CN112321557A

CN112321557A - Preparation method of Jiale musk

Info

Publication number: CN112321557A
Application number: CN202010959398.7A
Authority: CN
Inventors: 朱梦瑶; 刘杰; 张静; 任一臻; 陈来中; 张永振
Original assignee: Wanhua Chemical Group Co Ltd
Current assignee: Wanhua Chemical Group Co Ltd
Priority date: 2020-09-14
Filing date: 2020-09-14
Publication date: 2021-02-05
Anticipated expiration: 2040-09-14
Also published as: CN112321557B

Abstract

The invention discloses a preparation method of galaxolide, under the action of a supported Pd catalyst, hexamethyl indanol and a TEBBE reagent (CAS:67719-69-1) undergo a methylene etherification reaction and then undergo condensation cyclization to generate galaxolide, and a product is separated out through continuous rectification; the supported Pd catalyst is represented as Pd-X/Y, wherein X is selected from triphenylphosphine, tributylphosphine, tricyclohexylphosphine, bis-diphenylphosphinomethane, 1, 2-bis-diphenylphosphinoethane, 4, 5-bis-diphenylphosphino-9, 9-dimethylxanthene, and Y is selected from carbon nano tube, ordered mesoporous carbon, neutral alumina, silica, molecular sieve and kaolin. The process disclosed by the invention avoids the problems of complex process, serious equipment corrosion, low safety, environmental friendliness and the like in the prior art, and the conversion rate of raw materials and the selectivity of products can reach more than 93%.

Description

Preparation method of Jiale musk

Technical Field

The invention relates to a production method of galaxolide, in particular to a method for producing galaxolide by carrying out methylene etherification reaction on hexamethylindanol and a TEBBE reagent and then carrying out condensation cyclization, and belongs to the technical field of chemical industry.

Technical Field

Galaxolide (Galaxolide) is a widely used musk type synthetic perfume, and the product has strong fragrance, good stability, safety and no toxicity to human bodies, and is low in price compared with natural perfumes and popular with flavourists. At present, the problems of low reaction yield, high production cost, serious equipment corrosion, difficult three-waste treatment and the like generally exist in the process for synthesizing the galaxolide in China, so that the research on a new, efficient and environment-friendly method for synthesizing the galaxolide has important significance.

The existing production process of galaxolide mainly adopts a three-step method, namely, intermediate pentamethyl indan and hexamethyl indan alcohol (2- (1,1,2,3, 3-pentamethyl indan) isopropanol) are obtained through condensation reaction and hydroxyisopropylation reaction, and are subjected to chloromethyl etherification with paraformaldehyde, and cyclization condensation to obtain galaxolide. The reaction of hexamethylindanol and paraformaldehyde needs to be catalyzed by HCl gas first, then NaOH solution is added to complete condensation cyclization, the process is complicated, the operation is complex, and the corrosion to equipment is serious; meanwhile, HCl gas reacts with polyformaldehyde to generate chloromethyl ether which is a highly toxic byproduct, so that the safety is low and the harm to operators is large.

Aiming at the defects in the process, a novel preparation method of galaxolide musk is urgently needed to be developed to replace a methylene reagent paraformaldehyde, and the problems of complex and fussy process, serious equipment corrosion, low safety, environmental friendliness and the like in the existing production are solved.

Disclosure of Invention

One of the objects of the present invention is to provide a novel process for the preparation of galaxolide.

Another object of the present invention is to provide a catalyst for use in the novel process for the preparation of galaxolide described above and a process for the preparation thereof.

In order to realize the first purpose of the invention, the invention provides a preparation method of galaxolide, and particularly relates to a method for generating galaxolide by carrying out methylene etherification reaction on hexamethylindanol and a TEBBE reagent (CAS:67719-69-1) and then carrying out condensation cyclization under the action of a supported Pd catalyst. The method can avoid the use of paraformaldehyde and catalyst HCl gas, reduce potential safety hazards and corrosion to equipment, is simple in process flow, and can be used for reacting hexamethylindanol with a methylene reagent TEBBE reagent to generate galaxolide under the action of the catalyst, so that the use of NaOH solution is avoided, and the operation steps are simplified. The adopted scheme comprises the following steps:

a preparation method of Jiale musk comprises the following steps: under the action of a supported Pd catalyst, hexamethylindanol and a TEBBE reagent (CAS:67719-69-1) undergo a methylene etherification reaction, condensation and cyclization are carried out to generate reaction liquid containing the galaxolide, and a galaxolide product is separated through continuous rectification.

The reaction route of the invention is as follows:

in the preparation method, the amount of the supported Pd catalyst is 3-7 wt% relative to the hexamethylindanol.

In the preparation method, the molar ratio of hexamethylindanol to the TEBBE reagent is 1:1-1:2, preferably 1:1.2-1: 1.4.

