Fluoride In Acetonitrile Research Articles

Darstellung von 1,3,5-Trimethyl-4,6-dioxo-1,3,5,2λ3-triazaphosphinanen; Einkristall-Röntgenstrukturanalyse eines Platin(II)-Komplexes/Preparation of 1,3,5-Trimethyl-4,6-dioxo-1,3,5,2λ3-triazaphosphinanes; Single Crystal X-Ray Diffraction Study of a Platinum(II)-Complex

A new synthesis for 2-chloro-1,3,5-trimethyl-4,6-dioxo-1,3,5,2λ3-triazaphosphinane (1) is described. Chlorine-fluorine exchange in 1 by means of sodium fluoride in acetonitrile in the presence of catalytic amounts of a crown ether furnished 2-fluoro-1,3,5-trimethyl-4,6-dioxo-1,3,5,2λ3-triazaphosphinane (2). The synthesis of the bromine and iodine analogues, 3 and 4, by metathesis of 1 with the appropriate trimethylsilyl halides, Me3SiBr and Me3SiI, respectively, is also described. The syntheses of an iron(0)tetracarbonyl complex (5) and of a dichloroplatinum( II) complex (6) are reported. A single crystal X-ray diffraction study was conducted on 6. [P21/c, a = 1161.3(3), b = 1423.2(3), c = 1247.7(3) pm, β = 109.42(2)°, R = 0.028], There are deviations from ideal square planar geometry at platinum. The heterocycles display a flattened boat conformation. A Staudinger reaction of 1 with Me3SiN3 led to the formation of a substituted cyclotriphosphazene.

The reaction of pentafluorophenyltrimethylsilane with perfluorinated internal azaalkenes in the presence of cesium fluoride

Pentafluorophenyltrimethylsilane reacts with perfluorinated internal azaalkenes in the presence of cesium fluoride in acetonitrile.

A Variant of Peterson Olefination: Nitrophenyl-Substituted Methylenecyclopropa[b]naphthalenes

The successful use of a gem-disilyl compound in Peterson olefination with nitrosubstituted aromatic aldehydes and ketones is achieved for 1,1-bis( trimethylsilyl )-1H-cyclopropa[b]naphthalene (9) by employing potassium fluoride in acetonitrile and using a catalytic quantity of tetrabutylammonium fluoride as the fluoride ion transfer agent.

Synthesen und Kristallstrukturen der Kronenether-Komplexe (18-Krone-6) · 2CH3CN, [Na-15-Krone-5][ReO4] · CH3CN und [Na-15-Krone-5]PF6 / Syntheses and Crystal Structures of the Crown Ether Complexes (18-Crown-6) · 2 CH3CN, [Na-15-Crown-5][ReO4] · CH3CN, and [Na-15-Crown-5]PF6

Single crystals of (18-crown-6) · 2 CH3CN were obtained by cooling a solution of 18-crown-6 in acetonitrile to 4 °C. Space group P21/n, Z = 2, 629 observed independent reflexions, R = 0.062. Lattice dimensions at 19°C: a = 911.7(1), b = 852.0(1), c = 1370.0(2) pm; β = 104.61(1)°. The compound forms a molecular structure with approximate D3d symmetry of the crown ether molecule, and C—H ··· O interactions of the acetonitrile molecules with the crown ether, the Η···Ο distances being 243, 253, and 267 pm, respectively. [Na-15-crown-5][ReO4] · CH3CN is formed as a by-product of the reaction of ReNCl4 with sodium fluoride in acetonitrile in the presence of 15-crown-5 and traces of water. Space group Ρ 1̄ , Ζ = 2, 3107 observed independent reflexions, R = 0.045. Lattice dimensions at 19°C: a = 823.4(1), b = 1078.8(1), c = 1204.0(1) pm; α = 112.40(1)°, β = 94.35(1)°, γ = 104.63(1)°. The compound forms ion pairs, in which the sodium atom is sixfold coordinated by the five oxygen atoms of the crown ether molecule, as well as by one oxygen atom of the ReO4- ion, which is only slightly distorted. The bond length Na—OReO3 is 237.8(8) pm, the bond angle NaORe is 164.3(5)°. [Na-15-crown-5]PF6 is formed in the reaction of [ReCl3(NSCl)2 · POC13] with sodium fluoride in acetonitrile solution in the presence of 15-crown-5. Space group Pna21, Ζ = 4, 1130 observed independent reflexions, R = 0.123. The high R value is due to disorder of the skeletal atoms of the crown ether molecule. The compound forms ion pairs, in which the sodium atom is sevenfold coordinated by the five oxygen atoms of the crown ether molecule, as well as by two fluorine atoms of the PF6 - ion with Na—F bond lengths of 240(2), and 246(2) pm, respectively.

