Fluorocyclohexane

A polymeric form of the reagent from hydrogen fluoride and poly(4-vinylpyndine) is especially easy to handle [I0 Other tertiary amines can also be employed [II], and a two-phase mixture of hydrogen fluoride-melamine-pentane hydrofluorinates cyclohexene to fluorocyclohexane m 98% yield [12]... 

The preferential syn elimination of hydrogen fluoride from trans-l-bromo-2-fluorocyclohexane to give 1 -bromocyclohexene is achieved only when a strong base such as sodamide is used [55, 56] Potassium rcrt-butoxide causes elimination of hydrogen bromide to form 3-fluorocyclohexene [56] (equation 27)... 

Under the foregoing conditions, fluorocyclohexane gives cyclo-... 

It is believed that equatorial substituents such as chlorine or bromine would increase the guest diameter beyond the allowed values (assuming that the guest molecules stack roughly parallel to the canal68)). Support for this comes from the study of fluorocyclohexane where the population of the axial conformer is not enhanced to any major extent70. Nitro-71) and cyano-cyclohexane, trans-l,2-dichloro-, trans-1,2-dibromo-, tram-1,4-dichloro-, trans-1,4-dibromo-, and trans-l-bromo-4-chloro-cyclohexane all pack most efficiently in the thiourea canals as the axial or diaxial conformer 68,72. Tram-2,3-dichloro-1,4-dioxane behaves similarly73. In contrast isocyanato-, tram-1,4-diiodo-, trans-1 -bromo-4-iodo-, and tram-1 -chloro-4-iodo-cyclohexane are present as mixtures of the axial/equatorial or diaxial/diequatorial conformations as appropriate 68,72). The reason for this anomalous behaviour of the iodosubstituted cyclohexanes is not clear. 

Fooking more closely at fluorocyclohexane systems, it has been observed that a fluorine substituent in the axial position is much more highly shielded than one in the equatorial position. Of course,... 

More evidence for the existence of several conformational isomers, at least in liquid and gaseous substances comes from infrared and also Raman spectra. For example each conformer has its own I.R. spectrum, but the peak positions are often different. Thus the C-F bond in equatorial fluorocyclohexane absorbs at 1062 Cm-1, the axial C-F bonds absorbes at 1129 Cm . So the study of infrared spectrum tells, which conformation a molecule has. Not only this, it also helps to tell what percentage of each conformation is present in a mixture and since there is relationship between configuration and conformation in cyclic compounds the configuration can also be frequently determined. 

Hendrickson et al. 24 using the Westheimer-Allinger 19 method. Our calculated activation energy (6.0 kcal/mole) is less than those reported by Anet et al25) (10.3, 10.8 kcal/mole). Since, however, the barrier to inversion in per-fluorocyclohexane is 7.5 kcal/mole 26 and since the rates of inversion of cyclohexene and perfluorocyclohexane are very similar, the barrier reported for cyclohexane may be too large. 

The isolation of benzene and cyclohexane from chlorobenzene and thiophenol, and cyclohexane from fluorobenzene, suggests the preferential reductive cleavage of the substituent prior to hydrogenation of the ring. However, fluorocyclohexane decomposes slowly to cyclohexene, which could give rise to the cyclohexane higher yields of fluorocyclohexane are obtained at lower temperatures. 

Nucleophilic displacement using [ F] fluoride works well in aUphatic systems where reactive haUdes or sulfonates esters can undergo substitution at unhindered sites. In order to introduce a F fluorine atom in a secondary or tertiary position, a two steps strategy was developed. It involves a F-bromofluorination of alkenes, followed by reductive debromination (n-BujSnH, AIBN). [ F]BrF is usually generated in situ from [ F]potassium fluoride and l,3-dibromo-5,5-dimethylhydantoin (DBH) in sulfuric acid. This methodology was successfully applied to label steroids at the 11 and 6a positions [245] (Scheme 60) and to prepare [ F]fluorocyclohexanes [246]. 

Molecular motion in solids has been the object of many studies in the field of physical chemistry of polymers , but dynamic processes in molecular crystals of organic and inorganic compounds are less well investigated. In fact, the average chemist is not aware of the fact that processes like internal rotation or ring inversion proceed in solids quite often with barriers which are not very different from those found for these types of internal motion in the liquid state. Thus, for the equatorial axial ring inversion of fluorocyclohexane values of 42.4 and 43.9 kJ mol have been measured in the liquid and the solid, respectively. The familiar thermal ellipsoids of individual atoms obtained from X-ray studies are qualitative indicators of molecular motion in the crystal, but a more quantitative study of such processes is only possible after appropriate solid state NMR techniques are applied. 

All models (except STO-3G and semi-empirical models) reproduce the significant reduction in dipole moment observed in going from equatorial to axial fluorocyclohexane, but all underestimate the even... 

Except for fluorocyclohexane and chlorocyclohexane, the lower-energy conformer for all molecules examined has the smaller dipole moment. This is in accord with Coulomb s law (increased separation of charge leads to increased energy). 

