CN113929647A - Preparation method of ambrox with low cost - Google Patents

Preparation method of ambrox with low cost Download PDF

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Publication number
CN113929647A
CN113929647A CN202111234327.1A CN202111234327A CN113929647A CN 113929647 A CN113929647 A CN 113929647A CN 202111234327 A CN202111234327 A CN 202111234327A CN 113929647 A CN113929647 A CN 113929647A
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reaction
organic solvent
ambrox
sulfonic acid
low cost
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吴习荧
庄子翀
张建斌
叶欣怡
叶敏怡
白济嘉
宋玢
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Guangzhou Baihua Flavors And Fragrances Co ltd
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Guangzhou Baihua Flavors And Fragrances Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/02—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the alkali- or alkaline earth metals or beryllium
    • B01J23/04—Alkali metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0215—Sulfur-containing compounds
    • B01J31/0225—Sulfur-containing compounds comprising sulfonic acid groups or the corresponding salts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00—Catalysts, in general, characterised by their form or physical properties
    • B01J35/19—Catalysts containing parts with different compositions
    • 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
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4288—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using O nucleophiles, e.g. alcohols, carboxylates, esters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • 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
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a preparation method of ambrox with low cost, which comprises the following steps: dissolving sclareolide in a first organic solvent, adding a catalyst, and carrying out a reduction reaction on the sclareolide under a heating condition to generate ambergris diol, wherein the catalyst is a boron hydride of r-group sulfonic acid and monovalent metal; and (3) after removing the first organic solvent, adding a second organic solvent, and taking r-based sulfonic acid in the first-step reaction as a dehydrating agent to continue the reduction reaction. Compared with the prior art, the method uses r-sulfonic acid as a catalyst of the first-step reaction, and has the effects of strengthening the formation of acid centers, reducing the pH of a reaction system and reducing the generation of saponification byproducts as much as possible; r-radical sulfonic acid is also used as a dehydrating agent for the second step reaction; therefore, the whole reaction process is continuously completed and can be carried out in the same reaction container, the reaction operation steps are simplified, the production efficiency is improved, and the reaction cost is reduced.

Description

Preparation method of ambrox with low cost
Technical Field
The invention relates to the technical field of perfume synthesis, and in particular relates to a preparation method of ambrox.
Background
Natural ambergris is a high-grade spice, which is derived from offwhite soft stones in the intestines and stomach of sperm whale, and the amount of the ambergris is very small. Ambrox is an artificially synthesized perfume with ambergris flavor, and is used as a substitute for natural ambergris. The ambrox 'ambergris effect' can greatly improve the diffusion effect of the essence, is used in the essence of high-grade perfume and cosmetics, has no stimulation to human body, and is suitable for the perfuming of skin, hair and fabrics, such as the perfuming and the fragrance fixing of soap, talcum powder, cream, shampoo and the like. The ambergris raw material can also be applied to cigarettes, is a key aroma component of the cigarettes, and the ambergris ether is a spice with a particularly prominent effect and has important contribution to the smoke of mixed cigarettes.
In the prior art, fen Mei Yi company uses ether as a solvent and lithium aluminum tetrahydride to reduce sclareolide into ambroxol; then the ambroxol is dehydrated to generate the ambrox under the conditions of vacuum, 135 ℃ and the existence of beta-naphthalenesulfonic acid. The disadvantages of this technique are: the lithium aluminum tetrahydride used in the first step is dangerous because it is a flammable explosive substance; the vacuum and 135 ℃ conditions required in the second step have high energy consumption and cost. It has also been reported in the literature that sclareolide can be reduced by adding 1.75 equivalents of potassium borohydride to 1.75 equivalents of lithium chloride, which can enhance the reduction of potassium borohydride, but the price of lithium chloride is still relatively expensive.
The information disclosed in this background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
Disclosure of Invention
The invention aims to overcome the defects and shortcomings of the prior art, solve the technical problems of complex reaction steps and high operation labor cost of ambrox in the prior art, and provide a method for preparing ambrox, which simplifies the process steps and reduces the reaction cost.
The invention also aims to provide a preparation method of ambrox, aiming at the defects and shortcomings of the prior art and solving the technical problems of high price, poor safety and low yield of the catalyst in the prior art.
