JPH045757B2 - - Google Patents

Description

[Detailed description of the invention]

"Object of the Invention" Industrial Field of Application The present invention relates to a method for producing 2,4,5-triamino-6-hydroxypyrimidine by electrolytic reduction, which is advantageous as an industrial production method. 2,4,5-triamino-6-hydroxypyrimidine is a compound useful as an intermediate raw material for synthesizing pharmaceuticals such as folic acid. Prior Art 2,4,5-triamino-6-hydroxypyrimidine (2) is produced by using 2,4-diamino-5-isonitroso-6-oxypyrimidine (2) as a raw material and reducing it. As such reduction methods, chemical reduction methods and catalytic hydrogenation methods are known, but the former method has a low yield and requires less than the theoretical amount of reducing agent. also require a large amount of
Furthermore, it is not easy to purify the product after the reaction. In the latter method, special reaction equipment is required because the reaction is carried out under hydrogen pressure, and a decomposition recovery operation is essential after the reaction. Furthermore, the decomposition cost accounts for a large proportion of the manufacturing cost, and furthermore, it is necessary to take sufficient safety measures when using hydrogen. Furthermore, methods using electrolytic reduction were introduced, for example, by
Publication No. 24-4909 or Electrochemistry Vol. 21 376-379
Known by page. These documents describe a method of electrolytically reducing an isonitron body () in an aqueous suspension using lead, zinc, copper, iron, or nickel as a cathode and caustic alkali, specifically sodium hydroxide, as a cathode electrolyte. It has been reported that the target triamino compound () can be obtained with a yield of 86 to 92%. Problems to be Solved by the Invention However, in the above-mentioned known methods, the current density that can be efficiently passed is limited to about 4 to 6 A/ ^dm2 , and this is not always possible from the viewpoint of the yield of the target product, current efficiency, etc. However, it cannot be said to be an industrially advantageous method. The inventors of the present application have completed the present invention through extensive studies in order to establish an industrially advantageous electrolytic reduction method. "Structure of the Invention" Means for Solving the Problems The inventors of the present application believe that the main reason why the yield of the target product is only approximately 90% when electrolytic reduction is performed in an alkaline aqueous solution is as follows. We focused on the fact that the isonitroso compound (), which is the raw material, is unstable in an alkaline aqueous solution. Therefore, as a result of searching for a cathode material that has sufficient corrosion resistance against alkali and also exhibits a higher limiting current density when electrolytically reducing the isonitroso compound () in an alkaline aqueous solution, it was found that titanium and its alloys are preferable. I found out. The inventors of the present invention have also discovered that when potassium hydroxide is used among alkalis, the solubility of the raw material is high and the decomposition of the raw material is extremely small. The present invention was made based on these findings, and thereby enabled electrolytic reduction at a high current density, and succeeded in dramatically improving the processing capacity per unit area of the electrode plate. That is, the present invention is characterized in that 2,4-diamino-5-isonitroso-6-oxypyrimidine is electrolytically reduced in an aqueous solution using titanium or its alloy as a cathode and an alkali metal hydroxide as a cathode electrolyte. 2,4,5-triamino-6
- A method for producing hydroxypyrimidine. The titanium used as the cathode in the present invention includes what is called industrially pure titanium. Specifically, for example, industrially pure titanium of type 1, type 2, or type 3 classified according to JIS industrial standards (JIS4600, JIS4650) can be used. Also, as a titanium alloy, for example, an alloy of titanium and palladium (Ti-0.05~0.5%Pd)
Or an alloy of titanium and molybdenum (Ti−15
~20%Mo). These electrodes may have any shape, such as a plate, a net, a rod, or a cylinder. Examples of the alkali metal hydroxide used as the cathode electrolyte include sodium hydroxide and potassium hydroxide. These electrolytes are dissolved in water to form an aqueous solution having a concentration of generally 0.5 to 10% by weight, preferably 1.5 to 5% by weight, and an aqueous solution having such a concentration is used as the catholyte. In addition to the electrolyte, an auxiliary electrolyte may be added to the catholyte, such as a highly dissociated salt such as sodium chloride or potassium chloride. The concentration of the isonitroso material raw material () in the catholyte depends on the type of electrolyte used or the reaction temperature, but is generally maintained at approximately 0.5 to 5% by weight, preferably 1.5 to 3.5% by weight. When potassium hydroxide is used as the electrolyte, the raw materials can be dissolved at particularly high concentrations. The reaction may proceed in a state where some of the raw materials are suspended. The reaction is carried out at a temperature of the catholyte of 0 to 30°C, preferably 5°C.
The temperature is maintained at ~15°C. The anode should be made of acid-resistant material, such as platinum-plated titanium, tantalum, or
Niobium or the like can be used. As the anolyte, for example, an aqueous solution of a mineral acid such as sulfuric acid may be used. The reduction reaction of the present invention is carried out in an electrolytic cell having two chambers with negative and positive electrodes separated by a diaphragm. As a diaphragm, a cation exchange membrane (for example, CMV
Membrane: Manufactured by Asahi Glass Industries Co., Ltd.; Nafion Membrane: Du
(manufactured by Pont, etc.) can be used. Various types of such electrolytic cells are known, such as a tank type, a filter press type, and a plate and frame type. Industrially, it is preferable to use a filter press type or a plate and frame type, and during the reaction, the anode and anode liquids are generally circulated through their respective relay tanks. To prevent a decrease in current efficiency, the flow rate of both liquids in the cell should be reduced to 10
It is desirable to maintain it at or above cm/sec. After starting the reaction,
As the reaction progresses, raw materials and electrolyte solution are supplied from outside the system. In order to efficiently carry out the electrolytic reduction of the present invention, 5 to 20 A/dm ² , preferably 8 to 18 A/dm ²
Set the current to flow at a current density of . It is desirable to lower the current density near the end of the reaction to increase current efficiency. After the reaction is completed, the generated 2,4,5
In order to recover -triamino-6-hydroxypyrimidine, conventional recovery and purification means can be used, such as adding sulfuric acid to the reaction solution and extracting it as sulfate crystals. Also,
The reaction solution obtained by the method of the present invention can be used as it is for producing folic acid by simply neutralizing it with hydrochloric acid. "Effects of the Invention" According to the method of the present invention, since the electrolytic reaction can proceed at a high current density, there is an advantage that the processing capacity per unit electrode area is large, and thus the device efficiency can be increased. . Also, almost
It is an extremely useful method industrially because it can produce the desired product with a yield of 95 to 98%. EXAMPLES The present invention will be described in more detail below with reference to Examples. Example 1 Electrolytic reduction of 2,4-diamino-5-isonitroso-6-oxypyrimidine was carried out using a filter press type electrolytic cell. (1) Structure of filter press type electrolytic cell Cathode: Titanium plate (JISTP35C, thickness 2mm) Effective area 1dm ² (8cm x 12.5cm) Anode: Platinum-plated titanium plate (metallic thickness 2μm, titanium thickness 2mm; manufactured by Engelhard Japan) Effective area: 1 dm ² (8 cm x 12.5 cm) Ion exchange membrane: Nafion -315 (manufactured by Dupont) Distance between ion exchange membrane and electrode plate: 1.5 mm (2) Electrolytic reaction conditions Catholyte at the start of electrolytic reaction: 2 ,4-diamino-
5-isonitroso-6-oxypyrimidine
10.0g, aqueous solution containing 10g of potassium hydroxide
350ml Raw material supplied to the cathode side after the reaction started: Slurry aqueous solution containing 87.0g of 2,4-diamino-5-isonitroso-6-oxypyrimidine
250ml Electrolyte solution supplied to the cathode after the reaction started: 90ml of 40% by weight potassium hydroxide aqueous solution Anolyte: 250ml of 2% by weight sulfuric acid aqueous solution Liquid flow rate in electrolytic cell: 15cm/sec for both catholyte and anode Catholyte during reaction Temperature setting: 13±1°C Current value during reaction: Lowered stepwise as shown below.

