CN110818651A - Method for synthesizing alkenyl trifluoromethyl oxazolidine compound from alkynylamide - Google Patents
Method for synthesizing alkenyl trifluoromethyl oxazolidine compound from alkynylamide Download PDFInfo
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- CN110818651A CN110818651A CN201911130550.4A CN201911130550A CN110818651A CN 110818651 A CN110818651 A CN 110818651A CN 201911130550 A CN201911130550 A CN 201911130550A CN 110818651 A CN110818651 A CN 110818651A
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- trifluoromethyl
- oxazolidine
- silver
- alkynylamide
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- -1 alkenyl trifluoromethyl oxazolidine compound Chemical class 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 25
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 claims abstract description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 6
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000001953 recrystallisation Methods 0.000 claims abstract description 4
- 238000000746 purification Methods 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 239000007810 chemical reaction solvent Substances 0.000 claims description 15
- 239000003208 petroleum Substances 0.000 claims description 11
- 229940096017 silver fluoride Drugs 0.000 claims description 11
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 6
- 239000003480 eluent Substances 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- DUVJRPDWSFYUOD-UHFFFAOYSA-N 3-hex-1-ynyl-1,3-oxazolidin-2-one Chemical compound CCCCC#CN1CCOC1=O DUVJRPDWSFYUOD-UHFFFAOYSA-N 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- MBLWAEXRFFPBHD-UHFFFAOYSA-N 3-(2-cyclopropylethynyl)-1,3-oxazolidin-2-one Chemical compound C1(CC1)C#CN1C(OCC1)=O MBLWAEXRFFPBHD-UHFFFAOYSA-N 0.000 claims description 2
- GBUSLWYYBBBMGC-UHFFFAOYSA-N 3-(2-phenylethynyl)-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C#CC1=CC=CC=C1 GBUSLWYYBBBMGC-UHFFFAOYSA-N 0.000 claims description 2
- ODFSHDNJZJJGEC-UHFFFAOYSA-N 3-(2-thiophen-2-ylethynyl)-1,3-oxazolidin-2-one Chemical compound S1C(=CC=C1)C#CN1C(OCC1)=O ODFSHDNJZJJGEC-UHFFFAOYSA-N 0.000 claims description 2
- 229910021607 Silver chloride Inorganic materials 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 238000002156 mixing 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
- 229940071536 silver acetate Drugs 0.000 claims description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- 229910001923 silver oxide Inorganic materials 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
- HSYLTRBDKXZSGS-UHFFFAOYSA-N silver;bis(trifluoromethylsulfonyl)azanide Chemical compound [Ag+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F HSYLTRBDKXZSGS-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 4
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 7
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 230000035484 reaction time Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000006692 trifluoromethylation reaction Methods 0.000 description 4
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- VPAYJEUHKVESSD-UHFFFAOYSA-N trifluoroiodomethane Chemical compound FC(F)(F)I VPAYJEUHKVESSD-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- DOIVPHUVGVJOMX-UHFFFAOYSA-N 1,10-phenanthroline;ruthenium Chemical compound [Ru].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 DOIVPHUVGVJOMX-UHFFFAOYSA-N 0.000 description 1
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 1
- OFIDJMJLBNOBIL-UHFFFAOYSA-N 2-silylethynylsilane Chemical group [SiH3]C#C[SiH3] OFIDJMJLBNOBIL-UHFFFAOYSA-N 0.000 description 1
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000005799 fluoromethylation reaction Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940054565 sustiva Drugs 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- UKRDPEFKFJNXQM-UHFFFAOYSA-N vinylsilane Chemical group [SiH3]C=C UKRDPEFKFJNXQM-UHFFFAOYSA-N 0.000 description 1
- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical compound [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a novel method for directly synthesizing alkenyl trifluoromethyl oxazolidine compounds from alkyne amide raw materials. According to the method, silver salt and trimethyl (trifluoromethyl) silane are used for forming a trifluoromethyl source, ethyl acetate, acetonitrile, N-methylpyrrolidone, dimethyl sulfoxide or N, N-dimethylformamide are used as solvents under the condition of nitrogen, the reaction is carried out for 0.5-24 h at the temperature of 25-150 ℃, then, the vacuum concentration is carried out, and the alkenyl trifluoromethyl oxazolidine compound is obtained through recrystallization or column chromatography purification, wherein the yield is 34-69%. The method has the advantage of good reaction selectivity, and the Z/E is 95: 5; the preparation from the alkyne amide raw material to the alkenyl trifluoromethyl oxazolidine is realized for the first time; the alkyl substrate has wide application range and can synthesize the alkenyl trifluoromethyl oxazolidine compound in gram scale; also has the advantages of high chemical selectivity, easy separation of products, short reaction time and the like.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing a hydrogentrifluoromethyl methylation product of alkynylamide by taking a trifluoromethyl free radical as a trifluoromethyl source.