In order to realize the purposes of simplifying the process steps and reducing the reaction cost, the invention provides a preparation method of ambrox, which has low cost, and the preparation method comprises the following steps:
step 1, dissolving sclareolide in a first organic solvent, adding a catalyst, and carrying out a reduction reaction on the sclareolide under a heating condition to generate ambergris diol, wherein the catalyst is r-sulfonic acid and a monovalent boron hydride;
step 2, after removing the first organic solvent, adding a second organic solvent, and taking the r-based sulfonic acid in the reaction in the first step as a dehydrating agent to continue the cyclization reaction;
the r-group sulfonic acid is used as a catalyst for the first step reaction and is also used as a dehydrating agent for the second step reaction, thereby simplifying the reaction process and reducing the production cost.
Preferably, the r groups include methyl, tolyl, dodecyl and the like.
Preferably, the boron hydride of a monovalent metal includes potassium borohydride, sodium borohydride, lithium borohydride, and the like.
In order to realize the second purpose of the invention, the borohydride of univalent metal and r-sulfonic acid are used as the catalyst together, thereby further reducing the cost of the catalyst on the basis of ensuring the reaction yield and safety. The invention provides a preparation method of ambrox, which comprises the following steps:
in the step 1, borohydride of monovalent metal and r-group sulfonic acid are jointly used as catalysts, so that the reaction conditions are mild and the reaction yield is high.
Preferably, the boron hydride of the monovalent metal comprises at least one of potassium borohydride or sodium borohydride.
Preferably, in the step 1, the mass ratio of sclareolide is 1, the mass ratio of the first organic solvent is 1 to 20, the mass ratio of r-ylsulfonic acid is 0.5 to 10, and the mass ratio of the borohydride of the monovalent metal is 0.5 to 5.
In the step 2, the mass part of the second organic solvent is 1-20 parts.
Preferably, the first organic solvent is an alcohol solvent such as methanol, ethanol, n-propanol, isopropanol and the like;
the second organic solvent is a dehydration solvent such as cyclohexane, toluene and the like.
Preferably, in the step 1, sclareolide is dissolved in a first organic solvent at 50-120 ℃ to form a reaction system, and the reaction system is stirred and refluxed;
dissolving r-sulfonic acid in a first organic solvent outside a reaction system, and slowly dripping into the reaction system within 0.1-8 hours after stirring and refluxing are started;
and (4) continuously stirring and refluxing for 0.1-8 hours until the reaction in the step (1) is finished.
Preferably, in the step 2, after the first organic solvent is vacuumized, the second organic solvent is added, and the reflux is continued in the same container for 0.1 to 10 hours until the reaction is completed.
Preferably, after the step 2, the method further comprises the step 3: washing with saturated brine to remove extraneous components, rotary evaporating the organic layer to remove the second solvent to obtain crude product, and recrystallizing the crude product to obtain purified product.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a preparation method of ambrox with low cost, which comprises the following steps: dissolving sclareolide in a first organic solvent, adding a catalyst, and carrying out a reduction reaction on the sclareolide under a heating condition to generate ambergris diol, wherein the catalyst is r-group sulfonic acid and a borohydride of a monovalent metal; step 2, after removing the first organic solvent, adding a second organic solvent, and continuing the reduction reaction by taking the r-based sulfonic acid in the reaction in the first step as a dehydrating agent; the r-group sulfonic acid is used as a catalyst for the first step reaction and is also used as a dehydrating agent for the second step reaction, thereby simplifying the reaction process and reducing the production cost. Compared with the prior art, the method uses r-sulfonic acid as a catalyst of the first-step reaction, and has the effects of strengthening the formation of acid centers, reducing the pH of a reaction system and reducing the generation of saponification byproducts as much as possible; r-radical sulfonic acid is also used as a dehydrating agent for the second step reaction; therefore, the whole reaction process is continuously completed and can be carried out in the same reaction container, the reaction operation steps are simplified, the production efficiency is improved, and the reaction cost is reduced.
