Journal of Fluorine Chemistry最新文献

A simple and efficient method to produce a CF₂ group vicinal to a CX₂ group (X = chlorine or bromine) through double halofluorination reaction of alkynes using trihaloisocyanuric acid as halogenating agent and Pyridine.(HF)_x (Olah's reagent) as fluoride source is presented. The alkynes used were 1-hexyne, 3-hexyne, phenylacetylene, 1-phenyl-1-butyne, and diphenylacetylene, obtaining, mainly, the desired products in 30–88 % yields. Among the trihaloisocyanuric acids studied, the tribromoisocyanuric acid gave the best yields and the most selective reactions, while trichloroisocyanuric acid, although the most reactive, had less selectivity in the reactions studied, giving in some cases several by-products.

An improved, greener, column chromatography free and cost effective process for the preparation of ticagrelor in short route with an overall yield of 70% and 99.7% purity is reported. The process is substantially free from impurities such as hydroxy ticagrelor and amino ticagrelor, etc. In addition to this, the present process is highly robust in controlling all impurity percentages to be within the desired quality of ticagrelor.

The research focuses on the inversion of configuration at C3 of 1,2-O-isopropylidene-d-arabinofuranoside and d-ribofuranoside promoted by DAST. Both the initial configuration and the presence of C5 acyl group in d-furanosides are the key factors for this inversion due to the formation of cyclic oxonium ion intermediates. This inversion of configuration has been successfully applied to scalable synthesis of d-lyxose and 2′,5′-di-O-benzoyl-3′-fluoro-3′-deoxy-β-d-ribofuranosyl-7-halogen-7-deazapurine.

The popular multiplicity-edited heteronuclear single quantum coherence experiment has been modified for ¹⁹F-¹³C experiments by insertion of broadband inversion and refocusing pulses in ¹⁹F. This experiment has particular utility in distinguishing CF₃ from CF₂X, and CF₂ from CFX (X = O or halide). Examples are shown of 1,1,2-trichloro-1,2,2-trifluoroethane, a mixture of 1,1,2-trichloro-1,2,2-trifluoroethane and two perfluoroolefins, and a mixture of poly(hexafluoropropylene oxide) and perfluorohexyl iodide. Phase distortions are minimized by careful selection of the value of J_CF for which delays are optimized; a slight overstatement of J_CF yielded no distortions, while an understatement did. Large ¹⁹F homonuclear couplings do not report cleanly in-phase. A one-dimensional version of the experiment yielded analogous editing by phase.

(3R,5R)-5-(3-([¹⁸F]fluoromethoxy-d₂)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([¹⁸F]FMPEP-d₂) is a promising positron emission tomography (PET) radiopharmaceutical for the imaging of cannabinoid type 1 receptors in human studies. To facilitate widespread use of [¹⁸F]FMPEP-d₂ we herein report a simplified one-pot synthesis procedure that is broadly applicable for ¹⁸F-fluoromethylation of phenols and can be applied for routine clinical production using a commercial radiofluorination module (GE TRACERlab FX2 N). The present method overcomes previous challenges in the [¹⁸F]FMPEP-d₂ synthesis related to intermediate purification of a [¹⁸F]fluoromethyl building block by using ditosylmethane-d₂ and reacting it directly with (3R,5R)-5-(3-hydroxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidine-2-one in a one-pot nucleophilic reaction with [¹⁸F]fluoride (K₂CO₃, K₂₂₂, CH₃CN, 80 °C, 10 min). After purification of the product by semi-preparative HPLC under isocratic conditions and formulation, [¹⁸F]FMPEP-d₂ was obtained in a decay-corrected radiochemical yield of 8 ± 1 %, a radiochemical purity >95 % and a molar activity of 322 ± 101 GBq/µmol in a synthesis time of 70 ± 5 min (n = 8). Validation and regulatory submission of [¹⁸F]FMPEP-d₂ is underway with the new methodology and will facilitate widespread human use as well as multi-center clinical trials.

