Trifluoroethyl Ether Research Articles

2,2,2-Trifluoroethoxy Aromatic Heterocycles: Hydrolytically Stable Alternatives to Heteroaryl Chlorides.

Herein we describe the 2,2,2-trifluoroethoxy group as an alternative leaving group for hydrolytically unstable heteroaryl chlorides. This group provides improved shelf stability by years while maintaining reactivity toward nucleophiles in SNAr reactions. A highlighted trifluoroethyl ether was shown to be tolerant to aqueous Suzuki conditions, permitting sequential Suzuki/SNAr processes inaccessible to the heterocyclic chlorides. The strategic use of trifluoroethyl ethers enables storage of otherwise unstable heterocyclic chlorides and limits costly decomposition.

ChemInform Abstract: Base Mediated Deprotection Strategies for Trifluoroethyl (TFE) Ethers, a New Alcohol Protecting Group.

A trifluoroethyl (TFE) ether is specifically introduced as a protecting group in organic chemistry. Its first strategic application and removal in the total synthesis of vinigrol is discussed. Two lithium base mediated deprotection strategies for its removal are presented in this Letter. In one deprotection approach, the trifluoroethyl ether is converted to a difluorovinyl ether and then catalytically cleaved using osmium tetraoxide, while in the second approach a difluorovinyl anion is formed and trapped with an electrophilic oxygen reagent (MoOPH) to form a labile difluoroacetate. To further aid the reader, a summary of approaches for forming trifluoroethyl ethers is included as well as a discussion of alternate deprotection strategies.

Evolution of an oxidative dearomatization enabled total synthesis of vinigrol.

The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group's importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations.

Base mediated deprotection strategies for trifluoroethyl (TFE) ethers, a new alcohol protecting group

A trifluoroethyl (TFE) ether is specifically introduced as a protecting group in organic chemistry. Its first strategic application and removal in the total synthesis of vinigrol is discussed. Two lithium base mediated deprotection strategies for its removal are presented in this Letter. In one deprotection approach, the trifluoroethyl ether is converted to a difluorovinyl ether and then catalytically cleaved using osmium tetraoxide, while in the second approach a difluorovinyl anion is formed and trapped with an electrophilic oxygen reagent (MoOPH) to form a labile difluoroacetate. To further aid the reader, a summary of approaches for forming trifluoroethyl ethers is included as well as a discussion of alternate deprotection strategies.

Design, Synthesis and Biological Activities of Novel Anthranilic Diamide Insecticide Containing Trifluoroethyl Ether

AbstractTwo series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal X‐ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg−1 were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond‐back moth were 100% at 0.1 mg·kg−1. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond‐back moth when the concentration was reduced to 0.05 mg·kg−1, which was higher than the commercialized Chlorantraniliprole.

Hyperaromatic Stabilization of Arenium Ions: Cyclohexa- and Cycloheptadienyl Cations—Experimental and Calculated Stabilities and Ring Currents

Measurements of pK(R) show that the cycloheptadienyl cation is less stable than the cyclohexadienyl (benzenium) cation by 18 kcal mol(-1). This difference is ascribed here to "hyperaromaticity" of the latter. For the cycloheptadienyl cation a value of K(R) = [ROH][H(+)]/[R(+)] is assigned by combining a rate constant for reaction of the cation with water based on the azide clock with a rate constant for the acid-catalyzed formation of the cation accompanying equilibration of cycloheptadienol with its trifluoroethyl ether in TFE-water mixtures. Comparison of pK(R) = -16.1 with pK(R) = -2.6 for the cyclohexadienyl cation yields the difference in stabilities of the two ions. Interpretation of this difference in terms of hyperconjugative aromaticity is supported by the effect of benzannelation in reducing pK(R) for the benzenium ion: from -2.6 down to -3.5 for the 1H-naphthalenium and -6.0 for the 9H-anthracenium ions, respectively. MP2/6-311+G** and G3MP2 calculations of hydride ion affinities of benzenium ions show an order of stabilities for substituents at the methylene group consistent with their hyperconjugative abilities, i.e., (H(3)Si)(2) > cyclopropyl > H(2) > Me(2)> (HO)(2) > F(2). Calculations of ring currents show a similar ordering. No conventional ring current is seen for the cycloheptadienyl cation, whereas currents in the F(2)-substituted benzenium ion are consistent with antiaromaticity. Arenium ions where the methylene group is substituted with a single OH group show characteristic energy differences between conformations, with C-H or C-OH bonds respectively occupying or constrained to axial positions favorable to hyperconjugation. The differences were found to be 8.8, 6.3, 2.4, and 0.4 kcal mol(-1) for benzenium, naphthalenium, phenanthrenium, and cyclohexenyl cations, respectively.

