Method for synthesizing borneol aldehyde and application thereof

Abstract

The application relates to the field of organic synthesis and discloses a method for synthesizing campholenic aldehyde, which comprises the following steps: contacting 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene and an oxidant in the presence of a first catalyst and a second catalyst, wherein the oxidant is an organic solution of a neutral organic peroxide, the first catalyst is an oxidation catalyst, and the second catalyst contains alkali metals and / or alkaline earth metals. The method can directly prepare campholenic aldehyde through two reactions of epoxidation and isomerization rearrangement in the same reaction system, the reaction process is reduced, the selectivity and yield of the campholenic aldehyde product are relatively high, the catalyst is easy to separate and has high recycling utilization rate, and the method has the advantages of simple operation steps and low production cost.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for synthesizing borneol and its application. Background Technology

[0002] Borneol is an important intermediate in the synthesis of sandalwood fragrances, serving as a starting material for a range of sandalwood fragrances. Borneol-based sandalwood fragrances synthesized from it are closer to natural sandalwood oil in terms of aroma and odor persistence than terpenoid cyclohexanols, and have therefore long attracted the attention of researchers. Numerous borneol-based sandalwood products developed by international perfume brands, including Firmenich sandalwood, White Lehman sandalwood, and Javanese sandalwood, have consistently received close attention and enjoyed strong sales.

[0003] Bornenaldehyde can be generated by further isomerization rearrangement of 2,3-epoxypinene obtained from the epoxidation reaction of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene (α-pinene). Existing production processes generally require two independent reaction steps: epoxidation and isomerization rearrangement. The two reactions involve product distillation and solvent recycling to collect pure or crude products, resulting in low final product yield, complex process steps, and high energy consumption in this two-step technical route.

[0004]

[0005] Currently, the oxidation of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to prepare epoxide pinane mainly relies on the peracetic acid method, which has problems such as high operational requirements, severe equipment corrosion, high safety risks, and significant environmental pollution. When the concentration of peracetic acid, used as the epoxidizing agent, is too low, the product yield decreases; when the concentration is too high, equipment corrosion intensifies, and the decomposition of peracetic acid accelerates, resulting in high safety risks. CN103833690 discloses a method for preparing 2,3-epoxide pinane using 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene. This method uses a low concentration of 18% peracetic acid as the oxidant and chloroform as the polar solvent below 20°C to increase the peroxide concentration in the organic phase. Simultaneously, sodium carbonate is added to the system to maintain neutrality and prevent ring-opening hydrolysis of the product. This method is complex to operate, and the final conversion rate of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene is 85.90%, while the selectivity for 2,3-epoxypinene is 80.84%. The peracetic acid method for synthesizing epoxypinene is only suitable for small-batch production, and safe and efficient large-scale synthesis processes are still lacking.

[0006] For the isomerization rearrangement of 2,3-epoxypine to produce bentonite aldehyde, US6515186B2 describes a method and apparatus for preparing bentonite aldehyde by reactive distillation of 2,3-epoxypine. This method pumps the raw material into a reactor containing zinc chloride, zinc bromide, or a mixture thereof from bottom to top, and uses post-distillation processing to recover toluene or benzene solvent and collect the bentonite aldehyde product. However, this method, using inorganic salts as catalysts in a fixed-bed reactor, easily clogs the liquid flow path, making it difficult to scale up for industrial production. CN1660746A discloses a method for synthesizing bentonite aldehyde from 2,3-epoxypine and a reactor for implementing this method. This process uses toluene or benzene as a solvent and Lewis acids such as zinc chloride or zinc bromide as catalysts. The isomerization rearrangement of 2,3-epoxypine is catalyzed in a scraped-plate reactor, and bentonite aldehyde is obtained through polymerization inhibition, water washing, and distillation. This method has low catalyst utilization and high energy consumption.

[0007] In summary, there is still a lack of efficient, convenient, and scalable process methods for the one-step preparation of borneol from pinene via epoxidation and isomerization rearrangement. Summary of the Invention

[0008] The purpose of this invention is to overcome the complex process in the prior art of synthesizing borneol in two steps, which requires the use of peroxidized organic acids as oxidants for the epoxidation reaction and Lewis acids as catalysts for the rearrangement reaction. The former has high reaction safety risks and severe equipment corrosion, while the latter requires additional distillation and purification of raw materials. This invention provides a method for synthesizing borneol, which can directly prepare borneol in one step by undergoing epoxidation and isomerization rearrangement reactions in the same reaction system. This reduces the number of reaction steps, and the borneol product has high selectivity and yield. The catalyst is easy to separate and has a high recycling rate. It has the advantages of simple operation steps and low production cost.

