CN103012142A - (E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound and preparation method thereof - Google Patents
(E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound and preparation method thereof Download PDFInfo
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- CN103012142A CN103012142A CN2012105446575A CN201210544657A CN103012142A CN 103012142 A CN103012142 A CN 103012142A CN 2012105446575 A CN2012105446575 A CN 2012105446575A CN 201210544657 A CN201210544657 A CN 201210544657A CN 103012142 A CN103012142 A CN 103012142A
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Abstract
The invention discloses a (E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound and a preparation method thereof. By using dichloromethane or tetrahydrofuran as a solvent and triethylamine as an acid binding agent, chloracetyl chloride and resveratrol used as reactants are subjected to esterification reaction at 0-28 DEG C for 2-5 hours to obtain the white solid (E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound. The (E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound has stable structure, and can not be easily oxidized; the preparation method has the characteristic of simple preparation process and is convenient to operate; and meanwhile, the obtained (E)-4-(3,5-dihydroxystyryl)-2-phenyl chloroacetate compound has similar structural features to resveratrol, and reserves the group having drug effect in the resveratrol.
Description
Technical field
The present invention relates to a kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound and preparation method thereof.
Background technology
Trans-resveratrol is to contain the non-flavonoid polyphenolic substance of stilbene class formation and have the multiple pharmacologically actives such as atherosclerosis, anticoagulation, the oxidation of lipotropism matter, antisepsis and anti-inflammation, immunomodulatory, neuroprotective, liver protecting.The chemical structural formula synoptic diagram of trans-resveratrol as shown in Figure 1.As can be seen from Figure 1 contain 3 phenol-OH in the resveratrol molecule, therefore very unstable, very easily oxidized.
Studies show that, the anti-oxidant activity of the position of hydroxyl and quantity and Verakanol derivative is closely related on the toluylene phenyl ring, and the present invention mainly carries out structural modification to the hydroxyl in its structure take it as lead compound, synthetic corresponding derivative is to strengthen its stability and oxidation-resistance.
Summary of the invention
One of purpose of the present invention is very unstable in order to solve above-mentioned trans-resveratrol, very easily oxidized technical problem and provide a kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound.
Two of purpose of the present invention is a kind of (E)-4-(3 of providing above-mentioned, 5-dihydroxy-benzene vinyl)-preparation method of 2-phenyl chloroacetate compound.
Technical scheme of the present invention
A kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound is white solid, and molecular weight is 304, and its structural formula is as shown in Figure 2.
Above-mentioned a kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-preparation method of 2-phenyl chloroacetate compound, its synthetic reaction process synoptic diagram as shown in Figure 3, namely take trans-resveratrol and chloroacetyl chloride as reactant, take methylene dichloride or tetrahydrofuran (THF) as solvent, be 0～28 ℃ take triethylamine as acid binding agent in temperature, time is (the E)-4-(3 that gets white solid under 2～5h by esterification, 5-dihydroxy-benzene vinyl)-and 2-phenyl chloroacetate compound, its preparation process specifically may further comprise the steps:
(1), trans-resveratrol is dissolved in obtains resveratrol solution in the organic solvent, under condition of ice bath, the organic bases triethylamine is joined in the resveratrol solution, and then with the chloroacetyl chloride adding wherein, the control temperature is 0～28 ℃, time is that 2～5h carries out esterification, and reaction finishes namely to get reaction solution;
Described organic solvent is methylene dichloride or tetrahydrofuran (THF);
Above-mentioned trans-resveratrol, organic solvent, organic bases triethylamine and chloroacetyl chloride calculate by the mole volume ratio, be trans-resveratrol: organic solvent: the organic bases triethylamine: chloroacetyl chloride is 1mol:9～20ml:0.4～3ml:1～3mol, is preferably 1mol:9.09ml:0.45ml:1mol;
(2), gained reaction solution in the step (1) is carried out the concentrating under reduced pressure first time, crude product after concentrated is with methylene dichloride, ethyl acetate, sherwood oil or the methanol extraction of its 1～5 times of volume, the gained extraction liquid is through saturated aqueous common salt or distilled water washing, anhydrous sodium sulphate or anhydrous magnesium sulfate drying, then with Büchner funnel filter, the filtrate of gained carries out the concentrating under reduced pressure second time, concentrated thick product is carried out silica gel column chromatography to be separated, namely get (the E)-4-(3 of white solid, 5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound;
Described concentrating under reduced pressure process control first time bath temperature is 20～40 ℃, and pressure is 0.07～0.1MP;
Described concentrating under reduced pressure process control second time bath temperature is 20～40 ℃, and pressure is 0.07～0.1MP;
Described silica gel column chromatography sepn process, the gradient of moving phase is calculated by volume, i.e. methylene dichloride: methyl alcohol is 150:1～10:1, the outflow product when collecting 20:1 are (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound;
Or the gradient of moving phase calculates by volume, i.e. sherwood oil: ethyl acetate is 10:1～1:1, and the outflow product when collecting 1:1 are (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound;
Silica gel in the described silica gel column chromatography is 100～400 orders, preferred 300～400 orders.
