CN110615737A - Beta-caryophyllenol derivative and preparation method and preparation device thereof - Google Patents

Abstract

The embodiment of the invention discloses a beta-caryophyllenol derivative and a preparation method and a preparation device thereof, wherein the preparation device comprises a cold and hot water placing groove (1) with a containing cavity (101), a mixing unit (2) at least partially arranged in the containing cavity (101), an elution column and a stirring reflux unit (3) which are arranged outside the cold and hot water placing groove (1). The invention simplifies the whole preparation process by carrying out one-time preparation on the whole preparation process from the beta-caryophyllene to the beta-caryophyllenol derivative, and adjusts the integral controllability of a preparation device on the basis of simplification, thereby solving the problems of complicated preparation process and poor operability.

Description

A kind of β-caryophyllenol derivative and its preparation method and preparation device

technical field

The embodiment of the present invention relates to the technical field of preparation of β-caryophyllenol derivatives, in particular to a β-caryophyllenol derivative and its preparation method and preparation device.

Background technique

β-Caryophyllenol, also known as syringenol, is a sesquiterpene alcohol compound with strong physiological activity. It is used in many fields such as food seasoning or medicine, but its derivatives are rare various reports. Since its derivatives (for example, ester derivatives) have similar structures, different structures can be obtained through the replacement of substituents, and some other physiologically active substances may be obtained.

However, since β-caryophyllenol generally exists in some plants, it is necessary to extract essential oils from plants and then further process and separate them. Not only is the output scarce, but the cost is high. At the same time, this method of extracting natural β-caryophyllenol is also more complicated. . Therefore, the preparation of β-caryophyllene is often obtained through the processing and synthesis of β-caryophyllene. At the same time, even if β-caryophyllenol is obtained, since the alcoholic hydroxyl group of β-caryophyllenol is located at the bridgehead carbon, it is a tertiary alcohol with great steric hindrance, therefore, in the process of preparing its derivatives, changes in reaction conditions There are more requirements, the reaction process is more complicated, and different utensils need to be replaced according to different conditions during the preparation process.

And as we said before, according to the different substituents, the types of its derivatives are even more diverse. Therefore, under the premise that the physiological activity of its derivatives is not clear, it is often necessary to use a large number of raw materials with different substituents. Substitution is used to prepare different derivatives, and this will undoubtedly require switching back and forth in more preparation equipment, resulting in the complexity of the entire preparation process. Also because of this, the preparation and research of its derivatives are rarely reported.

Contents of the invention

For this reason, an embodiment of the present invention provides a β-caryophyllene alcohol derivative and its preparation method and preparation device, so as to simplify the entire preparation process from β-caryophyllene to β-caryophyllene alcohol derivative through one-time preparation. The preparation process, and adjust the overall controllability of the preparation device on the basis of simplification, so as to solve the problems of complicated preparation process and poor operability.

In order to achieve the above object, embodiments of the present invention provide the following technical solutions:

In one aspect of the embodiments of the present invention, a method for preparing a β-caryophyllenol derivative is provided, comprising:

100. In the condition of an ice-water bath and the presence of the first solvent, add concentrated sulfuric acid to β-caryophyllene and mix to obtain a mixed solution;

200. After stirring and mixing the above mixed solution at a temperature not higher than 5°C for 8-12 hours, continue to add a saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and the first organic layer is obtained by separation;

300. Distill the first organic layer, collect the distillate, and dry to obtain a crude product;

400. In the presence of the second solvent, mix the crude product, carboxylic acid and catalyst, stir and reflux for 12-24 hours, then continue to add saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and obtain second organic layer;

500. The second organic layer was washed alternately with saturated sodium carbonate and water for 2-3 times, dried, and then eluted by column chromatography to obtain β-caryophyllenol derivatives; wherein,

The eluents in the elution process are petroleum ether and acetone.

