CN110615737A - Beta-caryophyllenol derivative and preparation method and preparation device thereof - Google Patents
Beta-caryophyllenol derivative and preparation method and preparation device thereof Download PDFInfo
- Publication number
- CN110615737A CN110615737A CN201910978259.6A CN201910978259A CN110615737A CN 110615737 A CN110615737 A CN 110615737A CN 201910978259 A CN201910978259 A CN 201910978259A CN 110615737 A CN110615737 A CN 110615737A
- Authority
- CN
- China
- Prior art keywords
- beta
- stirring
- preparation
- caryophyllenol
- mixing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/48—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by oxidation reactions with formation of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
- C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/78—Benzoic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/32—All rings being cycloaliphatic the ring system containing at least eleven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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
Technical Field
The embodiment of the invention relates to the technical field of preparation of beta-caryophyllenol derivatives, and particularly relates to a beta-caryophyllenol derivative and a preparation method and a preparation device thereof.
Background
Beta-caryophyllenol, also known as eugenol, is a sesquiterpene alcohol compound, has strong physiological activity, is used in a plurality of fields such as food seasoning or medicine, and has few reports on derivatives thereof. Since the derivatives (e.g., ester derivatives) have similar structures, the substitution of the substituents may result in different structures and possibly other physiologically active substances.
However, since the beta-caryophyllenol generally exists in some plants, the plants need to be further processed and separated after extracting essential oil, so that the yield is rare, the cost is high, and the way of extracting the natural beta-caryophyllenol is more complicated. Therefore, the preparation of the beta-caryophyllenol is usually obtained by processing and synthesizing the beta-caryophyllene. Meanwhile, even if the beta-caryophyllenol is obtained, because the alcoholic hydroxyl group of the beta-caryophyllenol is positioned at the bridgehead carbon and is tertiary alcohol with large steric hindrance, the requirements on the change of reaction conditions are more in the process of preparing the derivative of the beta-caryophyllenol, the reaction process is more complicated, and different appliances need to be replaced according to different conditions in the preparation process.
As mentioned above, the derivatives are various in types according to the difference of the substituents, so that under the premise of not defining the physiological activity of the derivatives, the different derivatives are often prepared by replacing a large amount of raw materials with different substituents, which undoubtedly causes the need of changing back and forth in more preparation devices, resulting in the complexity of the whole preparation process. And due to the fact, the preparation and research of the derivatives are rarely reported.
Disclosure of Invention
Therefore, embodiments of the present invention provide a β -caryophyllenol derivative, and a preparation method and a preparation apparatus thereof, so as to simplify the entire preparation process by performing one-time preparation on the entire preparation process from β -caryophyllene to β -caryophyllenol derivative, and adjust the overall controllability of the preparation apparatus on the basis of simplification, thereby solving the problems of complicated preparation process and poor operability.
In order to achieve the above object, an embodiment of the present invention provides the following:
in one aspect of the embodiments of the present invention, there is provided a method for preparing a β -caryophyllenol derivative, including:
100. adding concentrated sulfuric acid into beta-caryophyllene in an ice water bath in the presence of a first solvent, and mixing to obtain a mixed solution;
200. stirring and mixing the mixed solution for 8-12h at the temperature of not higher than 5 ℃, continuously dropwise adding a saturated sodium carbonate solution into the mixed solution under the ice-water bath condition until the mixed solution is layered, and separating to obtain a first organic layer;
300. distilling the first organic layer, collecting distillate, and drying to obtain a crude product;
400. in the presence of a second solvent, mixing the crude product, carboxylic acid and a catalyst, stirring and refluxing for 12-24h, continuously dropwise adding a saturated sodium carbonate solution into the mixture under the condition of ice-water bath until layering, and separating to obtain a second organic layer;
500. washing the second organic layer with saturated sodium carbonate and water for 2-3 times, drying, and eluting by column chromatography to obtain beta-caryophyllenol derivative; wherein the content of the first and second substances,
the eluent used in the elution process is petroleum ether and acetone.
As a preferable embodiment of the present invention, the first solvent is ethanol or diethyl ether;
and the mixing process in step 100 comprises the following steps:
101. mixing beta-caryophyllene and a first solvent, and stirring for 5-10min to obtain a beta-caryophyllene solution;
102. adding concentrated sulfuric acid into the beta-caryophyllene solution at a speed of not more than 10mL/min, and stirring and mixing to obtain a mixed solution; and the number of the first and second electrodes,
in step 100, the concentrated sulfuric acid is concentrated sulfuric acid with the concentration not lower than 93%;
and relative to 1g of the beta-caryophyllene, the dosage of the first solvent is 1-2mL, and the dosage of the concentrated sulfuric acid is 0.2-0.5 mL.
