Step 1. Preparation of maleyl urea making use of concentrated sulfuric acid as driver
Take 4000g toluene, 1000g maleic anhydride as well as 1300g urea, use 98% (mass percent) focused sulfuric acid (100g dosage) as a catalyst, react at 70 ° C for 1 hr, filter, clean and completely dry to acquire horseradish. To urea, the product pureness is 80% as well as the return is 85%.
According to the above experimental approach, the experimenters performed the preparation of maleyl urea 4-6 times, with a reaction time of 1-3 hours. As a result, the pureness of the item was 75% -88%, and the return was 80% -90%.
Step 2. Preparation of crude orotic acid
Take 500g maleyl urea, bromine (the mass ratio of maleyl urea to bromine is 1:1.5) and also 3000g water, respond at 20 ° C for 10 hrs to prepare the bromide intermediate. Take 1L of 10% salt hydroxide remedy, heat it to 60 ° C, after that put the bromide intermediate into the warm alkali solution, regulate the temperature level at 60 ° C, stir and also react for 5 hours to obtain a clear remedy. After that make use of concentrated hydrochloric acid (readily offered) to readjust the pH of the reaction solution to 1, and also obtain solid precipitation. After filtering, cleaning, and drying, unrefined orotic acid is obtained. The product pureness is 96% and also the item return is 80%.
According to the above experimental method, the experimenters accomplished the prep work of orotic acid 4-6 times. Amongst them, the mass proportion of maleyl urea to bromine is 1:1.5 -3.0, the reaction temperature of maleyl urea and bromine is 5-20 ° C, as well as the reaction time is 10-25h; the usage quantity of 10% salt hydroxide service is 1 -2 L, when putting the bromide, the temperature level is kept at 55-85 ° C; the mixing time is 5-10h. Because of this, the pureness of the orotic acid product was 90% -96%, and the item return was 72% -90%.
Action 3. Refining crude orotic acid
Take 150g of unrefined orotic acid as well as deionized water (the dosage is 1000g), as well as stir at 60 ° C. The option system will show up white and milky; then include 100g of ammonia water dropwise to the system, and also stir for 3 hrs. Filter to get the filtrate, acidify with hydrochloric acid until the pH is 1, stir and cool to area temperature, filter, laundry with water, gather the solid, and completely dry to acquire an orotic acid monohydrate item with an item pureness of 96% as well as a return of 70%.
According to the above experimental technique, the experimenters carried out the refining of orotic acid 4-6 times. Among them, the very first dose of ammonia water is 100-300g, the mixing temperature is 55-85 ° C, as well as the stirring time is 3-5 hours. The second dosage of ammonia water is 100-300g, and also the stirring reaction is 3-5 hours. Consequently, the product pureness of orotic acid monohydrate is ≥ 96%, as well as the return is 65% -85%.
The preparation method of orotic acid, the particular actions are as adheres to:
( 1) Synthesis of carbamoyl aspartic acid: Add 39.9 g of aspartic acid to the response vessel, after that include 21g of salt cyanate, then add 119.7 ml of water, respond at 75 ° C for 4.5 hours, awesome normally and then include mass The portion is 38% focused hydrochloric acid till the pH is 2.3, carbamoyl aspartic acid is precipitated, filteringed system and also dried to acquire 28.5 g of product, with a yield of 65%.
( 2) Synthesis of hydantoin acetic acid: In the reaction vessel, include 28.5 g of carbamoylaspartic acid, add 85 ml of 20wt% hydrochloric acid, warmth as well as vaporize to dry skin, as well as the residue is recrystallized in water and filtered to obtain Filter the residue and dry it to obtain 22.8 g of hydantoin acetic acid, with a yield of 76%.
( 3) Synthesis of carboxymethylhydantoin: In the reaction vessel, add 22.8 g hydantoin acetic acid, after that add 11.4 mL fluid bromine, then include 45.6 ml glacial acetic acid, as well as warm at 100 ° C for 2 hours. Pour the suspension into 150 ml of boiling water within 15 mins, great as well as take shape, filter to get a filter residue, and also dry the filter deposit at 100-105 ° C to obtain 15.9 g of carboxymethylhydantoin with a yield of 73%.
( 4) Synthesis of orotic acid: Add 15.9 g of carboxymethylhydantoin to the reaction vessel, include 31.8 ml of 20wt% sodium hydroxide, raise the temperature to 65 ° C at a temperature level surge price of 5 ° C per min, and also keep it cozy for 15 minutes. Add 2.5 g of triggered carbon for decolorization, filter, as well as acidify the filtrate to pH 4.5 with hydrochloric acid, stir for half a hr at 30 rpm, cool, filter, as well as completely dry to get 11.2 g of orotic acid, with a return of 68%.
