A method for preparing an intermediate of a diagnostic reagent

Abstract

This patent application discloses a method for preparing an intermediate of a diagnostic reagent, comprising the following steps: A. Take furfural, purified water, and alcohol solvent, add them to a reactor, control the temperature at 0-20°C, and stir for 0.5-1h; B. Control the temperature at 0-30°C to drip sodium hydroxide into the solution of step A, dissolve and clarify the solution, and obtain a photoreaction solution; C. Add the photoreaction solution obtained in step B to a photoreactor, start stirring, and illuminate with a photoreaction device for 6-8h; D. Remove alcohol from the reaction solution obtained in step C by vacuum concentration, then add dichloromethane to extract, separate the liquids, and collect the organic phase; After the organic phase is vacuum concentrated to dryness, add anhydrous ethanol to recrystallize, filter, and dry to obtain the product furil. This preparation method does not introduce any metal ions, has simple process conditions, is easy to operate, and has a high yield.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemical industry, and in particular to a method for preparing an intermediate of a diagnostic reagent. Background Art

[0002] Iron measurements are often used as an auxiliary means of monitoring and diagnosing anemia, hemochromatosis, chronic inflammatory diseases, hepatitis and lead poisoning. The detection reagent based on furan triazine disodium salt uses a reliable and convenient spectrophotometric method with simple operation for measuring iron in serum. The production process of furan triazine disodium salt used for the preparation of furan triazine disodium salt at home and abroad is complicated, iron ions are easily introduced during the reaction process, and the yield is generally not high.

[0003] For example, CN107556183 reported in 2018 used iron powder to catalyze 2-furoyl chloride in DMF to obtain furil, and used iron ions as catalysts, which greatly increased the risk of iron ion introduction.

[0004] For example, the oxidation method reported in Green Chemistry; vol. 19; nb. 22; (2017); p. 5356–5360 has a reaction time of 16 h and requires continuous introduction of carbon dioxide, which greatly increases the reaction time and time cost.

[0005] For example, Synthetic Communications; vol. 44; nb. 2; (2014); p. 259–266 reported the use of copper chloride and potassium iodide to oxidize furfural. The copper ions used also increased the risk of introducing iron ions because the solution also contained iron ions. Summary of the invention

[0006] In order to overcome the deficiencies of the prior art, the object of the present invention is to provide a method for preparing an intermediate of a diagnostic reagent, which does not introduce any metal ions, has simple process conditions, is easy to operate, and has a high yield.

[0007] The technical solution adopted by the present invention is as follows:

[0008] A method for preparing an intermediate of a diagnostic reagent comprises the following steps:

[0009] A. Take furfural, purified water and alcohol solvent, add them into the reactor, control the temperature at 0-20℃, and stir for 0.5-1h;

[0010] B. Control the temperature to 0-30°C and drip sodium hydroxide into the solution of step A, and the solution is dissolved and clarified to obtain a photoreaction solution;

[0011] C. Add the photoreaction solution obtained in step B into the photoreactor, start stirring, and irradiate with light using the photoreaction device for 6 to 8 hours;

[0012] D. The reaction solution obtained in step C is concentrated under reduced pressure to remove alcohol, and then dichloromethane is added for extraction, and the liquids are separated to collect the organic phase; after the organic phase is concentrated under reduced pressure to dryness, anhydrous ethanol is added for recrystallization, and the product furil is filtered and dried to obtain.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] 1. The present invention uses furfural as a raw material and discovers new methods and conditions for preparing furil. Compared with the prior art, the process conditions for the synthesis are improved to increase the production capacity of the process. At the same time, green light energy is used as a catalyst to avoid the introduction of metal ions, simplify the process steps, save process energy consumption, and the product yield can reach nearly 90% or more, greatly increasing the utilization rate of raw materials.

[0015] 2. The raw materials of alcohol solvents and dichloromethane are easy to recycle, which not only speeds up the site clearance, reduces costs, and reduces the total amount of three wastes, but also reduces occupational health hazards, achieving excellent results in energy saving, consumption reduction and environmental protection.

[0016] As a preferred embodiment of the present invention, in step A, the alcohol solvent is one or more of methanol, ethanol, and isopropanol. In this scheme, the above alcohol solvents are selected so as not to absorb UV radiation above 240nm or have a low absorption rate, so as not to hinder the photochemical reaction effect of furfural, and at the same time, they can be fully mixed with furfural to improve the reaction efficiency.