As a preferable 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 steps of:
401. adding the crude product and the carboxylic acid into a second solvent, and stirring and mixing to obtain a mixed solution;
402. adding a catalyst into the mixed solution at a speed of not more than 10mL/min, and stirring and refluxing; and the number of the first and second electrodes,
the dosage of the second solvent is 30-60mL, the dosage of the carboxylic acid is 0.003-0.005mol, and the dosage of the catalyst is 3-8mL relative to 1g of the beta-caryophyllene;
the volume ratio of the petroleum ether to the 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 preparation method, wherein the β -caryophyllenol derivative has a structure shown in formula (I),
wherein R is an ester group.
In another aspect of an embodiment of the present invention, there is provided a preparation apparatus for the preparation method as described above, including a hot and cold water placing tank formed with a containing cavity, a mixing unit at least partially disposed in the containing cavity, and an elution column and a stirring reflux unit disposed outside the hot and cold water placing tank; and the number of the first and second electrodes,
the mixing unit comprises a first material placing barrel and a second material placing barrel which are arranged in the accommodating cavity at intervals, the first material placing barrel and the second material placing barrel are communicated and connected through a connecting pipe, the first material placing barrel and the second material placing barrel are respectively provided with a feeding port, the upper surface of the connecting pipe is vertically provided with a titration port in a through mode, and one end, close to the second material placing barrel, of the connecting pipe is provided with a pressurizing film in a vertical mode;
a discharging pipe extending to the outside of the cold and hot water placing groove is arranged at the bottom of the first material placing barrel or the connecting pipe in a closable manner, the discharging pipe is detachably communicated with a feeding hole of the stirring and refluxing unit, and at least part of the side wall of the connecting pipe is formed into a transparent visual window;
a sealing plate capable of moving along the vertical direction is hermetically arranged on the inner side wall of the second charging barrel, and a charging opening of the second charging barrel is positioned below the sealing plate;
and stirring paddles are arranged on the inner side wall of the connecting pipe.
As a preferable scheme of the invention, a plurality of speed-reducing stoppers are further arranged on the inner side wall of the second charging barrel along the vertical direction, and the speed-reducing stoppers are arranged below the charging opening;
two adjacent speed-reducing stoppers are arranged on the opposite inner side walls of the second charging barrel.
As a preferable scheme of the invention, the deceleration stopper comprises an extension rod and a stop plate which are sequentially connected from the inner side wall of the second charging barrel, and at least part of two adjacent stop plates are positioned on the same vertical surface;
and the axis direction of the extension rod and the vertical direction form an included angle of 15-45 degrees, the stop plate extends downwards from the extension rod in an inclined mode, and the axis direction of the extension rod and the plane where the upper surface of the stop plate is located form an included angle of 10-30 degrees.
As a preferable scheme of the invention, the stop plate is formed into a fan shape, the arc surface of the fan shape is arranged at one end far away from the extension rod, and a plurality of sunken drainage grooves are formed in the upper surface of the stop plate in a manner that the upper surface extends from one side close to the extension rod to the arc surface;
an arc-shaped bulge is arranged on the inner bottom surface of the drainage groove, and the height of the arc-shaped bulge is 1/3-1/2 of the depth of the drainage groove;
the distance between two end points of the cambered surface is m, and the distance between the drainage grooves close to the two end points of the cambered surface and the two end points of the cambered surface is 1/4-1/3 of m.
As a preferred scheme of the present invention, the sealing plate includes a plate body and a sealing ring sleeved on an outer side surface of the plate body;
the sealing plate is connected to a pneumatic unit which drives the sealing plate to move along the vertical direction through a connecting rod;
be provided with temperature sensing module in the cold and hot water standing groove, temperature sensing module has alarm module through the control module electricity, works as when the temperature in the cold and hot water standing groove is greater than or is less than the temperature threshold value that sets up, control module can received signal and control alarm module warns.
As a preferable scheme of the invention, the stirring paddle comprises a first cross bar and a second cross bar which are horizontally arranged, and the first cross bar is connected with the second cross bar through a plurality of vertical bars;
the lateral surface of montant is formed with many guiding gutters along vertical direction, and set up in the guiding gutter on montant upper portion extends downwards to one side, set up in the guiding gutter of montant lower part extends upwards to one side.
The embodiment of the invention has the following advantages:
1. the beta-caryophyllene is directly subjected to multi-step operation to prepare the beta-caryophyllene alcohol derivative, and the beta-caryophyllene alcohol derivative is only subjected to washing, eluting and other operations in the last step, so that the operations of multiple times of washing and the like in the preparation process are avoided, the effective utilization of raw materials is facilitated, in addition to the drying and stirring reflux after primary distillation which independently exists in the whole process, other steps can be completed in one vessel in the embodiment of the invention, the conversion among multiple vessels is avoided, and the preparation efficiency is effectively improved.
