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Improved method for the total synthesis of thiofentanyl
Journal of Heterocyclic Chemistry ( IF 2.0 ) Pub Date : 2020-04-08 , DOI: 10.1002/jhet.3983 M. J. Taghizadeh 1 , S. J. Hosseini 1 , S. M. Moosavi 1 , H. Parsa 1
Journal of Heterocyclic Chemistry ( IF 2.0 ) Pub Date : 2020-04-08 , DOI: 10.1002/jhet.3983 M. J. Taghizadeh 1 , S. J. Hosseini 1 , S. M. Moosavi 1 , H. Parsa 1
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Thiofentanyl is a potent analgesic and anesthetic drug that belongs to the microreceptor agonist group and is mainly used in animal's anesthesia. We present an optimized synthesis route for synthesis of thiofentanyl using nanocatalysts such as MCM-41-SO3H and SBA-15-Ph-PrSO3H as green, heterogeneous and recyclable catalysts according to the strategy. The intermediate 2-(thiophen-2-yl) ethyl methanesulfonate (1) easily obtained after conversion of the alcohol functional group into the mesylate leaving group using methanesulfonyl chloride (97% yield). The alkylation of commercially available 4-piperidone monohydrate hydrochloride with 2-(thiophen-2-yl) ethyl methanesulfonate in the presence of phase transfer catalyst was then carried out giving N-[2-(2-thienyl) ethyl]-4-piperidone (2) with 90% yield. N-[2-(2-thienyl)ethyl]-4-piperidone was then reacted with aniline in the presence of MCM-41-SO3H catalyst giving the imine derivative which reduced with sodium triacetoxyborohydride to N-phenyl-1-(2-(thiophen-2-yl)ethyl) piperidine-4-amine (ANTP) (4) with 80% yield. ANTP was finally acylated using propionyl chloride to achieve thiofentanyl (5) with 90% yield. High yields, mild reaction conditions, decreased reaction times, and convenient workup were the advantages of this method compared to the previous work.
中文翻译：
硫芬太尼全合成的改进方法
硫芬太尼是一种强效镇痛麻醉药，属于微受体激动剂组，主要用于动物的麻醉。根据该策略，我们提出了使用 MCM-41-SO 3 H 和 SBA-15-Ph-PrSO 3 H等纳米催化剂作为绿色、多相和可回收催化剂合成硫芬太尼的优化合成路线。使用甲磺酰氯将醇官能团转化为甲磺酸酯离去基团后，很容易得到中间体甲磺酸2-(噻吩-2-基)乙酯( 1 )(97%收率)。市售4-的烷基化哌啶酮一水合物盐酸盐与 2-(噻吩-2-基) 甲磺酸乙酯在相转移催化剂存在下进行，得到 N-[2-(2-噻吩基)乙基]-4-哌啶酮 ( 2 )，收率为90 % . 然后， N -[2-(2-噻吩基)乙基]-4-哌啶酮与苯胺在 MCM-41-SO 3 H 催化剂存在下反应，得到亚胺衍生物，亚胺衍生物用三乙酰氧基硼氢化钠还原为N -苯基-1-( 2-(噻吩-2-基)乙基)哌啶-4-胺 (ANTP) ( 4 )，产率为 80%。最后使用丙酰氯将 ANTP 酰化以获得硫芬太尼 ( 5) 收率为 90%。与以往的工作相比，该方法具有产率高、反应条件温和、反应时间短、后处理方便等优点。
更新日期：2020-04-08
中文翻译：
硫芬太尼全合成的改进方法
硫芬太尼是一种强效镇痛麻醉药，属于微受体激动剂组，主要用于动物的麻醉。根据该策略，我们提出了使用 MCM-41-SO 3 H 和 SBA-15-Ph-PrSO 3 H等纳米催化剂作为绿色、多相和可回收催化剂合成硫芬太尼的优化合成路线。使用甲磺酰氯将醇官能团转化为甲磺酸酯离去基团后，很容易得到中间体甲磺酸2-(噻吩-2-基)乙酯( 1 )(97%收率)。市售4-的烷基化哌啶酮一水合物盐酸盐与 2-(噻吩-2-基) 甲磺酸乙酯在相转移催化剂存在下进行，得到 N-[2-(2-噻吩基)乙基]-4-哌啶酮 ( 2 )，收率为90 % . 然后， N -[2-(2-噻吩基)乙基]-4-哌啶酮与苯胺在 MCM-41-SO 3 H 催化剂存在下反应，得到亚胺衍生物，亚胺衍生物用三乙酰氧基硼氢化钠还原为N -苯基-1-( 2-(噻吩-2-基)乙基)哌啶-4-胺 (ANTP) ( 4 )，产率为 80%。最后使用丙酰氯将 ANTP 酰化以获得硫芬太尼 ( 5) 收率为 90%。与以往的工作相比，该方法具有产率高、反应条件温和、反应时间短、后处理方便等优点。
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