In the preparation method, the reaction temperature is 0-30 ℃; the reaction time is 2-7 h.

In the preparation method, the product can be rectified by a known method, such as triangular spiral packing, the number of the trays is 20-40, the reflux ratio is 2-4, and the pressure is 2-5 mmHg.

In order to achieve another object of the above invention, the present invention provides a supported Pd catalyst.

A supported palladium catalyst is represented as Pd-X/Y. In the catalyst, Pd is an active component; x is a ligand selected from one or more of triphenylphosphine, tributylphosphine, tricyclohexylphosphine, bis (diphenylphosphinomethane), 1, 2-bis (diphenylphosphinoethane), 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, preferably 1, 2-bis (diphenylphosphinoethane) and/or bis (diphenylphosphinomethane); y is a carrier and is selected from one or more of carbon nano tube, ordered mesoporous carbon, neutral alumina, silicon dioxide, molecular sieve and kaolin, preferably one or more of neutral alumina, 4A molecular sieve and kaolin.

In the catalyst, based on the total weight of the catalyst, the mass fraction of Pd is 10-25%, the mass fraction of X is 30-55%, and the mass fraction of Y is 25-50%; preferably, the mass fraction of Pd is 15-22%, the mass fraction of X is 35-50%, and the mass fraction of Y is 30-45%.

The invention also provides a preparation method of the catalyst, which comprises the following steps:

(1) fully mixing a Pd-containing compound with an aqueous solution of a ligand X to obtain a mixed salt aqueous solution, and then dispersing a carrier Y in the mixed salt aqueous solution to obtain slurry;

(2) adjusting the pH value of the slurry to 8-10 by using an alkaline precipitator, and aging to obtain slurry;

(3) and carrying out post-treatment on the slurry to obtain the supported palladium catalyst.

In the preparation method of the catalyst, in the step (1), the amount of water used is not particularly limited, and the Pd-containing compound and X added may be completely dissolved.

In the preparation method of the catalyst, in the step (1), the Pd-containing compound is selected from one or more of palladium acetate, palladium chloride and tetratriphenylphosphine palladium, and palladium chloride is preferred.

In the preparation method of the catalyst, in the step (2), the alkaline precipitator is selected from one or more of sodium carbonate, sodium bicarbonate, ammonium carbonate, ammonium bicarbonate and ammonia water, and can be an aqueous solution with the concentration of 15-30 wt%; the aging time is 1-3h, and the aging temperature is 60-90 ℃.

In the preparation method of the catalyst, in the step (3), the post-treatment specifically comprises the following steps: and filtering and washing the slurry to obtain a filter cake, drying the filter cake, and then roasting, crushing, tabletting and forming. Wherein the drying temperature is preferably 90-110 ℃, and the drying time is preferably 6-10 h; the roasting temperature is preferably 250 ℃ to 450 ℃, and the roasting time is preferably 5 to 14 hours.

The invention has the beneficial effects that:

1. the method has a simple process route, and avoids the problems of potential safety hazards of personnel, serious equipment corrosion, environment unfriendliness and the like caused by the use of paraformaldehyde and HCl gas in the prior art; the used supported Pd catalyst is environment-friendly.

2. According to the novel supported Pd catalyst, the coordination bond formed by the lone pair of electrons on P in the catalyst framework and Pd is easy to interact with the hydroxyl and the benzene ring to form a bond, the concentration of reactants on the surface of the catalyst is increased in the catalytic reaction process of the catalyst, and the methylene etherification reaction and the condensation cyclization reaction of the catalyst under the catalysis of Pd are promoted.

3. The invention can obtain galaxolide musk through methylene etherification, condensation cyclization under simpler operation conditions, the conversion rate of raw materials reaches more than 93 percent, and the selectivity of products is more than 93 percent.

Detailed Description

The present invention is further illustrated in detail by the following examples, but the scope of the present invention is not limited to these examples.

Gas chromatography analysis conditions of the product: shimadzu gas chromatograph, RTX-DB-5 column, injection port temperature: 320 ℃; detector temperature: 350 ℃; temperature rising procedure: keeping at 80 deg.C for 2min, and heating to 200 deg.C at 10 deg.C/min; raising the temperature to 350 ℃ at the temperature of 20 ℃/min, and keeping the temperature for 5 min.

The sources of the apparatus and reagents in the following examples are shown in table 1 below:

TABLE 1

Instrument and reagent	Source	Specification of
			ICP spectrometer	Agilent	ICP-OES 720 model
Gas chromatograph	Shimadzu
			Hexamethylindanol	Is commercially available	>98％
TEBBE reagent	Is commercially available	>99％

The inorganic salts used in the following examples are all commercially available unless otherwise specified.