2. The pressure membrane and the sealing plate are matched, so that the flow rate control of the whole feeding process is improved by aiming at the concentrated sulfuric acid which is a raw material, the controllability of the whole preparation process is further improved, and the problems of serious carbonization and the like caused by poor flow rate control of sulfuric acid in the conventional sulfuric acid adding process are solved. Meanwhile, a connecting pipe is arranged between the first material placing barrel and the second material placing barrel, so that a relatively proper space is formed, and raw materials on two sides can be mixed at a more reasonable speed. And in the whole operation process, the controllability of the separation of the layered products can be better controlled when the materials are discharged through the discharging pipe due to the further arrangement of the visual window.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. It should be apparent that the drawings in the following description are merely exemplary, and that other embodiments can be derived from the drawings provided by those of ordinary skill in the art without inventive effort.
The structures, ratios, sizes, and the like shown in the present specification are only used for matching with the contents disclosed in the specification, so as to be understood and read by those skilled in the art, and are not used to limit the conditions that the present invention can be implemented, so that the present invention has no technical significance, and any structural modifications, changes in the ratio relationship, or adjustments of the sizes, without affecting the effects and the achievable by the present invention, should still fall within the range that the technical contents disclosed in the present invention can cover.
FIG. 1 is a flow chart of a process for preparing a β -caryophyllenol derivative provided in an embodiment of the present invention;
FIG. 2 is a schematic structural diagram of a manufacturing apparatus provided in an embodiment of the present invention;
FIG. 3 is a partial top view of a second material loading cartridge provided by an embodiment of the present invention;
FIG. 4 is a schematic diagram of a deceleration stop provided by an embodiment of the present invention;
FIG. 5 is a cross-sectional view of a seal plate provided by an embodiment of the present invention;
fig. 6 is a schematic structural diagram of a vertical rod according to an embodiment of the present invention.
In the figure:
1-cold and hot water placing grooves; 2-a mixing unit; 3-stirring and refluxing unit;
101-a containment chamber;
201-a first cartridge; 202-a second charging barrel; 203-connecting pipe; 204-a feed inlet; 205-titration port; 206-pressure membrane; 207-discharge pipe; 208-a sealing plate; 209-stirring slurry; 210-a deceleration stop; 211-a viewable window; 212-a connecting rod;
2011-extension rod; 2012-a stopper plate; 2013-a drainage groove;
2081-a plate body; 2082-sealing ring;
2091-first cross bar; 2092-second cross bar; 2093-vertical bar; 2094-guiding gutter.
Detailed Description
The present invention is described in terms of particular embodiments, other advantages and features of the invention will become apparent to those skilled in the art from the following disclosure, and it is to be understood that the described embodiments are merely exemplary of the invention and that it is not intended to limit the invention to the particular embodiments disclosed. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
As shown in fig. 1, the present invention provides a method for preparing a β -caryophyllenol derivative, comprising:
100. adding concentrated sulfuric acid into beta-caryophyllene in an ice water bath in the presence of a first solvent, and mixing to obtain a mixed solution;
200. stirring and mixing the mixed solution for 8-12h at the temperature of not higher than 5 ℃, continuously dropwise adding a saturated sodium carbonate solution into the mixed solution under the ice-water bath condition until the mixed solution is layered, and separating to obtain a first organic layer;
300. distilling the first organic layer, collecting distillate, and drying to obtain a crude product;
400. in the presence of a second solvent, mixing the crude product, carboxylic acid and a catalyst, stirring and refluxing for 12-24h, continuously dropwise adding a saturated sodium carbonate solution into the mixture under the condition of ice-water bath until layering, and separating to obtain a second organic layer;
500. washing the second organic layer with saturated sodium carbonate and water for 2-3 times, drying, and eluting by column chromatography to obtain beta-caryophyllenol derivative; wherein the content of the first and second substances,
the eluent used in the elution process is petroleum ether and acetone.
According to the embodiment of the invention, by controlling reaction conditions and reaction environment, beta-caryophyllene and concentrated sulfuric acid are directly mixed for reaction, the product is dried and then directly reacts with carboxylic acid, and the organic product after reaction is directly washed and eluted to obtain the beta-caryophyllene alcohol derivative. The whole reaction process is carried out in the process of not introducing other intermediate products, and other raw materials and the like in the whole reaction process do not need to be further processed in the preparation process, so that the conversion among a plurality of appliances is effectively avoided, and the preparation efficiency is improved.
The first solvent can be selected from common organic solvents, so that the whole reaction system is carried out in a solution environment, and in a preferred embodiment of the invention, the first solvent is ethanol or diethyl ether.
