JPS619587A - Manufacture of 2,4,5-triamino-6-hydroxypyrimidine - Google Patents

Abstract

PURPOSE:To manufacture 2,4,5-triamino-6-hydroxypyrimidine with superior current efficiency in a high yield by electrolytically reducing 2,4-diamino-5-isonitroso-6-oxypyrimidine in an aqueous KOH soln. as a catholyte using stainless steel as a cathode. CONSTITUTION:An acid-proof anode such as Ti plated with Pt and stainless steel as a cathode are placed in an electrolytic cell provided with a diaphragm. An aqueous sulfuric acid soln. asan anolyte and 1.5-5% aqueous soln. of KOH as a catholyte are fed to the cell, and 1.5-4% 2,4-diamino-5-isonitroso-6-oxypyrimidine is added to the catholyte. The oxypyrimidine is electrolytically reduced at 5-15 deg.C and 6-12A/dm<2> current density to manufacture 2,4,5-triamino-6- hydroxypyrimidine with superior current efficiency in a high yield.

Description

[Detailed Description of the Invention] "Object of the Invention" Industrial Application Field The present invention is applicable to electrolytic reduction, which is advantageous as an industrial production method! 2,
The present invention relates to a method for producing 4.5-triamino-6-hydroxypyrimidine.

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-) Riamino-6-hydroxypyrimidine (I[) is 2,4-diamino-5-isonitroso-
It is produced by using 6-oxypyrimidine (I) as a raw material and reducing it.

(1) (π) As such reduction methods, firstly, chemical mercury method or catalytic hydrogenation method are known, but the former method has a low yield and a high reduction rate. It requires a larger amount of agent than the theoretical amount, and 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 catalyst recovery operation is essential after the reaction. Furthermore, the catalyst cost accounts for a large proportion of the manufacturing cost, and furthermore, sufficient safety measures must be taken when using hydrogen.

Furthermore, methods using electrolytic reduction, for example,
Publication No. 909 or Electrochemistry Vol. 21, 376-379
Known by page. In these documents, lead, zinc, copper, iron, or nickel μ is used as the cathode, and caustic alkali, specifically sodium hydroxide, is used as the cathode electrolyte to electrolytically reduce isonitroso compound (I) in an aqueous suspension. A method has been proposed, and it has been reported that the target triamino compound (II) can be obtained in a yield of 86 to 92%.

Problems to be Solved by the Invention The current density that can be efficiently passed in the above-mentioned known electrolytic reduction is limited to about 4 to 5 A/(1111"), and from the viewpoint of the yield of the target product, current efficiency, etc., it is not necessary. It cannot necessarily be said that this is an industrially advantageous method.The inventors of the present application have completed the present invention after extensive studies in order to establish an industrially advantageous method using electrolytic reduction.

"Structure of the Invention" Means for Solving Problems The inventors of the present application believe that the main reason why the yield of the target product stops at approximately 90% in the case of electrolytic reduction in an alkaline aqueous solution is that It was noted that the isonitroso compound (I) 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 isonitroso compound (I) in an alkaline aqueous solution, it was found that stainless steel is preferable. I found out. Still, the inventors of the present application
It has been found 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 has been made based on these findings, and thereby enables electrolytic reduction at high current density, and furthermore, dramatically improves the processing capacity per unit area of the electrode plate. succeeded in.

That is, the present invention uses stainless steel as the cathode and potassium hydroxide as the cathode electrolyte in an aqueous solution.
This is a method for producing 2,4,5-)lyamino-6-hytrosibirimidine, which is characterized by electrolytically reducing diamino-5-iso-6-oxypyrimidine.

The stainless steel used as the cathode in the present invention has a high carbon content.
r steel or high Cr-Ni steel, such as 13Cr, 18Cr steel and 18Cr-81ii
Examples include steel, and improved types based on these. Specifically, for example, 5US416, 5US4
20,5US430.5US304,5US316,5
U8316L or the like can be used. In particular, it is preferable to use austenitic stainless steel such as 5U3304.5US316 and 5US316L. The shape of these electrodes may be any shape, such as a plate shape, an m shape, a rod shape, or a cylindrical shape.

