Method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin

Abstract

The invention relates to the field of preparation of an intermediate for synthesizing vitamin B6, and discloses a method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin, characterized in that the method comprises the following steps: (1) mixing a compound A represented by a general formula RCHO with cis-2-butene-1,4-diol to obtain a pre-reaction liquid, and passing the pre-reaction liquid through a strongly acidic catalytic resin column a to perform a primary reaction to obtain a primary reaction liquid; (2) first stirring the primary reaction liquid and a first extractant, passing the obtained first mixed liquid through a strongly acidic catalytic resin column b to perform a secondary reaction, and separating to obtain a secondary reaction liquid and a water layer; (3) passing the secondary reaction liquid through a strongly acidic catalytic resin column c to perform a tertiary reaction to obtain a tertiary reaction liquid; (4) distilling the tertiary reaction liquid to obtain 2-propyl-4,7-dihydro-1,3-dioxepin represented by formula (1); wherein R is n-propyl or isopropyl.

Description

Technical Field

[0001] The invention relates to the field of preparation of an intermediate for synthesizing vitamin B6, and in particular to a method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin. Background Art

[0002] Vitamin B6 belongs to the water-soluble B vitamins and participates in a variety of human physiological activities as a coenzyme, including the metabolism of proteins, amino acids, and carbohydrates, maintaining the balance of sodium and potassium in the body, and participating in the production of red blood cells. Due to its significant functions in promoting metabolism, nourishing nerves, and inhibiting vomiting, vitamin B6 is often used clinically as an auxiliary treatment for vitamin B6 deficiency or other diseases in humans and animals.

[0003] The industrial production of vitamin B6 usually adopts the "oxazole method". The main reactions include Diels-Alder addition, aromatization, hydrolysis, etc. 2-propyl-4,7-dihydro-1,3-dioxetane is one of the main intermediates of the "oxazole method".

[0004] 2-propyl-4,7-dihydro-1,3-dioxepin is generally obtained by the condensation reaction of butyraldehyde or isobutyraldehyde with cis-2-butene-1,4-diol (referred to as butenediol). The chemical reaction equation is shown below:

[0005]

[0006] The above reaction is a reversible reaction. In the traditional production process, a strong acid such as sulfuric acid is usually used as a reaction system for the catalyst, and a water-carrying agent is added to remove the water produced in the system through azeotropic dehydration, so that the reaction is moved to the right and the conversion of the raw material butenediol is completely promoted. Under high temperature and acidic reaction conditions, the raw material butenediol is prone to polymerization reaction to form a coke-like polymer, which is easy to clog the pipeline and is not conducive to production operation, while butyraldehyde is prone to intermolecular reaction to form aldol condensation by-products, so the yield of the product 2-propyl-4,7-dihydro-1,3-dioxepin is not high. The use of strong acid not only causes corrosion to the equipment, but also increases wastewater discharge. In addition, the operation mode of solvent azeotropic dehydration significantly increases production energy consumption.

[0007] "Synthesis of 2-n-propyl-4,7-dihydro-1,3-dioxetane catalyzed by strong acid ion exchange resin" (Zhang Genbao et al., Applied Chemical Industry, 2012, 41(8), 1372-1374) discloses a method for synthesizing 2-n-propyl-4,7-dihydro-1,3-dioxetane by azeotropic dehydration using butenediol and n-butyraldehyde as raw materials, strong acid ion exchange resin as catalyst, and cyclohexane. The advantage of this method is that it uses low-toxic alkanes to replace the highly toxic benzene in the traditional process as a water-carrying agent, eliminates the use of strong acids such as sulfuric acid, and the hourly yield can reach 95 mol%. However, when the method is industrially scaled up, the catalyst is used dynamically and is easy to break. After the reaction, the catalyst needs to be filtered and separated, and a long period of reflux dehydration is required, resulting in a long production cycle and high energy consumption.

[0008] In view of the above-mentioned deficiencies, there is an urgent need to improve the preparation method of 2-propyl-4,7-dihydro-1,3-dioxepin. Summary of the invention

[0009] The purpose of the present invention is to overcome the problems of high pollution, high energy consumption and long production cycle in the existing method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin, and to provide a method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin.