Radiosynthesis of the tumor hypoxia marker [ 18F]TFMISO via O-[ 18F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles

The MRI hypoxia marker trifluoromisonidazole (TFMISO) [1-(2-nitro-1 H-imidazol-1-yl)-3-(2,2,2-trifluoroethoxy)propan-2-ol] was successfully labeled with 18F to expand its role into a bimodal PET/MRI probe. 18F-Labeling was achieved via a three-step procedure in which 2,2,2-[ 18F]trifluoroethyl p-toluenesulfonate prepared by 18F- 19F exchange served as the [ 18F]trifluoroethylating agent. The O-[ 18F]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[ 18F]trifluoroethoxy)propane, with approximately 60% of 18F incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [ 18F]TFMISO. Approximately 40% of the [ 18F]trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[ 18F]trifluoroethyl iodide failed to produce [ 18F]TFMISO, giving instead 1,1-[ 18F]difluoro-2-iodoethoxy and 1-[ 18F]fluoro-2-iodovinyloxy analogs of [ 18F]TFMISO. Thus, this investigation has identified 2,2,2-[ 18F]trifluoroethyl tosylate as an excellent [ 18F]trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [ 18F]trifluoroethyl ether.

ChemInform Abstract: Rate and Product Analytical Study of the Solvolysis of 3-Chlorobenzyl Arenesulfonates in Aqueous 2,2,2-Trifluoroethanol.

The rates of solvolysis of 3-chlorobenzyl 4-methyl-, 4-methoxy-, and 4-bromo-benzenesulfonates at different temperatures in 1 : 1 (v/v) 2,2,2-trifluoroethanol–water have been measured and the activation parameters determined. Qualitatively, the rate constants show the expected dependence upon the substituent in the benzenesulfonate leaving group, and the toluenesulfonate is 42 times less reactive (at 25 °C) than benzyl toluenesulfonate itself. In the product analytical study, the ratio of the 3-chlorobenzyl alcohol to the 3-chlorobenzyl trifluoroethyl ether was determined in each of the three cases, and shown to be independent of the nature of the nucleofuge. Introduction of the 3-chloro substituent into the electrophile, however, causes the selectivity for water as opposed to trifluoroethanol to be increased by ca. 50%. The results are discussed in terms of a substitution reaction which is concerted but not synchronous, a solvent-induced, largely uncoupled SN2 mechanism.

Acid‐catalysed hydrolysis of methoxy‐substituted trityl trifluoroethyl ethers: a kinetic and computational investigation of leaving group effects