Potassium hydroxide used as the catholyte is dissolved in water to form an aqueous solution with a concentration of generally 0.5 to 10% by weight or 1.5 to 5% by weight, and an aqueous solution with such a concentration is used as the catholyte. used as In addition to the electrolyte, an auxiliary electrolyte may be added to the catholyte, such as a highly dissociated potassium salt such as potassium chloride.

The concentration of the isonitroso compound raw material (I) in the catholyte depends on the reaction temperature, but is generally maintained at 0.5 to 5% by weight, preferably 1.5 to 4% by weight. The reaction may proceed in a state where the raw materials are partially suspended.

The reaction is carried out at a temperature of the catholyte of 0 to 30°C, preferably 5 to 1°C.
The temperature is maintained at 5°C.

As the anode, an acid-resistant material such as platinum-plated titanium, tantalum, or niobium can be used. As the anolyte, for example, an aqueous solution of a mineral acid such as sulfuric acid may be used.

The concentration of these mineral acids used is usually about 1 to 10% by weight.

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, cation exchange membranes (for example, CMV membranes: Asahi Glass Industries (+:?
[Si! ; Nafion membrane (manufactured by Du Pont, etc.) can be used. Various types of electrolytic μ such as seed type, filter press type and plate and frame type are known. 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. In order to prevent a decrease in current efficiency, the flow rate of both liquids during the
/sec or higher. As the reaction progresses, the raw material concentration decreases, so the reaction progresses while constantly adding raw materials.

In order to efficiently carry out the electrolytic reduction of the present invention, 5 to 1
The current is set to flow at 5 A/dm2, preferably from 6 to 12 A/dm2. Near the end of the reaction, the stain flow rate can be increased by lowering the current density.

After the reaction is complete, the 2,4,5-triamino-6-hydroxypyrimidine produced from the reaction solution can be recovered by conventional methods such as adding sulfuric acid to the reaction solution and extracting it as crystals of sulfuric acid. Conventional recovery and purification means can be used. Further, when the triamino compound produced by the method of the present invention is used as it is as an intermediate for folic acid, the reaction solution can be neutralized with hydrochloric acid and used as it is for the production of folic 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 therefore the device efficiency can be increased. can. Furthermore, it is an extremely useful method industrially because the desired product can be produced with a yield of approximately 95 to 98%.

Hereinafter, the present invention will be explained in more detail 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 μ.

(1) Structure of filter press type electrolytic cell Cathode: Stainless steel μ plate (J Engineering SUS Hibiki 1, thickness 2III
rrl) Effective surface @ ldm2 (8cmX12.5fi) anode:
Platinum-plated titanium plate (plating thickness 2 μm.

Titanium thickness 2) Effective serum 1d1112 (8 sides x 12.5 pieces) Ion exchange membrane: 1anorP-31s (manufactured by DuPont) Distance between ion exchange membrane and electrode plate = 1.5 meters (2) Electrolytic reaction conditions Electrolysis Catholyte at the start of the reaction = 2.4-diamino-5-isonitroso-6-oxypyrimidine 1α09. 350 wt of aqueous solution containing 109 potassium hydroxide Raw material supplied to the cathode side after the start of the reaction: 2,4-diamino-
80 pieces of slurry aqueous solution containing 239 5-isonitroso-6-oxypyrimidine 1 Electrolyte solution supplied to the cathode side after the start of the reaction: 36 ml of 40% by weight potassium hydroxide aqueous solution Anolyte: 250 pieces of 2% by weight sulfuric acid aqueous solution /Liquid flow rate during electrolysis: both cathode and anode l
Setting temperature of catholyte during 5 m/sec reaction: 13±
The energization value at 1°C reaction was lowered step by step as shown below.

Note that the raw material solution and the electrolyte solution were evenly supplied to the cathode side 2 hours after the start of the reaction.