Synthesis of cedranoid sesquiterpenes. V. The biotols

Reduction of dimethyl 3-hydroxy-4,4,8-trimethyl-6-oxo-cis-bicyclo[3.3.0]octa-2,7-diene-1,2-dicarboxylate (8) with lithium and ammonia gives dimethyl 3-hydroxy-4,4,exo-8-trimethyl-6-oxo-cis-bicyclo[3.3.0]oct-2-ene-1,2-dicarboxylate (9), which on acetylation, reduction with sodium borohydride, and methanolysis gives dimethyl 3,exo-6-dihydroxy-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]oct-2-ene-1,2-dicarboxylate (12). This on 2-decarbomethoxylation followed by treatment with lithium acetylide in the presence of cerium trichloride gives methyl 3-ethynyl-3,exo-6-dihydroxy-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]octane-1-carboxylate (21), which on hydration, diacetylation, and treatment with tri-n-butyltin hydride and azoisobutyronitrile is converted to methyl exo-6-acetoxy-3-acetyl-4,4,exo-8-trimethyl-cis-bicyclo[3.3.0]octane-1-carboxylate (31). Methanolysis of 31. tert-butyldimethylsilylation, and reaction with potassium tert-butoxide in tert-butyl alcohol gives exo-4-tert-butyldimethylsilyloxy-exo-2,6,6-trimethyl[5.3.11,5]undecane-8,10-dione (35). This on treatment with lithium aluminum hydride followed by oxidation and hydrogenation provides the corresponding 10-deoxo compound, 39. Reaction of this with methyllithium, dehydration, and desilylation with hydrogen fluoride in acetonitrile gives a mixture of (±)-α-biotol (1) and (±)-β-biotol (2); desilylation with hydrogen chloride in methanol gives solely (±)-1.

A new synthesis of 2‐deoxy‐2‐[18f]fluoro‐D‐galactose using [18f]fluoride ion

AbstractA nucleophilic radiofluorination of methyl 3,4‐0‐isopropylidene‐2‐0‐(trifluoromethanesulfonyl)‐6‐0‐trityl‐β‐D‐ talopyranoside (1) with aminopolyether (Kryptofix 2.2.2.) supported potassium [18F]fluoride in acetonitrile gave methyl 2‐deoxy‐2‐(18F) fluoro‐3,4‐o‐isopropylidene‐6‐0‐trityl‐β‐D‐galactopyranoside (2). Hydrolysis of 2 with 6N HCl followed by passage through an ion retardation resin column and a neutral alumina column gave 2‐deoxy‐2‐[18F]fluoro‐D‐galactose (2‐18FDGal) in 36–39% overall radiochemical yield without correction for decay. The total preparation time was about 90 min from start of the radiofluorination.

Alternative synthesis of no‐carrier‐added 2‐deoxy‐2‐[18F]fluoro‐D‐glucose using [18F] fluoride ion

AbstractTwo alternative routes to no‐carrier‐added synthesis of 2‐deoxy‐2‐[18F]fluoro‐D‐glucose (2‐18FDG) involving nucleophilic displacements of methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐O‐(trifluoromethanesulfonyl) ‐β‐D‐mannopyranoside (1) and 1,6‐anhydro‐3, 4‐di‐O‐benzyl‐2‐O‐(trifluoromethanesulfonyl)‐β‐D‐mannopyranose (2) are described. The triflates (1 and 2) reacted with aminopolyether (Kryptofix 222) supported potassium [18F]fluoride and tetra‐n‐butylammonium [18F]fluoride in acetonitrile to give methyl 3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐2‐[18F] fluoro‐β‐D‐glucopyranoside (3) and 1,6‐anhydro‐3,4‐di‐O‐benzyl‐2‐deoxy‐2‐[18F] fluoro‐β‐D‐glucopyranose (4), respectively. The displacement yield with 1 was consistently higher than that with 2. Hydrolysis of 3 with 6N HCl, followed by passage through an ion retardation resin column and a neutral alumina column, gave 2‐18FDG in 34–43% overall radiochemical yield without correction for decay. Removal of the protecting groups from 4 with 6N HCl or 50% CH3SO3H led to incomplete hydrolysis. The total preparation time was about 80 min from start of the radiofluorination.

