CN116903471A - 一种单氟/二氟氧代烯丙基酯类化合物及其制备方法 - Google Patents
一种单氟/二氟氧代烯丙基酯类化合物及其制备方法 Download PDFInfo
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- -1 difluoro oxo allyl ester compound Chemical class 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 239000000126 substance Substances 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 25
- 229940125782 compound 2 Drugs 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- 229940126214 compound 3 Drugs 0.000 claims abstract description 12
- 229940125904 compound 1 Drugs 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- 230000001590 oxidative effect Effects 0.000 claims abstract description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 238000000605 extraction Methods 0.000 claims description 14
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- KQTXIZHBFFWWFW-UHFFFAOYSA-L disilver;carbonate Chemical compound [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 229910021608 Silver(I) fluoride Inorganic materials 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- UVBXZOISXNZBLY-UHFFFAOYSA-L palladium(2+);triphenylphosphane;diacetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UVBXZOISXNZBLY-UHFFFAOYSA-L 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 claims description 2
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 2
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000011734 sodium Substances 0.000 description 27
- 239000003814 drug Substances 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000006462 rearrangement reaction Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- GVKYFODEMNCLGS-ONEGZZNKSA-N (E)-4-oxohex-2-enal Chemical class CCC(=O)\C=C\C=O GVKYFODEMNCLGS-ONEGZZNKSA-N 0.000 description 1
- VOOIEVFVJUZYJR-NSCUHMNNSA-N (E)-5,5-difluoro-4-oxohex-2-enal Chemical class FC(C(/C=C/C=O)=O)(C)F VOOIEVFVJUZYJR-NSCUHMNNSA-N 0.000 description 1
- FHCSDLAVXOWFGV-UHFFFAOYSA-N 2,2-difluoro-2-iodo-1-(4-methoxyphenyl)ethanone Chemical compound FC(C(=O)C1=CC=C(C=C1)OC)(I)F FHCSDLAVXOWFGV-UHFFFAOYSA-N 0.000 description 1
- LBZPHZBNFDOCCR-UHFFFAOYSA-N 2-(4-bromo-2-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Br)C=C1[N+]([O-])=O LBZPHZBNFDOCCR-UHFFFAOYSA-N 0.000 description 1
- MYSAXQPTXWKDPQ-UHFFFAOYSA-N 2-nitro-4-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O MYSAXQPTXWKDPQ-UHFFFAOYSA-N 0.000 description 1
- HOWBVGXZCYNPOU-UHFFFAOYSA-N 29640-98-0 Chemical compound OC(=O)CC1=CC(F)=CC=C1[N+]([O-])=O HOWBVGXZCYNPOU-UHFFFAOYSA-N 0.000 description 1
- HGGRAOYTQNFGGN-UHFFFAOYSA-N 4,5-difluoro-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1[N+]([O-])=O HGGRAOYTQNFGGN-UHFFFAOYSA-N 0.000 description 1
- QRRSIFNWHCKMSW-UHFFFAOYSA-N 5-methyl-2-nitrobenzoic acid Chemical compound CC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 QRRSIFNWHCKMSW-UHFFFAOYSA-N 0.000 description 1
- 239000000877 Sex Attractant Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/58—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/59—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C205/60—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms in ortho-position to the carboxyl group, e.g. nitro-salicylic acids
Abstract
本发明涉及一种单氟/二氟氧代烯丙基酯类化合物及其制备方法,该化合物化学结构式为:其中,R1包括苯基或取代苯基,R2为取代苯基,Rf包括单氟或二氟;该方法包括以下步骤:分别加入化合物3、催化剂和氧化剂混合,然后取化合物1或2溶于溶剂后加入,搅拌反应,然后冷却至室温;得到的反应液经萃取、分离后得到化合物4,即单氟/二氟氧代烯丙基酯类化合物;化学方程式为:
Description