As a preferred version of the present invention, the first solvent is ethanol or ether;

And the mixing process in step 100 comprises the following steps:

101. Mix β-caryophyllene and the first solvent and stir for 5-10 minutes to obtain a β-caryophyllene solution;

102. Add concentrated sulfuric acid to the β-caryophyllene solution at a rate not greater than 10 mL/min and stir and mix to obtain a mixed solution; and,

In step 100, the concentrated sulfuric acid is concentrated sulfuric acid with a concentration not lower than 93%;

And relative to 1 g of the β-caryophyllene, the amount of the first solvent used is 1-2 mL, and the amount of the concentrated sulfuric acid used is 0.2-0.5 mL.

As a preferred version of the present invention, the second solvent is one of chloroform, acetone and petroleum ether;

The catalyst is N, N'-carbonyldiimidazole or 4-dimethylaminopyridine;

And the mixing process in step 400 comprises the following steps:

401. Add the crude product and the carboxylic acid into the second solvent and stir and mix to obtain a mixed solution;

402. Add the catalyst to the above mixed solution at a rate not greater than 10mL/min, then stir and reflux; and,

Relative to 1 g of the β-caryophyllene, the amount of the second solvent is 30-60 mL, the amount of the carboxylic acid is 0.003-0.005 mol, and the amount of the catalyst is 3-8 mL;

The volume ratio of petroleum ether and acetone in the eluent is 3-6:1.

In another aspect of the embodiments of the present invention, there is provided a β-caryophyllenol derivative prepared according to the above-mentioned preparation method, the structure of the β-caryophyllenol derivative is shown in formula (I) ,

Wherein, R is an ester group.

In another aspect of the embodiments of the present invention, there is provided a preparation device used in the above-mentioned preparation method, comprising a cold and hot water storage tank formed with an accommodation chamber, a mixing chamber at least partially arranged in the accommodation chamber material unit, and an elution column and a stirring reflux unit arranged outside the cold and hot water storage tank; and,

The mixing unit includes a first material cylinder and a second material cylinder arranged at intervals in the accommodating chamber, and the first material cylinder and the second material cylinder are connected through a connecting pipe, The first feeding cylinder and the second feeding cylinder are respectively provided with a feeding port, the upper surface of the connecting pipe is vertically penetrated with a titration port, and the connecting pipe is close to the second One end of the barrel is provided with a pressure film along the vertical direction;

The bottom of the first storage cylinder or the connecting pipe can be closedly provided with a discharge pipe extending to the outside of the cold and hot water storage tank, and the discharge pipe is connected to the feed hole of the stirring and reflux unit are detachably connected, and at least part of the side wall of the connecting pipe is formed as a transparent viewing window;

A sealing plate capable of moving in the vertical direction is sealed on the inner wall of the second barrel, and the feeding port of the second barrel is located below the sealing plate;

A stirring paddle is arranged on the inner side wall of the connecting pipe.

As a preferred solution of the present invention, a plurality of deceleration stops are arranged on the inner wall of the second feeding cylinder along the vertical direction, and the plurality of deceleration stops are arranged below the feeding port;

The two adjacent deceleration blocks are arranged on the opposite inner walls of the second barrel.

As a preferred solution of the present invention, the deceleration stopper includes an extension rod and a stop plate sequentially connected from the inner side wall of the second charging cylinder, and two adjacent stop plates are at least partly located on the same vertical line. straight face;

And the axial direction of the extension rod and the vertical direction form an included angle of 15°-45°, the stop plate extends obliquely downward from the extension rod, and the axis direction of the extension rod is in line with the stop The plane where the upper surface of the baffle is located forms an included angle of 10°-30°.

As a preferred solution of the present invention, the stopper plate is formed in a fan shape, and the arc surface of the fan shape is arranged at an end away from the extension rod, and the upper surface of the stopper plate starts from the end close to the extension rod. A plurality of concave drainage grooves are formed extending from one side to the arc surface;

An arc-shaped protrusion is provided on the inner bottom surface of the drainage groove, and the height of the arc-shaped protrusion is 1/3-1/2 of the depth of the drainage groove;

The distance between the two endpoints of the arc surface is m, and the distance between the drainage grooves near the two endpoints of the arc surface and the two endpoints of the arc surface is 1/4-1/3 of m .

