CN101531571B - Method for oxidation synthesis of stilbenes by hexamethylenetetramine - Google Patents
Method for oxidation synthesis of stilbenes by hexamethylenetetramine Download PDFInfo
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Abstract
The invention discloses a method for oxidation synthesis of stilbenes by hexamethylenetetramine, comprising the following steps: preparing halogenated hydrocarbon by substituted benzyl alcohol, oxidizing the halogenated hydrocarbon by the hexamethylenetetramine to prepare corresponding substituted benzaldehydes, and preparing stilbene derivatives by condensation of Wittig-Horner. The method is simple and easy to implement; the reactants involved in the process of synthesis are safe; the resultants produce no pollution to the environment, have low cost and high yield and are suitable for industrially producing stilbenes having antibacterial action, such as resveratrol, pterostilbene and 3, 5-dimethoxy-4-isopropyl stilbene, etc.
Description
Technical field
The present invention relates to a kind of synthetic method with compound of toluylene skeleton, specifically a kind of method of utilizing oxidation synthesis of stilbenes by hexamethylenetetramine.
Background technology
Compound and polymkeric substance thereof with stilbene skeleton are generically and collectively referred to as stilbenes compound, have higher chemistry and pharmaceutical activity.The compound that contains different substituents has different purposes because its chemical property is different, substituent position mainly concentrates on 3 of toluylene molecule, 5,4,4 ' position, when 3,5,4 ' position has obvious medicine physiologically active when containing respectively methoxyl group, hydroxyl or amino, such as 3, that the toluylene (trans-resveratrol) that all replaced by hydroxyl of 5,4 ' position is found to have after deliberation is anticancer, antibacterium and fungi, anti-lipid effect, also has anti-platelet aggregation, suppresses cardiovascular diseases, prevents and treats the physiologically actives such as tissue canceration and tumour generation; The toluylene (Pterostilbene, trans-resveratrol homologue) that 3,5 methoxy substitutions, 4 ' the position hydroxyl replaces has stronger antimycotic, anti-lipid effect, except the physiologically active with trans-resveratrol, also has obvious anti-diabetic activity; The toluylene (benzene alkene is moral not) of 3,5 hydroxyl replacements, 4 alkyl replacements has obvious anti-mycotic activity.These compound ubiquities cis and trans two kinds of structures, and trans physiologically active is apparently higher than cis.
The skeleton of the synthetic diphenylethylene compounds of recent domestic bibliographical information is generally realized by the Wittig-Horner condensation, condensation reaction is carried out between substituted benzyl diethyl phosphoric acid and substituted benzaldehyde, some complicated substituted benzaldehydes are generally synthetic by the benzyl alcohol oxidation that replaces, for preventing the generation of substituted benzoic acid, guarantee that oxidation rests on the stage of aldehyde, usually adopt special oxidising agent, such as the PCC (pyridinium chlorochromate) of high poison and carinogenicity and PDC (chlorine dichromic acid pyridine) etc., although oxidization-hydrogenation ratio is higher, but a large amount of chrome waste liquids that produce after excessive PCC and PDC and the reaction can do great damage to environment, are difficult to realize suitability for industrialized production.
Summary of the invention
The technical problem to be solved in the present invention, provide a kind of synthetic method of the diphenylethylene compounds with anti-microbial effect, present method prepares halohydrocarbon by substituted benzyl alcohol, then adopt hexamethylenetetramine oxidation halohydrocarbon to prepare the method for corresponding substituted benzoyl aldehyde compound, then prepare the toluylene analog derivative through the Wittig-Horner condensation.The method is simple, related reactant safety in the building-up process, and resultant can be to environment, and cost is low, and yield is high, is fit to suitability for industrialized production.
