A method for the cyclodehydration synthesis of salicylates

Abstract

The application provides a method for synthesizing salicylate by cyclization and dehydrogenation, specifically, C3 aldehyde and acetoacetic ester are subjected to gas phase cyclization reaction under the catalysis of a solid base to obtain 2-oxo-3-cyclohexene acid ester intermediate, and the intermediate is then subjected to dehydrogenation aromatization under the action of a dehydrogenation catalyst and an assistant to obtain salicylate product. The application uses cheap and readily available C3 aldehyde and acetoacetic ester as starting materials, quickly synthesizes salicylate through two steps, has a short synthesis route, high yield, less waste and good cost advantage; in the gas phase condensation cyclization reaction, lithium phosphate and potassium salt solid mixture are used as the catalyst to efficiently catalyze the condensation reaction of C3 aldehyde and acetoacetic ester, and 2-oxo-3-cyclohexene acid ester intermediate is obtained; in the dehydrogenation reaction, the dehydrogenation catalyst and nitrite assistant are used in combination, the nitrite promotes the isomerization between the ketonic form and the enolic form of 2-oxo-3-cyclohexene acid ester, reduces the temperature required for the dehydrogenation reaction, and promotes the dehydrogenation reaction.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of fine chemical and essence and perfume, and particularly relates to a method for rapidly synthesizing salicylate by two-step reactions of condensation and dehydroaromatization, using C3 aldehyde and acetoacetate as raw materials. BACKGROUND

[0002] Salicylate compounds have a wide range of uses, many of which can be used as perfumes. Common salicylates include methyl salicylate, ethyl salicylate, isoamyl salicylate, benzyl salicylate, etc. Methyl salicylate, also known as methyl o-hydroxybenzoate, methyl salicylate, etc., is naturally present in essential oils such as wintergreen oil, birch oil, green tea seed oil, clove oil, etc. Methyl salicylate has a strong wintergreen oil aroma and can be used to formulate various types of daily chemical fragrances, such as ylang-ylang, tuberose, orchid, acacia, etc. Its most common use is in toothpaste. There is no limit to its use amount IFRA. Ethyl salicylate and methyl salicylate have similar wintergreen oil aroma and can be used to formulate acacia, locust, ylang-ylang, lily, etc. They can replace and modify the aroma and odor of methyl salicylate in toothpaste and other oral care products. Salicylate esters derived from higher alcohols have better aroma, such as isoamyl salicylate, which has a scent similar to orchid and clover, and also has a certain sweetness. It can be used to formulate fruit type for food and is one of the most important products of salicylate derivatives. n-Pentyl salicylate has a lily of the valley scent and can be used in soap fragrances. Benzyl salicylate has a weak aroma, but has a high boiling point and strong solubility. It is a very good solvent and fixative and is commonly used as a cosolvent and fixative in floral fragrances. It can also be used as a bactericidal preservative.

[0003] Currently, salicylate is generally obtained by salicylate esterification in industry. The catalyst is usually a cheap strong acid such as concentrated sulfuric acid. Although this process is relatively simple, the strong acid has strong corrosion to the equipment, and the treatment of waste acid is difficult, the wastewater volume is large, and the environmental pollution is serious. In addition, the oxidation of concentrated sulfuric acid is strong, causing many side reactions, which further reduces the product yield. The raw material salicylic acid is usually prepared from phenol. First, phenol reacts with sodium hydroxide to obtain sodium phenoxide. After distillation and dehydration, carbon dioxide is introduced for carboxylation. The reaction system requires strict water-free, and the reaction raw materials need to be dehydrated and dried in advance. When the reaction pressure reaches 0.7-0.8 MPa, stop introducing carbon dioxide, and continue to react at a temperature of 140-180℃. After the reaction is completed, add water to dissolve the sodium salicylate, then decolorize, filter, and then acidify with sulfuric acid to precipitate salicylic acid. After filtration, washing, and drying, the salicylic acid product is obtained. The production process of salicylic acid also produces a large amount of high-COD wastewater, which is difficult to biologically treat.

[0004]

[0005] In summary, salicylate compound is a very important basic fine chemical product, widely used in medicine, pesticide, perfume and other fields, its preparation method is generally using esterification method, that is, salicylic acid and alcohol are esterified and dehydrated under the catalysis of concentrated sulfuric acid, no matter the esterification process or the production process of raw material salicylic acid, there are problems of harsh reaction conditions (strong acid, high heat), strong corrosion to equipment, and much wastewater. Therefore, at present, it is necessary to develop a new type of high-efficiency synthesis route of salicylate, which can synthesize salicylate product simply, efficiently and under mild conditions, reduce the three wastes of process, improve the economy of project, and protect the ecological environment. SUMMARY

[0006] The purpose of the present application is to provide a method for synthesizing salicylate by 2-step reactions of cyclization and dehydroaromatization, taking C3 aldehyde and acetoacetic ester as raw materials.

[0007] In order to achieve the above-mentioned purposes and achieve the above-mentioned technical effects, the present application adopts the following technical solutions:

[0008] A method for synthesizing salicylate by cyclization and dehydrogenation reaction: taking C3 aldehyde and acetoacetic ester as raw materials, under the action of solid alkali microparticle catalyst, the two undergo gas phase condensation and cyclization reaction to obtain 2-oxo-3-cyclohexene ester intermediate, then the intermediate is dehydrogenated and aromatized under the action of dehydrogenation catalyst and adjuvant to obtain salicylate product; the reaction equation is shown as follows.