[0009] In this invention, the substrate raw material is pinene, CAS: 7785-26-4. Scientific name: (1S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene, also known as (1S)-(-)-alpha pinene.

[0010] This invention provides a method for synthesizing borneol, the method comprising: reacting 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene with an oxidant in the presence of a first catalyst and a second catalyst, wherein the oxidant is an organic solution of a neutral organic peroxide, the first catalyst is an oxidation catalyst, and the second catalyst contains an alkali metal and / or an alkaline earth metal.

[0011] According to a preferred embodiment of the present invention, the water content in the organic solution of the neutral organic peroxide is less than 10 wt%. The present invention, by performing oxidation in a system with lower aqueous content, enables the product, bornyl aldehyde, to exhibit higher selectivity (>70%).

[0012] In this invention, there are no special requirements for the type of neutral organic peroxide. Commonly used neutral organic peroxides are all applicable to this invention. The following is an illustrative description, but it does not limit the scope of this invention. According to a preferred embodiment of this invention, the neutral organic peroxide is one or more of tert-butanol hydroperoxide, cumene hydroperoxide, and ethylbenzene hydroperoxide, preferably one or more of cumene hydroperoxide and ethylbenzene hydroperoxide.

[0013] In this invention, the concentration of the organic solution of the neutral organic peroxide is not particularly required. It can be provided alone or as a solution. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the concentration of the organic solution of the neutral organic peroxide is 1-90 wt%, preferably 20-50 wt%.

[0014] In this invention, there are no special requirements for the type of organic solvent in the organic solution of the neutral organic peroxide. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the organic solvent in the organic solution of the neutral organic peroxide is one or more of acetonitrile, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, benzene, toluene, xylene, pentane, hexane, octane, cyclohexane, tert-butanol, n-butanol, methanol, ethanol, isopropanol, cyclohexanol, cumene, and ethylbenzene, preferably one or more of cumene and ethylbenzene.

[0015] According to a preferred embodiment of the present invention, the organic solution of the neutral organic peroxide is a cumene / isocumene hydroperoxide solution and / or an ethylbenzene / ethylbenzene hydroperoxide solution.

[0016] According to a preferred embodiment of the present invention, the concentration of the cumene hydroperoxide / cumene solution is 1-90 wt%, preferably 15-55 wt%.

[0017] According to a preferred embodiment of the present invention, the concentration of the hydrogen peroxide ethylbenzene / ethylbenzene solution is 1-45 wt%, preferably 10-40 wt%.

[0018] The aforementioned preferred technical solution can realize the conversion of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene into borneol in the same reaction system, which has the advantages of high product selectivity and yield, simple operation steps and low production cost.

[0019] In this invention, the contact reaction is carried out under dynamic conditions, such as by stirring. The stirring speed can be selected from a wide range. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the stirring speed is 500-1000 r / min.

[0020] In this invention, the weight ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the first catalyst can be selected within a wide range. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the weight ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the first catalyst is 0.2-100:1, preferably 2-6:1.

[0021] In this invention, the weight ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the organic solution of neutral organic peroxide can be selected within a wide range. The following is an illustrative example, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the organic solution of neutral organic peroxide is 30-90 g / 100 mL, preferably 60-90 g / 100 mL. This invention uses an excess of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene for the reaction, which is beneficial for improving the selectivity and yield of the bornene aldehyde product and reducing the risk of decomposition of residual organic peroxide during the distillation process.

[0022] In the contact reaction of the present invention, the reaction temperature can be selected within a wide range. The following is an illustrative description, but it does not limit the scope of the present invention. According to a preferred embodiment of the present invention, the reaction temperature is 25-130°C, preferably 60-120°C.

[0023] In the contact reaction of the present invention, the reaction pressure can be selected from a wide range. The following is an illustrative description, but it does not limit the scope of the present invention. According to a preferred embodiment of the present invention, the reaction pressure is 0.1-3 MPa, preferably 0.1-1 MPa.

[0024] In the contact reaction of the present invention, the reaction time can be selected within a wide range and can be adjusted according to the temperature. The following is an illustrative description, but it does not limit the scope of the present invention. According to a preferred embodiment of the present invention, the contact reaction time is 1-5 hours.