[Table] The electrolytic reduction reaction was carried out for 6.5 hours under the above conditions. The raw material solution and electrolyte solution were evenly supplied from outside the system to the cathode side over a period of 4 hours after the start of the reaction. After the reaction, the catholyte was extracted from the system together with washing water, and the pH was adjusted to 0.5 with an aqueous hydrochloric acid solution. This reaction solution was analyzed using high-performance liquid chromatography [Analytical column: Uniseal C _18-10 μm (sold by Gascro Industries Co., Ltd.), column length 4 mm ⁱⁿ × 30 cm, mobile phase: concentration in aqueous solution, phosphate-ammonium (NH ₄ H ₂ PO ₄ ) 0.09W/V%, Pic-B-7
(Made by Waters Associates) 0.71V/V%, methanol 1.8V/V%, acetonitrile 1.6V/V%,
As a result of quantitative analysis using a mobile phase of PH 3.0 and a measurement wavelength of UV 245 nm, the yield of the target product, 2,4,5-triamino-6-hydroxypyrimidine, was 86.1 g. (Theoretical yield 97.6%, current efficiency
96.2%) Example 2 Electrolytic reduction of 2,4-diamino-5-isonitroso-6-oxypyrimidine was carried out in the same manner as in Example 1 except for the following. Catholyte at the start of the reaction: 350 ml of an aqueous solution containing 5 g of the raw material nitrosate and 8 g of sodium hydroxide. Raw material supplied to the cathode side after the start of the reaction: 85 ml of slurry-like aqueous solution containing 28 g of raw nitroso compound
ml. After the reaction started, the electrolyte solution supplied to the cathode side: 36 ml of 40% by weight aqueous sodium hydroxide solution. Current value during reaction: It was lowered stepwise as shown below.