[0009]

[0010] In the present application, the C3 aldehyde is selected from one or more of propenal, 3-hydroxypropanal, 3-methoxypropanal, 3-ethoxypropanal, 3-chloropropanal, 3-acetyloxypropanal and the like, and acetal derivatives of the above-mentioned C3 aldehyde such as dimethoxy acetal, diethoxy acetal, ethylene glycol acetal and the like; the acetoacetic ester is selected from one or more of methyl acetoacetate, ethyl acetoacetate, benzyl acetoacetate, n-pentyl acetoacetate and isoamyl acetoacetate.

[0011] In the present application, the solid alkali catalyst is a mixture of lithium salt and potassium salt, the lithium salt is selected from one or more of lithium hydroxide, lithium carbonate and lithium phosphate, preferably lithium phosphate; the potassium salt is selected from one or more of potassium fluoride, potassium carbonate and potassium phosphate, preferably potassium fluoride; the mass ratio of the two is 4-19:1.

[0012] In the present application, the reaction weight hourly space velocity is 0.2-2.0h -1 , preferably 0.5-2.0h -1 .

[0013] In the present application, the feed molar ratio of the C3 aldehyde, acetoacetic ester is preferably 1:2-1:4; the condensation reaction temperature is preferably 260-310 DEG C, and the reaction pressure is normal pressure.

[0014] In the present application, the gas phase condensation feed liquid can be added with a solvent or without a solvent, and preferably without a solvent; if a solvent is added, the solvent can be but is not limited to ethyl acetate, tetrahydrofuran, methyl tert-butyl ether, ethanol, acetonitrile, diethyl ether, etc.

[0015] In the present application, the dehydrogenation catalyst is selected from one or more of 0.5-10% palladium on carbon, 0.5-10% palladium on alumina, 0.5-10% palladium on silica, 0.5-10% platinum on carbon, 0.5-10% ruthenium on carbon, 0.5-10% rhodium on carbon, platinum oxide, Raney nickel, Raney cobalt, the amount of the dehydrogenation catalyst is 0.1-5.0 wt% of 2-oxo-3-cyclohexene acid ester, preferably 0.5-2.0 wt%; the auxiliary agent is selected from one or more of lithium nitrite, sodium nitrite, potassium nitrite, magnesium nitrite, zinc nitrite, copper nitrite, iron nitrite, the amount of the auxiliary agent is 0.1-1.0 wt% of 2-oxo-3-cyclohexene acid ester, preferably 0.2-1.0 wt%.

[0016] In the present application, the dehydrogenation aromatization reaction can be carried out under solvent-free conditions or in high-boiling solvents such as toluene, dimethylbenzene, trimethylbenzene, tert-butyl, triethylbenzene, decane, decahydronaphthalene, undecane, dodecane, dimethyl phthalate, dimethyl terephthalate, etc.

[0017] In the present application, the dehydrogenation aromatization reaction is carried out under normal pressure; and / or, the reaction temperature is 150-200 DEG C; and / or, the reaction time is 2-4 hours.

[0018] The present application adopts the above technical solution and has the following positive effects:

[0019] 1. The synthesis route of the present application is novel, and the inexpensive and readily available C3 aldehyde, acetoacetic ester is used as the starting material to quickly synthesize salicylate through 2-step reactions, the synthesis route is short, the yield is high, and the cost advantage is good;

[0020] 2. In the gas phase condensation reaction, a solid mixture of lithium phosphate and potassium fluoride is used as the catalyst to efficiently catalyze the condensation reaction of C3 aldehyde and acetoacetic ester to obtain the 2-oxo-3-cyclohexene acid ester intermediate;

[0021] 3. In the dehydrogenation reaction, the dehydrogenation catalyst and the nitrite auxiliary agent are used in combination, the nitrite promotes the isomerization between the keto form and the enol form of 2-oxo-3-cyclohexene acid ester, reduces the temperature required for the dehydrogenation reaction, and promotes the dehydrogenation reaction. DETAILED DESCRIPTION

[0022] The present application is described in detail below by examples, but the present application is not limited to the following examples.

[0023] The main raw material information is as follows:

[0024] Propenal, 3-methoxypropanal, Anjie Chemical, 99%; Methyl acetoacetate, ethyl acetoacetate, benzyl acetoacetate, n-pentyl acetoacetate, iso-pentyl acetoacetate, Macklin Biochemical, 99%; Potassium fluoride, sodium fluoride, magnesium fluoride, Xilong Reagent, 99%; Lithium phosphate, lithium carbonate, Sanen Chemical, 99%;

[0025] 1% palladium on carbon, 2% palladium on carbon, Xinuke; Mesitylene, dimethyl phthalate, diethyl terephthalate, National Reagent, AR;

[0026] 5% palladium on carbon, 5% palladium on silica, platinum oxide, 2% ruthenium on carbon; Lithium nitrite, magnesium nitrite, iron nitrite, potassium nitrite, zinc nitrite, Sigma Reagent, 98-99%; 2-Iodobenzoic acid, Macklin, 97%; Dimethyl sulfoxide, National Medicine, AR.