技术领域
本发明属于有机合成技术领域,涉及一种单氟/二氟氧代烯丙基酯类化合物及其制备方法。
背景技术
α-卤代-α′,β′-不饱和酮分子骨架,尤其是那些以氟修饰的分子骨架,作为合成生物活性靶标药物的关键中间体结构,已开始在专利文献中受到广泛关注。例如2019年宁君等人在专利CN112094181A公开了一种4-氧代-反-2-己烯醛类似物的合成方法,其中的一种5,5-二氟-4-氧代反-2-己烯醛类似物可以作为一种释放缓慢、持效期长且具较强的性引诱能力、绿色环保的新型杀虫剂。
通过文献调研可以发现,向有机化合物分子中引入氟原子或者含氟基团,可以使得有机化合物或药物的物理、化学及生理性质比其母体分子有显著的提升。在候选药物中选择性地引入氟或氟化基团已被认为是药物设计和筛选中的一种强有力的策略。Indiummediated barbier-type allylation:Synthesis of highly functionalizedhomoallylic difluorohydrins已成功合成了一系列可以作为底物的砌块。
发明内容
本发明的目的就是为了克服上述现有技术存在的至少一种缺陷而提供一种单氟/二氟氧代烯丙基酯类化合物及其制备方法,本发明以已合成的α-羟基碘代偕单氟/二氟甲基类化合物砌块为底物,在过渡金属和氧化剂的促进下,合成了一系列单氟/二氟氧代烯丙基酯类化合物,具有高效、高收率、条件温和、环境友好等优点。
本发明的目的可以通过以下技术方案来实现:
本发明的技术方案之一在于,提供一种单氟/二氟氧代烯丙基酯类化合物,该化合物化学结构式为:
其中,R1包括苯基或取代苯基,R2为取代苯基,Rf包括单氟或二氟。
进一步地,所述的R1为取代苯基,该取代苯基中的取代基选自苯基、氢、氟、氯、溴、甲氧基、甲基和三氟甲基中的一种或多种;
所述的R2为取代苯基,该取代苯基中的取代基选自硝基、氢、氟、氯、溴、甲氧基、亚甲基、甲基和三氟甲基中的一种或多种。
进一步地,所述的单氟氧代烯丙基酯类化合物包括(E)-5-氟-4-氧代-5-苯基-2-烯-1-基-4,5-二氟-2-硝基苯甲酸酯、(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(5-氟-2-硝基苯基)乙酸酯、(E)-5-氟-4-氧-5-苯基戊-2-烯-1-基-2-(4-溴-2-硝基苯基)乙酸酯或(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(2-硝基-4-(三氟甲基)苯基)乙酸酯。
进一步地,所述的二氟氧代烯丙基酯类化合物包括(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-甲氧基苯基)-4-氧代-2-烯-1-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(3-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(2-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基2-硝基苯甲酸酯、(E)-5-(3-氯苯基)-5,5-二氟-4-氧代-2-烯-1-基2-硝基苯甲酸酯、(E)-5,5-二氟-5-(萘-2-基)-4-氧-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-氟-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-3-氯-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-5-溴-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯基-4,5-二甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-(2-硝基苯基)乙酸酯、(E)-5,5-二氟-4-氧代-5-(邻甲苯基)戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5-(2-氯苯基)-5,5-二氟-4-氧杂戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-(4-三氟甲基苯基)戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-4-甲基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-甲基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-2-甲基-6-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-氯-2-硝基苯甲酸酯或(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基-4-(三氟甲基)苯甲酸酯。
本发明的技术方案之一在于,提供一种单氟/二氟氧代烯丙基酯类化合物的制备方法,该方法包括以下步骤:
(1)分别加入化合物3、催化剂和氧化剂混合,然后取化合物1或2溶于溶剂后加入,搅拌直至反应完全,然后冷却至室温;
(2)得到的反应液经萃取、分离后得到化合物4,即单氟/二氟氧代烯丙基酯类化合物;
化学方程式为:
进一步地,步骤(1)中催化剂选自醋酸钯(II)、双(三苯膦基)醋酸钯(II)、四(乙腈)四氟硼酸钯(II)、二乙酸-1,2-双(苯亚磺酰)乙基钯(II)、六氟乙酰丙酮钯(II)、(2,2'-联吡啶)二氯化钯(II)、双三苯基磷二氯化钯(II)、二氯化钯(II)和四(三苯基膦)钯(0)中的一种或多种;
氧化剂选自氧化银(I)、三氟甲磺酸银(I)、乙酸银(I)、三氟乙酸银(I)、氟化银(I)和碳酸银(I)中的一种或多种;
溶剂选自六氟异丙醇(HFIP)、叔丁醇(TBA)、异丙醇(IPA)、三氟乙醇(TFE)、乙醇(EtOH)、二甲基酮(DMK)、乙腈(ACN)、四氢呋喃(THF)、二甲基酰胺(DMF)和二甲基亚砜(DMSO)中的一种或多种。
进一步地,步骤(1)中化合物1或2、化合物3与氧化剂的摩尔比为(0.15-0.5):(0.35-0.7):(0.005-0.5),催化剂用量为化合物1或2的10-20mmol%。
进一步地,步骤(1)中反应温度为20-80℃,时间为8-12h。
进一步地,步骤(2)中萃取采用萃取液进行,所述的萃取液为乙酸乙酯,所述的萃取液与反应液的体积比为1:(1-1.5),所述的萃取次数为3-4次。
进一步地,步骤(2)中分离采用洗脱剂在层析柱中进行提纯,所述的洗脱剂为体积比为(1-200):1的石油醚与乙酸乙酯,所述的洗脱时间为1-2h。
与现有技术相比,本发明具有以下优点:
(1)本发明的制备方法通过自由基诱导的重排反应,具有原料易得、高效、高收率、条件温和、环境友好等优点,在医药及农药领域具有较大的应用潜力;
(2)本发明以已合成的α-羟基碘代偕单氟/二氟甲基类化合物砌块为原料,添加催化剂和氧化剂,大大缩短反应时间,反应条件温和,且收率较高;
(3)本发明制备的单氟/二氟氧代烯丙基酯类化合物具有α-氟-不饱和酮或α,α-二氟-不饱和酮分子骨架,可以作为合成药物中间体的通用砌块,存在潜在的生物活性,并且操作简便,有利于工业化生产。
具体实施方式
下面结合具体实施例对本发明进行详细说明。本实施例以本发明技术方案为前提进行实施,给出了详细的实施方式和具体的操作过程,但本发明的保护范围不限于下述的实施例。
下述各实施例中所采用的设备如无特别说明,则表示均为本领域的常规设备;所采用的试剂如无特别说明,则表示均为市售产品或采用本领域的常规方法制备而成,以下实施例中没有做详细说明的均是采用本领域常规实验手段就能实现。
