Fluorocarbon derivatives of nitrogen. Part I. Some reactions of perfluoro-1-azacyclohexene

Controlled displacement of fluorine from perfluoro-1-azacyclo-hexene (I) by the nucleophilic reagents Me₂NH, Et₂NH, $\text{CH}{}_2\text{CH}{}_2\text{O(CH}{}_2\text{)}{}_2\text{N}$H, C₆Cl₅ONa, and (CF₃)₂NONa provides the derivatives (II) - (IV), respectively. The last of these can also be obtained by treatment of the parent compound (I) with mercury^II bistrifluoromethylnitroxide.     

Fluorocarbon derivatives of nitrogen. Part IV [1]. Perfluoro-1-azacyclohex-1-ylcaesium

Caesium fluoride combined with perfluoro-1-azacyclohexene in acetonitrile to yield perfluoro-1-azacyclohex-1-ylcaesium (1), which was characterised by ¹⁹F n.m.r. spectroscopy and by treatment with iodomethane to give 2,2,3,3,4,4,5,5,6,6-decafluoro-1-methyl-1-azacyclohexane (2). Attempts to derivatize the caesium salt with chlorotrimethylsilane provided fluorotrimethylsilane, perfluoro-[1-(1-azacyclohex-1-en-2-yl)-1-azacyclohexane] (4), and 2-chloro-3,3,4,4,5,5,6,6-octafluoro-1-azacyclohexene (5); information on the course of this reaction was obtained through experiments in which perfluoro-1-azacyclohexene was shown to undergo conversion into its chloro-analogue (5) and its dimer (4) $\text{via}$ treatment with chlorotrimethylsilane and fluoride ion, respectively. Aluminium chloride also converts perfluoro-1-azacyclohexene into its chloro-analogue (5).     

Fluorocarbon derivatives of nitrogen. Part VII [1]. Reaction of N-iminopyridinium ylide with perfluoro-1-azacyclohexene,perfluoro-2-azapropene,and perfluoroacetonitrile

The novel ylides (II) and (III) have been obtained $\text{via}$ treatment of perfluoro-1-azacyclohexene and perfluoro-2-azapropene, respectively, with $\text{N}$-iminopyridinium ylide (I) generated $\text{in}$$\text{situ}$ from $\text{N}$-aminopyridinium iodide and anhydrous potassium carbonate in methylene chloride. A mixture of the $\text{s}$-triazolo[1,5-$\text{a}$]pyridine (IV) and a compound thought to be its dihydro-analogue (V) were isolated following attack on perfluoroacetonitrile by the parent ylide (I); the former product was also prepared by heating 1,2-diamino-pyridinium iodide with trifluoroacetic anhydride.     

Fluorocarbon derivatives of nitrogen. Part 11. Synthesis of some 2-(trifluoromethyl)imidazo[1,2-a]pyridines from trifluoroacetonitrile

3-(t-Butoxycarbonyl)-2-(trifluoromethyl)imidazo[1,2-$\text{a}$]-pyridine, prepared from trifluoroacetonitrile and pyridinium t-butoxycarbonylmethylide, reacts smoothly with trifluoroacetic acid to provide 2-(trifluoromethyl)imidazo[1,2-$\text{a}$]pyridine-3-carboxylic acid, which gives 2-(trifluoromethyl)imidazo[1,2-$\text{a}$]-pyridine when heated. 3-Cyano-2-(trifluoromethyl)imidazo[1,2-$\text{a}$]pyridine can be obtained $\text{via}$ treatment of trifluoroacetonitrile with pyridinium cyanomethylide, which is sufficiently reactive to effect nucleophilic displacement of fluorine from pentafluoropyridine under mild conditions [→pyridinium cyano(tetrafluoro-4-pyridyl)methylide].     

Nitroxide chemistry. Part XIX. Reaction of bistrifluoromethyl nitroxide with diphenylketene and related compounds (Ph2CHCOX,X  OH,Cl, NH2)

The following reactions have been accomplished: 2(CF₃)₂NO· + Ph₂CCO → Ph₂C[ON(CF₃)₂]CO₂N(CF₃)₂ → (on hydrolysis) Ph₂C[ON(CF₃)₂]CO₂H; 2 (CF₃)₂NO· + Ph₂CHCOX → (CF₃)₂NOH + Ph₂C[ON(CF₃)₂]COX (X  OH, Cl,NH₂).     