[0010] In order to achieve the above purpose, the inventors of the present invention have conducted a large number of studies, and found that at room temperature, raw material compound A can react with cis-2-butene-1,4-diol (referred to as butenediol), and compared with traditional high temperature reflux reaction, the reaction selectivity at low temperature is greatly improved, and the colloidal polymer formed by butenediol under acidic conditions is significantly reduced. The non-polar extractant selected by the present application can significantly improve the conversion rate of butenediol, and after the catalytic reaction of the strong acid resin column, the byproduct water in the reaction solution can be removed by layering operation. Through conventional concentration or solvent extraction methods, it is difficult to recover the unreacted raw material butenediol remaining in the water layer, but the water layer is mixed with raw material compound A and butenediol through an acidic resin column, and reaction extraction can be performed to recover butenediol, so the product yield of preparing 2-propyl-4,7-dihydro-1,3-dioxacyclo can be further improved, shortening the cycle, improving production efficiency, reducing pollution and reducing energy consumption.

[0011] Based on the above findings, the present invention provides a method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin, wherein the method comprises the following steps:

[0012] (1) mixing a compound A represented by the general formula RCHO with cis-2-butene-1,4-diol to obtain a pre-reaction liquid, and passing the pre-reaction liquid through a strong acid catalytic resin column a to perform a primary reaction to obtain a primary reaction liquid;

[0013] (2) the primary reaction liquid and the first extractant are first stirred, the obtained first mixed liquid is passed through a strongly acidic catalytic resin column b for a secondary reaction, and the secondary reaction liquid and the water layer are separated;

[0014] (3) passing the secondary reaction liquid through a strong acid catalytic resin column c for a tertiary reaction to obtain a tertiary reaction liquid;

[0015] (4) distilling the tertiary reaction liquid to obtain 2-propyl-4,7-dihydro-1,3-dioxepin as shown in formula (1),

[0016]

[0017] Wherein, R is n-propyl or isopropyl.

[0018] Through the above technical scheme, the content and yield of the product 2-propyl-4,7-dihydro-1,3-dioxepin are high, and its content can reach more than 99wt%, and the yield can reach more than 93%. At the same time, the preparation method adopts a fixed bed form to reduce the resin breakage rate, and adopts a low-temperature continuous reaction method to avoid repeated evaporation of the azeotropic dehydration solvent in the traditional process, so the three wastes are discharged less, the energy consumption is low, and the production cycle is short. DETAILED DESCRIPTION

[0019] The endpoints and any values ​​of the ranges disclosed in this article 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 each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0020] In order to achieve the above object, the present invention provides a method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin, wherein the method comprises the following steps:

[0021] (1) mixing a compound A represented by the general formula RCHO with cis-2-butene-1,4-diol to obtain a pre-reaction liquid, and passing the pre-reaction liquid through a strong acid catalytic resin column a to perform a primary reaction to obtain a primary reaction liquid;

[0022] (2) the primary reaction liquid and the first extractant are first stirred, the obtained first mixed liquid is passed through a strongly acidic catalytic resin column b for a secondary reaction, and the secondary reaction liquid and the water layer are separated;

[0023] (3) passing the secondary reaction liquid through a strong acid catalytic resin column c for a tertiary reaction to obtain a tertiary reaction liquid;

[0024] (4) distilling the tertiary reaction liquid to obtain 2-propyl-4,7-dihydro-1,3-dioxepin as shown in formula (1),

[0025]

[0026] Wherein, R is n-propyl or isopropyl.

[0027] In the present invention, a column filled with a strong acid catalytic resin is used as a fixed bed reactor to carry out a continuous flow reaction to prepare 2-propyl-4,7-dihydro-1,3-dioxepin, which not only improves the content and yield of the product, but also improves the production efficiency of the product and shortens the production cycle of the product.

[0028] In the present invention, the compound A is n-butyraldehyde or isobutyraldehyde.

[0029] In the present invention, after the raw material undergoes a primary reaction, its conversion rate is about 60-80%; the primary reaction liquid is stirred with an extractant and then undergoes a secondary reaction, and the extractant can remove the product from the local contact reaction system in the acid resin column, thereby promoting the reaction in a positive direction; after the secondary reaction liquid undergoes a tertiary reaction, the conversion rate of the raw material can reach more than 96%.

[0030] According to the present invention, in step (1), the mass ratio of compound A to cis-2-butene-1,4-diol is 1-5:1, preferably 1.5-3:1.

[0031] In the present invention, when the mass ratio of the raw materials meets the above range, it has the effect of promoting the conversion of cis-2-butene-1,4-diol and can increase the yield of 2-propyl-4,7-dihydro-1,3-dioxepin; the above preferred mass ratio can achieve a better yield.

[0032] According to the present invention, in step (2), the mass ratio of the primary reaction liquid to the first extractant is 0.5-2:1, preferably 1-1.5:1.

