Study On The Synthesis Process Of Chloramphenicol Derivatives

Chloramphenicol palmitate is chloramphenicol precursors drugs. It is the use of chloramphenicol structural characteristics, after the synthesis it's 3-OH and Palmitic acid' s -COOH to esters,we get the derivatives of chloramphenicol,by changing the chemical properties of drugs, raw after being modified to improve drug adverse smells. when it enters body, via enzymatic hydrolysis of the duodenum release of chloramphenicol and express effects, so its antibiotic is the same as chloramphenicol, it advantage to eliminate bitterness and especially suited to children. According to reports, chloramphenicol palmitate have A, B, C and several kinds Crystal form. Type A is stable. Type B is Sub-stable. Type C and type amorphous is unstable, creating moments after the transition to A or B type, so it is does not exist in the original drug actually. To the Effect of A type, After oral administration, it has low concentration in the blood, poor effect so this kind called inactive crystal forms; only B type is easy to absorb, in high concentrations in the blood, called crystal with clinical activity.Experimental purposes:1. Optimization synthesis technology of chloramphenicol palmitate.2. Optimizing the crystallization process of chloramphenicol palmitate make b-type of chloramphenicol palmitate.Experimental methods and results:1. Benzoyl chloride on traditional methods for process optimizationIn contrast the traditional process of two benzoyl peroxide reagents, by acylation reaction reagent SOC12 resulting product advantages such as easier to remove impurities, so we embarked more in-depth research on it. because the amount of SOC12 impact on yields of products, we determine the amount of its reaction is best for n (Palmitic acid):n (thionyl chloride)=1.0:1.5. At the same time the study of mechanism of acyl, a screening study on catalysts for the reaction catalyzed by comparing the effects of different acylating agents of benzoyl peroxide, with the comprehensive assessment, finally the Triethylamine catalyst is for optimal.2. the exploration on ester exchange synthesisPalmitic acid ethyl esters or Palmitic acid methyl ester as raw material, in alkaline or acid catalyst React with chloramphenicol then get products. Final use of Palmitic acid methyl ester Under the effect of catalyst NaOH produced target compounds.3. Proceeding from the principle of Crystal, we try on the recrystallization, volatile, diffusion law, crush grinding method and other methods, finally found a breakthrough in recrystalliz ation. through the determination of melting point and X-diffraction on crystalline confirmed reliable results.4. By melting point measurement, UV, TLC, HPLC, IR, NMR to structural characterization of the product, identify products is chloramp henicol palmitate, that is Palmitic acid has allready bond on the chloramphenicol.5. According to the Pharmacopoeia on quality control of chloramphe nicol palmitate. It Certified that products quality meet Codex standards.Experimental Conclusions:1. Palmitic acid benzoyl chloride with thionyl chloride is good, finally passed comprehensive evaluation considers thionyl chloride to the best of acylated reagents and determines the optimum dosage, both the Triethylamine catalyst for optimal. Acylation reaction of this research on the similar reference reference.2. Use palmitic acid methyl esters as raw material and Sodium hydroxide for optimum catalyst, through three levels of the four factors of orthogonal design Study on synthesis of Transester ification process,we also made three batch validation tests, indicating that the technique is stable and viable, the yield is higher. The process for the synthesis of Palmitic acid ester derivatives opened a new idea, a certain reference and practical value.3. Using ethanol as solvent crystallization to get b-type chloramphenicol palmitate, It can further optimize the cost and recovery rates higher and more stable than other methods.