本实施例采用了一种温和的钯催化α-羟基碘代偕单氟/二氟甲基类化合物(化合物1和2为已成功合成的砌块,具体制备方法可参考文章:Indium mediated barbier-typeallylation:Synthesis of highly functionalized homoallylic difluorohydrins)与邻硝基苯甲酸及其取代物的自由基诱导的重排反应方法,合成了一系列单氟/二氟氧代烯丙基酯类化合物,化学方程式为:
实施例1:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,具体步骤如下:
(1)在烘箱干燥的装有搅拌子的10mL反应管中,分别加入2-硝基苯甲酸(0.45mmol,1.5equiv)、醋酸钯(II)(Pd(OAc)2,20mmol%)和氧化银(I)(Ag2O,0.225mmol,0.75equiv);然后取1,1-二氟-1-碘-2-苯基-4-烯-2-醇(0.30mmol,1.0equiv)溶于六氟异丙醇(HFIP,1.5mL)后加入反应管,用橡胶塞将反应管盖住,并在50℃条件下搅拌12h;反应至薄层色谱法(TLC)监测原料反应完全,然后冷却至室温;
(2)垫硅藻土抽吸过滤,采用萃取液进行萃取,萃取液为乙酸乙酯,萃取液与反应液的体积比为1:(1-1.5),萃取次数为3-4次,合并的有机相用无水硫酸钠(Na2SO4)干燥,并在0.6-0.8kPa下浓缩,采用洗脱剂在层析柱中进行分离提纯,洗脱剂为体积比(5-20):1的石油醚与乙酸乙酯,洗脱时间为1-2h,最后得到淡黄色油状液体(82.38mg,收率为76%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.94(d,J=10.0Hz,1H),7.77(d,J=10.0Hz,1H),7.71(q,J=10.0Hz,2H),7.57(d,J=10.0Hz,2H),7.49-7.46(m,3H),7.16(dd,J=20.0,4.0Hz,1H),6.76(d,J=10.0Hz,1H),5.05-5.02(m,2H);
13C NMR(125MHz,CDCl3)δ=187.54(t,2JC-F=40.0Hz),164.69,148.37,143.58,133.12,132.39,131.92(t,2JC-F=31.25Hz),131.14,130.15,128.94,126,71,125.77(t,3JC-F=8.75Hz),124.13,122.28,116.12(t,1JC-F=315.0Hz),64.52;
19F NMR(376MHz,CDCl3)δ=-106.89(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H13O5NF2:384.0654;found:384.0656.
实施例2:
一种(E)-5,5-二氟-5-(4-甲氧基苯基)-4-氧代-2-烯-1-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(4-甲氧基苯基)戊-4-烯-2-醇,最后得到淡黄色油状液体(102.14mg,收率为87%),即(E)-5,5-二氟-5-(4-甲氧基苯基)-4-氧代-2-烯-1-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.94(d,J=10.0Hz,1H),7.77-7.76(m,1H),7.73-7.68(m,2H),7.49(d,J=5.0Hz,2H),7.16-7.11(m,1H),6.95(d,J=5.0Hz,2H),6.73(d,J=15.0Hz,1H),5.02(d,J=5.0Hz,2H),3.82(s,3H);
13C NMR(125MHz,CDCl3)δ=187.58(t,2JC-F=32.5Hz),164.65,161.70,148.30,143.25,133.07,132.54,132.33,130.10,127.33(t,3JC-F=6.25Hz),126.67,124.07,122.36,116.28(t,1JC-F=252.5Hz),114.32,64.50,55.41;
19F NMR(376MHz,CDCl3)δ=-104.68(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O6NF2:414.0760;found:414.0754.
实施例3:
一种(E)-5,5-二氟-5-(3-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(3-甲氧基苯基)戊-4-烯-2-醇,最后得到淡黄色油状液体(97.44mg,收率为83%),即(E)-5,5-二氟-5-(3-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.93(d,J=5.0Hz,1H),7.76-7.75(m,1H),7.72-7.66(m,2H),7.37-7.34(m,1H),7.17-7.13(m,2H),7.07(s,1H),7.00(d,J=10.0Hz,1H),6.75(d,J=15.0Hz,1H),5.02(d,J=5.0Hz,2H),3.80(s,3H);
13C NMR(125MHz,CDCl3)δ=187.33(t,2JC-F=31.25Hz),164.62,159.91,148.30,143.63,133.19(t,2J C-F=25.0Hz),133.09,132.37,130.14,130.10,126.61,124.05,122.15,117.89(t,3JC-F=6.25Hz),117.08,115.91(t,1JC-F=252.5Hz),110.85,64.45,55.44;
19F NMR(376MHz,CDCl3)δ=-104.90(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O6NF2:414.0760;found:414.0756.
实施例4:
一种(E)-5,5-二氟-5-(2-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(2-甲氧基苯基)戊-4-烯-2-醇,最后得到淡黄色油状液体(93.92mg,收率为80%),即(E)-5,5-二氟-5-(2-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.95(d,J=10.0Hz,1H),7.76-7.74(m,1H),7.72-7.68(m,2H),7.63(d,J=10.0Hz,1H),7.40-7.38(m,1H),7.32-7.29(m,1H),7.25-7.18(m,2H),6.73(d,J=15.0Hz,1H),5.05(d,J=5.0Hz,2H),2.35(s,3H);
13C NMR(125MHz,CDCl3)δ=186.86(t,2JC-F=32.5Hz),164.66,148.24,143.28,136.94(t,3JC-F=3.75Hz),133.10,132.33,132.07,131.03,130.10(t,2JC-F=22.5Hz),130.02,126.67,126.30(t,3JC-F=10.0Hz),126.12,124.08,122.58,116.66(t,1JC-F=252.5Hz),64.45,19.89;
19F NMR(376MHz,CDCl3)δ=-102.76(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O6NF2:414.0760;found:414.0757.