Background
The methodology for developing trifluoromethylations with high efficiency is of great significance. Trifluoromethyl is commonly used as a bioisostere to produce derivatives by substituting chloride or methyl. This can be used to modulate the steric and electronic properties of the lead compound, or to protect the reactive methyl group from metabolic oxidation. Some notable drugs containing a trifluoromethyl group include efavirenz (sustiva), an HIV reverse transcriptase inhibitor; fluoxetine (baryjel), an antidepressant; and celecoxib (Celebrex), a non-steroidal anti-inflammatory drug.
In 2004, the Itsumaro Kumadaki group used α -unsaturated ketone in the presence of Et2Zn and RhCl (PPh3)3 using trifluoroiodomethane as a fluorine source to give α -trifluoromethylated product (Sato, K.; Omote, M.; Ando, A.; Kumadaki, I.Org.Lett., 2004, 6, 4359.)
In 2010, the Qingfengling group developed a simple synthetic method for direct trifluoromethylation at the benzyl position in a nitrogen-containing heterocycle by a benzoyl peroxide-promoted reaction. Therefore, by using three methyl (three methyl fluoride) silane and potassium fluoride treatment of 1, 2, 3, 4-four hydrogen isoquinoline, prepared various 1-three fluoromethylation four hydrogen isoquinoline derivatives, yield 45 ~ 83%. (Chu, L.; Qing, F. -L.chem.Commun.2010, 46, 6285.)
In 2011, Kantak group developed the olefin trifluromethylation of inert olefins by visible light redox catalysis with trifluoromethyl iodide (CF)3I) Is a trifluoromethyl group, [ Ru (phen)3]Cl2As a catalyst, and oxidation-reduction catalysis using a 14W household lamp. (Kantak, A.A.; Potavathri, S.; Barham, R.A.; Romano, K.M.; DeBoef, B.J.Am.chem.Soc., 2011, 133, 19960)
In 2012, the Mikiko Sodeoka group successfully trifluoromethylates allylsilanes in methanol at room temperature using CuI and a trifluoromethylated higher iodine derivative to produce branched terminal olefins and vinylsilanes, both containing trifluoromethyl groups at the allylic position. (Shimizu, R.; Egami, H.; Hamashima, Y.; Sodeoka, M.Angew.chem., int.Ed., 2012, 51, 4577.)
In 2018, the Liu national topic group synthesizes a trifluoromethylated silane product by using styrene and disilylacetylene, using Cu (CH3CN)4PF6 as a catalyst, a Togni reagent as a fluorine source, bisoxazoline as a ligand and dichloroethane and N, N-dimethylaniline as a mixed solvent. (Fu, L.; Zhou, S.; Wan, X.; Chen, P.; Liu, G.; J.am. chem.Soc., 2018, 140, 10965-
In summary, the current methods for synthesizing trifluoromethyl compounds have the following disadvantages:
1. a triple bond hydrogen trifluoromethylation reaction is not realized, and only iodine trifluoromethylation is realized;
2. reagents with strong toxicity are used in the reaction, and the environmental pollution is serious.
Disclosure of Invention
The invention provides a method for preparing an alkenyl trifluoromethyl oxazolidine compound, which has the advantages of simple raw material acquisition, high yield and environmental friendliness.
