CN114989013B - 一种反-2-顺-4-癸二烯酸乙酯的合成方法 - Google Patents
一种反-2-顺-4-癸二烯酸乙酯的合成方法 Download PDFInfo
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/515—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an acetalised, ketalised hemi-acetalised, or hemi-ketalised hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Abstract
本发明公开了一种反‑2‑顺‑4‑癸二烯酸乙酯的合成方法,涉及有机合成技术领域,本发明以3,3‑二甲氧基‑1‑丙炔和卤代戊烷为原料,依次经取代反应、水解反应、氢化反应制得反‑2‑顺‑4‑癸二烯酸乙酯;本发明所提供的合成方法能够替换现有专利技术中采用有机铜锂催化剂进行金属催化制备反‑2‑顺‑4‑癸二烯酸乙酯的方法,避免了无水无氧的严苛反应条件,提高了反应效率,便于工业化生产。
Description
技术领域:
本发明涉及有机合成技术领域,具体涉及一种反-2-顺-4-癸二烯酸乙酯的合成方法。
背景技术:
反-2-顺-4-癸二烯酸乙酯是一种可食用香料成分,为国际食品香料工业组织(IOFI)、美国食品香料与萃取着协会(FEMA)、欧盟食用香料委员会(FLAVIS)所认可的一种食品添加剂,GB2760-1996规定为暂时允许使用的食品用香料。反-2-顺-4-癸二烯酸乙酯的结构式如下:
反-2-顺-4-癸二烯酸乙酯为淡黄色或无色油状液体,密度0.905g/mL at 25℃(lit.),沸点70-72℃ at 0.05mm Hg(lit.),折射率:n20/D 1.486(lit.),闪点>230°F,熔点-60℃,可溶解于乙醇,甲苯,植物油等有机溶剂中,也可溶于水,有蜡、梨、青草、苹果和水果似尖锐香气,天然品存在于苹果、巴梨以及康科德葡萄中。
反-2-顺-4-癸二烯酸乙酯通常作为香料,食品添加剂用于饮料和奶制品调味,其使用限量FEMA(mg/kg):软饮料、冷饮、糖果、胶冻、布丁均为10.0;其还可与变性淀粉组合制备香料颗粒,用于洗衣和清洁。
目前,关于反-2-顺-4-癸二烯酸乙酯的合成方法主要有:
Takeda等人报道了一种使用联烯来制备反-2-顺-4-癸二烯酸乙酯的方法(Organic Synthesis,1993,8,251),首先通过正己醇与乙炔反应得到炔醇,随后在丙酸条件下与原乙酸三乙酯发生Claisen重排反应得到联烯结构的中间体,该中间体在氧化铝条件下发生异构化产物得到反-2-顺-4-癸二烯酸乙酯。该反应路线的整体收率为70%,但反应温度较高,第一步温度在150℃左右,第二步异构化反应需要200℃,并且反应中需不断采出生成的乙醇并补加原甲酸三乙酯,反应连续性差,能耗较大。
Normant等人采用1-溴庚烯为起始原料,将其制成金属铜盐后,与丙炔酸酯反应制备反-2-顺-4-癸二烯酸乙酯(Tetrahedron,1980,36,1961),该反应路线的整体收率为65%,但有机铜试剂的制备较为复杂,需要在无水无氧条件下反应,并且该方法制得产物纯度为92%左右,含有异构体,需要多次分离纯化。
发明内容:
本发明所要解决的技术问题在于提供一种反-2-顺-4-癸二烯酸乙酯的合成方法,不仅提高了中间体和产物收率,还减少了反应废弃物的排放,降低了成本,简化了操作,从而适用于工业化生产。
本发明所要解决的技术问题采用以下的技术方案来实现:
一种反-2-顺-4-癸二烯酸乙酯的合成方法,以3,3-二甲氧基-1-丙炔为原料,在碱性物质A存在下与卤代戊烷经取代反应制得1,1-二甲氧基-2-辛炔,1,1-二甲氧基-2-辛炔在稀酸条件下经水解反应制得2-辛醛,2-辛醛在碱性物质B存在下与膦酰基乙酸三乙酯经Wittig反应制得4-炔基反-2-癸烯酸乙酯,4-炔基反-2-癸烯酸乙酯在催化剂存在下经氢化反应制得反-2-顺-4-癸二烯酸乙酯。
本发明的有益效果是:本发明所提供的合成方法能够替换现有专利技术中采用有机铜锂催化剂进行金属催化制备反-2-顺-4-癸二烯酸乙酯的方法,避免了无水无氧的严苛反应条件,提高了反应效率,便于工业化生产。
附图说明:
图1为本发明合成的产品反-2-顺-4-癸二烯酸乙酯的核磁氢谱;
图2为本发明合成的产品反-2-顺-4-癸二烯酸乙酯的核磁碳谱。
具体实施方式:
为了使本发明实现的技术手段、创作特征、达成目的与功效易于明白了解,下面结合具体实施例和图示,进一步阐述本发明。