实施例5:
一种(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为2,2-二氟-2-碘-1-(4-甲氧基苯基)乙烷-1-酮(0.3121g,1mmol),最后得到淡黄色油状液体(85.34mg,收率为75%),即(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.94(d,J=5.0Hz,1H),7.78-7.77(m,1H),7.73-7.68(m,2H),7.58-7.56(m,2H),7.18-7.12(m,3H),6.75(d,J=15.0Hz,1H),5.04(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=187.29(t,2JC-F=32.5Hz),164.60(t,1JC-F=157.5Hz),148.36,143.87,133.06,132.40,130.17,128.14,128.07,126.56,124.06,121.95,116.19,116.01,115,75(t,1JC-F=252.5Hz),64.44;
19F NMR(376MHz,CDCl3)δ=-60.76(s,2F),-102.66(s,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12O5NF3:402.0560;found:402.0558..
实施例6:
一种(E)-5-(3-氯苯基)-5,5-二氟-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为2-(3-氯苯基)-1,1-二氟-1-碘-4-烯-2-醇,最后得到淡黄色油状液体(104.48mg,收率为88%),即(E)-5-(3-氯苯基)-5,5-二氟-4-氧代-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.95(d,J=5.0Hz,1H),7.79-7.77(m,1H),7.74-7.68(m,2H),7.57(s,1H),7.46-7.45(m,2H),7.41-7.28(m,1H),7.18(d,J=2.0Hz,1H),6.77(d,J=15.0Hz,1H),5.04(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=186.95(t,2JC-F=32.5Hz),164.60,148.36,144.18,135.03,133.96,133.75,133.07,132.39,131.32,130.28,130.14,126.56,126.03(t,3JC-F=6.25Hz),124.07(t,3JC-F=6.25Hz),121.81,115,25(t,1JC-F=252.5Hz),64.42;
19F NMR(376MHz,CDCl3)δ=-104.89(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12ClO5NF2:418.0264;found:418.0267.
实施例7:
一种(E)-5,5-二氟-5-(萘-2-基)-4-氧-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(萘-2-基)戊-4-烯-2-醇,最后得到淡黄色油状液体(90.09mg,收率为73%),即(E)-5,5-二氟-5-(萘-2-基)-4-氧-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.14(s,1H),7.93(d,J=5.0Hz,3H),7.87(d,J=5.0Hz,1H),7.74-7.73(m,1H),7.67-7.65(m,2H),7.61(d,J=5.0Hz,1H),7.57-7.55(m,2H),7.18(d,J=2.0Hz,1H),6.84(d,J=15.0Hz,1H),5.02(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=187.50(t,2JC-F=32.5Hz),164.63,148.31,143.66,134.30,133.05,132.60,132.33,130.11,129.10,128.78,127.86,127.82,127.02,126.60,126.22(t,3JC-F=7.5Hz),124.05,122.26,122.00(t,3JC-F=6.25Hz),116.34(t,1JC-F=252.5Hz),64.47;
19F NMR(376MHz,CDCl3)δ=-104.77(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C22H15O5NF2:434.0811;found:434.0802.
实施例8:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(99.79mg,收率为85%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.84(d,J=10.0Hz,2H),7.61(d,J=5.0Hz,2H),7.51-7.46(m,3H),7.28-7.27(m,1H),7.18-7.15(m,2H),6.79(d,J=15.0Hz,1H),5.00(d,J=5.0Hz,2H),3.94(s,3H);
13C NMR(125MHz,CDCl3)δ=187.50(t,2JC-F=31.5Hz),163.63,162.84,150.94,143.82,132,45,131.91(t,2JC-F=25.0Hz),131.07,128.88,125.72(t,3JC-F=6.25Hz),121.96,117.39,116.77,116.10(t,1JC-F=252.5Hz),109.46,64.17,56.27;
19F NMR(376MHz,CDCl3)δ=-104.54(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O6NF2:414.0706;found:414.0764.
实施例9:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-氟-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(88.75mg,收率为78%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-氟-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.86-7.83(m,1H),7.60-7.56(m,3H),7.50-7.45(m,3H),7.42-7.39(m,1H),7.14(d,J=15.0Hz,1H),6.75(d,J=15.0Hz,1H),5.01(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=187.43(t,2JC-F=32.5Hz),163.41(t,1JC-F=180.0Hz),143.32,132,67,132.60,131.12,129.17,128.90,125.70(t,3JC-F=7.5Hz),122.25,120.06,119.88,116.07(t,1JC-F=252.5Hz),112.25,112.04,64.60;
19F NMR(376MHz,CDCl3)δ=-104.88(s,2F),-155.64(s,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12O5NF3:402.0560;found:402.0565.
实施例10:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-3-氯-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(91.42mg,收率为77%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-3-氯-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.01(d,J=10.0Hz,1H),7.76(d,J=10.0Hz,1H),7.61-7.55(m,3H),7.49-7.46(m,3H),7.12(d,J=20.0Hz,1H),6.80(d,J=15.0Hz,1H),5.01(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=187.48(t,2JC-F=31.25Hz),161.48,148.78,142.94,135.31,131.12,130.92,130.01,129.27,128.91,126.52,125.74(t,3JC-F=6.25Hz),123.69,122.23,116.09(t,1JC-F=252.5Hz),64.75;
19F NMR(376MHz,CDCl3)δ=-104.53(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12ClO5NF2:418.0264;found:418.0268.
