Complex catalyst and its application in preparing musk toniferum intermediate

Abstract

The invention discloses a complex catalyst and an application thereof in preparing a tounamusk intermediate. The preparation method of the complex catalyst comprises the following steps: under stirring, tert-butyl chloride is dripped into a mixed solution containing p-isopropyltoluene, a cyclic hydrocarbon solvent and aluminum chloride to obtain the complex catalyst; the dripping temperature of the tert-butyl chloride is 15-35 DEG C, the dripping time is controlled at 0.5-1h, and the reaction time after the dripping is 0.5-2h; the method prepares the aluminum chloride into a complex state of p-isopropyltoluene carbon cation and aluminum chloride by pre-positioning, and the complex catalyst can be used for efficiently catalyzing the preparation of 1,1,3,4,4,6-hexamethyltetralin, thereby improving the reaction yield and meeting the requirements of industrial scale-up production.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, in particular to a complex catalyst and an application thereof in preparing a tonalis musk intermediate. Background Art

[0002] 1,1,3,4,4,6-Hexamethyltetralin (HMT) is a key intermediate in the synthesis of polycyclic musks, musk tonamide. Musk tonamide is a fixative with excellent properties and is widely used in perfumes, cosmetics and other cleaning products. The current production of 1,1,3,4,4,6-hexamethyltetralin is mainly based on p-isopropyltoluene, 2,3-dimethyl-1-butene, and tert-butyl chloride, which are cyclized under the catalysis of Lewis acids. Commonly used Lewis acids include aluminum chloride, ferric chloride, etc., and commonly used solvents include cyclohexane, ethylene dichloride, etc. The specific reaction route is as follows:

[0003]

[0004] US patents US4284818A, US4877915A, US4877916A, etc. mention that the use of aluminum chloride can achieve a maximum yield of nearly 70%. However, in actual production, the cyclization reaction has a significant amplification effect. Taking a 3000L reactor as an example, the actual yield differs from the maximum yield by 15-20%, which cannot meet the requirements of industrial amplification production.

[0005] According to the report of the reaction mechanism in the literature "J.Org.Chem.1963,28,9,2248-2255", if you want to accelerate the forward movement of the reaction or reduce the production of side reactions, it is particularly important to accelerate the production of p-isopropyltoluene carbon cations. It is not easy to form a single p-isopropyltoluene carbon cation. Therefore, the addition of tert-butyl chloride during the reaction not only acts as a hydrogen absorber, but also plays a role in carbon cation transfer.

[0006] Therefore, it is necessary to provide a catalyst to achieve efficient catalytic preparation of 1,1,3,4,4,6-hexamethyltetralin to meet the yield requirements of industrial scale-up production. Summary of the invention

[0007] The invention provides a complex catalyst and an application thereof in preparing a tonalis musk intermediate. The complex catalyst can achieve high-efficiency catalytic preparation of 1,1,3,4,4,6-hexamethyltetralin to meet the yield requirement of industrial scale-up production.

[0008] In view of this, the scheme of the present invention is:

[0009] The first aspect of the present invention provides a method for preparing a complex catalyst, comprising the steps of: adding tert-butyl chloride to a mixed solution containing p-isopropyl toluene, a cyclic hydrocarbon solvent, and aluminum chloride under stirring to obtain a complex catalyst; the tert-butyl chloride is added at a temperature of 15 to 35° C., the addition time is controlled at 0.5 to 1 h, and the reaction time after the addition is completed is 0.5 to 2 h.

[0010] Preferably, the molar ratio of p-isopropyltoluene, cyclic hydrocarbon solvent, aluminum chloride and tert-butyl chloride is (1-3): (3-5): (0.25-0.45): (0.3-0.5).

[0011] More preferably, the molar ratio of p-isopropyltoluene, cyclopentane solvent, aluminum chloride and tert-butyl chloride is 1.2:4:0.45:0.5;

[0012] Preferably, the cyclohydrocarbon solvent is cyclohexane;

[0013] Preferably, when preparing the above complex, since the reaction will produce hydrogen chloride gas, cyclohexane, p-isopropyltoluene and aluminum chloride are first added to the reactor, the gas absorption system is turned on before stirring, and tert-butyl chloride is slowly added dropwise to ensure that hydrogen chloride is discharged to prevent the reactor from being in a positive pressure state causing safety risks.

[0014] Preferably, the kettle temperature is controlled at about 15°C during the reaction, the tert-butyl chloride is added dropwise over 45 minutes, and the reaction is stirred for 1 hour to dissolve the aluminum chloride solid. After completion, the lower layer of the complex is transferred to a kettle kept warm at 5°C for storage pending use, and at the same time, part of the upper layer of the clear liquid is transferred to isolate it from air and moisture to prevent the complex from being inactivated by contact with water and air.