[0033] In the present invention, the extractant can promote the reaction in the positive direction. When the amount of the extractant is too high, the promotion effect no longer increases, and the loss increases; when the amount of the extractant is too low, the extraction effect decreases. Therefore, it is necessary to control the stretching ratio within a suitable range to keep the yield at a high level.

[0034] According to the present invention, in step (1), the mixing temperature is 0-20°C, preferably 5-15°C; the mixing time is 1-10 min, preferably 1-5 min.

[0035] In the present invention, the mixing temperature has an important influence on the yield of the product. When the raw material compound A is mixed with cis-2-butene-1,4-diol, hemiacetal, i.e., the pre-reaction liquid, can be obtained by addition; when the mixing temperature is higher than 20°C, cis-2-butene-1,4-diol is prone to side reactions, resulting in a decrease in the yield of the product; when the mixing temperature is controlled at 0-20°C, the damage of the raw materials can be reduced, thereby improving the yield of the product.

[0036] According to the present invention, in step (1), the temperature of the primary reaction is 20-40°C, preferably 25-35°C.

[0037] In the present invention, when the primary reaction temperature is controlled within the above range, the reaction yield can be improved and the reaction energy consumption is low.

[0038] According to the present invention, in step (2), the temperature of the secondary reaction is 20-40°C, preferably 25-35°C.

[0039] According to the present invention, in step (3), the temperature of the tertiary reaction is 50-80°C, preferably 55-65°C.

[0040] In the present invention, when the temperature of the tertiary reaction is controlled to meet the above range, the reaction selectivity can be improved, thereby obtaining the beneficial effect of increasing the yield.

[0041] According to the present invention, the strongly acidic catalytic resin columns a, b and c are each a strongly acidic ion exchange resin.

[0042] In the present invention, the strongly acidic ion exchange resin contains a sulfonic acid group -SO3H.

[0043] According to the present invention, the volumetric total exchange capacity of the strongly acidic ion exchange resin is not less than 1.5 mmol / mL, preferably not less than 1.7 mmol / mL. It can be a commercially available resin, such as D001 macroporous strongly acidic cationic resin, with a volumetric total exchange capacity of 1.8 mmol / mL.

[0044] According to the present invention, the strongly acidic ion exchange resin is selected from gel-type resins and / or macroporous resins.

[0045] According to the present invention, the first extractant is selected from at least one of petroleum ether, n-hexane, cyclohexane and n-heptane, preferably petroleum ether.

[0046] According to the present invention, the flow rate of the pre-reaction liquid flowing through the strong acid catalytic resin column a is 1-10 BV / h, preferably 2-5 BV / h, and more preferably 2-4 BV / h.

[0047] According to the present invention, the flow rate of the mixed solution flowing through the strong acid catalytic resin column b is 1-10 BV / h, preferably 2-5 BV / h, and more preferably 2-4 BV / h.

[0048] According to the present invention, the flow rate of the secondary reaction liquid flowing through the strong acid catalytic resin column c is 1-10 BV / h, preferably 2-5 BV / h, and more preferably 2-4 BV / h.

[0049] In the present invention, in order to ensure that the reaction materials have sufficient contact time with the strong acid catalytic resin column, it is necessary to control the appropriate flow rate. Too fast a flow rate is not conducive to the full reaction of the raw materials, while too slow a flow rate affects the utilization efficiency of the catalytic resin column.

[0050] According to the present invention, the method further comprises: in step (2), the water layer, compound A and the second extractant are subjected to a second stirring, the obtained second mixed liquid is passed through the strong acid catalytic resin column d for a quaternary reaction, and the liquids are separated to obtain an extract and a wastewater layer.

[0051] In the present invention, the water layer contains reaction raw materials, and after the fourth-stage reaction, the obtained extract contains the product 2-n-propyl-4,7-dihydro-1,3-dioxepin, which can reduce the loss of raw materials and improve the product yield.

[0052] According to the present invention, the mass ratio of the water layer, compound A and the second extractant is 1:0.1-0.5:1-4, preferably 1:0.2-0.45:2-3.

[0053] According to the present invention, the second extracting agent is selected from at least one of petroleum ether, n-hexane, cyclohexane and n-heptane; preferably, the second extracting agent is the same as the first extracting agent.

[0054] According to the present invention, the extracting liquid is circulated and added into the pre-reaction liquid.

[0055] According to the present invention, the mass ratio of the circulating amount of the extract to cis-2-butene-1,4-diol is 0.4-1:1, preferably 0.5-0.8:1.

[0056] According to the present invention, the flow rate of the second mixed liquid flowing through the strong acid catalytic resin column d is 1-10 BV / h, preferably 2-5 BV / h, and more preferably 2-4 BV / h.

