Method for synthesizing sandalwood ether from melonal

Abstract

The invention provides a method for synthesizing santalyl ether from melonal, which comprises the following steps: carrying out etherification reaction on melonal and methanol under the action of a catalyst to obtain methoxy melonal, and carrying out addition on the methoxy melonal by using a methyl metal reagent to obtain the santalyl ether. The synthetic route is novel and short, the inexpensive and easily available melonaldehyde is used as the raw material, the sandalwood ether product is obtained through etherification and Grignard addition two-step reaction, and the method has the advantages of high reaction yield, few three wastes, simplicity and convenience in operation and the like, and is easy for large-scale production. Compared with a traditional dihydromyrcene route, the method does not involve high-pressure hydrogenation and does not produce a methoxy citronellol byproduct, and the route yield is remarkably improved.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals and flavors and fragrances, and specifically relates to a method for synthesizing sandalwood ether by taking melonaldehyde as a raw material. Background Art

[0002] Sandalwood is a rare plant that originates overseas. High-quality natural sandalwood oil can only be extracted from sandalwood that is over 30 years old. Natural sandalwood oil has a rich and elegant aroma, with a slight cool feeling. It not only has good permeability, but also has a long lasting fragrance. It is a very precious fragrance raw material. Currently, the most precious sandalwood oil in the world is produced in eastern India. Due to the very limited sandalwood resources and the strict control of the Indian government in recent years, natural sandalwood oil is in short supply and the price has soared, causing many downstream customers to turn to look for substitutes for natural sandalwood oil, which has greatly promoted the research, development and application of synthetic sandalwood.

[0003] The main aroma components of natural santalol are α-santalol and β-santalol, of which β-santalol is the main source of its aroma. The structural formulas of the two are shown below. Since the chemical structure of β-santalol is very complex and artificial synthesis requires multi-step reactions, the cost of synthesizing natural β-santalol is high and its practical application is limited. In order to obtain cheap sandalwood fragrance, synthetic chemists have developed a variety of santalol substitutes, such as santalum 208, santalum 210, white sandalwood, black sandalwood, etc. These substitutes have the characteristic aroma of sandalwood and are low in cost, which has promoted the promotion and application of sandalwood fragrances.

[0004]

[0005] Sandalwood ether is an important monomer fragrance with the aroma of sandalwood and flowers, which is rich and pleasant. Sandalwood ether is also a substitute for β-santalol. It was first discovered by Bush Boake Allen in 1973 and is the only known linear sandalwood fragrance. Sandalwood ether is a colorless and transparent liquid at room temperature. Its chemical properties are stable and it is not easy to cause discoloration when added to downstream products. Sandalwood ether has a fresh, elegant and delicate sandalwood aroma, as well as a certain floral fragrance. It has good permeability and is widely used in various daily chemical products such as soaps, cosmetics, and perfumes.

[0006] The main synthesis route of sandalwood ether is as follows (DE2255119). First, natural dihydromyrcene reacts with methanol under the action of an acid catalyst to obtain methoxydihydromyrcene, followed by further epoxidation to obtain epoxide, and finally hydrogenation reduction to obtain the sandalwood ether product. This is the current mainstream synthesis route of sandalwood ether. Its raw material dihydromyrcene is cheap and easy to obtain in large quantities, and has good feasibility of amplification production. However, it is worth noting that this route also has some obvious defects, such as a long synthesis route, low hydrogenation selectivity, and more methoxycitronellol as a by-product. These factors cause the cost of sandalwood ether to be higher, and it cannot compete with relatively cheap products such as sandalwood 803 and sandalwood 210, which limits the widespread use of sandalwood ether.

[0007]

[0008] In summary, santal ether is a very good synthetic sandalwood product with elegant and delicate fragrance, stable chemical properties, and no discoloration. At present, the main synthesis route of santal ether is to use dihydromyrcene as raw material, and synthesize it through three steps of etherification, epoxidation, and hydrogenation. The long synthesis route and poor hydrogenation selectivity lead to high cost of santal ether, which limits the promotion and use of santal alcohol.