For solving the problems of the technologies described above, the technical solution adopted in the present invention is:
A kind of method of oxidation synthesis of stilbenes by hexamethylenetetramine, the method be the hexamethylenetetramine oxidation synthetic 3,4 ', 5-trihydroxy-toluylene is the method for trans-resveratrol, its reaction scheme is suc as formula (I):
The method of synthesizing resveratrol is carried out according to following step order:
a
1.3, the preparation of 5-dimethoxybenzyl bromide
3,5-3,5-dimethoxybenzoic alcohol mixes with ether, stirs, the ice bath cooling drips phosphorus tribromide in the time of-2～2 ℃, be warming up to room temperature reaction after dropwising, TLC monitoring, react complete after, in reaction solution impouring frozen water, stir, tell organic layer, washing, drying, suction filtration, steaming desolventizes, get i.e. 3, the 5-dimethoxybenzyl bromide of compd A 1;
b
1.3, the preparation of 5-dimethoxy benzaldehyde
Compd A 1 mixes with hexamethylenetetramine, water, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves the steaming desolventizing, getting compound B-11 is 3,5-dimethoxy benzaldehyde;
c
1.3,4 ', the preparation of 5-trimethoxy toluylene
The methoxy-benzyl etherophosphoric acid is mixed with anhydrous tetrahydro furan, stir N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of B1, dropwises rear temperature rising reflux, TLC monitoring react and is added water after complete, and ethyl acetate extraction is washed organic phase, drying, suction filtration revolves steaming, get Compound C 1 namely 3,4 ', 5-trimethoxy toluylene;
d
1.3,4 ', the preparation of 5-trihydroxy-toluylene
Compound C 1 is mixed with pyridine hydrochloride, 165～220 ℃ of oil bath reflux, and TLC monitoring react and is added water after complete, ethyl acetate extraction, the washing organic phase is revolved steaming, get product D1 and be 3,4 ', 5-trihydroxy-toluylene.
The present invention also provide the hexamethylenetetramine oxidation synthesize 3,5-dimethoxy-4 ' '-hydroxy stibene is the method for Pterostilbene, reaction scheme is suc as formula (II):
The method of described synthetic Pterostilbene is carried out according to following step order:
a
2.3, the preparation of 5-dimethoxy benzyl chlorine
3,5-3,5-dimethoxybenzoic alcohol, methylene dichloride mix, and stir, cooling ,-2～2 ℃ drip sulfur oxychloride, are warming up to room temperature reaction after dropwising, TLC monitoring is reacted and is added water after complete, tells organic layer, dichloromethane extraction, the washing organic layer, drying, suction filtration, revolve and steam to such an extent that product A 2 is 3,5-dimethoxy benzyl chlorine;
b
2.3, the preparation of 5-dimethoxy benzaldehyde
Product A 2 is mixed with hexamethylenetetramine, water, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves and steams to such an extent that compd B 2 is 3,5-dimethoxy benzaldehyde;
c
2.3, the 5-dimethoxy-4 ' '-preparation of tertiary butyl dimethyl Si base toluylene
4-tertiary butyl dimethyl Si base Bian base triphenyl phosphonium chloride mixes with tetrahydrofuran (THF), stirs ice bath, drip tert-butyl lithium in the time of-22～-10 ℃, be warming up to room temperature after dropwising, stir 25～35min, drip the tetrahydrofuran solution of B2, the TLC monitoring is reacted and is added water after complete, ethyl acetate extraction, washing, drying, suction filtration, revolve steaming, get Compound C 2 namely 3,5-dimethoxy-4 ' '-tertiary butyl dimethyl Si base toluylene;
d
2.3, the 5-dimethoxy-4 ' '-preparation of hydroxy stibene
Get C2 and tetrahydrofuran (THF) mix and blend, drip the tetrahydrofuran solution of tetra-n-butyl Neutral ammonium fluoride, room temperature reaction 12～18min removes solvent under reduced pressure, column chromatography for separation, get product D2 namely 3,5-dimethoxy-4 ' '-hydroxy stibene.
