CN100384801C - (E)-3,5-dimethox-4'-hydroxy diphenyl ethylene synthesis method - Google Patents
(E)-3,5-dimethox-4'-hydroxy diphenyl ethylene synthesis method Download PDFInfo
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Abstract
The present invention discloses a synthesis method for (E)-3, 5-dimethoxy-4-hydroxy diphenyl ethylene, namely pterostilbene. P-hydroxybenzene acetic acid and 3, 5-dimethoxybenzaldehyde are used as raw materials by the method and are subjected to Perkin reaction to obtain (Z)-2-(4-acetoxy phenyl)-3-(3, 5-dimethoxyphenyl) acrylic acid. The compound can be respectively deacetylated firstly and decarboxylated secondly, or decarboxylated firstly and deacetylated secondly to obtain the target product, namely (E)-3, 5-dimethoxy-4-hydroxy diphenyl ethylene. In the present invention, the cheap and easily acquired raw materials are used, and a simple and direct synthetic process and the convenient operating method are adopted to obtain pterostilbene with a trans-form diphenyl ethylene structure in a high yield mode. The synthesis method has the advantages of low cost, good atom economy, green and environment-friendly synthetic process, and easy industrial production.
Description
Technical field
The present invention relates to a kind of chemical synthesis process of polyhydroxystilbene compounds, be meant a kind of (E)-3 especially, the 5-dimethoxy-4 ' '-hydroxy stibene (red sandalwood Stilbene, synthetic method Pterostilbene).
Background technology
(E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene (red sandalwood Stilbene, English name: Pterostilbene) be the homologue of trans-resveratrol, has trans toluylene skeleton structure, it is grape, blueberry, important activity composition in dragon's blood goods and the India's anti-diabetic herbal medicine " Bijasar ", existence is also arranged in Chinese Dracaena cochinchinensis, its pharmacological action except that to trans-resveratrol have part similar, also has stronger anti-mycotic activity, cancer chemoprophylaxis activity, induce MDR apoptosis activity, PPAR α agonist activity etc., its hypolipidemic activity is better than Win-35833, anti-diabetic activity and N1,N1-Dimethylbiguanide are suitable, demonstrate important researching value and good prospects for application.At present, the red sandalwood Stilbene has become the marker of dragon's blood goods and India herbal medicine " Bijasar " quality control.
At present, the red sandalwood Stilbene mainly depends on to extract from natural phant and gets, and it is limited to originate.Therefore, the source problem that comes that adopts chemical process to solve the red sandalwood Stilbene has important economic value and Significance for Environment.Synthesizing of relevant red sandalwood Stilbene only has one piece of Chinese invention patent (Zou Yong etc., CN1539805A), this patent adopts para-nitrotoluene and 3, and the reaction of 5-dimethoxy benzaldehyde obtains (E)-3, the 5-dimethoxy-4 ' '-the nitro diphenyl ethylene process is reduced, the method for diazotization hydrolysis has been synthesized the red sandalwood Stilbene.Aspect employing Perkin reaction method structure toluylene skeleton, document (Org Syn, Coll.Vol4,777, Org Syn, Coll.Vol4,857) adopt the Perkin reaction takes place phenyl aldehyde and toluylic acid product through obtaining product after the decarboxylation, need further configuration conversion just can obtain the transconfiguration toluylene based on cis-configuration.
Summary of the invention
In order to solve the weak point that above-mentioned prior art exists, the object of the present invention is to provide a kind of red sandalwood Stilbene ((E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene) synthetic method.This method adopts p-hydroxyphenylaceticacid and 3; the 5-dimethoxy benzaldehyde is a raw material; the Perkin reaction takes place in the presence of alkali obtain (Z)-2-(4-acetoxyl group phenyl)-3-(3; the 5-Dimethoxyphenyl) vinylformic acid, then respectively through decarboxylation, deprotection or deprotection, decarboxylation directly obtains the target product of transconfiguration again.The present invention has that raw material is cheap and easy to get, synthesis technique is simple and direct, operation is simple, Atom economy reaches the yield advantages of higher well, is easy to realize industrialization production.