[0009] In order to prepare sandalwood ether products more economically, it is urgent to develop new synthesis routes, improve the synthesis yield, and reduce the production cost of sandalwood ether. Summary of the invention

[0010] The purpose of the present invention is to provide a method for synthesizing santal ether in a simple and efficient manner using melonaldehyde as a raw material. The method realizes the efficient and low-cost synthesis of santal ether, uses cheap and readily available melonaldehyde as a raw material, and obtains the santal ether product through two-step reactions such as etherification and Grignard addition, and has the characteristics of high overall synthesis yield, less "three wastes", simple operation, and easy scale-up production; in addition, compared with the traditional dihydromyrcene route, the method does not involve high-pressure hydrogenation and has the advantages of no methoxycitronellol by-product, etc.

[0011] In order to achieve the above objectives and the above technical effects, the present invention adopts the following technical solutions:

[0012] A method for synthesizing santal ether from melonaldehyde comprises the following steps:

[0013] S1, melonaldehyde and methanol undergo etherification reaction under the action of a catalyst to obtain methoxymelonaldehyde;

[0014] S2. Methyl metal reagents react with methoxymelonaldehyde to obtain sandalwood ether.

[0015] The reaction equation for synthesizing santal ether from melonaldehyde of the present invention is shown as follows:

[0016]

[0017] In the present invention, the reactor in S1 is a stacked bed or a tube-in-tube reactor, in which the catalyst is loaded; the reaction material is fed in a top-in and bottom-out or bottom-in and top-out manner.

[0018] In the present invention, the catalyst used in S1 is an acid resin solid catalyst, which may be but is not limited to one or more of sulfonic acid resin, phosphoric acid resin, carboxylic acid resin, phenolic hydroxyl resin, preferably sulfonic acid resin.

[0019] In the present invention, the reaction temperature of the etherification reaction in S1 is 60-110°C, preferably 70-80°C; and / or, the reaction pressure is 0.1-0.5 MPaG, preferably 0.1-0.2 MPaG; and / or, the mass space velocity is 0.2-6.0 h -1 .

[0020] In the present invention, the feed liquid in S1 is composed of melonal, methanol and water, wherein the feed molar ratio of melonal to methanol is 1:13 to 1:30; the feed molar ratio of melonal to water is 1:0.3 to 1:1; preferably, the feed liquid also includes a small amount of silanol, and the molar ratio of melonal to silanol is 20 to 200:1; more preferably, the feed temperature is room temperature.

[0021] In the present invention, the methyl metal reagent in S2 is selected from at least one of methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, dimethylzinc, trimethylaluminum, and methyllithium, preferably methylmagnesium chloride and methylmagnesium bromide; preferably, the amount of the methyl metal reagent is 80 to 150 mol% of the molar amount of methoxymelonaldehyde.

[0022] In the present invention, the reaction in S2 is carried out in the presence of an aprotic solvent, and preferably the aprotic solvent is selected from one or more of diethyl ether, propyl ether, isopropyl ether, butyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, benzene, and toluene, and more preferably tetrahydrofuran and diethyl ether; preferably, the amount of the solvent used is 1.5 to 4.0 times the mass of methoxymelonal.

[0023] In the present invention, the reaction temperature of the S2 addition reaction is -20 to 50°C, preferably 0 to 20°C, and / or the reaction pressure is normal pressure, and the reaction time is 2 to 4 hours.

[0024] In the present invention, after the addition reaction is complete, a step of adding a quenching agent to quench the reaction is also included. The quenching agent can be, but is not limited to, water, ammonium chloride aqueous solution, ammonium sulfate aqueous solution, ammonium phosphate aqueous solution, acetic acid aqueous solution, dilute hydrochloric acid, etc. The added volume of the quenching agent is 0.22 to 0.70 times the volume of the methyl metal reagent.

[0025] The present invention adopts the above technical solution and has the following positive effects:

[0026] 1. The synthetic route of the present invention is novel and short. The inexpensive and readily available melonaldehyde is used as a raw material. The sandalwood ether product is obtained through two-step reactions of etherification and Grignard addition. The invention has the advantages of high reaction yield, less "three wastes", simple operation, etc., and is easy to scale up production.

