CN110294704A - A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound - Google Patents

A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound Download PDF

Info

Publication number
CN110294704A
CN110294704A CN201810248047.8A CN201810248047A CN110294704A CN 110294704 A CN110294704 A CN 110294704A CN 201810248047 A CN201810248047 A CN 201810248047A CN 110294704 A CN110294704 A CN 110294704A
Authority
CN
China
Prior art keywords
cdcl
nmr
unsubstituted
milligrams
synthesis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201810248047.8A
Other languages
Chinese (zh)
Inventor
孙逊
俞立挺
孟志
唐美麟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fudan University
Original Assignee
Fudan University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fudan University filed Critical Fudan University
Priority to CN201810248047.8A priority Critical patent/CN110294704A/en
Publication of CN110294704A publication Critical patent/CN110294704A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
    • 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
    • C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
    • 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
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/56—Radicals substituted by oxygen atoms
    • 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
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • 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
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • 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
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/44—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Abstract

The invention belongs to fluorine organic compound synthesis technical fields, are related to a kind of method prepared containing single fluoroalkyl vinyl hydrocarbon compound, and in particular to utilize the method together with-two fluoroolefins and carboxylic acid reactive's Lipase absobed list fluoroalkyl vinyl hydrocarbon compound.The present invention will efficiently be converted into corresponding single fluoroalkyl vinyl hydrocarbon compound using carboxylic acid reactive's ester as alkylating reagent under the action of zinc simple substance in N N'- dimethyl acetamide together with-two fluoroolefins.Reaction condition of the present invention is mild, easily operates, and has good chemo-selective and functional group compatibility, is the synthetic method of effective single fluoroalkyl vinyl hydrocarbon compound.