AbstractTrityl trifluoroethyl (TFE) ether and its 4‐methoxy, 4,4′‐dimethoxy‐, and 4,4′,4″‐trimethoxy‐substituted analogues have been prepared; the dimethoxy and trimethoxy compounds undergo ready acid‐catalysed hydrolysis at constant ionic strength = 1 mol dm−3 at 25°C. The monomethoxy compound is less reactive and the parent trityl analogue showed minimal reactivity. Using presently reported and literature kinetics results with pKa values of protonated substrates, first‐order rate constants covering 12 orders of magnitude have been determined for heterolysis/dissociation of 11 protonated dimethoxytrityl derivatives DMTrYH+ where YH = H2O, CF3CH2OH, ArNH2 and RNH2. There is a good correlation between logarithms of these rate constants and the pKa values of the conjugate acids (Y) of the nucleofuges YH. Enthalpies and corresponding free energies at 25°C for the dissociation of the specifically solvated ions CH3 (YH = MeOH and CF3CH2OH, n = 1; H2O, n = 2; and NH3, n = 3) have been calculated at the B3LYP/6‐31+G* level. Corresponding gas phase calculations have also been carried out for Ph3C (YH = H2O, n = 2; MeOH, n = 1; CF3CH2OH, n = 1 and NH3, n = 3) and, in addition, structures for these solvated ions with (YH = H2O, MeOH and NH3) have been calculated. The specifically solvated ion Ph3CO(H)CH2CF3(H2O)+ does not correspond to a stable bonded species in the gas phase, which suggests that acid‐catalysed fragmentation of methoxy‐substituted analogues of Ph3COCH2CF3 in aqueous solution are concerted with proton transfer in which case the hydrolytic cleavage will be general acid catalysed. Copyright © 2008 John Wiley & Sons, Ltd.

Fluorinated Polar Heads Can Strikingly Increase or Invert the Dipole Moments at the Langmuir Monolayer−Water Boundary: Possible Effects from Headgroup Conformations

The dipole potential of lipid monolayers and bilayers is positive toward their nonpolar moiety. In previous papers, we have shown that designed molecules with fluorinated polar heads can invert the polarity of un-ionized Langmuir films. Monolayers of long-chain trifluoroethyl ester RCOOCH2CF3 and trifluoroethyl ether ROCH2CF3 exhibit large negative DeltaV values, shifted by 150-200% from the positive dipole potentials of their non-fluorinated analogs (Petrov and Möhwald J. Phys. Chem. 1996, 100, 18458; Petrov et al. J. Phys. Chem. B 2005, 109, 14102). Here we report large positive surface (dipole) potentials of monolayers of N-trifluoroethyl docosanamide RCONHCH2CF3 and a 300% DeltaV shift with respect to the non-fluorinated N-ethyl docosanamide films. Comparing the dipole potentials and normal dipole moments of the RCONHCH2CF3 and RCOOCH2CF3 monolayers and the maps of the local electrostatic potential (MEP) and lipophilicity (MLP) of their molecules in vacuum, we conclude that the opposite DeltaV shifts and the difference of 1480 mV between the films of these structurally similar amphiphiles seem to be due to strongly different conformations of their heads. The large positive DeltaV values of the N-trifluoroethyl amide monolayer was related to the network of -NH...O=C- bonds fixing the orientation of the hydrophobic delta+C-F3delta- dipoles toward water. The trifluoroethyl ester heads do not form H-bonds and can adjust their energetically optimal conformation orienting the hydrophobic delta+C-F3delta- dipoles toward air. The opposite signs of the dipole potential and the apparent normal dipole moments of the trifluoroethyl ester and ethyl ester monolayers were explained via energy minimization of 36 upright closely packed molecules with "hook-like" heads. The equilibrium architecture of this ensemble shows statistical distribution of the headgroup conformations and a nano-rough monolayer-water boundary as known from X-ray reflectivity experiments and molecular dynamic simulations of phospholipid monolayers and bilayers. The average of the vertical molecular dipole moments at equilibrium agree fairly well with the measured values of mu perpendicular, and the mean molecular area in the ensemble 19.3 A2 matches the value of 18.9 +/- 0.2 A2 determined via X-ray diffraction at gracing incidence surprisingly well. These results reflect the balance of the attractive and repulsive forces between the closely packed "dry" amphiphilic molecules, but a more sophisticated molecular modeling explicitly including water would better serve to reveal the mechanism of the observed effects.

