Structure and generation mechanism of a novel degradation product formed by oxidatively induced coupling of miconazole nitrate with butylated hydroxytoluene in a topical ointment studied by HPLC-ESI-MS and organic synthesis.
Structure and generation mechanism of a novel degradation product formed by oxidatively induced coupling of miconazole nitrate with butylated hydroxytoluene in a topical ointment studied by HPLC-ESI-MS and organic synthesis.
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DOI：
10.1002/jps.10591
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发表时间：
2004-02
影响因子：
3.8
通讯作者：
Fa Zhang;M. Nunes
中科院分区：
文献类型：
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作者：
Fa Zhang;M. Nunes
在含有硝酸咪康唑（1）作为活性成分和2，6-二叔丁基-4-甲基苯酚（BHT）作为载体抗氧化剂的凡士林基局部软膏制剂中，硝酸咪康唑和BHT之间发生氧化诱导偶联反应，形成新型加合物1-（3，5-二叔丁基-4-羟基-苄基）-3-[2-（2，4-二氯-苄氧基）-2-（2，4-二氯-苯基）-乙基]-3H-咪唑-1-鎓硝酸盐（2）。采用高效液相色谱-电喷雾质谱联用技术对2的结构进行了确证，并与合成的参比化合物进行了比较。反应通过来自BHT的醌甲基化物中间体进行。建立了两种合成2。
In a petrolatum based topical ointment formulation containing miconazole nitrate (1) as the active ingredient and 2,6-di-t-butyl-4-methylphenol (BHT) as a vehicle antioxidant, an oxidatively induced coupling reaction between miconazole nitrate and BHT occurred to form a novel adduct 1-(3,5-di-tert-butyl-4-hydroxy-benzyl)-3-[2-(2,4-dichloro-benzyloxy)-2-(2,4-dichloro-phenyl)-ethyl]-3H-imidazol-1-ium nitrate (2). The structure of 2 was established using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry and was confirmed by comparing with a synthesized reference compound. The reaction proceeded through a quinone methide intermediate from BHT. Two synthetic methods were established for preparing 2.