Description

A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound
Technical field
The invention belongs to fluorine organic compound synthesis technical field, be related to fluorine-containing medicines, pesticide, material intermediate synthesis side Method, and in particular to utilize the method together with-two fluoroolefins and carboxylic acid reactive's Lipase absobed list fluoroalkyl vinyl hydrocarbon compound.
Background technique
It is past that single fluoroolefins is introduced prior art discloses the isostere each other such as single fluoroolefins and amide, alkene, in molecule Toward the stability, fat-soluble that can effectively improve molecule, so as to improve the physiological activity, metabolic stability, blood of small organic molecule Brain Barrier penetrability and attention (a) R.J.Sciotti increasingly by the fields such as medicine, pesticide and material, M.Pliushchev,P.E.Wiedeman,D.Balli,R.Flamm,A.M.Nilius,K.Marsh,D.Stolarik, R.Jolly,R.Ulrich,S.W.Djuric,Bioorg.Med.Chem.Lett.2002,12,2121；b)S.Couve- Bonnaire,D.Cahard,X.Pannecoucke,Org.Biomol.Chem.2007,5,1151；c)C.E.Jakobsche, A.Choudhary,S.J.Miller,R.T.Raines,J.Am.Chem.Soc.2010,132,6651；d)S.Oishi, H.Kamitani,Y.Kodera,K.Watanabe,K.Kobayashi,T.Narumi,K.Tomita,H.Ohno,T.Naito, E.Kodama,M.Matsuoka,N.Fujii,Org.Biomol.Chem.2009,7,2872；e)Y.Asahina,K.Iwase, F.Iinuma,M.Hosaka,T.Ishizaki,J.Med.Chem.2005,48,3194.)
There is studies have shown that although single fluoroolefins study on the synthesis increases (a) G.Landelle, M.Bergeron, M.- increasingly O.Turcotte-Savard,J.-F.Paquin,Chem.Soc.Rev.2011,40,2867；b)H.Yanai,T.Taguchi, Eur.J.Org.Chem.2011,2011,5939；c)W.Zhang,W.Huang,J.Hu,Angew.Chem.Int.Ed.2009, 48,9858；d)C.Schneider,D.Masi,S.Couve-Bonnaire,X.Pannecoucke,C.Hoarau, Angew.Chem.Int.Ed.2013,52,3246；e)M.Vandamme,J.-F.Paquin,Org.Lett.2017,19, 3604.) but wherein need to use expensive catalyst (such as metallic catalyst Pd, Rh), severe reaction conditions (anhydrous nothing Oxygen, high temperature), expensive fluorination reagent (needing multistep preparation in advance) etc., therefore limit the practical amplification application of single fluoroolefins.
Together with-two fluoroolefins due to raw material cheap and easily-available (raw material: aldehyde and difluoro sodium chloroacetate), easy preparation, yield height, appearance The also attention increasingly by fields such as medicine, pesticide and materials of the advantages that easy purification, special physicochemical property, but so far, from The research for being alkylated building carbon-carbon bond by defluorinate together with-two fluoroolefins is still few.The reports Grignard Reagent such as Cao Song in 2016 exists Have copper or without under copper catalysis, to the defluorinates of two fluoroolefins alkylation (W.Dai, H.Shi, X.Zhao, S.Cao, Org.Lett.2016,18,4284.), but this method needs previously prepared Grignard Reagent, there are obvious danger；2017 Defluorinate of the report halogenated alkyl objects such as year Fu Yao under the catalysis of N (COD) 2 is alkylated (X.Lu, Y.Wang, B.Zhang, J.- J.Pi,X.-X.Wang,T.-J.Gong,B.Xiao,Y.Fu,J.Am.Chem.Soc.2017,139,12632.)；Meanwhile Fu Hua Deng report by a-amino acid under the action of photochemical catalyst decarboxylation to together with-two fluoroolefins defluorinate alkylation (J.Li, Q.Lefebvre, H.Yang, Y.Zhao, H.Fu, Chem.Commun.2017,53,10299.), although both methods condition Compare mild, do not need using relatively hazardous reagent, but be required to metallic catalyst (10-20mol%) and ligand, need compared with More solvents.
Status based on the prior art, present inventor is quasi- to provide a kind of prepare containing single fluoroalkyl vinyl hydrocarbon compound Method, more particularly to using alkyl carboxylic acid active ester as a kind of mild free based precursor, taken off with to together with-two fluoroolefins Fluoroalkylation preparation contains single fluoroalkyl vinyl hydrocarbon compound, and this method reaction is mild, simple, efficient, is not necessarily to catalyst and ligand, fits Close industrial large-scale production.
Summary of the invention
The status of the prior art provides a kind of method prepared containing single fluoroalkyl vinyl hydrocarbon compound, and this method is by following anti- Answer formula, using together with-two fluoroolefins and carboxylic acid reactive's ester as raw material, in dry organic solvent and atmosphere of inert gases, in zinc list Under the action of matter, defluorinate generates single fluoroalkyl alkene；This method reaction is mild, simple, efficient, is not necessarily to catalyst and ligand, fits Close industrial large-scale production.
Wherein, part A be phenyl that is unsubstituted or optionally replacing, unsubstituted or optional substituted indyl, it is unsubstituted or The benzothienyl that optionally replaces, unsubstituted or optional substituted naphthalene, unsubstituted or optional substituted pyridyl group, it is unsubstituted or The thienyl that optionally replaces, unsubstituted or optional substituted furyl；Quinolyl that is unsubstituted or optionally replacing；It is unsubstituted or appoint Choose the isoquinolyl in generation；Thiazolyl that is unsubstituted or optionally replacing；Pyrazolyl that is unsubstituted or optionally replacing；It is unsubstituted or appoint Choose the imidazole radicals in generation；
Wherein, part B is selected from the cyclic alkyl or bridged cyclic group that C atomicity that is unsubstituted or optionally replacing is 3-10；Not The cycloalkenyl that substitution or the C atomicity optionally replaced are 3-10；- seven yuan of saturation nitrogen-containing heterocycles of quaternary that are unsubstituted or optionally replacing Base, oxygen-containing heterocycle；The alkyl or alkenyl that C atomicity that is unsubstituted or optionally replacing is 1-10；
In products therefrom fluoroolefin and the carbon atom of part B be connected.
In embodiments of the present invention, described in part A optionally replace in substituent group can be selected from cyano, methoxycarbonyl group, Dichlorophenyl, halogen, C1-6Alkoxy, benzothienyl, picolyl, trifluoro ethoxy, C1-6Alkyl, p-fluorophenyl；Institute Stating halogen is fluorine, chlorine, bromine, iodine.
In embodiments of the present invention, the substituent group in optionally replacing described in part B can be selected from halogen, C1-6Alkyl, C1-6Alkoxy, t-butoxycarbonyl amino, phenyl, methoxycarbonyl, phenoxy group, the thienyl, acetyl group that dimethyl is replaced； The halogen is fluorine, chlorine, bromine, iodine.
Further, the carbon atom being wherein connected in part B with fluoroolefin is optionally by methyl, tertbutyloxycarbonyl ammonia Base, phenyl replace.
In embodiments of the present invention, wherein part A can be selected from:
In embodiments of the present invention, wherein part B can be selected from:
In the present invention, reaction dissolvent can be selected from N N'- dimethyl acetamide (DMA), N, N'- dimethylformamide (DMF), Dimethyl sulfoxide (DMSO), the mixed solvent of N-Methyl pyrrolidone (NMP) and above-mentioned one or more solvents；Reaction temperature It can be carried out in zero degree to 60 degrees Celsius, the reaction time 2~72 hours, preferable reaction temperature is room temperature (20~30 degrees Celsius), instead It is 24~48 hours between seasonable；
In the present invention, the molar ratio together with-two fluoroolefins, carboxylic acid reactive's ester and zinc simple substance is 1:2~4:2~4；Preferably 1: 3:3；