Alumina supported potassium fluoride promoted reaction of nitroalkanes with electrophilic alkenes : synthesis of 4,5-dihydro furans and isoxazoline n-oxides

The reaction of secondary nitro alkanes 1 with α,β-unsaturated ketones 2 in the presence of alumina-supported potassium fluoride in acetonitrile gave 4,5-dihydrofurans 3 in high yields ; 1-nitropropane reacted with 2 to give a mixture of 4,5-dihydrofurans and furans. Nitroalkenes 17 reacted with nitroalkanes to give isoxazoline N-oxides 18 and 19 in good overall yields.

Preparation of ortho-substituted aryldifluorophosphines, 2-XC 6H 4PF 2 (X = MeO or Me 2N), and some of their derivatives. X-ray crystal structure determination of (2-MeOC 6H 4P) 4 and of the platinum complex, Cl 2Pt(2-MeOC 6H 4PF 2) 2

The preparation of the ortho-substituted aryldifluorophosphines 2-MeOC 6H 4PF 2 and 2-Me 2NC 6H 4PF 2 by chlorine-fluorine exchange from the corresponding dichlorophosphines using sodium fluoride in acetonitrile in the presence of a crown ether is described. The ortho-substituted aryldichlorophosphines 2-MeOC 6H 4PCl 2 and 2-Me 2NC 6H 4PCl 2 were prepared from the respective bis( N, N-dimethylamino) phosphines by cleavage of the PN bonds with hydrogen chloride. The reaction of 4-fluoroanisole and 2-methoxy-phenyllithium with phosphorus trichloride did not yield the expected chlorophosphines, i.e. 2-MeO-5-F-C 6H 3PCl 2 and 2-MeOC 6H 4PCl 2, but led to formation of 4-fluorophenyldichlorophosphite in the former, and to tris(2-methoxyphenyl)phosphine in the latter case. The difluorophosphine 2-MeOC 6H 4PF 2 was found to undergo a spontaneous oxidation-reduction reaction with formation of the tetrafluorophosphorane 2-MeOC 6H 4PF 4, and the cyclotetraphosphine (2-MeOC 6H 4P) 4. A single-crystal X-ray structure determination of the latter indicated the presence of a strongly puckered four-membered ring with PP bond lengths ranging between 222 and 223 pm, and endocyclic bond angles of 84°. Vicinal MeOC 6H 4 groups were found arranged trans to each other. Dichloroplatinum(II) complexes were prepared, involving the two new fluorophosphines, 2-XC 6H 4PF 2 (X = MeO or Me 2N), as ligands. In neither case was any evidence found for coordination between platinum and oxygen or nitrogen, and the fluorophosphines were found to function solely as phosphorus donors. The absence of interaction between platinum and the oxygen atom in the ortho position of the ligand 2-MeOC 6H 4PF 2 was confirmed in a single-crystal X-ray determination of the complex Cl 2(2-MeOC 6H 4PF 2) 2Pt. The compound was found to exist as a planar, cis-coordinated species with PtCl bond lengths between 232 and 234 pm, and a PtP bond length of 218 pm. All compounds were characterized by NMR spectroscopy ( 1H, 31P and 19F, where applicable).

The dimethylsulfonium moiety as a leaving group in aromatic radiofluorination using tetra-n-butylammonium [ 18F]fluoride

The reaction of aryldimethylsulfonium methylsulfates with tetra-n-butylammonium [ 18F]fluoride in acetonitrile or dimethyl sulfoxide has been studied. Fluorine-18 incorporation into the aromatic ring of the selected aryldimethylsulfonium salts was observed, depending greatly on the substituent group on the aromatic ring. It was found that the displacement yields with the p-nitro- and o-nitro-substituted substrates are consistently greater using a polymethylpentene vessel than those using a Pyrex vessel. The nucleophilic displacement of the dimethylsulfonium group was not a good general method for labeling aromatic compounds with 18F, because of the facile demethylation of the sulfonium salt by a nucleophile present.