实施例11:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-5-溴-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(110.93mg,收率为84%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-5-溴-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.86-7.84(m,2H),7.81-7.79(m,1H),7.57-7.55(m,2H),7.49-7.44(m,2H),7.41-7.37(m,1H),7.13(d,J=15.0Hz,1H),6.74(d,J=20.0Hz,1H),5.03(d,J=5.0Hz,2H);
13C NMR(125MHz,CDCl3)δ=187.38(t,2JC-F=32.5Hz),163.44,149.06,143.12,135.19,132.90,131.13,129.32,128.92,128.66,127.07,125.70,125.62,122.46,116.05(t,1J C-F=252.5Hz),64.78;
19F NMR(376MHz,CDCl3)δ=-104.88(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12BrO5NF2:461.9759;found:461.9760.
实施例12:
一种(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-2-(4-氟苯基)-1-碘戊基-4-烯-2-醇,最后得到淡黄色油状液体(98.24mg,收率为80%),即(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.82(d,J=10.0Hz,1H),7.59-7.56(m,2H),7.24-7.23(m,1H),7.16-7.11(m,4H),6.75(d,J=15.0Hz,1H),4.98(d,J=5.0Hz,2H),3.91(s,3H);
13C NMR(125MHz,CDCl3)δ=187.31(t,2J C-F=32.5Hz),163.59(t,1J C-F=216.25Hz),162.88,150.95,144.18,132.53,128.14,128.07,121.64,117.36,116.64,116.16,115.99,115.77(t,1J C-F=252.5Hz),109.44,64.15,56.26;
19F NMR(376MHz,CDCl3)δ=-60.98(s,1F),-104.88(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H14O6NF3:432.0665;found:432.0666.
实施例13:
一种(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯基-4,5-二甲氧基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(115.99mg,收率为88%),即(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯基-4,5-二甲氧基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.55-7.53(m,2H),7.44(s,1H),7.13-7.09(m,4H),6.74(d,J=15.0Hz,1H),5.00(d,J=5.0Hz,2H),3.96(s,6H);
13C NMR(125MHz,CDCl3)δ=187.28(t,2J C-F=32.5Hz),164.95,163.30(t,1J C-F=248.75Hz),152.49,150.90,144.18,141.56,128.11,128.04,121.83,120.30,116.15,115.98,115.75(t,1J C-F=252.5Hz),111.03,107.03,64.37,56.65(t,J=3.75Hz);
19F NMR(376MHz,CDCl3)δ=-61.65(s,1F),-104.89(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H16O7NF3:462.0771;found:462.0768.
实施例14:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-(2-硝基苯基)乙酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(85.58mg,收率为76%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-(2-硝基苯基)乙酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(400MHz,CDCl3)δ=8.16(d,J=8.0Hz,1H),7.66-7.62(m,1H),7.56-7.52(m,3H),7.50-7.46(m,3H),7.39(d,J=8.0Hz,1H),7.10(dt,J=16.0,8.0Hz,1H),6.66(d,J=16.0Hz,1H),4.84-4.82(m,2H),4.10(s,2H);
13C NMR(125MHz,CDCl3)δ=187.61(t,2J C-F=32.0Hz),169.30,148.59,144.69,133.96,133.56,131.94(t,2J C-F=25.0Hz),131.15,129.35,129.06,128.69,125.75(t,3JC-F=6.0Hz),125.55,121.60,116.11(t,1J C-F=252.0Hz),63.41,39.80;
19F NMR(376MHz,CDCl3)δ=-106.89(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O5NF2:398.0668;found:398.0665.
实施例15:
一种(E)-5,5-二氟-4-氧代-5-(邻甲苯基)戊-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(邻甲苯基)-4-烯-2-醇,最后得到淡黄色油状液体(86.70mg,收率为77%),即(E)-5,5-二氟-4-氧代-5-(邻甲苯基)戊-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.95(d,J=10.0Hz,1H),7.76-7.69(m,3H),7.63(d,J=10.0Hz,1H),7.40-7.38(m,1H),7.32-7.29(m,1H),7.25-7.19(m,2H),6.73(d,J=20.0Hz,1H),5.05(s,2H),2.36(s,3H);
13C NMR(125MHz,CDCl3)δ=186.86(t,2J C-F=32.5Hz),164.62,148.34,143.41,136.93(t,3J C-F=3.75Hz),133.10,132.34,132.12,131.03,130.11(t,2J C-F=22.5Hz),130.03,126.70,126.33(t,3J C-F=10.0Hz),126.11,124.14,122.60,116.73(t,1J C-F=252.5Hz),64.41,19.90;
19F NMR(376MHz,CDCl3)δ=-102.61(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O5NF2:398.0811;found:398.0809.
实施例16:
一种(E)-5-(2-氯苯基)-5,5-二氟-4-氧杂戊-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为2-(2-氯苯基)-1,1-二氟-1-碘-4-烯-2-醇,最后得到淡黄色油状液体(93.79mg,收率为79%),即(E)-5-(2-氯苯基)-5,5-二氟-4-氧杂戊-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.96(d,J=5.0Hz,1H),7.80-7.70(m,4H),7.45-7.42(m,3H),7.28-7.23(m,1H),6.90(d,J=20.0Hz,1H),5.11-5.10(m,2H);
13C NMR(125MHz,CDCl3)δ=186.64(t,2JC-F=32.5Hz),164.71,148.23,143.48,133.10,132.33,132.10,130.87,130.70,130.04,129.61,127.94(t,3JC-F=8.75Hz),127.04,126.90,124.13,122.52,114.69(t,1JC-F=252.5Hz),64.53;
19F NMR(376MHz,CDCl3)δ=-102.32(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12ClO5NF2:418.0264;found:418.0263.