It is the not method of moral of benzene alkene that the present invention also provides the hexamethylenetetramine oxidation to synthesize 3,5-dihydroxyl-4-isopropyl toluylene, and its reaction scheme is suc as formula (III):
The described synthetic benzene alkene not method of moral carries out according to following step order
a
3.3, the preparation of 5-dimethoxy-4 '-sec.-propyl benzyl chlorine
3,5-dimethoxy-4 '-Isobutyl Benzyl Carbinol mixes with methylene dichloride, stirs, the ice bath cooling drips sulfur oxychloride in the time of-2～2 ℃, be warming up to room temperature reaction after dropwising, TLC monitoring is reacted and is added water after complete, tells organic layer, washing, drying, suction filtration revolves to boil off and desolventizes, get i.e. 3, the 5-dimethoxy-4 '-sec.-propyl benzyl chlorine of compound A-13;
b
3.3, the preparation of 5-dimethoxy-4 '-isopropyl benzene formaldehyde
Get A3 and mix with hexamethylenetetramine, water, stir, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves the steaming desolventizing, getting compd B 3 is 3,5-dimethoxy-4 '-isopropyl benzene formaldehyde;
c
3.3, the preparation of 5-dimethoxy-4 '-isopropyl toluylene
Benzyl etherophosphoric acid, anhydrous tetrahydro furan mix, and stir N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of B3, is warming up to backflow after dropwising, TLC monitoring react and is added water after complete, and ethyl acetate extraction is washed, drying, suction filtration revolves and steams to such an extent that Compound C 3 is 3,5-dimethoxy-4 '-isopropyl toluylene;
d
3.3, the preparation of 5-dihydroxyl-4-isopropyl toluylene
C3 mixes with pyridine hydrochloride, reflux, and TLC monitoring react and is added water after complete, ethyl acetate extraction, washing, drying, suction filtration revolves steaming, and getting product D3 is 3,5-dihydroxyl-4-isopropyl toluylene.
Technique scheme of the present invention prepares halohydrocarbon by substituted benzyl alcohol, then adopts hexamethylenetetramine oxidation halohydrocarbon to prepare the method for corresponding substituted benzoyl aldehyde compound, then prepares the toluylene analog derivative through the Wittig-Horner condensation.The technical progress that the present invention obtains is: the method is simple, related reactant safety in the building-up process, resultant can be to environment, cost is low, yield is high, be fit to suitability for industrialized production, for the synthesis of diphenylethylene compounds as having anti-microbial effect trans-resveratrol, Pterostilbene, benzene alkene Mo De etc.
The present invention below in conjunction with specific embodiment to being described in further detail.
Embodiment
Embodiment one
Present embodiment be the hexamethylenetetramine oxidation synthetic 3,4 ', 5-trihydroxy-toluylene is the method for trans-resveratrol, its reaction scheme is suc as formula (I):
Its reaction process is a1 → b1 → c1 → d1, and it is as follows that each goes on foot reaction formula:
Present method is carried out according to the following steps order:
a
1. compd A 13, the preparation of 5-dimethoxybenzyl bromide
Get 3,5-3,5-dimethoxybenzoic alcohol 10.60g (63.10mmol), ether 100mL and join in the 250mL four-hole boiling flask, stir, cooling drips phosphorus tribromide 7.10mL (75.72mmol) in the time of 0 ℃, rise to room temperature reaction after dropwising, the TLC monitoring.React complete aftertreatment, in reaction solution impouring frozen water, stir, tell organic layer, washing, drying, suction filtration revolves and steams to get product A 1 11.90g (51.51mmol).Yield 81.62%.
b
1. compound B-11 3, the preparation of 5-dimethoxy benzaldehyde:
Upper step gained A1 and hexamethylenetetramine 7.20g (51.51mmol) g, water 100mL join in the four-hole boiling flask, reflux the TLC monitoring.React the dilute hydrochloric acid of complete rear adding 5%, ethyl acetate extraction, washing, drying, suction filtration revolves and steams to get product B 1 5.30g (31.93mmol).Yield 62%.
c
1. Compound C 13,4 ', the preparation of 5-trimethoxy toluylene:
Get and methoxy-benzyl etherophosphoric acid 9.35g (38.32mmol), anhydrous tetrahydro furan 50mL are joined in the four-hole boiling flask stirring, N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of the B1 of upper step gained, dropwises rear temperature rising reflux, the TLC monitoring.React and add water after complete, ethyl acetate extraction, washing, drying, suction filtration revolves and steams to get product C 1 7.60g (28.15mmol).Yield 88%.
d
1. Compound D 13,4 ', the preparation of 5-trihydroxy-toluylene:
Upper step gained C1 and pyridine hydrochloride 19.5g (168.83mmol) join in the 100mL single port bottle, 170 ℃ of oil bath reflux, TLC monitoring.React and add water after complete, ethyl acetate extraction, washing, drying, suction filtration revolves and steams to get product D1 1.93g (8.46mmol), yield 30%.