Studies in azide chemistry. Part 12. One-pot conversion of 4-azidotetrafluoropyridine to 1,3,4-trifluoro-7,9-dimethyl-11H-pyrido[4,3-c]benzo[1,2]diazepine

Thermolysis of 4-azidotetrafluoropyridine in the presence of an excess of mesidine at 170 °C yields tetrafluoro-4-(2,4,6-trimethylphenylazo)- pyridine, which undergoes intramolecular dehydrofluorination $\text{in situ}$ to provide 1,3,4-trifluoro-7,9-dimethyl-11$\text{H}$-pyrido[4,3-$\text{c}$]benzo[1,2]diazepine.     

Nuclear magnetic resonance spectra of polyfluorobuta-1,3-dienes. Part II [1]. Variable temperature study of two 2-azabutadienes

The two perfluoro-azadienes CF₂N.CRCF₂ (R = CF₃ or CF₂Cl) show temperature dependent ¹⁹F n.m.r. spectra, with non-equivalent fluorine nuclei of the CF₂N portion at low temperatures, which coalesce due to inversion at the nitrogen at higher temperatures (ΔG3 = 60 kJ mol^?1). N.m.r. parameters have been obtained. One of the five-bond FF coupling constants is much larger ($\text{ca}$. 24 Hz) than the remainder (0·5–5·5 Hz), possibly due to ‘through-space’ coupling of fluorines in the $\text{cis}$-skew conformation.     

A variable temperature study of the 19-F N.M.R. spectra of some fluoroalkylhydroxylamines: Conformational changes at the nitrogen atom [1]

The fluoroalkylhydroxylamines (I) - (VII) have been examined by variable temperature 19-F n.m.r. spectroscopy, and free energies of activation obtained for the process which renders equivalent the fluorines of the CF₂N group in (I), and the trifluoromethyl groups of the (CF₃)₂CFN group in (IV), and of the trifluoromethyl groups of the (CF₃)₂N group nearest to the asymmetric carbon atom in (V) - (VII). The possible conformational processes at the nitrogen atom are discussed. Δ$\text{G}$^≠/kJ mol^-1 (I) (CF₃CF₂CF₂)₂NOCF₂CF₂CF₃ 72 ± 6 (II) CF₃CF₂CF₂N(CF₃)OCF₂CF₂CF₃ (III) CF₃CF₂CF₂N(CF₃)OCF₃ (IV) (CF₃)₂CFN(CF₃)OCF(CF₃)₂ 71 ± 4 (V) (CF₃)₂NOCH₂CHClON(CF₃)₂ 60 ± 4 (VI) (CF₃)₂NOCH₂CHFON(CF₃)₂ 59 ± 4 (VII) (CF₃)₂NOCF₂CHFON(CF₃)2 59 ± 4 The perfluorotrialkylhydroxylamines (II) - (IV) were prepared by photochemical reaction of a perfluoroalkyl iodide with a perfluoroalkyl nitroso compound.Since it was observed that some alkyl hydroxylamines show magnetic non-equivalence in their low temperature n.m.r. spectra [2,3] there has been a number of studies of conformational changes in such compounds. For cyclic derivations [4,5] it is generally agreed that the changes are associated with hindered inversion at the nitrogen atom, but for acyclic compounds these have been variously ascribed to hindered inversion at the nitrogen atom [6,7] and to restricted rotation about the N-O bond [8,9]. The former explanation has received theoretical justification [10].     