Fluorination of the Hydrophilic Head Accelerates the Collapse of the Monolayer but Stabilizes the Bilayer of a Long-Chain Trifluoroethyl Ether on Water

A comparison of the collapse of Langmuir monolayers of docosyl trifluoroethyl ether (DFEE) and docosyl ethyl ether (DEE) on water shows that in both films the 3D phase is formed layer-by-layer. The substitution of CH3 by a CF3 group in the hydrophilic head yields a more stable bilayer exhibiting lower equilibrium spreading pressure, pi(esp)(DFEE) < pi(esp)(DEE). Upon lateral compression, the DFEE bilayer fractures abruptly as a compact solid body whereas the DEE bilayer breaks down gradually as a polycrystalline material. A comparison of the collapse kinetics of the two films at the same constant supersaturation pi-pi(esp) = 7 mN/m shows that the fluorinated DFEE monolayer transforms more quickly, yielding a stable bilayer of closely packed upright molecules, whereas the DEE film undergoes a continuous monolayer-bilayer-multilayer transition. Brewster angle microscopy allows us to visualize different collapse mechanisms of the DFEE and DEE films; the domains of the fluorinated DFEE bilayer grow laterally at constant thickness and density, and the collapse of the nonfluorinated DEE monolayer occurs through a sequence of disordered stripelike and broken elongated textures. The characteristic molecular areas of the monolayer and bilayer collapse suggest that the 2D-3D transition in the DFEE and DEE films is accompanied by at least partial dehydration of their headgroups. The faster collapse of the fluorinated monolayer could result from a lower energy barrier due to the more hydrophobic CF3 group in the heads. The increased stability of the DFEE bilayer could be associated with the electrostatic attraction between the -C(F delta-)3 versus (H delta+)3C- terminals at the heads-to-tails contact plane of the top and the bottom layer, contrasting with the repulsion between the -C(H delta+)3 versus (H delta+)3C- terminals of the top-layer heads and the bottom-layer tails in the DEE bilayer.

Negative Dipole Potentials of Uncharged Langmuir Monolayers Due to Fluorination of the Hydrophilic Heads

The dipole potential, affecting the structure, functions, and interactions of biomembranes, lipid bilayers, and Langmuir monolayers, is positive toward the hydrocarbon moieties. We show that uncharged Langmuir monolayers of docosyl trifluoroethyl ether (DFEE) exhibit large negative dipole potentials, while the nonfluorinated docosyl ethyl ether (DEE) forms films with positive dipole potentials. Comparison of the Delta V values for these ethers with those of the previously studied(37-39) monolayers of trifluoroethyl ester (TFEB) and ethyl ester of behenic acid (EB) shows that the reversal of the sign of Delta V causes the same change Delta(Delta V) = -706 +/- 16 mV due to fluorination of heads. The Delta V values of both TFEB and EB films differ by -122 +/- 16 mV from those of DFEE and DEE monolayers, respectively, with the same density. Such quantitative coincidence points to a common mechanism of reversal of the sign of the dipole potential for the ether and ester films despite the different structure of their heads. The mechanical properties and phase behaviors of these monolayers show that both fluorinated heads are less hydrated, suggesting that the change of the sign of Delta V could, at least partially, be related to different hydration water structure. The same negative contribution of the carbonyl bond in both TFEB and EB films contrasts with the generally accepted positive contribution of the C(delta+)=O(delta-) bond in condensed Langmuir monolayers of fatty acids, their alcohol esters, glycerides, and phospholipids but concurs with the theoretical analysis of Delta V of stearic acid monolayers. Both results question the literature values of the molecular dipole moments of these substances calculated via summation of bonds and atomic group contributions. Mixed monolayers of DFEE and DEE show smooth monotonic variation of Delta V from +450 to -235 mV, indicating a way for adjustment of the sign and magnitude of the dipole potential at the membrane-water boundary and regulation of such membrane behaviors as binding and translocation rate of hydrophobic ions and ion-carriers, adsorption and penetration of amphiphilic peptides, polarization of hydration water, and short-range repulsion. The interaction of the hydrophobic ions tetraphenylboron TPhB- and tetraphenylphosphonium TPhP+ with DFEE and DEE monolayers qualitatively follows the theory of binding of such ions to lipid bilayers, but the shifts Delta(Delta V) from the values obtained on water are much smaller than those for DPPC monolayers. This difference seems to be due to the solid (polycrystalline) character of the DFEE and DEE films that hampers the penetration of TPhB- and TPhP+ in the monolayers and reduces the attractive interaction with the hydrophobic moiety. This conclusion orients the future synthesis of amphiphiles with fluorinated heads to those which could form liquid-expanded Langmuir monolayers.