实施例17:
一种(E)-5,5-二氟-4-氧代-5-(4-三氟甲基苯基)戊-2-烯-1-基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物2为1,1-二氟-1-碘-2-(4-三氟甲基苯基)戊-4-烯-2-醇,最后得到淡黄色油状液体(105.61mg,收率为82%),即(E)-5,5-二氟-4-氧代-5-(4-三氟甲基苯基)戊-2-烯-1-基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.95-7.94(m,1H),7.80-7.78(m,1H),7.73-7.70(m,6H),7.21-7.17(m,1H),6.80(d,J=15.0Hz,1H),5.05-5.06(m,2H);
13C NMR(125MHz,CDCl3)δ=186.91(t,2JC-F=32.5Hz),164.63,148.40,144.43,135.58,133.29,133.03,132.42,130.21,126.54(t,3JC-F=6.25Hz),125.88(q,1JC-F=3.75Hz),124.60,124.13,122.51,121.72,115,43(t,1JC-F=252.5Hz),64.4;
19F NMR(376MHz,CDCl3)δ=-60.91(s,3F),-104.88(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H12O5NF5:452.0528;found:452.0526.
实施例18:
一种(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-4-甲基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为4-甲基-2-硝基苯甲酸,最后得到淡黄色油状液体(85.58mg,收率为76%),即(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-4-甲基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.68(d,J=10.0Hz,2H),7.57(d,J=10.0Hz,2H),7.48-7.45(m,4H),7.17-7.12(m,1H),6.76(d,J=15.0Hz,1H),4.99(s,2H),2.48(s,3H);
13C NMR(125MHz,CDCl3)δ=187.49(t,2JC-F=32.5Hz),164.44,148.81,144.08,143.83,133.30,131.90(t,2JC-F=25.0Hz),131.13,130.31,128.94,125.70(t,3JC-F=6.25Hz),124.33,123.21,122.07,116.12(t,1JC-F=252.5Hz),64.31,21.33;
19F NMR(376MHz,CDCl3)δ=-104.94(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O5NF2:398.0811;found:398.0815.
实施例19:
一种(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-甲基-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为5-甲基-2-硝基苯甲酸,最后得到淡黄色油状液体(102.47mg,收率为91%),即(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-甲基-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.91-7.89(m,1H),7.59(s,2H),7.51-7.48(m,5H),7.20-7.16(m,1H),6.79(d,J=15.0Hz,1H),5.04(s,2H),2.50(s,3H);
13C NMR(125MHz,CDCl3)δ=187.51(t,2JC-F=32.5Hz),165.10,145.72,144.93,143.77,132.42,131.86(t,2JC-F=25.0Hz),131.10,130.21,128.87,127.24,125.70(t,3JC-F=6.25Hz),124.28,122.33,116.14(t,1JC-F=252.5Hz),64.40,21.41;
19F NMR(376MHz,CDCl3)δ=-104.67(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O5NF2:398.0811;found:398.0817.
实施例20:
一种(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-2-甲基-6-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为6-甲基-2-硝基苯甲酸,最后得到淡黄色油状液体(86.70mg,收率为77%),即(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-2-甲基-6-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.04-8.03(m,1H),7.58-7.57(m,3H),7.51-7.48(m,3H),7.24-7.20(m,1H),6.79(d,J=10.0Hz,1H),5.10(s,2H),2.43-2.42(m,3H);
13C NMR(125MHz,CDCl3)δ=187.51(t,2JC-F=32.5Hz),165.73,146.30,143.88,137.71,136.19,131.93(t,2JC-F=25.0Hz),131.11,130.23,128.94,128.50,125.69(t,3JC-F=6.25Hz),122.53,122.01,116.14(t,1JC-F=252.5Hz),64.27,19.22;
19F NMR(376MHz,CDCl3)δ=-104.65(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H15O5NF2:398.0811;found:398.0813.
实施例21:
一种(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-氯-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为5-氯-2-硝基苯甲酸,最后得到淡黄色油状液体(92.60mg,收率为78%),即(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-氯-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.95(d,J=5.0Hz,1H),7.70(d,J=5.0Hz,1H),7.65-7.63(m,1H),7.57-7.56(m,2H),7.49-7.46(m,3H),7.17-7.12(m,1H),6.75(d,J=15.0Hz,1H),5.03-5.04(m,2H);
13C NMR(125MHz,CDCl3)δ=187.43(t,2JC-F=32.5Hz),163.61,149.07,146.23,143.11,139.87,132.14,131.12,130.04,128.92,128.66(t,3JC-F=12.5Hz),127.11,125.74(t,3JC-F=12.5Hz),122.52,116.01(t,1JC-F=252.5Hz),64.83;
19F NMR(376MHz,CDCl3)δ=-104.90(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H12ClO5NF2:418.0264;found:418.0264.