To achieve the above object, the present invention provides a method for synthesizing an alkenyltrifluoromethyloxazolidine compound from an alkynylamide, comprising the steps of: adding an alkynylamide raw material, a silver salt and trimethyl (trifluoromethyl) silane into a reaction solvent, carrying out catalytic reaction for 0.5-24 h at the temperature of 25-150 ℃ in nitrogen and in a stirring state, removing the reaction solvent in a reaction liquid, and purifying to obtain an alkenyl trifluoromethyl oxazolidine compound; wherein the molar volume ratio of the alkynylamide raw material, the silver fluoride, the trimethyl (trifluoromethyl) silane and the reaction solvent is (0.3-6.0) mmol, (0.03-0.06) mmol, (3.0-60) mL.
Preferably, the alkynamide starting material is any one of 3- (phenylethynyl) oxazolidine-2-one, 3- (butylethynyl) oxazolidine-2-one, 3- (octylethynyl) oxazolidine-2-one, 3- (thienylethynyl) oxazolidine-2-one, 3- (cyclopropylethynyl) oxazolidine-2-one or 3- (propenylethynyl) oxazolidine-2-one.
Preferably, the silver salt is any one of silver nitrate, silver trifluoroacetate, silver trifluorformate, silver fluoride, silver bis (trifluoromethanesulfonyl) imide, silver acetate, silver oxide or silver chloride.
Preferably, the alkyne amide raw material is 3- (butyl ethynyl) oxazolidine-2-ketone, and the synthesis method of the 3- (butyl vinyl) -2-trifluoromethyl-oxazolidine-2-ketone compound comprises the following steps:
A. adding 3- (butyl ethynyl) oxazolidine-2-ketone, silver fluoride and trimethyl (trifluoromethyl) silane into acetonitrile at room temperature, stirring and uniformly mixing at room temperature, and reacting for 12 hours to obtain a reaction mixture; wherein the molar ratio of the 3- (butyl ethynyl) oxazolidine-2-ketone to the silver fluoride to the trimethyl (trifluoromethyl) silane is 1: 1-2: 2-3;
B. the reaction mixture was subjected to removal of the solvent under reduced pressure, and the residue was purified by recrystallization using petroleum ether and ethyl acetate as a mixed solvent or by silica gel chromatography (using petroleum ether and ethyl acetate as eluents) to give 3- (butylvinyl) -2-trifluoromethyl-oxazolidin-2-one as a yellow oily liquid.
Preferably, the reaction solvent is any one of ethyl acetate, acetonitrile, N-methylpyrrolidone, dimethyl sulfoxide or N, N-dimethylformamide;
the method for removing the reaction solvent adopts extraction and reduced pressure distillation for treatment;
the purification adopts column chromatography, and the eluent is petroleum ether/ethyl acetate (3: 1).
Preferably, the reaction solvent is acetonitrile.
Preferably, the method for synthesizing the alkenyl trifluoromethyl oxazolidine compound from the alkynylamide can prepare 3- (butylvinyl) -2-trifluoromethyl-oxazolidine-2-one
By the process of the invention. According to the method, alkynylamide is used as a raw material, silver salt and trimethyl (trifluoromethyl) silane are used as reaction solvents in nitrogen, ethyl acetate, acetonitrile, N-methyl pyrrolidone, dimethyl sulfoxide and N, N-dimethylformamide are used as reaction solvents, the reaction solvents in reaction liquid are removed after the reaction is carried out for 0.5-24 h at the temperature of 30-150 ℃ under the stirring state, the residue is purified through recrystallization (petroleum ether and ethyl acetate are used as mixed solvents) or silica gel chromatography (petroleum ether and ethyl acetate are used as eluent), and a yellow oily liquid 3- (butylvinyl) -2-trifluoromethyl-oxazolidine-2-one derivative is obtained, wherein the yield is 34-69%.