Effect of Fluorination of the Hydrophilic Heads on Morphology and Molecular Structure of Langmuir Monolayers of Long-Chain Ethers

Brewster angle microscopy (BAM) and grazing incidence X-ray diffraction (GIXD) were used to compare morphology and molecular structure of Langmuir monolayers of docosyl trifluoroethyl ether (DFEE) and docosyl ethyl ether (DEE) on water. When spread at a molecular area of 70 Å2/molecule both substances form islands of condensed phase and suspension of small 2D microcrystals attaching at the borderlines under compression. The DEE islands and the DEE monolayer at low surface pressure exhibit strong in-plane optical anisotropy, while the DFEE islands and the compact DFEE film are isotropic. The anisotropy of the DEE monolayer disappears at 10 mN/m, and above this surface pressure the monolayers with fluorinated and nonfluorinated heads are visually the same. The GIXD analysis identifies a L2‘ phase with NNN molecular tilt and NN lattice distortion in the DEE islands and DEE monolayer at low surface pressure. The maximum tilt angle at zero compression is 22.6°. The islands and the compact DFEE film consist of closely packed upright molecules forming an S phase. At high surface pressure both monolayers have the same upright molecular arrangement with centered rectangular lattice and practically the same unit cell parameters and lattice distortion. Under such conditions the DFEE and DEE molecules occupy the same area of the water surface Axy = A0 = 19.1 Å2. Since the van der Waals radius of the CF3 group is by 16% larger as compared to that of the CH3 group, the same A0 value of the two films means a significantly thinner hydration shell of the fluorinated head. Substitution of the terminal CH3 group in the DEE head by the CF3 group in the DFEE head removes the low-pressure tilted phase and causes formation of the condensed phase of upright fluorinated molecules even at no compression. The decreased headgroup hydration of DFEE could be responsible for the upright versus tilted orientation of the DFEE and DEE molecules at low surface pressure. We suppose that the mechanism of the continuous tilting transition causing erection of the DEE chains is related to an increasing dehydration of the headgroups under compression.

Solvolysis of Tricyclo[4.1.0.02,7]hept‐4‐en‐3‐yl and Tricyclo[4.1.0.02,7]hept‐3‐yl Methanesulfonates and p‐Nitrobenzoates – Remarkably Small Enthalpy Difference between the C7H7 Cations Tricyclo[4.1.0.02,7]hept‐4‐en‐3‐yl and 7‐Norbornadienyl

AbstractIn an extension of previous work, tricyclo[4.1.0.02,7]heptan‐3‐ol (5) was synthesised in four steps from benzvalene. Methanesulfonates 12 and 6b, c, prepared from 5 and 4‐halotricyclo[4.1.0.02,7]hept‐4‐en‐3‐ols 4b, c, were too unstable to be isolated, but were unambiguously characterised by their NMR spectra. On treatment of the unsubstituted tricycloheptenol 4a with methanesulfonyl chloride, the expected mesylate 6a could not be observed. Even at −40°C, only its consecutive products 3‐chlorotricyclo[4.1.0.02,7]hept‐4‐en (7a) and 7‐chloronorbornadiene (8a) were discernible. The analogous reaction of 6b occurred only at room temperature, with formation of the dichlorotricycloheptene 7b and the dichloronorbornadiene 8b. Rearrangement products of 6b and 12 were the chloronorbornadiene mesylate 10b and anti‐7‐norbornenyl mesylate (13), respectively. – The solvolysis of 6b, c in aqueous ethanol and of 6b in 2,2,2‐trifluoroethanol (TFE) gave nonrearranged products exclusively, i.e. the alcohols 4b, c, the ethyl ethers 17b, c, and the trifluoroethyl ether 18b. In contrast, from 12 only rearranged products arose, namely anti‐7‐norbornenol (30) and its ethyl ether 31. The solvolysis of the unsubstituted tricycloheptenyl p‐nitrobenzoate 11a in 80% aqueous ethanol proceeded about equally fast in parallel reactions with cycloalkyl‐oxygen and acyl‐oxygen cleavage. In addition to the tricycloheptenol 4a, the tricycloheptenyl ethyl ether 17a, ethyl 7‐norbornadienyl ether (19), 7‐norbornadienyl p‐nitrobenzoate (20), and ethyl p‐nitrobenzoate were formed. No acyl‐oxygen cleavage took place in TFE as solvent, where the tricycloheptenyl trifluoroethyl ether 18a, 20, 7‐norbornadienyl trifluoroethyl ether (21), and the cyclopentadienylvinyl trifluoroethyl ethers 22/23 were produced. A new mechanism is proposed for the route to the major products 22/23 via the intermediate 7‐norbornadienyl cation (9a), which was attacked by TFE at the two‐membered bridge stabilising the positive charge. Thus formed, tricyclo‐[3.2.0.02,7]hept‐3‐en‐endo‐6‐yl trifluoroethyl ether (24) underwent a Diels‐Alder cycloreversion generating the cyclopentadienylvinyl trifluoroethyl ether 25, the immediate precursor of 22/23. – From kinetic data for these processes and thermochemical data for appropriate hydrocarbons, the enthalpy difference between the C7H7 cations, tricyclo‐[4.1.0.02,7]hept‐4‐en‐3‐yl (3a) and 7‐norbornadienyl (9a), was calculated to be only 8 kcal mol−1.