After the reaction, the catholyte was extracted from the system along with washing water, and the reaction solution was adjusted to pH 0.5 with an aqueous hydrochloric acid solution and subjected to high performance liquid chromatography [Analytical column: Unisea/L'C
IB 10 μm (sold by Gas Kuro Kogyo ■), column length 4 mm ”φx3Qz, mobile phase: concentration in aqueous solution,
Ammonium phosphate (N1(4H2PO4)0.09
w/v%, Pic-B-7 (Water8A8aoc
manufactured by Iatea) 0.71 V/V%, methanol i,
sv/v%, psetonitrile 1.6V/V%, mobile phase p
As a result of capacity analysis at H3,0, measurement wavelength: TYV254 nm), the target product 2,4.5-)riamino-6-
The yield as hydroxypyrimidine is 29. It was Of.

(Theoretical yield 96.6%, W: fluidity 93.8%) Example 2 2.4-diamino-5-isonitroso-6 - Electrolytic reduction of oxypyrimidine was carried out.

Cathode Ni stainless steel plate (SUS304; thickness 2mm) Effective area 1 dm2 (8elRx 12.5a) After the reaction, the reaction solution was treated in the same manner as in Example 1, and as a result of quantitative analysis using high-speed fluid chromatography, the target product was detected. The yield of the triamino compound was 28.89. (Theoretical yield 9
5.9%, current efficiency 93.1%) Comparative Example 1 2.4-diamino-5 was prepared in the same manner as in Example 1 except for the following.
-Innitroso-6-oxypyrimidine was electrolytically reduced.

Cathode: Iron plate (88-41, thickness 2cm) Effective area 1 dm2 (8aX 12.51?l”) Cathode fluid at the start of reaction: 50nl of aqueous solution containing 5g of raw material isonitroso and 8g of 11 cum hydroxide Cathode side Raw material solution supplied to: Raw material isonitroso compound 28Q
Electrolyte solution supplied to the cathode side: 40% by weight aqueous solution of sodium hydroxide 36a1 The current flow value during the reaction was lowered as shown below.

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 26.59. (Theoretical yield g8.4%, [
(Fluidity: 87.5%) A comparison of the results of Examples 1 and 2 and Comparative Example 1 is shown in Table I below.

-'' As is clear from the table above, the combination of stainless steel and potassium hydroxide has a yield of target material per unit area of the electrode plate that is approximately 2 times higher than that of the combination of iron and sodium hydroxide.
Improved twice.

Reference example 1 Seed-type electrolysis cell [Yin-yang bipolar liquid is an ion exchange membrane (C.

The cathode material and cathode electrolyte were as follows: Using the above combination, electrolytic reduction of the raw material innitroso compound was carried out in an aqueous solution in which the isonitroso compound was suspended.

1) Cathode material and cathode electrolyte 2) Electrolytic conditions Cathode fluid: Raw material isonitrosomer 69. Slurry aqueous solution containing 2.4 ml of electrolyte 12 Or/Anolyte: 2 W/V% dilute sulfuric acid 120 gal Cathode dimensions: Thickness 1 mm, effective area Q, 3 dm” (6cm*×5 units) Anode: Platinum plating Titanium plate (plating thickness 2 μ general, titanium plate thickness 1 mm) Effective surface @ 0.3 dm2 (6etrr x 5eIX)
Reaction temperature: 15±1° C. Under the above conditions, the maximum current density that could be passed without generating hydrogen gas was measured, and the following results were obtained.

As is clear from the above table, the combination of stainless steel and potassium hydroxide is excellent for the electrolytic reduction of 2,4-diamino-5-isonitroso-6-oxypyrimidine.

Claims (1)

[Claims] 2,4,5-triamino-6, characterized in that 2,4-diamino-5-isonitroso-6-oxypyrimidine is electrolytically reduced in an aqueous solution using stainless steel as a cathode and potassium hydroxide as a cathode electrolyte. - A method for producing hydroxypyrimidine.