CN112574079A - 2,2-二氟-n-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物及合成方法 - Google Patents
2,2-二氟-n-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物及合成方法 Download PDFInfo
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title claims abstract description 30
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- 238000000034 method Methods 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- RMVRSNDYEFQCLF-UHFFFAOYSA-N phenyl mercaptan Natural products SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 19
- -1 thiophenol compound Chemical class 0.000 claims abstract description 18
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- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 6
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- 230000002194 synthesizing effect Effects 0.000 claims description 6
- VEZUQRBDRNJBJY-UHFFFAOYSA-N cyclohexanone oxime Chemical class ON=C1CCCCC1 VEZUQRBDRNJBJY-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
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- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 claims description 3
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 claims description 3
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 3
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- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 3
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims description 3
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- QGRKONUHHGBHRB-UHFFFAOYSA-N 2,3-dichlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1Cl QGRKONUHHGBHRB-UHFFFAOYSA-N 0.000 claims description 2
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- SKDFIEXQBHUNIU-UHFFFAOYSA-N n-(4-propan-2-ylcyclohexylidene)hydroxylamine Chemical compound CC(C)C1CCC(=NO)CC1 SKDFIEXQBHUNIU-UHFFFAOYSA-N 0.000 claims description 2
- ABRSWKYXHXBBKX-UHFFFAOYSA-N n-(4-propylcyclohexylidene)hydroxylamine Chemical compound CCCC1CCC(=NO)CC1 ABRSWKYXHXBBKX-UHFFFAOYSA-N 0.000 claims description 2
- XIOIFAFSEIOPFO-UHFFFAOYSA-N n-(4-tert-butylcyclohexylidene)hydroxylamine Chemical compound CC(C)(C)C1CCC(=NO)CC1 XIOIFAFSEIOPFO-UHFFFAOYSA-N 0.000 claims description 2
- OENGSNXUALAIFP-UHFFFAOYSA-N n-cycloheptylidenehydroxylamine Chemical compound ON=C1CCCCCC1 OENGSNXUALAIFP-UHFFFAOYSA-N 0.000 claims description 2
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- 229910000358 iron sulfate Inorganic materials 0.000 claims 1
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- JTLAHVRPWDIEMU-UHFFFAOYSA-N n-(4-phenylcyclohexylidene)hydroxylamine Chemical compound C1CC(=NO)CCC1C1=CC=CC=C1 JTLAHVRPWDIEMU-UHFFFAOYSA-N 0.000 claims 1