As a preferred solution of the present invention, the sealing plate includes a plate body and a sealing ring sleeved on the outer surface of the plate;

The sealing plate is connected to the pneumatic unit that drives the sealing plate to move vertically through a connecting rod;

The cold and hot water storage tank is provided with a temperature sensing module, and the temperature sensing module is electrically connected to an alarm module through the control module. When the water temperature in the cold and hot water storage tank is greater than or lower than the set temperature threshold, the A control module is capable of receiving signals and controlling the alarm module to alert.

As a preferred solution of the present invention, the stirring blade includes a first horizontal bar and a second horizontal bar, and the first horizontal bar and the second horizontal bar are connected by a plurality of vertical bars;

The outer surface of the vertical rod is formed with a plurality of diversion grooves along the vertical direction, and the diversion grooves arranged on the upper part of the vertical rod extend obliquely downward, and the diversion grooves arranged on the lower part of the vertical rod extend obliquely upward .

Embodiments of the present invention have the following advantages:

1. Directly process β-caryophyllene through multi-step operations to prepare β-caryophyllene alcohol derivatives, and only wash and elute them in the last step, avoiding multiple cleaning operations during the preparation process, which is beneficial to raw materials In the whole process, except drying after distillation and stirring and reflux, which exist independently in the whole process, other steps can be completed in one vessel in the embodiment of the present invention, avoiding the conversion between multiple utensils , effectively improving the preparation efficiency.

2. With the cooperative setting of the pressurized film and the sealing plate, the control of the flow rate of the overall feeding process is improved for the raw material of concentrated sulfuric acid in the present invention, which not only further improves the controllability of the entire preparation process, but also avoids the conventional addition of sulfuric acid Poor control of the flow rate of sulfuric acid in the process leads to serious problems such as carbonization. At the same time, a connecting pipe is arranged between the first and second feeding cylinders to form a relatively suitable space, so that the raw materials on both sides can be mixed at a more reasonable speed. And in the whole operation process, the further setting of the viewing window makes it possible to better control the controllability of the separation of the stratified product when the material is discharged through the discharge pipe.

Description of drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the accompanying drawings that are required in the description of the embodiments or the prior art. Apparently, the drawings in the following description are only exemplary, and those skilled in the art can also obtain other implementation drawings according to the provided drawings without creative work.

The structures, proportions, sizes, etc. shown in this manual are only used to cooperate with the content disclosed in the manual, so that people familiar with this technology can understand and read, and are not used to limit the conditions for the implementation of the present invention, so there is no technical In the substantive meaning above, any modification of structure, change of proportional relationship or adjustment of size shall still fall within the scope of the technical content disclosed in the present invention without affecting the functions and objectives of the present invention. within the range that can be covered.

Fig. 1 is the flow chart of the preparation method of the β-caryophyllenol derivative that the embodiment of the present invention provides;

Fig. 2 is a schematic structural view of a preparation device provided by an embodiment of the present invention;

Fig. 3 is a partial top view of the second cartridge provided by the embodiment of the present invention;

Fig. 4 is a schematic structural diagram of a deceleration gear provided by an embodiment of the present invention;

Fig. 5 is a cross-sectional view of a sealing plate provided by an embodiment of the present invention;

Fig. 6 is a schematic structural diagram of a vertical bar provided by an embodiment of the present invention.

In the picture:

1-Cold and hot water storage tank; 2-mixing unit; 3-stirring and reflux unit;

101-accommodating cavity;

201-the first barrel; 202-the second barrel; 203-connecting pipe; 204-feeding port; 205-titration port; 206-pressure film; Stirring paddle; 210-reduction block; 211-visible window; 212-connecting rod;

2011-extension rod; 2012-stop baffle; 2013-drainage groove;

2081-board body; 2082-sealing ring;

2091-the first horizontal bar; 2092-the second horizontal bar; 2093-the vertical bar; 2094-the diversion groove.