The method adopts the convenient and easily obtained alkyne amide as a raw material, and the raw material can be obtained by coupling reaction of alkyne bromide and corresponding amine through a carbon-nitrogen bond or can be obtained through a commercial way;
furthermore, there is no other method available in the art to produce related products;
drawings
FIG. 1 is an NMR chart of (Z) -3- (1, 1, 1-trifluorohept-2-enyl) -2-oxazolidinone in example 1 of the present invention1H spectrum
FIG. 2 is an NMR chart of (Z) -3- (1, 1, 1-trifluorohept-2-enyl) -2-oxazolidinone in example 1 of the present invention19F spectrum
FIG. 3 is an NMR chart of (Z) -3- (1, 1, 1-trifluoroundecyl-2-alkenyl) -2-oxazolidinone in example 1 of the present invention1H spectrum
Detailed Description
Example 1
1.67 g of 3- (1-hexynyl) -2-oxazolidinone, 2.52g of silver fluoride and 3.7mL of trimethyl (trifluoromethyl) silane were successively introduced into a 250mL reaction flask under nitrogen, 100mL of acetonitrile was added, and the mixture was placed in an oil bath at 25 ℃ for 12 hours. 200mL of water was added, followed by extraction with 60mL of ethyl acetate three times, and the organic phases were combined, washed with 30mL of saturated brine, dried over anhydrous sodium sulfate, filtered, distilled under reduced pressure to remove excess solvent, and column chromatography (petroleum ether: ethyl acetate ═ 3: 1) was performed to give 1.63 g of (Z) -3- (1, 1, 1-trifluorohept-2-enyl) -2-oxazolidinone. A colorless liquid. ,1H NMR(400MHz，CDCl3)δ7.13(s，1H)，4.46-4.50(t，2H)，4.05-4.09(t，2H)，2.24-2.29(m，2H)，1.50-1.52(m，2H)，1.34-1.48(m，2H)，0.93-0.96(t，3H)；19F NMR(376MHz，CDCl3)δ-64.9ppm。
example 2
2.23 g of 3- (1-decynyl) -2-oxazolidinone, 2.52g of silver fluoride and 3.7mL of trimethyl (trifluoromethyl) silane were successively introduced into a 250mL reaction flask under nitrogen, 100mL of acetonitrile was added, and the mixture was placed in an oil bath at 25 ℃ for 12 hours. 200mL of water was added, followed by extraction three times with 60mL of ethyl acetate, and the organic phases were combined, washed with 30mL of saturated brine, dried over anhydrous sodium sulfate, filtered, distilled under reduced pressure to remove excess solvent, and column chromatography (petroleum ether: ethyl acetate ═ 3: 1) was performed on 1.75g of (Z) -3- (1, 1, 1-trifluoroundecyl-2-alkenyl) -2-oxazolidinone as a yellow liquid,1H NMR(400MHz，CDCl3)δ7.13(s，1H)，4.46-4.50(t，2H)，4.05-4.09(t，2H)，2.23-2.27(m，2H)，1.48-1.50(m，2H)，1.25-1.35(m，10H)，0.86-0.90(t，3H)。19F NMR(376MHz，CDCl3)δ-64.9ppm。
example 3
1.93 g of 3- (thiophene-2-ethynyl) -2-oxazolidinone, 2.52g of silver fluoride and 3.7mL of trimethyl (trifluoromethyl) silane were successively charged into a 250mL reaction flask under nitrogen, 100mL of acetonitrile was added, and the mixture was placed in an oil bath at 25 ℃ for reaction for 12 hours. 200mL of water was added, followed by extraction three times with 60mL of ethyl acetate, and the organic phases were combined, washed with 30mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to remove excess solvent, and column chromatography (petroleum ether: ethyl acetate ═ 3: 1), 0.89g of a transparent liquid (E) -3- (3, 3, 3-trifluoro-1- (thienyl) prop-1-enyl) -2-oxazolidone,1H NMR(400MHz，CDCl3)δ7.42(s，4H)，7.26(s，1H)，4.44-4.48(t，2H)，3.37-3.38(t，2H)。19F NMR(376MHz，CDCl3)δ-67.2ppm。
although the present invention has been described in detail with reference to the preferred embodiments, it is not to be construed as limiting the invention thereto. Various modifications and alterations may be made by those skilled in the art without departing from the spirit and scope of the invention. The scope of the invention should therefore be considered as defined in the appended claims.