The organic fluorinating agents [bis(2-methoxyethyl)amino]sulfur trifluoride (Deoxo-fluor®), diethylaminosulfur trifluoride (DAST), and N-fluorobenzenesulfonimide (NFSI) were used to inspect the efficiency of fluorination of monovanadate, H_xVO₄^(3−x)− (V₁), and decavanadate, H_xV₁₀O₂₈^(6−x)− (V₁₀), in solution by ⁵¹V NMR spectroscopy. It was observed that either VOF₄⁻ or VO₂F₂⁻ can be generated in acetonitrile solutions at room temperature after one hour selectively for H_xVO₄^(3−x)−, while H_xV₁₀O₂₈^(6−x)− is more sensitive towards reduction and only NFSI can be used to generate VOF₄⁻. The differences in reactivity can be attributed to the electrophilicity of fluorine in Deoxo-fluor® and DAST, and its nucleophilicity in NFSI. Tetrabutylammonium fluoride, triethylamine trifluoride, and hydrogen fluoride–pyridine adduct were also used under the same conditions for comparison of the efficiency and selectivity of fluorination. It was observed that only HF.pyridine provided a complete transformation of V₁ and V₁₀ into VOF₄⁻. The pilot experiments introduced in this work are the first example of fluorination of polyoxometalates with organic fluorination agents and other less commonly used fluorides with organic cations and show their great potential in the synthesis of polyoxometalates with fluorido ligand.

The nature of the structural configuration of fluorinated ethers has been widespread as a crucial component for improving high performance polymers, industrial agrochemicals, and targets for important pharmaceutical drugs. This is a result of countless advances in organo-fluorine methodologies with this unique substructure in order to overcome many traditional synthetic challenges. In this work, we expand on the preparation of fluorinated ethers by introducing hetero-nucleophiles to a highly electrophilic aryl trifluorovinyl ether affording a new class of difunctional aryl/alkyl fluorinated ethers that would serve as useful intermediates. The facile reaction chemistry of various nucleophile substrates, effect of base concerning regio-selectivity, and structural elucidation trends of the synthesized aryl/alkyl fluoroethers will be discussed.

A catalytic trifluoromethylation of stereoisomeric 6-ketomorphinans using Ruppert–Prakash reagent and tetrabutylammonium fluoride (TBAF) was studied. 14β-Hydroxycodeinone, 4-O-methylsinomenine and 1-iodo-4-O-methylsinomenine provided good to excellent yields of the corresponding 6-trifluoromethylated compounds. The new morphinan derivative (6-deoxo-1-iodo-6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol) was involved in some catalytic transformations for introduction of additional substituent on C-1 position of the morphinan core. The palladium-catalyzed carbonylation–cross coupling reaction of 1-iodo-derivative with phenylacetylene in the presence of PdCl₂-(1-Ad)₂PBn catalytic system and Mo(CO)₆ as a source of carbon monoxide in MeCN proceeds with high selectivity with the formation of alkynyl ketone as the main product. The cyclocondensation with acetamidine hydrochloride afforded the arylpyrimidine – 6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol hybrid compound. The action of the dehydration system (SOCl₂-Py-DMAP) on 6-deoxo-6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol have led to the formation оf 8β‑chloro-6,7-didehydro-6-(trifluoromethyl)morphinan which showed inhibition the main viral protease (3CLpro) of SARS-CoV-2 at IC₅₀ value of 25 μM.

InF₃(H₂O)₂ is a new monoclinic C2/m phase [a = 5.774(2) Å, b = 10.239(3) Å, c = 4.1150(8) Å, β = 118.16(2)°]. It is obtained fortuitously as very few single crystals during the synthesis in sealed tubes of the phases in the system InF₃-TeO₂. It can also be prepared by direct dissolution of InF₃ or In₂O₃ in HF 40 %, followed by a slow evaporation of the solution about 50–70 °C. It corresponds to an intermediate unstable dihydrate in the process of hydration of InF₃ at air to a stable trihydrate InF₃(H₂O)₃.

InF₃(H₂O)₂ structure is composed of trans-chains [InF₃(H₂O)₂]_n of InF₄(OH₂)₂ octahedra sharing F vertices, interconnected via strong OH···F hydrogen bonds between equatorial O/F of adjacent chains with short O···F bonds of 2.57 Å and 2.60 Å. A medium range order between F(1) and O(1) equatorial anions is proposed. InF₃(H₂O)₂ seems to be the first simple dihydrate of trivalent metal fluorides. It is compared to InF₃(H₂O)₃ and to other trihydrates presenting some similar structural features.

The design of fluorinated pharmaceuticals has become an important approach in drug discovery given fluorine's ability to modulate properties such as lipophilicity, pK_a, metabolic stability, and bioavailability offering desired therapeutic advancements over a drug's hydrogen counterpart. Characterizing these compounds builds our understanding of how fluorine's structural and positional attributes influence the properties of these pharmaceuticals. NMR spectroscopy is a powerful structural characterization tool well-suited for this purpose. In this paper we present a quantitative pharmaceutical application using fluorine NMR and aSICCO (artificial Signal Insertion for Calculation of Concentration Observed) for analyzing pure or crude samples containing fluorinated pharmaceuticals and fluorinated residual solvents. We demonstrate that the method can be applied to samples measured with routine NMR instrumentation, achieving reproducible results to within ± 5 percent.