[0057] In the present invention, the strongly acidic catalytic resin column d is a strongly acidic ion exchange resin, and the volumetric total exchange capacity of the strongly acidic ion exchange resin is not less than 1.5 mmol / mL, preferably not less than 1.7 mmol / mL.

[0058] According to the present invention, the temperature of the fourth-stage reaction is 50-80°C, preferably 55-65°C.

[0059] According to the present invention, in step (4), the distillation is atmospheric pressure distillation and negative pressure distillation.

[0060] In the present invention, the tertiary reaction liquid contains a very small amount of water, which can be ignored and the distillation step is directly performed.

[0061] According to the present invention, the distillation process includes: first subjecting the tertiary reaction liquid to atmospheric distillation to recover the first extractant, the second extractant and the compound A, and then subjecting the tertiary reaction liquid to negative pressure distillation to obtain 2-propyl-4,7-dihydro-1,3-dioxepin.

[0062] The present invention will be described in further detail below through specific examples.

[0063] In the following examples, the strongly acidic ion exchange resin is a D001 macroporous strongly acidic cationic resin purchased from Zhejiang Zhengguang Industrial Co., Ltd., with a volumetric total exchange capacity of 1.8 mmol / mL, and the pretreatment method is based on GB / T 5476-1996 "Ion Exchange Resin Pretreatment Method".

[0064] In the following examples, gas chromatography (Shimadzu GC-14C) was used to analyze the components in the product, and the quantitative analysis was performed by calibration normalization method, which can be carried out with reference to the existing technology. On this basis, evaluation indicators such as the conversion rate of the reactants, the yield and selectivity of the products were calculated.

[0065] The yield formula is shown below:

[0066]

[0067] Wherein, m, M, a are the mass, molecular weight and mass percentage of the product 2-propyl-4,7-dihydro-1,3-dioxetane respectively; m0, M0, a0 are the feed mass, molecular weight and content of cis-2-butene-1,4-diol respectively; η is the yield of 2-propyl-4,7-dihydro-1,3-dioxetane.

[0068] In the following examples, the term “after application of the extractant” refers to the yield of 2-propyl-4,7-dihydro-1,3-dioxepin calculated after the reaction system of the example runs smoothly.

[0069] Other raw materials used in the examples and comparative examples are all commercially available.

[0070] Example 1

[0071] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0072] (1) 2000 g of cis-2-butene-1,4-diol (content 98.5 wt%) and 3000 g of n-butyraldehyde were respectively pumped into a static mixer for mixing at 10° C. for 3 min to obtain a pre-reaction liquid.

[0073] The pre-reaction liquid was transported by a peristaltic pump to flow through D001 type strong acid ion exchange resin a (resin column specification is φ2.5cm×30cm) for primary reaction. The primary reaction temperature was controlled at 30°C and the flow rate was 2BV / h to obtain 5000g of primary reaction liquid.

[0074] (2) Under the peristaltic pump, the primary reaction liquid was mixed with 2500g of petroleum ether through a static mixer, and then flowed through D001 type strong acid ion exchange resin b (resin column specification: φ2.5cm×30cm) for secondary reaction. The secondary reaction temperature was controlled at 30°C and the flow rate was 3BV / h. 474g of the effluent was separated from the water layer to obtain 6894g of secondary reaction liquid (detected by gas chromatography, containing 2985.8g of 2-propyl-4,7-dihydro-1,3-dioxepin).

[0075] (3) The secondary reaction liquid was pumped through D001 type strong acid ion exchange resin c (resin column specification: φ2.5 cm×30 cm) for tertiary reaction. The temperature of the tertiary reaction was controlled at 60°C, the flow rate was 3BV / h, and the effluent was the tertiary reaction liquid (detected by gas chromatography, containing 3017.6 g of 2-propyl-4,7-dihydro-1,3-dioxepin).

[0076] The water layer of step (2), 200 g of n-butyraldehyde and 1000 g of petroleum ether were conveyed in sequence through a static mixer by a pump. The mass ratio of the water layer, compound A and the second extractant was 1:0.42:2.1. The second mixed liquid obtained by mixing was passed through a D001 type strongly acidic ion exchange resin d (resin column specification: φ2.5 cm×30 cm) for a quaternary reaction. The flow rate of the quaternary reaction was 3 BV / h. 435 g of the wastewater layer was separated from the effluent to obtain 1235 g of an extract (containing 97.7 g of 2-n-propyl-4,7-dihydro-1,3-dioxepin as determined by gas chromatography). The extract was used for the next batch of reaction and the wastewater layer could be discharged.

