Synthesis of the stereoisomers of the methylesters of 3-isopropyl-5-methoxy-6-ketoheptanoic acid and of 2-methoxy-4-isopropylhexandioic acid

The four stereoisomers of 3-isopropyl-5-methoxy-6-ketoheptanoic acid methylester and those of 2-methoxy-4-isopropylhexandioic acid methylester were synthesized from R(?)- and S(+)-carvone. The combined data given provide a basis for specific enantiomer assignment to natural product degradation materials.     

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].     

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.     

Gas-phase electron diffraction determination of the molecular structure of perfluoro(methyloxirane)

The molecular geometry of perfluoro(methyloxirane) has been studied using gas-phase electron diffraction data, effective least-squares refinement of the structure being achieved with the aid of constraints to limit the number of variable parameters. With the CCF₃ bond constrained to be 0.078 Å longer than the ring CC, the refined bond- length values CF (av.) = 1.323(2), CO (av.) = 1.410(8), and CC (ring) = 1.467(7) Å ($\text{r}$_g values, with e.s.d. in parentheses) were obtained; the angles between ring bonds and substituent CF bonds were CCF (av.) 121(1) and OCF (av.) 114(1)^o, the corresponding parameters involving the bulkier CCF₃ fragment being larger by 3^o in each case [∠CCCF₃ 124(1)^o∠OCCF₃ 117(2)^o]. The remaining refined parameters were ∠CCF(of CF₃) = 110.6(4)^o and τ , a torsion angle defining the orientation of the CF bonds of the CF₃ group with respect to ring bonds, = 29(2)^o. Dependent bond angles possessed the values 62.7 (COC), 58.7 [OCC (ring)], 108.3 [FCF (CF₃ group)], 114 [FCF (ring CF₂)], and 111^o (FCCF₃).     

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].     

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.     

Photochemical and thermal transformations of azomethine imines

The thermal and photochemical fragmentations of a few bisazoalkenes have been investigated. 2-Phenyl-4,5-disubstituted-1, 2,3-triazoles were obtained both in the thermolysis and photolysis of 1, 2-bisphenylazo-(4, 4′-dichloro) stilbene, 1, 2-bisphenylazo(4, 4′-dimethoxy)stilbene, 1, 2-bisphenylazocyclohexene and o-(phenylazo) phenyldiazocyanide. Both 2, 3-bisphenylazo-2-butene and 1, 2-bisphenylazoethylene failed to undergo either photolysis or thermolysis in the expected manner. However, 2, 3-bisphenylazo-2-butene underwent an acid-catalysed valence isomerisation to anhydro 1-phenylimino-2-phenyl-4, 5-dimethyl-1, 2, 3-trizolium hydroxide, which on photolysis gave 2-phenyl-4, 5-dimethyl-1, 2, 3-triazole. The same iminotriazolium intermediate gave a cycloadduct, 2, 6-diphenyl-3, 3a-dimethyl-4, 5-dicarbomethoxypyrazolino [2.3.c][1.2.3] triazole, on treatment with dimethyl acetylenedicarboxylate, whereas treatment with carbon disulphide gave 2-phenyl-4, 5-dimethyl-1, 2, 3-triazole. Both photolysis and thermolysis of C-biphenylene-N^α(4-chlorophenyl)-N^β-cyanoazomethine imine gave 9-fluorenone-N- (4-chlorophenyl) anil. Photolysis of 1, 2-bisphenylazoacenaphthylene in methanol gave acenaphthenequinone monophenylhydrazone.     

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.     

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).     

Lewis acid catalyzed addition of 2,2,2-trifluorodiazoethane to unactivated aldehydes

Condensations of 2,2,2-trifluorodiazoethane with pentanal, cyclohexancarboxaldehyde and benzaldehyde have been performed in presence of antimony pentachloride or boron trifiuoride. These reactions lead mainly to homologated aldehydes or ketones α substituted by a trifluoromethyl group.     

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.     

Reactions of dimethyl acetylenedicarboxylate—VI : Reaction with aldehyde and ketone phenylhydrazones

Benzaldehyde phenylhydrazone with dimethyl acetylenedicarboxylate gives dimethyl 1,3-diphenylpyrazoline-4,5-dicarboxylate, dimethyl 1,3-diphenylpyrazole-4,5-dicarboxylate and trimethyl 1-phenylpyrazole-3,4,5-tricarboxylate; p-chlorobenzaldehyde phenylhydrazone gives trimethyl 1-phenyl-3,4,5-tricarboxylate and 1,2-(bis-phenylazo)-1,2-di-p-chlorophenylethane. Under similar conditions, p-tolualdehyde phenylhydrazone gives only trimethyl 1-phenylpyrazole-3,4,5- tricarboxylate. Acetophenone phenylhydrazone with dimethyl acetylenedicarboxylate gives dimethyl 1,3-diphenylpyrazole-4,5-dicarboxylate. Benzophenone phenylhydrazone, on the other hand, gives a mixture of dimethyl 1,3-diphenylpyrazoline-4,5-dicarboxylate and dimethyl 1,3-diphenylpyrazole-4,5- dicarboxylate. Benzyl methyl ketone and dimethyl acetylenedicarboxylate gives an enamine maleate, which is the Michael addition product.     

Polymerization of methylmethacrylate by organometallic compounds—vii. The n-butyl magnesium bromide-di-n-butyl magnesium system in THF + toluene solution

The molar-mass distributions of the products at 223°K and below were multimodal having three distinct and separate components, viz. volatile side-products, methanol-soluble polymer ($\text{DP}{}_{\mathrm{n}}\text{≈ 50}$) and methanol-insoluble polymer ($\text{DP}{}_{\mathrm{n}}\text{= 200–600}$). At low THF concentrations, with n-BuMgBr, small amounts of a third distinct and independent polymeric product appeared at higher molar mass. The distributions of configurational triads of the chains of the methanol-soluble and insoluble polymers were non-Bernoullian but different. It is proposed that the two components are formed at two distinct and independent active centres. This eneidic mechanism explains the very high values of $\text{DP}{}_{\mathrm{w}}$/ $\text{DP}{}_{\mathrm{n}}$ reported in previous studies of Grignard initiation of MMA.The configurational triad distribution of the methanol-soluble and insoluble components remained unchanged both when n-Bu₂Mg replaced n-BuMgBr as initiator and when excess MgBr₂ was present. It is proposed that the same active centres operated throughout. In contrast to t-BuMg systems, there is no evidence that MgBr₂ or BrMg- groups play any other role in the polymerization than to reduce the initiator efficiency.The effects of temperature and the addition of strongly solvating solvents were tested. Tetraethylene glycol dimethyl ether caused the precipitation of MgBr₂ from the initiator solution but did not otherwise affect the mechanism. However when hexamethylphosphoroamide was added at 223°K the polymerization took a different mechanism.Sixteen per cent of n-BuMg- groups remain unreacted during the polymerization. It is proposed that the presence of these groups at the active centre accounts for the influence of the Bu group on the stereospecificity of the polymerization.     

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].