446867-23-8

Upstream product

• 75-89-8 2,2,2-trifluoroethanol 
• 53218-10-3 4-methoxybenzyl 4-nitrobenzoate 
• 29180-19-6 4-methoxybenzyl carbocation 
• 98821-07-9 1-methoxy-4-((trifluoromethylsulfonyl)methyl)benzene 
• 824-94-2 p-methoxybenzyl chloride 
• 64-17-5 ethanol 

Downstream Products

• 446867-21-6 p-methoxybenzyl 2,2-difluorovinyl ether 

Relevant academic research and scientific papers

2,2-Disubstituted analogues of the natural hormone 1α,25-dihydroxyvitamin D3: Chemistry and biology

Six new 2,2-disubstituted analogues of the natural hormone calcitriol have been prepared. Chemical novelty includes (1) the first example of an inverse-electron-demand Diels-Alder cycloaddition using a pyrone diene and a difluorinated vinyl ether dienophi

Solvolysis of substituted benzyl azoxyarenesulfonates: Characterisation of the transition state and the selectivity of benzylic intermediates in 50% aqueous 2,2,2-trifluoroethanol

Thirteen substituted benzyl azoxyarenesulfonates have been prepared and rate constants for solvolysis of twelve have been measured in 50% (v/v) aqueous 2,2,2-trifluoroethanol over a range of temperatures from which activation parameters and rate constants at 25°C have been determined. A six-point Hammett correlation for substituents in the benzylic electrofuge, with azoxytoluene-p-sulfonate as the common nucleofuge, gives ρ(σ+) = -3.27. With 4-methylbenzyl as a common electrofuge, four substituents in the azoxybenzenesulfonate nucleofuge give ρ(σ) = 1.07. Comparison with model reactions indicates a synchronous concerted rate-limiting fragmentation for these substrates. With the less reactive 3-chlorobenzyl as electrofuge, ρ for substituents in the nucleofuge is only ca. 0.7 which indicates a lower degree of charge development in the arenesulfonate in the transition state for these reactions. Product analyses have been carried out for compounds of high, intermediate, and low reactivity. These indicate a reactivity-selectivity relationship for capture of the substituted benzylic electrophiles by water and 2,2,2-trifluoroethanol. Substituted benzaldehydes are formed from the less reactive substrates, indicating trapping of the first-formed benzylic carbenium ion by nitrous oxide and subsequent elimination of nitrogen and a proton; but yields are low and decrease as the substituted benzyl cation becomes increasingly stable.

Lifetimes and UV-visible absorption spectra of benzyl, phenethyl, and cumyl carbocations and corresponding vinyl cations. A laser flash photolysis study

Benzyl (4-MeO, 4-Me, and 4-methoxy-1-naphthylmethyl), phenethyl (4- Me2N, 4-MeO, 3,4-(MeO)2, 4-Me, 3-Me, 4-F, 3-MeO, 2,6-Me2, parent, and 4- methoxy-1-naphthylethyl) and cumyl (4-Me2N, 4-MeO, 4-Me, parent) cations have been studied by laser flash photolysis (LFP) in 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). In most cases styrene or α-methylstyrene precursors were employed for the phenethyl and cumyl ions, the intermediate being obtained by solvent protonation of the excited state. Benzyl cations were generated by photoheterolysis of trimethylammonium and chloride precursors. While a 4-MeO substituent provides sufficient stabilization to permit observation of cations in TFE, cations with less stabilizing substituents usually require the less nucleophilic HFIP. Even in this solvent, the parent benzyl cation is too short-lived (lifetime 6H4C+(R)-CH3 (R = Me, Et, i-Pr, t-Bu, cyclopropyl, C6H5, 4-MeOC6H4) were generated in TFE via the photoprotonation route. The alkyl series shows that steric effects are important in the decay reaction. The cation with R = cyclopropyl is a factor of 1.5 less reactive than the cation where R = phenyl. Several vinyl cations have also been generated by photoprotonation of phenylacetylenes. ArC+=CH2 has a reactivity very similar to that of its analog ArC+H-CH3, the vinyl cation being slightly (factors of 2-5) shorter-lived. For the various series of cations, including vinyl, substituents in the aryl ring have a consistent effect on the κ(max), a shift to higher wavelength relative to hydrogen of 15 nm for 4-Me, 30 nm for 4-MeO, and 50 nm for 4-Me2N.

Solvolytic Reactions in Fluorinated Alcohols. Role of Nucleophilic and Other Solvation Effects

