阅读说明：本技术 一种一步法合成异戊烯基腺嘌呤或其衍生物的方法 (Method for synthesizing isopentenyl adenine or derivatives thereof by one-step method ) 是由 韩见生 李旭 薛倩倩 徐辉 徐升升 张盼盼 于 2020-05-11 设计创作，主要内容包括：本发明涉及一种一步法合成异戊烯基腺嘌呤或其衍生物的方法,由式(II)所示化合物和式(III)所示化合物在碱性试剂存在的条件下反应,制备得到式(I)所示化合物。本发明的技术方案通过一步法合成内源植物细胞分裂素-N6-异戊烯基腺嘌呤或其衍生物,能有效降低生产成本,为今后内源性植物激素在农业上的广泛使用提供便利；并且克服了现有技术中存在的原有方法合成步骤长、后处理复杂的缺点,具有产品收率高、无需复杂后处理步骤即可得到高纯度产品的优点。(The invention relates to a method for synthesizing isopentenyl adenine or a derivative thereof by a one-step method, which comprises the step of reacting a compound shown in a formula (II) with a compound shown in a formula (III) in the presence of an alkaline reagent to prepare the compound shown in the formula (I). According to the technical scheme, the endogenous plant cytokinin-N6-isopentenyl adenine or the derivative thereof is synthesized by a one-step method, so that the production cost can be effectively reduced, and convenience is provided for wide agricultural use of endogenous plant hormones in future; and overcomes the defects of long synthesis steps and complex post-treatment of the original method in the prior art, and has the advantages of high product yield and capability of obtaining a high-purity product without complex post-treatment steps.)

1. A one-step method for synthesizing isopentenyl adenine or derivatives thereof is characterized in that a compound shown as a formula (I) is prepared by reacting a compound shown as a formula (II) with a compound shown as a formula (III) in the presence of an alkaline reagent

Wherein X, Y in the formulas (I) and (III) are respectively and independently selected from H, C_1-6Alkyl, halogen substituted C_1-6Alkyl radical, C_1-6Alkoxy, halogen substituted C_1-6Alkoxy radical, C_3-6Cycloalkyl, aryl substituted by substituents, C substituted by aryl_1-6Alkyl, aryl substituted C_1-6Alkoxy, aryl substituted C_1-6Alkyl substituted C_1-6An alkoxy group.

2. The method of claim 1, wherein X, Y in formulas (I) and (III) are each independently selected from H, C_1-4Alkyl, halogen substituted C_1-4Alkyl radical, C_1-4Alkoxy, halogen substituted C_1-4Alkoxy radical, C_3-6Cycloalkyl, phenyl, by halogen or C_1-4Alkyl-substituted phenyl, phenyl-substituted C_1-4Alkyl, phenyl substituted C_1-4Alkoxy, phenyl substituted C_1-4Alkyl substituted C_1-4An alkoxy group;

preferably, X, Y are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, trichloromethyl, tribromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, monofluoromethyl, chloromethyl, monobromomethyl, -CH₂CF₃、-CH₂CCl₃、-CH₂CBr₃Methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, trifluoromethoxy, trichloromethoxy, tribromomethoxy, difluoromethoxy, dichloromethoxy, dibromomethoxy, monofluoromethoxy, monochloromethoxy, monobromomethoxy, -OCH₂CF₃、-OCH₂CCl₃、-OCH₂CBr₃Cyclopropyl, cyclopentyl, cyclohexyl, phenyl, -CH₂Ph、-CH₂OPh、-CH₂OCH₂Ph；

More preferably, X, Y are each independently selected from H, methyl, ethyl, methoxy, ethoxy, phenyl, -CH₂Ph、-CH₂OPh、-CH₂OCH₂Ph；

Still more preferably, X, Y are each independently selected from H, methyl;

more preferably, X is methyl and Y is H.

3. The method of claim 1, wherein the alkaline agent is an inorganic alkaline agent or an organic alkaline agent; preferably, the inorganic base reagent is a simple substance of an element in IA group or IIA group, hydroxide and/or salt thereof, and the organic base is triethylamine or must; still preferably, the inorganic base reagent is lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium ethoxide, sodium methoxide, potassium carbonate, sodium metal, potassium metal or potassium tert-butoxide.

4. The method according to claim 1, wherein the mass ratio of the compound represented by the formula (II) to the compound represented by the formula (III) is 1:5 to 1:20, preferably 1: 10.

5. The process according to claim 1, wherein the mass ratio of the compound of formula (II) to the alkaline agent is 1:1 to 1:4, preferably 1: 2.

