Synthetic method of ornamental blue

Abstract

The invention relates to the technical field of pigment synthesis, and particularly discloses a synthetic method of ornamental blue. According to the synthetic method, 5-hydroxy-3-iminopyridine-2, 6-diketone is adopted as a raw material, enol interconversion is performed on the raw material under the alkaline condition (under the action of an alkali catalyst), heating is performed, and chemical condensation reaction is performed to obtain the ornamental blue. The synthetic method of the ornamental blue provided by the invention is simple in process and high in reaction selectivity, the yield and purity of the product are high, the yield of the ornamental blue product is more than or equal to 80%, the purity of the ornamental blue product is more than 99%, the synthetic method has obvious advantages, no potential safety hazard exists in the process, and industrial production can be realized.

Description

Technical Field

[0001] This application relates to the technical field of pigment synthesis, and particularly to a method for synthesizing indigoidine. Background Art

[0002] Indigoidine is a natural blue pigment synthesized by microorganisms, with the molecular formula C 10 H8N4O4, and the chemical name 5,5'-diamino-4,4'-dihydroxy-3,3'-diazodibenzoquinone-(2,2'). It is insoluble in water and most organic solvents, and soluble in pyridine, DMF, DMSO, and THF. Indigoidine has properties similar to the blue pigment indigo and can be used as a substitute in industries such as textiles and food.

[0003] Indigoidine is a natural blue pigment obtained through microbial fermentation, with the characteristics of being green, safe, non-toxic, antibacterial, and having the ability to scavenge free radicals. Indigoidine is mainly produced by fermentation of strains such as Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, and Rhodosporidium toruloides. However, there is currently no report on the chemical synthesis of indigoidine. Summary of the Invention

[0004] The purpose of this application is to overcome the deficiencies of the above-mentioned prior art and provide a method for synthesizing indigoidine. The synthesis method of this application uses a non-toxic solvent, has a simple process, high reaction selectivity, and the obtained indigoidine product has a high yield and high purity, making it suitable for industrial production.

[0005] To achieve the above purpose, the technical solution adopted in this application is as follows:

[0006] This application provides a method for synthesizing indigoidine, including the following steps:

[0007] S1. Dissolve 5-hydroxy-3-iminopyridine-2,6-dione in water, add a base catalyst, and heat for sufficient reaction to obtain a crude mixture;

[0008] S2. Perform solid-liquid separation on the crude mixture obtained in step S1 to obtain a precipitate;

[0009] S3. Wash and centrifuge the precipitate obtained in step S2 to obtain a wet product;

[0010] S4. Dry the wet product obtained in step S3 to obtain indigoidine;

[0011] The structural formula of 5-hydroxy-3-iminopyridine-2,6-dione is as follows:

[0012]

[0013] In this application, 5-hydroxy-3-iminopyridine-2,6-dione with the above structural formula is used as the raw material. Under alkaline conditions (under the action of an alkali catalyst), the raw material undergoes enol-keto tautomerism, and chemical condensation reaction is carried out by heating to obtain Guanhong.

[0014] The solvent of the synthesis method provided by this application is non-toxic, the process is simple, the reaction selectivity is high, and the yield and purity of the obtained Guanhong product are high. The yield of the Guanhong product of this method is ≥80%, which has obvious advantages and is suitable for industrial production.

[0015] The chemical equation of the above synthesis method of Guanhong is as follows:

[0016]

[0017] This application uses water as the solvent, with less amount of three wastes, and uses common alkalis that are cheap and easily available as catalysts, which is in line with green environmental protection economy.

[0018] As a preferred implementation mode of the synthesis method of Guanhong described in this application, in the step S1, the alkali catalyst includes alkali metal salts.

[0019] This application uses 5-hydroxy-3-iminopyridine-2,6-dione as the raw material. Under the action of an alkali catalyst such as alkali metal salts, the raw material undergoes enol-keto tautomerism, and then chemical condensation reaction is carried out to obtain Guanhong.