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- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 11
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- 229910052739 hydrogen Inorganic materials 0.000 description 11
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
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- 229910052799 carbon Inorganic materials 0.000 description 9
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 2
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- YKAYMASDSHFOGI-UHFFFAOYSA-N 4-phenylcyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CC=CC=C1 YKAYMASDSHFOGI-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 125000000101 thioether group Chemical group 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
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Abstract
本发明涉及2,2‑二氟‑N‑(2‑硫醚基环己‑1‑烯‑1‑基)乙酰胺及其衍生物及合成方法,在铁催化剂和添加剂的共同作用下,环状酮肟衍生物与二氟乙酸酐、硫酚类化合物发生双官能化重组生成新的C‑N和C‑S键,一锅多组分反应生成2,2‑二氟‑N‑(2‑硫醚基环己‑1‑烯‑1‑基)乙酰胺及其衍生物。本发明的产物具有分子结构稳定、化学性质优良,分子切块和化合物片段包含丰富的生物活性和药理活性:本发明的方法克服了现有2,2‑二氟‑N‑(2‑硫醚基环己‑1‑烯‑1‑基)乙酰胺类化合物的合成方法存在合成步骤复杂,需要采取多步合成工艺才能完成的缺点;具有反应体系简单、反应条件温和、反应设备较少、实验操作简便、用料来源广泛、用户和应用易于扩展、产品利用价值较高等优点。
Description
技术领域
本发明涉及2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物及合成方法,属于有机合成化学领域。
背景技术
酰胺类化合物在医药、农药及功能材料领域具有广泛的应用,2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物是一类特殊的酰胺类化合物,其结构中同时含有二氟甲基和硫醚基,事实证明,这两类功能基团是具有良好的生物活性和药理活性,在农药和医药等领域都有着极高潜在的应用价值。而关于该类物质的合成方法报道极少,大多需要采用过渡金属催化下的多步反应才能获得,这不利于该类物质的大规模生产,因此,开发高效、简便的合成该类物质的方法具有重要的发明意义。
发明内容
针对上述情况,本发明的目的是提供一类新的化合物即2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物,它分子结构稳定、化学性质优良,具有潜在的医用和药用价值。
本发明的又一目的是提供一种合成2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物的方法,该方法具有工艺简单、操作方便、原料廉价易得、反应步骤少、所需设备简单等优点。
为了实现上述目的一种2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物,它的通式为:
其中
n=1,2,3,4;R1选自氢原子,烷基,卤素,芳香基;
R2选自取代或非取代的苯基、噻吩基、萘基。
为了实现上述另一目的,一种合成2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物的方法,在催化剂和添加剂的共同作用下,将环状酮肟衍生物、硫酚类化合物、二氟乙酸酐在有机溶剂中经加热搅拌反应、纯化得到产物。
为了提高本发明的综合性能,实现结构、效果优化,其进一步措施是:
所述的催化剂为四氧化三铁、硫酸亚铁、氯化亚铁、铁粉、硫酸铁、三氟甲磺酸铁、三氧化二铁、氯化铁、乙酰丙酮铁、硝酸铁中的一种,优选四氧化三铁。
所述的添加剂为N-碘代丁二酰亚胺、N-溴代丁二酰亚胺、N-氯代丁二酰亚胺、单质碘、氯化碘、溴化碘中的一种,优选N-碘代丁二酰亚胺。
所述的有机溶剂为1,2-二氯乙烷、1,1,2,2-四氯乙烷、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、1,4-二氧六环、甲苯、氯苯、N-甲基吡咯烷酮、吡啶中的一种,优选1,2-二氯乙烷。
所述的环状酮肟衍生物、硫酚类化合物、二氟乙酸酐、催化剂、添加剂的摩尔比为1∶1~2∶3~5∶0.02~0.1∶0.5~1.5,优选1∶1.5∶4∶0.05∶1。
所述的反应温度为40~100℃,优选60℃。
所述反应时间为6~24h,优选12h。
其中,n=1,2,3,4;R1选自氢原子,烷基,卤素,芳香基;进一步选自:环己酮肟,4-甲基环己酮肟,4-乙基环己酮肟,4-正丙基环己酮肟,4-异丙基环己酮肟,4-正丁基环己酮肟,4-叔丁基环己酮肟,4-正戊基环己酮肟,4-苯基环己酮肟,3-甲基环己酮肟,2-甲基环己酮肟,2-氯环己酮肟,环戊酮肟,环庚酮肟,环辛酮肟。
所述的硫酚类化合物的通式为R2-SH。
