* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
196 g (2.2 moles) of N-methylglycine was dissolved in 360 g of water, heated to 80C, and the hot solution was quickly added to the above S-carboxymethylisothiourea aqueous solution to keep the temperature of the reaction system at not lower than 60 ° C. The reaction was stirred for 3 hours. The heating was stopped. The system was cooled to 0-5 ° C in an ice-water bath. The filter cake was washed with a small amount of absolute ethanol and dried to give 238 g of white crystals, melting at 294 ° C. Acid, yield 80percent.The filtrate was extracted four times with 300 ml of chloroform, and the extracts were combined. The chloroform was recovered at normal pressure and the residue was distilled under reduced pressure (vacuum 0.098 MPa). The fractions were collected at 104-106 ° C to give 156 g of thioglycolic acid in a yield of 85percent, and 156 g
Reference:
[1] Patent: CN105777594, 2016, A, . Location in patent: Paragraph 0025; 0026
2
[ 420-04-2 ]
[ 4316-73-8 ]
[ 6020-87-7 ]
Reference:
[1] Patent: US5719319, 1998, A,
[2] Patent: CN104086461, 2016, B, . Location in patent: Paragraph 0014; 0041; 0042
Stage 2 The aqueous solution obtained in Stage 1 was added dropwise over the course of 3 h at 20 to 30 C. to a mixture of 55.4 g of a 40% by weight aqueous sodium sarcosinate solution and 16 g of 50% strength sulfuric acid. The pH of the solution was kept at 10 by means of 50% strength NaOH. After the addition, the mixture was stirred at room temperature for 5 h and then filtered at 60 C., and the filtrate was concentrated to about 50 to 60% of the total weight under reduced pressure at max. 60 C. The precipitate which separated out after cooling was filtered off, washed with 3*20 ml of cold water and dried. 22.6 g of creatine monohydrate with a purity >99% were obtained.
EXAMPLE 6 Analogously to Example 1, a 40% by weight aqueous potassium sarcosinate solution was reacted with cyanamide. The yield of pure creatine monohydrate was 1875 g (75.3% of theory).
Among the compounds of formula (III), mention may be made especially of the following particularly preferred compounds: ... 1,3-diaminoguanidine hydrochloride 1-methylguanidine hydrochloride 1,1-dimethylguanidine hydrochloride 1-ethylguanidine hydrochloride creatine monohydrate creatinine hydrochloride agmatine agmatine sulfate ...
2
[ 420-04-2 ]
[ 4316-73-8 ]
[ 6020-87-7 ]
Yield
Reaction Conditions
Operation in experiment
In water;
EXAMPLE 5 493.2 g (1.78 moles) of a technical 40% by weight aqueous solution of <strong>[4316-73-8]sodium sarcosinate</strong> and 214 g of water was placed in a four-necked flask equipped with a stirrer, thermometer and pH meter. At 20 C., a pH value of 9.93 was adjusted with acetic acid, while stirring. The temperature was then adjusted 70 C. With intensive stirring, 138.2 g (1.65 moles) of a 50.2% by weight aqueous solution of cyanamide (SKW cyanamide L 500) were uniformly added dropwise with the help of a dosing pump over the course of 90 minutes at an internal temperature of 70 to 72 C. After ending of the cyanamide addition, the reaction mixture was further stirred for 60 minutes at an internal temperature of 70 C. After cooling to 15 C., the crystalline, readily filterable precipitate was filtered off with suction and, without washing, suspended in 330 g of water. The suspension was stirred for 1 hour at 20 C. The precipitate was filtered off with suction and subsequently, without washing, dried at 30 C. in a vacuum drying cabinet for 16 hours. The yield was 177.7 g (72.2% of theory) of creatine monohydrate.
