Elemental fluorine. Part 13. Gas-liquid thin film microreactors for selective direct fluorination

Continuous flow gas-liquid thin film microreactors have been effectively used for the selective fluorination of a range of 1,3-dicarbonyl and aromatic substrates and, additionally, the conversion of aromatic disulfides to the corresponding sulfur pentafluorides. Scale-up was demonstrated by the application of a three channel microreactor device fabricated by replication of a single channel system.     

New inhalation anaesthetics: I. Fluorinated 1,3-dioxolane derivatives

A range of fluorochlorodioxolane derivatives has been prepared by chlorination, fluorination and reduction of polyfluoroalkyl-1,3-dioxolanes, for screening as potential inhalation anaesthetics. Only 2-trifluoromethyl -1,3-dioxolane showed good anaesthesia without side effects, but is expected to be flammable at clinical concentrations.     

Elemental fluorine : Part 20. Direct fluorination of deactivated aromatic systems using microreactor techniques

Continuous flow microreactor technology has been used for the direct fluorination of a range of deactivated di- and tri-substituted aromatic systems.     

Metal triflate-catalyzed cationic benzylation and allylation of 1,3-dicarbonyl compounds

The rare earth metal and hafnium triflate-catalyzed secondary benzylation and allylation of 1,3-diketones, ketoesters, and ketoamides are described. The procedure was carried out under non-anhydrous conditions. Various 1-phenylethyl cations were generated from substituted 1-phenylethanols using 0.5 mol % of the metal triflates in CH3NO2. The cations reacted with 1,3-diketones and ketoesters to give benzylated products in high yields. Following the GC analysis, the reaction conditions were easily optimized by the selection of catalysts based on the Lewis acidity of the triflates and reaction temperature. A tertiary-alkylated diketone and a corresponding ketoester were also benzylated to afford products with a quaternary carbon atom in 57-84% yield. The ketoamide reactions required stronger Lewis acids than those used in the diketone and ketoester reactions. The reactions of benzylic alcohols possessing various substituents on the aromatic ring and dibenzoylmethane (2b) as a diketone were examined in the presence of Hf(OTf)4. Electron-rich benzylic alcohols reacted with 2b in 86-96% yield, and electron-deficient alcohol gave the desired product in 79-65% yield. Despite possessing a strong electron-withdrawing group, the reaction of 1-(4-nitrophenyl)ethanol gave the corresponding product in 61% yield. It was also possible to use allylic alcohols directly for the allylation of diketone 2b. The catalyst can be recovered by water extraction and reused up to five times.     

Microwave-assisted rapid electrophilic fluorination of 1,3-dicarbonyl derivatives with Selectfluor

A microwave-assisted fluorination method for 1,3-dicarbonyl compounds using Selectfluor^® has been developed. 2-Monofluorinated products can be obtained in high yield in neutral reaction conditions with addition of 1 eq. of Selectfluor^®. Treatment of 1,3-dicarbonyls with 3 eq. of Selectfluor^® in the presence of tetrabutylammonium hydroxide (TBAH) as the base results in the formation of 2,2-difluorinated derivatives only.     

A practical and convenient fluorination of 1,3-dicarbonyl compounds using aqueous HF in the presence of iodosylbenzene

A simple, practical, and convenient fluorination of 1,3-dicarbonyl compounds was achieved by direct use of aqueous hydrofluoric acid and iodosylbenzene (PhIO). The reaction of ethyl benzoylacetate with the reagent system of aqueous HF and PhIO in CH(2)Cl(2) gave ethyl 2-fluoro-2-benzolyacetate in 98% yield. Other 1,3-dicarbonyl compounds including β-keto esters and 1,3-diketones underwent the fluorination reaction to give the corresponding fluorinated products in good yields.     

Arsenorgano-Verbindungen : XXII. Zur synthese der 1,3-benzazarsoline

o-Aminophenylarsine is prepared by reduction of o-nitrophenylarsonic acid. Metallation and subsequent treatment with alkyl halides give the secondary o-aminophenylarsines. o-Aminophenylarsines react with aldehydes, ketones and ketoesters forming derivates of the 1,3-benzazarsoline. Exceptions are redox reactions between o-aminophenylarsine and aldehydes. The properties of the compounds are described in more detail.     

Fluorination of carbinols with 2,2-difluoro-1,3-dimethylimidazolidine in ionic liquid

The utility of ionic liquids for fluorination using 2,2-difluoro-1,3-dimethylimidazolidine (DFI) is described. Further, the fluorination of chiral epoxyalcohols gave the chiral monofluoromethylated epoxides.     

Elemental fluorine. Part 16. Versatile thin-film gas-liquid multi-channel microreactors for effective scale-out

Versatile and conveniently operated microreactor devices, suitable for long term chemical synthesis for both laboratory and industrial use, are described. Direct fluorination of ethyl acetoacetate by fluorine gas is used as a model reaction to illustrate the successful application of reactors having either 9, 18 or 30 microchannels, with all channels supplied from single reagent sources, to provide significant quantities of fluorinated products. Convenient reactor maintenance, simple design, versatility and the enhanced safety features of using such modular microreactor devices, make these systems appropriate for synthesis on the large scale.     