[Table] The above raw material solution and electrolyte solution were evenly supplied from outside the system to the cathode side over 2.75 hours after the start of the reaction. After the reaction, the reaction solution was treated in the same manner as in Example 1. As a result of quantitative analysis of the treated solution, the yield of the target triamino compound was 28.3 g. (Theoretical yield 94.3%, current efficiency 89.5%) Example 3 2,4-
Electrolytic reduction of diamino-5-isonitroso-6-oxypyrimidine was carried out. Cathode: titanium-palladium alloy plate (palladium
Contains 0.15% by weight, thickness 2mm; manufactured by Nippon Engelhard Co., Ltd.) Effective area 1dm ² (8cm x 12.5cm) After the reaction, the reaction solution was quantitatively analyzed in the same manner as in Example 1. As a result, the yield of the target product was 86.3g. It was hot. (Theoretical yield 97.8%, current efficiency 96.4%) Example 4 2,4-diamino-5-isonitroso-6- Electrolytic reduction of oxypyrimidine was carried out. After the reaction, quantitative analysis of the reaction solution revealed that the yield of the target product was 28.4 g. (Theoretical yield 94.5%,
Current efficiency 89.7%) Comparative Example 1 Electrolytic reduction of 2,4-diamino-5-isonitroso-6-oxypyrimidine was carried out in the same manner as in Example 1 except for the following. Cathode: Iron plate (JIS SS-41, thickness 2mm) Effective area
1dm ² (8cm x 12.5cm) Catholyte at the start of reaction: 5g of raw material isonitroso compound,
350ml of aqueous solution containing 8g of sodium hydroxide Raw material solution supplied to the cathode side: Raw material isonitroso compound
85 ml of an aqueous slurry solution containing 28 g Electrolyte solution supplied to the cathode side: 36 ml of an aqueous solution of 40% by weight sodium hydroxide. Current value during reaction: lowered as shown below.

[Table] Note that the raw material solution and the electrolyte solution were evenly supplied over 4 hours after the start of the reaction. As a result of quantitative analysis of the reaction solution in the same manner as in Example 1,
The yield of the target product was 26.5g. (Theoretical yield 88.4
%, current efficiency 87.5%) The results of Examples 1 to 4 and Comparative Example 1 are compared together as shown in the table below.

[Table] As is clear from the table above, the combination of titanium (or its alloy) and potassium hydroxide yields approximately the same amount of target material per unit area of the electrode plate as compared to the combination of iron and sodium hydroxide. Improved by over 3 times. Furthermore, a similar improvement of just under two times was observed in the combination of titanium (or its alloy) and sodium hydroxide.

Claims (1)

[Claims] 1. 2,4-diamino-5-isonitroso-6- in an aqueous solution using titanium or its alloy as a cathode and an alkali metal hydroxide as a cathode electrolyte.
A method for producing 2,4,5-triamino-6-hydroxypyrimidine, which comprises electrolytically reducing oxypyrimidine.