[0025] According to a preferred embodiment of the present invention, the contact reaction is carried out in an oxygen-free environment, preferably in an inert atmosphere, for example, the contact reaction can be carried out in a nitrogen atmosphere.

[0026] In this invention, there are no special requirements for the reactor used in the contact reaction. Any reactor that can meet the requirements of this invention can be used in this invention. For example, the contact reaction can be carried out in a batch reactor equipped with a temperature detector, a pressure detector and a constant speed stirrer.

[0027] In this invention, the method for synthesizing borneol further includes: distilling the reactants after the contact reaction to recover the raw materials and solvents, and purifying and collecting the borneol product. Subsequent distillation and purification steps have no special requirements and can be carried out according to conventional methods in the art, which will not be elaborated here. This invention further purifies and collects the borneol product and recovers 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene and organic solvents through distillation. Furthermore, the catalyst in this invention is easy to separate; for example, it can be recycled after separating the catalyst by filtration and recovering the liquid-phase product.

[0028] In this invention, the mass ratio of the first catalyst to the second catalyst can be selected within a wide range. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the mass ratio of the first catalyst to the second catalyst is 0.1-10:1, preferably 0.1-1:1.

[0029] In this invention, the range of types of the first catalyst is relatively wide, and commonly used oxidation catalysts such as titanium-silicon oxidation catalysts are all applicable to this invention. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the first catalyst is one or more of mesoporous titanium-silicon molecular sieves and modified mesoporous oxides.

[0030] According to a preferred embodiment of the present invention, the first catalyst is one or more of Ti-MCM-41, Ti-MCM-48, Ti-SBA-15, Ti-HMS, Ti-MTS-9, mesoporous TS-1, mesoporous TS-2, mesoporous Ti-beta, mesoporous Ti-MWW, mesoporous Ti-ZSM-12, mesoporous Ti-ZSM-48, mesoporous Ti-MCM-68, mesoporous Ti-FER, mesoporous Ti-MOR, mesoporous Ti-UTD molecular sieve, mesoporous Ti-supported amorphous silica, and mesoporous titanium silica oxide, preferably one or more of Ti-HMS molecular sieve and Ti-MCM-41 molecular sieve.

[0031] In this invention, the Ti content, specific surface area, and bulk density of the first catalyst are not subject to special requirements and can be selected according to actual needs. For example, the Ti content of the first catalyst can be 1.5-3 wt%, and the specific surface area can be 300-600 m². 2 / g, with a bulk density of 0.3-0.6.

[0032] In this invention, there are no special requirements for the type of the second catalyst. The following is an illustrative description, but it does not limit the scope of the invention. According to a preferred embodiment of the invention, the second catalyst is one or more of alkali metal oxides, alkali metal inorganic salts, alkaline earth metal oxides, and alkaline earth metal inorganic salts.

[0033] According to a preferred embodiment of the present invention, the second catalyst is one or more of calcium oxide, magnesium oxide, potassium oxide, sodium oxide, calcium sulfate, magnesium sulfate, potassium sulfate, sodium sulfate, calcium chloride, magnesium chloride, potassium chloride, sodium chloride, calcium carbonate, magnesium carbonate, potassium carbonate, and sodium carbonate, preferably one or more of calcium sulfate, magnesium sulfate, and sodium sulfate.

[0034] The method for synthesizing borneol provided by this invention enables the direct one-step preparation of borneol from pinene through a two-step reaction involving epoxidation and isomerization rearrangement within a single reactor, exhibiting high selectivity and yield of the borneol product. This method avoids the cumbersome steps of distillation and purification required in two-stage reaction processes, reducing the number of reaction steps. Furthermore, the catalyst is easily separated and recovered after the reaction, with a high recycling rate, offering advantages such as simple operation and low production cost.

[0035] This invention provides the application of the method described herein in the synthesis of sandalwood fragrance. The borneol obtained by this invention is an important intermediate in the synthesis of sandalwood fragrance and can be further used to synthesize a series of sandalwood fragrances. Detailed Implementation

[0036] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0037] The present invention will be described in detail below through embodiments. In the following embodiments, In this invention, an Agilent 7890B gas chromatograph (GC, Agilent Technologies, USA) was used for quantification, equipped with a flame ionization detector (FID) and an HP-1 nonpolar capillary column. The test conditions for the gas chromatograph were as follows: Injection volume: 1 μL, via autosampler Inlet temperature: 250℃, split ratio: 60:1 Column temperature: initial temperature 120℃, holding time 5 min. HP-1 chromatographic column The detector is set at 250°C.