6. The method according to claim 1, wherein the compound of formula (II) and the compound of formula (III) are reacted in the presence of an alkaline reagent at a reaction temperature of 100 ℃ to 180 ℃, preferably at a reaction temperature of 100 ℃ and after the reaction is stabilized, the reaction temperature is adjusted to 150 ℃.

7. The method according to claim 1, wherein the compound of formula (II) and the compound of formula (III) are reacted in the presence of a basic agent for a period of time ranging from 3 to 8 hours.

8. The method according to claim 1, further comprising a post-processing step of: reacting a compound shown in a formula (II) with a compound shown in a formula (III) in the presence of an alkaline reagent, and performing post-treatment to obtain the compound shown in the formula (I).

9. The method of claim 8, wherein the post-treating step comprises adding water to the reaction mixture, extracting the unreacted starting material with an organic solvent, and neutralizing the aqueous phase with an acidic reagent to obtain a product; preferably, the organic solvent is an ester or a halogenated alkane; still preferably, the organic solvent is ethyl acetate, propyl acetate, butyl acetate, propyl formate, dichloromethane or dichloroethane.

10. The method of claim 9, wherein the acidic agent is a protic acid; preferably, the acidic reagent is glacial acetic acid, sulfuric acid, hydrochloric acid or phosphoric acid.

Technical Field

The invention belongs to the field of organic synthesis methods, and particularly relates to a method for synthesizing isopentenyl adenine or derivatives thereof by a one-step method.

Background

Cytokinins are one of five major classes of phytohormones (auxin, gibberellin, cytokinins, abscisic acid, ethephon) known to humans at present. The adenine derivative with side chain substituted at the N6-position is a main free natural cytokinin existing in nature, and the cytokinin has close relation with the growth and development of plants, including the germination of seeds, cell proliferation, vascular bundle development, apical dominance, leaf senescence and the like. The main functions of plants in vivo are trans-zeatin (tZ-CTK) and isopentenyl adenine (ip-CTK), wherein trans-zeatin and its nucleoside, isopentenyl adenine and its nucleoside are the most important functional components.

In recent years, trans-zeatin and isopentenyl adenine are successfully applied to plant tissue culture and the like, and are highly regarded by agricultural scientists. However, the prior method for synthesizing isopentenyl adenine or derivatives thereof has the disadvantages of complex synthesis steps, high pollution and high cost, so that the popularization and the application of the isopentenyl adenine or derivatives thereof in agriculture cause great hindrance. The invention relates to a method for synthesizing isopentenyl adenine or a derivative thereof by a one-step method, which has the advantages of simple operation, easily obtained raw materials, less pollution and high yield, effectively reduces the production cost and has high practical value for popularization and use of endogenous plant hormones.

The method for synthesizing N6-isopentenyl adenine reported in the literature at present takes 6-chloropurine and isopentenyl bromide as raw materials for synthesis:

the method has the biggest problems that the synthesis steps are long, the starting material isopentenyl bromide needs to be prepared and used at present and cannot be stored for a long time, a large amount of bromine or hydrogen bromide is needed when the isopentenyl bromide is prepared, the volatilization is easy, the strong toxicity and corrosion are caused, the environment is seriously polluted, the synthesis yield of the key intermediate isopentenyl amine obtained by further reacting the isopentenyl bromide is very low, the reaction process is not easy to monitor, in addition, the boiling point of n-butyl alcohol used as a solvent for reaction is high, the viscosity is large, and the post-treatment is very troublesome.

Disclosure of Invention

The invention aims to overcome the defects of long synthesis steps and complex post-treatment of the original method in the prior art, and the technical scheme of the invention can effectively reduce the production cost and provide convenience for wide agricultural use of endogenous plant hormones in the future by a method for synthesizing endogenous plant cytokinin-N6-isopentenyl adenine or derivatives thereof through a one-step method.