Further, in order to better improve the yield of the whole reaction system, the mixing process in step 100 comprises the following steps:
101. mixing beta-caryophyllene and a first solvent, and stirring for 5-10min to obtain a beta-caryophyllene solution;
102. adding concentrated sulfuric acid into the beta-caryophyllene solution at a speed of not more than 10mL/min, and stirring and mixing to obtain a mixed solution; and the number of the first and second electrodes,
in step 100, the concentrated sulfuric acid is concentrated sulfuric acid with the concentration not lower than 93%;
and relative to 1g of the beta-caryophyllene, the dosage of the first solvent is 1-2mL, and the dosage of the concentrated sulfuric acid 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 steps of:
401. adding the crude product and the carboxylic acid into a second solvent, and stirring and mixing to obtain a mixed solution;
402. adding a catalyst into the mixed solution at a speed of not more than 10mL/min, and stirring and refluxing; and the number of the first and second electrodes,
the dosage of the second solvent is 30-60mL, the dosage of the carboxylic acid is 0.003-0.005mol, and the dosage of the catalyst is 3-8mL relative to 1g of the beta-caryophyllene;
the volume ratio of the petroleum ether to the acetone in the eluent is 3-6: 1.
The invention provides a beta-caryophyllenol derivative prepared by the preparation method, the structure of the beta-caryophyllenol derivative is shown as the formula (I),
wherein R is an ester group.
As shown in fig. 2, the present invention provides a preparation apparatus for the preparation method as described above, comprising a hot and cold water holding tank 1 formed with a holding chamber 101, a mixing unit 2 disposed at least partially in the holding chamber 101, and an elution column and a reflux mixer unit 3 disposed outside the hot and cold water holding tank 1; and the number of the first and second electrodes,
the mixing unit 2 comprises a first material placing barrel 201 and a second material placing barrel 202 which are arranged in the accommodating cavity 101 at intervals, the first material placing barrel 201 and the second material placing barrel 202 are connected in a penetrating manner through a connecting pipe 203, the first material placing barrel 201 and the second material placing barrel 202 are respectively provided with a material inlet 204, the upper surface of the connecting pipe 203 is provided with a titration opening 205 in a penetrating manner along the vertical direction, and one end, close to the second material placing barrel 202, in the connecting pipe 203 is provided with a pressurizing film 206 along the vertical direction;
a discharge pipe 207 extending to the outside of the cold and hot water placing tank 1 is arranged at the bottom of the first charging barrel 201 or the connecting pipe 203 in a closable manner, the discharge pipe 207 is detachably communicated with a feeding hole of the stirring and refluxing unit 3, and the side wall of the connecting pipe 203 is at least partially formed into a transparent visual window 211;
a sealing plate 208 capable of moving in the vertical direction is hermetically arranged on the inner side wall of the second charging barrel 202, and the feed inlet 204 of the second charging barrel 202 is positioned below the sealing plate 208;
the inner side wall of the connecting pipe 203 is provided with a stirring paddle 209.
Further illustration is made here:
for step 101, directly adding β -caryophyllene and the first solvent through the feeding port 204 on the first charging barrel 201, the raw materials enter the connecting tube 203 and the first charging barrel 201 (of course, the bottom of the connecting tube 203 and the bottoms of the first charging barrel 201 and the second charging barrel 202 are on the same plane, meanwhile, in order to ensure the stability of the whole container, the first charging barrel 201, the second charging barrel 202 and the connecting tube 203 are further formed into an integrated structure, and do not affect the actual use), and the stirring paddle 209 in the connecting tube 203 starts to stir;
for step 102, sulfuric acid is directly added through the feed port 204 on the second charging barrel 202, then the feed port 204 is sealed, the sealing plate 208 is pushed downwards to increase the pressure in the second charging barrel 202, so that the sulfuric acid is extruded, permeates into the connecting pipe 203 through the pressurized membrane 206 and participates in the mixing reaction (the pressurized membrane 206 is an acid-resistant reverse osmosis membrane, although the invention is not limited thereto, and the type that can be understood by those skilled in the art can be used here), here, the permeation speed of the sulfuric acid can be controlled by the pushing speed of the sealing plate 208, and further, the whole reaction speed and the reaction efficiency can be controlled;
in step 200, the whole reaction process can be effectively observed by combining the matching of the titration opening 205 and the visible window 211 (here, the bottom of the visible window 211 embedded in the connecting pipe 203 is flush with the bottom of the connecting pipe 203 to ensure that the layering condition in the whole reaction system can be effectively observed, of course, the top of the visible window 211 is flush with the top of the connecting pipe 203 as much as possible to better observe the whole reaction condition), and the reaction product can be discharged and collected by opening the connecting part of the discharging pipe 207 and the first charging barrel 201 or the connecting pipe 203. It should be further noted that, the opening and closing structure at the connection position of the discharging pipe 207 and the first charging barrel 201 or the connecting pipe 203 may be in a manner that can be understood and used by those skilled in the art, for example, reference may be made to a piston structure in an acid burette, etc., and of course, the embodiment of the present invention is not limited thereto;
for step 400, the recovered crude product, the carboxylic acid and a part of the second solvent are added into the first charging barrel 201, the catalyst and another part of the second solvent are mixed to exist in the form of solution, and are further mixed with the mixed solution in the first charging barrel 201 in a pressurizing manner through the second charging barrel 202 at a controlled rate (similar to the mixing manner in step 102), and then the mixture is discharged into the stirring and refluxing unit 3 for stirring and refluxing, and after the completion, the mixture is placed into the first charging barrel 201, and the subsequent operation is performed under the ice-water bath condition.