[0020] As a preferred implementation mode of the synthesis method of Guanhong described in this application, the alkali metal salt is at least one of sodium hydroxide, potassium carbonate, potassium hydroxide, sodium carbonate, alkoxide, basic amine, metal hydride and lithium amide.

[0021] As a preferred implementation mode of the synthesis method of Guanhong described in this application, the alkoxide includes sodium alkoxide; the basic amine includes tertiary amine; the metal hydride includes NaH; the lithium amide includes lithium diisopropylamide.

[0022] As a preferred implementation mode of the synthesis method of Guanhong described in this application, the alkali metal salt is sodium hydroxide, potassium carbonate, potassium hydroxide, sodium carbonate.

[0023] When the alkali catalyst is preferably the above-mentioned types of alkalis, the raw material 5-hydroxy-3-iminopyridine-2,6-dione can better undergo enol-keto tautomerism under the action of the alkali, and better chemical condensation reaction can be carried out to obtain Guanhong.

[0024] As a preferred implementation mode of the synthesis method of Guanhong described in this application, in the step S1, the molar ratio of 5-hydroxy-3-iminopyridine-2,6-dione to the alkali catalyst is 1:(0.5 - 1.5).

[0025] In the technical solution of the present application, when the molar ratio of 5-hydroxy-3-iminopyridine-2,6-dione to the base catalyst is 1:(0.5-1.5), the tautomerism of the enol form can be controlled to reach a stable equilibrium state, and the catalytic reaction can proceed under heating conditions.

[0026] As a preferred embodiment of the method for synthesizing the blue pigment described in the present application, in step S1, the heating temperature is 50-80°C and the heating time is 5-8 h.

[0027] When the heating temperature is higher than the above temperature, the yield of the blue pigment will decrease. Reacting at a temperature exceeding a certain level will cause the blue pigment to decompose and the yield to decrease. When the heating temperature is lower than the above temperature, the yield will decrease significantly, indicating that temperature affects the reaction rate.

[0028] Preferably, in step S2, the crude mixture obtained is directly subjected to solid-liquid separation to recover the solvent, and a precipitate is obtained.

[0029] In step S2, the above solid-liquid separation operation is used to remove the solvent.

[0030] As a preferred embodiment of the method for synthesizing the blue pigment described in the present application, in step S3, deionized water or pure water is used for washing, and the washing is carried out 1-3 times. Preferably, deionized water is used for washing.

[0031] In the method for synthesizing the blue pigment of the present application, the precipitate is washed 1-3 times with deionized water or pure water, which can remove the base catalyst and unreacted raw materials.

[0032] As a preferred embodiment of the method for synthesizing the blue pigment described in the present application, in step S3, the mass ratio of the deionized water or pure water to the precipitate is (1-2):1.

[0033] Preferably, the mass ratio of the deionized water or pure water to the precipitate is 1.5:1.

[0034] As a preferred embodiment of the method for synthesizing the blue pigment described in the present application, in step S4, the drying temperature is 50-100°C.

[0035] As a preferred embodiment of the method for synthesizing the blue pigment described in the present application, in step S4, the drying temperature is 80°C.

[0036] This application uses a unique 5-hydroxy-3-iminopyridine-2,6-dione raw material. Using water as a solvent and an alkali as a catalyst, the entire process is simple and has high reaction selectivity. The final reaction product of the method is solid indigo, and the product can be effectively separated by a simple solid-liquid separation method, and the solvent and raw materials can be recovered for subsequent reactions. In the solid precipitate, only water washing is needed to wash away the alkali and substrate in the crude product, obtaining an indigo product with high purity, greatly reducing the production cost and process difficulty. At the same time, the purity and content of the indigo product obtained by this method will not affect the dyeing effect of the product.

[0037] This application uses a unique raw material for the high-reaction-selectivity chemical synthesis of indigo. The chemical synthesis process has simple operation, mild reaction conditions, high yield, and the product can be purified by simple solid-liquid separation and water washing operations, and the solvent can be recovered as a raw material for subsequent production, which is conducive to large-scale industrial production.