[0017] As a preferred embodiment of the present invention, in step A, the mass volume ratio of furfural, purified water and alcohol solvent is 1:(0.5-2):(2-5). In this solution, the materials are mixed uniformly and the reaction efficiency is high.

[0018] As a preferred embodiment of the present invention, in step A, the mass volume ratio of furfural, purified water and alcohol solvent is 1: (1-1.5): (2.5-4). In this solution, the material ratio is more uniformly mixed and the reaction efficiency is higher.

[0019] As a preferred embodiment of the present invention, in step B, the sodium hydroxide is a 1-20% aqueous solution, and the amount thereof is such that the mass volume ratio of furfural to sodium hydroxide is 1:(1-2). In this scheme, the material ratio has a good reaction effect.

[0020] As a preferred embodiment of the present invention, in step B, the sodium hydroxide is a 5-10% aqueous solution, and the amount thereof is such that the mass volume ratio of furfural to sodium hydroxide is 1:(1.2-1.5). In this scheme, this material ratio has a good reaction effect and generates less waste liquid.

[0021] As a preferred embodiment of the present invention, in step D, the mass volume ratio of furfural to dichloromethane and anhydrous ethanol is 1:(20-30):(10-20). In this solution, the material ratio has good extraction effect and crystallization effect.

[0022] As a preferred embodiment of the present invention, in step D, the mass volume ratio of furfural to dichloromethane and anhydrous ethanol is 1:(22-25):(13-15). In this solution, this material ratio ensures the extraction effect and crystallization effect while reducing the amount of organic solvent and saving costs.

[0023] As a preferred embodiment of the present invention, in step C, the light source of the photoreaction equipment is a 500W-2000W high-pressure mercury lamp, and the light controls the temperature of the reaction liquid at 20-30°C. In this solution, a 500W-2000W high-pressure mercury lamp is used, and the material is not easily degraded and does not affect the reaction. However, the traditional low-pressure and medium-pressure mercury lamps have strong spectral energy, and the material is easily degraded, which is not suitable for the reaction. The temperature of the reaction liquid is controlled at 20-30°C, which is conducive to improving the reaction efficiency.

[0024] As a preferred embodiment of the present invention, the drying in step D is reduced pressure drying, the drying temperature is controlled to be 35-55°C, the drying time is 4-6h, and the vacuum degree is -0.095--0.08MPa. In this scheme, the product can be completely dried by using this drying temperature, drying time and vacuum degree. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a process flow chart of an embodiment of the present invention. DETAILED DESCRIPTION

[0026] Typical embodiments that embody the features and advantages of the present invention will be described in detail in the following description. It should be understood that the present invention can have various changes in different embodiments without departing from the scope of the present invention, and the descriptions and illustrations therein are essentially used for illustration purposes rather than for limiting the present invention.

[0027] In the present invention, in the “mass volume ratio of furfural, purified water and alcohol solvent”, “mass volume ratio of furfural: sodium hydroxide” and “mass volume ratio of furfural to dichloromethane and anhydrous ethanol”, furfural is by mass, and purified water, alcohol solvent, sodium hydroxide, dichloromethane and anhydrous ethanol are by volume.

[0028] Example 1

[0029] See also Figure 1 As shown, this embodiment discloses a method for preparing an intermediate of a diagnostic reagent, comprising the following steps:

[0030] A. Take 50g of furfural and add it into the reactor, then add 50ml of purified water and 150ml of anhydrous ethanol, control the temperature at 10℃, and stir for 0.5-1h;

[0031] B. Control the temperature of the water bath at 10°C and drop 75 ml of 5% sodium hydroxide solution into the solution in step A. The solution is dissolved and clarified to obtain a photoreaction solution;

[0032] C. Add the photoreaction solution obtained in step B into the photoreactor, start stirring, turn on the light source, set the output power to 1000W, and illuminate the photoreaction device for 6 hours;

[0033] D. The reaction solution obtained in step C was placed in a water bath at 35-45° C., ethanol was removed by concentrating under reduced pressure, and then 1250 ml of dichloromethane was added for extraction, and the organic phase was separated and collected; the organic phase was again concentrated under reduced pressure, and a water bath at 30-40° C. was placed, and after concentrating under reduced pressure to dryness, 750 ml of anhydrous ethanol was added and the temperature was raised to reflux until the solution was dissolved and clarified, and then the temperature was lowered to 0-10° C. and the crystallization was carried out for 8 h, and the product furil was obtained by filtering and drying. The weight of the prepared product furil was weighed and the yield was calculated as shown in Table 1.