[0027] The gas chromatography test conditions of the present application are as follows:

[0028] Instrument model: Shimadzu GC; Chromatographic column: Agilent Wax (60 m x 0.25 mm x 0.25 μm); Column temperature: initial temperature 40℃, temperature rising to 100℃ at 5℃ / min, then temperature rising to 230℃ at 10℃ / min, maintaining for 6 min; Injection port temperature: 250℃; FID detector temperature: 250℃; Split injection, split ratio 40:1; Injection amount: 2.0 μL; H2 flow rate: 40 mL / min; Air flow rate: 360 mL / min.

[0029] Example 1:

[0030] Synthesis of 2-oxo-3-cyclohexenyl acid methyl ester by propenal and methyl acetoacetate gas phase cyclization

[0031] A tubular reactor was used for the gas phase condensation reaction. The length of the reaction tube was 80 cm, and the inner diameter was 2.5 cm. The middle part of the reaction tube was filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer were filled with quartz sand. The solid base catalyst used was mixed by lithium phosphate and potassium fluoride powder in a mass ratio of 9:1, ground, and then extruded and granulated (particle size 0.2 mm). When the gas phase condensation experiment was carried out, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas was sequentially discharged through the vaporization tank, the reaction tube, and the phase separation tank at a flow rate of 100 mL / min, with the carrier gas entering from the top and exiting from the bottom of the reaction tube. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 280°C. The vaporization tank accompanying heat on the feed line was turned on, and its temperature was raised to 200°C. After the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and methyl acetoacetate with a molar ratio of 1:4. The feed rate of the raw material liquid was 0.67 g / min, and the liquid-gas space velocity was 4.0 h -1 After the raw material liquid was vaporized in the vaporization tank, it passed through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurred on the surface of the catalyst. After the reaction gas phase exited the reaction tube, it entered the 1st stage phase separation tank for quenching and phase separation. The gas phase entering the 2nd stage phase separation tank was condensed and separated again, and then discharged as tail gas. The 1st stage and 2nd stage phase separation tanks controlled the reaction liquid to be continuously discharged to the buffer tank under the control of the back pressure valve and the liquid level meter. The sample was taken at the inlet pipeline of the reaction liquid buffer tank at a fixed time, and GC chromatography analysis was performed. The acrolein reaction conversion rate was stable at about 97%, and the selectivity was 98%.

[0032] Example 2:

[0033] Synthesis of 2-oxo-3-cyclohexenyl acid methyl ester by gas phase cyclization of acrolein and methyl acetoacetate

[0034] A tubular reactor was used for the gas phase condensation reaction. The length of the reaction tube was 80 cm, and the inner diameter was 2.5 cm. The middle part of the reaction tube was filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer were filled with quartz sand. The solid base catalyst used was mixed by lithium phosphate and potassium fluoride powder in a mass ratio of 9:1, ground, and then extruded and granulated (particle size 0.2 mm). When the gas phase condensation experiment was carried out, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas was sequentially discharged through the vaporization tank, the reaction tube, and the phase separation tank at a flow rate of 80 mL / min, with the carrier gas entering from the top and exiting from the bottom of the reaction tube. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 260°C. The vaporization tank accompanying heat on the feed line was turned on, and its temperature was raised to 200°C. After the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and methyl acetoacetate with a molar ratio of 1:2. The feed rate of the raw material liquid was 0.33 g / min, and the liquid-gas space velocity was 0.2 h-1 The raw material liquid is vaporized in the vaporization tank and then passes through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurs on the surface of the catalyst. After the reaction gas phase exits the reaction tube, it enters the first-stage phase separation tank for quenching and phase separation. The gas phase of the first-stage phase separation enters the second-stage phase separation tank, and the liquid phase remains at the bottom of the tank. The gas entering the second-stage phase separation tank is condensed and separated again and then discharged as tail gas. The first-stage and second-stage phase separation tanks continuously extract the reaction liquid to the buffer tank under the control of the back pressure valve and the liquid level meter. Sampling is performed at regular intervals on the inlet pipeline of the reaction liquid buffer tank, and GC chromatographic analysis is performed. The propenal reaction conversion rate is stable at >99%, and the selectivity is 92%.

[0035] Example 3:

[0036] Synthesis of 2-oxo-3-cyclohexenyl acid methyl ester by gas phase condensation and cyclization of propenal and acetyl methyl ester