Detailed ways

The implementation mode of the present invention is illustrated by specific specific examples below, and those who are familiar with this technology can easily understand other advantages and effects of the present invention from the contents disclosed in this description. Obviously, the described embodiments are a part of the present invention. , but not all examples. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

As shown in Figure 1, the invention provides a kind of preparation method of β-caryophyllenol derivative, comprising:

100. In the condition of an ice-water bath and the presence of the first solvent, add concentrated sulfuric acid to β-caryophyllene and mix to obtain a mixed solution;

200. After stirring and mixing the above mixed solution at a temperature not higher than 5°C for 8-12 hours, continue to add a saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and the first organic layer is obtained by separation;

300. Distill the first organic layer, collect the distillate, and dry to obtain a crude product;

400. In the presence of the second solvent, mix the crude product, carboxylic acid and catalyst, stir and reflux for 12-24 hours, then continue to add saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and obtain second organic layer;

500. The second organic layer was washed alternately with saturated sodium carbonate and water for 2-3 times, dried, and then eluted by column chromatography to obtain β-caryophyllenol derivatives; wherein,

The eluents in the elution process are petroleum ether and acetone.

In the embodiment of the present invention, by controlling the reaction conditions and the reaction environment, β-caryophyllene and concentrated sulfuric acid are directly mixed and reacted, and the product is dried and then directly reacted with carboxylic acid, and the reacted organic product is directly washed and eluted, A β-caryophyllenol derivative is obtained. The entire reaction process is carried out without introducing other intermediate products, and there is no need to further process other raw materials in the entire reaction process during the preparation process, effectively avoiding the conversion between multiple instruments, and improving the preparation efficiency.

The first solvent here can be a common organic solvent, so that the entire reaction system can be carried out in a solution environment. In a preferred embodiment of the present invention, the first solvent is ethanol or ether.

Further, in order to better improve the productive rate of the whole reaction system, the mixing process in step 100 includes the following steps:

101. Mix β-caryophyllene and the first solvent and stir for 5-10 minutes to obtain a β-caryophyllene solution;

102. Add concentrated sulfuric acid to the β-caryophyllene solution at a rate not greater than 10 mL/min and stir and mix to obtain a mixed solution; and,

In step 100, the concentrated sulfuric acid is concentrated sulfuric acid with a concentration not lower than 93%;

And relative to 1 g of the β-caryophyllene, the amount of the first solvent used is 1-2 mL, and the amount of the concentrated sulfuric acid used is 0.2-0.5 mL.

Likewise, in another preferred embodiment of the present invention, the second solvent is one of chloroform, acetone and petroleum ether;

The catalyst is N, N'-carbonyldiimidazole or 4-dimethylaminopyridine;

And the mixing process in step 400 comprises the following steps:

401. Add the crude product and the carboxylic acid into the second solvent and stir and mix to obtain a mixed solution;

402. Add the catalyst to the above mixed solution at a rate not greater than 10mL/min, then stir and reflux; and,

Relative to 1 g of the β-caryophyllene, the amount of the second solvent is 30-60 mL, the amount of the carboxylic acid is 0.003-0.005 mol, and the amount of the catalyst is 3-8 mL;

The volume ratio of petroleum ether and acetone in the eluent is 3-6:1.

The present invention provides a kind of β-caryophyllenol derivatives prepared according to the above-mentioned preparation method, the structure of the β-caryophyllenol derivatives is shown in formula (I),

Wherein, R is an ester group.

As shown in FIG. 2 , the present invention provides a preparation device for the above-mentioned preparation method, which includes a cold and hot water storage tank 1 formed with an accommodating chamber 101, at least partly arranged in the accommodating chamber 101 a mixing unit 2, and an elution column and a stirring reflux unit 3 arranged outside the cold and hot water storage tank 1; and,

The mixing unit 2 includes a first material cylinder 201 and a second material cylinder 202 arranged at intervals in the accommodating chamber 101, between the first material cylinder 201 and the second material cylinder 202 Through connection through the connecting pipe 203, the first feeding cylinder 201 and the second feeding cylinder 202 are respectively provided with a feeding port 204, and the upper surface of the connecting pipe 203 is vertically provided with a titration port 205. , and one end of the connecting pipe 203 close to the second barrel 202 is provided with a pressure film 206 along the vertical direction;

The bottom of the first storage cylinder 201 or the connecting pipe 203 is closably provided with a discharge pipe 207 extending to the outside of the cold and hot water storage tank 1, and the discharge pipe 207 is connected to the stirring backflow The feeding holes of the unit 3 are detachably connected, and at least part of the side wall of the connecting pipe 203 is formed as a transparent viewing window 211;

The inner wall of the second cartridge 202 is sealed with a sealing plate 208 that can move in the vertical direction, and the feeding port 204 of the second cartridge 202 is located below the sealing plate 208;

A stirring paddle 209 is provided on the inner wall of the connecting pipe 203 .