Embodiment two
Present embodiment be synthetic 3, the 5-dimethoxy-4 ' of hexamethylenetetramine oxidation '-hydroxy stibene is the method for Pterostilbene, its reaction scheme is suc as formula (II):
Its reaction process is a2 → b2 → c2 → d2, and it is as follows that each goes on foot reaction formula:
Present method is carried out according to following step order:
a
2.3,5-dimethoxy benzyl chlorine is the preparation of A2:
3,5-3,5-dimethoxybenzoic alcohol 10.82g (64.40mmol), methylene dichloride 110mL join in the 250mL four-hole boiling flask, stir, and cooling drips sulfur oxychloride 5.61mL (77.28mmol) in the time of 0 ℃, rise to room temperature reaction after dropwising, the TLC monitoring.React and add water after complete, tell organic layer, washing, drying, suction filtration revolves to boil off and desolventizes to get A29.61g (51.53mmol), yield 80%.
b
2. the i.e. preparation of 3,5-dimethoxy benzaldehyde of compd B 2:
Upper step gained A2 and hexamethylenetetramine 7.20g (51.53mmol), water 100mL join in the four-hole boiling flask, reflux the TLC monitoring.React complete aftertreatment, add 5% dilute hydrochloric acid, ethyl acetate extraction, washing, drying.Suction filtration revolves the steaming desolventizing and gets product B 2 5.30g (31.93mmol).Yield 62%.
c
2. Compound C 2 namely 3,5-dimethoxy-4 ' '-preparation of tertiary butyl dimethyl Si base toluylene:
Getting 4-tertiary butyl dimethyl Si base Bian base triphenyl phosphonium chloride 16.57g (31.93mmol) and tetrahydrofuran (THF) 160mL joins in the 500mL four-hole bottle, drip tert-butyl lithium 20.00mL (31.93mmol) during ice bath-20 ℃, rise to room temperature after dropwising, stir about 30min, the THF solution 110mL of step gained B2 in the dropping, the TLC monitoring.React and add water after complete, ethyl acetate extraction, washing, drying is revolved steaming, gets product C 2 6.14g (16.60mmol).Yield 52%.
d
2. Compound D 2 namely 3,5-dimethoxy-4 ' '-preparation of hydroxy stibene (Pterostilbene):
Upper step gained C2 and THF110mL join in the 250mL four-hole bottle, stir, and drip (n-Bu)
4The THF solution (11.10mL/1M) of NF, the about 15min of room temperature reaction.Remove solvent under reduced pressure, column chromatography for separation gets product D2 (Pterostilbene) 2.25g (8.79mmol).Yield 53%.
Embodiment three
Present embodiment is that synthetic 3, the 5-dimethoxy-4 '-isopropyl toluylene of hexamethylenetetramine oxidation is the not method of moral of benzene alkene, and its reaction scheme is suc as formula (III):
Its reaction process is a3 → b3 → c3 → d3, and it is as follows that each goes on foot reaction formula:
Present method is carried out according to following step order:
a
3. compound A-13 i.e. the preparation of 3,5-dimethoxy-4 '-sec.-propyl benzyl chlorine:
Get 3,5-dimethoxy-4 '-Isobutyl Benzyl Carbinol 10.81g (51.48mmol), methylene dichloride 110mL and join in the 250mL four-hole boiling flask, stir, the ice bath cooling, drip sulfur oxychloride 4.50mL (61.77mmol) in the time of 0 ℃, rise to room temperature reaction after dropwising, the TLC monitoring.React and add water after complete, dichloromethane extraction, washing is revolved to boil off and is desolventized to get product A 3 10.00g (43.76mmol).Yield 85%.