[0027] 2. In the etherification reaction, the present invention adopts a fixed bed continuous process and uses a solid acid catalyst, which has the advantages of stable process and high raw material conversion.

[0028] 3. The present invention adds a small amount of water to the etherification reaction feed liquid to inhibit the generation of acetal by-products, thereby effectively improving the selectivity of methoxymelonaldehyde. DETAILED DESCRIPTION

[0029] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0030] The main raw material information is as follows:

[0031] Melonaldehyde, Beida Zhengyuan, 85%, used after distillation and purification; Strong acid cationic resin 001*7, 001*4, D201, Dandong Mingzhu, industrial grade; Strong acid cationic resin Diaion PLK228, Amberlite IR-120, Sigma-Aldrich reagent. Methanol, Aladdin reagent, chromatographic grade; Trimethylsilanol, 97%, Xianghui Pharmaceutical.

[0032] Anhydrous tetrahydrofuran, ether, methyl tert-butyl ether, chromatographically pure, Aladdin reagent. Methylmagnesium chloride, Xiya reagent, 2M THF solution; methylmagnesium bromide, Myrel reagent, 1M THF solution; dimethylzinc, Aladdin reagent, 1M toluene solution; trimethylaluminum, Aike reagent, 2M toluene solution; methylmagnesium iodide, Aladdin reagent, 3M ether solution; methyllithium, Aladdin reagent, 1.6M THF solution. Anhydrous ammonium chloride, sodium sulfate, sodium chloride, Sinopharm reagent, AR.

[0033] The gas chromatography test conditions of the present invention are as follows:

[0034] Instrument model: Agilent 7890B; Chromatographic column: Capillary column HP-5 (60m×0.30mm×0.25μm); Initial temperature 40.0℃, rise to 100.0℃ at a rate of 5.0℃ / min; then rise to 200.0℃ at a rate of 10.0℃ / min, keep for 15.0min; then rise to 240.0℃ at a rate of 20.0℃ / min, keep for 5.0min. Carrier gas high-purity nitrogen, split ratio 30:1, split flow 42.0mL / min. Carrier gas saving: 28.0mL / min, start waiting time 5.0min. Injection temperature 250.0℃, detector is FID, detector temperature 280.0℃, air flow 350.0mL / min, hydrogen flow 30.0mL / min, tail gas flow 50.0mL / min, injection volume 0.2μL.

[0035] Example 1

[0036] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0037] First, prepare the feed liquid. Add methanol (100.9 g, 3.15 mol), melonaldehyde (29.5 g, 0.21 mol), water (1.13 g, 0.063 mol) and trimethylsilanol (0.2 g, 0.0021 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0038] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm long and has an inner diameter of 2.2 cm. The middle part of the reaction tube is filled with Dandong Mingzhu 001*7 strong acid resin catalyst (100 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor, and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 60°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 3.3 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 2.0 h -1 Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 96%, and the selectivity of methoxymelonaldehyde is 98%.

[0039] The product methoxymelonal is a known compound, and its GC peak time is consistent with that of the standard. The high-resolution mass spectrometry data are as follows: HRMS-EI M + Calcd for C 10 H 20 O2:172.1463, found 172.1462.

[0040] Example 2

[0041] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0042] First, prepare the feed liquid. Add methanol (147.4 g, 4.6 mol), melonaldehyde (32.3 g, 0.23 mol), water (4.1 g, 0.23 mol) and trimethylsilanol (0.21 g, 0.0023 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0043] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm long and has an inner diameter of 2.2 cm. The middle part of the reaction tube is filled with Dandong Mingzhu 001*7 strong acid resin catalyst (100 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor, and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 80°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 5.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 3.0 h -1 Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 99%, and the selectivity of methoxymelonaldehyde is 98%.