[0038] Compared with the prior art, this application has the following beneficial effects:

[0039] In view of the blank in the chemical synthesis of indigo, this application provides a method for synthesizing indigo. This application uses 5-hydroxy-3-iminopyridine-2,6-dione as a raw material. Under alkaline conditions (under the action of an alkali catalyst), the raw material undergoes keto-enol tautomerism and is heated for chemical condensation reaction to obtain indigo. The indigo synthesis method provided by this application has a simple process, high reaction selectivity, high product yield and high purity. The yield of the indigo product is ≥80%, and the purity of the indigo product is above 99%. It has obvious advantages, there are no safety hazards in the process, and industrial production can be realized. The chemical synthesis method adopted in this application has a faster reaction rate, shorter production cycle, higher production efficiency, lower production cost, and simpler process operation compared with the currently reported biological synthesis methods, and industrial production can be realized. Description of the Drawings

[0040] Figure 1 It is the HPLC chromatogram of the liquid phase of the initial reaction solution in Example 1.

[0041] Figure 2 It is the HPLC chromatogram of the liquid phase of the reaction solution after adding alkali in Example 1.

[0042] Figure 3 It is the HPLC chromatogram of the liquid phase of the reaction solution at the end of the reaction in Example 1.

[0043] Figure 4 It is the ultraviolet absorption spectrum of the raw material in Example 1.

[0044] Figure 5 It is the ultraviolet absorption spectrum of the product in Example 1.

[0045] Figure 6 It is the dry powder of the product obtained in Example 1. Detailed implementation manners

[0046] To better illustrate the purpose, technical solution and advantages of the present application, the present application will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0047] In the following examples and comparative examples, unless otherwise specified, the experimental methods used are all conventional methods, and the materials, reagents, etc. used, unless otherwise specified, can all be obtained from commercial channels, and the component raw materials used in each parallel experiment are all of the same kind.

[0048] The 5-hydroxy-3-iminopyridine-2,6-dione involved in the present application is provided by Nanjing Hegu Life Biotechnology Co., Ltd., and the raw material is derived from the pyridone compound with the application number 2025103789489.

[0049] Example 1. A method for synthesizing guanyan

[0050] This embodiment provides a synthesis method of Guanlan, including the following steps:

[0051] Put 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.57 g of NaOH (14.28 mmol, 1.0 eq), then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.51 g of blue-black solid, which is Guanlan, with a yield of 85.28% and a purity of 99.41%.

[0052] The liquid phase of the reaction raw material 5-hydroxy-3-iminopyridine-2,6-dione is as Figure 1 shown, the liquid phase of the product is as Figure 3 shown, the liquid phase of the initial reaction solution is as Figure 1 shown, the liquid phase of the reaction solution after adding alkali is as Figure 2 shown, and the liquid phase of the reaction solution at the end of the reaction is as Figure 3 shown. The maximum absorption of the reaction raw material 5-hydroxy-3-iminopyridine-2,6-dione is as Figure 4 shown, the maximum absorption of the product is as Figure 5 shown. The appearance of the product powder is as Figure 6 shown.

[0053] Example 2. A method for synthesizing guanyan

[0054] This embodiment provides a synthesis method of Guanlan, including the following steps:

[0055] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.14 g of NaOH (7.14 mmol, 1.0 eq). Then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.43 g of blue-black solid, which is guanlan, with a yield of 80.72% and a purity of 99.43%.

[0056] Example 3. A method for synthesizing guanyan

[0057] This example provides a method for synthesizing guanlan, including the following steps:

[0058] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.86 g of NaOH (21.41 mmol, 1.5 eq). Then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.42 g of blue-black solid, which is guanlan, with a yield of 80.23% and a purity of 99.55%.

[0059] Example 4. A method for synthesizing guanyan

[0060] This example provides a method for synthesizing guanlan, including the following steps:

[0061] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.80 g of KOH (14.28 mmol, 1.0 eq). Then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.52 g of blue-black solid, which is guanlan, with a yield of 85.93% and a purity of 99.38%.