b
3. the i.e. preparation of 3,5-dimethoxy-4 '-isopropyl benzene formaldehyde of compd B 3:
Get step gained A3 and hexamethylenetetramine 24.51g (175mmol), water 100mL join in the four-hole boiling flask, stir, reflux, the TLC monitoring.React complete aftertreatment, add 5% dilute hydrochloric acid, ethyl acetate extraction, washing is revolved the steaming desolventizing and is got product B 3 5.38g (25.87mmol).Yield 56%.
c
3. the i.e. preparation of 3,5-dimethoxy-4 '-isopropyl toluylene of Compound C 3:
Get benzyl etherophosphoric acid 6.64g (31.03mmol), anhydrous tetrahydro furan 550mL and join in the four-hole boiling flask, stir N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of upper step gained B2, is warming up to backflow after dropwising, the TLC monitoring.React and add water after complete, ethyl acetate extraction, washing is revolved and is steamed to such an extent that product C 3 is 6.13g (21.74mmol).Yield 84%.
d
3. compound d3 i.e. the preparation of 3,5-dihydroxyl-4-isopropyl toluylene (benzene alkene is moral not):
Upper step gained C3 and pyridine hydrochloride 12.55g (108.70mmol) join in the 100mL single port bottle, reflux, TLC monitoring.React and add water after complete, ethyl acetate extraction, washing is revolved and is steamed to get product D3 (benzene alkene is moral not) 4.1416.30mmol).Yield 75%.
Embodiment four
Repeat embodiment one by described same routes, process, step, still:
a
1In 3, the 5-3,5-dimethoxybenzoic alcohol mixes with ether, drip phosphorus tribromide after the cooling of stirring, ice bath in the time of-2 ℃;
d
1Middle Compound C 1 is mixed in 220 ℃ of oil bath reflux with pyridine hydrochloride;
Product yield is 30.5%.
Embodiment five
Repeat embodiment one by described same routes, process, step, still:
a
1In 3, the 5-3,5-dimethoxybenzoic alcohol mixes with ether, drip phosphorus tribromide after the cooling of stirring, ice bath in the time of 2 ℃;
d
1Middle Compound C 1 is mixed in 165 ℃ of oil bath reflux with pyridine hydrochloride;
Product yield is 29.8%.
Embodiment six
Repeat embodiment two by described same routes, process, step, still:
a
2In in the time of 2 ℃, drip sulfur oxychloride;
c
2In in the time of-10 ℃, drip tert-butyl lithium, be warming up to room temperature after dropwising, stir 25min;
d
2Middle room temperature reaction 18min;
Product yield is 54%.
Embodiment seven
Repeat embodiment two by described same routes, process, step, still:
a
2In in the time of-2 ℃, drip sulfur oxychloride;
c
2In in the time of-22 ℃, drip tert-butyl lithium, be warming up to room temperature after dropwising, stir 35min;
d
2Middle room temperature reaction 12min;
Product yield is 52.3%.
Embodiment eight
Repeat embodiment three by described same routes, process, step, still:
a
3In in the time of-2 ℃, drip sulfur oxychloride;
Product yield is 75.1%.
Embodiment nine
Repeat embodiment three by described same routes, process, step, still:
a
3In in the time of 2 ℃, drip sulfur oxychloride;
Product yield is 75.2%.