[0034] Example 2

[0035] See also Figure 1 As shown, this embodiment discloses a method for preparing an intermediate of a diagnostic reagent, comprising the following steps:

[0036] A. Take 100g of furfural and add it into the reactor, then add 150ml of purified water and 400ml of anhydrous ethanol, control the temperature at 15℃, and stir for 0.5-1h;

[0037] B. Control the temperature of the water bath at 15°C and drop 120 ml of 10% sodium hydroxide solution into the solution in step A. The solution is dissolved and clarified to obtain a photoreaction solution;

[0038] C. Add the photoreaction solution obtained in step B into the photoreactor, start stirring, turn on the light source, set the output power to 2000W, and illuminate with the photoreaction equipment for 6 hours;

[0039] D. The reaction solution obtained in step C was placed in a water bath at 35-45° C., ethanol was removed by concentrating under reduced pressure, and then 2200 ml of dichloromethane was added for extraction, and the organic phase was separated and collected; the organic phase was again concentrated under reduced pressure, and a water bath at 30-40° C. was placed in a water bath, and after concentrating under reduced pressure to dryness, 1500 ml of anhydrous ethanol was added and the temperature was raised to reflux until the solution was dissolved and clarified, and then the temperature was lowered to 0-10° C. and the crystallization was carried out for 8 h, and the product furil was obtained by filtering and drying. The weight of the prepared product furil was weighed and the yield was calculated as shown in Table 1.

[0040] Example 3

[0041] The difference between this embodiment and embodiment 1 is that the reaction temperature of step A and step B is 5° C., and other conditions remain unchanged.

[0042] Example 4

[0043] The difference between this embodiment and embodiment 1 is that the reaction temperature of step A and step B is 15° C., and other conditions remain unchanged.

[0044] Example 5

[0045] The difference between this embodiment and embodiment 1 is that the concentration of sodium hydroxide used in step B is 15%, and other conditions remain unchanged.

[0046] Example 6

[0047] The difference between this embodiment and embodiment 1 is that the concentration of sodium hydroxide used in step B is 20%, and other conditions remain unchanged.

[0048] Example 7

[0049] The difference between this embodiment and embodiment 1 is that the mass volume ratio of furfural, purified water and alcohol solvent used in step A is 1:1:4, specifically 50 g of furfural, 50 ml of purified water and 200 ml of anhydrous ethanol, and other conditions remain unchanged.

[0050] Example 8

[0051] The difference between this embodiment and embodiment 1 is that the mass volume ratio of furfural, purified water and alcohol solvent used in step A is 1:1.5:3, specifically 50 g of furfural, 75 ml of purified water and 150 ml of anhydrous ethanol, and other conditions remain unchanged.

[0052] Example 9

[0053] The difference between this embodiment and embodiment 1 is that the mass volume ratio of furfural and sodium hydroxide used in step B is 1:1.3, specifically 50 g of furfural and 65 ml of sodium hydroxide, and other conditions remain unchanged.

[0054] Example 10

[0055] The difference between this embodiment and embodiment 1 is that the mass volume ratio of furfural, dichloromethane and ethanol used in step D is 1:23:15, specifically 50 g of furfural, 1150 ml of dichloromethane and 750 ml of ethanol, and other conditions remain unchanged.

[0056] Comparative Example 1

[0057] The difference between this embodiment and embodiment 1 is that the reaction temperature of step A is 25° C., the reaction temperature of step B is 35° C., and other conditions remain unchanged.

[0058] Comparative Example 2

[0059] The difference between this embodiment and embodiment 1 is that the concentration of sodium hydroxide used in step B is 0.5%, and other conditions remain unchanged.

[0060] Comparative Example 3

[0061] The difference between this embodiment and embodiment 1 is that the concentration of sodium hydroxide used in step B is 25%, and other conditions remain unchanged.