In order to achieve the technical purpose, the invention provides the following technical scheme: a one-step method for synthesizing isopentenyl adenine or a derivative thereof is characterized in that a compound shown as a formula (I) is prepared by reacting a compound shown as a formula (II) with a compound shown as a formula (III) in the presence of an alkaline reagent

Wherein X, Y in the formulas (I) and (III) are respectively and independently selected from H, C_1-6Alkyl, halogen substituted C_1-6Alkyl radical, C_1-6Alkoxy, halogen substituted C_1-6Alkoxy radical, C_3-6Cycloalkyl, aryl substituted by substituents, C substituted by aryl_1-6Alkyl, aryl substituted C_1-6Alkoxy, aryl substituted C_1-6Alkyl substituted C_1-6An alkoxy group;

further, X, Y in the formulas (I) and (III) are respectively and independently selected from H, C_1-4Alkyl, halogen substituted C_1-4Alkyl radical, C_1-4Alkoxy, halogen substituted C_1-4Alkoxy radical, C_3-6Cycloalkyl, phenyl, by halogen or C_1-4Alkyl-substituted phenyl, phenyl-substituted C_1-4Alkyl, phenyl substituted C_1-4Alkoxy, phenyl substituted C_1-4Alkyl substituted C_1-4An alkoxy group;

still further, X, Y are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, and trisChloromethyl, tribromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, monofluoromethyl, monochloromethyl, monobromomethyl, -CH₂CF₃、 -CH₂CCl₃、-CH₂CBr₃Methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, trifluoromethoxy, trichloromethoxy, tribromomethoxy, difluoromethoxy, dichloromethoxy, dibromomethoxy, monofluoromethoxy, monochloromethoxy, monobromomethoxy, -OCH₂CF₃、-OCH₂CCl₃、-OCH₂CBr₃Cyclopropyl, cyclopentyl, cyclohexyl, phenyl, -CH₂Ph、-CH₂OPh、-CH₂OCH₂Ph；

Still further, X, Y are each independently selected from H, methyl, ethyl, methoxy, ethoxy, phenyl, -CH₂Ph、-CH₂OPh、-CH₂OCH₂Ph；

Still further, X, Y are each independently selected from H, methyl;

still further, X is methyl and Y is H;

further, the alkaline reagent is an inorganic alkaline reagent or an organic alkaline reagent;

still further, the inorganic alkali reagent is simple substance of IA group or IIA group element, hydroxide and/or salt thereof, and the organic alkali is triethylamine or must;

still further, the inorganic base reagent is lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium ethoxide, sodium methoxide, potassium carbonate, sodium metal, potassium metal or potassium tert-butoxide;

further, the mass ratio of the compound shown in the formula (II) to the compound shown in the formula (III) is 1:5-1:20, and the preferred mass ratio is 1: 10;

further, the mass ratio of the compound shown in the formula (II) to the alkaline reagent is 1:1-1:4, preferably 1: 2;

further, the reaction temperature of the compound shown in the formula (II) and the compound shown in the formula (III) in the presence of an alkaline reagent is 100-180 ℃;

further, the reaction temperature is firstly 100 ℃, and is adjusted to 150 ℃ after the reaction is stable;

further, the compound shown in the formula (II) and the compound shown in the formula (III) react for 3 to 8 hours in the presence of an alkaline reagent;

further, the method also comprises a post-processing step, namely: reacting a compound shown in a formula (II) with a compound shown in a formula (III) in the presence of an alkaline reagent, and then carrying out a post-treatment step to obtain a compound shown in a formula (I);

further, the post-treatment step comprises adding water to the reaction mixture, extracting unreacted raw materials by using an organic solvent, and neutralizing the water phase by using an acidic reagent to obtain a product;

still further, the organic solvent is an ester or a halogenated alkane; still preferably, the organic solvent is ethyl acetate, propyl acetate, butyl acetate, propyl formate, dichloromethane or dichloroethane;

further, the acidic reagent is a protic acid;

still further, the acidic reagent is glacial acetic acid, sulfuric acid, hydrochloric acid or phosphoric acid.

Due to the adoption of the technology, compared with the prior art, the invention has the remarkable advantages that:

1) the adenine and the corresponding 2-enol analogue are dehydrated under alkalinity and high temperature by replacing the traditional synthesis mode with a one-step reaction, the product can be obtained by cooling, adding water and extracting an organic solvent after the reaction is finished, neutralizing the water phase with acid, and the raw materials contained in the organic phase can be recycled, so that the production cost is reduced, and the method is suitable for industrial expanded production;

2) by controlling the temperature (firstly, the intermediate temperature is increased, and then the temperature is increased), the generation of polymers of byproducts and reactants is avoided, the reaction yield is improved, the post-treatment operation is simplified, and a product can be obtained by neutralizing a water layer after the reaction;

3) the product content can reach more than 96 percent, and the yield can reach at least more than 70 percent (calculated by the compound of the formula II).

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of isopentenyl adenine as described herein.

Detailed Description

In order to make the technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to specific examples, but the scope of the present invention is not limited thereby.