Solvolysis of [3- 13C]-3,4-dimethyl-4-homoadamantyl p-nitrobenzoate. Comparison of the barriers to the Wagner-Meerwein rearrangement of the secondary and tertiary 4-homoadamantyl cations

The trifluoroethanolysis of [3- 13C]-3,4-dimethyl-4-homoadamantyl p-nitrobenzoate gave 3,4-dimethyl-4-homoadamantene ( 10), 3-methyl-4-methylenehomoadamantane ( 11), and trifluoroethyl ether ( 12a) in the ratio 62:36:2 at 40 °C. The 13C labels were exclusively distributed at the positions C(3) and C(4), and redistribution ratios were 92.8:7.2 in 10, 93.3:6.7 in 11, and 61.1:38.9 in 12a. Comparison of these results with those for the solvolysis of secondary [3- 13C]-4-homoadamantyl p-toluenesulfonate suggests that the barrier to the Wagner-Meerwein rearrangement of the tertiary 4-homoadamantyl cation is higher than that of the secondary cation by at most 3.3 kcal mol −1.

Rate and product analytical study of the solvolysis of 3-chlorobenzyl arenesulfonates in aqueous 2,2,2-trifluoroethanol

The rates of solvolysis of 3-chlorobenzyl 4-methyl-, 4-methoxy-, and 4-bromo-benzenesulfonates at different temperatures in 1 : 1 (v/v) 2,2,2-trifluoroethanol–water have been measured and the activation parameters determined. Qualitatively, the rate constants show the expected dependence upon the substituent in the benzenesulfonate leaving group, and the toluenesulfonate is 42 times less reactive (at 25 °C) than benzyl toluenesulfonate itself. In the product analytical study, the ratio of the 3-chlorobenzyl alcohol to the 3-chlorobenzyl trifluoroethyl ether was determined in each of the three cases, and shown to be independent of the nature of the nucleofuge. Introduction of the 3-chloro substituent into the electrophile, however, causes the selectivity for water as opposed to trifluoroethanol to be increased by ca. 50%. The results are discussed in terms of a substitution reaction which is concerted but not synchronous, a solvent-induced, largely uncoupled SN2 mechanism.