Specific embodiment
In order to which the present invention is further explained, below with reference to embodiment, the present invention is further elaborated, but these embodiments Definitely not any limitation of the invention.
Typical reaction example of the invention are as follows:
In DMA (0.67M), room temperature, under inert gas shielding, together with-two fluoroolefins (1 equivalent), (3 work as with carboxylic acid reactive's ester Amount) in the presence of zinc simple substance (3 equivalent), it reacts 24-48 hours, list fluoroolefins is made.
Products therefrom structural formula is as follows:
Embodiment 1: the synthesis of monofluoroethylene derivative 3aa
It is added in reaction tube together with-two fluoroolefins 1 (33 milligrams, 0.2 mM), (224 milligrams, 3 work as carboxylic acid reactive's ester 2 Amount), dry NN'- is added with air 6 times in nitrogen displacement reaction tube in zinc powder (39 milligrams, 3 equivalents) and magnetic stir bar Dimethyl acetamide (0.3 milliliter), seals rubber stopper.After being vigorously stirred 24 hours at room temperature, it is dilute that ethyl acetate (5 milliliters) are added It releases, then filters out insoluble matter with silica gel, solid is washed with ethyl acetate (50 milliliters), the filtrate concentration being collected into, and uses silicagel column It purifies (petroleum ether: ethyl acetate=100:0-90:10), obtains 55.1 milligrams of white solids of target product, yield 83%.
1H NMR(400MHz,CDCl3) δ=7.58 (d, J=8.3,2H), 7.53 (d, J=8.3,2H), 5.50 (d, J= 39.1,1H), 4.20 (s, 2H), 2.75 (s, 2H), 2.42 (dd, J=26.1,11.9,1H), 1.89 (d, J=12.6,2H), 1.60–1.45(m,11H).
13C NMR(100MHz,CDCl3) δ=165.82 (d, J=272.6), 154.77,138.27,132.31,128.99 (d, J=8.1), 119.06,110.26 (d, J=2.7), 103.79 (d, J=8.1), 79.86,43.55,40.07 (d, J= 25.1),28.99,28.56.
19F NMR(376MHz,CDCl3) δ=- 100.60 (s, 1F)
HRMS(ESI)calcd for C19H23FN2O2Na+[(M+Na)+]353.1636,found 353.1647.。
Embodiment 2: the synthesis of monofluoroethylene derivative 3ab
The same 3aa of method, 36 milligrams of colourless liquid, yield 68%.
1H NMR(400MHz,CDCl3) δ=7.59 (d, J=8.5,2H), 7.54 (d, J=8.5,2H), 5.54 (d, J= 39.1,1H), 2.49-2.28 (m, 1H), 2.20 (dt, J=13.7,7.5,2H), 2.04 (d, J=9.8,2H), 1.90-1.67 (m,4H).
13C NMR(100MHz,CDCl3) δ=165.30 (dd, J=272.7,2.3), 138.16 (d, J=2.2), 132.33,129.02 (d, J=8.1), 122.63 (dd, J=242.6,239.9), 119.03,110.37 (d, J=2.8), 104.04 (d, J=8.1), 39.68 (d, J=25.0), 33.16 (dd, J=25.6,23.7), 26.13 (dd, J=9.8, 2.2).
19F NMR(376MHz,CDCl3) δ=- 92.52 (d, J=237.6,1F), -100.08 (s, 1F), -102.18 (d, J=237.5,1F)
HRMS(ESI)calcd for C15H15F3N+[(M+H)+]266.1151,found 266.1153.。
Embodiment 3: the synthesis of monofluoroethylene derivative 3ac
The same 3aa of method, 57.7 milligrams of colourless liquid, yield 83%.
1H NMR(400MHz,CDCl3) δ=7.62-7.51 (m, 4H), 5.55 (d, J=40.3,1H), 3.55-3.36 (m, 4H),1.93–1.83(m,2H),1.56–1.48(m,2H),1.44(s,9H),1.26(s,3H).
13C NMR(100MHz,CDCl3) δ=168.24 (d, J=274.9), 154.89,138.36 (d, J=1.7), 132.28,129.11 (d, J=8.3), 119.03,110.26 (d, J=2.8), 103.94 (d, J=9.2), 79.77,39.86, 37.87 (d, J=22.4), 33.93,28.54,23.96.
19F NMR(376MHz,CDCl3) δ=- 105.89 (s, 1F)
HRMS(ESI)calcd for C20H25FN2O2Na+[(M+Na)+]367.1792,found 367.1800.。
Embodiment 4: the synthesis of monofluoroethylene derivative 3ad
The same 3aa of method, 36.2 milligrams of white solid, yield 79%.
1H NMR(400MHz,CDCl3) δ=7.61-7.50 (m, 4H), 5.46 (d, J=39.4,1H), 2.33-2.17 (m, 1H), 1.99-1.90 (m, 2H), 1.86-1.77 (m, 2H), 1.72 (d, J=12.1,1H), 1.40-1.20 (m, 5H)
13C NMR(100MHz,CDCl3) δ=167.99 (d, J=273.6), 138.91 (d, J=2.2), 132.24, 128.87 (d, J=8.2), 119.19,109.81 (d, J=2.7), 102.88 (d, J=8.4), 41.79 (d, J=23.9), 30.00 (d, J=2.1), 25.95,25.89.
19F NMR(376MHz,CDCl3) δ=- 99.23 (s, 1F)
HRMS(ESI)calcd for C15H17FN+[(M+H)+]230.1340,found 230.1342.。
Embodiment 5: the synthesis of monofluoroethylene derivative 3ae
The same 3aa of method, 54 milligrams of white solid, yield 96%.
1H NMR(400MHz,CDCl3) δ=7.62-7.49 (m, 4H), 5.44 (d, J=40.1,1H), 2.07 (s, 3H), 1.84 (d, J=1.2,6H), 1.74 (dd, J=25.9,12.2,6H)
13C NMR(100MHz,CDCl3) δ=170.88 (d, J=274.3), 139.12 (d, J=1.8), 132.19, 129.01 (d, J=8.4), 119.19,109.74 (d, J=2.8), 101.63 (d, J=9.1), 39.20 (d, J=2.0), 37.62 (d, J=22.7), 36.62,27.97.
19F NMR(376MHz,CDCl3) δ=- 108.15 (s, 1F)
HRMS(ESI)calcd for C19H21FN+[(M+H)+]282.1653,found 282.1655.。
Embodiment 6: the synthesis of monofluoroethylene derivative 3af
The same 3aa of method, 33 milligrams of colourless liquid, yield 82%.
1H NMR(400MHz,CDCl3) δ=7.57 (d, J=8.4,2H), 7.51 (d, J=8.5,2H), 5.66-5.48 (m, 1H), 1.37-1.31 (m, 3H), 1.15-1.08 (m, 2H), 0.68 (t, J=5.1,2H)
13C NMR(100MHz,CDCl3) δ=166.46 (d, J=267.2), 139.02 (d, J=2.7), 132.30, 128.62 (d, J=8.2), 119.28,109.53,102.52 (d, J=10.5), 21.28 (d, J=4.1), 17.75 (d, J= 25.4),13.95,13.92.
19F NMR(376MHz,CDCl3) δ=- 107.63 (s, 1F)
HRMS(ESI)calcd for C13H13FN+[(M+H)+]202.1027,found 202.1025.。
Embodiment 7: the synthesis of monofluoroethylene derivative 3ag
The same 3aa of method, 26.5 milligrams of colourless liquid, yield 61%.
1H NMR(400MHz,CDCl3) δ=7.61-7.53 (m, 4H), 5.82 (d, J=38.3,1H), 4.57-4.48 (m, 1H),4.05–3.98(m,1H),3.94–3.85(m,1H),2.23–2.13(m,1H),2.09–1.93(m,3H).
13C NMR(100MHz,CDCl3) δ=162.41 (d, J=274.1), 137.88 (d, J=2.5), 132.33, 129.16 (d, J=7.8), 119.03,110.53 (d, J=2.8), 104.58 (d, J=5.6), 76.53,69.28,29.88, 25.81.
19F NMR(376MHz,CDCl3) δ=- 111.59 (s, 1F)
HRMS(ESI)calcd for C13H13FNO+[(M+H)+]218.0976,found 218.0977.。
Embodiment 8: the synthesis of monofluoroethylene derivative 3ah
The same 3aa of method, 27.7 milligrams of colourless liquid, yield 67%.
1H NMR(400MHz,CDCl3) δ=7.65-7.55 (m, 4H), 5.78 (d, J=38.2,1H), 3.95-3.82 (m, 1H), 3.40 (s, 3H), 1.43 (d, J=6.5,3H)
13C NMR(100MHz,CDCl3) δ=161.97 (d, J=277.6), 137.64 (d, J=2.5), 132.37, 129.22 (d, J=7.9), 118.97,110.72 (d, J=2.9), 105.58 (d, J=5.7), 76.10 (d, J=29.3), 57.04,18.75.
19F NMR(376MHz,CDCl3) δ=- 111.66 (s, 1F)
HRMS(ESI)calcd for C12H13FNO+[(M+H)+]206.0976,found 206.0974.。
Embodiment 9: the synthesis of monofluoroethylene derivative 3ai
The same 3aa of method, 61 milligrams of white solid, yield 91%.
1H NMR(400MHz,CDCl3) δ=7.63-7.51 (m, 4H), 5.89 (d, J=39.2,1H), 4.27-3.80 (m, 4H), 3.61 (t, J=10.8,1H), 3.09-2.87 (m, 2H), 1.47 (s, 9H)
13C NMR(100MHz,CDCl3) δ=158.96 (d, J=270.3), 154.55,137.26 (d, J=2.2), 132.36,129.35 (d, J=7.7), 118.85,111.02,106.09 (d, J=4.2), 80.69,73.66 (d, J= 33.2),66.51,46.29,43.51,28.47.
19F NMR(376MHz,CDCl3) δ=- 110.87 (s, 1F)
HRMS(ESI)calcd for C18H21FN2O3Na+[(M+Na)+]355.1428,found 355.1437.。
Embodiment 10: the synthesis of monofluoroethylene derivative 3aj
The same 3aa of method, 52 milligrams of white solid, yield 86%.
1H NMR(400MHz,CDCl3) δ=7.55 (d, J=8.2,2H), 7.48 (d, J=8.4,2H), 5.77 (d, J= 37.5,1H),5.24(s,1H),1.45(s,9H),1.38(s,2H),1.15(s,2H).
13C NMR(100MHz,CDCl3) δ=162.03 (d, J=270.1), 155.08,138.32 (d, J=2.9), 132.25,128.77 (d, J=7.8), 119.09,109.98,103.40 (d, J=8.8), 80.48,33.38 (d, J= 36.2),28.42,15.48
19F NMR(376MHz,CDCl3) δ=- 112.49 (s, 1F)
HRMS(ESI)calcd for C17H19FN2O2Na+[(M+Na)+]325.1323,found 325.1325.。
Embodiment 11: the synthesis of monofluoroethylene derivative 3ak
The same 3aa of method, 55.2 milligrams of white solid, yield 87%.
1H NMR(400MHz,CDCl3) δ=7.58 (d, J=9.4,4H), 5.82 (d, J=38.0,1H), 5.10 (s, 1H), 2.54 (dd, J=15.1,11.2,2H), 2.23 (d, J=24.4,2H), 1.98 (ddd, J=26.3,13.9,6.4, 2H),1.41(s,9H).
13C NMR(100MHz,CDCl3) δ=163.18 (d, J=274.6), 154.09,138.20,132.24,129.15 (d, J=7.8), 119.04,110.28,103.77,80.13,57.27 (d, J=30.7), 31.59,28.43,15.39.