Beneficial effect of the present invention
A kind of (E)-4-(3 of the present invention; 5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound; owing to have the non-flavonoid polyphenolic substance that contains the stilbene class formation of trans-resveratrol; therefore has the performance of the multiple pharmacologically actives such as atherosclerosis, anticoagulation, the oxidation of lipotropism matter, antisepsis and anti-inflammation, immunomodulatory, neuroprotective, liver protecting; and with respect to trans-resveratrol; a kind of Verakanol derivative of the present invention; because the introducing of ester bond; therefore its structure is more stable, is difficult for oxidized.
In addition, a kind of (E)-4-(3 of the present invention, 5-dihydroxy-benzene vinyl)-that the preparation method of 2-phenyl chloroacetate compound has preparation process is simple, easy to operate, the characteristics of reaction conditions gentleness.
Description of drawings
The structural formula synoptic diagram of Fig. 1, trans-resveratrol;
Fig. 2, (E)-4-(3,5-dihydroxy-benzene vinyl)-the structural formula synoptic diagram of 2-phenyl chloroacetate compound;
Fig. 3, (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound preparation feedback process synoptic diagram.
Embodiment
Below by embodiment the present invention is further set forth, but do not limit the present invention.
Used raw material, the reagent of the present invention is commercially available AR, CP level.
Gained final product of the present invention adopts nuclear magnetic resonance spectrometer (Avance III 500M, Switzerland Bruker company) to detect.
Embodiment 1
A kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, specifically may further comprise the steps:
(1), in the there-necked flask of 100mL, add 114mg(2.2mmol) trans-resveratrol, 20mL methylene dichloride stir behind 5～15min to get white opacity liquid;
The white opacity liquid of above-mentioned gained is added the 1mL triethylamine under condition of ice bath, get yellow clear liquor behind complete stirring 2～5min;
Under condition of ice bath, slowly drip 248mg (2.2mmol) chloroacetyl chloride in the yellow clear liquor of above-mentioned gained, dropwise and remove ice bath and rise to temperature and be 25 ℃ and carry out esterification 2～5h and obtain reaction solution;
(2), it is 20～40 ℃ that the reaction solution of step (1) gained is controlled bath temperature, pressure is that 0.07～0.1MPa carries out after concentrating under reduced pressure for the first time removes unnecessary methylene dichloride and triethylamine solvent in the reaction mother liquor, add ethyl acetate extraction, extract 3 times, merge organic phase after the extraction, after using anhydrous sodium sulfate drying, filter through Büchner funnel, the filtrate control bath temperature of gained is 20～40 ℃, pressure is that 0.07～0.1MPa carries out the concentrating under reduced pressure second time, crude product after concentrated is carried out column chromatography with 300-400 purpose silica gel, the gradient of moving phase is calculated by volume, i.e. methylene dichloride: methyl alcohol is 150:1～10:1, and the outflow product when collecting 20:1 are (the E)-4-(3 of white solid, 5-dihydroxy-benzene vinyl)-and 2-phenyl chloroacetate compound, productive rate is 21.4%.
The white solid of above-mentioned gained identifies that through nucleus magnetic resonance the result is as follows:
1H?NMR?(500?MHz,?DMSO)?δ?9.29?(s,?2H),?7.65?(d,?
J?=?8.6?Hz,?2H),?7.18?(d,?
J?=?8.5?Hz,?2H),?7.06?(s,?2H),?6.45?(d,?
J?=?1.8?Hz,2H),?6.17?(s,?1H),?4.70?(s,?2H)。
Can draw thus, the white solid of above-mentioned gained is structural formula (E)-4-(3 as shown in Figure 2,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound, molecular weight is 304.
Embodiment 2
A kind of (E)-4-(3,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, specifically may further comprise the steps:
(1), in the there-necked flask of 100mL, add 114mg(2.2mmol) trans-resveratrol, 20mL tetrahydrofuran (THF) stir behind 5～15min to get white clear liquor;
The white clear liquor of above-mentioned gained is added the 1mL triethylamine under condition of ice bath, get white opacity liquid behind complete stirring 2～5min;
Under condition of ice bath, slowly drip 248mg (2.2mmol) chloroacetyl chloride in the white opacity liquid of above-mentioned gained, dropwise and remove ice bath and rise to temperature and be 25 ℃ and carry out esterification 2～5h and obtain reaction solution;
(2), it is 20～40 ℃ that the reaction solution of step (1) gained is controlled bath temperature, pressure is that 0.07～0.1MPa carries out after concentrating under reduced pressure for the first time removes tetrahydrofuran (THF) and triethylamine solvent in the reaction solution, add ethyl acetate extraction, extract 3 times, merge organic phase after the extraction, after using anhydrous magnesium sulfate drying, filter through Büchner funnel, the filtrate control bath temperature of gained is 20～40 ℃, pressure is that the crude product that 0.07～0.1MPa will carry out after will concentrate behind the concentrating under reduced pressure second time carries out column chromatography with 300～400 purpose silica gel, the gradient of moving phase is calculated by volume, be sherwood oil: ethyl acetate is 10:1～1:1, outflow product when collecting 1:1 are white solid (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound.