[0037] A tubular reactor is used for the gas phase condensation reaction. The length of the reaction tube is 80 cm, and the inner diameter is 2.5 cm. The middle part of the reaction tube is filled with spherical solid base catalyst (100 g). The upper end and lower end of the catalyst layer are filled with quartz sand. The solid base catalyst used is a mixture of lithium phosphate and potassium fluoride powder in a mass ratio of 9:1. After grinding, it is extruded and granulated to obtain particles with a diameter of 0.2 mm. During the gas phase condensation experiment, the power of the fixed bed reactor is turned on first. The N2 carrier gas inlet and outlet valves are opened, and the nitrogen carrier gas is turned on. The carrier gas passes through the vaporization tank, the reaction tube, and the phase separation tank in sequence and is then discharged. The flow rate is 185 mL / min, and the carrier gas enters from the top of the reaction tube and exits from the bottom. The reaction tube heating jacket is turned on, and the temperature of the reaction tube is raised to 310°C. The vaporization tank heating jacket on the feed line is turned on, and its temperature is raised to 220°C. After the temperatures of the vaporization tank and the reaction tube are stable for 0.5 h, the plunger pump is turned on to pump the raw material liquid into the vaporization tank. The raw material liquid is a mixture of propenal and acetyl methyl ester with a molar ratio of 1:3. The feed rate of the raw material liquid is 3.33 g / min, and the liquid hourly space velocity is 2.0 h -1 The raw material liquid is vaporized in the vaporization tank and then passes through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurs on the surface of the catalyst. After the reaction gas phase exits the reaction tube, it enters the first-stage phase separation tank for quenching and phase separation. The gas phase of the first-stage phase separation enters the second-stage phase separation tank, and the liquid phase remains at the bottom of the tank. The gas entering the second-stage phase separation tank is condensed and separated again and then discharged as tail gas. The first-stage and second-stage phase separation tanks continuously extract the reaction liquid to the buffer tank under the control of the back pressure valve and the liquid level meter. Sampling is performed at regular intervals on the inlet pipeline of the reaction liquid buffer tank, and GC chromatographic analysis is performed. The propenal reaction conversion rate is stable at >99%, and the selectivity is 92%.

[0038] Example 4:

[0039] Synthesis of 2-oxo-3-cyclohexenyl acid ethyl ester by gas phase condensation and cyclization of 3-methoxypropionaldehyde and acetyl ethyl ester

[0040] A tubular reactor was used for the gas phase condensation reaction. The length of the reaction tube was 80 cm, and the inner diameter was 2.5 cm. The middle part of the reaction tube was filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer were filled with quartz sand. The solid base catalyst used was mixed by lithium phosphate and potassium fluoride powder in a mass ratio of 80:20, ground, and then extruded and granulated (particle size 0.2 mm). When the gas phase condensation experiment was carried out, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas was sequentially discharged through the vaporization tank, the reaction tube, and the phase separation tank at a flow rate of 100 mL / min, with the carrier gas entering from the top and exiting from the bottom of the reaction tube. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 280°C. The vaporization tank accompanying heat on the feed line was turned on, and its temperature was raised to 200°C. After the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and methyl acetoacetate, with a molar ratio of 1:3. The feed rate of the raw material liquid was 0.83 g / min, and the liquid quality space velocity was 0.5 h -1 After the raw material liquid was vaporized in the vaporization tank, it passed through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurred on the surface of the catalyst. After the reaction gas phase exited the reaction tube, it entered the 1st stage phase separation tank for quenching and phase separation. The gas phase entering the 2nd stage phase separation tank was condensed and separated again, and then discharged as tail gas. The 1st stage and 2nd stage phase separation tanks controlled the reaction liquid to be continuously discharged to the buffer tank under the control of the back pressure valve and the liquid level meter. The sample was taken at the inlet pipeline of the reaction liquid buffer tank at regular time intervals, and GC chromatography analysis was performed. The acrolein reaction conversion rate was stable at about 97%, and the selectivity was 98%.

[0041] Example 5:

[0042] Gas phase cyclization of acrolein and benzyl acetoacetate to synthesize 2-oxo-3-cyclohexenyl benzoate

[0043] A tubular reactor was used for the gas phase condensation reaction. The length of the reaction tube was 80 cm, and the inner diameter was 2.5 cm. The middle part of the reaction tube was filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer were filled with quartz sand. The solid base catalyst used was mixed by lithium phosphate and potassium fluoride powder in a mass ratio of 93:7, ground, and then extruded and granulated (particle size 0.2 mm). When the gas phase condensation experiment was carried out, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas was sequentially discharged through the vaporization tank, the reaction tube, and the phase separation tank at a flow rate of 150 mL / min, with the carrier gas entering from the top and exiting from the bottom of the reaction tube. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 260°C. The vaporization tank accompanying heat on the feed line was turned on, and its temperature was raised to 220°C. After the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and benzyl acetoacetate, with a molar ratio of 1:2. The feed rate of the raw material liquid was 1.0 g / min, and the liquid quality space velocity was 0.6 h-1 The raw material liquid is vaporized in the vaporization tank and then passes through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurs on the surface of the catalyst. After the reaction gas phase exits the reaction tube, it enters the first-stage phase separation tank for quenching and phase separation. The gas phase of the first-stage phase separation enters the second-stage phase separation tank, and the liquid phase remains at the bottom of the tank. The gas entering the second-stage phase separation tank is condensed and separated again and then discharged as tail gas. The first-stage and second-stage phase separation tanks continuously extract the reaction liquid to the buffer tank under the control of the back pressure valve and the liquid level meter. Sampling is performed at regular intervals on the inlet pipeline of the reaction liquid buffer tank, and GC chromatographic analysis is performed. The propenal reaction conversion rate is stable at about 96%, and the selectivity is 97%.

