisindione - Google Patents
Method for synthesizing 6-hydroxyl-1-anisindione Download PDFInfo
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- CN101597226B CN101597226B CN2008100434397A CN200810043439A CN101597226B CN 101597226 B CN101597226 B CN 101597226B CN 2008100434397 A CN2008100434397 A CN 2008100434397A CN 200810043439 A CN200810043439 A CN 200810043439A CN 101597226 B CN101597226 B CN 101597226B
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- indenone
- hydroxide radical
- reaction
- phenol
- hydroxyl
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- WRAQQYDMVSCOTE-UHFFFAOYSA-N C=CC(Oc1ccccc1)=O Chemical compound C=CC(Oc1ccccc1)=O WRAQQYDMVSCOTE-UHFFFAOYSA-N 0.000 description 1
- GCBVTWNEWLJIDO-UHFFFAOYSA-N OC(CC1)c2c1ccc(O)c2 Chemical compound OC(CC1)c2c1ccc(O)c2 GCBVTWNEWLJIDO-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention relates to a method for synthesizing 6-hydroxyl-1-anisindione, which mainly solves the technical problems of long route of the existing synthesis method, difficult obtained raw materials, and the like. Phenol and acryloyl chloride react to obtain corresponding crylic acid phenol ester; under the action of trifluorosulfonic acid, the crylic acid phenol ester closes the ring to obtain the 6-hydroxyl-1-anisindione, and a reaction formula is disclosed in the specification. The 6-hydroxyl-1-anisindione has wide application in medicinal chemistry and organic synthesis.
Description
Technical field:
The present invention relates to a kind of new synthetic method of 6-hydroxide radical-1-indenone.
Background technology:
6-hydroxide radical-1-indenone and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthetic synthetic 6-hydroxide radical-1-indenone of following three kinds of methods that mainly contains of present this compounds:
Method A is take 6-amino-1-indone as raw material, by the Sandermyer reaction corresponding amino is converted into hydroxyl (RFerranti, A.; Garuti, L.; Giovanninetti, G.; Brigidi, P.; FRPSAX; FarmacoEd.Sci., 1983; 167-172), the method raw material is synthetic by multistep.
The route of document synthetic method A:
Method B is take 6-methoxyl group-1-indone as raw material, becomes hydroxyl (US6166006 by the hydrolysis methoxyl group; Ref.1 6086837; Tetrahedron Lett.1997; 8749-8752.), the method raw material 6-methoxyl group-1-indone also will obtain by multistep is synthetic.
The route of document synthetic method B:
Method C is following (Corey, E.J.; Estreicher, Herbert; Tetrahedron Lett.1981; 603-606.).The method raw material also is difficult for.
The route of document synthetic method C:
The route of document synthetic method D:
In sum, the shortcoming such as the 6-hydroxide radical-1-indenone synthetic method raw material of both having known at present is difficult to obtain or route is oversize is difficult for fast preparation in the laboratory.
Summary of the invention:
The objective of the invention is to develop a kind of synthetic comparatively easy, be easy to the fast new synthesis technique of 6-hydroxide radical-1-indenone of preparation of laboratory.Mainly solve existing synthetic method route long, raw material such as is difficult to obtain at the technical problem.
Technical scheme of the present invention:
The present invention obtains corresponding vinylformic acid phenol ester with phenol and acrylate chloride reaction, and it obtains the 6-hydroxide radical-1-indenone at effect ShiShimonoseki of trifluoromethane sulfonic acid ring, and reaction formula is as follows:
In the above-mentioned technique, the first step reaction conditions is: phenol is dissolved in anhydrous methylene chloride, adds 1 equivalent triethylamine and makes alkali, is cooled to 0 ℃, adds 1.1 equivalent acrylate chlorides, and 0 ℃ was stirred stirring at room 1 hour 1 hour.Second step is take trifluoromethane sulfonic acid as solvent, and the add-on of trifluoromethane sulfonic acid is 5-20 equivalent, and temperature of reaction is 120-170 ℃.
Beneficial effect of the present invention:
The invention solves the synthesising method reacting condition route of both having known at present long, raw material such as is difficult to obtain at the shortcoming.Obtain corresponding vinylformic acid phenol ester with industry raw material commonly used with phenol and acrylate chloride reaction, it obtains the 6-hydroxide radical-1-indenone at effect ShiShimonoseki of trifluoromethane sulfonic acid ring.The last ring closure reaction aftertreatment of this technique is simple, and yield is higher, is easy to amplify, and can realize that 6-hydroxide radical-1-indenone laboratory prepares fast.
Embodiment:
Embodiment 1
1.3-chloropropionic acid phenol ester synthesis
Phenol (5g, 53mmol) is dissolved in anhydrous methylene chloride (50mL), adds triethylamine (5.35g, 53mmol), is cooled to 0 ℃.Under nitrogen protection, drip acrylate chloride (5.29g, 58mmol), 0 ℃ was stirred stirring at room 1 hour 1 hour.Reaction solution is first by washing, and 1M NaOH washes, washing, and the saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, and concentrating under reduced pressure obtains vinylformic acid phenol ester (6.7g, productive rate 85%)
1H NMR (CDCl
3): .6.03 (d, 1H), 6.37 (dd, 1H), 6.62 (d, 1H), 7.16 (m, 2H), 7.25 (m, 1H), 7.41 (m, 2H).
