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Chemical Structure| 393-56-6

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Yuhao Yang ;

Abstract: The fluorine (F) atom has distinctive properties such as the highest electronegativity, small size, low polarizability, and strong C–F bond strength. Not surprisingly, fluorinated organic compounds have garnered significant attention in the pharmaceutical, agrochemical, and material fields. Since organofluorides are very rare in nature, we need fluorination reagents to help us transfer fluorine into the organic molecules. In past decades, a vast number of fluorination reagents have been developed and many of them are commercially available now. However,there is still much room for the improvement of these reagents. Our target is to develop novel and practical fluorination reagents to make up for the shortcomings of the currently popular ones. We have developed a novel fluorinating agent, N-fluoro-N-(tert-butyl)-tertbutanesulfonamide (NFBB), which was prepared in excellent yield using Nfluorobenzenesulfonimide (NFSI) or F2/N2 and was purified by simple distillation. Its easy preparation and purification made NFBB a reagent suitable for large scale production. NFBB provided unprecedented high-yielding fluorination of highly basic organolithium species, which has been an unsolved problem for a long time. With NFBB, a conceptually new base-catalyzed, self-sustaining fluorination of active methylene compounds was discovered. NFBB also fluorinated other carbanions such as Grignard reagents and enolates in good yields. NFBB is expected to play an important role in the preparation of many useful fluorinated compounds and it is now commercialized by Tokyo Chemical Industry Co., Ltd. (TCI). The trifluoromethylthio (CF3S) group has the highest lipophilicity among the common fluorine-containing moieties. Therefore, introducing a fluorine atom or a CF3S group into a bioactive molecule could produce dramatic effects on its physical, chemical, and biological properties. We have developed a novel trifluoromethylthiolating reagent, S-trifluoromethyl trifluoromethanesulfonothioate (TTST). Unlike conventional CF3S reagents, TTST can be easily prepared in one step from commercially inexpensive sodium trifluoromethanesulfinate and triflicanhydride. TTST is a highly reactive, versatile, and atom-efficient reagent that can generate CF3S+, CF3S-, and CF3S• /CF3• reactive species. Many kinds of C, O, S, and N-nucleophiles were trifluoromethylthiolated by TTST in high yields. Notably, TTST reacted with sodium phenoxides to provide a new series of hitherto difficult to prepare aryl trifluoromethanesulfenates that were found to undergo a novel acid-catalyzed CF3S(II)-rearrangement reaction. By means of Cu or TDAE/Ph3P combination, TTST generated two CF3S anion species that are useful to prepare trifluoromethylthio compounds in high atom-economy fashion. Photocatalytic radical trifluoromethyl-trifluoromethylthiolation of alkenes with only one equivalent of TTST was achieved in high yield as well as in high atom-efficiency. TTST is expected to be a compelling alternative to the current CF3S reagents in terms of preparation, reactivity, and practicality. The trifluoromethylthio (CF3S) group has the highest lipophilicity among the common fluorine-containing moieties. Therefore, introducing a fluorine atom or a CF3S group into a bioactive molecule could produce dramatic effects on its physical, chemical, and biological properties. We have developed a novel trifluoromethylthiolating reagent, S-trifluoromethyl trifluoromethanesulfonothioate (TTST). Unlike conventional CF3S reagents, TTST can be easily prepared in one step from commercially inexpensive sodium trifluoromethanesulfinate and triflicanhydride. TTST is a highly reactive, versatile, and atom-efficient reagent that can generate CF3S+, CF3S-, and CF3S• /CF3• reactive species. Many kinds of C, O, S, and N-nucleophiles were trifluoromethylthiolated by TTST in high yields. Notably, TTST reacted with sodium phenoxides to provide a new series of hitherto difficult to prepare aryl trifluoromethanesulfenates that were found to undergo a novel acid-catalyzed CF3S(II)-rearrangement reaction. By means of Cu or TDAE/Ph3P combination, TTST generated two CF3S anion species that are useful to prepare trifluoromethylthio compounds in high atom-economy fashion. Photocatalytic radical trifluoromethyl-trifluoromethylthiolation of alkenes with only one equivalent of TTST was achieved in high yield as well as in high atom-efficiency. TTST is expected to be a compelling alternative to the current CF3S reagents in terms of preparation, reactivity, and practicality. We also found a novel application of the fluorinated solvent, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), which assisted the hydrohalogenation of alkenes with inactive aqueous hydrogen halide solutions via hydrogen bonding. Dynamic studies showed this reaction is hydrogen bond acidity-dominated and dilution-accelerated. Both aqueous HCl, HBr, and HI provided good yields of the hydrohalogenated products in this system.

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Product Details of [ 393-56-6 ]

CAS No. :393-56-6
Formula : C8H10FN
M.W : 139.17
SMILES Code : CN(C)C1=CC=CC=C1F
MDL No. :MFCD01862018
InChI Key :DUMMWWNKDSKGRZ-UHFFFAOYSA-N
Pubchem ID :2774264

Safety of [ 393-56-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Application In Synthesis of [ 393-56-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 393-56-6 ]