Here are further examples:

For step 101, β-caryophyllene and the first solvent are directly added through the feeding port 204 on the first feeding cylinder 201, and the raw materials will enter the connecting pipe 203 and the first feeding cylinder 201 (of course, the connecting pipe here The bottom of 203 is on the same plane as the bottom of the first charging cylinder 201 and the second charging cylinder 202. At the same time, in order to ensure the stability of the entire container, the first charging cylinder 201, the second charging cylinder 202 and the connection Pipe 203 further forms an integral structure, does not affect actual use), and the stirring paddle 209 in the connecting pipe 203 starts to stir;

For step 102, the sulfuric acid is directly added through the feed port 204 on the second feed cylinder 202, and then the feed port 204 is sealed, and by pushing down the sealing plate 208, the pressure in the entire second feed cylinder 202 is increased, and then the sulfuric acid Extruded, permeate into the connecting pipe 203 through the pressurized membrane 206, and participate in the mixing reaction (the pressurized membrane 206 here is an acid-resistant reverse osmosis membrane, certainly, the present invention is not limited thereto, those skilled in the art can understand Types can be used here), where the penetration rate of sulfuric acid can be controlled by the driving speed of the sealing plate 208, and then the whole reaction speed and reaction efficiency can be controlled;

For step 200, the whole reaction process can be effectively observed in conjunction with the cooperation of titration port 205 and viewing window 211 (here the bottom of viewing window 211 embedded on connecting pipe 203 is flush with the bottom of connecting pipe 203 to ensure that it can be effectively observed The stratification situation in the whole reaction system, of course, the top of viewing window 211 is flush with connecting pipe 203 top as far as possible, to better observe overall reaction situation), the product after reaction passes through opening discharge pipe 207 and the first place The reaction product can be discharged and collected at the joint of the barrel 201 or the connecting pipe 203 . It should be further explained that the opening and closing structure of the connection between the discharge pipe 207 and the first feeding cylinder 201 or the connecting pipe 203 can adopt a method that can be understood and used by those skilled in the art, for example, refer to the acid formula The piston structure in the burette, etc., of course, the embodiments of the present invention are not limited thereto;

For step 400, the recovered crude product and carboxylic acid and part of the second solvent are added to the first loading cylinder 201, and the catalyst and another part of the second solvent are mixed to exist in the form of a solution, and the second loading cylinder 202 is used to add The way of pressure is further mixed with the mixed liquid in the first storage barrel 201 at a controlled rate (similar to the mixing method in step 102), and then the material is fed into the stirring reflux unit 3 for stirring and reflux, and then passed through the first placing Cartridge 201 is put into, and follow-up operation is carried out under ice-water bath condition.

At the same time, during the entire operation process, the reaction conditions can be effectively controlled by adjusting the water temperature in the cold and hot water storage tank 1. The entire reaction environment can be adjusted at any time, and the preparation can be carried out directly without changing the experimental equipment. It also effectively improves the utilization efficiency of raw materials.

As shown in FIG. 3 , a plurality of deceleration stops 210 are also arranged on the inner wall of the second feeding cylinder 202 along the vertical direction, and the plurality of deceleration stops 210 are arranged below the feeding port 204 ; The two adjacent deceleration blocks 210 are arranged on the opposite inner walls of the second cartridge 202 . That is, a plurality of deceleration stops 210 are arranged in sequence along the bottom of the discharge port 204, so as to avoid that when the raw material is poured inward from the discharge port 204 of the second barrel 202, the raw material will generate a certain pressure due to gravity, resulting in The impact on the pressurized membrane 206 thus leads to problems with slightly uncontrollable reaction rates and reaction times.

At the same time, in order to better guide the speed of the poured raw materials, as shown in FIG. , two adjacent stop plates 2012 are at least partly located on the same vertical plane; The extension rod 2011 extends obliquely downward, and the axis direction of the extension rod 2011 forms an included angle of 10°-30° with the plane where the upper surface of the stop plate 2012 is located.