On the basis, in the step 1, the borohydride of univalent metal and r-sulfonic acid are jointly used as the catalyst, so that the reaction condition is mild, the reaction yield is high, and the catalyst cost is further reduced on the basis of ensuring the reaction yield and the safety. The difference from the prior art is that: 1. compared with the prior art that lithium aluminum hydride is used as the catalyst, the catalyst of the invention has high safety coefficient, mild reaction conditions required by the second step, low energy consumption and low cost; 2. compared with the prior art that sodium borohydride/potassium borohydride is used as a catalyst, the catalyst has stronger reducibility, the reaction yield of the borohydride of univalent metal and r-sulfonic acid which are used as the catalyst is higher and can reach 75 percent at most, and more importantly, the cost of the combined catalyst is low; 3. compared with the prior art which uses lithium chloride, the catalyst of the invention has the advantage that the cost is obviously reduced under the condition of ensuring higher reaction yield.
The invention will be further described with reference to the accompanying drawings.
Drawings
FIG. 1 shows the chemical reaction formula of the reduction of sclareolide to ambergris diol in the preferred embodiment of the present invention.
Fig. 2 is a chemical reaction formula of the reduction of ambroxol to ambrox in the preferred embodiment of the present invention.
Detailed Description
The present invention is further explained and illustrated by the following embodiments, which should be understood to make the technical solution of the present invention clearer and easier to understand, and not to limit the scope of the claims.
As shown in fig. 1 and 2, the preparation method of ambrox of the invention comprises the following steps:
step 1, sclareolide takes r-sulfonic acid and borohydride of univalent metal as catalysts to carry out reduction reaction in a solvent to generate ambroxol;
the r radical can be methyl or tolyl or dodecyl;
the boron hydride of the monovalent metal includes potassium borohydride, sodium borohydride, lithium borohydride, and the like.
Step 2, carrying out reduction reaction on ambroxol by taking r-based sulfonic acid as a dehydrating agent to generate ambrox;
r-sulfonic acid is used as a catalyst of the first step reaction, and has the effects of strengthening the formation of acid centers, reducing the pH of a reaction system and reducing the generation of saponification byproducts as much as possible; and also as a dehydrating agent for the second step reaction; therefore, the whole reaction process is continuously completed, and the reaction can be carried out in the same reaction container, so that the reaction operation steps are simplified, and the production efficiency is improved.
In a preferred embodiment, in step 1, a borohydride of monovalent metal and r-sulfonic acid are used as the catalyst together, compared with the prior art that lithium aluminum tetrahydride is used as the catalyst, the catalyst of the invention has high safety factor, and the reaction conditions required by the second step are mild, and the energy consumption and the cost are low; compared with the prior art that lithium aluminum hydride or potassium borohydride and lithium chloride are used as the catalyst, the catalyst has higher safety and lower cost. The reaction yield of the borohydride of univalent metal and r-sulfonic acid as the catalyst is high, the total yield can reach 75 percent at most, and more importantly, the cost of the composite catalyst is low; compared with the prior art which uses lithium aluminum hydride or lithium chloride, the catalyst of the invention has the advantage that the cost is obviously reduced under the condition of ensuring higher reaction yield.
Specifically, in the second reaction step, the solvent in the first reaction step is directly vacuum-pumped.
Specifically, the reactant composition in the first step reaction is as follows: putting 1 part of sclareolide, 0.5-5 parts of potassium borohydride, 5-10 parts of absolute ethyl alcohol into a 250ml three-necked bottle, and 0.5-10 parts of methanesulfonic acid (the outside of a reaction system is firstly dissolved in 0.5-2 parts of absolute ethyl alcohol, and then slowly dripping into the reaction system).
Specifically, in the first step of reaction, sclareolide, potassium borohydride and a solvent are refluxed and stirred for reaction at the temperature of 50-120 ℃; and (3) slowly dripping methanesulfonic acid into the other part of the methanesulfonic acid solvent within 0.1-8 hours after the reflux starts, and keeping stirring and refluxing for 0.1-8 hours after the dripping is finished.
Specifically, after the first step reaction is completed, ethanol in the bottle is pumped out under negative pressure, 50ml of cyclohexane is added, and reflux dehydration is carried out for 8 hours.
Specifically, after the second step reaction, the mixture was washed twice with 30ml of saturated brine, and cyclohexane was removed by a rotary evaporator to obtain 4.2g of crude ambrox. Recrystallizing with ethanol to obtain 3.0g of ambrox product with a yield of 64%.
The present invention will be further illustrated by the following specific examples.
