1-羟基-1,2-苯碘酰-3(1H)-酮-1-氧化物(IBX)的合成及在他唑巴坦合成中的应用

首先以邻氨基苯甲酸为原料,与NaNO2和KI在酸性条件下反应制得邻碘苯甲酸,收率92%。再以水为溶剂,70～73℃下用2KHSO5-KHSO4-K2SO4氧化得1 羟基 1,2 苯碘酰 3(1H) 酮 1 氧化物(IBX),收率81%,总收率74 5%。然后用IBX为氧化剂室温氧化6 溴青霉烷酸二苯甲酯得6 溴青霉烷酸二苯甲酯亚砜,最后6 溴青霉烷酸二苯甲酯亚砜经超声波锌粉脱溴制得青霉烷酸二苯甲酯亚砜。在青霉烷酸二苯甲酯亚砜的合成中,每步反应产物不经分离,总收率82%。尤其在氧化反应中,用IBX代替了高质量分数的过氧乙酸,使反应在室温下进行,易于控制。反应过程绿色化,提高了原子经济性。产品用1HNMR、IR表征。

Synthesis and Application of 1-Hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide(IBX) in the Synthesis of Tazobactam

2-Aminobenzoic acid was firstly iodinated with KI and NaNO_2 in HCl to get 2-iodobenzoic acid in 92% yield,which was then oxidized by 2KHSO_5-KHSO_4-K_2SO_4 in aqueous solution at 70～73 ℃ to get 1-hydroxy-1,2-benziodoxol-3(1H)-one-1-oxide (IBX) in 81% yield.IBX was used at room tempereture as oxidant to oxidize 6α-bromopenicillanic acid to benzhydryl 6α-bromopenicillanate-1-oxide(Ⅰ).Benzhydryl penicillanate-1-oxide was eventually prepared by the treatment of Ⅰ with zinc dust under ultrasonic.In the synthetic process of Ⅰ,no separation of intermediate was made and the total yield was 82%.By using IBX as oxidant instead of peracetic acid,the reaction was carried out at room temperature instead of 0 ℃.The whole process is a green procedure and the molecular economics is improved.The product was corroborated by ~1HNMR and IR.