19F NMR(376MHz,CDCl3) δ=- 112.60 (s, 1F)
HRMS(ESI)calcd for C18H21FN2O2Na+[(M+Na)+]339.1479,found 339.1482.。
Embodiment 12: the synthesis of monofluoroethylene derivative 3al
The same 3aa of method, 57 milligrams of white solid, yield 86%.
1H NMR(400MHz,CDCl3) δ=7.60-7.48 (m, 4H), 5.78 (d, J=38.4,1H), 4.82 (s, 1H), 2.11–2.00(m,4H),1.79(s,4H),1.41(s,9H).
13C NMR(100MHz,CDCl3) δ=163.64 (d, J=275.7), 154.45,138.36 (d, J=2.1), 132.19,129.11 (d, J=8.0), 119.08110.12,103.85 (d, J=8.5), 79.97,64.58 (d, J=27.5), 36.95,28.42,23.48.
19F NMR(376MHz,CDCl3) δ=- 108.62 (s, 1F)
HRMS(ESI)calcd for C19H23FN2O2Na+[(M+Na)+]353.1636,found 353.1644.。
Embodiment 13: the synthesis of monofluoroethylene derivative 3am
The same 3aa of method, 53.6 milligrams of white solid, yield 88%.
1H NMR(400MHz,CDCl3) δ=7.62-7.50 (m, 4H), 5.76 (d, J=38.5,1H), 4.79 (s, 1H), 1.53(s,6H),1.40(s,9H).
13C NMR(100MHz,CDCl3) δ=164.68 (d, J=276.0), 154.16,138.25 (d, J=2.3), 132.20,129.19 (d, J=8.2), 119.05,110.26 (d, J=2.8), 103.61 (d, J=8.2), 79.93,54.02 (d, J=26.1), 28.41,26.21.
19F NMR(376MHz,CDCl3) δ=- 110.05 (s, 1F)
HRMS(ESI)calcd for C17H21FN2O2Na+[(M+Na)+]327.1479,found 327.1490.。
Embodiment 14: the synthesis of monofluoroethylene derivative 3an
The same 3aa of method, 62.7 milligrams of white solid, yield 85%.
1H NMR(400MHz,CDCl3) δ=7.56 (d, J=8.1,2H), 7.48 (d, J=8.2,2H), 7.33-7.15 (m, 5H), 5.56 (d, J=38.3,1H), 4.90 (d, J=7.0,1H), 4.70-4.50 (m, 1H), 3.06-3.00 (m, 2H), 1.41(s,9H).
13C NMR(100MHz,CDCl3) δ=160.34 (d, J=273.8), 154.80,137.49 (d, J=2.2), (136.18,132.24,129.36,129.10 d, J=7.6), 128.68,127.09,118.91,110.59,106.22, 80.34,53.76 (d, J=26.3), 38.61,28.36.
19F NMR(376MHz,CDCl3) δ=- 111.66 (s, 1F)
HRMS(ESI)calcd for C22H23FN2O2Na+[(M+Na)+]389.1636,found 389.1637.。
Embodiment 15: the synthesis of monofluoroethylene derivative 3ao
The same 3aa of method, 54.7 milligrams of white solid, yield 82%.
1H NMR(400MHz,CDCl3) δ=7.61-7.52 (m, 4H), 5.56 (d, J=38.8,1H), 5.03 (s, 1H), 4.05 (d, J=13.8,1H), 2.90 (t, J=12.1,1H), 2.09 (d, J=13.5,1H), 1.73-1.61 (m, 3H), 1.52–1.38(m,11H).
13C NMR(100MHz,CDCl3) δ=161.33 (d, J=278.7), 155.12,137.89 (d, J=2.0), 132.29,129.02 (d, J=8.1), 118.96,110.43 (d, J=2.7), 105.78 (d, J=7.0), 80.41,51.75 (d, J=24.6), 40.73,28.45,26.08,25.10,19.94.
19F NMR(376MHz,CDCl3) δ=- 104.37 (s, 1F)
HRMS(ESI)calcd for C19H23FN2O2Na+[(M+Na)+]353.1636,found 353.1645.。
Embodiment 16: the synthesis of monofluoroethylene derivative 3ap
The same 3aa of method, 55 milligrams of white solid, yield 87%.
1H NMR(400MHz,CDCl3) δ=7.57 (d, J=8.5,2H), 7.52 (d, J=8.5,2H), 5.45 (d, J= 39.8,1H), 3.66 (s, 3H), 1.86 (dd, J=13.3,4.6,6H), 1.78 (dd, J=13.3,4.6,6H)
13C NMR(100MHz,CDCl3) δ=177.83,169.26 (d, J=272.7), 138.67 (d, J=2.0), 132.26,129.04 (d, J=8.3), 119.12), 110.03 (d, J=2.8), 102.67 (d, J=9.1), 51.92, 38.67,35.87 (d, J=23.1), 28.07 (d, J=1.9), 27.85.
19F NMR(376MHz,CDCl3) δ=- 103.71 (s, 1F)
HRMS(ESI)calcd for C19H21FNO2 +[(M+H)+]314.1551,found 314.1554.。
Embodiment 17: the synthesis of monofluoroethylene derivative 3aq
The same 3aa of method, 63.8 milligrams of white solid, yield 90%.
1H NMR(400MHz,CDCl3) δ=7.63-7.53 (m, 4H), 7.02 (d, J=7.5,1H), 6.66 (t, J= 10.0,1H), 6.64 (s, 1H), 5.61 (d, J=39.7,1H), 3.96 (t, J=5.8,2H), 2.31 (s, 3H), 2.20 (s, 3H),1.85–1.71(m,4H),1.27(s,6H).
13C NMR(100MHz,CDCl3) δ=169.41 (d, J=275.0), 157.02,138.72 (d, J=1.7), (136.58,132.23,130.45,129.04 d, J=8.3), 123.66,120.90,119.14,112.11,110.00 (d, J =2.6), 103.44 (d, J=9.1), 67.95,38.93 (d, J=22.5), 36.31,25.62 (d, J=3.3), 25.03, 21.47,15.85.
19F NMR(376MHz,CDCl3) δ=- 104.08 (s, 1F)
HRMS(ESI)calcd for C23H27FNO+[(M+H)+]352.2071,found 352.2074.。
Embodiment 18: the synthesis of monofluoroethylene derivative 3bc
The same 3aa of method, 57.7 milligrams of white solid, yield 83%.
1H NMR(400MHz,CDCl3) δ=7.97 (d, J=8.4,2H), 7.52 (d, J=8.4,2H), 5.57 (d, J= 40.9,1H),3.89(s,3H),3.52–3.39(m,4H),1.93–1.83(m,2H),1.56–1.47(m,2H),1.47(s, 9H),1.26(s,3H).
13C NMR(100MHz,CDCl3) δ=167.18 (d, J=272.0), 166.93,154.90,138.31 (d, J= 1.8), 129.82,128.50 (d, J=8.0), 128.39 (d, J=2.0), 104.44 (d, J=9.4), 79.67,52.12, 39.92,37.78 (d, J=22.7), 33.99,28.53,24.18.
19F NMR(376MHz,CDCl3) δ=- 107.57 (s, 1F)
HRMS(ESI)calcd for C21H28FN2O4Na+[(M+Na)+]400.1895,found 400.1906.。
Embodiment 19: the synthesis of monofluoroethylene derivative 3bu
The same 3aa of method, 38 milligrams of white solid, yield 80%.
1H NMR(400MHz,CDCl3) δ=7.97 (d, J=8.0,2H), 7.54 (d, J=8.0,2H), 5.58 (d, J= 40.1,1H),3.90(s,3H),1.23(s,9H).
13C NMR(100MHz,CDCl3) δ=169.96 (d, J=273.5), 167.10,138.96 (d, J=2.0), 129.80,128.44 (d, J=8.0), 128.09 (d, J=2.3), 102.05 (d, J=9.4), 52.11,35.79 (d, J= 23.5), 27.50 (d, J=2.7)
19F NMR(376MHz,CDCl3) δ=- 105.38 (s, 1F)
HRMS(ESI)calcd for C14H18FO2 +[(M+H)+]237.1285,found 237.1287.。
Embodiment 20: the synthesis of monofluoroethylene derivative 3cc
The same 3aa of method, 54.4 milligrams of colourless liquid, yield 46%.
1H NMR(400MHz,CDCl3) δ=7.86 (d, J=9.2,2H), 7.76 (d, J=8.2,2H), 7.64 (s, 1H), 7.43-7.36 (m, 2H), 7.22 (d, J=8.1,2H), 5.59 (d, J=41.0,1H), 3.46 (t, J=10.3,4H), 2.35 (d, J=17.0,3H), 1.97-1.84 (m, 2H), 1.59-1.50 (m, 2H), 1.46 (s, 9H), 1.28 (s, 3H)
13C NMR(100MHz,CDCl3) δ=167.02 (d, J=269.8), 154.92,145.36135.09,133.23, (131.54,130.12,127.79,126.96,125.97 d, J=14.8), 122.04,116.90,115.18,114.04, (94.11 d, J=14.3), 79.71,40.03,37.55 (d, J=22.2), 34.0028.56,24.15,21.68.
19F NMR(376MHz,CDCl3) δ=- 102.44 (s, 1F)
HRMS(ESI)calcd for C28H32BrFN2O4SNa+[(M+Na)+]613.1142,found 613.1125.。
Embodiment 21: the synthesis of monofluoroethylene derivative 3dc
The same 3aa of method, 56.8 milligrams of white solid, yield 75%.
1H NMR(400MHz,CDCl3) δ=7.79 (d, J=7.5,1H), 7.71 (d, J=7.2,1H), 7.30 (tt, J= ), 8.3,3.6,2H 7.23 (s, 1H), 5.93 (d, J=40.1,1H), 3.48 (d, J=3.8,4H), 1.98-1.85 (m, 2H), 1.58–1.51(m,2H),1.47(s,9H),1.29(s,3H).
13C NMR(100MHz,CDCl3) δ=165.82 (d, J=271.6), 154.91,140.09 (d, J=8.1), 139.35,136.18 (d, J=3.2), 124.40,124.35,123.27 (d, J=1.5), 122.83 (d, J=4.0), 122.08,100.35 (d, J=13.0), 79.69,40.01,37.49 (d, J=22.0), 33.95,28.56,24.16.
19F NMR(376MHz,CDCl3) δ=- 106.04 (s, 1F)
HRMS(ESI)calcd for C21H26FNO2SNa+[(M+Na)+]398.1561,found 398.1564.。
Embodiment 22: the synthesis of monofluoroethylene derivative 3dr
The same 3aa of method, 30.7 milligrams of white solid, yield 46%.
1H NMR(400MHz,CDCl3) δ=7.80 (d, J=7.3,1H), 7.72 (d, J=7.0,1H), 7.36-7.27 (m, 2H), 7.25 (s, 1H), 6.00 (d, J=37.3,1H), 4.13 (p, J=8.5,4H), 3.46 (qd, J=15.0,7.5, 1H),1.46(s,9H).
13C NMR(100MHz,CDCl3) δ=158.39 (d, J=265.9), 156.26,140.29 (d, J=7.5), 139.30,135.31 (d, J=4.5), 124.65,124.54,123.49 (d, J=1.3), 123.41 (d, J=4.3), 122.17,102.70 (d, J=12.2), 80.01,52.17,31.39 (d, J=28.2), 28.51.
19F NMR(376MHz,CDCl3) δ=- 108.86 (s, 1F)
HRMS(ESI)calcd for C18H20FNO2SNa+[(M+Na)+]356.1091,found 356.1103.。
Embodiment 23: the synthesis of monofluoroethylene derivative 3bu
The same 3aa of method, 38 milligrams of white solid, yield 77%.
1H NMR(400MHz,CDCl3) δ=7.80 (d, J=7.7,1H), 7.71 (d, J=7.6,1H), 7.36-7.27 (m, 2H), 7.22 (s, 1H), 5.96 (d, J=38.1,1H), 5.75 (s, 2H), 3.30-3.12 (m, 1H), 2.62 (ddd, J= 22.5,14.7,8.5,4H).
13C NMR(100MHz,CDCl3) δ=163.63 (d, J=268.6), 140.08 (d, J=7.7), 139.52, 136.50 (d, J=3.9), 129.50,124.37,124.22,123.23 (d, J=1.5), 122.28 (d, J=4.1), 122.12,100.08 (d, J=12.8), 40.71 (d, J=24.8), 36.72 (d, J=1.9)
19F NMR(376MHz,CDCl3) δ=- 102.02 (s, 1F)
HRMS(ESI)calcd for C15H14FS+[(M+H)+]245.0795,found 245.0793.。
Embodiment 24: the synthesis of monofluoroethylene derivative 3dt