Fluorination of trimethylamine over cobalt(III) fluoride : Novel cyclisation of trimethylamine to polyfluoro-1,3-dimethylimidazolidines (characterised by mass spectrometry and nmr spectroscopy); cation-radical

Trimethylamine has been fluorinated with cobalt(III) fluoride to give eleven novel highly fluorinated products including seven polyfluoro-1,3-dimethylimidazolidines. Mass spectrometry and NMR spectroscopy were used to assign product structures. On fluorination under comparable conditions 1,2-bisdimethylamino-ethane and bisdimethylaminomethane gave mixtures containing all the products characterised from the title fluorination. A cation-radical mechanism of fluorination is proposed.     

FeCl3‐Catalyzed Addition of 1,3‐Dicarbonyl Compounds to Aromatic Olefins

A direct, intermolecular addition of 1,3‐dicarbonyl compounds to styrenes in the presence of FeCl₃ as an inexpensive and disposable catalyst has been developed for the straightforward and practical synthesis of arylated diketones and ketoesters. The reactions proceed under mild conditions for most substrates (50–80 °C), and no strong acid or base is required. The synthetic value of the method is demonstrated by 15 examples, including the synthesis of the current pharmaceutical drug warfarin in one step and 42 % yield from commercially available substrates.     

2,2-Difluor-1,2,3-trimethyl-1,3-diaza-2λ5-phospholidin

2,2-Difluoro-1,2,3-trimethyl-1,3-diaza-2λ⁵-phospholidine The title compound 1 is obtained in about 50% yield by oxidative fluorination of 1,2,3-trimethyl-1,3-diaza-2λ³-phospholidine, 6 , with IF₅. 1 is characterized by its nmr, mass, and ir spectra.     

Iodine as a versatile catalyst for the hydroalkylation of vinyl arenes with 1,3-diketones

The vinyl arenes undergo smooth hydroalkylation with 1,3-diketones in the presence of 10 mol % of iodine to afford phenethyl diketones and ketoesters in good yields in short reaction times. The use of inexpensive and readily available molecular iodine makes this method quite simple, more convenient and practical.     

Elemental fluorine in organic chemistry (1997-2006)

The use of elemental fluorine as a reagent over the period 1997-2006 for carbon-fluorine bond formation in organic synthesis is reviewed. Recent advances in the exhaustive fluorination of ethers and esters to give perfluorinated systems, selective direct fluorination of aliphatic, aromatic, heterocyclic and carbonyl systems and the application of microreactor techniques to direct fluorination are discussed.     

Development of fluorination methods using continuous-flow microreactors

The safe and reliable use of various fluorination methods including nucleophilic fluorination (DAST), trifluoromethylation (Ruppert's reagent) and electrophilic fluorination (Selectfluor^®) in a continuous-flow microreactor is reported. Special attention was given to the use of in-line scavenging procedures in order to obtain clean products without the need for further purification.     

Highly Homogeneous Stereocontrolled Construction of Quaternary Hydroxyesters by Addition of Dimethylzinc to α‐Ketoesters Promoted by Chiral Perhydrobenzoxazines and B(OEt)3

A highly efficient enantioselective addition of Me₂Zn to α‐ketoesters, assisted by a chiral perhydro‐1,3‐benzoxazine ligand, is described. This novel catalytic system offers homogeneous elevated enantioselectivities in the preparation of α‐hydroxyesters that bear a quaternary stereocenter, with a minor dependence on electronic and steric effects when aromatic, heteroaromatic, or aliphatic α‐ketoesters are employed. The catalyst can be recovered and reused without loss of activity.     

Catalytic fluorination of 1,3-dicarbonyl compounds using iodoarene catalysts

Catalytic fluorination of 1,3-dicarbonyl compounds with aqueous hydrofluoric acid proceeded efficiently with the aid of iodoarene catalysts in the presence of m-CPBA as a terminal oxidant. o-Iodotoluene, o-iodoanisole, and o-ethyliodobenzene showed a high catalytic efficiency to give 2-fluoro-1,3-dicarbonyl compounds in good yields.     

Perfluorotetramethylenesulfur difluoride and its derivatives. Perfluoro-1,3-dithietane octafluoride and perfluoro-1,4-dithiane octafluoride

The fluorination of perfluorotetramethylene sulfide with chlorine monofluoride under controlled conditions results in the formation of both sulfur(IV) and sulfur(VI) compounds as main products. While perfluorotetramethylenesulfur tetrafluoride is very stable to thermolysis and to chemical attack, the hydrolysis of the novel perfluorotetramethylenesulfur difluoride affords perfluorotetramethylene sulfoxide, and its pyrolysis gives perfluro(di-n-butyl)disulfide. Chlorine monofluoride converts perfluorotetramethylene sulfoxide to perfluorotetramethyl-enesulfur oxyfluoride, and perfluorotetramethylene sulfone is obtained quantitatively as a decomposition product in contact with Pyrex glass. Perfluoro-1,3-dithietane octafluoride and perfluoro-1,4-dithiane octafluoride are also formed by the reaction of corresponding perfluorocyclic sulfides with CIF at ambient temperature. Infrared, mass and ¹⁹F NMR spectroscopic as well as thermodynamic data are reported.     

使用DBDMH和Et3N·3HF的苯乙酮一锅法α-亲核氟代

报道一种通过溴代和氟代的一锅法操作,从苯乙酮直接制备α-氟代苯乙酮的新方法.使用1,3-二溴-5,5-二甲基海因(DBDMH)作为溴代试剂,三乙胺三氟化氢作为氟代试剂,除了p-和m-硝基苯乙酮之外,α-氟代苯乙酮以82%～87%的收率被获得.本方法使用的试剂价廉、收率较高、操作简单方便,有较高的应用价值.