Preparation Of Rifamycin S By Oxidation Of Rifamycin SV

Rifamycin S,an important intermediate in the synthesis of rifamycin antibiotics,is traditionally manufactured from rifamycin S V via oxidation with hypochlorite as an oxidant.In order to avoid the intergranular corrosion of chloride ion to stainless steel equipment,the glass lined reactors are used in industry.However,some problems,such as mixture unevenness and rifamycin S degradation due to the long-time treatment,have showed up.To use stainless steel reactors to achieve the continuous production of rifamycin S,a chloride-free oxidant is urgent to be explored.The research has developed a potential oxidation system for the preparation of rifamycin S from rifamycin SV,and the main contents include:(1)The determination of oxidation system.With the suitable solution decided,H2O2 was chosen as a potential oxidant for rifamycin SV oxidation based on the comparison of Oxidation-Reduction potential of different oxidants,which were usually applied in synthetic process of rifamycin antibiotics.To promote and control the oxidation process,Fe(II)was decided as the catalyst.Due to the fast reaction,H2O2 was added into the reaction system in a semi-batch manner to avoid overoxidation.(2)The optimization of reaction conditions.The appropriate reaction conditions were determined by the yield of the rifamycin S.The results of oxidation indicated that:although both CH3OH and H2SO4 could dissolve rifamycin SV well,H2SO4 was more suitable for reaction system when Fe(?)/H2O2 were selected as the oxidant;in pH=3.5 H2SO4 solvent,under T=10? with semi-batch addition of 1%H2O2 at speed of 0.3mL/min,the yield of rifamycin S could achieve 53.09%and the yield could be increased to 72.09%through changing the feeding pattern of H2O2;with semi-batch manner adding H2O2,the oxidation reaction,according to the matlab simulation,was approaching to first order reaction under specific condition.The apparent activation energy of oxidation was 10.8740 kJ/mol and the reaction rate equation could be expressed as k:= 13.32exp(-1307.84/T).(3)The optimization of technology and the recycle of catalyst.To improve rifamycin's yield and decrease the Fe(?)desposition,the oxidation process was optimized and the recovery of Fe(?)by normal ways were investigated,the results showed that:Zn(?),which had been proved to be an inhibitor in some Fenton reaction,did not inhibit the degradation of rifamycin S;the yield of rifamycin S could be improved to 76.36%and the degradation of rifamycin S could be avoided when catalyst was changed from Fe(?)to Fe(?)in certain conditions,but when pH changed,the system would transform from Fe(?)/H2O2 to Fe(?)/H2O2 and the degradation showed up again;although the catalyst could be successfully separated and recycled from the first reaction system by NaOH or NaOH/Al(?),it was difficult to reuse them due to the decrease of catalyst activity.Through the oxidation system selected in this paper�Fe(?)/H2O2,and the corresponding optimized process parameters,the yiled of rifamycin S can be finally obtained by 76.36%.It does show certain guiding significances to the industrial production of rifamycin S.