其中,R2选自取代或非取代的苯基、噻吩基、萘基;进一步选自:4-甲基苯硫酚,4-甲氧基苯硫酚,4-叔丁基苯硫酚,4-氟苯硫酚,4-氯苯硫酚,4-溴苯硫酚,3-甲基苯硫酚,3-甲氧基苯硫酚,2-甲基苯硫酚,2-甲氧基苯硫酚,2-乙基苯硫酚,2-氟苯硫酚,2-氯苯硫酚,2-溴苯硫酚,2-萘硫酚,2-噻吩硫酚,2,3-二氯苯硫酚。
本发明技术方案,具有如下优点:
本发明主要涉及一种2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物及合成方法,在廉价易得的铁催化剂和添加剂的共同作用下,环状酮肟衍生物与二氟乙酸酐、硫酚类化合物发生双官能化重组生成新的C-N和C-S键,一锅多组分反应生成2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物。本发明的产物具有分子结构稳定、化学性质优良,分子切块和化合物片段包含丰富的生物活性和药理活性;本发明的方法克服了现有2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺类化合物的合成方法存在合成步骤复杂,需要采取多步合成工艺才能完成的缺点;具有反应体系简单、反应条件温和、反应设备较少、实验操作简便、用料来源广泛、用户和应用易于扩展、产品利用价值较高等优点。
附图说明
为了证明本发明的产物,本发明提供部分实施例的核磁氢谱图、核磁碳谱图和核磁氟谱图。
图1a实施例1产物的核磁氢谱图。图1b实施例1产物的核磁碳谱图。图1c实施例1产物的核磁氟谱图。
图2a实施例18产物的核磁氢谱图。图2b实施例18产物的核磁碳谱图。图2c实施例18产物的核磁氟谱图。
图3a实施例23产物的核磁氢谱图。图3b实施例23产物的核磁碳谱图。图3c实施例23产物的核磁氟谱图。
图4a实施例24产物的核磁氢谱图。图4b实施例24产物的核磁碳谱图。图4c实施例24产物的核磁氟谱图。
图5a实施例26产物的核磁氢谱图。图5b实施例26产物的核磁碳谱图。图5c实施例26产物的核磁氟谱图。
图6a实施例27产物的核磁氢谱图。图6b实施例27产物的核磁碳谱图。图6c实施例27产物的核磁氟谱图。
图7a实施例28产物的核磁氢谱图。图7b实施例28产物的核磁碳谱图。图7c实施例28产物的核磁氟谱图。
图8a实施例31产物的核磁氢谱图。图8b实施例31产物的核磁碳谱图。图8c实施例31产物的核磁氟谱图。
图9a实施例33产物的核磁氢谱图。图9b实施例33产物的核磁碳谱图。图9c实施例33产物的核磁氟谱图。
图10a实施例38产物的核磁氢谱图。图10b实施例38产物的核磁碳谱图。图10c实施例38产物的核磁氟谱图。
图11为本发明的2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物合成方法的反应体系通式。
具体实施方式
下面将结合附图对本发明的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
下面所描述的本发明不同实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互结合。
2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺及其衍生物合成方法的反应体系通式,如下:
包括以下步骤:
(1)往反应容器中加入环状酮肟衍生物、硫酚类化合物、二氟乙酸酐、催化剂、添加剂、有机溶剂;
(2)将反应物充分混合后,进行加热;
(3)反应后进行纯化得到产物;
其中,所述的催化剂为四氧化三铁、硫酸亚铁、氯化亚铁、铁粉、硫酸铁、三氟甲磺酸铁、三氧化二铁、氯化铁、乙酰丙酮铁、硝酸铁中的一种,优选四氧化三铁;所述的添加剂为N-碘代丁二酰亚胺、N-溴代丁二酰亚胺、N-氯代丁二酰亚胺、单质碘、氯化碘、溴化碘中的一种,优选N-碘代丁二酰亚胺;所述的有机溶剂为1,2-二氯乙烷、1,1,2,2-四氯乙烷、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、1,4-二氧六环、甲苯、氯苯、N-甲基吡咯烷酮、吡啶中的一种,优选1,2-二氯乙烷;所述的环状酮肟衍生物、硫酚类化合物、二氟乙酸酐、催化剂、添加剂的摩尔比为1∶1~2∶3~5∶0.02~0.1∶0.5~1.5,优选1∶1.5∶4∶0.05∶1;所述的反应温度为40~100℃,优选60℃;所述反应时间为6~24h,优选12h。
上述式I化合物2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺衍生物是一类重要的分子切块,它分子结构稳定、化学性质优良,含有很强的生理活性和药理活性;总之,本发明化合物具有反应原料廉价易得且不需要进行预处理,反应为一锅直接合成等特点;它解决了现有采用多步合成方法带来的成本较高等难题;它反应条件温和,反应所需温度大大低于以往多步合成的反应温度;合成的一系列2,2-二氟-N-(2-硫醚基环己-1-烯-1-基)乙酰胺类化合物具有相当高的潜在应用价值。
表1实施例1-40的反应物、催化剂、添加剂、摩尔比、有机溶剂、反应温度、反应时间
*为环状酮肟衍生物、硫酚类化合物、二氟乙酸酐、催化剂及添加剂的摩尔比
表2实施例1-40反应的产率及产物结构式
部分实施例的产物的核磁数据如下:
实施例1产物的核磁数据:
1H NMR(400MHz,CDCl3,ppm)δ8.91(s,1H),7.17-7.08(m,4H),5.85(t,J=54.5Hz,1H),2.88(t,J=5.9Hz,2H),2.32(s,3H),2.24(t,J=5.8Hz,2H),1.74(dt,J=11.6,5.9Hz,2H),1.64(dd,J=11.0,5.6Hz,2H).13C NMR(100MHz,CDCl3,ppm)δ160.19,159.95,159.71,138.49,136.93,130.04,129.89,129.50,115.76,111.09,108.56,106.03,30.60,27.97,23.08,22.32,21.03.19F NMR(376MHz,CDCl3,ppm)δ-125.37.