Example 1

89.7g of palladium acetate and 113.4g of tricyclohexylphosphine are mixed in 500g of distilled water, the temperature is increased to 60 ℃, stirring is carried out for 3 hours, and 127.5g of 4A molecular sieve is added under the stirring state to be mixed to obtain slurry A;

taking a 20 wt% sodium bicarbonate solution as an alkaline precipitant B, respectively heating the slurry A and the alkaline precipitant B to 30 ℃, slowly dropwise adding the alkaline precipitant B into the slurry A until the pH of the system is 9, and controlling the reaction temperature in the precipitation process to be 30 ℃; then aging for 2h at 80 ℃ to obtain slurry;

and filtering the slurry, washing with deionized water to obtain a filter cake, drying the filter cake at 100 ℃ for 7h, roasting at 300 ℃ for 12h, crushing, tabletting and forming to obtain the catalyst 1. ICP analysis determines that in the catalyst 1, the following components in percentage by mass of the total mass of the catalyst 1 are: 15% of Pd, 40% of tricyclohexylphosphine and 45% of 4A molecular sieve.

Example 2

Mixing 84.0g of palladium chloride and 148.2g of 1, 2-bis (diphenylphosphinoethane) in 500g of distilled water, heating to 50 ℃, stirring for 6 hours, and adding 97.8g of neutral alumina under the stirring state to obtain slurry A;

taking a 20 wt% ammonium carbonate solution as an alkaline precipitant B, respectively heating the slurry A and the alkaline precipitant B to 40 ℃, slowly dropwise adding the alkaline precipitant B into the slurry A until the pH of the system is 8.0, and controlling the reaction temperature in the precipitation process to be 40 ℃; then aging for 1.5h at 90 ℃ to obtain slurry;

and filtering the slurry, washing with deionized water to obtain a filter cake, drying the filter cake at 110 ℃ for 9h, roasting at 450 ℃ for 7h, crushing, tabletting and forming to obtain the catalyst 2. ICP analysis determines that the catalyst 2 comprises the following components in percentage by mass of the total mass of the catalyst 2: pd 17%, 1, 2-bis (diphenylphosphinoethane) 50%, and neutral alumina 33%.

Example 3

431.3g of tetratriphenylphosphine palladium and 83.4g of tributylphosphine are mixed in 1000g of distilled water, the temperature is increased to 70 ℃, stirring is carried out for 4 hours, and after that, 75.5g of silicon dioxide is added and mixed under the stirring state to obtain slurry A;

taking 15 wt% ammonia water solution as an alkaline precipitator B, respectively heating the slurry A and the alkaline precipitator B to 40 ℃, slowly dropwise adding the alkaline precipitator B into the slurry A until the pH value of the system is 10.0, and controlling the reaction temperature in the precipitation process to be 40 ℃; then aging for 3h at 70 ℃ to obtain slurry;

and filtering the slurry, washing with deionized water to obtain a filter cake, drying the filter cake at 90 ℃ for 10h, roasting at 400 ℃ for 10h, crushing, tabletting and forming to obtain the catalyst 3. ICP analysis determines that the following components in the catalyst 3 account for the total mass of the catalyst 3 in percentage by mass: 20% of Pd, 42% of tributyl phosphine and 38% of silicon dioxide.

Example 4

Mixing 117.4g of palladium chloride and 112.0g of bis (diphenylphosphino) methane in 500g of distilled water, heating to 70 ℃, stirring for 5 hours, and adding 137.7g of kaolin under the stirring state to obtain slurry A;

taking 25 wt% ammonium bicarbonate solution as an alkaline precipitant B, respectively heating the slurry A and the alkaline precipitant B to 50 ℃, slowly dropwise adding the alkaline precipitant B into the slurry A until the pH value of the system is 9.0, and controlling the reaction temperature in the precipitation process to be 50 ℃; then aging for 3h at 75 ℃ to obtain slurry;

and filtering the slurry, washing with deionized water to obtain a filter cake, drying the filter cake at 100 ℃ for 6h, roasting at 250 ℃ for 14h, crushing, tabletting and forming to obtain the catalyst 4. ICP analysis determines that the catalyst 4 comprises the following components in percentage by mass of the total mass of the catalyst 4: pd 22%, bis-diphenylphosphinomethane 35% and kaolin 43%.

Example 5

Catalyst 1(9.6g, 3 wt%) and hexamethylindanol (320.3g, 1.3mol) were added to a reaction kettle equipped with a mechanical stirrer, thermocouple, condenser, and the TEBBE reagent solution (443.9g, 1.56mol) was added dropwise over 1h while maintaining the reaction temperature at about 25 ℃ using an external cooling bath. After the end of the dropwise addition, the reaction mixture was stirred for a further 2h at 25 ℃. Filtering to remove the solid catalyst, separating out reaction liquid, and rectifying the obtained crude mixture to obtain the product galaxolide with the boiling point of 135-.

