CN102050702A

CN102050702A - Method for promoting synthesis of resveratrol by micro waves

Info

Publication number: CN102050702A
Application number: CN2010105823223A
Authority: CN
Inventors: 蒋勇
Original assignee: Individual
Current assignee: Individual
Priority date: 2010-12-10
Filing date: 2010-12-10
Publication date: 2011-05-11
Anticipated expiration: 2030-12-10
Also published as: CN102050702B

Abstract

The invention discloses a new method for promoting the synthesis of resveratrol by utilizing micro waves, which comprises the following steps of: mixing 3,5-dimethoxy benzaldehyde serving as a raw material and p-methoxyphenyl acetonitrile according to a molar ratio of 1:1, and heating and condensing the mixture by the micro waves in silica gel serving as a carrier under the alkaline condition to obtain 2-(4-metoxybenzene)-3-(3,5-dimethoxybenzene)-acrylonitrile serving as an intermediate (1); heating, hydrolyzing the intermediate (1) by the micro waves and decarboxylating the product of hydrolysis to obtain trans 3,4',5-trimethoxy stilbene serving as an intermediate (2); performing deprotection on the intermediate (2) by using a micro wave-promoted N-methyl pyrrolidone-NaCl (NMP-Nacl) system; and finally, recrystallizing to obtain pure resveratrol. The raw material used by the method is a common raw material reagent, and is readily available and low in cost; and the method has few synthetic steps, simple process, high efficiency and yield and single products, and is easy and convenient to operate and environmentally-friendly.

Description

Microwave promotes the method for synthesizing resveratrol

Technical field

The invention belongs to chemosynthesis technical field, specifically, relate to the method that a kind of microwave promotes synthesizing resveratrol.

Background technology

Trans-resveratrol is a kind of natural antioxidant; has multiple pharmacologically active; as antibiotic, anti-oxidant, preventing heart disease, anticancer, anti-platelet aggregation, protection liver, estrogen effect, radioprotective, immunomodulatory, anti-AIDS activity etc., also can repair the cell DNA damage due to the atypical pneumonia prescription.Particularly importantly trans-resveratrol does not damage normal human body cell, and has good pharmacologically active.In clinical application, be used for the acute icteric infectious hepatitis, blood stasis amenorrhoea, rheumatism type arthrodynia, bones and muscles pain, sand pouring, blood pouring, trachitis, damp-heat type gall stone; Be used for blood cholesterol and triglyceride level is too high; Be used for anti-oxidant, delay senility, be the raw material of antitumor drug exploitation.

At present, mainly contain three kinds of approach and obtain trans-resveratrol: (1) is the plant extract method.This method cost height, throughput are little; (2) be biological fermentation or transgenosis method.This method production cycle, enzyme long, that process is complicated, required was difficult for making; (3) be chemical synthesis.Witting reaction, Heck reaction and the three kinds of methods of Perkin reaction of mainly containing are concluded in chemosynthesis.The simple gentleness of Witting reaction conditions, raw material are easy to get, but route is long, consumption is big, cost is high, pollution is big, and it generates product is the cis-trans diolefine, and product is complexity comparatively; The Heck reaction scheme is short, and the product configuration is single, but raw material is not easy to obtain, and agents useful for same toxicity is bigger; The Perkin reaction scheme is long, and cost is higher.Recently, the novel method of the synthesizing Resveratrol by means of organic zinc halide reagent of CN101519342A report, this method has improved synthesis yield, has reduced production cost, but operational condition harshness, loaded down with trivial details.

Summary of the invention

For solving above technical problem, the object of the present invention is to provide a kind of raw material to be easy to get, with low cost, the method for the synthesizing resveratrol that synthesis step is few, technology is simple, easy and simple to handle.

A kind of microwave promotes the method for synthesizing resveratrol; in the presence of alkaline silica gel; under alkaline environment, be carrier promptly with silica gel; 3; basic formaldehyde of 5-dimethoxy and the reaction of PARA METHOXY PHENYL ACETONITRILE heated by microwave; gained intermediate (1) is without purifying; directly microwave heating hydrolysis in the alkaline ethanol aqueous solution; hydrolysate also need not to separate; add sulfuric acid transfer to acid and once more the microwave heating decarboxylation obtain intermediate (2), NaCl exists down, this intermediate heated by microwave deprotection in NMP; behind the recrystallization purifying, promptly get the pure product of trans-resveratrol.In the above-mentioned reaction, the first step speed of response is fast, the yield height, and efficient is very high, and silica gel is recyclable recycles.Second step, utilize the microwave heating hydrolysis decarboxylation, shortened the reaction times greatly, want more than 10 hours the time to compare with common heating reaction, well improved efficient.The 3rd step, adopt NMP-NaCl system demethoxylation protection, this method is dirt cheap, efficiently, and existing relatively deprotection method does not pollute very environmental protection.And, in the treating processes in each step, seldom with an organic solvent, very friendly to environment.

Trans-resveratrol preparation method's provided by the present invention reaction process is as follows:

Figure 2010105823223100002DEST_PATH_IMAGE001

Wherein, intermediate is mixed with mol ratio 1:1 with PARA METHOXY PHENYL ACETONITRILE by 3,5-dimethoxy benzaldehyde shown in the formula (1), adds silica gel and alkali NaOH, and the heated by microwave reaction obtains.