The hydrofluorination of alkenes with anhydrous hydrogen fluoride has been already described extensively in Houben-Weyl, Vol. 5/3, pp 100-101. In the case of ethene, the yield of fluoroethane increases on raising the temperature (90°C, 20-25 atm), however, the procedure should be carried out at lower temperatures with higher alkenes because of their tendency to polymerize thus, 2-fluoropropane is formed in 60-75% yield at 0-45 C. Similar procedures have been described for 2-fluorobutane, 2-fluoro-2-methylpropane and 2-fluoro-2-methyl-butane from but-l-ene, 2-methylpropene and 2-methylbut-2-ene, respectively.63 Cyclohexene reacts at — 78 C with hydrogen fluoride to give fluorocyclohexane (70%) at 100 C polymerization is observed.59,60 Two equivalents of hydrogen fluoride to allene are taken up at — 70 C, to form 2,2-difluoropropane (50%).64... 

A solution of HF/melamine (86 14 w/w) was prepared by gradually dissolving solid melamine (2.1 g. 16.7 mmol) in anhyd HF (12.9 mL, 0.65 mol) in a 100-mL polyethylene reaction vessel with stirring at 0 C. Cyclohexenc (0.5 mL, 5 mmol) dissolved in pentane (3 mL) or CC14 was then added diopwise to the stirred solution. The mixture was further stirred at 0 C for 10 min. The organic layer was then separated (free from HF) and distilled to isolate fluorocyclohexane yield 98-100% bp 100 C. 

Chlorofluorination of various alkenes and two acetylenes (phenylacetylene, methylphenylacety-lene) have been reported with an /V-chlorosaccharin/pyridine system.338 Depending on the substrate, the addition proceeds either exclusively anti or with high anti stereoselectivity. The reactivity of this system was initially tested in a reaction of cyclohexene. Reaction at room temperature or in an ice bath (10 min) results in a complete chlorofluorination to practically pure P an.s-l-chloro-2-fluorocyclohexane. 

Heating the xenon difluoride hexane mixture to 80-90"C in a sealed glass tube leads to its inflammation. If the xenon difluoride and hexane (1 5 mol) are heated in a Teflon tube at 105 "C, the products are 1-, 2- and 3-fluorohexanes (28 42 30) with a total yield of 15-20%.13 Under the same conditions cyclohexane has been converted to fluorocyclohexane in 18 % yield. 

Bromofluorination of Alkenes with the DBH/PVPHF (64/36) System l-Bromo-2-fluorocyclohexane Typical Procedure (Method B) 41... 

Chlorocyclohexene (20 g. 0.17 mol) was added to BF3 OEt2 (24 g, 0.17 mol) and HF (3.4 g, 1.7 mol) dissolved in anhyd Et20. After neutralization with i-PrNH2 in anhyd Et20 the solid formed was filtered and the solvent was evaporated under reduced pressure. Distillation then gave I -chloro-l-fluorocyclohexane (18) yield 3g (13%) bp 6(TC. 

To a stirred solution of N02 BF4 (6.64 g, 50 mmol) in PPHF (70 30, 30 mL) in a 200-mL polyethylene bottle at — 5°C under a dry N2 atmosphere was added dropwise 1-bromocyclohexane (6.52g, 40mmol) over a period of 10 min. The mixture was stirred at — 5 °C for 15 h and was then poured into ice water (200 mL). The resulting mixture was extracted with Et20 (2 x 200 mL), and the combined ethereal extract was washed several times with 10% aq NaHC03 followed by brine soln until neutral. The neutral Et20 extract was dried (Na2S04) and concentrated in vacuo. The remaining residue was distilled under vacuum to provide pure tra .s-l-bromo-2-fluorocyclohexane yield 5.0 g (69%) bp 75-77 C/ll Torr. 

A convenient method for the chlorofluorination of cyclohexene, with a mixture of lead(IV) acetate and anhydrous hydrogen fluoride in the presence of sodium or copper(II) chloride in 1,1,2-trichlorotrifluoroethane (Halon-113) at room temperature, has been described.22 The major product in this reaction is /ranj-l-chloro-2-fluorocyclohexane obtained in 70% yield. Byproducts are 2-chlorocyclohexanol and l-acetoxy-2-chlorocyclohexane which are obtained in 25 and 5 % yield, respectively. 

The further fluorination of partially fluorinated compounds has been extensively used, particularly to elucidate the structures of such compounds. Two examples from a vast number are56,57 the fluorination of 1 //.4//./2//-hcptafluorocyclopenmne (12) and l//,2//.4// 5//-octa-fluorocyclohexane (21). 

Bromopentafluorobenzene and cobalt(III) fluoride react at 100 °C to give77 bromoundeca-fluorocyclohexane in over 50 % yield as the major product,... 

There are many possible sources of error in the calculation of equilibrium from dipole moments. It is difficult to calculate accurately the moments of model compounds. As has been pointed out,124 the carbon skeleton itself contributes to the moment, as shown by the different dipole moments of ethyl bromide (2.069 D) and n-hexyl bromide (2.156 D) and of axial and equatorial fluorocyclohexane (1.81 D and 2.11 D, respectively). For nonsym-metrical molecules in general, the estimation of the precise direction of a dipole moment is subject to considerable error. 

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