[0044] Example 3

[0045] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0046] First, prepare the feed liquid. Add methanol (1268.9 g, 39.6 mol), melonaldehyde (185.1 g, 1.32 mol), water (11.9 g, 0.66 mol) and trimethylsilanol (5.95 g, 0.066 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0047] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm in length and 2.2 cm in inner diameter. The middle part of the reaction tube is filled with Dandong Mingzhu 001*4 strong acid resin catalyst (80 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers for fixing and supporting the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor, and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 110°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 8.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 6.0 h -1 Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 96%, and the selectivity of methoxymelonaldehyde is 98%.

[0048] Example 4

[0049] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0050] First, prepare the feed liquid. Add methanol (842.1 g, 26.3 mol), melonaldehyde (204.7 g, 1.46 mol), water (13.2 g, 0.73 mol) and trimethylsilanol (1.32 g, 0.0146 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0051] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm long and has an inner diameter of 2.2 cm. The middle part of the reaction tube is filled with Dandong Mingzhu D201 strong acid resin catalyst (110 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers for fixing and supporting the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor, and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 60°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 2.75 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 1.5 h -1 Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 97%, and the selectivity of methoxymelonaldehyde is 98%.

[0052] Example 5

[0053] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0054] First, prepare the feed liquid. Add methanol (182.6 g, 5.7 mol), melonaldehyde (53.3 g, 0.38 mol), water (4.1 g, 0.23 mol) and trimethylsilanol (0.34 g, 0.0038 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0055] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm long and has an inner diameter of 2.2 cm. The middle part of the reaction tube is filled with Diaion PLK228 strong acid resin catalyst (121 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor, and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the reaction tube jacket, raise the temperature of the reaction tube to 60°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 0.4 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 0.2h -1Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 99%, and the selectivity of methoxymelonaldehyde is 98%.

[0056] Example 6

[0057] Synthesis of Methoxymelonal from Melonal Catalyzed by Resin

[0058] First, prepare the feed liquid. Add methanol (495.7 g, 15.5 mol), melonaldehyde (166.9 g, 1.19 mol), water (15.0 g, 0.83 mol) and trimethylsilanol (0.54 g, 0.006 mol) into a wide-mouth bottle in sequence. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir thoroughly, and mix evenly to obtain a clear, transparent, and uniform feed liquid with a slight yellow color.

[0059] This step of the reaction is carried out in a tubular reactor. The reaction tube used is 60 cm long and has an inner diameter of 2.2 cm. The middle part of the reaction tube is filled with Amberlite IR-120 strong acid resin catalyst (106 g, purity 99%). The upper and lower ends of the reaction tube are filled with ceramic ball fillers for fixing and supporting the resin catalyst. In the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Turn on the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 90°C, and turn on the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 5.3 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 3.0 h -1 Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals. The internal standard n-octane is added to the reaction liquid, and then analyzed by GC chromatography. The results show that the conversion rate of raw material melonaldehyde is 97%, and the selectivity of methoxymelonaldehyde is 99%.

[0060] Example 7

[0061] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Grignard Reagent

[0062] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (33.6g) and raw material methoxymelonaldehyde (22.4g, 0.13mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put a tetrahydrofuran solution of methylmagnesium chloride (71.5mL, 2.0M) into a constant pressure dropping funnel, and add it dropwise to the three-necked flask under rapid stirring. Control the dropping speed of methylmagnesium chloride to keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring the reaction for 1 hour, sample analysis, GC detection, the raw material methoxymelonaldehyde is basically reacted completely, the conversion rate is>99.0%, and the selectivity of the product santal ether is>99.0%.

[0063] Saturated ammonium chloride aqueous solution (50 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution first became suspended, then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel. After the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in sequence. After the organic phase was dried over anhydrous sodium sulfate, the sandalwood ether product was obtained by filtering and distillation.

[0064] The obtained sandalwood ether product is a known compound, and its GC peak time is consistent with that of the standard product. The high-resolution mass spectrometry data are as follows: HRMS-EI M + Calcd for C 11 H 24 O2:188.1776, found 188.1778.