本发明提供了一种反-2-顺-4-癸二烯酸乙酯的合成方法,以3,3-二甲氧基-1-丙炔为原料,在碱性物质A存在下与卤代戊烷经取代反应制得1,1-二甲氧基-2-辛炔,1,1-二甲氧基-2-辛炔在稀酸条件下经水解反应制得2-辛醛,2-辛醛在碱性物质B存在下与膦酰基乙酸三乙酯经Wittig反应制得4-炔基反-2-癸烯酸乙酯,4-炔基反-2-癸烯酸乙酯在催化剂存在下经氢化反应制得反-2-顺-4-癸二烯酸乙酯。
优选地,所述取代反应中3,3-二甲氧基-1-丙炔与卤代戊烷的摩尔比为1:(0.1~2)。
优选地,所述取代反应中的卤代戊烷选自氯戊烷、溴戊烷、碘戊烷中的至少一种。
优选地,所述取代反应中的碱性物质A选自氢化钠、氢化钾、氢氧化钠、氨基钠中的至少一种,用量为3,3-二甲氧基-1-丙炔摩尔用量的0.1~2倍。
优选地,所述取代反应的溶剂选自甲醇、乙醇、液氨、四氢呋喃、异丙醇中的至少一种。
优选地,所述水解反应中的稀酸选自稀盐酸、稀硫酸、稀醋酸、稀硝酸中的至少一种。
优选地,所述水解反应的溶剂选自甲苯、四氢呋喃、环己烷、乙酸乙酯中的至少一种。
优选地,所述Wittig反应中2-辛醛与膦酰基乙酸三乙酯的摩尔比为1:(0.5~2)。
优选地,所述Wittig反应中的碱性物质B选自丁基锂、苯基锂、氢化钠、氢氧化钠、氨基钠、乙醇钠中的至少一种,用量为2-辛醛摩尔用量的0.1~2倍。
优选地,所述Wittig反应的溶剂选自四氢呋喃、N,N-二甲基甲酰胺、二甲基亚砜、乙醚中的至少一种。
优选地,所述氢化反应的溶剂选自二甲醚、四氢呋喃、乙酸乙酯、环己烷中的至少一种。
优选地,所述氢化反应的压力为0.5~5MPa。
优选地,所述氢化反应中的催化剂为Lindlar催化剂,用量为4-炔基反-2-癸烯酸乙酯摩尔用量的0.05~0.5倍。
Lindlar催化剂是由钯吸附在载体(碳酸钙或硫酸钡)上并加入少量抑制剂(醋酸铅或喹啉)制备而成,钯含量为5-10%。在催化氢化反应中使用Lindlar催化剂对炔键进行顺式加成,生成顺式烯烃。以下实施例中使用的Lindlar催化剂购自陕西瑞科新材料股份有限公司,钯含量为5%。
本发明采用碱作为Wittig反应催化剂,但该步反应所制4-炔基反-2-癸烯酸乙酯的收率较低,为此本发明加入了适量的氟硼酸钠作为助催化剂,提高反应活性,将该步反应的收率提升20%以上。
实施例1
将3,3-二甲氧基-1-丙炔(1mol,100.0g),氨基钠(1.1mol,42.9g)以及300mL甲醇加入反应釜中,冷却至-30℃反应,在搅拌条件下向反应釜中滴加溴戊烷(1.2mol,181.2g),2h滴加完毕,随后继续保温应2h,负压回收甲醇230g,有机相经萃取,闪蒸得到1,1-二甲氧基-2-辛炔,收率85.8%。
实施例2
将1,1-二甲氧基辛二炔(0.5mol,85.0g)溶解于300mL乙酸乙酯中,冷却至0℃,搅拌条件下向反应釜中加入10%稀盐酸(90.0g)维持釜温在5℃以下,常压反应4h,水解完全,分液,负压回收乙酸乙酯280mL,闪蒸得到2-辛醛,收率92.0%。
实施例3
无水条件下将乙醇钠(0.33mol,22.4g)与THF(500g)加入反应釜中冷却至0℃,搅拌条件下向反应釜中缓慢滴加膦酰基乙酸三乙酯(0.32mol,71.7g)约2h滴加完毕,保温搅拌30min,随后将2-辛醛(0.3mol,37.2g)缓慢加入反应液中约1h加毕,加完后升温至75℃回流反应20h,GC监测反应完全,冷却至室温加入100mL水搅拌30min,分液,水相加入50g×2乙酸乙酯萃取两次,合并有机相,负压回收溶剂,闪蒸分离得到4-炔基反-2-癸烯酸乙酯,收率52.9%。
实施例4
将4-炔基反-2-癸烯酸乙酯(0.15mol,29.1g)与Lindlar催化剂(1.5g)加入加氢反应釜中,并向釜中加入50mL环己烷作为溶剂,对体系进行氮气置换保护,随后氢气置换三次,之后在30℃,1.0MPa氢气压力条件下,加氢反应12h,反应结束后对体系进行过滤,除去不溶物,收集滤液,回收溶剂后进行柱层析分离,得到反-2-顺-4-癸二烯酸乙酯,收率76.5%。1H NMR(400MHz,CDCl3):δ0.90(t,J=7.0Hz,3H),11.2-1.6(m,9H),2.35(m,2H),4.20(q,J=7.0Hz,2H),5.62(d,J=18.0Hz,1H),6.10(d,J=18.0Hz,1H),6.72(d,J=18.0Hz,1H),7.27(t,J=7.0Hz,1H).13C NMR(100MHz,CDCl3):δ166.7,145.9,145.5,127.0,115.6,59.9,33.1,31.6,28.6,22.6,14.4,14.1.HRMS(ESI)m/z calculated for C12H19O2[M+H]+195.2724,found 195.2721.
