1.4- Dioxane, fluorination

The enamines, enol ethers and enol acetates of A -3-keto steroids provide important substrates for fluorination with FCIO3. Reaction of such A -enol ethers and acetates (6) with perchloryl fluoride results in 6a- and 6jff-fluoro-A -3-ketones (7) and (8), the latter representing the more abundant isomer. Tetrahydrofuran or dioxane-water mixtures appear to be particu-... 

However, when the chlorine atoms are more dispersed through a polychlorofluorocarbon, both chlorine and fluorine may be removed by zinc. In these cases, triphenylphosphine in dioxane can be used to prepare dechlonnated products in high purity and good yield [6S](equations 36 and 37)... 

The spectral properties of pentafluorophenylcopper te-tramer are as follows infrared (Nujol) cm. 1630 medium 1391 medium 1353 medium 1275 medium 1090,1081, and 1071 strong triplet 978 strong 785 medium fluorine magnetic resonance (tetrahydrofuran with trichlorofluoromethane as internal reference) 8 (multiplicity, number of fluorines, assignment, coupling constant J in Hz.) 107.2 (20-line multiple , 2, ortho F), 153.4 (triplet of triplets, 1, para F, J= 1.3 and 20), 162.3 (17-line multiplet, 2, meta F). Absorptions at 820-900, 1100-1125, and 1290 cm.- in the infrared spectrum and at 8 3.05 in the proton magnetic resonance spectrum indicate that dioxane is still present. 

In table I we present the molar Kerr constants and mean square dipole moments of three fluorinated polymers, poly (trifluoroethylene) (PFjE), polylvinylidene fluoride) (PVF2) and poly(fluoromethylene) (PFM), dissolved in p-dioxane. The results show the sensitivity of mK to the degree and type of fluorination varying over an order of magnitude and also changing sign. Calculations of mK and for comparison are in progress (5). 

In this example the solvent - a fluorinated alcohol - forms higher order aggregates and activates for the epoxidation of electron rich olefins. HFIP accelerates this oxidation reaction up to 100,000-fold (relative to that in 1,4-dioxane as solvent). Which hydrogen bond network involving olefin, and fluorinated alcohol gives rise to such spectacular accelerations ... 

A new class of liquid crystals with strongly negative dielectric anisotropy was explored by employing the ambivalent characteristics of the 1,3-dioxane moiety <2006EJ04819> due to both the polarity of 1,3-dioxane and axial fluorination, compounds 238-240 proved to have very useful mesogenic and electrooptical properties. 

Testosterone enol diacetate reacts with perchloryl fluoride in aqueous dioxane to give 6a- and 6/i-fluorotestostcrone 17-acetatc (18 X = a-F, /i-F) as the major products along with 6a- and 6/3-hydroxytestosterone 17-acetate (18 X = a-OH, /j-OH) and also 17/i-hydroxyandrostane-3,6-dione 17-acctate.31 The enamine derivative 3-(pyrrolidin-l-yl)estra-3,5-dien-17/i-ol can be fluorinated in methanol at —25 to — 35 C to provide 4/J-fluoro-3a-methoxycstr-5-ene-3/f 17/ -diol (19),32 while various 2-fluoro-3-oxoestranc derivatives 20 are formed by fluorination of a number of 3-methoxyestrane derivatives in tetrahydrofuran/water mixture with perchloryl fluoride.33... 

In the reaction of rnr-3,6-dimethyl-l,4-dioxane-2,5-dione (m.-lactide) with sulfur tetrafluoride in hydrogen fluoride solution, together with fluorination of both carbonyl groups, substitution of one of the tertiary hydrogen atom by fluorine also occurs a diastcrcomeric mixture of 2,3,3.6,6-pcntafluoro-2,5-dimethyl-l,4-dioxane (12) is formed in 75% yield (cf. Section 8.2.7.).166... 