[0065] Example 8

[0066] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Grignard Reagent

[0067] First, place a 1L three-necked flask in a low-temperature bath, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (103.2g) and raw material methoxymelonaldehyde (25.8g, 0.15mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put a tetrahydrofuran solution of methylmagnesium bromide (225.0mL, 1.0M) into a constant pressure dropping funnel, and add it dropwise to the three-necked flask under rapid stirring. Control the dropping speed of methylmagnesium bromide to keep the reaction solution in the three-necked flask at about -20°C, and the maximum does not exceed -15°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring and reacting for 3 hours, sample analysis, GC detection, the raw material methoxymelonaldehyde is basically reacted completely, the conversion rate is>99.0%, and the selectivity of the product santal ether is>99.0%.

[0068] Saturated ammonium chloride aqueous solution (50 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution first became suspended, then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel. After the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in sequence. After the organic phase was dried over anhydrous sodium sulfate, the sandalwood ether product was obtained by filtering and distillation.

[0069] Example 9

[0070] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Dimethylzinc Reagent

[0071] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent ether (48.2g) and raw material methoxymelonaldehyde (24.1g, 0.14mol) to the three-necked flask in turn, start stirring, and mix evenly to obtain a clear and transparent liquid. Put a toluene solution of dimethyl zinc (154.0mL, 1.0M) into a constant pressure dropping funnel, and add it dropwise to the three-necked flask under rapid stirring. Control the dropping speed of the dimethyl zinc solution to keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. The reaction solution was heated to 50°C, and the stirring reaction was continued for 2 hours. Samples were taken for analysis and GC detection. The raw material methoxymelonaldehyde was basically reacted completely, the conversion rate was>99.0%, and the selectivity of the product santalin ether was>99.0%.

[0072] 10% ammonium acetate aqueous solution (50 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted dimethyl zinc reagent. The reaction solution first became suspended, then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel, and after the oil and water phases were separated, the organic phase was washed with a saturated ammonium chloride aqueous solution and a saturated saline solution in sequence. After the organic phase was dried over anhydrous sodium sulfate, the sandalwood ether product was obtained by filtering and distillation.

[0073] Example 10

[0074] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Trimethylaluminum Reagent

[0075] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent methyl tert-butyl ether (88.7g) and raw material methoxymelonaldehyde (35.3g, 0.205mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. The toluene solution of trimethylaluminum (82.0mL, 2.0M) is loaded into the constant pressure dropping funnel, and added dropwise to the three-necked flask under rapid stirring. The dripping speed of the trimethylaluminum solution is controlled to keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition is completed within 1 hour, and the reaction solution is light gray and slightly suspended. The reaction solution is heated to 50°C, and the stirring reaction is continued for 3 hours. Sample analysis and GC detection show that the raw material methoxymelonaldehyde is basically reacted completely, the conversion rate is>99.0%, and the selectivity of the product santalin ether is>99.0%.

[0076] Saturated ammonium chloride aqueous solution (50 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted trimethylaluminum reagent, and the reaction solution first became suspended, and then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel, and after the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in sequence, and the organic phase was dried over anhydrous sodium sulfate, and then filtered and distilled to obtain the sandalwood ether product.

[0077] Embodiment 11

[0078] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Grignard Reagent

[0079] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent ether (98.1g) and raw material methoxymelonaldehyde (32.7g, 0.19mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put methylmagnesium iodide ether solution (69.7mL, 3.0M) into the constant pressure dropping funnel, and add it dropwise to the three-necked flask under rapid stirring. Control the dripping speed of methylmagnesium iodide solution to keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring and reacting for 2 hours, sample analysis, GC detection, the raw material methoxymelonaldehyde is basically reacted completely, the conversion rate is>99.0%, and the selectivity of the product santalin ether is>99.0%.

[0080] 10% acetic acid aqueous solution (40 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent, and the reaction solution first became suspended, and then gradually clarified and separated. After post-treatment, the reaction solution was first placed in a separating funnel, and after the oil and water were separated, the organic phase was washed with a saturated ammonium chloride aqueous solution and a saturated salt water solution in sequence, and the organic phase was dried over anhydrous sodium sulfate, and then filtered and distilled to obtain the sandalwood ether product.