Nuclear magnetic analysis results of the product:

¹H NMR(CDCl₃,400MHz):δ7.24(s,1H),7.19(s,1H),4.62(s,2H),3.66(m,2H),3.27(t,J＝7.0Hz,1H),2.17(q,J＝6.8Hz,1H),1.40(s,12H),1.25(d,J＝6.8Hz,3H),0.96(d,J＝6.8Hz,3H).

example 6

Catalyst 2(15.5g, 7 wt%) and hexamethylindanol (221.8g, 0.9mol) were added to a reaction kettle equipped with a mechanical stirrer, thermocouple, condenser, and the TEBBE reagent solution (332.9g, 1.17mol) was added dropwise over 1h while maintaining the reaction temperature at about 20 ℃ using an external cooling bath. After the end of the dropwise addition, the reaction mixture was stirred for a further 3h at 20 ℃. Filtering to remove the solid catalyst, separating out reaction liquid, and rectifying the obtained crude mixture to obtain the product galaxolide with the boiling point of 135-.

Example 7

Catalyst 3(24.6g, 4 wt%) and hexamethylindanol (616.0g, 2.5mol) were added to a reaction kettle equipped with a mechanical stirrer, thermocouple, condenser, and the TEBBE reagent solution (996.0g, 3.5mol) was added dropwise over 2h while maintaining the reaction temperature at about 0 ℃ using an external cooling bath. After the end of the dropwise addition, the reaction mixture was stirred for a further 5h at 0 ℃. Filtering to remove the solid catalyst, separating out reaction liquid, and rectifying the obtained crude mixture to obtain the product galaxolide with the boiling point of 135-.

Example 8

Catalyst 4(25.1g, 6 wt%) and hexamethylindanol (418.9g, 1.7mol) were added to a reaction kettle equipped with a mechanical stirrer, thermocouple, condenser, and the TEBBE reagent solution (604.7g, 2.13mol) was added dropwise over 1h while maintaining the reaction temperature at about 10 ℃ using an external cooling bath. After the end of the dropwise addition, the reaction mixture was stirred for a further 4h at 10 ℃. Filtering to remove the solid catalyst, separating out reaction liquid, and rectifying the obtained crude mixture to obtain the product galaxolide with the boiling point of 135-.

The results for examples 5-8 are shown in Table 2:

TABLE 2

Catalyst and process for preparing same	Conversion of hexamethylindanol%	Selectivity of galaxolide musk
			1	96	97
2	95	97
			3	93	95
4	98	99

Claims

1. A preparation method of Jiale musk comprises the following steps: under the action of a catalyst, hexamethylindanol reacts with a TEBBE reagent to generate reaction liquid containing galaxolide, and the reaction liquid is separated to obtain a product.

2. The process according to claim 1, wherein the catalyst is used in an amount of 3 to 7 wt% with respect to the hexamethylindanol.

3. The process according to claim 1 or 2, characterized in that the molar ratio of hexamethylindanol to TEBBE reagent is between 1:1 and 1:2, preferably between 1:1.2 and 1: 1.4.

4. The production method according to any one of claims 1 to 3, wherein the reaction temperature is 0 to 30 ℃; the reaction time is 2-7 h.

5. The process according to any one of claims 1 to 4, characterized in that the catalyst is a supported palladium catalyst, expressed as Pd-X/Y;

wherein X is a ligand selected from one or more of triphenylphosphine, tributylphosphine, tricyclohexylphosphine, bis (diphenylphosphinomethane), 1, 2-bis (diphenylphosphinoethane) and 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene;

y is carrier selected from one or more of carbon nanotube, ordered mesoporous carbon, neutral alumina, silica, molecular sieve and kaolin.

6. The process according to claim 5, wherein the mass fraction of Pd is 10 to 25%, the mass fraction of X is 30 to 55%, and the mass fraction of Y is 25 to 50%, based on the total weight of the catalyst.

7. The method according to claim 5 or 6, wherein the catalyst is prepared by a process comprising the steps of:

8. The method according to claim 7, wherein in the step (1), the Pd-containing compound is one or more selected from palladium acetate, palladium chloride and palladium tetratriphenylphosphine.

9. The preparation method according to claim 7 or 8, wherein in the step (2), the alkaline precipitant is selected from one or more of sodium carbonate, sodium bicarbonate, ammonium carbonate, ammonium bicarbonate and ammonia water; the aging time is 1-3h, and the aging temperature is 60-90 ℃.

10. The production method according to any one of claims 7 to 9, wherein in the step (3), the post-treatment comprises: filtering and washing the slurry to obtain a filter cake, drying the filter cake, and then roasting, crushing and tabletting the filter cake;

the drying temperature is 90-110 ℃, and the drying time is 6-10 h; the roasting temperature is 250-450 ℃, and the roasting time is 5-14 h.