Synthesis Of ?-arbutin

?-Arbutin is a kind of glucoside which containing hydroquinone as aglycone that has anti-inflammatory,antitussive,expectorant,diuresis,whitening and many other functions.Research has shown that it is an inhibitor of tyrosinase that can effectively restrain the generation of melanin through the blocking of synthesis of dopamine and dopamine quinine.It can be used as a skin whitening without any poisonousness and harmful side effects.It has been widely used in medicine health,food,health care,cosmetics and other industries that has important economic value and broad market prospects.The previous researches were reviewed,and the Helferich reaction was adopted and inproved in this study.P-Arbutin was synthesized from hydroquinone and glucose as the starting material via acetylation,condensation,secondary acetylation and deacetylation.The innovations and explorations of the preparation of P-Arbutin are listed respectively as follows:(1)Using cheap easily-accessible raw material as the foundation,a new synthesis process of ?-Arbutin is developed.As the process is simplified,the synthetic cost is reduced.(2)In the glycosidic reaction,we use combination of lewis acid and base as catalyst,for the first time.The combined catalyst can reduce the demands of reaction conditions and increase the stereoselectivity and yield of the product.(3)The post-processing of product is very simple.High quality products is obtained effectively by crystallization that we explored though experiments.The unreacted hydroqulinone may be recovered easily by toluene dilution,therefor the synthetic cost is reduced.(4)Each step in the preparation of ?-arbutin is optimized,the results are listed respectively as follows:1)Using sodium sulfate anhydrous(20%,m/m)as a catalyst,glucose and acetic anhydride in 1:6 molar ratio was stirred in toluene at 105?for 3 h then crude product crystallized in ethanol(m/V,1/3)to give P-D-glucopyranosyl pentaacetate in a yield of 75.6%.2)P-D-glucopyranosyl pentaacetate and hydrazine acetate in 1:1.1 molar ratio was stirred in tetrahydrofuran at room temperature for 4 h then crude product washed by hot water and crystallized in 70%ethanol to give ?-D-glucose-2,3,4,6-tetraacetate in a yield of 85.6%.3)??-D-glucopyranosyl pentaacetate,hydroquinone,boron fluoride ether ate and trethylamine in 1:2:2:1 molar ratio was refluxed in dichloromethane for 20 h to give 4-hydroxy-?-arbutin in a yield of 90%.?Using trifluoroacetic anhydride(30%,m/m)and boron trifluoride etherate(10%,m/m)as catalysts,?-D-glucose-2,3,4,6-tetraacetate,hydroquinone and trifluoroacetic anhydride in 1:2:2 molar ratio was stirred at 25? for 1 h,after then stirred in dichloromethane at-20? for 50 min to give 4-hydroxy-?-arbutin in a yield of 86.5%.4)Hydroquinone and acetic anhydride in 2:1 molar ratio was stirred in acetic acid at 110?for 20h and use 70%ethanol to crystallize to give 4-hydroxyphenylacetate in a yield of 74.7%.5)?4-hydroxy-?-arbutin,acetic anhydride and sodium sulfate anhydrous in 1:2:1 molar ratio was stirred in toluene at 110?for 3 h and use 70%ethanol to crystallize that give the yield of penta-O-acetyl-?-arbutin was 88.9%??Using trifluoroacetic anhydride(30%,m/m)and boron trifluoride etherate(10%,m/m)as catalysts,?-D-glucose-2,3,4,6-tetraacetate,4-hydroxyphenylacetate and trifluoroacetic anhydride in 1:1.5:2 molar ratio was stirred at 25? for 1 h,after then stirred in dichloromethane at-20? for 50 min to give 4-hydroxy-?-arbutin in a yield of 87.8%.6)penta-O-acetyl-?-arbutin,sodium methano late(1%,m/m)and methanol(1/7.5,m/V)was stirred at 60? for 4 h and use ethyl acetate to crystallize that give the yield of ?-Arbutin was 80.0%.The products were confirmed by IR,NMR,Melting Point and HPLC.The reaction goes well at atmospheric pressure and is simple to operate,the starting materials are readily available,and the yields are high.This method is suitable for preparation on a small scale in laboratory,also suitable for large-scale in industrial production.