In a preferred embodiment of the present invention, in order to better guide the flow direction and impact force of the raw material, the stop plate 2012 is formed into a fan shape, and the arc surface of the fan shape is set away from the extension rod 2011 The upper surface of the stop plate 2012 extends from the side close to the extension rod 2011 to the arc surface to form a plurality of concave drainage grooves 2013; the inner bottom surface of the drainage groove 2013 is provided with an arc shaped protrusion, and the height of the arc-shaped protrusion is 1/3-1/2 of the depth of the drainage groove 2013; the distance between the two endpoints of the arc surface is m, and the The distance between the drainage grooves 2013 at the two ends and the two ends of the arc surface is 1/4-1/3 of m. Through such a setting, after the raw material is poured into the second barrel 202, it can basically pass through each stopper plate 2012 in sequence. Thereafter, the flow direction is guided by the drainage groove 2013 so that it is located in the middle, effectively avoiding the impact force given to the pressurized film 206 when it finally falls.

In a preferred embodiment of the present invention, in order to further improve the sealing effect and ensure the controllability of the overall reaction environment, the sealing plate 208 includes a plate body 2081 and a sealing ring 2082 sleeved on the outer surface of the plate body 2081; The sealing plate 208 is connected to a pneumatic unit that drives the sealing plate 208 to move vertically through a connecting rod 212 . At the same time, it is further explained that the sealing plate 208 here is as shown in Figure 5, wherein the inner wall of the sealing ring 2082 near the plate body 2081 is a vertical and smooth surface, so as to fit the plate body 2081 as much as possible, and its outer wall forms It is a plurality of corrugated structures arranged in sequence along the vertical direction, and the heights of the ends of the multiple corrugated structures are the same, thereby forming a multi-channel closed system.

Further, the cold and hot water storage tank 1 is provided with a temperature sensing module, and the temperature sensing module is electrically connected to an alarm module through the control module. When the water temperature in the cold and hot water storage tank 1 is greater than or lower than the set temperature When the threshold is reached, the control module can receive the signal and control the alarm module to give an alarm.

When the raw material in the second barrel 202 enters the connecting pipe 203 after being squeezed, it often infiltrates from the lower part, especially in the case of a small test, the amount of raw material is not large enough, and it is easy to infiltrate from the lower part. Therefore, in a preferred embodiment of the present invention, the stirring blade 209 is further configured to include a first horizontal bar 2091 and a second horizontal bar 2092, and the first horizontal bar 2091 and the second horizontal bar 2092 They are connected by a plurality of vertical rods 2093; as shown in Figure 6, a plurality of diversion grooves 2094 are formed on the outer surface of the vertical rods 2093 along the vertical direction, and the diversion grooves arranged on the upper part of the vertical rods 2093 2094 extends obliquely downward, and the flow guide groove 2094 disposed at the bottom of the vertical bar 2093 extends obliquely upward. During the rotation process, the lower diversion groove 2094 drives the lower solution to spiral upward, and the upper diversion groove 2094 drives the upper solution downward to better ensure the stability and uniformity of the entire system.

Further description will be given below by way of examples.

Example 1

Fill ice water into the cold and hot water storage tank, add 5g (0.02447mol) β-caryophyllene and 10mL ether to the first storage cylinder, start the stirring paddle to rotate and stir; add 2g of 98% concentrated sulfuric acid to the second storage In the cylinder, slowly push the sealing plate through the air pump until the sulfuric acid enters the connecting pipe; continue to stir for 10h under this condition, then add saturated sodium carbonate dropwise through the titration port to separate layers, open the discharge pipe, collect the first organic layer, distill and dry , get the crude product;