A variable temperature study of the 19-F N.M.R. spectrum of perfluorohexamethyltetrazan: Novel restricted rotation and hindered inversion at the nitrogen atoms [1]

At low temperatures, the ¹⁹F n.m.r. spectrum of the tetrazan (CF₃)₂NN(CF₃)N(CF₃)N(CF₃)₂ shows the presence of two isomers with a free energy difference in stability Δ$\text{G}$ of 2.2 kJ mol^-1. Both isomers show three types of CF₃ group which coalesce at -15°C to three systems of equal intensity (Δ$\text{G}$≠ 52 kJ mol^-1). At 40 °C the two signals assigned to the terminal CF₃ groups coalesce to a single band (Δ$\text{G}$≠ 65 kJ mol^-1).The behaviour is discussed in terms of restricted inversion at the nitrogen atoms, and hindered rotation about the N-N bonds.The hydrazines (CF₃)₂NN(CF₃)NO and (CF₃)₂NN(CF₃)NO₂ have temperature independent spectra.     

Fluoro-olefin chemistry Part 20 [1]. Reaction of hexafluoropropene with alcohols

Reaction of hexafluoropropene (HFP) with a series of alcohols under thermal, photochemical or peroxide-initiated conditions affords the 1:1 adducts CF₃CHFCF₂CR¹R²OH (R¹ = H, R² = H, Me, Prⁿ or CF₃; R¹ = Me, R² = Me or Et) in high yield via a radical chain mechanism. Adduct are not formed with the alcohols (CF₃)₂CHOH and CF₃CHFCF₂CH₂OH. Other 1:1 adducts of structure CHF₂CF(CF₃)CH₂OH and CH₃(C₂H₃CF₂CHFCF₃)CH₂OH are formed as minor products in the methanol and $\text{n}$-butanol reactions, respectively.     

Studies in azide chemistry. Part IX [1]. Investigations involving fluorinated azidopyrimidines and 4-azido-3-chloro-2,5,6-trifluoropyridine

4-Azido-2,5,6-trifluoro- and 4,6-diazido-2,5-difluoro- pyrimidine were obtained by treating tetrafluoropyrimidine with sodium azide in acetonitrile; similar azidation of 5-chlorotrifluoropyrimidine gave 4-azido-5-chloro-2,6-difluoro- and 4,6-diazido-5-chloro-2-fluoro-pyrimidine. Each monoazide reacted with triphenylphosphine to yield the corresponding iminophosphorane (Staudinger reaction), and the trifluoro- compound gave cycloadducts when heated with phenylacetylene [→ 4-phenyl-1-(2,5,6-trifluoro-4-pyrimidinyl)-1,2,3- triazole] and acrylonitrile [→ 2-cyano-1-(2,5,6-trifluoro- 4-pyrimidinyl)aziridine]; attack on the trifluoro-azide by the sodium salt of pentafluoroaniline produced 4-azido-2,5- difluoro-6-(pentafluorophenylamino)pyrimidine and bis(4- azido-2,5-difluoro-6-pyrimidinyl)(pentafluorophenyl)amine. Attempts to intercept nitrenes during thermal decomposition of both mono-azides failed. Thermolysis of 4-azido-3-chloro- 2,5,6-trifluoropyridine in the presence of dimethyl sulphoxide, cyclohexane, or pentafluoroaniline gave products [py_FNS(O)Me₂, py_FNHC₆H₁₁, and py_FNNPh_F (PY_F = 3-chlorotrifluoro-4-pyridyl), respectively] compatible with release of the corresponding nitrene.     

Studies in azide chemistry. Part II. Thermolysis of 4-azidotetrafluoropyridine: Evidence for the occurrence of a nitrene-carbene rearrangement

Flow pyrolysis of vaporized 4-azidotetrafluoropyridine at 280–300 °C and atmospheric pressure in platinum gave dark-coloured intractable material containing $\text{trans}$-perfluoro[1,2-bis(pyrazinyl)ethene].     

A novel synthesis of 3-fluorophenylalanine and some of its derivatives

Ring opening of 2-cyano-3-phenylaziridine and 2-amido-3-phénylaziridine by HF/pyridine was found to give 2-amino-3-fluorophenylpropionitrile (IV) and 2-amino-3-fluorophenylalanamide (VII) respectively. 3-fluorophenylalanine (V) could be obtained by an acidic hydrolysis of (IV) or (VII) whereas isopropyl-3 fluorophenylalanate (VI) was isolated by esterification of (V) or by heating (IV) with iso-propanal-12 NHCl under reflux.     