[0038] The formula for calculating the conversion rate of CHP or EBHP is: Conversion rate = (1- ) 100%.

[0039] The formula for calculating the conversion rate of 2,3-epoxypine is: 100%.

[0040] The formula for calculating the selectivity of borneol (based on the change in the amount of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene (α-pinene) before and after the reaction) is as follows: 100%.

[0041] Example 1 10g of Ti-HMS molecular sieve (characteristic parameters: Ti content 2.6wt%, specific surface area 423m²) was used. 2 Calcium sulfate (with a bulk density of 0.45 g) and calcium sulfate in a mass ratio of 1:1, along with 50 g of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene, were added to a batch reactor and stirred at 800 r / min. High-pressure nitrogen was introduced, and the reactor was heated to the preset temperature and pressure: 70 °C and 1.0 MPa. Under these conditions, 60 mL of a 50 wt% cumene hydroperoxide (CHP) / cumene solution was added to the reactor. After reacting for 2 h, the product was filtered, and Ti-HMS was used to collect the solid calcium sulfate and the liquid product. The liquid product was analyzed by gas chromatography, and the results are shown in Table 1.

[0042] Example 2 10g of mesoporous modified Ti-MWW molecular sieve (characteristic parameters: Ti content 2.0wt%, specific surface area 486m²) was used. 2 Calcium chloride (with a bulk density of 0.45 g) and calcium chloride in a mass ratio of 1:1, along with 50 g of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene, were added to a batch reactor and stirred at 800 r / min. High-pressure nitrogen was introduced, and the reactor was heated to the preset temperature and pressure: 80 °C and 1.5 MPa. Under these conditions, 100 mL of a 20 wt% ethylbenzene hydrogen peroxide (EBHP) / ethylbenzene solution was added to the reactor. After reacting for 3 h, the product was filtered, and the Ti-MWW molecular sieve, calcium chloride solid, and liquid product were collected. The liquid product was analyzed by gas chromatography, and the results are shown in Table 1.

[0043] Example 3 10g of Ti-MCM-41 molecular sieve (characteristic parameters: Ti content 1.9wt%, specific surface area 335m²) was added. 2Magnesium sulfate and sodium sulfate (10g magnesium sulfate, 10g sodium sulfate) in a mass ratio of 1:2, along with 50g 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene, were added to a batch reactor and stirred at 1000 r / min. High-pressure nitrogen was introduced and the reactor was heated to the preset temperature and pressure (100℃ and 1.0 MPa). Under these conditions, 80 mL of a 30 wt% cumene hydroperoxide (CHP) / cumene solution was added to the reactor. After reacting for 4 h, the product was filtered, and the Ti-MCM-41 molecular sieve, magnesium sulfate, sodium sulfate solids, and liquid product were collected. The liquid product was analyzed by gas chromatography, and the results are shown in Table 1.

[0044] Example 4 The method was followed in Example 1, except that the mass ratio of the first catalyst to the second catalyst was 10:1, and the results are shown in Table 1.

[0045] Example 5 The method was followed in Example 1, except that the mass ratio of the first catalyst to the second catalyst was 1:10, and the results are shown in Table 1.

[0046] Example 6 The method of Example 1 was followed, except that the weight ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the first catalyst was 100:1, and the results are shown in Table 1.

[0047] Comparative Example 1 The method was followed in Example 1, except that calcium sulfate was not added. The results are shown in Table 1.

[0048] Comparative Example 2 The method of Example 1 was followed, except that Ti-HMS molecular sieve was not added. The results are shown in Table 1.

[0049] Comparative Example 3 The method of Example 2 was followed, except that calcium chloride was not added. The results are shown in Table 1.

[0050] Table 1. Conversion rates of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene and peroxides, and selectivity of each main and by-product, based on the product liquid composition. CHP / EBHP conversion rate 2,3-Epoxypine Conversion Borneol selectivity (calculated by the change in 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene before and after reaction) Example 1 99.7% 98.5% 87.1% Example 2 98.7% 98.3% 78.5% Example 3 98.2% 97.0% 81.4% Example 4 99.3% 98.2% 70.2% Example 5 98.2% 98.0% 80.8% Example 6 99.0% 96.1% 75.9% Comparative Example 1 99.4% 98.3% 41.4% Comparative Example 2 23.8%（*） 0.2% 0.0% Comparative Example 3 98.3% 97.6% 43.3% *CHP / EBHP conversion due to peroxide self-decomposition The preferred embodiments of the present invention have been described above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various specific technical features in any suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for synthesizing borneol, characterized in that, The method includes: reacting 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene with an oxidant in the presence of a first catalyst and a second catalyst, wherein the oxidant is an organic solution of a neutral organic peroxide, the first catalyst is an oxidation catalyst, and the second catalyst contains an alkali metal and / or an alkaline earth metal.