Meanwhile, in the whole operation process, the reaction conditions can be effectively controlled by adjusting the water temperature in the cold and hot water placing groove 1, the whole reaction environment can be adjusted at any time, the preparation is directly carried out on the premise of not changing the experimental apparatus basically, and the utilization efficiency of the raw materials is also effectively improved.
As shown in fig. 3, a plurality of deceleration stoppers 210 are further disposed on the inner side wall of the second material placing barrel 202 along the vertical direction, and the deceleration stoppers 210 are disposed below the material feeding port 204; two adjacent deceleration stoppers 210 are disposed on opposite inner sidewalls of the second charging barrel 202. That is, the plurality of decelerating blocking members 210 are sequentially arranged below the discharge port 204, so that the problem that when the raw material is poured inwards from the discharge port 204 of the second charging barrel 202, the raw material generates certain pressure due to the action of gravity, so that the pressurized membrane 206 is impacted, and the reaction rate and the reaction time are not controlled slightly is solved.
Meanwhile, in order to better guide the speed of the poured raw material, as shown in fig. 4, the decelerating barrier 201 includes an extension rod 2011 and a stop plate 2012 which are sequentially connected from the inner side wall of the second charging barrel 202, and two adjacent stop plates 2012 are at least partially located on the same vertical plane; and the axis direction of extension rod 2011 and vertical direction form the contained angle of 15 ° -45 °, backstop plate 2012 certainly extension rod 2011 extends downwards to the slant, and the axis direction of extension rod 2011 and the plane that the upper surface of backstop plate 2012 is located form the contained angle of 10 ° -30 °.
In a preferred embodiment of the present invention, in order to better guide the flow direction and the impact force of the raw material, the stopper 2012 is formed in a fan shape, the arc surface of the fan shape is disposed at an end far away from the extension bar 2011, and a plurality of concave drainage grooves 2013 are formed in the upper surface of the stopper 2012 extending from a side close to the extension bar 2011 to the arc surface; an arc-shaped bulge is arranged on the inner bottom surface of the drainage groove 2013, and the height of the arc-shaped bulge is 1/3-1/2 of the depth of the drainage groove 2013; the distance between the two end points of the cambered surface is m, and the distance between the drainage groove 2013 close to the two end points of the cambered surface and the two end points of the cambered surface is 1/4-1/3 of m. Through the arrangement, the raw materials can basically pass through each stop plate 2012 in sequence after being poured into the second material placing barrel 202, meanwhile, the impact stress is further broken through along with the arrangement of the arc-shaped bulges, and the raw materials are guided in the flow direction through the drainage groove 2013 and are located in the middle, so that the impact force on the pressurizing film 206 when the raw materials finally fall is effectively avoided.
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 an outer side surface of the plate body 2081; the sealing plate 208 is connected to a pneumatic unit that moves the sealing plate 208 in a vertical direction by a connecting rod 212. Meanwhile, it is further illustrated that, as shown in fig. 5, the inner side wall of the sealing plate 208, which is close to the plate body 2081, of the sealing ring 2082 is a vertical and smooth surface so as to be attached to the plate body 2081 as much as possible, the outer side wall of the sealing plate is formed into a plurality of corrugated structures which are sequentially arranged along the vertical direction, and the heights of the end points of the plurality of corrugated structures are the same, so that a multi-sealing system is formed.
Further, a temperature sensing module is arranged in the cold and hot water placing groove 1, the temperature sensing module is electrically connected with an alarm module through a control module, and when the water temperature in the cold and hot water placing groove 1 is larger than or smaller than a set temperature threshold value, the control module can receive a signal and control the alarm module to warn.
In the preferred embodiment of the present invention, the stirring paddle 209 further includes a first horizontal bar 2091 and a second horizontal bar 2092 which are horizontally disposed, and the first horizontal bar 2091 and the second horizontal bar 2092 are connected to each other through a plurality of vertical bars 2093; as shown in fig. 6, a plurality of flow guide grooves 2094 are formed on the outer side surface of the vertical rod 2093 in the vertical direction, the flow guide grooves 2094 disposed on the upper portion of the vertical rod 2093 extend obliquely downward, and the flow guide grooves 2094 disposed on the lower portion of the vertical rod 2093 extend obliquely upward. In the rotating process, the lower diversion groove 2094 drives the lower solution to rotate upwards in a spiral manner, and the upper diversion groove 2094 drives the upper solution downwards, so that the stability and uniformity of the whole system are better ensured.
The following examples further illustrate the present invention.
