A method for continuously synthesizing vitamin B6 intermediate propyldioxetane by microwave catalysis

Abstract

The invention discloses a method for continuously synthesizing a vitamin B6 intermediate, propyldioxetane, by microwave catalysis. The method comprises the following steps: uniformly mixing 1,4-butenediol and butyraldehyde; performing an aldol condensation reaction in a microwave continuous reactor at a temperature of 20 to 85°C; the reaction solution entering a continuous distillation device; recovering the unreacted butyraldehyde; recycling the butyraldehyde; and obtaining the product, propyldioxetane, as the distillation residue. The present invention promotes the aldol condensation reaction of an adduct under the action of a microwave continuous reactor, and has the advantages of simple operation, mild process conditions, short reaction time, and no wastewater generation.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for continuously synthesizing a vitamin B6 intermediate propyldioxetane through microwave catalysis. Background Art

[0002] Vitamin B6 is a key component of coenzymes and is involved in the normal metabolism of sugars, proteins, and fats. It can inhibit vomiting, treat arteriosclerosis, anemia, and leukopenia, treat developmental delay and Parkinson's disease, nourish nerves, boost immunity, prevent and treat gynecological diseases, promote lactation and prevent gestational diabetes, relieve asthma and convulsions, and improve hair.

[0003] Currently, the oxazole process is commonly used in industry to chemically synthesize vitamin B6, with propyldioxetane being a key raw material. Two methods are commonly used both domestically and internationally. One involves a batch reaction of butenediol and butyraldehyde in a traditional reactor, using toluenesulfonic acid as a catalyst and toluene, benzene, cyclohexane, and other agents as water-carrying agents. This involves heating, reflux, and dehydration of butenediol and butyraldehyde in a conventional reactor. This method suffers from long reaction times, the toxicity of the water-carrying agent benzene, and the inability to separate unreacted materials from the water-carrying agent. The other method uses an acidic resin as a catalyst, producing the heptacycle in a continuous cycle. This method also suffers from resin loss and decreased performance, requiring periodic resin replacement and periodic cleaning with a caustic soda solution, generating significant wastewater. Both processes require washing to remove the catalytic acid from the synthesized heptacycle, generating significant wastewater.

[0004] The reaction equation is shown below:

[0005]

[0006] It is necessary to develop a green and environmentally friendly method for producing propyldioxetine that does not use toxic reagents, produces less wastewater, has low catalyst costs. Summary of the Invention

[0007] In order to further improve the yield of aldol reaction and shorten the reaction time, the present invention provides a method for continuously synthesizing propyldioxetane under microwave catalysis. The method has the advantages of continuous operation, simple operation and short reaction time.

[0008] The technical solutions of the present invention are as follows:

[0009] A method for continuously synthesizing a vitamin B6 intermediate propyldioxetane using microwave catalysis comprises the following steps: uniformly mixing 1,4-butenediol and butyraldehyde, carrying out an aldol condensation reaction in a microwave continuous reactor at a temperature of 20 to 85° C., the reaction liquid entering a continuous distillation device to recover unreacted butyraldehyde, which is recycled, and the distillation residue being the product, the vitamin B6 intermediate propyldioxetane.

[0010] The propyldioxetane may be n-propyldioxetane or isopropyldioxetane.

[0011] The present invention continuously synthesizes propyldioxetane in a microwave continuous reactor, greatly shortens the reaction time, does not require the addition of catalyst acid, does not require water washing, has milder reaction conditions, can effectively inhibit the formation of by-products, and makes subsequent operations more convenient.

[0012] Furthermore, the butyraldehyde is n-butyraldehyde or isobutyraldehyde, and n-propyldioxetane or isopropyldioxetane is prepared accordingly.

[0013] Furthermore, the microwave frequency is 300MHz-300GHz, preferably 1000-3000MHz.

[0014] Furthermore, the mass ratio of the 1,4-butenediol to butyraldehyde is 1:0.82-5, preferably 1:0.82-3.

[0015] Furthermore, the temperature is 20-85°C.

[0016] Furthermore, the reaction time of the aldol condensation reaction is 1 to 30 minutes, preferably 2 to 30 minutes. The reaction time is the residence time in the microwave continuous reactor.

[0017] Generally speaking, the higher the reaction temperature, the shorter the reaction time, and the lower the reaction temperature, the longer the reaction time. However, within the reaction temperature range of the present invention, a higher yield can be obtained.

[0018] In the present invention, the continuous distillation device can be a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water are evaporated from the top of the tower, and formaldehyde and water are separated into layers. The upper layer of formaldehyde is recovered and reused as a raw material.