[0081] Example 12

[0082] Preparation of Santal Ether by Reaction of Methoxymelonaldehyde with Methyllithium Reagent

[0083] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (33.6g) and raw material methoxymelonaldehyde (29.3g, 0.17mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put methyl lithium ether solution (159.4mL, 1.6M) into the constant pressure dropping funnel, and add it dropwise to the three-necked flask under rapid stirring. Control the dropping speed of the methyl lithium solution to keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring and reacting for 3 hours, sample analysis, GC detection, the raw material methoxymelonaldehyde is basically reacted completely, the conversion rate is>99.0%, and the selectivity of the product santal ether is>99.0%.

[0084] Saturated ammonium chloride aqueous solution (50 mL) was added dropwise to the reaction solution through a constant pressure dropping funnel to quench the unreacted methyl lithium reagent, and the reaction solution first became suspended, and then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel, and after the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in sequence, and the organic phase was dried over anhydrous sodium sulfate, and then filtered and distilled to obtain the sandalwood ether product.

Claims

1. A method for synthesizing santal ether from melonaldehyde, characterized in that: The following steps are involved: S1, melonaldehyde and methanol undergo etherification reaction under the action of a catalyst to obtain methoxymelonaldehyde; S2. Methyl metal reagents react with methoxymelonaldehyde to obtain sandalwood ether.

2. The method according to claim 1, characterized in that The reactor in S1 is a stacked bed or a tube-in-tube reactor, in which the catalyst is loaded; Preferably, the reaction material feeding method is top-in and bottom-out or bottom-in and top-out.

3. The method according to claim 1 or 2, characterized in that: The catalyst in S1 is an acidic resin solid catalyst, preferably one or more of sulfonic acid resin, phosphoric acid resin, carboxylic acid resin, and phenolic hydroxyl resin, more preferably sulfonic acid resin.

4. The method according to claim 3, characterized in that The reaction temperature of the etherification reaction in S1 is 60 to 110° C., preferably 70 to 80° C.; and / or, The reaction pressure is 0.1 to 0.5 MPaG, preferably 0.1 to 0.2 MPaG; and / or, Mass space velocity is 0.2~6.0h -1 .

5. The method according to claim 4, characterized in that The feed liquid in S1 is composed of melonaldehyde, methanol and water, wherein the feed molar ratio of melonaldehyde to methanol is 1:13 to 1:30; the feed molar ratio of melonaldehyde to water is 1:0.3 to 1:1; Preferably, the feed solution also includes a small amount of silanol, and the molar ratio of melonaldehyde to silanol is 20 to 200:1; More preferably, the feed temperature is room temperature.

6. The method according to claim 1, characterized in that The methyl metal reagent in S2 is selected from at least one of methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, dimethylzinc, trimethylaluminum, and methyllithium, preferably methylmagnesium chloride or methylmagnesium bromide; Preferably, the amount of the methyl metal reagent used is 80 to 150 mol % of the molar amount of methoxymelonaldehyde.

7. The method according to claim 1 or 6, characterized in that: The reaction in S2 is carried out in the presence of an aprotic solvent; Preferably, the aprotic solvent is selected from one or more of diethyl ether, propyl ether, isopropyl ether, butyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, benzene, and toluene, preferably tetrahydrofuran or diethyl ether; More preferably, the amount of the aprotic solvent is 1.5 to 4.0 times the mass of methoxymelonal.

8. The method according to claim 7, characterized in that The reaction temperature of the S2 addition reaction is -20 to 50°C, preferably 0 to 20°C, and / or The reaction pressure is normal pressure, and the reaction time is 2 to 4 hours.

9. The method according to claim 1, characterized in that: After the addition reaction is completed, the method further includes adding a quenching agent to quench the reaction.

10. The method according to claim 9, characterized in that The quenching agent is selected from any one of water, ammonium chloride aqueous solution, ammonium sulfate aqueous solution, ammonium phosphate aqueous solution, acetic acid aqueous solution, and dilute hydrochloric acid; Preferably, the added volume of the quencher is 0.22 to 0.70 times the volume of the methyl metal reagent.

Images