Above said content only is the basic explanation of the present invention under conceiving, and according to technical scheme of the present invention institute
Any equivalent transformation of doing all should belong to protection scope of the present invention.
Claims (8)
1. (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound, it is characterized in that its structural formula is:
2. (E)-4-(3 as claimed in claim 1,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, it is characterized in that it specifically comprises the steps:
(1), trans-resveratrol is dissolved in obtains resveratrol solution in the organic solvent, under condition of ice bath, the organic bases triethylamine is joined in the resveratrol solution, and then chloroacetyl chloride added wherein under condition of ice bath, the control temperature is 0～28 ℃, time is that 2～5h reacts, and reaction finishes namely to get reaction solution;
Described organic solvent is methylene dichloride or tetrahydrofuran (THF);
Above-mentioned trans-resveratrol, organic solvent, organic bases triethylamine and chloroacetyl chloride are pressed mole volume calculation, i.e. a trans-resveratrol: organic solvent: organic bases triethylamine: chloroacetyl chloride is 1mol:9～20ml:0.4～3ml:1～3mol;
(2), gained reaction solution in the step (1) is carried out the concentrating under reduced pressure first time, crude product after concentrated extracts with methylene dichloride, ethyl acetate, sherwood oil or the methyl alcohol of 1～5 times of its volume, the gained extraction liquid is through saturated aqueous common salt or distilled water washing, anhydrous sodium sulphate or anhydrous magnesium sulfate drying, then with Büchner funnel filter, the filtrate of gained carries out the concentrating under reduced pressure second time, concentrated thick product is carried out silica gel column chromatography to be separated, namely get (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound.
3. a kind of (E)-4-(3 as claimed in claim 2,5-dihydroxy-benzene vinyl)-preparation method of 2-phenyl chloroacetate compound, it is characterized in that the trans-resveratrol described in the step (1), organic solvent, organic bases triethylamine and chloroacetyl chloride calculate by the mole volume ratio, i.e. trans-resveratrol: organic solvent: organic bases triethylamine: chloroacetyl chloride is 1mol:9.09ml:0.45ml:1mol.
4. a kind of (E)-4-(3 as claimed in claim 3,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, it is characterized in that the esterification reaction process control temperature described in the step (1) is 25 ℃.
5. a kind of (E)-4-(3 as claimed in claim 4,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, it is characterized in that the silica gel in the silica gel column chromatography is 100～400 orders described in the step (2).
6. a kind of (E)-4-(3 as claimed in claim 5,5-dihydroxy-benzene vinyl)-and the preparation method of 2-phenyl chloroacetate compound, it is characterized in that the silica gel in the silica gel column chromatography is 300～400 orders described in the step (2).
7. a kind of (E)-4-(3 claimed in claim 6,5-dihydroxy-benzene vinyl)-preparation method of 2-phenyl chloroacetate compound, it is characterized in that described in the step (2) the first time concentrating under reduced pressure process the control bath temperature be 20～40 ℃, pressure is 0.07～0.1MP;
Described second time, the control bath temperature of concentrating under reduced pressure process was 20～40 ℃, and pressure is 0.07～0.1MP.
8. a kind of (E)-4-(3 claimed in claim 7,5-dihydroxy-benzene vinyl)-preparation method of 2-phenyl chloroacetate compound, it is characterized in that the silica gel column chromatography sepn process described in the step (2), the gradient of moving phase is calculated by volume, be methylene dichloride: methyl alcohol is 150:1～10:1, outflow product when collecting 20:1 are (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound;
Or the gradient of moving phase calculates by volume, i.e. sherwood oil: ethyl acetate is 10:1～1:1, and the outflow product when collecting 1:1 are (E)-4-(3,5-dihydroxy-benzene vinyl)-2-phenyl chloroacetate compound.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101659612A (en) * | 2009-09-24 | 2010-03-03 | 北京赛科药业有限责任公司 | Selective esterification method |
| CN102381968A (en) * | 2011-09-20 | 2012-03-21 | 广州合成材料研究院有限公司 | Method for preparing antioxidant of bisphenol monoacryate |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101659612A (en) * | 2009-09-24 | 2010-03-03 | 北京赛科药业有限责任公司 | Selective esterification method |
| CN102381968A (en) * | 2011-09-20 | 2012-03-21 | 广州合成材料研究院有限公司 | Method for preparing antioxidant of bisphenol monoacryate |
Non-Patent Citations (1)
| Title |
|---|
| PAMELA TORRES ET AL.,: "Regioselective lipase-catalyzed synthesis of 3-O-acyl-derivatives of resveratrol and study of their antioxidant properties", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》, vol. 58, 31 December 2010 (2010-12-31) * |
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Application publication date: 20130403 |