(PPh 4) 3Ag[WF 5(C 2I 2)] 2; synthese, IR-spektrum und kristallstruktur

The compound (PPh 4) 3Ag[WF 5(C 2I 2)] 2 is formed by the reaction of PPh 4[WCl 5(C 2I 2)] with an excess of silver fluoride in acetonitrile. The compound is soluble in CH 2Cl 2; when CCl 4 is added single red crystals are obtained. The complex is characterized by its IR spectrum and by an X-ray structural study (4060 observed, independent reflexions, R = 0.105). Crystal data: orthorhombic, space group P2 12 12, Z = 2, a 4464(2), b 1074(1), c 777,6(4) pm. The compound consists of PPh 4 + and Ag + ions, and the anions [WF 5(C 2I 2)] 2−, in which the tungsten atoms are seven-coordinated by five fluorine atoms and two carbon atoms. The diiodoacetylene ligand is symmetrically bonded sideways to the tungsten atom. The four equatorial F atoms have WF bond lengths of 191 pm, whereas the fluorine atom in trans-position to the WC 2 group is located 199 pm from the metal centre. The PPh 4 + ions are stacked in parallel columns.

Preparation of no carrier added fluorine-18 labeled 16-fluorohexadecanoic and fluoroacetic acids from highly reactive tetraethylammonium [ 18F]fluoride

No carrier added tetraethylammonium [ 18F]fluoride prepared via synthesis and hydrolysis of fluorotrimethylsilane was reacted with methyl 16-iodohexadecanoate in acetonitrile. At 80°C, yields of up to 80% were found with reaction times of 20–30 min. As would be expected for fluoride-for-iodide exchange, reactions were slower than previously-reported cyclic sulfate and triflate displacements. TLC and reverse-phase HPLC indicated that a single pure radioactive product was formed, which was hydrolyzed with alkali to the free acid. NMR spectroscopy of a carrier added preparation was consistent with assignment as 16-fluorohexadecanoic acid and no rearrangement to the 15-fluoro compound. [ 18F]Fluoroacetic acid was prepared analogously in high yield from ethyl iodoacetate. The results are discussed in terms of guidelines for syntheses of other 18F compounds and of the properties of near anhydrous tetraethylammonium fluoride in acetonitrile.

D,l-α-fluoropalmitic acid inhibits sphingosine base formation and accumulates in membrane lipids of cultured mammalian cells

d,l-α-Fluoropalmitic acid was synthesized by tosylation of methyI- d,l-α-hydroxypalmitate, and displacement of the tosylated function by tetrabutylammonium fluoride in acetonitrile. Uptake and utilization of the compound by cultured Balb/c 3T3 cells were studied after presentation of the fluoro fatty acid analogue complexed with bovine serum albumin. A concentration of 0.28 mM had very little effect on cell growth over several days of incubation, and cell morphology was unchanged. Chromatographie and mass spectrometric analyses at 6 and 12 h of incubation showed that d,l-α-fluoropalmitic acid was taken up by the cells and incorporated without modification as a fatty acyl moiety into select lipids. Significant levels of the compound were found at 12 h in phosphatidylcholine (1.6%) and sphingomyelin (0.6%) fatty acids, but not in those of other phospholipids or neutral lipids. d,l-α-Fluoropalmitic acid represented a significant percentage of the fatty acids of neutral glycosphingolipids (1.4%) and ceramides (0.8%) by 12 h. The fluoro fatty acid was not incorporated into long-chain sphingolipid bases, and mass spectrometry failed to reveal additional carbon-2 fluorine-substituted compounds in cellular lipids. Cellular levels of triacylglycerols and phosphatidylcholine remained essentially unchanged, or were slightly increased, while amounts of ceramide and gangliosides were decreased. Comparison of labeled palmitate incorporation into sphingolipid bases and fatty acids of sphingomyelin suggested inhibition of sphingosine synthesis by the fluoro fatty acid. d,l-α-Fluoropalmitic acid inhibited the formation of palmitoyl-CoA by Balb/c 3T3 long-chain acyl-CoA synthetase in vitro. The results support involvement of CoA thiol ester-independent steps in modification of membrane lipids.