The same 3aa of method, 32 milligrams of colourless liquid, yield 54%.
1H NMR(400MHz,CDCl3) δ=7.75 (d, J=7.5,1H), 7.63 (d, J=7.2,1H), 7.42 (d, J= 7.2,2H), 7.39-7.21 (m, 5H), 7.05 (s, 1H), 5.62 (d, J=37.7,1H), 1.50 (q, J=4.4,2H), 1.19 (s,2H).
13C NMR(100MHz,CDCl3) δ=163.35 (d, J=267.1), 140.68 (d, J=3.7), 140.02 (d, J =7.9), 139.48,136.66 (d, J=4.7), 130.17,128.75,127.55,124.33,124.15,123.18 (d, J =1.5), 122.13,122.08,101.63 (d, J=14.2), 28.04 (d, J=26.9), 13.70 (d, J=2.5)
19F NMR(376MHz,CDCl3) δ=- 106.29 (s, 1F)
HRMS(ESI)calcd for C19H16FS+[(M+H)+]295.0951,found 295.0953.。
Embodiment 25: the synthesis of monofluoroethylene derivative 3dp
The same 3aa of method, 55.9 milligrams of white solid, yield 81%.
1H NMR(400MHz,CDCl3) δ=7.77 (d, J=7.6,1H), 7.68 (d, J=7.6,1H), 7.34-7.23 (m, 2H), 7.19 (s, 1H), 5.81 (d, J=39.6,1H), 3.66 (s, 3H), 1.90-1.74 (m, 12H)
13C NMR(100MHz,CDCl3) δ=177.90166.90 (d, J=269.5), 140.03 (d, J=8.0), 139.43,136.51 (d, J=3.4), 124.34,124.21,123.18,122.52 (d, J=4.1), 122.06,98.90 (d, ), J=12.8 51.86,38.67,35.38 (d, J=22.7), 28.04 (d, J=1.5), 27.86.
19F NMR(376MHz,CDCl3) δ=- 104.00 (s, 1F)
HRMS(ESI)calcd for C20H22FO2S+[(M+H)+]345.1319,found 345.1316.。
Embodiment 26: the synthesis of monofluoroethylene derivative 3ep
The same 3aa of method, 61.8 milligrams of white solid, yield 80%.
1H NMR(400MHz,CDCl3) δ=7.91 (dd, J=6.7,2.4,1H), 7.30-7.24 (m, 1H), 6.90 (dd, ), J=9.9,8.9,1H 5.62 (d, J=40.0,1H), 3.67 (s, 3H), 1.86 (dd, J=12.9,4.3,6H), 1.79 (dd, J=12.9,4.3,6H)
13C NMR(100MHz,CDCl3) δ=177.91,168.80 (dd, J=271.2,2.2), 158.54 (d, J= 248.6), 132.74 (dd, J=14.8,2.9), 130.95 (d, J=7.2), 123.75 (d, J=13.5), 116.75 (d, J= 3.4), 116.75 (d, J=3.4), 94.35-94.08 (m), 51.90,38.69,35.90 (d, J=23.2), 28.04 (d, J= 1.9),27.87
19F NMR(376MHz,CDCl3) δ=- 105.42 (d, J=3.8,1F), -119.31 (t, J=7.0,1F)
HRMS(ESI)calcd for C18H20BrF2O2 +[(M+H)+]385.0609,found 385.0606.。
Embodiment 27: the synthesis of monofluoroethylene derivative 3fp
The same 3aa of method, 67 milligrams of white solid, yield 72%.
1H NMR(400MHz,CDCl3) δ=7.70 (d, J=1.7,1H), 7.35 (dd, J=8.6,1.9,1H), 6.85 (d, J=8.6,1H), 5.32 (d, J=40.0,1H), 4.38 (q, J=8.1,2H), 3.66 (s, 3H), 1.88-1.81 (m, 6H),1.79–1.72(m,6H).
13C NMR(100MHz,CDCl3) δ=177.97,166.95 (d, J=267.8), 152.76 (d, J=2.6), 133.73 (d, J=8.5), 130.48,128.74 (d, J=7.8), 123.22 (q, J=278.5), 115.12,113.09, (101.63 d, J=9.8), 67.40 (q, J=35.8), 51.88,38.67,35.55 (d, J=23.5), 28.08 (d, J= 1.7),27.90.
19F NMR(376MHz,CDCl3) δ=- 73.86 (s, 3F), -109.05 (s, 1F)
HRMS(ESI)calcd for C20H22BrF4O3 +[(M+H)+]465.0683,found 465.0678.。
Embodiment 28: the synthesis of monofluoroethylene derivative 3gp
The same 3aa of method, 61.2 milligrams of white solid, yield 79%.
1H NMR(400MHz,CDCl3) δ=7.51 (d, J=7.9,1H), 7.22 (dd, J=13.8,7.9,1H), 6.96 (t, J=8.2,1H), 5.81 (d, J=39.2,1H), 3.67 (s, 3H), 1.91-1.76 (m, 12H)
13C NMR(100MHz,CDCl3) δ=177.94,168.20 (d, J=271.1), 159.27 (d, J=245.4), 135.63,128.09 (d, J=8.3), 125.79 (dd, J=12.3,3.2), 114.31 (d, J=23.6), 110.48 (d, J= 20.4), 101.79 (dd, J=8.3,3.7), 51.90,38.70,35.88 (d, J=23.4), 28.04 (d, J=1.6), 27.89.
19F NMR(376MHz,CDCl3) δ=- 103.95 (s, 1F), -108.23 (s, 1F)
HRMS(ESI)calcd for C18H20BrF2O2 +[(M+H)+]385.0609,found 385.0606.。
Embodiment 29: the synthesis of monofluoroethylene derivative 3hp
The same 3aa of method, 34.7 milligrams of white solid, yield 51%.
1H NMR(400MHz,CDCl3) δ=7.98 (d, J=7.9,1H), 7.89-7.82 (m, 1H), 7.76 (d, J= 8.2,1H), 7.70 (d, J=7.1,1H), 7.54-7.43 (m, 3H), 6.07 (d, J=38.5,1H), 3.70 (s, 3H), 1.91 (s,12H).
13C NMR(100MHz,CDCl3) δ=178.10,166.93 (d, J=265.8), 133.77,131.58, (129.97,128.71,127.47,127.31 d, J=7.8,2H), 126.00,125.63 (d, J=11.2), 124.19, 100.20 (d, J=12.0), 51.89,38.78,35.70 (d, J=24.0), 28.27 (d, J=1.7), 28.03.
19F NMR(376MHz,CDCl3) δ=- 110.92 (s, 1F)
HRMS(ESI)calcd for C22H24FO2 +[(M+H)+]339.1755,found 339.1753.。
Embodiment 30: the synthesis of monofluoroethylene derivative 3ip
The same 3aa of method, 55.8 milligrams of white solid, yield 80%.
1H NMR(400MHz,CDCl3) δ=7.36 (d, J=7.9,1H), 7.01 (t, J=8.0,1H), 6.78 (d, J= 8.0,1H), 5.83 (d, J=42.1,1H), 3.84 (s, 3H), 3.77 (s, 3H), 3.66 (s, 3H), 1.83 (dd, J=20.2, 8.9,12H).
13C NMR(100MHz,CDCl3) δ=178.10,167.06 (d, J=267.8), 152.69,146.34,128.06 (d, J=2.4), 123.98,121.76 (d, J=13.5), 111.00,96.96 (d, J=8.0), 60.79,55.87,51.83, 38.71,35.74 (d, J=24.0), 28.16,27.97.
19F NMR(376MHz,CDCl3) δ=- 109.49 (d, J=17.3,1F)
HRMS(ESI)calcd for C20H26FO4 +[(M+H)+]349.1810,found 349.1810.。
Embodiment 31: the synthesis of monofluoroethylene derivative 3jp
The same 3aa of method, 68.7 milligrams of white solid, yield 79%.
1H NMR(400MHz,CDCl3) δ=7.52 (d, J=8.2,2H), 7.47 (d, J=1.3,1H), 7.35 (d, J= 8.1,2H), 7.30-7.22 (m, 2H), 5.46 (d, J=40.9,1H), 3.67 (s, 3H), 1.83 (ddd, J=13.8,11.7, 5.0,12H).
13C NMR(100MHz,CDCl3) δ=177.99,167.12 (d, J=268.3), 138.87,136.62 (d, J= 2.2), 133.70,133.65 (d, J=1.7), 133.32,132.10,129.82,129.48,128.35 (d, J=7.7), 127.25,103.08 (d, J=9.5), 51.86,38.69,35.61 (d, J=23.6), 28.13 (d, J=1.5), 27.95.
19F NMR(376MHz,CDCl3) δ=- 108.20 (s, 1F)
HRMS(ESI)calcd for C24H24Cl2FO2 +[(M+H)+]433.1132,found 433.1128.。
Embodiment 32: the synthesis of monofluoroethylene derivative 3gq
The same 3aa of method, 53.5 milligrams of white solid, yield 63%.
1H NMR(400MHz,CDCl3) δ=7.51 (d, J=7.9,1H), 7.22 (dd, J=13.7,8.1,1H), 6.98 (dd, J=14.7,7.7,2H), 6.65 (d, J=7.5,1H), 6.61 (s, 1H), 5.93 (d, J=38.9,1H), 3.94 (t, J =6.0,2H), 2.29 (s, 3H), 2.18 (s, 3H), 1.87-1.77 (m, 2H), 1.72 (dt, J=8.3,5.6,2H), 1.27 (s,6H).
13C NMR(100MHz,CDCl3) δ=177.19 (d, J=273.1), 168.29 (d, J=245.3), 166.07, (145.55,144.83,139.42,137.07 d, J=8.3), 134.82 (dd, J=11.8,3.2), 132.73,129.83, 123.29 (d, J=22.7), 121.12,119.48 (d, J=20.3), 111.71 (dd, J=8.6,3.6), 77.06,47.91 (d, J=22.8), 45.31,34.61 (d, J=3.3), 34.02,30.48,24.86.
19F NMR(376MHz,CDCl3) δ=- 104.06 (s, 1F), -108.91 (s, 1F)
HRMS(ESI)calcd for C22H26BrF2O+[(M+H)+]423.1130,found 423.1130.。
Embodiment 33: the synthesis of monofluoroethylene derivative 3kq
The same 3aa of method, 50 milligrams of colourless liquid, yield 54%.
1H NMR(400MHz,CDCl3) δ=8.08 (s, 1H), 7.97 (d, J=8.4,1H), 7.67 (q, J=8.6,5H), 7.51 (d, J=5.4,1H), 7.43 (d, J=5.4,1H), 7.07 (d, J=7.4,1H), 6.72 (d, J=7.4,1H), 6.67 (s, 1H), 5.66 (d, J=41.0,1H), 3.99 (t, J=6.0,2H), 2.36 (s, 3H), 2.26 (s, 3H), 1.87 (dt, J= 8.5,5.8,2H),1.81–1.74(m,2H),1.32(s,6H).
13C NMR(100MHz,CDCl3) δ=166.84 (d, J=269.9), 157.14,140.36,139.59, (138.87,137.40,136.57,133.01,130.43,129.10 d, J=7.7), 127.40,127.13,124.21, (123.81,123.72,122.83,121.86,120.81,112.12,104.01 d, J=9.6), 68.15,38.72 (d, J= 23.1), 36.44,25.83 (d, J=3.0), 25.11,21.53,15.94.
19F NMR(376MHz,CDCl3) δ=- 109.21 (s, 1F)
HRMS(ESI)calcd for C30H31FOSNa+[(M+Na)+]481.1972,found 481.1975.。
Embodiment 34: the synthesis of monofluoroethylene derivative 3jq
The same 3aa of method, 52 milligrams of colourless liquid, yield 55%.
1H NMR(400MHz,CDCl3) δ=7.56 (d, J=8.2,2H), 7.47 (d, J=1.2,1H), 7.37 (d, J= 8.1,2H), 7.30-7.23 (m, 2H), 7.00 (d, J=7.4,1H), 6.65 (d, J=7.5,1H), 6.60 (s, 1H), 5.59 (d, J=40.8,1H), 3.93 (t, J=5.9,2H), 2.29 (s, 3H), 2.19 (s, 3H), 1.87-1.76 (m, 2H), 1.71 (dd, J=9.2,5.9,2H), 1.25 (s, 6H)
13C NMR(100MHz,CDCl3) δ=167.23 (d, J=270.6), 157.13,138.94,136.64 (d, J= 2.1), 136.58,133.77,133.73,133.37,132.14,130.44,129.86,129.51,128.40 (d, J= 7.8), 127.28,123.73,120.83,112.12103.96 (d, J=9.5), 68.13,38.75 (d, J=23.1), 36.42,25.82 (d, J=3.1), 25.11,21.53,15.92.
19F NMR(376MHz,CDCl3) δ=- 108.58 (s, 1F)
HRMS(ESI)calcd for C28H29Cl2FONa+[(M+Na)+]493.1472,found 493.1478.。