Claims (6)
1. the method for an oxidation synthesis of stilbenes by hexamethylenetetramine is characterized in that: the method be the hexamethylenetetramine oxidation synthetic 3,4 ', 5-trihydroxy-toluylene is the method for trans-resveratrol, its reaction scheme is suc as formula (I):
2. the method for oxidation synthesis of stilbenes by hexamethylenetetramine according to claim 1 is characterized in that the method for described synthesizing resveratrol is carried out according to following step order:
a
1.3, the preparation of 5-dimethoxybenzyl bromide
3,5-3,5-dimethoxybenzoic alcohol mixes with ether, stirs, the ice bath cooling drips phosphorus tribromide in the time of-2～2 ℃, be warming up to room temperature reaction after dropwising, TLC monitoring, react complete after, in reaction solution impouring frozen water, stir, tell organic layer, washing, drying, suction filtration, steaming desolventizes, get i.e. 3, the 5-dimethoxybenzyl bromide of compd A 1;
b
1.3, the preparation of 5-dimethoxy benzaldehyde
Compd A 1 mixes with hexamethylenetetramine, water, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves the steaming desolventizing, getting compound B-11 is 3,5-dimethoxy benzaldehyde;
c
1.3,4 ', the preparation of 5-trimethoxy toluylene
The methoxy-benzyl etherophosphoric acid is mixed with anhydrous tetrahydro furan, stir N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of B1, dropwises rear temperature rising reflux, TLC monitoring react and is added water after complete, and ethyl acetate extraction is washed organic phase, drying, suction filtration revolves steaming, get Compound C 1 namely 3,4 ', 5-trimethoxy toluylene;
d
1.3,4 ', the preparation of 5-trihydroxy-toluylene
Compound C 1 is mixed with pyridine hydrochloride, 165～220 ℃ of oil bath reflux, and TLC monitoring react and is added water after complete, ethyl acetate extraction, the washing organic phase is revolved steaming, get product D1 and be 3,4 ', 5-trihydroxy-toluylene.
3. the method for an oxidation synthesis of stilbenes by hexamethylenetetramine is characterized in that: the method be synthetic 3, the 5-dimethoxy-4 ' of hexamethylenetetramine oxidation '-hydroxy stibene is the method for Pterostilbene, reaction scheme is suc as formula (II):
4. the method for oxidation synthesis of stilbenes by hexamethylenetetramine according to claim 3 is characterized in that the method for described synthetic Pterostilbene is carried out according to following step order:
a
2.3, the preparation of 5-dimethoxy benzyl chlorine
3,5-3,5-dimethoxybenzoic alcohol, methylene dichloride mix, and stir, cooling ,-2～2 ℃ drip sulfur oxychloride, are warming up to room temperature reaction after dropwising, TLC monitoring is reacted and is added water after complete, tells organic layer, dichloromethane extraction, the washing organic layer, drying, suction filtration, revolve and steam to such an extent that product A 2 is 3,5-dimethoxy benzyl chlorine;
b
2.3, the preparation of 5-dimethoxy benzaldehyde
Product A 2 is mixed with hexamethylenetetramine, water, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves and steams to such an extent that compd B 2 is 3,5-dimethoxy benzaldehyde;
c
2.3, the 5-dimethoxy-4 ' '-preparation of tertiary butyl dimethyl Si base toluylene
4-tertiary butyl dimethyl Si base Bian base triphenyl phosphonium chloride mixes with tetrahydrofuran (THF), stirs ice bath, drip tert-butyl lithium in the time of-22～-10 ℃, be warming up to room temperature after dropwising, stir 25～35min, drip the tetrahydrofuran solution of B2, the TLC monitoring is reacted and is added water after complete, ethyl acetate extraction, washing, drying, suction filtration, revolve steaming, get Compound C 2 namely 3,5-dimethoxy-4 ' '-tertiary butyl dimethyl Si base toluylene;
d
2.3, the 5-dimethoxy-4 ' '-preparation of hydroxy stibene
Get C2 and tetrahydrofuran (THF) mix and blend, drip the tetrahydrofuran solution of tetra-n-butyl Neutral ammonium fluoride, room temperature reaction 12～18min removes solvent under reduced pressure, column chromatography for separation, get product D2 namely 3,5-dimethoxy-4 ' '-hydroxy stibene.