[0044] Example 6:

[0045] Gas-phase condensation and cyclization of propenal and n-pentyl acetoacetate to synthesize n-pentyl 2-oxo-3-cyclohexenylate

[0046] A tubular reactor is used for the gas-phase condensation reaction. The length of the reaction tube is 80 cm, and the inner diameter is 2.5 cm. The middle part of the reaction tube is filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer are filled with quartz sand. The solid base catalyst used is a mixture of lithium phosphate and sodium fluoride powder in a mass ratio of 95:5. After grinding, it is extruded and granulated to obtain particles with a diameter of 0.2 mm. During the gas-phase condensation experiment, the power of the fixed bed reactor is turned on first. The N2 carrier gas inlet and outlet valves are opened, and the nitrogen carrier gas is turned on. The carrier gas passes through the vaporization tank, the reaction tube, and the phase separation tank in sequence and is then discharged. The flow rate is 100 mL / min, and the carrier gas enters from the top of the reaction tube and exits from the bottom. The reaction tube heating jacket is turned on, and the temperature of the reaction tube is raised to 290°C. The vaporization tank heating jacket on the feed line is turned on, and its temperature is raised to 220°C. After the temperatures of the vaporization tank and the reaction tube are stable for 0.5 h, the plunger pump is turned on to pump the raw material liquid into the vaporization tank. The raw material liquid is a mixture of propenal and n-pentyl acetoacetate with a molar ratio of 1:3. The feed rate of the raw material liquid is 0.83 g / min, and the liquid hourly space velocity is 0.5 h -1 The raw material liquid is vaporized in the vaporization tank and then passes through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurs on the surface of the catalyst. After the reaction gas phase exits the reaction tube, it enters the first-stage phase separation tank for quenching and phase separation. The gas phase of the first-stage phase separation enters the second-stage phase separation tank, and the liquid phase remains at the bottom of the tank. The gas entering the second-stage phase separation tank is condensed and separated again and then discharged as tail gas. The first-stage and second-stage phase separation tanks continuously extract the reaction liquid to the buffer tank under the control of the back pressure valve and the liquid level meter. Sampling is performed at regular intervals on the inlet pipeline of the reaction liquid buffer tank, and GC chromatographic analysis is performed. The propenal reaction conversion rate is stable at about 96%, and the selectivity is 97%.

[0047] Example 7:

[0048] Gas-phase condensation and cyclization of propenal and n-pentyl acetoacetate to synthesize n-pentyl 2-oxo-3-cyclohexenylate

[0049] A tubular reactor was used for the gas phase condensation reaction. The length of the reactor tube was 80 cm and the inner diameter was 2.5 cm. The middle part of the reactor tube was filled with spherical solid base catalyst (100 g). The upper end and the lower end of the catalyst layer were filled with quartz sand. The solid base catalyst used was prepared by mixing lithium phosphate and magnesium fluoride powder in a mass ratio of 9:1, grinding, and then extruding and granulating (particle size 0.3 mm). During the gas phase condensation experiment, the power supply of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas passed through the vaporization tank, the reactor tube, and the phase separation tank in sequence and was then exhausted at a flow rate of 100 mL / min. The reactor tube heating jacket was turned on, and the temperature of the reactor tube was raised to 300°C. The vaporization tank was heated, and its temperature was raised to 220°C. After the temperature of the vaporization tank and the reactor tube was stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and isoamyl acetoacetate in a molar ratio of 1:3. The feeding speed of the raw material liquid was 0.83 g / min, and the liquid hourly space velocity was 0.5 h -1 After the raw material liquid was vaporized in the vaporization tank, it passed through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurred on the surface of the catalyst. After the reaction gas phase exited the reactor tube, it entered the 1st stage phase separation tank for quenching and phase separation. The gas phase entering the 2nd stage phase separation tank entered the 2nd stage phase separation tank, and the liquid phase remained at the bottom of the tank. The gas entering the 2nd stage phase separation tank was condensed and separated again and then exhausted as tail gas. The 1st stage and 2nd stage phase separation tanks controlled the reaction liquid to be continuously discharged to the buffer tank under the control of the back pressure valve and the liquid level meter. The reaction liquid was sampled at the inlet pipeline of the buffer tank at regular time intervals, and GC chromatographic analysis was performed. The conversion rate of acrolein was stable at about 97%, and the selectivity was 96%.

[0050] Example 8

[0051] Dehydrogenation of 2-oxo-3-cyclohexenecarboxylic acid methyl ester to synthesize methyl salicylate using 5% palladium on carbon as catalyst

[0052] In air, at room temperature, 2-oxo-3-cyclohexenecarboxylic acid methyl ester (46.3 g, 0.3 mol), solvent trimethylbenzene (100 mL) and 5% palladium on carbon (0.46 g, 1.0 wt%) were added into a 250 mL three-necked flask equipped with a magnetic stirrer in sequence. Lithium nitrite (0.23 g, 0.5 wt%) was added as the last. The obtained suspension was put into an oil bath, and air was continuously bubbled into the system. The oil bath was stirred and heated (170°C) under reflux. A condenser was connected to the top of the three-necked flask to prevent the solvent and reactants from being volatilized into the reaction system. The slow air bubbling into the system promoted the complete dehydrogenation reaction. After 2 hours of heating under reflux, the reaction liquid was sampled for GC analysis. The conversion rate of 2-oxo-3-cyclohexenecarboxylic acid methyl ester was >99%, and the selectivity of methyl salicylate was 97%.