With water; at 20 - 80℃; for 1h;Large scale;
Example 3Add 1000kg (12.89kmol) of 40% (mass %concentration) aqueous methylamine solution in an enamel reaction tankcontaining condensate recovery unit ( the saidmass % concentration indicates the mass of the methylamine thatconstitutes the percentage of the total mass of the aqueous solution ofmethylamine). Cool to 10C using ice brine solution. Stir. Slowly add,dropwise, 400kg (3.16kmol) 45% aqueous glycolonitrile (the said mass %concentration indicates the mass of the glycolonitrile that constitutes thepercentage of the total mass of aqueous glycolonitrile). Control feeding rate.Maintain reaction temp at 10-20. Upon complete addition, stir reaction at 20Cfor 3h. Slowly add 500kg (3.75kmol) of 30% sodium hydroxide solution to theammoniated reaction liquid ( the saidmass % concentration indicates the mass of the sodium hydroxide thatconstitutes the percentage of the total mass of the aqueous sodium hydroxide). After completion ofaddition, heat to 75C. Incubate for 4h. At this point, the remaining aqueousmethylamine goes through the condensation unit and into the recovery tank.Naturally cool the reaction liquid to room temperature. Slowly stir. Adjust thepH to 9~10 using 732 strong acid hydrogen form cation exchange resin. Filter outresin. Transfer reaction liquid to cyanamide condensation tank. At 20C, Add,dropwise, 400kg (3.33kmol) of 35% cyanamide to the prepared aqueous sodiumsarcosinate ( the said mass % concentration indicates the mass ofthe cyanamide that constitutes thepercentage of the total mass of the aqueous cyanamide). Control feed rate(dripping rate 5kg/min). Reaction liquid temp should not exceed 60C. Afteraddition is completed, stir for 1h at 80C. After stirring, naturally coolreaction liquid to room temperature. Cool to 5~15C using ice brine solution.Incubate and stir for 2h. After centrifugal filtration, obtain crude creatinemonohydrate. Suspend the crude creatine monohydrate in 600kg deionizeed water.Stir for 2h at 50. Cool to 10-20C usingice brine solution. Stir for 3h (stirring speed 80r/min). Flet productcrystallize ocmpletely. Filter. Wash filter cake with deionized water. For each100kg, repeat twice. Dry solids using centrifugal drier. After drying at 40 under vacuum (a pressure of 40 mbar) for 3h, obtain 431.8kg of high puritycreatine monohydrate product. Yield 91.8% (calculated glyconitrile). Watercontent 11.45%, HPLC purity of 99.97%. No detected creatinine, dicyandiamide , dihydrotriazine.
disodium creatine phosphate tetrahydrate[ No CAS ]
[ 6020-87-7 ]
[ 60-27-5 ]
Yield
Reaction Conditions
Operation in experiment
Example 12 Conversion of Creatine to Creatinine The following tables illustrate the rate of conversion to creatinine from creatine monohydrate and disodium creatine phosphate tetrahydrate solutions.
disodium creatine phosphate tetrahydrate[ No CAS ]
[ 6020-87-7 ]
[ 60-27-5 ]
[ 57-00-1 ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 12 - CONVERSION OF CREATINE TO CREATININE The following tables illustrate the rate of conversion to creatinine from creatine monohydrate and disodium creatine phosphate tetrahydrate solutions.
196 g (2.2 moles) of N-methylglycine was dissolved in 360 g of water, heated to 80C, and the hot solution was quickly added to the above S-carboxymethylisothiourea aqueous solution to keep the temperature of the reaction system at not lower than 60 C. The reaction was stirred for 3 hours. The heating was stopped. The system was cooled to 0-5 C in an ice-water bath. The filter cake was washed with a small amount of absolute ethanol and dried to give 238 g of white crystals, melting at 294 C. Acid, yield 80%.The filtrate was extracted four times with 300 ml of chloroform, and the extracts were combined. The chloroform was recovered at normal pressure and the residue was distilled under reduced pressure (vacuum 0.098 MPa). The fractions were collected at 104-106 C to give 156 g of thioglycolic acid in a yield of 85%, and 156 g