The present invention is at first with p-hydroxyphenylaceticacid (formula II) and 3; 5-dimethoxy benzaldehyde (formula III) is a raw material; adopt the Perkin method to make up the toluylene skeleton structure; then through first deacetylation, again decarboxylation or first decarboxylation again deacetylation directly obtain the target compound red sandalwood Stilbene of transconfiguration, do not need further configuration conversion.
Purpose of the present invention is achieved through the following technical solutions: a kind of red sandalwood Stilbene (formula I, (E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene) synthetic method, comprise the steps:
Formula I
(1) p-hydroxyphenylaceticacid (formula II) and 3, the Perkin reaction takes place in 5-dimethoxy benzaldehyde (formula III) in the presence of acid anhydrides and organic bases, reacted 4～14 hours down in 80～140 ℃, reaction solution is joined in the frozen water, obtain (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (formula IV).Described p-hydroxyphenylaceticacid and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1: 1.
Formula II formula III
Formula IV
(2) (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (catalytic decarboxylation reaction) under the catalysis of catalyzer, 150～250 ℃ of following catalyzed reactions 1～5 hour, make (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene (formula V); (E)-3 then, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene refluxed in acid solution or alkaline solution 0.5～2 hour, recrystallization obtain the red sandalwood Stilbene (formula I, (E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene).
Formula V
Step of the present invention (2) can also be carried out as follows:
(2 ') is with (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid adds in the alkaline solution (hydrolysis reaction), 15～100 ℃ were stirred 1～8 hour down, add mass percentage concentration and be 10～37% hcl acidifying and obtain (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (formula VI); (Z)-2-(4-hydroxy phenyl)-3-(3 then, the 5-Dimethoxyphenyl) vinylformic acid (catalytic decarboxylation reaction) under the catalysis of catalyzer reacted 1～5 hour down in 150～250 ℃, and recrystallization obtains red sandalwood Stilbene (formula I, (E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene).
Formula VI
In order to realize the present invention better:
In the step (1), described acid anhydrides and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is preferably 1～5: 1, is preferably 3: 1 especially; Described organic bases and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1～5: 1, is preferably 2.5: 1 especially.
In the step (1), described acid anhydrides is diacetyl oxide, propionic anhydride or butyryl oxide etc., is preferably diacetyl oxide; Described organic bases is N, and dinethylformamide, ethamine, quadrol, triethylamine, quinoline, pyridine or piperidines etc. are preferably triethylamine.
In the step (1), preferred 120 ℃ of the temperature of Perkin reaction, preferred 8 hours of reaction times.
Catalytic decarboxylation reaction in the step (2), described catalyzer can be quinoline/copper powder, quinoline/Red copper oxide, quinoline/CuCr
2O (copper chromite), or quinoline/CuCr
2O-BaCr
2O (copper chromite-chromous acid barium), preferred quinoline/copper powder; Preferred 200 ℃ of temperature of reaction, preferred 3 hours of catalyzed reaction time.
In the step (2), described acid solution is hydrochloric acid soln-ethanol (hydrochloric acid soln and ethanol volume ratio are 1: 1) of 5～25%, sulphuric acid soln-methyl alcohol (sulphuric acid soln and methyl alcohol volume ratio are 1: 1) of 20～45% or hydrochloric acid soln-acetate (hydrochloric acid soln and acetate volume ratio are 2: 1) of 5～25%; Be preferably hydrochloric acid soln-ethanol of 17%; Described alkaline solution is 0.2～20% sodium hydroxide solution, 0.2～20% potassium hydroxide solution or sodium hydroxide-ethanolic soln (sodium hydroxide solution and ethanol volume ratio are 1: 1) of 0.2～20%, is preferably 5% sodium hydroxide solution; Above-mentioned each material is a mass percentage concentration.
In the step (2), described recrystallization solvent is ethanol, ethyl acetate, methyl alcohol, acetone, chloroform, sherwood oil, alcohol-water, ethanol-sherwood oil, ethyl acetate-sherwood oil, chloroform-sherwood oil, acetone-water or acetone-sherwood oil etc., be preferably sherwood oil, ethyl acetate-sherwood oil or alcohol-water especially, ethyl acetate wherein: the volume ratio of sherwood oil is preferably 1: 10, ethanol: the volume ratio of water is preferably 1: 8.