[0062] Example 5. A method for synthesizing guanyan

[0063] This example provides a method for synthesizing guanlan, including the following steps:

[0064] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 1.97 g of K2CO3 (14.28 mmol, 1.0 eq). Then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.51 g of blue-black solid, which is guanlan, with a yield of 85.43% and a purity of 99.49%.

[0065] Example 6. A method for synthesizing guanyan

[0066] This example provides a method for synthesizing Guanlan, which includes the following steps:

[0067] Put 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 1.51 g of Na2CO3 (14.28 mmol, 1.0 eq), then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.50 g of blue-black solid, which is Guanlan, with a yield of 84.92% and a purity of 99.27%.

[0068] Example 7. A method for synthesizing guanyan

[0069] This example provides a method for synthesizing Guanlan, which includes the following steps:

[0070] Put 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.57 g of NaOH (14.28 mmol, 1.0 eq), then stir and react at 50 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.49 g of blue-black solid, which is Guanlan, with a yield of 84.16% and a purity of 99.22%.

[0071] Example 8. A method for synthesizing guanyan

[0072] This example provides a method for synthesizing Guanlan, which includes the following steps:

[0073] Put 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water, and after the raw materials are dissolved, add 0.57 g of NaOH (14.28 mmol, 1.0 eq), then stir and react at 80 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.46 g of blue-black solid, which is Guanlan, with a yield of 82.39% and a purity of 99.18%.

[0074] Comparative Example 1

[0075] This comparative example provides a method for synthesizing Guanlan, which includes the following steps:

[0076] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water. Without adding base after the raw materials are dissolved, then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 0.22 g of blue-black solid, which is guanlan, with a yield of 12.69% and a purity of 99.32%.

[0077] Comparative Example 2

[0078] This comparative example provides a method for synthesizing guanlan, including the following steps:

[0079] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water. After the raw materials are dissolved, add 2.82 g of NaOH (71.38 mmol, 5.0 eq), then stir and react at 60 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 0.39 g of blue-black solid, which is guanlan, with a yield of 22.08% and a purity of 99.06%.

[0080] Comparative Example 3

[0081] This comparative example provides a method for synthesizing guanlan, including the following steps:

[0082] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water. After the raw materials are dissolved, add 0.57 g of NaOH (14.28 mmol, 1.0 eq), then stir and react at 100 °C for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 0.39 g of blue-black solid, which is guanlan, with a yield of 43.65% and a purity of 99.16%.

[0083] Comparative Example 4

[0084] This comparative example provides a method for synthesizing guanlan, including the following steps:

[0085] Add 2 g of 5-hydroxy-3-iminopyridine-2,6-dione (14.28 mmol, 1.0 eq) into a 2 L three-necked flask; add 1 L of water. After the raw materials are dissolved, add 0.57 g of NaOH (14.28 mmol, 1.0 eq), then stir and react at room temperature for 8 h. After filtration, wash with 1.5 times deionized water for 3 times, and then dry at 80 °C to obtain 1.51 g of blue-black solid, which is guanlan, with a yield of 55.28% and a purity of 98.89%.

[0086] Test Example

[0087] In the following examples, the high performance liquid chromatography detection method of the product is as described below.

[0088] Chromatographic conditions: Mobile phase: Gradient elution with methanol and pure water. The gradient table is as follows:

[0089] Time min A (pure water) % B (methanol) % 0 70 30 10 40 60 14 70 30 19 70 30

[0090] Wavelength 600 nm, flow rate 1.0 mL / min. Sampling solution: DMSO, injection volume: 10 μL, column temperature 35 °C, running time 20 min. Chromatographic column: Galasil EF C18M 4.6 mm id × 250 mm L (SN B06211801).