Claims (7)
1. A process for the synthesis of an alkenyltrifluoromethyloxazolidine compound from an alkynylamide, comprising the steps of: adding an alkynylamide raw material, a silver salt and trimethyl (trifluoromethyl) silane into a reaction solvent, carrying out catalytic reaction for 0.5-24 h at the temperature of 25-150 ℃ in nitrogen and in a stirring state, removing the reaction solvent in a reaction liquid, and purifying to obtain an alkenyl trifluoromethyl oxazolidine compound; wherein the molar volume ratio of the alkynylamide raw material, the silver fluoride, the trimethyl (trifluoromethyl) silane and the reaction solvent is (0.3-6.0) mmol, (0.03-0.06) mmol, (3.0-60) mL.
2. The method of claim 1, wherein the alkyne amide starting material is any one of 3- (phenylethynyl) oxazolidine-2-one, 3- (butylethynyl) oxazolidine-2-one, 3- (octylethynyl) oxazolidine-2-one, 3- (thienylethynyl) oxazolidine-2-one, 3- (cyclopropylethynyl) oxazolidine-2-one, or 3- (propenylethynyl) oxazolidine-2-one.
3. The method for synthesizing an alkenyltrifluoromethyloxazolidine compound from an alkynylamide as claimed in claim 1, wherein the silver salt is any one of silver nitrate, silver trifluoroacetate, silver triflate, silver fluoride, silver bistrifluoromethanesulfonimide, silver acetate, silver oxide or silver chloride.
4. The method of synthesizing an alkenyltrifluoromethyloxazolidine compound from an alkynylamide according to claim 1, where the alkynylamide starting material is 3- (butylethynyl) oxazolidin-2-one and the method of synthesizing the 3- (butylvinyl) -2-trifluoromethyl-oxazolidin-2-one compound comprises the steps of:
A. adding 3- (butyl ethynyl) oxazolidine-2-ketone, silver fluoride and trimethyl (trifluoromethyl) silane into acetonitrile at room temperature, stirring and uniformly mixing at room temperature, and reacting for 12 hours to obtain a reaction mixture; wherein the molar ratio of the 3- (butyl ethynyl) oxazolidine-2-ketone to the silver fluoride to the trimethyl (trifluoromethyl) silane is 1: 1-2: 2-3;
B. the reaction mixture was subjected to removal of the solvent under reduced pressure, and the residue was purified by recrystallization using petroleum ether and ethyl acetate as a mixed solvent or by silica gel chromatography (using petroleum ether and ethyl acetate as eluents) to give 3- (butylvinyl) -2-trifluoromethyl-oxazolidin-2-one as a yellow oily liquid.
5. The method for synthesizing an alkenyltrifluoromethyloxazolidine compound from alkynylamides according to claim 1, wherein the reaction solvent is any one of ethyl acetate, acetonitrile, N-methylpyrrolidone, dimethylsulfoxide, or N, N-dimethylformamide;
the method for removing the reaction solvent adopts extraction and reduced pressure distillation for treatment;
the purification adopts column chromatography, and the eluent is petroleum ether/ethyl acetate of 10: 1.
6. The process for the synthesis of an alkenyltrifluoromethyloxazolidine compound from an alkynylamide according to claim 5, where the reaction solvent is acetonitrile.
7. The process for the synthesis of an alkenyltrifluoromethyloxazolidine compound from an alkynylamide according to any of claims 1 to 6, wherein the synthesis of an alkenyltrifluoromethyloxazolidine compound from an alkynylamide results in the preparation of a 3- (butylvinyl) -2-trifluoromethyl-oxazolidin-2-one.
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| CN105622536A (en) * | 2015-12-30 | 2016-06-01 | 商丘师范学院 | Trifluoromethyl alkenyl isoxazole compound and preparation method and application thereof |
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| CN105622536A (en) * | 2015-12-30 | 2016-06-01 | 商丘师范学院 | Trifluoromethyl alkenyl isoxazole compound and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115043788A (en) * | 2022-07-28 | 2022-09-13 | 南京工业大学 | Trifluoromethyl oxazole-2-ketone compound and preparation method and application thereof |
| CN115043788B (en) * | 2022-07-28 | 2023-10-20 | 南京工业大学 | Trifluoromethyl oxazol-2-one compound and preparation method and application thereof |
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