Embodiment 35: the synthesis of monofluoroethylene derivative 3lq
The same 3aa of method, 59.6 milligrams of yellow liquid, yield 70%.
1H NMR(400MHz,CDCl3) δ=8.69 (s, 1H), 8.00 (dd, J=7.9,6.0,3H), 7.65 (d, J= 8.4,1H), 7.17 (t, J=8.6,2H), 7.04 (d, J=7.4,1H), 6.69 (d, J=7.4,1H), 6.64 (s, 1H), 5.61 (d, J=40.8,1H), 3.97 (t, J=5.8,2H), 2.32 (s, 3H), 2.23 (s, 3H), 1.80 (dd, J=23.5,8.5, 4H),1.30(s,6H).
13C NMR(100MHz,CDCl3) δ=168.73 (d, J=271.8), 163.56 (d, J=248.3), 157.06, 154.20,149.51 (d, J=6.0), 136.55,136.13 (d, J=10.5), 135.37 (d, J=3.0), 130.43, 128.64 (d, J=8.3), 128.52,123.66,120.85,119.86,115.72 (d, J=21.6), 112.08,100.96 (d, J=10.3), 68.00,38.83 (d, J=22.7), 36.33,25.67 (d, J=3.0), 25.06,21.48,15.88.
19F NMR(376MHz,CDCl3) δ=- 106.24 (s, 1F), -113.09 (d, J=20.0,1F)
HRMS(ESI)calcd for C27H30F2NO+[(M+H)+]422.2290,found 422.2309.。
Embodiment 36: the synthesis of monofluoroethylene derivative 3mq
The same 3aa of method, 50 milligrams of colourless liquid, yield 60%.
1H NMR(400MHz,CDCl3) δ=8.75 (d, J=1.5,1H), 7.78 (dd, J=8.0,2.1,1H), 7.60 (d, J=8.3,2H), 7.54 (d, J=8.3,2H), 7.22 (d, J=8.0,1H), 7.02 (d, J=7.4,1H), 6.67 (d, J =7.4,1H), 6.62 (s, 1H), 5.61 (d, J=40.8,1H), 3.95 (t, J=5.9,2H), 2.61 (s, 3H), 2.30 (s, 3H), 2.20 (s, 3H), 1.86-1.78 (m, 2H), 1.73 (dd, J=9.1,5.8,2H), 1.27 (s, 6H)
13C NMR(100MHz,CDCl3) δ=167.17 (d, J=270.5), 157.25,157.13,147.48, 136.57,136.16 (d, J=2.0), 134.57,133.70,133.47,130.43,129.25 (d, J=7.8), 126.95, (123.72,123.26,120.83,112.13,103.86 d, J=9.6), 68.14,38.74 (d, J=23.1), 36.43, 25.79 (d, J=3.1), 25.10,24.21,21.50,15.89.
19F NMR(376MHz,CDCl3) δ=- 108.72 (s, 1F)
HRMS(ESI)calcd for C28H33FNO+[(M+H)+]418.2541,found 418.2552.。
Embodiment 37: the synthesis of monofluoroethylene derivative 3nq
The same 3aa of method, 46.5 milligrams of colourless liquid, yield 51%.
1H NMR(400MHz,CDCl3) δ=7.87 (d, J=7.9,1H), 7.68 (d, J=7.7,1H), 7.33 (t, J= 7.5,1H), 7.03 (d, J=7.4,1H), 6.93 (dd, J=11.0,4.1,1H), 6.68 (d, J=7.5,1H), 6.64 (s, 1H), 5.82 (d, J=39.0,1H), 3.97 (t, J=6.1,2H), 2.32 (s, 3H), 2.21 (s, 3H), 1.91-1.83 (m, 2H), 1.74 (dd, J=11.3,4.8,2H), 1.30 (s, 6H)
13C NMR(100MHz,CDCl3) δ=167.01 (d, J=271.3), 157.14,139.24,137.07, (136.57,130.43,130.06 d, J=10.1), 128.44,128.18,123.79,120.83,112.18,108.66 (d, J =9.3), 100.22,68.18,38.73 (d, J=23.0), 36.38,25.68 (d, J=3.2), 25.1121.54,15.94.
19F NMR(376MHz,CDCl3) δ=- 111.98 (s, 1F)
HRMS(ESI)calcd for C22H27FIO+[(M+H)+]453.1085,found 453.1077.。
Embodiment 38: the synthesis of monofluoroethylene derivative 3lm
The same 3aa of method, 63.8 milligrams of white solid, yield 85%.
1H NMR(400MHz,CDCl3) δ=8.65 (d, J=1.1,1H), 8.02-7.90 (m, 3H), 7.62 (d, J= 8.3,1H), 7.13 (t, J=8.6,2H), 5.77 (d, J=39.5,1H), 4.82 (s, 1H), 1.56 (s, 6H), 1.42 (s, 9H).
13C NMR(100MHz,CDCl3) δ=164.27 (d, J=273.7), 163.73 (d, J=219.1), 154.48 (d, J=2.6), 154.26,149.69 (d, J=6.2), 136.28 (d, J=10.0), 135.32 (d, J=3.0), 128.66 (d, J=8.3), 128.07 (d, J=2.5), 119.83,115.73 (d, J=21.6), 101.32 (d, J=9.6), 79.92, 54.07 (d, J=26.1), 28.45,26.26.
19F NMR(376MHz,CDCl3) δ=- 113.08 (s, 1F)
HRMS(ESI)calcd for C21H25F2N2O2 +[(M+H)+]375.1879,found 375.1895.。
Embodiment 39: the synthesis of monofluoroethylene derivative 3mm
The same 3aa of method, 51.6 milligrams of white solid, yield 69%.
1H NMR(400MHz,CDCl3) δ=8.72 (d, J=1.8,1H), 7.76 (dd, J=8.0,2.3,1H), 7.57 (d, J=8.3,2H), 7.51 (d, J=8.3,2H), 7.19 (d, J=8.0,1H), 5.78 (d, J=39.6,1H), 4.81 (s, 1H), 2.56 (d, J=11.4,3H), 1.55 (s, 6H), 1.42 (s, 9H)
13C NMR(100MHz,CDCl3) δ=162.49 (d, J=271.3), 157.23,154.33,147.40,136.37 (d, J=2.1), 134.56,133.37,133.15 (d, J=2.1), 129.41 (d, J=7.6), 126.88,123.24, 104.14 (d, J=8.9), 79.73,54.11 (d, J=26.3), 28.45,26.26,24.15.
19F NMR(376MHz,CDCl3) δ=- 114.68 (s, 1F)
HRMS(ESI)calcd for C22H28FN2O2 +[(M+H)+]371.2129,found 371.2145.。
Embodiment 40: the synthesis of monofluoroethylene derivative 3ol
The same 3aa of method, 50 milligrams of white solid, yield 64%.
1H NMR(400MHz,CDCl3) δ=7.11 (s, 1H), 6.94 (s, 1H), 5.98 (d, J=38.0,1H), 4.75 (s, 1H), 2.04 (d, J=2.7,4H), 1.77 (d, J=4.7,4H), 1.42 (s, 9H)
13C NMR(100MHz,CDCl3) δ=162.52 (d, J=269.7), 154.45,137.20 (d, J=3.0), 128.63,122.42 (d, J=9.6), 109.73,99.15 (d, J=12.8), 80.01,64.20 (d, J=26.3), 36.90, 28.48,23.44
19F NMR(376MHz,CDCl3) δ=- 108.36 (s, 1F)
HRMS(ESI)calcd for C16H21BrFNO2SNa+[(M+Na)+]412.0353,found 412.0363.。
Embodiment 41: the synthesis of monofluoroethylene derivative 3dv
The same 3aa of method, 22.3 milligrams of white solid, yield 45%.
1H NMR(400MHz,CDCl3) δ=7.78 (d, J=7.5,1H), 7.70 (d, J=7.6,1H), 7.35-7.26 (m, 2H), 7.20 (s, 1H), 5.93 (d, J=38.0,1H), 2.82-2.74 (m, 2H), 2.73-2.61 (m, 2H), 2.20 (s, 3H).
13C NMR(100MHz,CDCl3) δ=206.37,159.94 (d, J=267.5), 140.10 (d, J=7.5), 139.40,135.96 (d, J=4.0), 124.43,124.37,123.34,122.60 (d, J=4.1), 122.12,102.00 (d, J=11.8), 39.91,30.10,26.81 (d, J=26.2)
19F NMR(376MHz,CDCl3) δ=- 97.72 (s, 1F)
HRMS(ESI)calcd for C14H14FOS+[(M+H)+]249.0744,found 249.0746.。
Embodiment 42: the synthesis of monofluoroethylene derivative 3dw
The same 3aa of method, 17.7 milligrams of white solid, yield 30%.
1H NMR(400MHz,CDCl3) δ=7.80 (d, J=7.4,1H), 7.71 (d, J=7.5,1H), 7.37-7.27 (m, 2H), 7.21 (s, 1H), 7.16 (d, J=4.7,1H), 6.97-6.93 (m, 1H), 6.87 (s, 1H), 5.90 (d, J= 38.0,1H), 3.18 (t, J=7.6,2H), 2.82-2.69 (m, 2H)
13C NMR(100MHz,CDCl3) δ=159.84 (d, J=268.2), 142.85,140.15 (d, J=7.7), (139.48,136.07 d, J=4.0), 127.05,125.00,124.43,124.36,123.73,123.32,122.57 (d, J =4.2), 122.14,102.28 (d, J=11.6), 35.04 (d, J=25.6), 26.88.
19F NMR(376MHz,CDCl3) δ=- 97.49 (s, 1F)
HRMS(ESI)calcd for C16H14FS2 +[(M+H)+]289.0515,found 289.0514.。
Embodiment 43: the synthesis of monofluoroethylene derivative 3ea
The same 3aa of method, 430 milligrams of colourless liquid, yield 53%.
1H NMR(400MHz,CDCl3) δ=7.92 (d, J=4.9,1H), 7.27 (s, 1H), 6.91 (t, J=9.1,1H), 5.67 (d, J=39.3,1H), 4.21 (s, 2H), 2.76 (s, 2H), 2.43 (d, J=12.1,1H), 1.90 (d, J=11.9, 2H),1.64–1.40(m,9H).
13C NMR(100MHz,CDCl3) δ=165.38 (dd, J=271.1,2.2), 158.48 (d, J=248.8), 154.79,132.73 (dd, J=14.2,2.9), 131.19 (d, J=8.5), 123.40 (dd, J=13.6,2.1), 117.02, (116.80 d, J=3.7), 95.40 (t, J=7.3), 79.81,43.46,40.11 (d, J=25.1), 28.99,28.57.
19F NMR(376MHz,CDCl3) δ=- 102.41 (s, 1F), -119.34 (s, 1F)
HRMS(ESI)calcd for C18H22BrF2NO2Na+[(M+Na)+]424.0694,found 424.0705.。
Embodiment 44: the synthesis of monofluoroethylene derivative 3ax
The same 3aa of method, 58 milligrams of white solid, yield 80%.
1H NMR(400MHz,CDCl3) δ=7.56 (dd, J=15.9,7.7,4H), 5.48 (d, J=39.8,1H), 2.51–2.18(m,8H),1.85(s,4H),1.79–1.61(m,2H).
13C NMR(100MHz,CDCl3) δ=168.07 (d, J=273.8), 138.40 (d, J=2.0), 132.27, 129.13 (d, J=8.3), 119.05,110.22 (d, J=2.7), 102.44 (d, J=8.8), 63.31,50.13 (d, J= 2.1), 48.20,41.98 (d, J=23.4), 37.46 (d, J=1.9), 34.58,31.70.
19F NMR(376MHz,CDCl3) δ=- 108.66 (s, 1F)
HRMS(ESI)calcd for C19H20BrFN+[(M+H)+]360.0758,found 360.0750.。
Embodiment 45: the synthesis of monofluoroethylene derivative 3dy
The same 3aa of method, 34.8 milligrams of white solid, yield 53%.
1H NMR(400MHz,CDCl3) δ=7.79 (d, J=7.6,1H), 7.71 (d, J=7.4,1H), 7.37-7.27 (m, 2H), 7.21 (s, 1H), 5.88 (d, J=38.1,1H), 3.43 (t, J=6.7,2H), 2.40 (dt, J=17.8,7.3, 2H), 1.91 (dt, J=14.1,6.9,2H), 1.66 (dt, J=14.6,7.2,2H), 1.59-1.50 (m, 2H)
13C NMR(100MHz,CDCl3) δ=161.21 (d, J=268.6), 140.03 (d, J=7.6), 139.48, 136.30 (d, J=3.9), 124.40,124.27,123.25 (d, J=1.4), 122.23 (d, J=4.2), 122.11, 101.42 (d, J=12.0), 33.56,32.56,32.51 (d, J=25.0), 27.60,25.52.
19F NMR(376MHz,CDCl3) δ=- 95.85 (s, 1F)
HRMS(ESI)calcd for C15H17BrFS+[(M+H)+]327.0213,found 327.0207.。