Example 1
Placing 5.0g sclareolide (0.02mol), 5.0g potassium borohydride (0.09mol) and 50g absolute ethyl alcohol in a 250ml three-necked flask, and carrying out reflux stirring reaction at 80 ℃. After the reflux was started, 4.0g of methanesulfonic acid (0.04mol) was dissolved in 10g of ethanol, and slowly added dropwise to the reaction system, and the dropwise addition was completed within 2 hours, and after the completion of the addition, the reaction was continued for 6 hours while maintaining the reflux and stirring. And monitoring the reaction process by HPLC, after the reaction is completed, pumping out ethanol in the bottle under negative pressure, adding 50ml of cyclohexane and 2g of methanesulfonic acid, and performing reflux dehydration for 8 hours. After the reaction is completed, washing the mixture twice with 30ml of saturated salt water, and removing cyclohexane by using an organic layer rotary evaporator to obtain 4..2g of crude ambrox. Recrystallizing with ethanol to obtain 3.0g of ambrox product with total yield of 60%.
Example 2
5.2g of sclareolide, 6g of potassium borohydride and 42g of ethanol are put into a 250ml three-necked flask, stirred and heated to the temperature of the system about 78 ℃ for reflux stirring reaction, 0.5g of methanesulfonic acid is dissolved in 5g of ethanol after reflux, the mixture is slowly dripped into the reaction system, and after about 2 hours of dripping, the reflux stirring reaction is continued for 8 hours. After the raw materials completely react, the ethanol in the bottle is pumped out under negative pressure, 50ml of cyclohexane and 4g of methanesulfonic acid are added, and reflux dehydration is carried out for 8 hours. After the reaction is completed, the mixture is washed twice by 30ml of salt water, and cyclohexane is removed by an organic layer rotary evaporator to obtain 3.5g of crude ambrox. Recrystallizing with ethanol to obtain 1.8g of ambrox product with a total yield of 34.6%.
Example 3
5.0g of sclareolide, 8g of potassium borohydride and 60g of ethanol are put into a 250ml three-necked flask, stirred and heated to the temperature of the system of about 80 ℃ for reflux stirring reaction, 4.5g of methanesulfonic acid is dissolved in 20g of ethanol after reflux, the mixture is slowly dripped into the reaction system, and after about 4 hours of dripping, the reflux stirring reaction is continued for 8 hours. After the raw materials completely react, the ethanol in the bottle is pumped out under negative pressure, 50ml of cyclohexane and 2g of methanesulfonic acid are added, and reflux dehydration is carried out for 8 hours. After the reaction is completed, the mixture is washed twice by 30ml of salt water, and cyclohexane is removed by an organic layer rotary evaporator to obtain 4.5g of crude ambrox. Recrystallizing with ethanol to obtain 3.8g of ambrox product with a total yield of 76%.
Example 4
5.4g of sclareolide, 5.0g of potassium borohydride and 40g of ethanol are put into a 250ml three-necked flask, stirred and heated to the temperature of the system about 90 ℃ for reflux stirring reaction, 2g of methanesulfonic acid is dissolved in 5g of ethanol after reflux, the mixture is slowly dripped into the reaction system, dripping is finished about 2 hours, and the reflux stirring reaction is continued for 8 hours. After the raw materials completely react, the ethanol in the bottle is pumped out under negative pressure, 50ml of cyclohexane and 2g of methanesulfonic acid are added, and reflux dehydration is carried out for 8 hours. After the reaction is completed, the mixture is washed twice by 30ml of salt water, and cyclohexane is removed by an organic layer rotary evaporator to obtain 3.5g of crude ambrox. Recrystallizing with ethanol to obtain 2.2g of ambrox product with a total yield of 40%.
Example 5
5.0g of sclareolide, 6g of potassium borohydride and 45g of ethanol are put into a 250ml three-necked flask, stirred and heated to the temperature of about 88 ℃ for reflux stirring reaction, 8g of methanesulfonic acid is dissolved in 25g of ethanol after reflux, the mixture is slowly dripped into the reaction system, dripping is finished about 4 hours, and the reflux stirring reaction is continued for 8 hours. After the raw materials completely react, the ethanol in the bottle is pumped out under negative pressure, and 50ml of cyclohexane is added for reflux dehydration for 8 hours. After the reaction is completed, the mixture is washed twice by 30ml of salt water, and cyclohexane is removed by an organic layer rotary evaporator to obtain 3.8g of crude ambrox. Recrystallizing with ethanol to obtain 2.8g of ambrox product with a total yield of 56%.