2. The method according to claim 1, wherein, The neutral organic peroxide is one or more of tert-butanol hydroperoxide, cumene hydroperoxide, and ethylbenzene hydroperoxide, preferably one or more of cumene hydroperoxide and ethylbenzene hydroperoxide.

3. The method according to claim 1 or 2, wherein, The concentration of the organic solution containing the neutral organic peroxide is 1-90 wt%, preferably 20-50 wt%; and / or The organic solvent in the organic solution of the neutral organic peroxide is one or more of acetonitrile, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, benzene, toluene, xylene, pentane, hexane, octane, cyclohexane, tert-butanol, n-butanol, methanol, ethanol, isopropanol, cyclohexanol, cumene, and ethylbenzene, preferably one or more of cumene and ethylbenzene.

4. The method according to any one of claims 1-3, wherein, The organic solutions of neutral organic peroxides are cumene / isocumene hydroperoxide solutions and / or ethylbenzene / ethylbenzene hydroperoxide solutions; Preferably, The concentration of the cumene hydroperoxide / cumene solution is 1-90 wt%, preferably 15-55 wt%. The concentration of the hydrogen peroxide / ethylbenzene solution is 1-45 wt%, preferably 10-40 wt%.

5. The method according to any one of claims 1-4, wherein, The conditions for a contact reaction include: The contact reaction takes place under dynamic conditions; and / or The weight ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to the first catalyst is 0.2-100:1, preferably 2-6:1; and / or The ratio of 2,6,6-trimethyl-bicyclo[3.1.1]hept-2-ene to a neutral organic peroxide in an organic solution is 30-90 g / 100 mL, preferably 60-90 g / 100 mL; and / or The reaction temperature is 25-130℃, preferably 60-120℃; and / or The reaction pressure is 0.1-3 MPa, preferably 0.1-1 MPa; and / or The reaction time is 1-5 hours; and / or The contact reaction is carried out in an oxygen-free environment, preferably in an inert atmosphere.

6. The method according to any one of claims 1-5, wherein, The method also includes: distilling the post-contact reaction stream to recover the raw materials and solvents, and purifying and collecting the borneol product.

7. The method according to any one of claims 1-6, wherein, The mass ratio of the first catalyst to the second catalyst is 0.1-10:1, preferably 0.1-1:

1.

8. The method according to any one of claims 1-7, wherein, The first catalyst is one or more of mesoporous titanium silica molecular sieves and modified mesoporous oxides; preferably, the first catalyst is one or more of Ti-MCM-41, Ti-MCM-48, Ti-SBA-15, Ti-HMS, Ti-MTS-9, mesoporous TS-1, mesoporous TS-2, mesoporous Ti-beta, mesoporous Ti-MWW, mesoporous Ti-ZSM-12, mesoporous Ti-ZSM-48, mesoporous Ti-MCM-68, mesoporous Ti-FER, mesoporous Ti-MOR, mesoporous Ti-UTD molecular sieves, mesoporous Ti-supported amorphous silica, and mesoporous titanium silica oxides, preferably one or more of Ti-HMS molecular sieves and Ti-MCM-41 molecular sieves.

9. The method according to any one of claims 1-8, wherein, The second catalyst is one or more of alkali metal oxides, alkali metal inorganic salts, alkaline earth metal oxides, and alkaline earth metal inorganic salts; preferably, the second catalyst is one or more of calcium oxide, magnesium oxide, potassium oxide, sodium oxide, calcium sulfate, magnesium sulfate, potassium sulfate, sodium sulfate, calcium chloride, magnesium chloride, potassium chloride, sodium chloride, calcium carbonate, magnesium carbonate, potassium carbonate, and sodium carbonate, and more preferably one or more of calcium sulfate, magnesium sulfate, and sodium sulfate.

10. The application of the method according to any one of claims 1-9 in the synthesis of sandalwood fragrance.

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