Example 1
Filling ice water into a cold and hot water placing groove, adding 5g (0.02447mol) of beta-caryophyllene and 10mL of diethyl ether into a first material placing barrel, and starting a stirring paddle to stir in a rotating manner; adding 2g of 98% concentrated sulfuric acid into a second charging barrel, and slowly pushing a sealing plate by an air pump until the sulfuric acid enters a connecting pipe; continuously stirring for 10 hours under the condition, then dropwise adding saturated sodium carbonate through a titration port until layering, opening a discharging pipe, collecting a first organic layer, distilling and drying to obtain a crude product;
mixing the crude product, 0.02mol of acetic acid and 180mL of petroleum ether, adding the mixture into a first material placing cylinder, stirring, adding 5mL of 4-dimethylaminopyridine and 20mL of petroleum ether into a second material placing cylinder, pushing the mixture into a connecting pipe for further mixing, discharging the mixture into a stirring and refluxing unit through a discharging pipe, stirring and refluxing for 18 hours, introducing the collected matter into the first material placing cylinder, continuously dripping saturated sodium carbonate under the condition of ice-water bath until layering, collecting a second organic layer, alternately washing the second organic layer for 3 times by the saturated sodium carbonate and water, and then mixing the organic layer by the petroleum ether and the acetone according to the proportion of 5: 1, and collecting the beta-caryophyllenol derivative A1. (product A1 was obtained in 4.5g, yield 70.29%)
Example 2
The procedure was as in example 1, except that benzoic acid was used instead of acetic acid, and beta-caryophyllenol derivative A2 was collected. (product A1 was obtained in 5.93g, yield 74.79%)
Example 3
The procedure was as in example 1, except that acetic acid was replaced with p-nitrobenzoic acid, and beta-caryophyllenol derivative A3 was collected. (product A1 was obtained in 6.7g, 74.2% yield)
As can be seen from the above examples, even though the whole operation steps are simplified, the yield is effectively ensured by controlling the whole preparation system, and the whole preparation process is simple and is easy to further study the derivatives thereof.
Although the invention has been described in detail above with reference to a general description and specific examples, it will be apparent to one skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. A preparation method of a beta-caryophyllenol derivative is characterized by comprising the following steps:
100. adding concentrated sulfuric acid into beta-caryophyllene in an ice water bath in the presence of a first solvent, and mixing to obtain a mixed solution;
200. stirring and mixing the mixed solution for 8-12h at the temperature of not higher than 5 ℃, continuously dropwise adding a saturated sodium carbonate solution into the mixed solution under the ice-water bath condition until the mixed solution is layered, and separating to obtain a first organic layer;
300. distilling the first organic layer, collecting distillate, and drying to obtain a crude product;
400. in the presence of a second solvent, mixing the crude product, carboxylic acid and a catalyst, stirring and refluxing for 12-24h, continuously dropwise adding a saturated sodium carbonate solution into the mixture under the condition of ice-water bath until layering, and separating to obtain a second organic layer;
500. washing the second organic layer with saturated sodium carbonate and water for 2-3 times, drying, and eluting by column chromatography to obtain beta-caryophyllenol derivative; wherein the content of the first and second substances,
the eluent used in the elution process is petroleum ether and acetone.
2. The method for preparing β -caryophyllenol derivative according to claim 1, wherein said first solvent is ethanol or diethyl ether;
and the mixing process in step 100 comprises the following steps:
101. mixing beta-caryophyllene and a first solvent, and stirring for 5-10min to obtain a beta-caryophyllene solution;
102. adding concentrated sulfuric acid into the beta-caryophyllene solution at a speed of not more than 10mL/min, and stirring and mixing to obtain a mixed solution; and the number of the first and second electrodes,
in step 100, the concentrated sulfuric acid is concentrated sulfuric acid with the concentration not lower than 93%;
and relative to 1g of the beta-caryophyllene, the dosage of the first solvent is 1-2mL, and the dosage of the concentrated sulfuric acid is 0.2-0.5 mL.
3. The method for producing a β -caryophyllenol derivative according to claim 1 or 2, wherein said 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 steps of:
401. adding the crude product and the carboxylic acid into a second solvent, and stirring and mixing to obtain a mixed solution;
402. adding a catalyst into the mixed solution at a speed of not more than 10mL/min, and stirring and refluxing; and the number of the first and second electrodes,
the dosage of the second solvent is 30-60mL, the dosage of the carboxylic acid is 0.003-0.005mol, and the dosage of the catalyst is 3-8mL relative to 1g of the beta-caryophyllene;
the volume ratio of the petroleum ether to the acetone in the eluent is 3-6: 1.
4. A beta-caryophyllenol derivative prepared by the preparation method according to any one of claims 1 to 3, wherein the beta-caryophyllenol derivative has a structure shown in formula (I),
wherein R is an ester group.