ChemInform Abstract: SYNTHESIS OF FLUORONAPHTHOQUINONES: HALIDE DISPLACEMENT BY NAKED FLUORIDE

AbstractDurch Komplexierung von KF mit 18‐Krone‐6 wird der Einsatz von nichtsolvatisiertem Fluorid möglich.

Fluoro norcholesterol analogues. Synthesis of 6 beta-(2'-fluoro) ethyl-19-norcholest-5(10)-en-3 beta-ol.

A synthetic route for labelling 6 beta-(2'-fluoro)ethyl-19-norcholest-5(10)-en-3 beta-ol (VII) with fluorine-18 was developed to evaluate the potential utility of VII as an adrenal imaging agent. 6 beta-p-Toluene-sulphonyloxymethyl-19-norcholest-5(10)-en-3 beta-ol acetate (I) was converted to the 6 beta-(2'-hydroxy)ethyl (VI) in a five-step process. The treatment of VI with N-N-diethyl (2-chloro-1,1,2,-trifluoroethyl)amine in methylene chloride and subsequent hydrolysis with base gave the required VII. Iodination of VI with triphenoxymethylphosphonium iodide followed by alkaline hydrolysis gave the 6 beta-(2'-iodo)ethyl (IX) which, on treatment with silver fluoride in acetonitrile, furnished the 6 beta-(2'-fluoro)ethyl (VII). Excellent conversion of the 6-beta-(2'-p-toluenesulphonyloxy)-ethyl (X) into VII was also achieved by heating with potassium fluoride for 2 hr in diethylene glycol in 76% yield, which is a readily applicable method for labelling with fluorine-18.

Polyfluoro-1,2-epoxy-alkanes and -cycloalkanes. Part I. Preparation of some polyfluoro-1,2-epoxycyclohexanes

Polyfluorocyclohexenes with hydrogen, bromine, and methoxy substituents yielded the corresponding 1,2-epoxides when treated with aqueous sodium hypochlorite containing some acetonitrile. 4,5-Dibromooctafluoro-1,2-epoxycyclohexane was debrominated with zinc dust to give a mixture of octafluoro- and 4H-heptafluoro-1,2-epoxycyolohex- 4-ene. Decafluoro- and 4,5-dibromo-octafluoro-1,2-epoxycyolohexane gave with potassium fluoride in acetonitrile the corresponding potassium perhalogenocyclohexyloxides; heating these gave the analogous cyclohexanones, and treatment with methyl iodide the methyl ethers. The unsaturated 1,2-epoxides also gave methyl ethers on treatment with KF, followed by methylation.

A new method of preparation of trialkyldifluorophosphoranes

Trialkyldifluorophosphoranes are obtained in good yields by the fluorination of bromotrialkylphosphonium bromides with sodium fluoride in acetonitrile.

A new sulfene synthesis

Treatment of trimethylsilylmethanesulfonyl chloride with cesium fluoride in acetonitrile at room temperature has been found to produce sulfene which can be trapped in good yield.

A CONVENIENT SYNTHESIS OF ACETYLENIC KETONES FROM β-DIKETONES USING α,α-DIFLUOROALKYLAMINES AND FREEZE-DRIED POTASSIUM FLUORIDE

Abstract α,α-Difluoroalkylamines, such as 1-diethylamino-2-chloro-1,1,2-trifluoroethane (1) and 1-diethylamino-1,1,2,3,3,3-hexafluoropropane (2), were found to be useful dehydrating agents for the synthesis of acetylenic ketones from β-diketones in the presence of freeze-dried potassium fluoride in acetonitrile.

Silicon tetrafluoride : Preparation and reduction with lithium aluminium hydride

Pure silicon tetrafluoride can be prepared in 66% yield from silicon tetrachloride by refluxing with lead fluoride in acetonitrile. The gas can be reduced to pure silane by lithium aluminum hydride in diethyl ether.