Example 6
Placing 10g of sclareolide, 16g of potassium borohydride and 80g of ethanol in a 500ml three-necked flask, stirring, heating to the system temperature of about 85 ℃, starting refluxing, dissolving 10g of methanesulfonic acid in 50g of ethanol after refluxing, slowly dripping into the reaction system, finishing dripping after about 4 hours, and continuously refluxing, stirring and reacting for 8 hours. After the raw materials completely react, the ethanol in the bottle is pumped out under negative pressure, 100ml of cyclohexane and 4g of methanesulfonic acid are added, and reflux dehydration is carried out for 8 hours. After the reaction, the mixture was washed twice with 80ml of brine, and cyclohexane was removed by a rotary evaporator to obtain 8.2g of crude ambrox. Recrystallizing with ethanol to obtain 6.5g of ambrox product with a total yield of 65%.
While the present invention has been described by way of examples, and not by way of limitation, other variations of the disclosed embodiments, as would be readily apparent to one of skill in the art, are intended to be within the scope of the present invention, as defined by the claims.

Claims (8)

1. A preparation method of ambrox with low cost is characterized in that:
step 1, dissolving sclareolide in a first organic solvent for dissolving alcohols, adding a catalyst, and carrying out a reduction reaction on the sclareolide under a heating condition to generate ambergris diol, wherein the catalyst is a boron hydride of r-radical sulfonic acid and monovalent metal;
step 2, after removing the first organic solvent, adding a second organic solvent for dewatering, and continuing the reduction reaction by taking r-based sulfonic acid in the reaction in the first step as a dehydrating agent;
the r-group sulfonic acid is used as a catalyst for the first step reaction and is also used as a dehydrating agent for the second step reaction, thereby simplifying the reaction process and reducing the production cost.
2. The method of preparing ambrox at low cost according to claim 1, characterized in that:
the r group comprises methyl, tolyl or dodecyl.
3. The method of preparing ambrox at low cost according to claim 1, characterized in that:
the boron hydride of the monovalent metal comprises at least one of potassium borohydride or sodium borohydride.
4. The method of preparing ambrox at low cost according to claim 1, characterized in that:
in the step 1, 1 part by mass of sclareolide, 1-20 parts by mass of a first organic solvent, 0.5-10 parts by mass of r-group sulfonic acid and 0.5-5 parts by mass of borohydride of monovalent metal are added.
In the step 2, the mass part of the second organic solvent is 1-20 parts.
5. The method of preparing ambrox at low cost according to claim 1, characterized in that:
the first organic solvent comprises methanol, ethanol, n-propanol or isopropanol solvent;
the second organic solvent comprises a cyclohexane or toluene solvent.
6. The method of preparing ambrox at low cost according to claim 1, characterized in that:
in the step 1, dissolving sclareolide in a first organic solvent at 50-120 ℃ to form a reaction system, and stirring and refluxing the reaction system;
dissolving r-sulfonic acid in a first organic solvent outside a reaction system, and slowly dripping into the reaction system within 0.1-8 hours after stirring and refluxing are started;
and (4) continuously stirring and refluxing for 0.1-8 hours until the reaction in the step (1) is finished.
7. The method of preparing ambrox at low cost according to claim 1, characterized in that:
and 2, after the first organic solvent is vacuumized and dried, adding a second organic solvent, and continuously refluxing for 0.1-10 hours in the same container.
8. The method of preparing ambrox at low cost according to claim 1, characterized in that:
after step 2, further comprising step 3: washing with saturated brine to remove extraneous components, and rotary evaporating the organic layer to remove the second solvent to obtain crude product.
CN202111234327.1A 2021-10-22 2021-10-22 Preparation method of ambrox with low cost Pending CN113929647A (en)

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CN105017191A (en) * 2015-07-06 2015-11-04 川渝中烟工业有限责任公司 Preparation method for ambrox
CN105037308A (en) * 2015-07-06 2015-11-11 川渝中烟工业有限责任公司 Preparation method for ambrox
US20190023679A1 (en) * 2015-10-23 2019-01-24 UNIVERSIDAD MICHOACANA DE SAN NICOLÁS DE HIDALGOú Method for synthesising ambroxide from ageratina jocotepecana

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