N-halogeno-compounds. Part II [1]. N.M.R. data for polyfluorocyclohexadienylideneamines obtained via N- chlorination of polyfluoroarylamines

N.m.r. parameters for nine (I-IX) $\text{N}$-chloropolyfluorocyclohexa-2,5-dienylideneamines are reported and discussed; the magnitudes of the FF-coupling constants fall into the following ranges:

$\text{J}$₁₂ 0-2.8; $\text{J}$₁₃, $\text{J}$₃₅ 6.0-6.8; $\text{J}$₁₄ <1; $\text{J}$₁₅ 0-2.6; $\text{J}$₂₃, $\text{J}$₃₄ 25.5-27.2; $\text{J}$₂₄ 0-6.0; $\text{J}$₂₅ 0-1.2; $\text{J}$₄₅ 5.4-9.8 Hz (I) X = Y = Z = F; (II) X = OMe, Y = Z = F; (III) X - CF₃, Y = Z = F; (IV) X = Ph, Y = Z = F; (V) X = Cl, Y = Z = F; (VI) X = Br, Y = Z = F; (VII) X = Y = F, Z = Cl; (VIII) X = Y = F, Z = Br; (IX) X = Z = F, Y = H. The spectra of $\text{N}$-methyl-4-chloropentafluorocyclohexa-2,5-dienyldeneamine have also been analysed. All the imines examined are configurationally stable at the nitrogen atom.     

Preparation,stability, reactivity and synthetic utility of a cadmium stabilized complex of difluoromethylene phosphonic acid ester

Diethyl bromodifluoromethyl phosphonate reacts readily with cadmium metal to form a stable cadmium complex. Depending on solvent, this functionalized organocadmium reagent exhibits stability for days to months. It reacts with a variety of electrophiles and serves as a synthetically useful source for the introduction of the difluoromethylene phosphonate group into organic compounds.The synthetic utility of a wide variety of fluoromethylene phosphonium ylides has been a major effort in our laboratory over the past several years [1]. The generation and capture of difluoromethylene ylides ($\text{1}$) as a general route to difluoromethylene olefins has been of especial interest to us [2]. In an effort to increase the nucleophilicity of the ylide, we have attempted to prepare the analogous phosphonate ylide ($\text{2}$). Although we have achieved modest success [3] by $\text{insitu}$ capture of ($\text{2}$) in the reaction of

sodium dialkyl phosphites with diethyl bromodifluoromethylphosphonate ($\text{3}$), attempts to pregenerate ($\text{2}$), either from diethyl difluoromethylphosphonate ($\text{4}$) or ($\text{3}$), have met with little success. ($\text{2}$) appears to have minimal stability even at low temperatures, and scale up processes of synthetic value would seem to be difficult.     

N-halogeno-compounds. Part 9 [1]. Azoxy- and azo-arenes derived from 4-(dichloroamino)tetrafluoropyridine; crystal structure of trans-2,3,5,6-tetrafluoro-4-(2,4,6-trimethylphenyl-onn-azoxy)pyridine

The nitrosoarenes ArNO (Ar = C₆H₅, 2-MeC₆H₄, 2,4,6- Me₃C₆H₂ and C₆F₅) have been condensed with 4-(dichloroamino)- tetrafluoropyridine to provide the azoxy-compounds py_FN$\text{N}\text{+}$($\text{N}\text{-}$)Ar (py_F = 2,3,5,6-tetrafluoro-4-pyridyl); de-oxygenation of the first three with triphenylphosphine or triethyl phosphite gave the corresponding azo-compounds, and the reverse reaction was achieved in the case of py_FNNC₆H₂Me₃-2,4,6 using peroxytrifluoroacetic acid. Thermolysis of 4-azidotetrafluoropyridine in the presence of pentafluoronitrosobenzene provided the perfluorinated azoxy-compound py_FN$\text{N}\text{+}$($\text{O}\text{-}$)C₆F₅. X-Ray methods have been used to determine the molecular geometry of py_FN$\text{N}\text{+}$($\text{O}\text{-}$)C₆H₂Me₃-2,4,6.