5. the method for an oxidation synthesis of stilbenes by hexamethylenetetramine is characterized in that: the method be the hexamethylenetetramine oxidation synthetic 3,5-dihydroxyl-the 4-isopropyl toluylene is the not method of moral of benzene alkene, its reaction scheme is suc as formula (III):
6. the method for oxidation synthesis of stilbenes by hexamethylenetetramine according to claim 5, it is characterized in that described synthetic benzene alkene not the method for moral carry out according to following step order:
a
3.3, the preparation of 5-dimethoxy-4 '-sec.-propyl benzyl chlorine
3,5-dimethoxy-4 '-Isobutyl Benzyl Carbinol mixes with methylene dichloride, stirs, the ice bath cooling drips sulfur oxychloride in the time of-2～2 ℃, be warming up to room temperature reaction after dropwising, TLC monitoring is reacted and is added water after complete, tells organic layer, washing, drying, suction filtration revolves to boil off and desolventizes, get i.e. 3, the 5-dimethoxy-4 '-sec.-propyl benzyl chlorine of compound A-13;
b
3.3, the preparation of 5-dimethoxy-4 '-isopropyl benzene formaldehyde
Get A3 and mix with hexamethylenetetramine, water, stir, reflux, the TLC monitoring, react complete after, add dilute hydrochloric acid, ethyl acetate extraction, washing, drying, suction filtration revolves the steaming desolventizing, getting compd B 3 is 3,5-dimethoxy-4 '-isopropyl benzene formaldehyde;
c
3.3, the preparation of 5-dimethoxy-4 '-isopropyl toluylene
Benzyl etherophosphoric acid, anhydrous tetrahydro furan mix, and stir N
2Protection, cooling adds NaH in the time of 0 ℃, then drip the tetrahydrofuran solution of B3, is warming up to backflow after dropwising, TLC monitoring react and is added water after complete, and ethyl acetate extraction is washed, drying, suction filtration revolves and steams to such an extent that Compound C 3 is 3,5-dimethoxy-4 '-isopropyl toluylene;
d
3.3, the preparation of 5-dihydroxyl-4-isopropyl toluylene
C3 mixes with pyridine hydrochloride, reflux, and TLC monitoring react and is added water after complete, ethyl acetate extraction, washing, drying, suction filtration revolves steaming, and getting product D3 is 3,5-dihydroxyl-4-isopropyl toluylene.
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| CN101838173A (en) * | 2010-05-07 | 2010-09-22 | 河北科技大学 | Method for synthesizing stilbene compound by utilizing Kornblum oxidation reaction |
| CN102050703B (en) * | 2010-12-15 | 2013-03-27 | 厦门大学 | Resveratrol derivate as well as preparation method and application thereof |
| CN103172497A (en) * | 2011-12-23 | 2013-06-26 | 重庆市科学技术研究院 | Industrialized production process of new medicament benvitimod for treating psoriasis |
| DK3229840T5 (en) | 2014-12-12 | 2020-11-16 | Dermavant Sciences GmbH | 3,5-DIHYDROXY-4-ISOPROPYL TRANS STILBEN FOR USE IN TOPIC TREATMENT OF ACNE |
| JP6912664B2 (en) | 2017-11-10 | 2021-08-04 | ダーマヴァント サイエンシーズ ゲーエムベーハー | Process for preparing tapinarov |
| CN108276267B (en) * | 2018-01-19 | 2021-09-24 | 上海应用技术大学 | Fluorine-containing 1, 1-stilbene derivative, preparation method and application thereof |
| CN108752167A (en) * | 2018-07-17 | 2018-11-06 | 上海华堇生物技术有限责任公司 | A kind of new preparation process of Stilbene triphenol |
| CN109516899B (en) * | 2018-11-13 | 2021-07-30 | 杭州瑞树生化有限公司 | Preparation method of high-purity resveratrol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1407978A (en) * | 1999-12-06 | 2003-04-02 | 陈庚辉 | Polyhydroxystilbenes and stibene oxides as antisoriatic agents and protein kinase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1407978A (en) * | 1999-12-06 | 2003-04-02 | 陈庚辉 | Polyhydroxystilbenes and stibene oxides as antisoriatic agents and protein kinase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| 李印钊等.天然产物（E）-白藜芦醇的全合成.《中国农业大学学报》.2005,第10卷(第1期),90-92. * |
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