[0077] (4) The tertiary reaction liquid is subjected to atmospheric distillation to recover petroleum ether and unreacted n-butyraldehyde, and then subjected to vacuum distillation under vacuum conditions of -0.098 MPa to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxepin. The content of the product is 99.5 wt % as determined by gas chromatography.

[0078] After the extract was used, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 97.6% based on cis-2-butene-1,4-diol.

[0079] Example 2

[0080] This example is used to illustrate the preparation method of 2-isopropyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0081] 2-isopropyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that isobutylaldehyde was used instead of n-butylaldehyde, and the other conditions remained unchanged to obtain the product 2-isopropyl-4,7-dihydro-1,3-dioxetane. The content of the product was 99.5 wt % as determined by gas chromatography.

[0082] After the extract was used, the total yield of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 97.8% based on cis-2-butene-1,4-diol.

[0083] Example 3

[0084] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0085] 2-n-propyl-4,7-dihydro-1,3-dioxane was prepared according to the method described in Example 1, except that in step (1), cis-2-butene-1,4-diol was 2000 g, n-butyraldehyde was 6000 g, and the obtained primary reaction liquid was 8000 g; in step (2), petroleum ether was 4000 g; in step (3), the water layer was mixed with n-butyraldehyde and petroleum ether in a mass ratio of 1:0.3:2, and the other conditions remained unchanged to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxane. The content of the product was 99.4 wt% as determined by gas chromatography.

[0086] After the extract was used, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 97.1% based on cis-2-butene-1,4-diol.

[0087] Example 4

[0088] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0089] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that the material flowed through D001 type strong acid ion exchange resins a, b, c and d (resin column specifications were all φ2.5cm×30cm), the flow rate was 5BV / h, and the other conditions remained unchanged to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxetane. The content of the product was 99.6wt% as determined by gas chromatography.

[0090] After the extract was used, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 96.5% based on cis-2-butene-1,4-diol.

[0091] Example 5

[0092] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0093] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that in step (1), cis-2-butene-1,4-diol was 2000 g, n-butyraldehyde was 10000 g, and the primary reaction liquid obtained was 12000 g; in step (2), petroleum ether was 24000 g; in step (3), the water layer was mixed with n-butyraldehyde and petroleum ether in a mass ratio of 1:0.3:2. The other conditions remained unchanged, and the product 2-n-propyl-4,7-dihydro-1,3-dioxetane was obtained. The content of the product was 99.3 wt % as determined by gas chromatography.

[0094] After the extract was used, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 96.5% based on cis-2-butene-1,4-diol.

[0095] Example 6

[0096] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0097] 2-n-propyl-4,7-dihydro-1,3-dioxane was prepared according to the method described in Example 1, except that in step (1), the primary reaction temperature was 20°C and the flow rate was 2BV / h; in step (2), the secondary reaction temperature was 20°C and the flow rate was 3BV / h; in step (3), the tertiary reaction temperature was 50°C and the flow rate was 3BV / h, and the other conditions remained unchanged to obtain the product 2-isopropyl-4,7-dihydro-1,3-dioxane. The content was 99.5wt% as determined by gas chromatography.

[0098] After the extract was used, the total yield of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 96.7% based on cis-2-butene-1,4-diol.

[0099] Example 7

[0100] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0101] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that in step (1), the primary reaction temperature was 40°C and the flow rate was 2BV / h; in step (2), the secondary reaction temperature was 40°C and the flow rate was 3BV / h; in step (3), the tertiary reaction temperature was 80°C and the flow rate was 3BV / h, and the other conditions remained unchanged to obtain the product 2-isopropyl-4,7-dihydro-1,3-dioxetane. The content was 99.4wt% as determined by gas chromatography.

[0102] After the extract was used, the total yield of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 96.5% based on cis-2-butene-1,4-diol.

[0103] Example 8

[0104] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0105] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that the material flowed through D001 type strong acid ion exchange resins a, b, c and d (resin column specifications were all φ2.5cm×30cm), the flow rate was 10BV / h, and the other conditions remained unchanged to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxetane. The content of the product was 99.5wt% as determined by gas chromatography.

[0106] After the extract was used, the total yield of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 95.4% based on cis-2-butene-1,4-diol.

[0107] Example 9

[0108] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0109] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that the water layer obtained in step (2) was discharged as waste liquid and did not undergo a quaternary reaction with petroleum ether and n-butyraldehyde. The other conditions remained unchanged to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxetane. The content of the product was 99.3 wt % as determined by gas chromatography.