[0053] Example 9

[0054] 5% palladium on carbon catalyzes the dehydrogenation of methyl 2-oxo-3-cyclohexenoate to synthesize methyl salicylate.

[0055] In air, at room temperature, methyl 2-oxo-3-cyclohexenoate (63.2 g, 0.41 mol), dimethyl phthalate (120 mL), and 5% palladium on carbon (0.06 g, 0.1 wt%) were added sequentially to a 250 mL three-necked flask equipped with a magnetic stirrer. Finally, lithium nitrite (0.06 g, 0.1 wt%) was added as an auxiliary agent. The resulting suspension was placed in an oil bath, and air was continuously and slowly introduced into the system. The oil bath was stirred and heated (200 °C), and the reaction was refluxed with rapid stirring. A condenser was connected to the top of the three-necked flask to prevent the solvent and reactants from evaporating from the reaction system. Air was slowly introduced into the system to promote complete dehydrogenation. After reflux for 4 hours, a sample was taken for GC analysis of the reaction solution composition. The conversion rate of methyl 2-oxo-3-cyclohexenoate was >99%, and the selectivity of methyl salicylate was 94%.

[0056] Example 10:

[0057] 5% palladium on carbon catalyzes the dehydrogenation of methyl 2-oxo-3-cyclohexenoate to synthesize methyl salicylate.

[0058] In air, at room temperature, methyl 2-oxo-3-cyclohexenoate (52.4 g, 0.34 mol), 110 mL of thallium solvent, and 2.62 g of 5% palladium on carbon (5.0 wt%) were added sequentially to a 250 mL three-necked flask equipped with a magnetic stirrer. Finally, lithium nitrite (0.52 g, 1.0 wt%) was added as an auxiliary agent. The resulting suspension was placed in an oil bath, and air was continuously and slowly introduced into the system. The oil bath was stirred and heated (150 °C), and the reaction was refluxed with rapid stirring. A condenser was connected to the top of the three-necked flask to prevent the solvent and reactants from evaporating from the reaction system. Air was slowly introduced into the system to promote complete dehydrogenation. After reflux for 2 hours, a sample was taken for GC analysis of the reaction solution composition. The conversion rate of methyl 2-oxo-3-cyclohexenoate was >99%, and the selectivity of methyl salicylate was 99%.

[0059] Example 11:

[0060] Platinum oxide-catalyzed dehydrogenation of ethyl 2-oxo-3-cyclohexenoate to synthesize ethyl salicylate

[0061] Into a 250 mL three-necked flask equipped with a magnetic stirrer, 2-oxo-3- cyclohexenyl acid ethyl ester (63.9 g, 0.38 mol), solvent trimethylbenzene (100 mL) and platinum oxide (0.64 g, 1.0 wt%) were added successively at room temperature under air, and finally a promoter, magnesium nitrite (0.19 g, 0.3 wt%) was added. The resulting suspension was placed in an oil bath, and air was continuously bubbled into the system. The oil bath was stirred and heated (150 °C), and the reaction was refluxed with rapid stirring. A condenser was connected to the top of the flask to prevent the solvent and reactants from being blown out of the reaction system. The air was slowly bubbled into the system to promote the complete dehydrogenation reaction. After 3 hours of heating and refluxing, the reaction liquid was sampled and analyzed by GC. The conversion of 2-oxo-3-cyclohexenyl acid ethyl ester was >99%, and the selectivity of ethyl salicylate was 96%.

[0062] Example 12:

[0063] Dehydrogenation of 2-oxo-3-cyclohexenyl acid benzyl ester catalyzed by 5% palladium on silicon to synthesize benzyl salicylate

[0064] Into a 250 mL three-necked flask equipped with a magnetic stirrer, 2-oxo-3- cyclohexenyl acid methyl ester (62.2 g, 0.27 mol), solvent dimethyl phthalate (130 mL) and 5% palladium on silicon (0.62 g, 1.0 wt%) were added successively at room temperature under air, and finally a promoter, iron nitrite (0.12 g, 0.2 wt%) was added. The resulting suspension was placed in an oil bath, and air was continuously bubbled into the system. The oil bath was stirred and heated (150 °C), and the reaction was refluxed with rapid stirring. A condenser was connected to the top of the flask to prevent the solvent and reactants from being blown out of the reaction system. The air was slowly bubbled into the system to promote the complete dehydrogenation reaction. After 2 hours of heating and refluxing, the reaction liquid was sampled and analyzed by GC. The conversion of 2-oxo-3-cyclohexenyl acid benzyl ester was >99%, and the selectivity of benzyl salicylate was 98%.