[0015] The second aspect of the present invention provides the use of the complex catalyst described in the first aspect in the catalytic preparation of 1,1,3,4,4,6-hexamethyltetralin.

[0016] Furthermore, the complex catalyst is used to improve the preparation yield of 1,1,3,4,4,6-hexamethyltetralin.

[0017] The third aspect of the present invention provides a method for preparing 1,1,3,4,4,6-hexamethyltetralin, comprising the steps of:

[0018] S1. Obtaining and preserving a catalyst; the catalyst being selected from the complex catalyst prepared by the preparation method described in the first aspect above, and / or recovering the catalyst;

[0019] S2. Under stirring, the mixture is added dropwise to the catalyst solution of the cyclic hydrocarbon solvent, the addition time is 5 to 6 hours, and the reaction temperature is 10 to 20 ° C; the mixture comprises p-isopropyl toluene, tert-butyl chloride and 3-dimethyl-1-butene;

[0020] S3. After the reaction is completed, the lower layer of complex is allowed to stand and separated to recover the catalyst. The upper layer of clear liquid is washed with water, desolventized, and recrystallized to obtain 1,1,3,4,4,6-hexamethylnaphthalene.

[0021] Furthermore, in step S1, the storage temperature of the complex catalyst is 0-10°C.

[0022] Furthermore, in step S2, the molar ratio of p-isopropyltoluene, tert-butyl chloride, 2,3-dimethyl-1-butene, cyclic hydrocarbon solvent and complex catalyst is (5-7):(3.5-4.5):(3.2-4.4):(14-17):(0.3-0.45).

[0023] Furthermore, in step S2, the molar ratio of p-isopropyltoluene, tert-butyl chloride, 2,3-dimethyl-1-butene, cyclic hydrocarbon solvent and complex catalyst is 5.97:3.67:3.57:15.47:0.39.

[0024] Furthermore, in step S3, the water washing process includes first performing a first water washing, then performing an alkaline water washing, and then performing a second water washing.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The preparation method of the complex of the present invention prepares aluminum trichloride into a complex state of p-isopropyltoluene carbon cation and aluminum chloride by pretreatment, which can be used for the efficient catalytic preparation of 1,1,3,4,4,6-hexamethyltetralin, thereby improving the reaction yield and meeting the requirements of industrial scale-up production.

[0027] 2. When preparing the 1,1,3,4,4,6-hexamethyltetralin of the present invention, a complex is first prepared, and then a cyclization reaction is carried out, so that the product yield is improved; after the reaction is completed and allowed to stand, the complex catalyst is located in the lower layer for easy recovery, and can be used up to 10 times, thereby reducing the amount of waste water and waste gas generated by hydrolysis when aluminum chloride is directly used as a catalyst; using a liquid complex as a catalyst solves the problem of having to reopen the kettle cover for each batch during the reaction to add aluminum chloride solid, thereby reducing potential safety hazards. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is the infrared spectrum of the complex catalyst of the present invention. DETAILED DESCRIPTION

[0029] The technical solution of the present invention will be clearly and completely described below in conjunction with the preferred embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] In one embodiment, a method for preparing a complex catalyst is provided, the steps comprising:

[0031] Under stirring, tert-butyl chloride is added dropwise to a mixed solution containing p-isopropylbenzene, cyclopentane solvent, and aluminum chloride to obtain a complex catalyst; the molar ratio of p-isopropylbenzene, cyclopentane solvent, aluminum chloride, and tert-butyl chloride is (1-3): (3-5): (0.25-0.45): (0.3-0.5); the tert-butyl chloride addition temperature is controlled at 15-35°C, and the reaction time is 0.5-2h. The infrared spectrum of the prepared complex catalyst is shown in FIG. Figure 1 As shown in the figure, IR (KBr): Vmax (cm -1 )3500.49, 2960.92, 1515.10, 1462.39, 814.54.

[0032] In another embodiment, the complex catalyst described in the above embodiment is taken out for hydrolysis, and the oil phase after hydrolysis is subjected to gas phase analysis, and two main peaks are found at the position of tert-butyl chloride and the position of cymene, respectively. Therefore, it is inferred that the following reaction process occurs, and the complex may be a mixed state of the following structure:

[0033]

[0034] In the above embodiment, by preparing aluminum chloride in advance as a partial complex state of p-isopropyltoluene carbon cation and aluminum chloride, it is beneficial to improve the reaction yield. In addition, according to the phenomenon observed in the actual reaction, in the process of preparing aluminum chloride as a complex, a large number of bubbles can be seen in the gas washing bottle, and a large amount of gas will be generated in the reaction.