实施例5
无水条件下将乙醇钠(0.33mol,22.4g)、氟硼酸钠(0.05mol,5.5g)、与THF(500g)加入反应釜中冷却至0℃,搅拌条件下向反应釜中缓慢滴加膦酰基乙酸三乙酯(0.32mol,71.7g)约2h滴加完毕,保温搅拌30min,随后将2-辛醛(0.3mol,37.2g)缓慢加入反应液中约1h加毕,加完后升温至75℃回流反应20h,GC监测反应完全,冷却至室温加入100mL水搅拌30min,分液,水相加入50g×2乙酸乙酯萃取两次,合并有机相,负压回收溶剂,闪蒸分离得到4-炔基反-2-癸烯酸乙酯,收率76.8%。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (10)
1.一种反-2-顺-4-癸二烯酸乙酯的合成方法,其特征在于:以3,3-二甲氧基-1-丙炔为原料,在碱性物质A存在下与卤代戊烷经取代反应制得1,1-二甲氧基-2-辛炔,1,1-二甲氧基-2-辛炔在稀酸条件下经水解反应制得2-辛醛,2-辛醛在碱性物质B存在下与膦酰基乙酸三乙酯经Wittig反应制得4-炔基反-2-癸烯酸乙酯,4-炔基反-2-癸烯酸乙酯在催化剂存在下经氢化反应制得反-2-顺-4-癸二烯酸乙酯。
2.根据权利要求1所述的合成方法,其特征在于:所述取代反应中3,3-二甲氧基-1-丙炔与卤代戊烷的摩尔比为1:(0.1~2)。
3.根据权利要求1所述的合成方法,其特征在于:所述取代反应中的卤代戊烷选自氯戊烷、溴戊烷、碘戊烷中的至少一种;
所述取代反应的溶剂选自甲醇、乙醇、液氨、四氢呋喃、异丙醇中的至少一种。
4.根据权利要求1所述的合成方法,其特征在于:所述取代反应中的碱性物质A选自氢化钠、氢化钾、氢氧化钠、氨基钠中的至少一种,用量为3,3-二甲氧基-1-丙炔摩尔用量的0.1~2倍。
5.根据权利要求1所述的合成方法,其特征在于:所述水解反应中的稀酸选自稀盐酸、稀硫酸、稀醋酸、稀硝酸中的至少一种;
所述水解反应的溶剂选自甲苯、四氢呋喃、环己烷、乙酸乙酯中的至少一种。
6.根据权利要求1所述的合成方法,其特征在于:所述Wittig反应中2-辛醛与膦酰基乙酸三乙酯的摩尔比为1:(0.5~2)。
7.根据权利要求1所述的合成方法,其特征在于:所述Wittig反应中的碱性物质B选自丁基锂、苯基锂、氢化钠、氢氧化钠、氨基钠、乙醇钠中的至少一种,用量为2-辛醛摩尔用量的0.1~2倍。
8.根据权利要求1所述的合成方法,其特征在于:所述Wittig反应的溶剂选自四氢呋喃、N,N-二甲基甲酰胺、二甲基亚砜、乙醚中的至少一种。
9.根据权利要求1所述的合成方法,其特征在于:所述氢化反应中的催化剂为Lindlar催化剂,用量为4-炔基反-2-癸烯酸乙酯摩尔用量的0.05~0.5倍。
10.根据权利要求1所述的合成方法,其特征在于:所述氢化反应的溶剂选自二甲醚、四氢呋喃、乙酸乙酯、环己烷中的至少一种;
所述氢化反应的压力为0.5~5MPa。
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