[ 393-56-6 ] Synthesis Path-Downstream   1~35

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  • [ 100-01-6 ]
  • [ 1426-46-6 ]
YieldReaction ConditionsOperation in experiment
57% With lithium iodide; 1-hexyl-3-methylimidazolium tetrafluoroborate; at 120℃; under 7500.75 Torr; for 12.0h;Autoclave; Inert atmosphere; General procedure: The lignin is reacted as a methyl source with an amine compound to prepare an N-methyl compound in a 16 ml PTFE-lined stainless steel reactor.A magnetic stirrer in the reactor.In the experiment, a certain amount of iodide catalyst and optionally a fluoroborate promoter, lignin or anisole,The amine and the reaction solvent are added to the reaction vessel,The reaction kettle was sealed and replaced three times with 1 MPa of nitrogen.The reactor is placed in an air bath at a constant temperature and chargedThe magnetic stirring speed was set to 800 rpm.After the reaction, the reaction vessel was placed in an ice water bath to be cooled.About 0.04 g of 1,3,5-trioxane was added as an internal standard to the liquid mixture after the reaction.The liquid mixture was then diluted with 10 ml of methanol and stirred for 5 minutes.The mixture was centrifuged and subjected to 1H NMR (Bruker Avance III 400HD).The tape reagent used was DMSO-d6.The experimental results of lignin to acetic acid under different reaction conditions are listed in the following tables.As can be seen from the table,The selectivity of the N-methylated product can reach nearly 100% under optimal reaction conditions.The yield was 72%.
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  • [ 445-17-0 ]
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  • [ 348-54-9 ]
  • [ 124-38-9 ]
  • [ 393-56-6 ]
YieldReaction ConditionsOperation in experiment
93% With [Ru(Triphos)(TMM)]; hydrogen; bis(trifluoromethanesulfonyl)amide; In tetrahydrofuran; at 150℃; under 60006.0 Torr; for 24.0h;Inert atmosphere; General procedure: EXAMPLE III: Methylation of various primary amines and amides Several primary amines and Acetanilide were reacted using the following conditions: Substituted primary aniline or amide (1.0 mmol), [Ru(Triphos)(TMM)] (2.5 mol%), HNTf2 (5 mol%), THF (2 mL), C02/H2 (20/60 bar), 150 C. The results are shown in the following Table III TABLE III
With [Ru(Triphos)(TMM)]; hydrogen; bis(trifluoromethanesulfonyl)amide; In tetrahydrofuran; at 150℃; under 60006.0 Torr; for 24.0h;Autoclave; General procedure: All high pressure batch experiments were conducted in stainless steel 10 mL autoclaves equipped with a glass inlet and a magnetic stir bar. Prior to use, the autoclave was dried under vacuum for 3 hours and repeatedly filled with argon. Under an argon atmosphere, catalyst [Ru(Triphos)(TMM)] (0.019 g, 0.025 mmol) and HNTf2 (0.014 g, 0.05 mmol) were weighed in a Schlenk tube. After dissolving in THF (1.0 mL), the mixture was transferred via cannula to the autoclave followed by the addition of the aniline substrate (1.0 mmol) in THF (1.0 mL). The autoclave was then pressurized with CO2 to 20 bar and then H2 was added up to a total pressure of 80 bar. The reaction mixture was stirred and heated to 150 C in an oil bath. After 10h, the autoclave was cooled in an ice bath and then carefully vented. The reaction solution was analyzed by 1H-NMR with internal standard mesitylene and the results confirmed by gas chromatography using dodecane as internal standard.
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  • [ 556-21-8 ]
  • [ 101-61-1 ]
  • [ 100-10-7 ]
YieldReaction ConditionsOperation in experiment
With N-fluorobis(benzenesulfon)imide; In chloroform; at 25℃; for 10.0h; General procedure: To a solution of amine (0.1mmol) in 3mL of CHCl3 the corresponding amount of NFSI in 2mL of the same solvent was added. The reaction mass was stirred at selected temperature during the time indicated in Table 1. The resulting solution was washed with water (2×15mL), dried over Na2SO4 and evaporated to dryness. The residue was analyzed either by GC/MS or separated by column chromatography.
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YieldReaction ConditionsOperation in experiment
6% With zirconium(IV) chloride; N-fluorobis(benzenesulfon)imide; In chloroform; for 5.0h;Reflux; General procedure: To a solution of amine (0.1mmol) in 3mL of CHCl3 the corresponding amount of NFSI in 2mL of the same solvent was added. The reaction mass was stirred at selected temperature during the time indicated in Table 1. The resulting solution was washed with water (2×15mL), dried over Na2SO4 and evaporated to dryness. The residue was analyzed either by GC/MS or separated by column chromatography.
  • 22
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  • (E)-ethyl 3-(2-(dimethylamino)-3-fluorophenyl)acrylate [ No CAS ]
  • 23
  • [ 393-56-6 ]
  • [ 775-12-2 ]
  • (4-diphenylsilanyl-2-fluorophenyl)dimethylamine [ No CAS ]
  • 24
  • [ 393-56-6 ]
  • [ 766-77-8 ]
  • 4-(dimethyl(phenyl)silyl)-2-fluoro-N,N-dimethylaniline [ No CAS ]
  • 26
  • [ 393-56-6 ]
  • [ 274-07-7 ]
  • C14H13BFNO2 [ No CAS ]
  • 27
  • [ 1978-38-7 ]
  • Kraft lignin [ No CAS ]
  • [ 393-56-6 ]
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  • [ 393-56-6 ]
  • [ 887268-20-4 ]
  • 29
  • [ 50-00-0 ]
  • [ 348-54-9 ]
  • [ 393-56-6 ]
  • 30
  • [ 201230-82-2 ]
  • [ 393-56-6 ]
  • 8-fluoro-1-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione [ No CAS ]
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  • [ 67-56-1 ]
  • [ 348-54-9 ]
  • [ 393-56-6 ]
  • 32
  • [ 393-56-6 ]
  • [ 121-45-9 ]
  • dimethyl (((2-fluorophenyl)(methyl)amino)methyl)phosphonate [ No CAS ]
  • 34
  • [ 393-56-6 ]
  • [ 333-27-7 ]
  • C9H13FN(1+)*CF3O3S(1-) [ No CAS ]
  • 35
  • [ 393-56-6 ]
  • [ 342-24-5 ]
 

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