In the step (2 '), described alkaline solution is 0.2～20% sodium hydroxide solution, 0.2～20% potassium hydroxide solution or sodium hydroxide-ethanolic soln of 0.2～20%, preferred 5% sodium hydroxide solution, and above-mentioned each material is a mass percentage concentration.Described hydrolysising reacting temperature is preferably 25 ℃, and the reaction times is preferably 3 hours.
In the step (2 '), described hydrochloric acid preferred mass percentage concentration is 37% hydrochloric acid.
The present invention is so that (Z)-2-(4 '-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid is raw material, adopts two kinds of strategies to synthesize target product: a kind of is that first decarboxylation removes 4 ethanoyl protections again, as step (2); Another kind is to remove 4 protections earlier to obtain the toluylene carboxylic acid derivative that contraposition is a hydroxyl, and further decarboxylation obtains target compound, as step (2 ').
The present invention compared with prior art, have following advantage and beneficial effect: the present invention adopts 3, after the reaction of 5-dimethoxy benzaldehyde and p-hydroxyphenylaceticacid, directly obtains the transconfiguration toluylene through decarboxylic reaction, does not need further configuration conversion.Raw material of the present invention and solvent are all inexpensive to be easy to get, and reaction process does not relate to the introducing of auxiliary group, and Atom economy is good; Reactions steps is simple and direct, reaction conditions is gentle, operation is simple, the yield height; Purification process all adopts the solvent of environmental protection to come recrystallization, and the cost of reaction is low; The waste residue that reaction produces is few, pollutes and lacks, and is beneficial to industrialization.Method provided by the invention is expected to provide a kind of simple and direct effective means for the suitability for industrialized production of red sandalwood Stilbene.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, but embodiments of the present invention are not limited thereto.
Embodiment 1
(1) (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) is 120 ℃ of reactions 8 hours down, reaction finishes and directly pours in the frozen water, suction filtration obtains faint yellow solid, i.e. (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid 33.86g, yield 99%;
MS?m/z：342(M
+)，300，255，240，225，134。
1H?NMR(400Hz，CDCl
3)2.280(s，3H，4’-COCH
3)；3.514(s，6H，3，5-CH
3)；6.237-6.242(d，2H，J＝2.0Hz，2，6-Ar-H)；6.335-6.346(t，1H，J＝2.0Hz，4-Ar-H)；7.079-7.106(d，2H，J＝6.8Hz，3’，5’-Ar-H)；7.255-7.282(d，2H，J＝6.8Hz，2’，6’-Ar-H)；7.864(s，1H，＝CH)。
IR(KBr，cm
-1)：3500-2500，2941，2841，1672，1591，1510，1460，1206。
(2) (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene synthetic: (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.42g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 200 ℃ of reactions 2 hours, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed till water layer near colourless, mass percentage concentration is that 5% sodium hydroxide solution is washed till neutrality, the anhydrous magnesium sulfate drying organic layer, concentrating and obtaining solid is (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene, ethanol/water (ethanol: the volume ratio of water is 1: 8) recrystallization obtains faint yellow needle-like crystal 1.79g, yield 60.0%.
MS?m/z：298(M
+)，256，240，225，210，181。
1H?NMR(400Hz，CDCl
3)2.290(s，3H，4’-COCH
3)；3.813(s，6H，3，5-CH
3)；6.377-6.388(t，1H，J＝2.4Hz，4-Ar-H)；6.639-6.645(d，2H，J＝2.4Hz，2，6-Ar-H)；6.940-6.981(d，1H，J＝16.4Hz，＝CH)；7.024-7.065(d，1H，J＝16.4Hz，＝CH)；7.056-7.077(d，2H，J＝6.4Hz，2’，6’-Ar-H)；7.478-4.499(d，2H，J＝6.4Hz，3’，5’-Ar-H)。
IR(KBr，cm
-1)：3003，2939，2839，1761，1595，1506，1460，1200，1157。
(3) the red sandalwood Stilbene is synthetic: (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene (2.98g, 0.01mol) to join mass percentage concentration be (20ml) in 5% the sodium hydroxide solution, back flow reaction 1 hour, add mass percentage concentration and be 17% hydrochloric acid and be neutralized to slightly acidic (PH5～6), the solid that obtains obtains 2.53g red sandalwood Stilbene, yield 98.8% through ethyl acetate-sherwood oil (ethyl acetate: the volume ratio of sherwood oil is 1: 10, down together) recrystallization.
