化学
苯基丁氮酮
亲核取代
溴化物
产量(工程)
溶剂
亲核细胞
SN2反应
比活度
药物化学
放射化学
核化学
组合化学
有机化学
催化作用
酶
冶金
材料科学
药理学
医学
作者
Anuradha Singh,Heldur Hakk,Sara J. Lupton
摘要
Metabolism, environmental fate, and low concentration food residue studies would be facilitated by the use of radiolabeled test articles that can be readily quantified within complex matrices. However, radiochemical approaches for such studies require high specific activities to allow analytical detection of correspondingly low masses of test article. The synthesis of high specific activity (>50 μCi/μmol) [ 14 C]‐radiolabeled phenylbutazone presents a challenge using existing methodology, mainly due to the low solvent volumes required and vigorous refluxing needed to close the pyrazolidinedione ring. Herein, we report on the significant modification of an existing method that allows the synthesis of low masses of high specific activity (>50 μCi/μmol) [ 14 C]‐phenylbutazone under mild conditions with simple purification and high yield. The closure of the pyrazolidinedione ring of 1,2‐diphenyl‐3,5‐pyrazolidinedione was accomplished as a first step with unlabeled 1,2‐diphenylhydrazine and diethyl malonate in 32% yield under gram‐scale conditions, which avoided the challenges of low solvent use and vigorous refluxing. Low mass of high specific activity n ‐[1‐ 14 C]‐butyl bromide was then added via a nucleophilic substitution reaction as a final step. Yields ranged from 65% to 92% during multiple synthetic attempts with unlabeled butyl bromide and were greatly influenced by reaction stoichiometry and the selection of base.
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