Mix the above-mentioned crude product, 0.02mol acetic acid and 180mL petroleum ether into the first cylinder for stirring, mix 5mL of 4-dimethylaminopyridine and 20mL petroleum ether into the second cylinder, push it into the connecting pipe for further mixing, Feed through the discharge pipe into the stirring reflux unit and stir and reflux for 18 hours, then import the collected material into the first feeding cylinder and continue to add saturated sodium carbonate dropwise under the condition of ice-water bath to separate layers, collect the second organic layer and pass through saturated sodium carbonate sequentially Alternately washed with water for 3 times, and then eluted with petroleum ether and acetone at a ratio of 5:1 to collect the β-caryophyllenol derivative A1. (obtaining product A1 is 4.5g, productive rate 70.29%)

Example 2

The operation was carried out as in Example 1, except that benzoic acid was used instead of acetic acid, and the β-caryophyllenol derivative A2 was collected. (obtaining product A1 is 5.93g, productive rate 74.79%)

Example 3

The operation was carried out as in Example 1, except that p-nitrobenzoic acid was used instead of acetic acid, and the β-caryophyllenol derivative A3 was collected. (obtaining product A1 is 6.7g, productive rate 74.2%)

From the above examples, it can be seen that even if the entire operation steps are simplified, the production rate can be effectively guaranteed through the control of the entire preparation system, and the entire preparation process is simple, which is easy for further research on its derivatives.

Although the present invention has been described in detail with general descriptions and specific examples above, it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present invention. Therefore, the modifications or improvements made on the basis of not departing from the spirit of the present invention all belong to the protection scope of the present invention.

Claims (10)