[0091] Perform liquid phase analysis on the blue sample and the standard product under these conditions. Sample treatment: Take 3 mg of the blue standard product into a 25 mL volumetric flask, add DMSO solution and ultrasonicate for 15 min to fully dissolve, cool down and make up the volume to the scale, and perform high performance liquid chromatography (HPLC) detection.

[0092] Test the dried weight, yield, and purity of the blue products prepared in Test Examples 1-8 and Comparative Examples 1-3.

[0093] The results are shown in Table 1.

[0094] Table 1

[0095]

[0096]

[0097] From the data in Table 1, it can be seen that by comparing the blue products obtained with different production parameters in Examples 1-8 and Comparative Examples 1-3, the production parameters in Examples 1-8 are within the parameter range of the synthesis method in this application, and products with higher purity and yield can be produced. Since the blue is insoluble in water while the substrate is soluble in water, purification by washing with water can ensure that the purity of the product does not change due to changes in reaction conditions.

[0098] The production process of Example 1 is the best process, which can achieve the best results in both purity and yield; comparing the keto-enol tautomerization ratio of the raw materials in the reaction solution in Comparative Example 1 Figure 1 and Figure 2 it can be found that the basic condition promotes the keto-enol tautomerization. On this basis, heating can make the condensation reaction proceed to obtain the blue.

[0099] In Examples 2 and 3 and Comparative Examples 1 and 2, it was found that the amount of the base catalyst affects the reaction yield. When the molar ratio of 5-hydroxy-3-iminopyridine-2,6-dione to the base is 1:0.5 - 1.5, the yield is ≥ 80%. A lower amount within this range will result in a lower reaction rate because methylene blue decomposes under conditions with a pH higher than 10, and a higher amount within this range will lead to a decrease in the yield; in Examples 4, 5, and 6, different base catalysts were replaced, and different base catalysts can all catalyze the reaction under the same molar ratio; by comparing Examples 1, 7, 8 and Comparative Example 3, it was found that as the reaction temperature increases from 50 °C to 80 °C, the reaction time becomes shorter, but the yield decreases. Reacting at a temperature exceeding a certain level will cause the decomposition of methylene blue and result in a decrease in the yield. In Comparative Example 4, the reaction was carried out at room temperature for 8 h, and the yield decreased significantly, indicating that temperature affects the reaction rate.

[0100] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present application and not to limit the protection scope of the present application. Although the present application has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present application can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present application.

Claims

1. A synthetic method of guanyan, characterized in that, It includes the following steps: S1. Dissolve 5-hydroxy-3-iminopyridine-2,6-dione in water, add an alkali catalyst, and heat for a sufficient reaction to obtain a crude mixture; S2. Perform solid-liquid separation on the crude mixture obtained in step S1 to obtain a precipitate; S3. Wash and centrifuge the precipitate obtained in step S2 to obtain a wet product; S4. Dry the wet product obtained in step S3 to obtain indigo blue; The structural formula of 5-hydroxy-3-iminopyridine-2,6-dione is as follows:

2. The synthesis method of guanylan as described in claim 1, characterized in that, In step S1, the alkali catalyst includes an alkali metal salt.

3. The synthesis method of guanamine according to claim 2, characterized in that, The alkali metal salt is at least one of sodium hydroxide, potassium carbonate, potassium hydroxide, sodium carbonate, alkoxide, basic amine, metal hydride, and lithium amide.

4. The synthesis method of guanylan as described in claim 3, characterized in that, The alkoxide includes sodium alkoxide; the basic amine includes tertiary amine; the metal hydride includes NaH; the lithium amide includes lithium diisopropylamide.

5. The synthesis method of guanylan as described in claim 1, characterized in that, In step S1, the molar ratio of 5-hydroxy-3-iminopyridine-2,6-dione to the alkali catalyst is 1:(0.5 - 1.5).

6. The synthesis method of guanylan as described in claim 1, characterized in that, In step S1, the heating temperature is 50 - 80 °C, and the heating time is 8 h.

7. The synthesis method of guanylan as described in claim 1, characterized in that, In step S4, the drying temperature is 80 °C.

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