CN107488155B - 一种α,β-不饱和γ-内酯的制备方法 - Google Patents

一种α,β-不饱和γ-内酯的制备方法 Download PDF

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CN107488155B
CN107488155B CN201710717868.7A CN201710717868A CN107488155B CN 107488155 B CN107488155 B CN 107488155B CN 201710717868 A CN201710717868 A CN 201710717868A CN 107488155 B CN107488155 B CN 107488155B
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孙宝国
丁瑞
田红玉
刘永国
蓝丽媛
李姝慧
杨绍祥
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Beijing Technology and Business University
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    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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Abstract

本发明涉及结构式如下所示的α,β‑不饱和γ‑内酯的制备方法:

Description

一种α,β-不饱和γ-内酯的制备方法
本发明涉及一种α,β-不饱和γ-内酯的制备方法。
饱和γ-内酯类化合物天然存在于各种水果中,是一类非常重要的食用香料,现已广泛用于各种饮料、焙烤食品和甜品中。但是相应的α,β-不饱和γ-内酯作为食用香料的应用还很有限,到目前为止只有γ-壬烯内酯通过了美国食用香料和萃取物制造者协会(Flavour and Extract Manufacturers’Association,FEMA)的安全评价,其FEMA号为4188。对α,β-不饱和γ-内酯类化合物的香气特性有待于进一步研究。
α,β-不饱和γ-内酯类化合物是许多具有生物活性的天然产物的重要结构单元,通常具有抗肿瘤、抗真菌活性,广泛应用在医药及农药等方面,关于其合成方法的研究越来越多。目前主要的合成方法有以下五种:(1)1′-烷基取代的丙烯酸烯丙酯在金属钌络合物的催化作用下发生关环置换反应得到α,β-不饱和γ-内酯;(2)以3-对甲苯磺酰基丙醛的二甲缩醛为原料,在丁基锂的作用下与醛反应,然后氧化得到3-对甲苯磺酰基-4-烷基-γ-内酯,在碱性条件下消除得到α,β-不饱和γ-内酯;(3)以烷基取代的2,3-二氢呋喃为原料,通过光致氧化作用得到过氧化物,然后在硫酸亚铁的作用下反应得到α,β-不饱和γ-内酯;(4)(E)-3-链烯酸在二苯基二硒的催化作用下,与二(三氟乙酰氧基)碘代苯反应得到α,β-不饱和γ-内酯;(5)(E)-3-链烯酸通过氧化和消除两步反应得到α,β-不饱和γ-内酯。这些合成方法为α,β-不饱和γ-内酯类化合物的制备提供了丰富的可选择途径,但存在不同的缺陷:试剂价格昂贵,路线较长,操作复杂。
本发明的目的是提供一种新的α,β-不饱和γ-内酯的制备方法。其特征是以(E)-3-链烯酸为起始原料,以二氯甲烷为溶剂,在二苯亚砜/草酰氯组合试剂(或二苯亚砜/草酰溴组合试剂)的作用下,加入碳酸钾和18-冠醚-6,可以一步得到α,β-不饱和γ-内酯。本发明的制备方法具有试剂价廉易得、操作简便、产率高的优点。反应式如下:
Figure BSA0000149538820000011
本发明涉及结构式如下所示的α,β-不饱和γ-内酯的制备方法:
Figure BSA0000149538820000012
其主要过程是:在-78℃先将二苯亚砜(1.5eq)的二氯甲烷溶液滴加至草酰氯(1.5eq)(或草酰溴(1.5eq))的二氯甲烷溶液中,再滴加原料(E)-3-链烯酸,再加入碳酸钾和18-冠醚-6,然后回室温反应,得到相应的α,β-不饱和γ-内酯,产率在80~85%。
本发明方法中制备的α,β-不饱和γ-内酯的结构都通过核磁共振进行了确认。分析结果附在实施例后。
具体实施方式
(1)γ-戊烯内酯的制备(通过二苯亚砜/草酰氯组合试剂)
氮气保护,在装有温度计的100mL三口烧瓶中,加入草酰氯(7.5mmol,0.65mL,1.5eq)和无水二氯甲烷(10mL)。液氮-乙醇浴-78℃下,用恒压滴液漏斗缓慢滴加二苯亚砜(7.5mmol,1.52g,1.5eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,再滴加(E)-3-戊烯酸(5mmol,500mg,1.0eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,加入碳酸钾(25mmol,3.45g,5.0eq)和18-冠醚-6(0.25mmol,66mg,0.05eq),然后回室温反应5h。抽滤,滤液中加入30mL蒸馏水,分液,取有机相,用饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥。过滤,旋蒸除去溶剂得粗品,经柱层析分离提纯(石油醚/乙酸乙酯=10∶1),得到γ-戊烯内酯415mg,产率为85%。1H NMR(300MHz,CDCl3)δ7.45(dd,J=5.4,1.2Hz,1H),6.10(dd,J=5.7,1.8Hz,1H),5.18-5.10(m,1H),1.46(d,J=6.9Hz,3H)。13C NMR(75MHz,CDCl3)δ173.17,157.39,121.47,79.73,18.95。