实施例22:
一种(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基-4-(三氟甲基)苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为2-硝基-4-(三氟甲基)苯甲酸,最后得到淡黄色油状液体(105.61mg,收率为82%),即(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基-4-(三氟甲基)苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.25(s,1H),7.98-7.90(m,2H),7.56(s,2H),7.48(s,3H),7.16-7.13(m,1H),6.75(d,J=15.0Hz,1H),5.06(s,2H);
13C NMR(125MHz,CDCl3)δ=187.43(t,2JC-F=32.5Hz),163.61,148.08,142.91,134.70,134.43,131.81(t,2JC-F=26.25Hz),131.13,130.91,130.03(t,3JC-F=5.0Hz),128.91,125.70(t,3JC-F=6.25Hz),123.33,122.58,121.61(t,3JC-F=3.75Hz),116.03(t,1JC-F=252.5Hz),64.91;
19F NMR(376MHz,CDCl3)δ=-61.19(s,3F),-102.83(s,2F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H12O5NF5:452.0528;found:452.0525.
实施例23:
一种(E)-5-氟-4-氧代-5-苯基-2-烯-1-基-4,5-二氟-2-硝基苯甲酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为4,5-二氟-2-硝基苯甲酸,化合物1为1-氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(83.06mg,收率为73%),即(E)-5-氟-4-氧代-5-苯基-2-烯-1-基-4,5-二氟-2-硝基苯甲酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=7.86-7.83(m,1H),7.61-7.55(m,2H),7.50-7.45(m,3H),7.15-7.11(m,1H),6.73(d,J=20.0Hz,1H),5.03-5.02(m,2H);
13C NMR(125MHz,CDCl3)δ=187.41(t,2J C-F=32.5Hz),162.72,153.63(t,3J C-F=11.25Hz),152.27(t,2J C-F=12.5Hz),151.03(t,3J C-F=11.25Hz),150.21(t,2J C-F=12.5Hz),144.23(t,3J C-F=7.5Hz),142.89,131.80(t,2J C-F=25.0Hz),131.13,128.91,125.74(t,3J C-F=6.25Hz),122.61,119.43(t,1J C-F=21.25Hz),116.03(t,1J C-F=252.5Hz),114.81(t,1J C-F=22.5Hz),64.90;
19F NMR(376MHz,CDCl3)δ=-123.99--125.02(m,2F),-155.84(d,J=48.5Hz,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H11O5NF3:398.0811;found:398.0810.
实施例24:
一种(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(5-氟-2-硝基苯基)乙酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为2-(5-氟-2-硝基苯基)乙酸,化合物1为1-氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(91.21mg,收率为81%),即(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(5-氟-2-硝基苯基)乙酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.23-8.21(m,1H),7.66-7.62(m,1H),7.55(s,2H),7.48-7.41(m,3H),7.19-7.18(m,1H),7.10-7.08(m,2H),6.68(d,J=15.0Hz,1H),4.84(s,2H),4.09-4.08(m,2H);
13C NMR(125MHz,CDCl3)δ=187.53(t,2J C-F=32.5Hz),168.71,165.94,163.81,144.43,132.78(t,2J C-F=8.75Hz),131.92(t,2J C-F=25.0Hz),131.07,128.91,128.43(t,3J C-F=5.0Hz),125.70(t,3J C-F=6.25Hz),121.83,120.41(t,1J C-F=23.75Hz),116.02(t,1J C-F=252.0Hz),115.88(t,2J C-F=11.25Hz),63.52,39.80;
19F NMR(376MHz,CDCl3)δ=-100.97(s,1F),-155.86(d,J=48.5Hz,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H14O5NF2:398.0810;found:398.0799.
实施例25:
一种(E)-5-氟-4-氧-5-苯基戊-2-烯-1-基-2-(4-溴-2-硝基苯基)乙酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为2-(4-溴-2-硝基苯基)乙酸,化合物1为1-氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(102.08mg,收率为78%),即(E)-5-氟-4-氧-5-苯基戊-2-烯-1-基-2-(4-溴-2-硝基苯基)乙酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.31(s,1H),7.78-7.76(m,1H),7.59-7.57(m,2H),7.52-7.49(m,3H),7.29-7.28(m,1H),7.13-7.09(m,1H),6.69(d,J=15.0Hz,1H),4.85-4.85(m,2H),4.07(s,2H);
13C NMR(125MHz,CDCl3)δ=187.52(t,2J C-F=31.25Hz),168.70,149.01,144.27,136.80,134.73,131.91,131.09,128.92,128.40,128.22,125.66(t,3J C-F=6.25Hz),122.10,121.83,116.01(t,1J C-F=252.0Hz),63.48,39.22;
19F NMR(376MHz,CDCl3)δ=-155.82(d,J=48.5Hz,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H14BrO5NF:458.0010;found:458.0098.
实施例26:
一种(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(2-硝基-4-(三氟甲基)苯基)乙酸酯化合物及其制备方法,与实施例1基本相同,不同之处在于,化合物3为2-(2-硝基-4-三氟甲基)苯基乙酸,化合物1为1-氟-1-碘-2-苯基-4-烯-2-醇,最后得到淡黄色油状液体(105.91mg,收率为83%),即(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(2-硝基-4-(三氟甲基)苯基)乙酸酯化合物,化学结构式为:
该化合物的基本参数如下:
1H NMR(500MHz,CDCl3)δ=8.45-8.44(m,1H),7.91-7.90(m,1H),7.58-7.58(m,3H),7.51-7.50(m,3H),7.14-7.11(m,1H),6.73-6.69(m,1H),4.87(s,2H),4.21-4.19(m,2H);
13C NMR(125MHz,CDCl3)δ=187.50(t,2JC-F=32.5Hz),168.46,148.71,144.23,134.41,133.10,131.93,131.58,131.14,130.22,128.90,125.73(t,3JC-F=5.0Hz),123.81,122.69,121.22,116.01(t,1JC-F=251.25Hz),63.63,39.54;
19F NMR(376MHz,CDCl3)δ=-61.08(s,3F),-155.87(d,J=48.5Hz,1F);
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H14O5NF4:448.0779;found:448.0778.