实施例18产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ9.02(s,1H),7.29(q,J=8.2,7.8Hz,2H),7.25-7.10(m,7H),5.91(t,J=54.4Hz,1H),3.23-3.13(m,1H),3.06-2.84(m,2H),2.58-2.39(m,2H),2.34(s,3H),2.16-2.08(m,1H),1.97-1.82(m,1H).13C NMR(100MHz,CDCl3,ppm)δ160.32,160.08,159.84,144.98,138.10,137.25,130.17,129.85,129.49,128.57,126.79,126.54,115.28,111.11,108.59,106.06,40.50,38.27,29.28,28.35,21.10.19F NMR(376MHz,CDCl3,ppm)δ-125.30.
实施例23产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.46(s,1H),7.13(q,J=8.2Hz,4H),5.85(t,J=54.4Hz,1H),2.89-2.82(m,2H),2.43-2.38(m,2H),2.32(s,3H),1.78-1.73(m,2H),1.72-1.67(m,2H),1.50(p,J=5.7Hz,2H).13C NMR(100MHz,CDCl3,ppm)δ160.35(t,J=24.2Hz),141.75,137.07,130.10,129.96,129.93,123.74,108.58(t,J=254.0Hz).34.63,31.63,30.57,26.43,25.19,21.05.19F NMR(376MHz,CDCl3,ppm)δ-125.54.
实施例24产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.93(s,1H),7.16(d,J=8.1Hz,2H),7.11(d,J=8.2Hz,2H),5.87(t,J=54.5Hz,1H),2.98-2.91(m,2H),2.39-2.34(m,2H),2.32(s,3H),1.79(s,2H),1.56(s,2H),1.53-1.45(m,4H).13C NMR(100MHz,CDCl3,ppm)δ159.76,159.52,159.28,139.58,137.05,130.28,129.97,129.97,119.02,111.19,108.66,106.13,31.45,29.29,29.13,27.26,26.55,26.02,21.04.19F NMR(376MHz,CDCl3,ppm)δ-125.31.
实施例26产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.93(s,1H),7.32(d,J=8.4Hz,2H),7.16(d,J=8.4Hz,2H),5.84(t,J=54.5Hz,1H),2.89(t,J=5.8Hz,2H),2.27(t,J=5.9Hz,2H),1.75(dt,J=11.7,6.0Hz,2H),1.69-1.63(m,2H),1.30(s,9H).13C NMR(100MHz,CDCl3,ppm)δ160.19,159.95,159.71,150.06,138.85,130.05,128.86,126.33,115.39,111.07,108.55,106.02,34.53,31.26,30.71,27.98,23.10,22.33.19F NMR(376MHz,CDCl3,ppm)δ-125.40.
实施例27产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.86(s,1H),7.26-7.18(m,2H),7.01(t,J=8.6Hz,2H),5.87(t,J=54.5Hz,1H),2.87(d,J=11.8Hz,2H),2.22(t,J=5.9Hz,2H),1.78-1.70(m,2H),1.68-1.62(m,2H).13C NMR(100MHz,CDCl3,ppm)δ163.27,160.81,160.20,159.96,159.72,138.72,131.44,131.36,128.53,128.50,116.55,116.33,115.68,111.08,108.55,106.02,30.53,28.03,23.04,22.26.19F NMR(376MHz,CDCl3,ppm)δ-114.77,-125.34.
实施例28产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.84(s,1H),7.27(d,J=6.9Hz,2H),7.14(d,J=8.5Hz,2H),5.85(t,J=54.4Hz,1H),2.89(t,J=6.2Hz,2H),2.25(t,J=6.2Hz,2H),1.79-1.72(m,2H),1.70-1.63(m,2H).13C NMR(100MHz,CDCl3,ppm)δ160.21,159.97,159.73,139.89,132.70,132.25,129.98,129.44,114.50,111.03,108.50,105.97,30.71,28.07,23.07,22.25.19F NMR(376MHz,CDCl3,ppm)δ-125.36.