(2)γ-壬烯内酯的制备(通过二苯亚砜/草酰氯组合试剂)
氮气保护,在装有温度计的100mL三口烧瓶中,加入草酰氯(7.5mmol,0.65mL,1.5eq)和无水二氯甲烷(10mL)。液氮-乙醇浴-78℃下,用恒压滴液漏斗缓慢滴加二苯亚砜(7.5mmol,1.52g,1.5eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,再滴加(E)-3-壬烯酸(5mmol,780mg,1.0eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,加入碳酸钾(25mmol,3.45g,5.0eq)和18-冠醚-6(0.25mmol,66mg,0.05eq),然后回室温反应5h。抽滤,滤液中加入30mL蒸馏水,分液,取有机相,用饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥。过滤,旋蒸除去溶剂得粗品,经柱层析分离提纯(石油醚/乙酸乙酯=20∶1),得到γ-壬烯内酯650mg,产率为83%。1H NMR(300MHz,CDCl3)δ7.44(dd,J=5.7,1.5Hz,1H),6.09(dd,J=5.7,2.1Hz,1H),5.03(ddt,J=7.2,5.4,1.8Hz,1H),1.77-1.64(m,2H),1.47-1.40(m,2H),1.35-1.28(m,4H),0.91-0.86(m,3H)。13C NMR(75MHz,CDCl3)δ173.28,156.42,121.64,83.57,33.28,31.58,24.76,22.53,14.04。
(3)γ-戊烯内酯的制备(通过二苯亚砜/草酰溴组合试剂)
氮气保护,在装有温度计的100mL三口烧瓶中,加入草酰溴(7.5mmol,1.1mL,1.5eq)和无水二氯甲烷(10mL)。液氮-乙醇浴-78℃下,用恒压滴液漏斗缓慢滴加二苯亚砜(7.5mmol,1.52g,1.5eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,再滴加(E)-3-戊烯酸(5mmol,500mg,1.0eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,加入碳酸钾(25mmol,3.45g,5.0eq)和18-冠醚-6(0.25mmol,66mg,0.05eq),然后回室温反应5h。抽滤,滤液中加入30mL蒸馏水,分液,取有机相,用饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥。过滤,旋蒸除去溶剂得粗品,经柱层析分离提纯(石油醚/乙酸乙酯=10∶1),得到γ-戊烯内酯400mg,产率为82%。核磁共振数据同(1)γ-戊烯内酯。
(4)γ-壬烯内酯的制备(通过二苯亚砜/草酰溴组合试剂)
氮气保护,在装有温度计的100mL三口烧瓶中,加入草酰溴(7.5mmol,1.1mL,1.5eq)和无水二氯甲烷(10mL)。液氮-乙醇浴-78℃下,用恒压滴液漏斗缓慢滴加二苯亚砜(7.5mmol,1.52g,1.5eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,再滴加(E)-3-壬烯酸(5mmol,780mg,1.0eq)的无水二氯甲烷(10mL)溶液。滴加完毕后,-78℃下继续搅拌10min,加入碳酸钾(25mmol,3.45g,5.0eq)和18-冠醚-6(0.25mmol,66mg,0.05eq),然后回室温反应5h。抽滤,滤液中加入30mL蒸馏水,分液,取有机相,用饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥。过滤,旋蒸除去溶剂得粗品,经柱层析分离提纯(石油醚/乙酸乙酯=20∶1),得到γ-壬烯内酯625mg,产率为80%。核磁共振数据同(2)γ-壬烯内酯。

Claims (1)

1.一种α,β-不饱和γ-内酯的制备方法,其特征是以(E)-3-链烯酸为起始原料,以二氯甲烷为溶剂,在-78℃下采用二苯亚砜/草酰氯组合试剂或二苯亚砜/草酰溴组合试剂,加入碳酸钾和18-冠醚-6,加料完毕后在室温条件下反应,可以一步得到α,β-不饱和γ-内酯,反应式如下:
Figure FSB0000185007430000011
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