Studies On The Synthesis Of Creatine

Creatine is a kind of endogenous nutrients existing in the human body naturally. Creatine is produced naturally in the human liver, pancreas, and kidneys. Creatine plays an important role to promote the synthesis of nucleic acid and protein, to increase the reserves of energy, to promote the growth of muscles, to delay fatigue and to speed up physical recovery. Supplements in the form of creatine monohydrate are well absorbed and tolerated by the human stomach.The synthesis of creatine is studied in this paper. First the preparation of sodium sarcosinate from monomethylamine and glycolonitrile, and O-methyl isourea sulfate from urea and dimethyl sulfate were done, then, creatine from sodium sarcosinate and O-methyl isourea sulfate were sythesised. The optimization conditions for each step arepresented. The preparation of sodium sarcosinate for condensation reaction of glycolonitrile and monomethyl amine, stoichiometric ratio of reactants is 1:1.2, reaction temperature is controlled at 10℃～15℃, heating time is for 1 h. The preparation of sodium sarcosinate for for hydrolysising reaction from N-methyl acetonitrile and sodium hydroxide, stoichiometric ratio of reactants is 1:1.5-1:1.6, reacting temperature is controlled at 100℃～105℃, hydrolysising time is for 1.5h. The preparation of O-methyl isopropyl urea from urea and dimethyl sulfate, the partial adding material, urea alkylation reaction temperature is controlled at 50℃～60℃, stoichiometric ratio of reactants urea, dimethyl sulfate and sulfate is 1.1:1:1.1. The synthesis of creatine from reaction of O-methyl isourea sulfateand sodium sulfate, stoichiometric ratio of reactant is 1:1.1, reaction temperature is controlled at about 55 ℃, reaction time is 2.Oh, and pH value is near 11.In order to get high yield with high purity and even particle size distributuon of creatine, the conditions for the crystallizing process of creatine are optimized. The experiments show the optimizations of stirring speed is at 120r/min, cooling rate is at 3℃/min, crystallizing time is at 1.5h, pH value is at 8.2.The product is analyzed qualitatively and comfirmed with the substance creatine "via infrared absorption spectroscopy, and thin layer chromatography, and quantitatively via high performance liquid chromatography (HPLC). The HPLC chromatographic conditions are optimized through the content determination with external standard method for quantitative analysis on the products, temperature at room one (25℃), mobile phase composition V(CH3OH):V(H2O)=5:95, flow speed at 1.0mL/min, detected wavelength for 210nm. The optimization of testing wavelength for ultraviolet spectroscopy method is 215nm, with which the linear is good. The result shows the quality of products reach the related standards. The process for synthesis of creatine production process is established. The pilot study on the pilot production equipment selection and the design and installation for pilot plant are accomplished, the operating rules, safety procedures and work instructions are formulated. The results of pilot production show that the technology application goes well, and the workshop trial production stage can be performed accordingly. Good stability and reproducibility can be derivated from this method for pilot process of creatine synthesis, which is achieved desired effect, and can be zoomed into the trial workshop production.