On the Acid-catalysed Alkylation of Lignins

Acid-catalysed alkylation of spruce lignin and model compounds has been studied. Alkylation of veratrylglycerol-β-guaiacyl ether in a mixture of equimolar amounts of metanol, ethanol and 2,2,2-trifluoroethanol resulted in a preferential formation of methyl benzyl ether; the yield of ethyl ether was slightly lower while only trace amounts of the trifluoroethyl ether was formed. When 2,2,2-trifluoroethanol was used as reaction medium, condensation reactions occurred

A rate and product study of the effect of solutes upon the solvolysis of benzyl toluene-p-sulphonate in aqueous trifluoroethanol

The effects of several electrolytes, including sodium perchlorate, thiocyanate, acetate, and halides, upon the rate and products of solvolysis of benzyl tosylate in 1 : 1 (v/v) aqueous trifluoroethanol at 25 °C have been investigated. In the absence of any electrolyte, the ratio of benzyl alcohol to benzyl trifluoroethyl ether is only marginally greater than the molar ratio of water to trifluoroethanol in the reaction medium. Sodium perchlorate gives rise to a kinetic salt effect but no detectable perturbation of the product ratio. Thiocyanate, iodide, and bromide lead to second-order rate terms and the formation of substitution products. Thiocyanate, the most effective nucleophile used, does not affect the internal ratio of the solvent-derived products. We find no evidence of nucleophilic capture of carbonium ion intermediates formed in prior rate-determining steps. Chloride, acetate, and hydroxide are very weak nucleophiles in this medium and do not lead to overall rate enhancements. Replacing a small proportion of the trifluoroethanol by ethanol leads to the formation of a low yield of benzyl ethyl ether. There is no evidence of benzyl tosylate reacting other than by SN2 mechanisms, either uncoupled in reactions with solvent and hard nucleophilic solutes, or coupled with soft nucleophiles such as iodide and thiocyanate.

Vinylic cations from solvolysis. Part XV. β-Phenyl and β-p-methoxyphenyl rearrangement during the solvolysis of 2,2-diaryl-1-phenylvinyl bromides

Triphenylvinyl bromide (1), trans- and cis-2-p-methoxyphenyl-1,2-diphenylvinyl bromides (2) and (3), and 2,2-bis-p-methoxyphenyl-1-phenylvinyl bromide (4) were solvolysed in 2,2,2-trifluoroethanol (TFE) and in 60% EtOH. In TFE, the products were the trifluoroethyl ether from (1), 15% of a 1 : 1 cis–trans mixture of the unrearranged and 85% of the β-phenyl rearranged trifluoroethyl ethers from (2) and (3), and a 1 : 1 cis–trans mixture of the β-p-methoxyphenyl rearranged trifluoroethyl ethers from (4). With toluene-p-thiolate ion, (4) gave only a rearranged sulphide, whilst the sulphides from (2) and (3) are 70% rearranged. The trifluoroethanolysis of (1)–(3) was accompanied by common ion rate depression. The relative initial k1(120°) values were 1(1) : 3·4 (2) : 3·7 (3) : 9·5 (4). In 60% EtOH the products were mostly the unrearranged acetophenone derivative from (2) and (3) and only the rearranged ketone from (4), and the relative k1(140°) values were 1 (1) : 2·14 (2) : 2·44 (3) : 5·45 (4). It is concluded that (a) the initial ionisation does not involve β-aryl participation, (b) the products are derived from free, open, linear vinyl cations, which return to covalent bromide (kBr), rearrange (kr), and react with the solvent (kROH) or toluene-p-thiolate ion (kSR′), (c)β-p-methoxyphenyl (An) rearrangement is the dominant process for the ion An2CCPh in the two solvents, (d)β-phenyl rearrangement is dominant for the ion AnC(Ph)CPh (19) in TFE (kBr : kr(Ph) : kROH= 214 : 5·7 : 1 at 120°) while in 60% EtOH kROH:kr(Ph)= 19 : 1; the apparent ‘abnormal’ order of migratory aptitudes Ph > An is either due to a hidden β-p-methoxyphenyl rearrangement or to a higher energy loss in the deconjugation of the migrating aryl group with the double bond than the energy gain in the briding by the migrating aryl, and (e) the effects of β-aryl substituents on the solvolysis rate are nearly additive.

Retrograde amnesic effects of diethyl ether and bis(trifluoroethyl) ether.

Retrograde amnesic effects of diethyl ether and bis(trifluoroethyl) ether.