CN116986969A - 一种氟代烯丙醇的合成方法 - Google Patents

一种氟代烯丙醇的合成方法 Download PDF

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CN116986969A
CN116986969A CN202310140286.2A CN202310140286A CN116986969A CN 116986969 A CN116986969 A CN 116986969A CN 202310140286 A CN202310140286 A CN 202310140286A CN 116986969 A CN116986969 A CN 116986969A
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陆晓雨
王子真
水富毅
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Chuzhou University
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Abstract

本发明属于有机合成化学领域，涉及一种氟代烯丙醇的合成方法。以氟代丙烯酸和醇类化合物为反应原料，以三(2‑苯基吡啶)合铱为催化剂、三乙烯二胺为碱、过氧化苯甲酸叔丁酯为引发剂、乙腈为溶剂在光照条件下反应，得到一类重要的氟代烯丙醇类化合物。该反应原料易得、产物收率和选择性高，官能团兼容性好，底物适用范围广，合成经济价值高。为氟代烯丙醇提供了高效、便捷、经济的制备方法。

Description

一种氟代烯丙醇的合成方法
技术领域
本发明涉及化合物制备，属于有机合成领域。具体涉及一种氟代烯丙醇的合成方法。
背景技术
醇类化合物是最容易获得和最重要的有机化合物，在天然产物和药物中广泛存在。其中氟代烯丙醇，是一种多功能的结构单元和重要的合成模块。这类化合物的高效合成在合成化学和药物化学中有着重大的需求。
常规合成的方法是使用格氏试剂与氟丙烯酸衍生物亲核加成反应(式1)。然而该方法路线长、格氏试剂活性高、官能团兼容性差，反应条件苛刻、需要较低的温度，操作麻烦。
偕-二氟环丙基锡烷的开环反应也可以用于合成氟代烯丙醇(式2)，然而该反应合成步骤长，反应需要零下78摄氏度的低温，偕-二氟环丙基锡烷合成困难，底物适用范围窄。
此外，Nozaki-Hiyama-Kishi型反应也提供了氟代烯丙醇的制备方法(式3)。然而，该反应需要使用过量的有毒性的金属铬，底物使用范围窄、只能用于合成二级醇。
发明内容
醇类化合物是一类非常容易获得的廉价化合物，直接以小分子醇类化合物合成氟代烯丙醇有着重大的合成价值。针对目前合成氟代烯丙醇存在的缺点：反应路线长、底物适用范围窄、官能团差、需要使用过量的有毒试剂、反应条件苛刻等缺点。本发明直接以廉价易得的醇类化合物为原料，高效、便捷的合成了氟代烯丙醇。
为解决上述技术问题，本发明采用如下技术方案：一种氟代烯丙醇的合成方法，其特征在于：以氟代丙烯酸和醇类化合物为原料，以三(2-苯基吡啶)合铱为催化剂、三乙烯二胺为碱、过氧化苯甲酸叔丁酯为引发剂、乙腈为溶剂，按下述反应式进行反应，得到具有通式(I)的一类氟代烯丙醇类化合物：
其中R1为氢、卤素、酯基、氰基、三氟甲基等；R2为氢、甲基，R3为甲基、乙基、酯基、氰基、羰基、卤素等。
优选地，所述三(2-苯基吡啶)合铱的物质的量为氟代丙烯酸的物质的量的1％。
优选地，所述三乙烯二胺为碱的物质的量为氟代丙烯酸的物质的量的1倍。
优选地，所述过氧化苯甲酸叔丁酯的物质的量为氟代丙烯酸的物质的量的3倍。
优选地，光照波长为465纳米，反应时间为24到48小时，反应温度为室温。
该方法第一次实现了以醇和氟代丙烯酸为原料，高效、高选择性地制备氟代烯丙醇。该反应原料廉价易得、产物收率和选择性高，本反应体系加料方式简单，官能团兼容性好，底物适用范围广，合成经济价值高。为氟代烯丙醇提供了高效、便捷、经济的制备方法。
具体实施方式
下面通过具体实施方式对本发明的技术方案进行做进一步说明：
实施例1，该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、2-氟代-3-苯基丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL异丙醇，在室温下465纳米光照下反应48小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为71％，Z/E＞30∶1，产物纯度100％。
实施例2
该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、2-氟代-3-对氟苯基丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL异丙醇，在室温下465纳米光照下反应48小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为71％，Z/E＞30∶1，产物纯度100％。
实施例3
该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、2-氟代-3-间碘苯基丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL异丙醇，在室温下465纳米光照下反应48小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为68％，Z/E＞30∶1，产物纯度100％。
实施例4
该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、2-氟代-3-苯基丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL乙二醇，在室温下465纳米光照下反应36小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为63％，Z/E＞30∶1，产物纯度100％。
实施例5
该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、2-氟代-3-苯基丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL1，4丁二醇，在室温下465纳米光照下反应36小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为55％，Z/E＞30∶1，产物纯度100％。
实施例6
该实施例的反应式如下所示：
(1)在空气下，三(2-苯基吡啶)合铱(1mol％)、三乙烯二胺(1equiv)、维生素E衍生的氟代丙烯酸(0.2mmol)加入到一个带支管、含有磁子的密封反应管中，反应管抽冲氩气三次。在氩气保护下，向反应管中加入0.5mL乙腈和0.5mL乙醇，在室温下465纳米光照下反应36小时。
(2)旋干步骤(1)中所得的有机相中的溶剂，得到粗产物，然后用硅胶柱纯化粗产物，分离收率为58％，Z/E＞30∶1，产物纯度100％。
所用的各物质的量及反应条件同实施例进行实验拓展，以说明本发明的技术方案具有良好的官能团兼容性。
以上已将本发明做一详细说明，以上所述，仅为本发明实施例，当不能限定本申请实施范围，即凡依本申请范围所作均等变化与修饰，皆应仍属本发明涵盖范围。
附图说明
图1为本发明制备的产物3的核磁共振氢谱；
图2为本发明制备的产物3的核磁共振氟谱；
图3为本发明制备的产物3的核磁共振碳谱。
图4为本发明制备的产物5的核磁共振氢谱；
图5为本发明制备的产物5的核磁共振氟谱；
图6为本发明制备的产物5的核磁共振碳谱。
图7为本发明制备的产物8的核磁共振氢谱；
图8为本发明制备的产物8的核磁共振氟谱；
图9为本发明制备的产物8的核磁共振碳谱。
图10为本发明制备的产物45的核磁共振氢谱；
图11为本发明制备的产物45的核磁共振氟谱；
图12为本发明制备的产物45的核磁共振碳谱。
图13为本发明制备的产物50的核磁共振氢谱；
图14为本发明制备的产物50的核磁共振氟谱；
图15为本发明制备的产物50的核磁共振碳谱。