5. A preparation apparatus for use in the preparation method according to claims 1-3, characterized by comprising a hot and cold water placing tank (1) formed with a containing chamber (101), a mixing unit (2) disposed at least partially in the containing chamber (101), and an elution column and a stir-reflux unit (3) disposed outside the hot and cold water placing tank (1); and the number of the first and second electrodes,
the mixing unit (2) comprises a first material placing barrel (201) and a second material placing barrel (202) which are arranged in the accommodating cavity (101) at intervals, the first material placing barrel (201) and the second material placing barrel (202) are connected in a penetrating manner through a connecting pipe (203), the first material placing barrel (201) and the second material placing barrel (202) are respectively provided with a feeding port (204), the upper surface of the connecting pipe (203) is provided with a titration port (205) in a penetrating manner along the vertical direction, and one end, close to the second material placing barrel (202), in the connecting pipe (203) is provided with a pressurizing film (206) along the vertical direction;
a discharging pipe (207) extending to the outside of the cold and hot water placing groove (1) is arranged at the bottom of the first material placing barrel (201) or the connecting pipe (203) in a closable manner, the discharging pipe (207) is detachably communicated with a feeding hole of the stirring and refluxing unit (3), and at least part of the side wall of the connecting pipe (203) is formed into a transparent visual window (211);
a sealing plate (208) capable of moving in the vertical direction is arranged on the inner side wall of the second charging barrel (202) in a sealing manner, and a charging opening (204) of the second charging barrel (202) is positioned below the sealing plate (208);
and stirring paddles (209) are arranged on the inner side wall of the connecting pipe (203).
6. The preparation device according to claim 5, wherein a plurality of deceleration stoppers (210) are further disposed on the inner side wall of the second charging barrel (202) along the vertical direction, and the deceleration stoppers (210) are disposed below the feeding port (204);
two adjacent deceleration stoppers (210) are arranged on the opposite inner side walls of the second charging barrel (202).
7. The preparation device according to claim 6, characterized in that the deceleration stopper (201) comprises an extension rod (2011) and a stop plate (2012) which are connected in sequence from the inner side wall of the second charging barrel (202), and two adjacent stop plates (2012) are at least partially located on the same vertical plane;
and the axis direction of extension rod (2011) and vertical direction are formed with the contained angle of 15 ° -45 °, backstop board (2012) certainly extension rod (2011) is down extended to the slope, and the axis direction of extension rod (2011) and the plane that the upper surface of backstop board (2012) is located form the contained angle of 10 ° -30 °.
8. The preparation device according to claim 7, wherein the stop plate (2012) is formed in a fan shape, the arc surface of the fan shape is disposed at one end far away from the extension bar (2011), and a plurality of concave drainage grooves (2013) are formed on the upper surface of the stop plate (2012) extending from one side close to the extension bar (2011) to the arc surface;
an arc-shaped bulge is arranged on the inner bottom surface of the drainage groove (2013), and the height of the arc-shaped bulge is 1/3-1/2 of the depth of the drainage groove (2013);
the distance between the two end points of the cambered surface is m, and the distance between the drainage groove (2013) close to the two end points of the cambered surface and the two end points of the cambered surface is 1/4-1/3 of m.
9. The manufacturing device according to any one of claims 5 to 8, wherein the sealing plate (208) comprises a plate body (2081) and a sealing ring (2082) sleeved on the outer side surface of the plate body (2081);
the sealing plate (208) is connected to a pneumatic unit which drives the sealing plate (208) to move along the vertical direction through a connecting rod (212);
be provided with the temperature-sensing module in cold and hot water standing groove (1), the temperature-sensing module has alarm module through the control module electricity, works as when the temperature in cold and hot water standing groove (1) is greater than or is less than the temperature threshold value that sets up, control module can received signal and control alarm module warns.