MS：256，240，224，210，181，165，152，128，115，91，76。
1H?NMR(400Hz，CDCl
3)3.811(s，6H，3，5-CH
3)；6.356-6.367(t，1H，J＝2.4Hz，4-Ar-H)；6.626-6.632(d，2H，J＝2.4Hz，2，6-Ar-H)；6.798-6.819(d，2H，J＝6.4Hz，2’，6’-Ar-H)；6.855-6.895(d，1H，J＝16.4Hz，＝CH)；6.987-7.027(d，1H，J＝16.4Hz，＝CH)；7.372-7.394(d，2H，J＝6.4Hz，3’，5’-Ar-H)。
IR(KBr，cm
-1)：3402，3024，2945，2837，1599，1587，1514，1456，1200，1169，957。
Embodiment 2
(1) (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) reacted 8 hours down at 120 ℃, reaction finishes and pours in the frozen water, it is in 5% the sodium hydroxide solution that the solid that suction filtration obtains is directly poured the 150ml mass percentage concentration into, 25 ℃ were stirred 3 hours, add mass percentage concentration and be 37% hcl acidifying to slightly acidic (PH5～6), obtaining the 29.52g faint yellow solid is (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid, yield are 98.4%.
MS?m/z：300(M
+)，282，271，255，240，225，210，181，139，134。
IR(KBr，cm
-1)：3431，3008，2949，1705，1591，1512，1462，1211，1159，833。
(2) the red sandalwood Stilbene is synthetic: (Z)-and 2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.00g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 200 ℃ of reactions 2 hours, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed till water layer near colourless, 5% sodium hydroxide solution is washed till neutrality, the anhydrous magnesium sulfate drying organic layer, concentrate and to obtain solid and obtain the faint yellow needle-like crystal 1.59g of red sandalwood Stilbene, yield 62.1% through the sherwood oil recrystallization.
Embodiment 3
(1) (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) is 80 ℃ of reactions 10 hours down, reaction finishes and directly pours in the frozen water, obtains a large amount of faint yellow solid 27.65g, yield 80.8%.
(2) (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene synthetic: (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.42g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 150 ℃ of reactions 5 hours, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed to water layer near colourless, and mass percentage concentration is that 5% sodium hydroxide solution is washed till neutrality, the anhydrous magnesium sulfate drying organic layer, concentrating and obtaining solid is (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene, recrystallization obtains faint yellow needle-like crystal 1.24g, yield 41.6%.
(3) the red sandalwood Stilbene is synthetic: (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene (2.98g, 0.01mol) join in the ethanol of 10ml, stirring and dissolving, add mass percentage concentration and be 17% hydrochloric acid soln (10ml), reaction is 2 hours under reflux state, adds mass percentage concentration and is 5% sodium hydroxide solution and be neutralized to slightly acidic (PH5～6), the solid that obtains obtains 2.47g red sandalwood Stilbene, yield 96.5% through ethyl acetate-sherwood oil recrystallization.
Embodiment 4
(1) (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) reacted 14 hours down at 80 ℃, reaction finishes and pours in the frozen water, it is in 5% the sodium hydroxide solution that the solid that suction filtration obtains is directly poured the 150ml mass percentage concentration into, 15 ℃ were stirred 8 hours down, add concentrated hydrochloric acid (mass percentage concentration is 37% hydrochloric acid) and be acidified to slightly acidic (PH5～6), obtaining the 29.02g faint yellow solid is (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid, yield are 96.7%.
(2) the red sandalwood Stilbene is synthetic: (Z)-and 2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.00g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 150 ℃ of reactions 5 hours, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed to acidity (PH5～6), mass percentage concentration is that 5% sodium hydroxide solution is washed till weakly alkaline (PH7～8), anhydrous magnesium sulfate organic layer drying, concentrate and to obtain solid and obtain faint yellow needle-like crystal 1.13g, yield 44.1% through the sherwood oil recrystallization.