[0110] The total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 93.8% based on cis-2-butene-1,4-diol.

[0111] Example 10

[0112] This example is used to illustrate the preparation method of 2-n-propyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0113] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that the first extractant and the second extractant were cyclohexane, and the other conditions remained unchanged to obtain the product 2-isopropyl-4,7-dihydro-1,3-dioxetane. The content of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 99.2 wt % as determined by gas chromatography.

[0114] After the extract was used, the total yield of 2-isopropyl-4,7-dihydro-1,3-dioxetane was 96.3% based on cis-2-butene-1,4-diol.

[0115] Embodiment 11

[0116] This example is used to illustrate the preparation method of 2-isopropyl-4,7-dihydro-1,3-dioxepin provided by the present invention.

[0117] 2-n-propyl-4,7-dihydro-1,3-dioxetane was prepared according to the method described in Example 1, except that in step (3), the water layer was mixed with n-butyraldehyde and petroleum ether in a mass ratio of 1:0.05:0.5, and the other conditions remained unchanged to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxetane. The content of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 99.4 wt % as determined by gas chromatography.

[0118] After the extract was used, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 95.6% based on cis-2-butene-1,4-diol.

[0119] Comparative Example 1

[0120] This comparative example is used to illustrate the method of preparing 2-n-propyl-4,7-dihydro-1,3-dioxepin by azeotropic dehydration catalyzed by sulfuric acid in the prior art.

[0121] 200g of cis-2-butene-1,4-diol, 300g of n-butyraldehyde, and 200g of petroleum ether were placed in a 1000mL three-necked round-bottom flask equipped with a thermometer, a reflux condenser, and a water separator, and 2g of concentrated sulfuric acid was added. Heat to 63°C under normal pressure and reflux, and continuously remove the water produced by the reaction. The reflux time was 8h until no water evaporated and the reaction was terminated. The reaction solution was cooled to room temperature, first washed with 50mL×2 water, then washed with 50mL of saturated sodium bicarbonate solution, and finally washed with 50mL of water. After washing, the reaction solution was first distilled at normal pressure to recover petroleum ether and remaining n-butyraldehyde. When the solution temperature reached 110°C, switch to negative pressure distillation, control the vacuum -0.098MPa, intercept the front fraction and apply it to the next batch of distillation, and continue distillation to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxacyclopentane. According to gas chromatography, the product content was 98.1wt%.

[0122] The total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane based on cis-2-butene-1,4-diol was 93.1%.

[0123] Comparative Example 2

[0124] This comparative example is used to illustrate the method for preparing 2-n-propyl-4,7-dihydro-1,3-dioxepin by catalytic azeotropic dehydration using a strong acidic ion exchange resin in the prior art.

[0125] 2-n-propyl-4,7-dihydro-1,3-dioxepin was prepared according to the method disclosed in "Synthesis of 2-n-propyl-4,7-dihydro-1,3-dioxepin by Catalysis of Strong Acidic Ion Exchange Resin" (Zhang Genbao et al., Applied Chemical Industry, 2012, 41(8), 1372-1374). Specifically, 200g of cis-2-butene-1,4-diol, 300g of n-butyraldehyde, and 200g of petroleum ether were placed in a 1000mL three-necked round-bottom flask equipped with a thermometer, a reflux condenser, and a water separator, and then 10g of D001 type strong acidic ion exchange resin was added. The mixture was heated to 63°C and refluxed under normal pressure, and the water produced by the reaction was continuously separated. The reflux time was 10h, until no water was evaporated, and the reaction was terminated. The strong acidic ion exchange resin was filtered to remove the strong acidic ion exchange resin, and then the petroleum ether and the remaining n-butyraldehyde in the reaction solution were recovered by distillation under normal pressure. When the liquid temperature reaches 110°C, switch to negative pressure distillation, control the vacuum to -0.098MPa, cut the front fraction and apply it to the next batch of distillation, and continue distillation to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxepin. The product content is 98.3wt% as determined by gas chromatography.

[0126] The total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane based on cis-2-butene-1,4-diol was 95.1%.

[0127] Comparative Example 3

[0128] (1) 2000 g of cis-2-butene-1,4-diol (content 98.5 wt%) and 3000 g of n-butyraldehyde were respectively pumped into a static mixer for mixing at 10° C. for 3 min to obtain a pre-reaction liquid.

[0129] The pre-reaction liquid was transported by a peristaltic pump to flow through D001 type strong acid ion exchange resin a (resin column specification is φ2.5cm×30cm) for primary reaction. The primary reaction temperature was controlled at 30°C and the flow rate was 2BV / h to obtain 5000g of primary reaction liquid.