上述的对实施例的描述是为便于该技术领域的普通技术人员能理解和使用发明。熟悉本领域技术的人员显然可以容易地对这些实施例做出各种修改,并把在此说明的一般原理应用到其他实施例中而不必经过创造性的劳动。因此,本发明不限于上述实施例,本领域技术人员根据本发明的揭示,不脱离本发明范畴所做出的改进和修改都应该在本发明的保护范围之内。
Claims (10)
1.一种单氟/二氟氧代烯丙基酯类化合物,其特征在于,该化合物化学结构式为:
其中,R1包括苯基或取代苯基,R2为取代苯基,Rf包括单氟或二氟。
2.根据权利要求1所述的一种单氟/二氟氧代烯丙基酯类化合物,其特征在于,所述的R1为取代苯基,该取代苯基中的取代基选自苯基、氢、氟、氯、溴、甲氧基、甲基和三氟甲基中的一种或多种;
所述的R2为取代苯基,该取代苯基中的取代基选自硝基、氢、氟、氯、溴、甲氧基、亚甲基、甲基和三氟甲基中的一种或多种。
3.根据权利要求1所述的一种单氟/二氟氧代烯丙基酯类化合物,其特征在于,所述的单氟氧代烯丙基酯类化合物包括(E)-5-氟-4-氧代-5-苯基-2-烯-1-基-4,5-二氟-2-硝基苯甲酸酯、(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(5-氟-2-硝基苯基)乙酸酯、(E)-5-氟-4-氧-5-苯基戊-2-烯-1-基-2-(4-溴-2-硝基苯基)乙酸酯或(E)-5-氟-4-氧代-5-苯基戊-2-烯-1-基-2-(2-硝基-4-(三氟甲基)苯基)乙酸酯。
4.根据权利要求1所述的一种单氟/二氟氧代烯丙基酯类化合物,其特征在于,所述的二氟氧代烯丙基酯类化合物包括(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-甲氧基苯基)-4-氧代-2-烯-1-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(3-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(2-甲氧基苯基)-4-氧代-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基2-硝基苯甲酸酯、(E)-5-(3-氯苯基)-5,5-二氟-4-氧代-2-烯-1-基2-硝基苯甲酸酯、(E)-5,5-二氟-5-(萘-2-基)-4-氧-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-4-氟-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-3-氯-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-5-溴-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯-1-基-4-甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-5-(4-氟苯基)-4-氧代-2-烯基-4,5-二甲氧基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-(2-硝基苯基)乙酸酯、(E)-5,5-二氟-4-氧代-5-(邻甲苯基)戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5-(2-氯苯基)-5,5-二氟-4-氧杂戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-(4-三氟甲基苯基)戊-2-烯-1-基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-4-甲基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-甲基-2-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-2-甲基-6-硝基苯甲酸酯、(E)-5,5-二氟-4-氧代-5-苯基戊-2-烯-1-基-5-氯-2-硝基苯甲酸酯或(E)-5,5-二氟-4-氧代-5-苯基-2-烯-1-基-2-硝基-4-(三氟甲基)苯甲酸酯。
5.一种如权利要求1至4任一项所述的单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,该方法包括以下步骤:
(1)分别加入化合物3、催化剂和氧化剂混合,然后取化合物1或2溶于溶剂后加入,搅拌反应,然后冷却至室温;
(2)得到的反应液经萃取、分离后得到化合物4,即单氟/二氟氧代烯丙基酯类化合物;
化学方程式为:
6.根据权利要求5所述的一种单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,步骤(1)中催化剂选自醋酸钯(II)、双(三苯膦基)醋酸钯(II)、四(乙腈)四氟硼酸钯(II)、二乙酸-1,2-双(苯亚磺酰)乙基钯(II)、六氟乙酰丙酮钯(II)、(2,2'-联吡啶)二氯化钯(II)、双三苯基磷二氯化钯(II)、二氯化钯(II)和四(三苯基膦)钯(0)中的一种或多种;
氧化剂选自氧化银(I)、三氟甲磺酸银(I)、乙酸银(I)、三氟乙酸银(I)、氟化银(I)和碳酸银(I)中的一种或多种;
溶剂选自六氟异丙醇、叔丁醇、异丙醇、三氟乙醇、乙醇、二甲基酮、乙腈、四氢呋喃、二甲基酰胺和二甲基亚砜中的一种或多种。
7.根据权利要求5所述的一种单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,步骤(1)中化合物1或2、化合物3与氧化剂的摩尔比为(0.15-0.5):(0.35-0.7):(0.005-0.5),催化剂用量为化合物1或2的10-20mmol%。
8.根据权利要求5所述的一种单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,步骤(1)中反应温度为20-80℃,时间为8-12h。
9.根据权利要求5所述的一种单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,步骤(2)中萃取采用萃取液进行,所述的萃取液为乙酸乙酯,所述的萃取液与反应液的体积比为1:(1-1.5),所述的萃取次数为3-4次。
10.根据权利要求5所述的一种单氟/二氟氧代烯丙基酯类化合物的制备方法,其特征在于,步骤(2)中分离采用洗脱剂在层析柱中进行提纯,所述的洗脱剂为体积比为(1-200):1的石油醚与乙酸乙酯,所述的洗脱时间为1-2h。
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