Thus, the reaction of 1,4-dioxane with sulfur tetrafluoride and hydrogen fluoride in the presence of small amounts of sulfur chlorides or chlorine (0.3 0.5 %) at 185-220°C results in the replacement of 3-5 hydrogen atoms by fluorine to give mixtures of a polyfluoro-1,4-dioxane 1 or 3 and 2-fluoroethyl-l,2,2,2-tetrafluoroethyl ether (2) in a ratio dependent on the reaction temperature.237 Using technical grade sulfur tetrafluoride without addition of a sulfur chloride or chlorine, this reaction is not reproducible, but when carefully purified sulfur tetrafluoride is used the reaction does not give fluorinated products, instead a tar is formed.237... 

The reaction of bis(2-methoxyethyl) ether (diglyme, 7) at 160°C results in elimination offluoro-methane, cyclization and substitution of three hydrogen atom by fluorine to give 2,2,3-trifluoro-1,4-dioxane (1).23S... 

The use of solvent has also proved to be necessary in the fluorination of 3,3,3-trichloro-l-phenylpropene18 and l-(4-bromophenyl)-3,3,3-trichloropropene19 with antimony(III) fluoride. 3,3,3-Trifluoro-l-phenylpropene and l-(4-bromophenyl)-3,3,3-trifluoropropene are obtained in 80 and 65% yield, respectively, by refluxing the reactants in dioxane for 7 hours. Tarring occurs in the absence of solvent.15... 

The reaction of 2,2-dichloro-l,3-benzodioxole with antimony(III) fluoride is so vigorous that, to prevent tarring, it is conducted in dioxane which complexes antimony(III) fluoride and essentially reduces its fluorinating activity,39 while 2,2-dichloro-5-chlorocarbonyl-l,3-ben-zodioxole is fluorinated in the absence of solvent.40 The products obtained are 2,2-difluoro-l, 3-benzodioxole (52% yield, bp 129-130 JC)39 and 2,2-difluoro-5-fluorocarbonyl-l,3-ben-zodioxole (82% yield, bp 75-76°C/17 Torr).40... 

Dioxane is partially fluorinated84 over cobalt(lll) fluoride and potassium tetra-fluorocobaltate(III). With cobalt(III) fluoride at 100°C yields are poor (ca. 15%), and the major products are 7-10 (as with the oxolanes, equilibrium occurs between the stereoisomers during the fluorination). With potassium tetrafluorocobaltate(III) at 220°C, compound 11 comprises 61 % of the product mixture in an overall yield of about 40%. 

Oxathiane has only been fluorinated84 over potassium tetrafluorocobaltate(III) (vide infra). and this gives products very similar in structure to those formed in the dioxane/cobalt(Hl) fluoride fluorination. 

The fluorination of oxathiane is described in Section 25.1.1.3.84 1,4-Dithiane reacts quite differently107 from dioxane and oxathiane over potassium tetrafluorocobaltate(III). The major products (ca. 60 % of the product mixture, itself in ca. 50 % yield) are the result of rearrangement to the 2-methyl-l, 3-dithiolane skeleton, e.g. 1-3. Fluorinated 1,4-dithiancs comprised about 30% of the product the major product is 4. The extent of fluorination, that is the number of fluorine atoms introduced, is much greater than that of dioxane under comparable conditions (tetrahydrothiophene and tetrahydrofuran show a similar contrast). 

Fluonnated ylides have also been prepared in such a way that fluorine is incorporated at the carbon p to the carbamomc carbon Various fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyllithium or lithium dusopropy-lamide did not lead to y hde formation, rather, deprotonation was accompanied by loss of fluonde ion However deprotonation with hydrated potassium carbonate in dioxane was successful and resulted in fluoroolefin yields of45-80% [59] (equation 54) p-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydride The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyllithium to form a new ylide, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [61] such as an acetylide to form a fluonnated enyne [62] (equation 56)... 

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