[0130] (2) The primary reaction liquid is subjected to atmospheric distillation to recover petroleum ether and unreacted n-butyraldehyde, and then subjected to vacuum distillation under vacuum conditions of -0.098 MPa to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxane. The content of the product is 99.2 wt % as determined by gas chromatography.

[0131] The total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane based on cis-2-butene-1,4-diol was 90.7%.

[0132] Comparative Example 4

[0133] (1) 2000 g of cis-2-butene-1,4-diol (content 98.5 wt%) and 3000 g of n-butyraldehyde were respectively pumped into a static mixer for mixing at 10° C. for 3 min to obtain a pre-reaction liquid.

[0134] The pre-reaction liquid was transported by a peristaltic pump to flow through D001 type strong acid ion exchange resin a (resin column specification is φ2.5cm×30cm) for primary reaction. The primary reaction temperature was controlled at 30°C and the flow rate was 2BV / h to obtain 5000g of primary reaction liquid.

[0135] (2) Under the peristaltic pump, the primary reaction liquid is mixed with 2500g of petroleum ether through a static mixer, and then flows through D001 type strong acid ion exchange resin b (resin column specification is φ2.5cm×30cm) for secondary reaction. The secondary reaction temperature is controlled at 30°C and the flow rate is 3BV / h. The effluent is separated into the water layer to obtain the secondary reaction liquid.

[0136] (3) The secondary reaction liquid is subjected to atmospheric distillation to recover petroleum ether and unreacted n-butyraldehyde, and then subjected to vacuum distillation under vacuum conditions of -0.098 MPa to obtain the product 2-n-propyl-4,7-dihydro-1,3-dioxepin. The content of the product is 99.3 wt % as determined by gas chromatography.

[0137] After the extract was applied, the total yield of 2-n-propyl-4,7-dihydro-1,3-dioxetane was 95% based on cis-2-butene-1,4-diol.

[0138] Table 1

[0139]

[0140] Examples 1-11 of the present invention adopt a multi-stage reaction, and the yield of the product 2-propyl-4,7-dihydro-1,3-dioxepin is high, which can reach more than 93%; when the water layer in step (2) is subjected to a four-stage reaction with the raw material and the second water layer in proportion, the extract is used for the next batch reaction, and the raw material loss is further reduced, and the product yield is higher, which can reach more than 95%; and the product content and yield of the preferred technical solution are higher; at the same time, the preparation method has the characteristics of low pollution, low energy consumption and short production cycle. Compared with Comparative Examples 3 and 4, the present application adopts a multi-stage reaction, which can significantly improve the product yield, and the yield of the preferred embodiment of the present invention is higher. In addition, the strongly acidic catalytic resin column in the embodiment can continuously contact the reaction, has high reaction efficiency, can shorten the reaction cycle, and can be recycled. In comparison, the dynamic use of the catalyst in Comparative Examples 1 and 2 not only has a low product yield and content, but is also easy to break and produce solid waste, and the reaction adopts solvent azeotropic dehydration, which consumes a lot of heat energy during production, increasing energy consumption.

[0141] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for preparing 2-propyl-4,7-dihydro-1,3-dioxepin, characterized in that: The method comprises the following steps: (1) mixing a compound A represented by the general formula RCHO with cis-2-butene-1,4-diol to obtain a pre-reaction liquid, and passing the pre-reaction liquid through a strong acid catalytic resin column a to perform a primary reaction to obtain a primary reaction liquid; (2) the primary reaction liquid and the first extractant are first stirred, the obtained first mixed liquid is passed through a strongly acidic catalytic resin column b for a secondary reaction, and the secondary reaction liquid and the water layer are separated; (3) passing the secondary reaction liquid through a strong acid catalytic resin column c for a tertiary reaction to obtain a tertiary reaction liquid; (4) distilling the tertiary reaction liquid to obtain 2-propyl-4,7-dihydro-1,3-dioxepin as shown in formula (1), Wherein, R is n-propyl or isopropyl; The first extractant is selected from at least one of petroleum ether, n-hexane, cyclohexane and n-heptane; In step (2), the mass ratio of the primary reaction liquid to the first extractant is 0.5-2.5:1; The mixing temperature is 0-20°C; the primary reaction temperature is 20-40°C; the secondary reaction temperature is 20-40°C; and the tertiary reaction temperature is 50-80°C.

2. The method according to claim 1, wherein: In step (1), the mass ratio of compound A to cis-2-butene-1,4-diol is 1-5:1; And / or, in step (2), the mass ratio of the primary reaction liquid to the first extractant is 1-2:

1.