实施例31产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.88(s,1H),7.22(d,J=8.6Hz,2H),6.85(d,J=8.6Hz,2H),5.88(t,J=54.5Hz,1H),3.79(s,3H),2.82(d,J=6.3Hz,2H),2.19(t,J=6.1Hz,2H),1.74-1.68(m,2H),1.66-1.59(m,2H).13C NMR(101MHz,CDCl3,ppm)δ160.17,159.93,159.69,159.31,136.89,132.37,123.61,117.26,114.89,111.15,108.62,106.10,55.39,30.31,27.94,23.03,22.32.19F NMR(376MHz,CDCl3,ppm)δ-125.31.
实施例33产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ9.18(s,1H),7.30-7.19(m,2H),6.96-6.86(m,2H),5.87(t,J=54.5Hz,1H),3.88(s,3H),2.85(t,J=6.0Hz,2H),2.25(t,J=5.9Hz,2H),1.77-1.68(m,2H),1.68-1.60(m,3H).13C NMR(100MHz,CDCl3,ppm)δ160.30,160.07,159.83,158.02,139.37,131.61,128.80,121.28,121.22,114.99,111.20,111.02,108.67,106.14,55.81,30.70,27.92,23.10,22.29.19F NMR(376MHz,CDCl3,ppm)δ-125.29.
实施例38产物的核磁数据如下:
1H NMR(400MHz,CDCl3,ppm)δ8.96(s,1H),7.78(q,J=9.8,9.1Hz,3H)97.68(s,1H),7.54-7.42(m,2H),7.30(q,J=8.5,1.5Hz,1H),5.85(t,J=54.4Hz,1H),2.95(t,J=6.0Hz,2H),2.31(t,J=5.9Hz,2H),1.84-1.74(m,2H),1.74-1.64(m,2H).13C NMR(100MHz,CDCl3,ppm)δ160.24,160.00,159.76,139.47,133.77,132.11,131.01,129.00,127.80,127.46,127.21,126.82,126.64,126.11,114.98,111.07,108.54,106.01,30.84,28.08,23.11,22.34.19F NMR(376MHz,CDCl3,ppm)δ-125.38.
以上述依据本发明的理想实施例为启示,通过上述的说明内容,相关工作人员完全可以在不偏离本项发明技术思想的范围内,进行多样的变更以及修改。本项发明的技术性范围并不局限于说明书上的内容,必须要根据权利要求范围来确定其技术性范围。
Claims (10)
3.根据权利要求1所述的方法,其特征在于,所述硫酚类化合物的通式为III:
R2-SH
III。
其中,R2选自取代或非取代的苯基、噻吩基、萘基;进一步选自:4-甲基苯硫酚,4-甲氧基苯硫酚,4-叔丁基苯硫酚,4-氟苯硫酚,4-氯苯硫酚,4-溴苯硫酚,3-甲基苯硫酚,3-甲氧基苯硫酚,2-甲基苯硫酚,2-甲氧基苯硫酚,2-乙基苯硫酚,2-氟苯硫酚,2-氯苯硫酚,2-溴苯硫酚,2-萘硫酚,2-噻吩硫酚,2,3-二氯苯硫酚。
5.根据权利要求1所述的方法,其特征在于,所述催化剂为四氧化三铁、硫酸亚铁、氯化亚铁、铁粉、硫酸铁、三氟甲磺酸铁、三氧化二铁、氯化铁、乙酰丙酮铁、硝酸铁中的一种,优选四氧化三铁。
6.根据权利要求1所述的方法,其特征在于,所述添加剂为N-碘代丁二酰亚胺、N-溴代丁二酰亚胺、N-氯代丁二酰亚胺、单质碘、氯化碘、溴化碘中的一种,优选N-碘代丁二酰亚胺。
7.根据权利要求1所述的方法,其特征在于,所述有机溶剂为1,2-二氯乙烷、1,1,2,2-四氯乙烷、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、1,4-二氧六环、甲苯、氯苯、N-甲基吡咯烷酮、吡啶中的一种,优选1,2-二氯乙烷。
8.根据权利要求1所述的方法,其特征在于,所述环状酮肟衍生物、硫酚类化合物、二氟乙酸酐、催化剂、添加剂的摩尔比为1∶1~2∶3~5∶0.02~0.1∶0.5~1.5,优选1∶1.5∶4∶0.05∶1。
9.根据权利要求1所述的方法,其特征在于,所述反应温度为40~100℃,优选60℃。
10.根据权利要求1所述的方法,其特征在于,所述反应时间为6~24h,优选12h。
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