Claims (11)

1. a kind of method prepared containing single fluoroalkyl vinyl hydrocarbon compound, characterized in that following reaction formula is pressed, together with-two fluoroolefins It is raw material with carboxylic acid reactive's ester, in dry organic solvent and inert gas conditions, under the action of zinc simple substance, defluorinate is generated Single fluoroalkyl alkene；
Wherein,
Part A is phenyl that is unsubstituted or optionally replacing, unsubstituted or optional substituted indyl, unsubstituted or optional substituted It is benzothienyl, unsubstituted or optional substituted naphthalene, unsubstituted or optional substituted pyridyl group, unsubstituted or optional substituted Thienyl, unsubstituted or optional substituted furyl；Quinolyl that is unsubstituted or optionally replacing；It is unsubstituted or optionally replace different Quinolyl；Thiazolyl that is unsubstituted or optionally replacing；Pyrazolyl that is unsubstituted or optionally replacing；Or it is unsubstituted or optionally replace Imidazole radicals；
Part B is selected from the cyclic alkyl or bridged cyclic group that C atomicity that is unsubstituted or optionally replacing is 3-10；It is unsubstituted or optional Substituted C atomicity is the cycloalkenyl of 3-10；It is unsubstituted or optionally replace-seven yuan of saturation nitrogen heterocycles of quaternary, containing oxa- Ring group；The alkyl or alkenyl that C atomicity that is unsubstituted or optionally replacing is 1-10；
In products therefrom fluoroolefin and the carbon atom of part B be connected.
2. the method as described in claim 1, characterized in that the substituent group in wherein optionally replacing described in part A is selected from cyanogen Base, methoxycarbonyl group, dichlorophenyl, halogen, C1-6Alkoxy, benzothienyl, picolyl, trifluoro ethoxy, C1-6Alkyl Or p-fluorophenyl；The halogen is fluorine, chlorine, bromine, iodine.
3. the method as described in claim 1, characterized in that the substituent group in wherein optionally replacing described in part B is selected from halogen Element, C1-6Alkyl, C1-6Alkoxy, t-butoxycarbonyl amino, phenyl, methoxycarbonyl, phenoxy group, the thiophene that dimethyl is replaced Base or acetyl group；The halogen is fluorine, chlorine, bromine, iodine.
4. method a method according to any one of claims 1-3, characterized in that the carbon atom being wherein connected in part B with fluoroolefin Optionally replaced by methyl, t-butoxycarbonyl amino or phenyl.
5. method according to claim 2, characterized in that wherein part A is selected from:
6. method as claimed in claim 3, characterized in that wherein part B is selected from:
7. the method as described in claim 1, characterized in that the rubbing together with-two fluoroolefins, carboxylic acid reactive's ester and zinc simple substance You are than being 1:2-4:2-4.
8. the method for claim 7, characterized in that the rubbing together with-two fluoroolefins, carboxylic acid reactive's ester and zinc simple substance You are than being 1:3:3.
9. the method as described in claim 1, characterized in that reaction temperature is 0-60 DEG C；Reaction time is 2-72 hours.
10. method as claimed in claim 9, characterized in that the reaction temperature is 20-30 DEG C；Reaction time is 24-48 Hour.
11. the method as described in claim 1, characterized in that the organic solvent be selected from N, N '-dimethyl acetamide, N, The mixed solvent of one of N '-dimethyl formamide, dimethyl sulfoxide and N-Methyl pyrrolidone or multi-solvents.
CN201810248047.8A 2018-03-24 2018-03-24 A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound Pending CN110294704A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810248047.8A CN110294704A (en) 2018-03-24 2018-03-24 A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810248047.8A CN110294704A (en) 2018-03-24 2018-03-24 A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound

Publications (1)

Publication Number Publication Date
CN110294704A true CN110294704A (en) 2019-10-01

Family

ID=68026087

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810248047.8A Pending CN110294704A (en) 2018-03-24 2018-03-24 A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound

Country Status (1)

Country Link
CN (1) CN110294704A (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110627718A (en) * 2019-10-28 2019-12-31 安阳师范学院 Synthesis method of (E) -beta-monofluoroalkyl-beta, gamma-unsaturated amide
CN113683481A (en) * 2021-07-09 2021-11-23 南昌大学 Substituted monofluoroallene compound, preparation method and application thereof
CN114605361A (en) * 2022-04-14 2022-06-10 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethylbutenolide compound
CN114634471A (en) * 2022-04-14 2022-06-17 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethyl exocyclic double bond butyrolactone compound
CN114957170A (en) * 2022-04-12 2022-08-30 滁州学院 Direct monofluoroolefination reaction of ether compound ortho-position carbon-hydrogen bond
CN115850111A (en) * 2023-01-03 2023-03-28 天津师范大学 Preparation method of nickel-catalyzed aliphatic amine containing gem-difluoroolefin structure

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1280978A (en) * 1994-06-09 2001-01-24 大金工业株式会社 Fluorine containing olefine
CN101801894A (en) * 2007-07-13 2010-08-11 苏威氟有限公司 Prepare halogen-containing and alkene hydrogen by metal fluoride catalysts
CN102770400A (en) * 2010-02-12 2012-11-07 大金工业株式会社 Process for producing fluorine-containing alkene compound
CN102781893A (en) * 2010-03-03 2012-11-14 大金工业株式会社 Method for producing substituted fluorine-containing olefin
CN104292165A (en) * 2014-04-04 2015-01-21 华东理工大学 Olefine compound containing fluorine and nitrogen heterocycle, and preparation method and application thereof
WO2016140201A1 (en) * 2015-03-03 2016-09-09 旭硝子株式会社 Method for manufacturing substrate into which organic group including fluorine atom and carbon-carbon double bond is introduced

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1280978A (en) * 1994-06-09 2001-01-24 大金工业株式会社 Fluorine containing olefine
CN101801894A (en) * 2007-07-13 2010-08-11 苏威氟有限公司 Prepare halogen-containing and alkene hydrogen by metal fluoride catalysts
CN102770400A (en) * 2010-02-12 2012-11-07 大金工业株式会社 Process for producing fluorine-containing alkene compound
CN102781893A (en) * 2010-03-03 2012-11-14 大金工业株式会社 Method for producing substituted fluorine-containing olefin
CN104292165A (en) * 2014-04-04 2015-01-21 华东理工大学 Olefine compound containing fluorine and nitrogen heterocycle, and preparation method and application thereof
WO2016140201A1 (en) * 2015-03-03 2016-09-09 旭硝子株式会社 Method for manufacturing substrate into which organic group including fluorine atom and carbon-carbon double bond is introduced

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110627718A (en) * 2019-10-28 2019-12-31 安阳师范学院 Synthesis method of (E) -beta-monofluoroalkyl-beta, gamma-unsaturated amide
CN110627718B (en) * 2019-10-28 2022-10-04 安阳师范学院 Synthesis method of (E) -beta-monofluoroalkyl-beta, gamma-unsaturated amide
CN113683481A (en) * 2021-07-09 2021-11-23 南昌大学 Substituted monofluoroallene compound, preparation method and application thereof
CN114957170A (en) * 2022-04-12 2022-08-30 滁州学院 Direct monofluoroolefination reaction of ether compound ortho-position carbon-hydrogen bond
CN114605361A (en) * 2022-04-14 2022-06-10 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethylbutenolide compound
CN114634471A (en) * 2022-04-14 2022-06-17 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethyl exocyclic double bond butyrolactone compound
CN114634471B (en) * 2022-04-14 2023-05-19 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethyl exocyclic double bond butyrolactone compound
CN114605361B (en) * 2022-04-14 2023-05-19 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethyl butenolide compound
CN115850111A (en) * 2023-01-03 2023-03-28 天津师范大学 Preparation method of nickel-catalyzed aliphatic amine containing gem-difluoroolefin structure

Similar Documents

Publication Publication Date Title
CN110294704A (en) A method of it prepares containing single fluoroalkyl vinyl hydrocarbon compound
Saito et al. New chiral diphosphine ligands designed to have a narrow dihedral angle in the biaryl backbone
Su et al. Nickel-catalyzed monofluoromethylation of aryl boronic acids
Yoshimura et al. Hypoiodite‐Mediated Metal‐Free Catalytic Aziridination of Alkenes
Wienand et al. Reactions of Fischer carbene complexes with electron-deficient olefins: scope and limitations of this route to donor-acceptor-substituted cyclopropanes
CN103113308B (en) Method for preparing dihydropyrimidinone derivative
Yan et al. Synthesis of new chiral ferrocenyl P, N-ligands with a benzoxazole ring and their application in Ag-catalyzed asymmetric [3+ 2] cycloaddition
CN109081807B (en) Method for preparing tri-substituted 4-aminocarbazole and di-substituted 1-aminodibenzo [ b, d ] thiophene compounds
CN105801575A (en) Synthetic method of imidazo[1,2-a]pyridine
Srivastav et al. Carbastannatranes: a powerful coupling mediators in Stille coupling
CN108164501A (en) A kind of method of organic catalyst catalysis of carbonyl sulphur Synthesis pentatomic sulphur heterocyclic compound
CN104592313B (en) Difunctional hydrogen bond organic catalyst based on ferrocene and its preparation method and application
CN104098607A (en) Complex and application of monophosphine monoazacyclo-carben nickel containing tricyclic hexyl phosphine
CN103058806B (en) A method for preparing beta-enaminones based on ketones and aromatic nitriles
CN107746392A (en) A kind of preparation method of the oxazole alkyl compound containing caged scaffold
CN113045530B (en) Method for preparing naphthopyran compounds by ruthenium catalysis
CN103467390B (en) Method for preparing 2-amino-4(3H)-quinazolinones
CN105237432B (en) The synthetic method of N, N di-2-ethylhexylphosphine oxide benzamide compound
CN107674034A (en) The new method of polyacid phase transfer catalysis (PTC) arylamine, ketone synthesizing heterocyclic aromatic compound
CN1629170A (en) Oxazolinyl ring metal catalyst with chiral center, synthesis and use thereof
CN104341459A (en) N-(4-ferrocenylphenyl)amide compounds, and synthesis method thereof application thereof
CN105622544B (en) A kind of synthetic method of N- sulfonyls -3,4- dihydro -2H-1,4- thiazines
CN104910090B (en) Dihydro-isoxazole class compound and its synthetic method
CN113651720B (en) Substituted alkenyl thiocyanate compound and preparation method thereof
US11891409B2 (en) Trifluoromethyl alkenylphosphonate and preparation method therefor

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination