Preparation background and overview of aminoguanidine bicarbonate
Aminoguanidine bicarbonate, also called aminoguanidine bicarbonate, is an important chemical product and is mainly used in the synthesis of cationic red 2BL and X-GRL in the dye industry. Used for the synthesis of the antiviral drug ribavirin drug intermediate 5-amino-1,2,4-triazole 3-carboxylic acid, and also used for the drugs tripidil, propionamidine hydrazone and the pesticide sentfurene The synthesis of hydrazones, etc. has a wide range of uses.
There are three preparation methods for aminoguanidine bicarbonate reported and used in domestic and foreign literature:
1. Use zinc powder to reduce nitroguanidine or nitrosoguanidine;
2. Hydrazine hydrolysis nitrosoguanidine or S-alkylthiourea;
3. Hydrazinolysis reaction of lime nitrogen with cyanamide, hydrazine hydrate and hydrazine salt.
Preparation of aminoguanidine bicarbonate
CN200810197402 provides a method for preparing aminoguanidine bicarbonate, which solves the problems of complex process and high cost in existing methods. The technical solution of the present invention is implemented as follows: it includes the following steps:
(1) Dissolve hydrazine hydrate in water and add dilute sulfuric acid dropwise to prepare aqueous hydrazine sulfate solution;
(2) Add lime nitrogen to the dihydrazine sulfate aqueous solution, and adjust the pH value to 7.2~7.8 with dilute sulfuric acid before adding lime nitrogen;
(3) After adding lime nitrogen, maintain the pH value at 7.2~7.8 and keep the reaction warm;
(4). After the reaction is completed, filter and separate, add ammonium bicarbonate to the filtrate, crystallize, and centrifuge to dry to obtain aminoguanidine bicarbonate.
Examples are as follows:
Put 1500L tap water and 150kg hydrazine hydrate (content ≥80%) into a 3000L glass-lined reactor equipped with a pH meter online monitoring device, add 40% dilute sulfuric acid dropwise until the pH value is 5 to 6, and add 1kg phosphoric acid Sodium dihydrogen stabilizer, add lime nitrogen in three times (the total amount of lime nitrogen is 360kg, the effective N content is ≥ 22%, and the lime nitrogen added each time is 120kg), stir vigorously, use a flow meter to continuously drip dilute sulfuric acid at a uniform speed, During the dropping process, use circulating water to control the temperature at about 45°C, and add dropwise until the pH of the reaction solution is 7.2 to 7.8. After the dropwise addition is completed, raise the temperature and keep it at 70°C for 3 hours. During the insulation process, keep the pH of the reaction solution at 7.2 to 7.8. Pour compressed air into the insulated reaction solution for 10 minutes, and then filter the reaction solution through a centrifuge and reduced pressure vacuum; during the filtration process, rinse the filter cake with warm water of about 40°C until the filtrate turns clear; the filtrate is concentrated Stir in a 3000L crystallization kettle, slowly and evenly add 300kg ammonium bicarbonate, wait for the aminoguanidine bicarbonate to crystallize for more than 4 hours, separate it through a centrifuge, and obtain 376kg of wet aminoguanidine bicarbonate, with a content of 8 benzylpyridine 3.6%, vacuum dried at 40°C to obtain 317kg of product with a content of 99.16%. The product yield calculated based on hydrazine hydrate was 96.3%.
Preparation and Application of Aminoguanidine Bicarbonate
CN201310419816.3 discloses a preparation method of lamotrigine. Lamotrigine was first developed by the British company GlaxoSmithKline. It was first launched in Australia in 1994 and has been launched in China in recent years. It has clinical It is used as an anti-epileptic drug, and the US FDA approved its indication for the treatment of bipolar disorder in 2003. The method includes two steps of chemical synthesis and refining. Aminoguanidine bicarbonate and 2,3-dichlorobenzoyl cyanide are produced under acidic conditions to generate 2-(2,3-dichlorophenyl)-2-(guanidine). Imino) acetonitrile salt, the product is neutralized with a base and cyclized by heating in an organic solvent to obtain 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-tri Lamotrigine is crude lamotrigine; the crude product is decolorized with activated carbon, recrystallized, washed, and vacuum dried to obtain fine lamotrigine. The method of the invention has mild reaction conditions, high crude/refined purity, high product yield, low cost, environmental friendliness, and is suitable for industrial large-scale production.
Preparation and analytical method of aminoguanidine bicarbonate
According to analysis, the content of aminoguanidine bicarbonate is not much, and there are iodometric methods and spectrophotometric methods, among which the iodometric method is simple to operate. Weigh 0.11~0.12g of the dry sample (accurate to 0.0002g) and place it in an Erlenmeyer flask, add distilled water and 8 mL of 1 mol/L sulfuric acid standard solution, and shake to completely dissolve it. Then add 0.1mol/L iodine standard solution, shake well, then add 1mol/L sodium hydroxide solution, shake until no bubbles occur, and the solution will turn yellow. If there is no yellow, add a small amount of sodium hydroxide solution until yellow appears. , then add 12mL of 1mol/L sulfuric acid, and titrate with 0.1mol/L sodium thiosulfate standard solution. When approaching the end point, the solution turns light yellow. At this time, add starch indicator and titrate until the blue color disappears, which is the end point. Calculate the product content according to the following formula:
In the formula, C1 is the concentration of sodium thiosulfate standard solution (mol/L); V1 is the volume of sodium thiosulfate standard solution consumed during titration (mL); C2 is the concentration of iodine standard solution (mol/L) L); V2 is the volume of the added iodine standard solution (mL); 0.03 dimethyl sulfoxide 402 is the mass of aminoguanidine bicarbonate equivalent to 1.00mL of iodine standard solution (g); m is the sample mass ( g). The difference between the results of two parallel measurements shall not be greater than 0.30%, and the arithmetic mean shall be taken as the measurement result.