3. The method according to claim 2, wherein: In step (1), the mass ratio of compound A to cis-2-butene-1,4-diol is 1.5-3:

1.

4. The method according to any one of claims 1 to 3, wherein: In step (1), the mixing temperature is 5-15°C and the mixing time is 1-10 min; And / or, in step (1), the temperature of the primary reaction is 25-35°C; And / or, in step (2), the temperature of the secondary reaction is 25-35°C; And / or, in step (3), the temperature of the tertiary reaction is 55-65°C.

5. The method according to claim 4, wherein: In step (1), the mixing time is 1-5 min.

6. The method according to any one of claims 1 to 3, wherein: The strong acid catalytic resin columns a, b and c are each a strong acid ion exchange resin.

7. The method according to claim 6, wherein: The volumetric total exchange capacity of the strongly acidic ion exchange resin is not less than 1.5 mmol / mL.

8. The method according to claim 7, wherein: The volumetric total exchange capacity of the strongly acidic ion exchange resin is not less than 1.7 mmol / mL.

9. The method according to claim 6, wherein: The strongly acidic ion exchange resin is selected from gel-type resin and / or macroporous resin.

10. The method according to any one of claims 1 to 3, wherein: The first extractant is petroleum ether.

11. The method according to any one of claims 1 to 3, wherein: The flow rate of the pre-reaction liquid flowing through the strong acid catalytic resin column a is 1-10 BV / h; And / or, the flow rate of the first mixed solution flowing through the strong acid catalytic resin column b is 1-10 BV / h; And / or, the flow rate of the secondary reaction liquid flowing through the strong acid catalytic resin column c is 1-10 BV / h.

12. The method according to claim 11, wherein: The flow rate of the pre-reaction liquid flowing through the strong acid catalytic resin column a is 2-5 BV / h; And / or, the flow rate of the first mixed solution flowing through the strong acid catalytic resin column b is 2-5 BV / h; And / or, the flow rate of the secondary reaction liquid flowing through the strong acid catalytic resin column c is 2-5 BV / h.

13. The method according to claim 12, wherein: The flow rate of the pre-reaction liquid flowing through the strong acid catalytic resin column a is 2-4 BV / h; And / or, the flow rate of the first mixed solution flowing through the strong acid catalytic resin column b is 2-4 BV / h; And / or, the flow rate of the secondary reaction liquid flowing through the strong acid catalytic resin column c is 2-4 BV / h.

14. The method according to any one of claims 1 to 3, wherein: The method further comprises: in step (2), the water layer, compound A and the second extractant are subjected to a second stirring, the obtained second mixed solution is passed through a strong acid catalytic resin column d for a quaternary reaction, and the liquids are separated to obtain an extract and a wastewater layer.

15. The method according to claim 14, wherein: The mass ratio of the water layer, compound A and the second extractant is 1:0.1-0.5:1-4.

16. The method according to claim 15, wherein: The mass ratio of the water layer, compound A and the second extractant is 1:0.2-0.45:2-3.

17. The method according to claim 14, wherein: The second extracting agent is selected from at least one of petroleum ether, n-hexane, cyclohexane and n-heptane.

18. The method according to claim 14, wherein: The extracting liquid is circulated and added into the pre-reaction liquid; And / or, the mass ratio of the circulating amount of the extract to cis-2-butene-1,4-diol is 0.4-1:

1.

19. The method according to claim 18, wherein: The mass ratio of the circulating amount of the extract to cis-2-butene-1,4-diol is 0.5-0.8:

1.

20. The method according to claim 14, wherein the flow rate of the second mixed solution flowing through the strong acid catalytic resin column d is 1-10 BV / h; And / or, the temperature of the fourth-stage reaction is 50-80°C.

21. The method according to claim 20, wherein: The flow rate of the second mixed liquid flowing through the strong acid catalytic resin column d is 2-5 BV / h; And / or, the temperature of the fourth stage reaction is 55-65°C.

22. The method according to claim 21, wherein: The flow rate of the second mixed liquid flowing through the strong acid catalytic resin column d is 2-4 BV / h.

23. The method according to any one of claims 1 to 3, wherein: In step (4), the distillation is atmospheric distillation and negative pressure distillation.

24. The method according to claim 23, wherein: The distillation process includes: firstly performing atmospheric distillation on the tertiary reaction liquid to recover the first extractant, the second extractant and the compound A, and then performing negative pressure distillation to obtain 2-propyl-4,7-dihydro-1,3-dioxepin.

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