2.6-hydroxide radical-1-indenone is synthetic
Vinylformic acid phenol ester (2g, 13.5mmol) is dissolved in the trifluoromethanesulfonic acid (10.1g, 67.6mmol), and reaction mixture is put into temperature and reached 170 ℃ oil bath under nitrogen protection, stirs 1h.The reactant cool to room temperature, pour in the 20mL frozen water, with dichloromethane extraction (20mL * 3), merge organic phase, use saturated sodium bicarbonate, water and saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, concentrating under reduced pressure, silica gel column chromatography (PE/EA=4/1～2/1) separation obtains 6-hydroxide radical-1-indenone (800mg, productive rate 40%).
1H?NMR(CDCl
3)：.2.71(m，2H)，3.05(t，2H)，5.99(s，1H)，7.14(d，1H)，7.21(s，1H)，7.33(d，1H)。
Embodiment 2
Synthesizing of 6-hydroxide radical-1-indenone
Phenyl acrylate (2g, 13.5mmol) is dissolved in the trifluoromethanesulfonic acid (20.2g, 135mmol), and reaction mixture is put into temperature and reached 170 ℃ oil bath under nitrogen protection, stirs 1h.The reactant cool to room temperature, pour in the 20mL frozen water, with dichloromethane extraction (30mL * 3), merge organic phase, use saturated sodium bicarbonate, water and saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, concentrating under reduced pressure, silica gel column chromatography (PE/EA=4/1～2/1) separation obtains 6-hydroxide radical-1-indenone (760mg, productive rate 38%).
1H?NMR(CDCl
3)：.2.71(m，2H)，3.05(t，2H)，5.99(s，1H)，7.14(d，1H)，7.21(s，1H)，7.33(d，1H)。
Embodiment 3
Synthesizing of 6-hydroxide radical-1-indenone
Phenyl acrylate (2g, 13.5mmol) is dissolved in the trifluoromethanesulfonic acid (40.4g, 270mmol), and reaction mixture is put into temperature and reached 170 ℃ oil bath under nitrogen protection, stirs 1h.The reactant cool to room temperature, pour in the 20mL frozen water, with dichloromethane extraction (40mL * 3), merge organic phase, use saturated sodium bicarbonate, water and saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, concentrating under reduced pressure, silica gel column chromatography (PE/EA=4/1～2/1) separation obtains 6-hydroxide radical-1-indenone (700mg, productive rate 35%).
1H?NMR(CDCl
3)：.2.71(m，2H)，3.05(t，2H)，5.99(s，1H)，7.14(d，1H)，7.21(s，1H)，7.33(d，1H)。
Embodiment 4
Synthesizing of 6-hydroxide radical-1-indenone
Vinylformic acid phenol ester (2g, 13.5mmol) is dissolved in the trifluoromethanesulfonic acid (10.1g, 67.6mmol), and reaction mixture is put into temperature and reached 120 ℃ oil bath under nitrogen protection, stirs 1h.The reactant cool to room temperature, pour in the 20mL frozen water, with dichloromethane extraction (20mL * 3), merge organic phase, use saturated sodium bicarbonate, water and saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, concentrating under reduced pressure, silica gel column chromatography (PE/EA=4/1～2/1) separation obtains 6-hydroxide radical-1-indenone (100mg, productive rate 5%).
1H?NMR(CDCl
3)：.2.71(m，2H)，3.05(t，2H)，5.99(s，1H)，7.14(d，1H)，7.21(s，1H)，7.33(d，1H)。
Embodiment 5
Synthesizing of 6-hydroxide radical-1-indenone
Phenyl acrylate (2g, 13.5mmol) is dissolved in the trifluoromethanesulfonic acid (20.2g, 135mmol), reaction mixture is put into oil bath under nitrogen protection, heats up gradually from 120 ℃ to 170 ℃ restir 1h.The reactant cool to room temperature, pour in the 20mL frozen water, with dichloromethane extraction (30mL * 3), merge organic phase, use saturated sodium bicarbonate, water and saturated common salt washing, anhydrous sodium sulfate drying removes by filter siccative, concentrating under reduced pressure, silica gel column chromatography (PE/EA=4/1～2/1) separation obtains 6-hydroxide radical-1-indenone (600mg, productive rate 30%).
1H?NMR(CDCl
3)：.2.71(m，2H)，3.05(t，2H)，5.99(s，1H)，7.14(d，1H)，7.21(s，1H)，7.33(d，1H)。
Claims (3)
1. the synthetic method of a 6-hydroxide radical-1-indenone is characterized in that may further comprise the steps: obtain the vinylformic acid phenol ester with phenol and acrylate chloride reaction, the vinylformic acid phenol ester obtains the 6-hydroxide radical-1-indenone at effect ShiShimonoseki of trifluoromethane sulfonic acid ring, and reaction formula is as follows:
2. the synthetic method of 6-hydroxide radical-1-indenone according to claim 1, it is characterized in that the first step reaction conditions is: phenol is dissolved in anhydrous methylene chloride, and adds 1 equivalent triethylamine and make alkali, and the add-on of acrylate chloride is 1.1 equivalents; Second step is take trifluoromethane sulfonic acid as solvent, and the add-on of trifluoromethane sulfonic acid is 5-20 equivalent.
3. the synthetic method of 6-hydroxide radical-1-indenone according to claim 1 is characterized in that the first step reaction respectively stirred 1 hour 0 ℃ and room temperature respectively, and the second step temperature of reaction is 120-170 ℃.
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