[0019] The beneficial effects of the present invention are:

[0020] The present invention provides a method for the continuous synthesis of a vitamin B6 intermediate, propyldioxetane, using microwave catalysis. By promoting an aldol reaction in a continuous microwave reactor, the method is simple to operate, does not require an additional catalyst, reduces production costs, and improves production efficiency. Side reactions are minimal, yields are high, and reaction time is significantly shortened. The reaction conditions are mild, and no wastewater is generated, thus facilitating industrial production. The yield of the vitamin B6 intermediate, propyldioxetane, produced through the aldol reaction, achieved by the present method is 98-99%. DETAILED DESCRIPTION

[0021] In order to make the technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0022] Example 1

[0023] 72 g of n-butyraldehyde and 88 g of 1,4-butenediol (molar ratio of 1:1) were uniformly mixed and added to a microwave continuous reactor via a metering pump. The mixture was catalytically heated with a microwave at a frequency of 1500 MHz and reacted at 85° C. The reaction mixture remained in the continuous reactor for 2 minutes. After 2 minutes, the reaction liquid was pumped into a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water were distilled off the top of the tower, separated into layers, and the upper layer of butyraldehyde was returned to the front as a raw material. The water layer was reused in other steps. The residue was distilled to obtain 139.38 g of the desired product, n-propyldioxetane, with a molar yield of 98%.

[0024] Example 2

[0025] 144 g of n-butyraldehyde and 88 g of butenediol were uniformly mixed and added to a microwave continuous reactor via a metering pump. The mixture was catalytically heated with a microwave at a frequency of 1800 MHz and reacted at 70° C. The residence time in the continuous reactor was 10 minutes. After 10 minutes, the reaction liquid was pumped into a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water were distilled off the top of the tower and separated into separate layers. The upper butyraldehyde layer was returned to the front as a raw material, and the water layer was reused in other steps. The residue was distilled to obtain 139.66 g of the desired product, n-propyldioxetane, with a molar yield of 98.2%.

[0026] Example 3

[0027] 310 g of n-butyraldehyde and 176 g of butenediol were uniformly mixed and added to a microwave continuous reactor via a metering pump. The mixture was catalytically heated with a microwave at a frequency of 2100 MHz at 55° C. The reaction was allowed to reside in the continuous reactor for 15 minutes. After 15 minutes, the reaction liquid was pumped into a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water were distilled off the top of the tower, separated into layers, and the upper layer of butyraldehyde was returned to the front as a raw material. The water layer was reused in other steps. The residue was distilled to obtain 279.88 g of the desired product, n-propyldioxetane, with a molar yield of 98.4%.

[0028] Example 4

[0029] 660 g of n-butyraldehyde and 264 g of butenediol were uniformly mixed and added to a microwave continuous reactor via a metering pump. The mixture was catalytically heated with a microwave at a frequency of 2500 MHz and reacted at 38° C. The reaction mixture remained in the continuous reactor for 22 minutes. After 22 minutes, the reaction liquid was pumped into a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water were distilled off the top of the tower and separated into separate layers. The upper butyraldehyde layer was returned to the front as a raw material, and the water layer was reused in other steps. The residue was distilled to obtain 421.11 g of the desired product, n-propyldioxetane, with a molar yield of 98.7%.

[0030] Example 5

[0031] 792 g of n-butyraldehyde and 264 g of butenediol were uniformly mixed and added to a microwave continuous reactor via a metering pump. The mixture was catalytically heated with a microwave at a frequency of 2900 MHz and reacted at 20° C. The residence time in the continuous reactor was 30 minutes. After 30 minutes, the reaction liquid was pumped into a continuous distillation tower with an internal pressure of 10 kPa and a top temperature below 35° C. Butyraldehyde and water were distilled off the top of the tower, separated into layers, and the upper layer of butyraldehyde was returned to the front as a raw material. The water layer was reused in other steps. The residue was distilled to obtain 422.39 g of the desired product, n-propyldioxetane, with a molar yield of 99%.

[0032] The embodiment described above is only a preferred solution of the present invention and does not limit the present invention in any form. Other variations and modifications are possible without exceeding the technical solution described in the claims.

Claims

1. A method for continuously synthesizing the vitamin B6 intermediate propyldioxetane by microwave catalysis, characterized in that: The method comprises the following steps: uniformly mixing 1,4-butenediol and butyraldehyde, carrying out an aldol condensation reaction in a microwave continuous reactor at a temperature of 20-85° C., and then introducing the reaction solution into a continuous distillation device, which is a continuous distillation tower. Butyraldehyde and water are distilled off the top of the tower, and the butyraldehyde and water are separated into layers. The butyraldehyde in the upper layer is recovered and recycled as a raw material, and the distillation residue is the product, propyldioxetane, an intermediate of vitamin B6. The mass ratio of the 1,4-butenediol to butyraldehyde is 1:0.82-5.

2. The method according to claim 1, characterized in that The butyraldehyde is n-butyraldehyde or isobutyraldehyde, and n-propyl dioxetane or isopropyl dioxetane is obtained accordingly.

3. The method according to claim 1, characterized in that The microwave frequency is 300 MHz-300 GHz.

4. The method according to claim 3, characterized in that The microwave frequency is 1000-3000 MHz.

5. The method according to claim 1, wherein The reaction time is 1 to 30 minutes.

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