[0062] The weight of the product furil prepared in the above embodiments and comparative examples was weighed and the yield was calculated, as shown in Table 1 below.

[0063] Table 1 Product furil weight and yield

[0064]

[0065] By comparing Example 1 with Comparative Example 1, it is found that the weight and yield of the product furil prepared in Example 1 are significantly higher. The difference between the two is that the reaction temperatures of step A and step B in Example 1 are set to 10°C, while those of Comparative Example 1 are set to 35°C. In addition, with reference to other embodiments, it can be seen that the reaction temperature of step A is controlled at 0-20°C, and the reaction temperature of step B is controlled at 0-30°C, which can make the weight and yield of the final product furil higher.

[0066] By comparing Example 1 with Comparative Example 2 and Comparative Example 3, it is found that the weight and yield of the product furil prepared in Example 1 are significantly higher. The difference between Example 1 and Comparative Example 2 and Comparative Example 3 is that the concentration of sodium hydroxide used in step B of Example 1 is 5%, the concentration of sodium hydroxide used in step B of Comparative Example 1 is 0.5%, and the concentration of sodium hydroxide used in step B of Comparative Example 3 is 20%. In addition, with reference to other embodiments, it can be seen that the concentration of sodium hydroxide is controlled at 1-20% aqueous solution, which can make the weight and yield of the final product furil higher. It is further preferred that sodium hydroxide adopts 5-10% aqueous solution.

[0067] The above-mentioned embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and substitutions made by technicians in this field on the basis of the present invention shall fall within the scope of protection required by the present invention.

Claims

1. A method for preparing an intermediate of a diagnostic reagent, characterized in that: The following steps are involved: A. Take furfural, purified water and alcohol solvent, add them into the reactor, control the temperature at 0-20℃, and stir for 0.5-1h; B. Control the temperature to 0-30°C and drip sodium hydroxide into the solution of step A, and the solution is dissolved and clarified to obtain a photoreaction solution; C. Add the photoreaction solution obtained in step B into the photoreactor, start stirring, and irradiate with light using the photoreaction device for 6 to 8 hours; D. The reaction solution obtained in step C is concentrated under reduced pressure to remove alcohol, then dichloromethane is added for extraction, the liquid is separated, and the organic phase is collected; after the organic phase is concentrated under reduced pressure to dryness, anhydrous ethanol is added for recrystallization, filtering, and drying to obtain the product furil; In step B, the sodium hydroxide is a 1-20% aqueous solution, and the amount thereof is such that the mass volume ratio of furfural:sodium hydroxide is 1:(1-2); In step C, the light source of the photoreaction equipment is a 500W-2000W high-pressure mercury lamp, and the temperature of the reaction liquid is controlled at 20-30°C by illumination.

2. The method for preparing an intermediate of a diagnostic reagent according to claim 1, characterized in that: In step A, the alcohol solvent is one or more of methanol, ethanol and isopropanol.

3. The method for preparing an intermediate of a diagnostic reagent according to claim 1, characterized in that: In step A, the mass volume ratio of furfural, purified water and alcohol solvent is 1: (0.5-2): (2-5).

4. The method for preparing an intermediate of a diagnostic reagent according to claim 3, characterized in that: In step A, the mass volume ratio of furfural, purified water and alcohol solvent is 1: (1-1.5): (2.5-4).

5. The method for preparing an intermediate of a diagnostic reagent according to claim 1, characterized in that: In step B, the sodium hydroxide is a 5-10% aqueous solution, and its usage is a mass volume ratio of furfural:sodium hydroxide of 1:(1.2-1.5).

6. The method for preparing an intermediate of a diagnostic reagent according to claim 1, characterized in that: In step D, the mass volume ratio of furfural to dichloromethane and anhydrous ethanol is 1: (20-30): (10-20).

7. The method for preparing an intermediate of a diagnostic reagent according to claim 6, characterized in that: In step D, the mass volume ratio of furfural to dichloromethane and anhydrous ethanol is 1:(22-25):(13-15).

8. The method for preparing an intermediate of a diagnostic reagent according to claim 1, characterized in that: The drying in step D is reduced pressure drying, the drying temperature is controlled to be 35 to 55° C., the drying time is 4 to 6 hours, and the vacuum degree is -0.095 to -0.08 MPa.

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