[0035] Preparation Example 1

[0036] Add 336kg cyclohexane, 162kg p-isopropyltoluene (hereinafter referred to as "cymene"), and 52kg aluminum trichloride to the reactor, start stirring, open the tail gas absorption system, slowly add 40kg tert-butyl chloride, control the temperature at around 15°C during the addition, control the addition to be completed within 45min, then stir and react for 1h until the solid particles are completely melted, open the bottom valve of the reactor and transfer the prepared 89kg complex into the catalyst insulation kettle, add 100kg supernatant as liquid seal after the transfer is completed to isolate water and air. Maintain the temperature of the insulation kettle at around 5°C for standby use.

[0037] Preparation Example 2

[0038] Add 390kg cyclohexane, 300kg cymene, and 60kg aluminum trichloride to the reactor, start stirring, open the tail gas absorption system, slowly add 45kg tert-butyl chloride, control the temperature at around 25°C during the addition, control the addition to be completed within 30min, then stir and react for 2h until the solid particles are completely melted, open the bottom valve of the reactor and transfer the prepared 100kg complex into the catalyst insulation kettle, add 100kg supernatant liquid as liquid seal after the transfer is completed to isolate water and air. Maintain the temperature of the insulation kettle at around 5°C for standby use.

[0039] Preparation Example 3

[0040] Add 260kg cyclohexane, 400kg cymene, and 35kg aluminum chloride to the reactor, start stirring, open the tail gas absorption system, slowly add 28kg tert-butyl chloride, control the temperature at around 30°C during the addition, control the addition to be completed within 1h, then stir and react for 1.5h until the solid particles are completely melted, open the bottom valve of the reactor and transfer the prepared 62kg complex into the catalyst insulation kettle, add 100kg supernatant as liquid seal after the transfer is completed to isolate water and air. Maintain the temperature of the insulation kettle at around 5°C for standby use.

[0041] Example 1

[0042] 800kg of cymene, 340kg of tert-butyl chloride and 300kg of 2,3-dimethyl-1-butene were put into the preparation kettle for mixing. 1300kg of cyclohexane and 89kg of the complex obtained in Preparation Example 1 were added into the cyclization reaction kettle, the reaction kettle was started for stirring, and the prepared mixed solution was added dropwise, the reaction temperature was controlled at 15-20°C, the dropping time was about 5-6h, and the stirring was stopped after the dropping was completed. After standing for 1h, the lower layer of the complex was released and transferred to the catalyst insulation kettle, the upper clear liquid was washed with 300L of water, 200L of alkaline water, and 300L of water, and the cyclohexane cymene was removed by decompression and desolventizing. After recrystallization and suction filtration, 550kg of white crystals were obtained, with a purity of 98.8% and a reaction yield of 70.5%.

[0043] Example 2

[0044] 800kg of cymene, 340kg of tert-butyl chloride and 300kg of 2,3-dimethyl-1-butene were put into the preparation kettle for mixing. 1300kg of cyclohexane and 89kg of the complex obtained in Preparation Example 2 were added into the cyclization reaction kettle, the reaction kettle was started for stirring, and the prepared mixed solution was added dropwise, the reaction temperature was controlled at 15-20°C, the dropping time was about 5-6h, and the stirring was stopped after the dropping was completed. After standing for 1h, the lower layer of the complex was released and transferred to the catalyst insulation kettle, the upper clear liquid was washed with 300L of water, 200L of alkaline water, and 300L of water, and the cyclohexane cymene was removed by decompression and precipitation, and 549kg of white crystals were obtained after recrystallization and suction filtration, with a purity of 98.5%, and the calculated yield of the reaction was 70.1%.

[0045] Example 3 Effect of Complex Storage Temperature on Reaction Yield

[0046] The complex was prepared according to the method in Example 1, and after the preparation was completed, it was transferred to an insulated kettle, and the temperature in the kettle was stored at -5 to 0°C, 0 to 5°C (excluding 0°C), 6 to 10°C, 11 to 15°C, 16 to 20°C, and 21 to 25°C, and the cyclization reaction was carried out according to the method in Example 1. When the storage temperature was lower than 0°C, the complex adhered and it was difficult to release it by opening the bottom valve of the insulated kettle, so the complex was stored above 0°C. The yield results are shown in Table 1.

[0047] Table 1:

[0048]

[0049] When the storage temperature is 5°C, the preparation yield in Example 1 is 70.5%. As can be seen from Table 1, when the storage temperature increases, the yield of HMT prepared gradually decreases, but a relatively high yield is still maintained at 6-10°C. Therefore, the preferred storage temperature of the complex catalyst is 0-10°C, preferably 0-5°C.

[0050] Example 4 Effect of the number of times the complex is applied on the reaction yield

[0051] The complex was prepared according to the method in Preparation Example 1, and the complex after each reaction was transferred to an insulated kettle and stored at 0-5°C. The complex catalyst was applied according to the preparation method in Example 1 and the yield was calculated as shown in Table 2.

