Research On Synthesis Process Of Clodinafop-propargyl

Clodinafop-propargyl is a kind of chrial,aryloxyphenoxypropionate and fluorinated hebicides which are ACCase depressors,it is highly effective to malignant gramineae weeds with a few quantities and can be easily metabolized,and little harmful to the environment.So,there is a fine development prospect of clodinafop-propargyl.There were many ways to synthesize clodinafop-propargyl.（1） After etherification, condensation reaction with chiral ester,hydrolysis and esterification with propargyl alcohol,clodinafop-propargyl could be synthesized from hydroquinone and 5-chloro-2,3-difluoropyridine,but the total yield of the product was less than 45%.（2） Clodinafop-propargyl could be synthesized from（R）-2-（4-hydroxyphenoxy） propionic acid propynyl ester and 5-chloro-2,3-difluoropyridine,the yield of which was 72%.（3） Using（R）-2-（4-hydroxyphenoxy） propionic acid,5-chloro-2,3-difluoropyridine and propargyl chloride as raw materials,clodinafop-propargyl could be get without isolation,it was called "one pot",the yield of which was 85%.The article was based on "one pot", with 5-chloro-2,3-difluoropyridine and（R）-2-（4-hydroxyphenoxy） propionic acid as raw materials,water as reaction medium,the synthesis process was improved and optimized.（R）-2-[4-（5-chloro-3-fluoro-2-pyridyloxy）-phenoxy]propanoic acid（intermediate） was synthesized from 5-chloro-2,3-difluoropyridine and（R）-2-（4-hydroxyphenoxy） propionic acid（HPPA）,using water as reaction medium.The conditions of etherificaion was researched by some experimental methods using K₂CO₃,Na₂CO₃ and NaOH as acid-binding agent independently.The optimal conditions for the reaction are concerned: K₂CO₃ as acid-binding agent,water as solvent medium,n（K₂CO₃）:n（HPPA）=2:1, m（water）:m（HPPA）=1.075:1,reaction temperature 106℃and reacion time 3 h.Yield of the product is 85.22%under the optimal conditions,the conversion of HPPA is 97.43% and the selectivity of the process is 87.47%,content of the product is 98.23%.it is concerned that the product of this process is（R）-2-[4-（5-chloro-3-fluro-2-pyridyloxy）-phenoxy]propanoic acid by analyzing the melting point and FTIR spectrum.Clodinafop-propargyl was sythesized from（R）-2-[4-（5-chloro-3-fluoro-2-pyridyloxy） -phenoxy]propanoic acid and propargyl chloride,using DMF as solvent,the optimal conditions for the reaction are:n（propargyl chloride）:n（intermediate）=1.2:1,m（DMF）: m（intermediate）=1.925:1,reaction temperature 70℃and reacion time 5h.With these conditions,yield of the product is 98.54%,the conversion of the intermediate is 99.62%, with the selectivity of the process is 98.92%,content of the product is 95.63%by the chiral anlytical column of HPLC.The total yield of clodinafop-propargyl is over 84%in this process,there are many advantages of this technic such as using a few kinds of solvents,easy to isolate and purificate,mild reaction conditions,etc.So,it is indicative in industrial production.