The method according to this invention, intermediate shown in the formula (2) is trans 3,4 ', 5-trimethoxy toluylene is by the microwave heating backflow 10min hydrolysis in the alkaline ethanol water of 1:1 earlier of intermediate shown in the formula (1), use sulfuric acid furnishing PH＜1 o'clock then, microwave heating backflow 30min decarboxylation and getting.

The method according to this invention, intermediate is trans 3,4 ', 5-trimethoxy toluylene and NaCl add among the NMP according to the mass ratio of 1:1.3, microwave heating backflow 30min, and decompression steams most of solvent then, pours into and contains 10g NH ₄In the 300ml frozen water of Cl, separate out solid, solid is after washing is drained, with aqueous ethanolic solution recrystallization and the dry white powder solid trans-resveratrol that gets.

The raw materials used reagent of the present invention is raw material reagent commonly used, and raw material is easy to get, and is with low cost; Synthesis step is few, technology is simple, easy and simple to handle, yield is high, product is single, very friendly to environment.

Embodiment

Synthesizing of A, intermediate (1) 2-(4-anisole)-3-(3,5-dimethoxy benzene)-vinyl cyanide

With 3 of the PARA METHOXY PHENYL ACETONITRILE of 14.7g, 16.6g, the 5-dimethoxy benzaldehyde mixes, and it is even to add 10g silica gel and the Powdered NaOH of 1g and thorough mixing, microwave heating reaction 2min, and top temperature is 150 ℃, cooling, CH ₂Cl ₂Extract 28.5g intermediate (1), 2-(4 '-anisole)-3-(3,5-dimethoxy benzene)-vinyl cyanide, yield 97%.

B, intermediate (2) (E)-3,4 ', 5-trimethoxy toluylene synthetic

20g intermediate 1 is added in the 250ml flask, add aqueous ethanolic solution 100ml and the 2gNaOH of 1:1 again, microwave heating backflow 10min postcooling, vitriol oil acid adjustment is to PH＜1, and microwave heating backflow 30min cools off again, NaOH transfers to neutrality, steams low boiling component, cooling, filter, the washing white solid, dry 15g is trans 3,4 ', 5-trimethoxy toluylene, yield 82%.

Synthesizing of C, trans-resveratrol

10g intermediate (2) is dissolved among the 50mlNMP, adds 13gNaCl, microwave heating backflow 30min, after decompression steamed most of solvent, residuum was poured into and is contained 10g NH ₄In the 300ml frozen water of Cl, filter, washing, drying gets white powder solid trans-resveratrol 6g, mp:255-257 ℃, HPLC behind the ethanol water recrystallization〉99%, be trans through the NMR analytical proof, total recovery 56%.

Present embodiment products therefrom (E)-3,4 ', 5-trihydroxy-toluylene nuclear magnetic data:

¹HNMR（400MHz，DMSO）：9.57（s，1H），9.22（s，2H），7.39（dd，2H， J?=?8.4），6.95（d，1H， J?=?16），6.83（d，1H， J?=?16.2），6.77（dd，2H， J?=?8.1），6.40（d，2H），6.14（t，1H， J?=?2.1）。

¹³CNMR（400MHz，DMSO）：δ=158.5，157.2，139.2，128.0，127.8，125.6，115.5，104.3，101.7。

Claims

1. a microwave promotes the method for synthesizing resveratrol, it is characterized in that: with 3,5-dimethoxy benzaldehyde is a raw material, with the mixed in molar ratio of PARA METHOXY PHENYL ACETONITRILE according to 1:1, silica gel is that the condensation of carrier heated by microwave obtains intermediate (1): 2-(4-anisole)-3-(3,5-dimethoxy benzene)-vinyl cyanide under alkaline condition; Intermediate (1) microwave heating hydrolysis, decarboxylation obtain intermediate (2): trans 3,4 ', 5-trimethoxy toluylene; Intermediate (2) deprotection, last recrystallization gets purified trans-resveratrol.

2. promote the method for synthesizing resveratrol according to the described microwave of claim 1, it is characterized in that: described alkaline condition is provided by NaOH, and the mass ratio of NaOH and 3,5-dimethoxy benzaldehyde is 1:17, silica gel and 3, the mass ratio of 5-dimethoxy benzaldehyde are 1:1.7.

3. promote the method for synthesizing resveratrol according to the described microwave of claim 1, it is characterized in that: with compound shown in the intermediate (1) is microwave heating back hydrolysis in the alkaline ethanol aqueous solution of 1:1 in volume ratio earlier, time is 10min, wherein, the NaOH consumption is intermediate (1): the NaOH mass ratio is 10:1, the cooling back transfers to PH＜1 with sulfuric acid, and microwave heating backflow 30min decarboxylation makes intermediate (2) again.

4. promote the method for synthesizing resveratrol according to the described microwave of claim 1, it is characterized in that: after mixing according to the mass ratio of 1:1.3 with intermediate (2) and NaCl, microwave heating backflow 30min in NMP, steam most of solvent after, pour into and contain NH ₄In the frozen water of Cl, separate out solid,, get the pure product of white powder solid trans-resveratrol after the drying through ethanol-water recrystallization.