[0052] Table 2:

[0053]

[0054] It is not difficult to see from Table 2 that the complex catalyst obtained in Preparation Example 1 can maintain a relatively high yield after being repeatedly used 10 times.

[0055] Comparative Example

[0056] 800kg of cymene, 340kg of tert-butyl chloride and 300kg of 2,3-dimethyl-1-butene were put into the preparation kettle for mixing. 1300kg of cyclohexane and 52kg of aluminum chloride were added into the cyclization reaction kettle, the reaction kettle was started for stirring, and the prepared mixed solution was added dropwise, the reaction temperature was controlled at 15-20°C, the dropping time was about 5-6h, and the stirring was stopped after the dropping was completed. The reaction solution was transferred to the hydrolysis kettle, hydrolyzed with 300L of water, washed with 200L of alkaline water and 300L of water, and cyclohexane cymene was removed by decompression and precipitation, and 448kg of white crystals were obtained after recrystallization and suction filtration, with a purity of 97.9% and a reaction yield of 57.3%.

[0057] It is not difficult to see that the actual yield of HMT prepared in Comparative Example 1 is quite different from the highest yield of 70% recorded in the literature. In addition, compared with Example 1 and Preparation Example 1, under the same conditions, the reaction yield of HMT prepared in the comparative example is significantly lower. In contrast, the complex catalyst prepared using this scheme can meet the yield requirements of industrial scale-up.

[0058] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a complex catalyst, characterized in that the steps include: Under stirring, tert-butyl chloride is added dropwise to a mixed solution containing p-isopropyl toluene, a cyclic hydrocarbon solvent, and aluminum chloride to obtain a complex catalyst; the tert-butyl chloride is added dropwise at a temperature of 15 to 35° C., the addition time is controlled at 0.5 to 1 h, and the reaction time after the addition is completed is 0.5 to 2 h.

2. The preparation method according to claim 1, characterized in that: The molar ratio of p-isopropyl toluene, cyclic hydrocarbon solvent, aluminum chloride and tert-butyl chloride is (1-3): (3-5): (0.25-0.45): (0.3-0.5).

3. The preparation method according to claim 1, characterized in that: The molar ratio of p-isopropyl toluene, cyclic hydrocarbon solvent, aluminum chloride and tert-butyl chloride is 1.2:4:0.45:0.5; and / or, the cyclohydrocarbon solvent is cyclohexane; And / or, the dropping temperature is controlled at 15°C, the dropping is completed in 45 minutes, and the stirring reaction is carried out for 1 hour after the dropping is completed; And / or, negative pressure is turned on during the dropping process.

4. The use of a complex catalyst in the catalytic preparation of 1,1,3,4,4,6-hexamethyltetralin, characterized in that: The complex catalyst is prepared by the preparation method described in claim 1.

5. The use according to claim 4, characterized in that: The complex catalyst is used for improving the preparation yield of 1,1,3,4,4,6-hexamethyltetralin.

6. The preparation method of 1,1,3,4,4,6-hexamethyltetralin, characterized in that the steps include: S1. Obtaining and preserving the catalyst, and / or recovering the catalyst; the catalyst is selected from the complex catalyst prepared by the preparation method according to any one of claims 1-3; S2. Under stirring, the mixed solution is added dropwise to the catalyst solution to which the cyclic hydrocarbon solvent is added, the addition time is 5 to 6 hours, and the reaction temperature is 10 to 20° C.; the mixed solution includes p-isopropyl toluene, tert-butyl chloride and 2,3-dimethyl-1-butene; S3. After the reaction is completed, the reaction mixture is allowed to stand and the lower complex is separated and stored to recover the catalyst. The upper clear liquid is washed with water, desolventized, and recrystallized to obtain 1,1,3,4,4,6-hexamethylnaphthalene.

7. The preparation method according to claim 6, characterized in that: In step S1, the storage temperature of the complex catalyst is 0-10°C.

8. The preparation method according to claim 6, characterized in that: In step S2, the molar ratio of p-isopropyltoluene, tert-butyl chloride, 2,3-dimethyl-1-butene, cyclic hydrocarbon solvent and complex catalyst is (5-7): (3.5-4.5): (3.2-4.4): (14-17): (0.3-0.45).

9. The preparation method according to claim 6, characterized in that: In step S2, the molar ratio of p-isopropyltoluene, tert-butyl chloride, 2,3-dimethyl-1-butene, cyclic hydrocarbon solvent and complex catalyst is 5.97: 3.67: 3.57: 15.47: 0.

39.

10. The preparation method according to claim 6, characterized in that: In step S3, the water washing process includes first performing a first water washing, then performing an alkaline water washing, and then performing a second water washing.

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