Embodiment 5
(1) (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) is 140 ℃ of reactions 4 hours down, reaction finishes and directly pours in the frozen water, obtains a large amount of faint yellow solid 28.75g, yield 84.1%.
(2) (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene synthetic: (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.42g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 250 ℃ of reactions 1 hour, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed to slightly acidic (PH5～6), and mass percentage concentration is that 5% sodium hydroxide solution is washed till neutrality, the anhydrous magnesium sulfate drying organic layer, concentrating and obtaining solid is (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene, recrystallization obtains faint yellow needle-like crystal 1.36g, yield 45.6%.
(3) the red sandalwood Stilbene is synthetic: (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene (2.98g, 0.01mol) to join mass percentage concentration be (20ml) in 0.2% the sodium hydroxide solution, back flow reaction 1 hour, add mass percentage concentration and be 17% hydrochloric acid and be neutralized to slightly acidic (PH5～6), the solid that obtains obtains 2.23g red sandalwood Stilbene, yield 87.1% through ethyl acetate-sherwood oil recrystallization.
Embodiment 6
(1) (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) acrylic acid synthetic: 3,5-dimethoxy benzaldehyde (16.6g, 0.1mol), p-hydroxyphenylaceticacid (15.2g, 0.1mol), the mixing solutions of diacetyl oxide (30g) and triethylamine (25g) reacted 4 hours down at 140 ℃, reaction finishes and pours in the frozen water, it is in 5% the sodium hydroxide solution that the solid that suction filtration obtains is directly poured the 150ml mass percentage concentration into, reflux and stir 1 hour (100 ℃), add concentrated hydrochloric acid (mass percentage concentration is 37% hydrochloric acid) and be acidified to slightly acidic (PH5～6), obtaining the 27.63g faint yellow solid is (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid, yield are 92.1%.
(2) the red sandalwood Stilbene is synthetic: (Z)-and 2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid (3.00g, 0.01mol), copper powder (3.0g) and quinoline (30.0g) were 250 ℃ of reactions 1 hour, be cooled to room temperature, add the 50ml ethyl acetate, mass percentage concentration is that 17% hydrochloric acid is washed to slightly acidic (PH5～6), mass percentage concentration is that 5% sodium hydroxide solution is washed till neutrality, the anhydrous magnesium sulfate drying organic layer, concentrate and to obtain solid and obtain faint yellow needle-like crystal 1.07g, yield 41.8% through the sherwood oil recrystallization.
Claims (10)
1. (E)-3, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, comprise the steps:
(1) p-hydroxyphenylaceticacid and 3, the 5-dimethoxy benzaldehyde reacted 8～14 hours down in 80～120 ℃ in the presence of acid anhydrides and organic bases, and reaction solution joins in the frozen water, obtain (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid; Described p-hydroxyphenylaceticacid and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1: 1;
(2) (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid under the catalysis of catalyzer, 150～250 ℃ of following catalyzed reactions 1～5 hour, make (E)-3, the 5-dimethoxy-4 ' '-acetoxy diphenyl ethylene; Refluxed in acid solution or alkaline solution 0.5～2 hour then, recrystallization obtains (E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene.
2. (E)-3, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, comprise the steps:
(1) p-hydroxyphenylaceticacid and 3, the 5-dimethoxy benzaldehyde reacted 8～14 hours down in 80～120 ℃ in the presence of acid anhydrides and organic bases, and reaction solution joins in the frozen water, obtain (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid; Described p-hydroxyphenylaceticacid and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1: 1;
(2) with (Z)-2-(4-acetoxyl group phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid adds in the alkaline solution, 15～100 ℃ were stirred 1～8 hour down, add mass percentage concentration and be 10～37% hcl acidifying and obtain (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid; (Z)-2-(4-hydroxy phenyl)-3-(3, the 5-Dimethoxyphenyl) vinylformic acid is under the catalysis of catalyzer then, and in 150～250 ℃ of following catalyzed reactions 1～5 hour, recrystallization obtained (E)-3, the 5-dimethoxy-4 ' '-hydroxy stibene.
3. (E)-3 according to claim 1, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: acid anhydrides and 3 described in the step (1), the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1～5: 1; Described organic bases and 3, the ratio of the amount of substance of 5-dimethoxy benzaldehyde is 1～5: 1.
