Study on the Intermediate of 21-Bromo-3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one with Lithium Imidazole

• Main Authors: Wei-Hsun Chen, 陳韋勳
• Other Authors: Mou-Yung Yeh
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/58585050163419663418

碩士 === 國立成功大學 === 化學系專班 === 94 === A study regarding the nucleophilic substitution of reacting 21-Bromo-3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one (compound 7) with lithium imidazole was described. TLC and HPLC were employed to monitor the reaction profile and an intermediate was observed in this reaction. The HPLC analysis of the reaction profile found that the reaction yield of this intermediate increased eith the decrease of reaction temperature. The identification of this intermediate was proposed based on the experiment that after the reaction of compound 7 went into completion, other nuceophiles, such as n-butyllithium, methyllithium, lithiumpiperidine, and lithium pyrrolidine were add respectively to the reaction mixture, a major product compound 8 and another nucleophile respectively replaced compound were obtained. This results together with the literature explanation proposed by Pearson and Weinstein in similar reaction leaded to this conclusion that the reaction of compound 7 with nucleophile lithium imidazole proceeded in two ways. The major reaction route is the nucleophilic replacement of bromide with imidazole anion to give compound 7 as the major product；another temperature dependent minor route is going through nucleophilic addition of imidazole anion to the carbonyl carbon followed by ring cyclization to give a three membered oxided as the intermediate. This intermediate was ustable as to be hydrolyzed to give a α-hydroxyl- ketone adduct (compound 20) during the product worked out procedure or react respectively with the nucleophiles added before the product been worked out to give compound 21-24.