Claims (5)

1.一种氟代烯丙醇的合成方法，其特征在于：以氟代丙烯酸和醇类化合物为原料，以三(2-苯基吡啶)合铱为催化剂、三乙烯二胺为碱、过氧化苯甲酸叔丁酯为引发剂、乙腈为溶剂，按下述反应式进行反应，得到具有通式(I)的一类氟代烯丙醇类化合物：
其中R1为氢、卤素、酯基、氰基、三氟甲基等；R2为氢、甲基，R3为甲基、乙基、酯基、氰基、羰基、卤素等。
2.一种氟代烯丙醇的合成方法，其特征在于：所述三(2-苯基吡啶)合铱的物质的量为氟代丙烯酸的物质的量的1％。
3.一种氟代烯丙醇的合成方法，其特征在于：三乙烯二胺的物质的量为氟代丙烯酸的物质的量的1倍。
4.一种氟代烯丙醇的合成方法，其特征在于：过氧化苯甲酸叔丁酯的物质的量为氟代丙烯酸的物质的量的3倍。
5.一种氟代烯丙醇的合成方法，其特征在于：光照波长为465纳米，反应时间为24到48小时，反应温度为室温。
CN202310140286.2A 2023-02-16 2023-02-16 一种氟代烯丙醇的合成方法 Pending CN116986969A (zh)

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