4. (E)-3 according to claim 1, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: acid anhydrides is diacetyl oxide, propionic anhydride or butyryl oxide described in the step (1); Described organic bases is N, dinethylformamide, ethamine, quadrol, triethylamine, quinoline, pyridine or piperidines..
5. (E)-3 according to claim 1, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: temperature of reaction is 120 ℃ described in the step (1), the reaction times is 8 hours.
6. (E)-3 according to claim 1 and 2, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: described catalyzer is quinoline/copper powder, quinoline/Red copper oxide, quinoline/copper chromite or quinoline/copper chromite-chromous acid barium; Described temperature is 200 ℃ of following catalyzed reactions 3 hours.
7. (E)-3 according to claim 1, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: acid solution described in the step (2) is hydrochloric acid soln-ethanol of 5～25%, sulphuric acid soln-methyl alcohol of 20～45% or hydrochloric acid soln-acetate of 5～25%; Described alkaline solution is 0.2～20% sodium hydroxide solution, 0.2～20% potassium hydroxide solution or sodium hydroxide-ethanolic soln of 0.2～20%;
Above-mentioned each material is a mass percentage concentration.
8. (E)-3 according to claim 1, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: recrystallization solvent is ethanol, ethyl acetate, methyl alcohol, acetone, chloroform, sherwood oil, alcohol-water, ethanol-sherwood oil, ethyl acetate-sherwood oil, chloroform-sherwood oil, acetone-water or acetone-sherwood oil described in the step (2).
9. (E)-3 according to claim 2, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: described alkaline solution is 0.2～20% sodium hydroxide solution, 0.2～20% potassium hydroxide solution or sodium hydroxide-ethanolic soln of 0.2～20%, and above-mentioned each material is a mass percentage concentration; Described temperature is 25 ℃ and stirred 3 hours down.
10. (E)-3 according to claim 2, the 5-dimethoxy-4 ' '-synthetic method of hydroxy stibene, it is characterized in that: described hydrochloric acid is that mass percentage concentration is 37% hydrochloric acid.
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| CN101343214B (en) * | 2008-08-21 | 2011-06-08 | 中国科学院广州化学研究所 | Preparation method for E-diarylethene derivant containing phenolic hydroxyl group or acetoxy group |
| CN101481300B (en) * | 2009-02-20 | 2012-11-28 | 中国科学院广州化学研究所 | Preparation of trans-polyhydroxy diphenyl ethylene |
| CN101665418B (en) * | 2009-08-03 | 2012-11-28 | 中国科学院广州化学研究所 | Methods for preparing E-3,5-dimethoxy-4'-oxhydryl diphenylethene and derivative thereof |
| CN102391081A (en) * | 2011-09-26 | 2012-03-28 | 中科院广州化学有限公司 | Method for preparing diphenylethylene by utilizing 2,3-diphenyl acrylic acid |
| CN102516043A (en) * | 2011-12-13 | 2012-06-27 | 北大国际医院集团西南合成制药股份有限公司 | Preparation method of Sarpogrelate intermediate 2-((3-methoxy) phenethyl) phenol |
| CN102924300B (en) * | 2012-10-15 | 2014-11-05 | 中科院广州化学有限公司 | Method for preparing diphenyl ethylene compound through decarboxylic reaction |
| CN103102254B (en) * | 2013-02-06 | 2015-08-26 | 浙江新赛科药业有限公司 | The synthetic method of a kind of Pterostilene |
| CN103288605B (en) * | 2013-06-06 | 2015-04-08 | 陕西师范大学 | Synthetic method of combretastatin |
| CN103319339B (en) * | 2013-07-06 | 2015-10-21 | 张家港威胜生物医药有限公司 | A kind of synthetic method of pterostilbene sodium succinate |
| CN104387246A (en) * | 2014-11-11 | 2015-03-04 | 中科院广州化学有限公司 | Preparation method of 3'-hydroxypterostilbene |
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| CN1354659A (en) * | 1999-05-18 | 2002-06-19 | 卡里克斯治疗公司 | Novel diphenylethylene compounds |
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| 顺、反式-3,4′,5-三羟基二苯乙烯的合成. 王志新，张学景，周玥，邹永.中国药学（英文版），第14卷第4期. 2005 * |
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