[0065] Example 13:

[0066] Dehydrogenation of 2-oxo-3-cyclohexenyl acid n-pentyl ester catalyzed by 2% ruthenium on carbon to synthesize n-pentyl salicylate

[0067] Into a 500 mL three-necked flask equipped with a magnetic stirrer, 2-oxo-3- cyclohexenyl acid n-pentyl ester (73.6 g, 0.35 mol), solvent terephthalic acid diethyl ester (150 mL) and 2% ruthenium on carbon (0.74 g, 1.0 wt%) were added successively at room temperature under air, and finally potassium nitrite (0.22 g, 0.3 wt%) was added. The resulting suspension was placed in an oil bath, and air was continuously bubbled into the system while stirring and heating (170 °C) was started. The reaction was refluxed with rapid stirring. A condenser was connected to the top of the flask to prevent the solvent and reactants from being blown out of the reaction system. The air was slowly bubbled into the system to promote the complete dehydrogenation reaction. After 4 hours of heating and refluxing, the reaction liquid composition was analyzed by GC sampling, and the conversion of 2-oxo-3-cyclohexenyl acid n-pentyl ester was >99% with a selectivity of 97% for n-pentyl salicylate.

[0068] Example 14:

[0069] Synthesis of isoamyl salicylate by dehydrogenation of 2-oxo-3-cyclohexenyl acid isoamyl ester catalyzed by 1% palladium on carbon

[0070] Into a 250 mL three-necked flask equipped with a magnetic stirrer, 2-oxo-3- cyclohexenyl acid methyl ester (69.4 g, 0.33 mol), solvent terephthalic acid dimethyl ester (140 mL) and 1% palladium on carbon (1.04 g, 1.5 wt%) were added successively at room temperature under air, and finally zinc nitrite (0.21 g, 0.3 wt%) was added. The resulting suspension was placed in an oil bath, and air was continuously bubbled into the system while stirring and heating (180 °C) was started. The reaction was refluxed with rapid stirring. A condenser was connected to the top of the flask to prevent the solvent and reactants from being blown out of the reaction system. The air was slowly bubbled into the system to promote the complete dehydrogenation reaction. After 4 hours of heating and refluxing, the reaction liquid composition was analyzed by GC sampling, and the conversion of 2-oxo-3-cyclohexenyl acid methyl ester was >99% with a selectivity of 96% for methyl salicylate.

[0071] Comparative Example 1

[0072] Methyl 2-oxo-3-cyclohexenecarboxylate was synthesized by gas phase condensation of acrolein and methyl acetoacetate. The gas phase condensation was carried out in a tubular reactor with a length of 80 cm and an inner diameter of 2.5 cm. The middle part of the reactor was filled with a spherical solid base catalyst (100 g), and the upper and lower ends of the catalyst layer were filled with quartz sand. The solid base catalyst used was potassium fluoride powder which was ground and then extruded to form granules (particle size 0.2 mm). During the gas phase condensation experiment, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas passed through the vaporization tank, the reaction tube, and the phase separation tank in sequence before being exhausted, with a flow rate of 100 mL / min. The carrier gas entered from the top of the reaction tube and exited from the bottom. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 280°C. The vaporization tank heating jacket on the feed line was turned on, and the temperature of the vaporization tank was raised to 200°C. After the temperatures of the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and methyl acetoacetate with a molar ratio of 1:4. The feed rate of the raw material liquid was 0.67 g / min, and the liquid hourly space velocity was 4.0 h-1. -1 The raw material liquid vaporized in the vaporization tank and passed through the catalyst layer in the form of gas, and the condensation and cyclization reactions occurred on the surface of the catalyst. After the reaction gas phase exited the reaction tube, it entered the first-stage phase separation tank for quenching and phase separation. The gas phase of the first-stage phase separation entered the second-stage phase separation tank, and the liquid phase remained at the bottom of the tank. The gas that entered the second-stage phase separation tank was condensed and separated again and then exhausted as tail gas. The reaction liquid was continuously collected from the first-stage and second-stage phase separation tanks to the buffer tank under the control of the back pressure valve and the liquid level meter. Samples were taken from the inlet line of the reaction liquid buffer tank at regular intervals, and GC chromatography analysis was performed. The conversion rate of acrolein was stable at about 53%, and the selectivity was 76%.

[0073] Comparative Example 2

[0074] Methyl 2-oxo-3-cyclohexenecarboxylate was synthesized by gas phase condensation of acrolein and methyl acetoacetate

[0075] The gas phase condensation was carried out in a tubular reactor with a length of 80 cm and an inner diameter of 2.5 cm. The middle part of the reactor was filled with a spherical solid base catalyst (100 g), and the upper and lower ends of the catalyst layer were filled with quartz sand. The solid base catalyst used was lithium phosphate which was extruded to form granules (particle size 0.2 mm). During the gas phase condensation experiment, the power of the fixed bed reactor was first turned on, the N2 carrier gas inlet and outlet valves were opened, and the nitrogen carrier gas was turned on. The carrier gas passed through the vaporization tank, the reaction tube, and the phase separation tank in sequence before being exhausted, with a flow rate of 100 mL / min. The carrier gas entered from the top of the reaction tube and exited from the bottom. The reaction tube heating jacket was turned on, and the temperature of the reaction tube was raised to 280°C. The vaporization tank heating jacket on the feed line was turned on, and the temperature of the vaporization tank was raised to 200°C. After the temperatures of the vaporization tank and the reaction tube were stable for 0.5 h, the plunger pump was turned on to pump the raw material liquid into the vaporization tank. The raw material liquid was a mixture of acrolein and methyl acetoacetate with a molar ratio of 1:4. The feed rate of the raw material liquid was 0.67 g / min, and the liquid hourly space velocity was 4.0 h-1.-1 The raw material liquid is vaporized in the vaporization tank and then passes through the catalyst layer in the form of gas, and the condensation and cyclization reaction occurs on the surface of the catalyst. After the reaction gas phase exits the reaction tube, it enters the first-stage phase separation tank for quenching and phase separation, and the gas phase enters the second-stage phase separation tank, and the liquid phase remains at the bottom of the tank. The gas entering the second-stage phase separation tank is condensed and separated again and then discharged in the form of tail gas. The first-stage and second-stage phase separation tanks control the continuous extraction of the reaction liquid to the buffer tank under the control of the back pressure valve and the liquid level meter. The sampling is performed at the inlet pipeline of the reaction liquid buffer tank at a fixed time, and the GC chromatographic analysis shows that the propylene aldehyde reaction conversion rate is stabilized at about 83%, and the selectivity is 71%.