1. a preparation method of β-caryophyllene alcohol derivatives, characterized in that, comprising: 100. In the condition of an ice-water bath and the presence of the first solvent, add concentrated sulfuric acid to β-caryophyllene and mix to obtain a mixed solution; 200. After stirring and mixing the above mixed solution at a temperature not higher than 5°C for 8-12 hours, continue to add a saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and the first organic layer is obtained by separation; 300. Distill the first organic layer, collect the distillate, and dry to obtain a crude product; 400. In the presence of the second solvent, mix the crude product, carboxylic acid and catalyst, stir and reflux for 12-24 hours, then continue to add saturated sodium carbonate solution dropwise to it in an ice-water bath until the layers are separated, and obtain second organic layer; 500. The second organic layer was washed alternately with saturated sodium carbonate and water for 2-3 times, dried, and then eluted by column chromatography to obtain β-caryophyllenol derivatives; wherein, The eluents in the elution process are petroleum ether and acetone. 2. the preparation method of a kind of β-caryophyllenol derivative according to claim 1, is characterized in that, described first solvent is ethanol or ether; And the mixing process in step 100 comprises the following steps: 101. Mix β-caryophyllene and the first solvent and stir for 5-10 minutes to obtain a β-caryophyllene solution; 102. Add concentrated sulfuric acid to the β-caryophyllene solution at a rate not greater than 10 mL/min and stir and mix to obtain a mixed solution; and, In step 100, the concentrated sulfuric acid is concentrated sulfuric acid with a concentration not lower than 93%; And relative to 1 g of the β-caryophyllene, the amount of the first solvent used is 1-2 mL, and the amount of the concentrated sulfuric acid used is 0.2-0.5 mL. 3. the preparation method of a kind of β-caryophyllenol derivative according to claim 1 and 2, is characterized in that, described second solvent is the one in chloroform, acetone and sherwood oil; The catalyst is N, N'-carbonyldiimidazole or 4-dimethylaminopyridine; And the mixing process in step 400 comprises the following steps: 401. Add the crude product and the carboxylic acid into the second solvent and stir and mix to obtain a mixed solution; 402. Add the catalyst to the above mixed solution at a rate not greater than 10mL/min, then stir and reflux; and, Relative to 1 g of the β-caryophyllene, the amount of the second solvent is 30-60 mL, the amount of the carboxylic acid is 0.003-0.005 mol, and the amount of the catalyst is 3-8 mL; The volume ratio of petroleum ether and acetone in the eluent is 3-6:1. 4. a kind of β-caryophyllenol derivatives that the preparation method described in any one according to claim 1-3 makes, it is characterized in that, the structure of described β-caryophyllenol derivatives is as formula (I) as shown, Wherein, R is an ester group. 5. A preparation device for the preparation method according to claim 1-3, characterized in that, it comprises a cold and hot water placement tank (1) formed with an accommodating cavity (101), at least partly arranged in the accommodating The mixing unit (2) in the cavity (101), and the elution column and the stirring reflux unit (3) arranged outside the cold and hot water storage tank (1); and, The mixing unit (2) includes a first material cylinder (201) and a second material cylinder (202) arranged at intervals in the accommodation chamber (101), and the first material cylinder (201) and The second charging cylinders (202) are connected through a connecting pipe (203), and the first charging cylinder (201) and the second charging cylinder (202) are each provided with a feeding port (204) ), the upper surface of the connecting pipe (203) is provided with a titration port (205) through the vertical direction, and one end of the connecting pipe (203) close to the second charging cylinder (202) is vertically The direction is provided with a pressure film (206); The bottom of the first storage cylinder (201) or the connecting pipe (203) can be closedly provided with a discharge pipe (207) extending to the outside of the cold and hot water storage tank (1), and the discharge pipe (207) can be closed. The material pipe (207) is detachably connected with the feeding hole of the stirring reflux unit (3), and the side wall of the connecting pipe (203) is at least partially formed as a transparent viewing window (211); A sealing plate (208) capable of moving in the vertical direction is sealed on the inner side wall of the second storage cylinder (202), and the feeding port (204) of the second storage cylinder (202) is located at the Below the sealing plate (208); A stirring blade (209) is arranged on the inner side wall of the connecting pipe (203). 6. The preparation device according to claim 5, characterized in that, a plurality of deceleration stops (210) are also arranged vertically on the inner side wall of the second charging cylinder (202), and the plurality of deceleration blocks (210) The deceleration block (210) is arranged below the feeding port (204); Two adjacent deceleration blocks (210) are arranged on the opposite inner sidewalls of the second loading cylinder (202). 7. The preparation device according to claim 6, characterized in that, the deceleration block (201) comprises an extension rod (2011) connected sequentially from the inner side wall of the second barrel (202) and a stopper. The baffle (2012), two adjacent stop baffles (2012) are at least partly located on the same vertical plane; And the axial direction of the extension rod (2011) forms an included angle with the vertical direction of 15°-45°, the stop plate (2012) extends obliquely downward from the extension rod (2011), and the The axial direction of the extension rod (2011) forms an included angle of 10°-30° with the plane where the upper surface of the stop plate (2012) is located. 8. The preparation device according to claim 7, characterized in that, the stop plate (2012) is formed into a fan shape, and the arc surface of the fan shape is arranged at an end away from the extension rod (2011), the The upper surface of the stopper plate (2012) extends from the side close to the extension rod (2011) to the arc surface to form a plurality of concave drainage grooves (2013); An arc-shaped protrusion is provided on the inner bottom surface of the drainage groove (2013), and the height of the arc-shaped protrusion is 1/3-1/2 of the depth of the drainage groove (2013); The distance between the two endpoints of the arc surface is m, and the distance between the drainage groove (2013) near the two endpoints of the arc surface and the two endpoints of the arc surface is 1/4- 1/3. 9. The preparation device according to any one of claims 5-8, characterized in that, the sealing plate (208) comprises a plate body (2081) and a sleeve sleeved on the outer surface of the plate body (2081) Sealing ring (2082); The sealing plate (208) is connected to the pneumatic unit that drives the sealing plate (208) to move vertically through a connecting rod (212); The cold and hot water storage tank (1) is provided with a temperature sensing module, and the temperature sensing module is electrically connected to an alarm module through the control module. When the water temperature in the cold and hot water storage tank (1) is greater than or lower than the set When the temperature threshold is reached, the control module can receive a signal and control the alarm module to give an alarm. 10. The preparation device according to any one of claims 5-8, characterized in that, the stirring blade (209) comprises a horizontally arranged first crossbar (2091) and a second crossbar (2092), and The first horizontal bar (2091) and the second horizontal bar (2092) are connected by a plurality of vertical bars (2093); The outer surface of the vertical rod (2093) is formed with a plurality of diversion grooves (2094) along the vertical direction, and the diversion grooves (2094) arranged on the upper part of the vertical rod (2093) extend obliquely downward, and are arranged on The diversion groove (2094) at the lower part of the vertical bar (2093) extends obliquely upward.