10. The device according to any one of claims 5 to 8, characterized in that said stirring paddle (209) comprises a first horizontal bar (2091) and a second horizontal bar (2092) arranged horizontally, and said first horizontal bar (2091) and said second horizontal bar (2092) are connected by a plurality of vertical bars (2093);
the lateral surface of montant (2093) is formed with many guiding gutter (2094) along vertical direction, and set up in guiding gutter (2094) on montant (2093) upper portion extend downwards to one side, set up in guiding gutter (2094) of montant (2093) lower part extend upwards to one side.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910978259.6A CN110615737A (en) | 2019-10-15 | 2019-10-15 | Beta-caryophyllenol derivative and preparation method and preparation device thereof |
| CN202011006015.0A CN111892500B (en) | 2019-10-15 | 2020-09-23 | Preparation method and preparation device of beta-caryophyllenol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910978259.6A CN110615737A (en) | 2019-10-15 | 2019-10-15 | Beta-caryophyllenol derivative and preparation method and preparation device thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110615737A true CN110615737A (en) | 2019-12-27 |
Family
ID=68925805
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910978259.6A Pending CN110615737A (en) | 2019-10-15 | 2019-10-15 | Beta-caryophyllenol derivative and preparation method and preparation device thereof |
| CN202011006015.0A Expired - Fee Related CN111892500B (en) | 2019-10-15 | 2020-09-23 | Preparation method and preparation device of beta-caryophyllenol derivative |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011006015.0A Expired - Fee Related CN111892500B (en) | 2019-10-15 | 2020-09-23 | Preparation method and preparation device of beta-caryophyllenol derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN110615737A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111892500A (en) * | 2019-10-15 | 2020-11-06 | 重庆医药高等专科学校 | Preparation method and preparation device of beta-caryophyllenol derivative |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11335327A (en) * | 1998-05-18 | 1999-12-07 | Yasuhara Chemical Co Ltd | Production of sesquiterpene acrylate or sesquiterpene methacrylate |
| CN1560004A (en) * | 2004-03-02 | 2005-01-05 | �Ϻ���ͨ��ѧ | Process for producing beta-pink caryophyllenol |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20130050380A (en) * | 2010-09-30 | 2013-05-15 | 디아이씨 가부시끼가이샤 | Micromixer |
| US9555379B2 (en) * | 2013-03-13 | 2017-01-31 | Bayer Healthcare Llc | Fluid path set with turbulent mixing chamber, backflow compensator |
| CN203598777U (en) * | 2013-11-25 | 2014-05-21 | 四川省德阳昌盛至轩石油化工厂 | Rapid preparation system for lubricating oil |
| CN207546262U (en) * | 2017-10-18 | 2018-06-29 | 马鞍山钢铁股份有限公司 | A kind of gas mixer |
| CN110038458A (en) * | 2019-05-10 | 2019-07-23 | 无锡顺盟科技有限公司 | A kind of even mixed device of gas pipeline |
| CN110615737A (en) * | 2019-10-15 | 2019-12-27 | 重庆医药高等专科学校 | Beta-caryophyllenol derivative and preparation method and preparation device thereof |
-
2019
- 2019-10-15 CN CN201910978259.6A patent/CN110615737A/en active Pending
-
2020
- 2020-09-23 CN CN202011006015.0A patent/CN111892500B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11335327A (en) * | 1998-05-18 | 1999-12-07 | Yasuhara Chemical Co Ltd | Production of sesquiterpene acrylate or sesquiterpene methacrylate |
| CN1560004A (en) * | 2004-03-02 | 2005-01-05 | �Ϻ���ͨ��ѧ | Process for producing beta-pink caryophyllenol |
Non-Patent Citations (2)
| Title |
|---|
| 曹玉蓉等: "β-石竹烯醇的合成研究", 《高等学校化学学报》 * |
| 曹玉蓉等: "β-石竹烯醇羧酸酯的合成研究", 《高等学校化学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111892500A (en) * | 2019-10-15 | 2020-11-06 | 重庆医药高等专科学校 | Preparation method and preparation device of beta-caryophyllenol derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111892500B (en) | 2021-08-03 |
| CN111892500A (en) | 2020-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110615737A (en) | Beta-caryophyllenol derivative and preparation method and preparation device thereof | |
| CN110423187A (en) | A kind of tunnel ultrasound and thermo-circulation distillation combination extraction cannabidiol (CBD) method | |
| CN201643778U (en) | Non-stirring type extracting tower | |
| CN109776646B (en) | Method for preparing high-purity cholesterol by continuous countercurrent micro-channel extraction | |
| CN113750941B (en) | Production equipment and production method of ethyl acetate | |
| CN214861352U (en) | Bio-pharmaceuticals active material separator | |
| CN204816416U (en) | Acryl resin preparation facilities with adjustable | |
| CN202193772U (en) | Dealcoholizing device for biodiesel fuel via adopting methyl esterification | |
| CN201668976U (en) | Phosphoric acid extraction device | |
| CN109534994B (en) | Continuous feeding adipic acid mono-esterification production device and application thereof | |
| CN112755589B (en) | Extraction method and device of refined coenzyme Q10 | |
| CN111574348B (en) | Vitamin K1 purification process | |
| CN211936912U (en) | Reactor for synthesizing methyl iodide-d 3 and ethyl iodide-d 5 | |
| CN209348631U (en) | A kind of solid catalysis esterification production system | |
| CN1562433A (en) | Equipment of continuous counter current extracting Chinese traditional medicine | |
| CN113976014A (en) | High-content sodium trifluoromethanesulphinate refining equipment and manufacturing method thereof | |
| CN2684908Y (en) | Chinese herb medicines continuous counter-current extracting apparatus | |
| CN218910203U (en) | Beta-arbutin fermentation liquor decoloration device | |
| CN207786000U (en) | Basket-hanging cycle extraction unit | |
| CN216755647U (en) | Biological filter equipment that draws | |
| CN205730456U (en) | A kind of shell and tube continuous liquid-liquid countercurrent extraction equipment | |
| CN220860711U (en) | Medicine intermediate production extraction layering water phase jar | |
| CN212282978U (en) | Continuous extraction device for aminoacetic acid | |
| CN219743978U (en) | Single-chamber extraction tank | |
| CN220071557U (en) | Neutralization device for producing methyl chloroacetate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20191227 |