[0076] Comparative Example 3

[0077] 2-iodoxybenzoic acid (IBX) catalyzed dehydrogenation of methyl 2-oxo-3-cyclohexenecarboxylate to synthesize methyl salicylate In a 100 mL three-necked flask equipped with a magnetic stirrer, 2-oxo-3-cyclohexenecarboxylate (1.54 g, 10.0 mmol) and solvent DMSO (20 mL) were sequentially added at room temperature, and the three-necked flask was placed in a 60°C oil bath. After stirring and mixing, a clear solution was obtained. 2-Iodoxybenzoic acid (3.36 g, 12.0 mmol) was added to a constant pressure dropping funnel, and solvent DMSO (30 mL) was added to completely dissolve it, and then it was slowly added to the three-necked flask (1 h). After the addition was completed, the reaction was stirred for 10 hours, and the reaction liquid composition was analyzed by GC sampling. The conversion rate of 2-oxo-3-cyclohexenecarboxylate was >99%, and the selectivity of methyl salicylate was 35%, and other main products were raw material oxidation hydroxylation products.

Claims

1. A method for synthesizing a salicylate ester by cyclization, dehydrogenation, the method comprising: The raw material C3 aldehyde and acetoacetate ester are subjected to gas phase cyclization reaction under the catalysis of solid base to obtain 2-oxo-3-cyclohexene acid ester intermediate, and then the intermediate is subjected to dehydrogenation aromatization under the catalysis of dehydrogenation catalyst and auxiliary agent to obtain salicylate product; the C3 aldehyde is propenal or 3-methoxypropanal, the solid base catalyst is a mixture of lithium salt and potassium salt, wherein the lithium salt is one or more selected from lithium carbonate and lithium phosphate, and the potassium salt is potassium fluoride, the dehydrogenation catalyst is one or more selected from 0.5-10% palladium-carbon, 0.5-10% palladium-alumina, 0.5-10% palladium-silica, 0.5-10% platinum-carbon, 0.5-10% ruthenium-carbon, 0.5-10% rhodium-carbon, platinum oxide, Raney nickel and Raney cobalt, and the auxiliary agent is one or more selected from lithium nitrite, sodium nitrite, potassium nitrite, magnesium nitrite, zinc nitrite, copper nitrite and iron nitrite.

2. The method of claim 1, wherein, The mass ratio of lithium salt to potassium salt in the solid base catalyst is 4-19:

1.

3. The method of claim 1, wherein, The gas phase cyclization reaction has a weight hourly space velocity of 0.2-2.0 h -1 .

4. The method according to any one of claims 1-3, characterized in that, The feed molar ratio of the C3 aldehyde to acetoacetate ester is 1:2-1:4, the reaction temperature of the gas phase cyclization reaction is 260-310 DEG C, and the reaction pressure is normal pressure.

5. The method according to any one of claims 1-3, characterized in that, The reaction temperature of the gas phase cyclization reaction is 280-300 DEG C.

6. The method according to any one of claims 1-3, characterized in that, The feed liquid of the gas phase cyclization reaction can be added with solvent or without solvent; if the solvent is added, the solvent is one or more selected from ethyl acetate, tetrahydrofuran, methyl tert-butyl ether, ethanol, acetonitrile and diethyl ether.

7. The method of any one of claims 1-3, characterized in that, The dehydrogenation catalyst is used in an amount of 0.1-5.0 wt% of 2-oxo-3-cyclohexene acid ester, and / or the auxiliary agent is used in an amount of 0.1-1.0 wt% of 2-oxo-3-cyclohexene acid ester.

8. The method of any one of claims 1-3, characterized in that, The dehydrogenation aromatization reaction can be carried out under solvent-free condition or in toluene, dimethylbenzene, trimethylbenzene, tert-butyl, triethylbenzene, decane, decahydronaphthalene, undecane, dodecane, dimethyl phthalate or dimethyl terephthalate.

9. The method of any one of claims 1-3, characterized in that, The pressure of the dehydrogenation aromatization reaction is normal pressure, the reaction temperature of the dehydrogenation aromatization reaction is 150-200 DEG C, and the reaction time of the dehydrogenation aromatization reaction is 2-4 hours.

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