Rate constants and products for solvolyses of chlorodiphenylmethane (Ph2CHCl) and p-methoxybenzyl chloride in 2,2,2-trifluoroethanol (TFE)/water and TFE/ethanol are reported, along with additional kinetic data for solvolyses of tert-butyl and other alkyl halides (RX) in 97% w/w TFE/water and in 97% w/w hexafluoropropan-2-ol/water (HFIP). Results are discussed in terms of the solvent ionizing power (Y) and the solvent nucleophilicity (N), and contributions from other solvation effects are considered. Comparisons with other SN1 solvolyses show that solvolyses of Ph2CHCl in TFE mixtures are unexpectedly fast, but product ratios are unexceptional. An additional solvation effect influences solvolyses leading to delocalized cations, and a delocalized cationic transition state for concerted elimination may explain the recent results of Takeuchi et al., (J. Org. Chem. 1997, 62, 4904) without the need to postulate additional specific solvation effects for adamantyl systems, such as Bronsted-base solvation of α- and β-hydrogen atoms; concerted elimination may occur because simple tertiary alkyl cations are too unstable to form in predominantly aqueous media. Iodide/bromide and bromide/chloride rate ratios are very similar for 1-adamantyl halides and corresponding solvolyses of tert-butyl halides; these ratios decrease in the order aq EtOH > TFE > HFIP, as expected for an electrophilic solvation effect (this effect can readily be incorporated into Y values). From kinetic data for a series of tertiary alkyl chlorides in 97% TFE/water, it is shown that the susceptibility of rates of solvolyses of RCl to N decreases with an increase in steric hindrance or with an increase in charge stabilization. Also, the small kinetic solvent isotope effects for typical solvolyses (e.g., methyl tosylate) indicate that nucleophilic attack lags behind heterolysis of the C-X bond.

Mechanisms of benzyl group transfer in the decay of (E)-arylmethanediazoates and aryldiazomethanes in aqueous solutions

Rate constants are reported for the buffer-independent decay of ten (E)-arylmethanediazoates in aqueous media at 25 °C, ionic strength 1 M (NaClO4), 4% 2-propanol, in the region of pH 4-12. The rate constants are proportional to hydrogen ion concentration at high pH and become pH independent in the low-pH region. Varying concentrations of oxyanion, amine, and hydrazine buffers over the range 0.05-0.2 M increased the pseudo-first-order rate constant for decay of the diazoates by less than 10%. The azide - water selectivities, ka/ks, for partitioning of the benzyl groups in the decay of (E)-(3,5-bis(trifluoromethyl)phenyl)methanediazoate and the (3,5-bis(trifluoromethyl)phenyl)diazomethane are determined to be 0.20 and 0.21 M-1, respectively, in phosphate buffered water and 0.27 and 0.26 M-1, respectively, in 20/80 DMSO-water. It is concluded that these two reactants decompose, in these media, via a common free diazonium ion intermediate that is formed in the case of the diazoate upon unassisted N-O bond cleavage of the diazoic acid. A common rate-limiting step is indicated for all the diazoates by the correlation line for the plot of log k1, the pH independent rate constant, against σ that has a slope q = -1.23. Product ratios for trapping of benzyl groups derived from other pairs of arylmethanediazoates and aryldiazomethanes with less electron withdrawing groups are different outside experimental error, indicating the importance of different nitrogen-separated ion pairs in these reactions. The (E)-(p-methoxy)phenyl)methane-16O-diazoate decomposes in 16O/18O water to give alcohol that has an "excess" abundance of 16O compared to solvent. Decomposition of the same compound in 50/50 trifluoroethanol-water with varying concentrations of azide indicates that azide ion appears to trap a limiting amount, ～80%, of the p-methoxybenzyl group. Quantitative analysis of the data indicates that 16% of the p-methoxybenzyl cation is trapped by solvent at the nitrogen-separated ion pair stage, in the absence of azide ion. There is a 9-fold enhancement of selectivity for trifluoroethanol at the ion pair stage that is ascribed to a proton switch initiated by the leaving hydroxide ion in the ion pair. The values of Ka/ks ～ 0.2 M-1 and kT/kH ～ 0.5-0.6 for the trifluoroethanol-water selectivity and kET/kT ～ 1 for the ethanol-trifluoroethanol selectivity are independent of substituent in the decay of arylmethanediazoates (X = H and EWG) in water, water-trifluoroethanol (50/50), and water-trifluoroethanol-ethanol (50/40/10), respectively. It is concluded from this that the productdetermining steps do not involve chemical bonding but rather rotational/translational reorientation of the nucleophiles in the first solvation sphere of the carbocation intermediates. It is concluded that the values of kH/kT = 0.5-0.6 indicate preferential solvation of the cation precursor by trifluoroethanol. It is shown that a preferential interaction for trifluoroethanol of 1 kcal/mol is required to generate the observed selectivities.

Distinguishing between Solvation Effects and Mechanistic Changes. Effects Due to Differences in Solvation of Aromatic Rings and Alkyl Groups

Solvolytic rate constants at 25 deg C are reported for p-methoxybenzylchloride (1) in aqueous binary mixtures with acetone, acetonitrile, dioxane, dimethyl sulfoxide, ethanol, methanol, and 2,2,2-trifluoroethanol and for benzoyl chloride and p-methoxybenzoyl chloride (2) in aqueous acetonitrile and aqueous dioxane.Product selectivities are reported for solvolyses of 1 in aqueous ethanol and methanol.Logarithms of rate constants for solvolyses of 2 correlate linearly with solvolyses of 1 (unit slope and only a small "dispersion" - the tendency for the various binary mix tures to show seperate correlations), showing that the solvation requirements of SN1 reactions of aromatic carboxylic acid chlorides are very similar to those of benzylic chlorides.Similar good correlations are reported vs solvolyses of α-phenylethyl chloride and vs Z values.For SN1 reactions of chlorides in binary mixtures having similar electrophilicities, the phenomenon of dispersion in Grunwald-Winstein plots (vs Y) and the poor correlation vs YCl (reported previously) appears to be due to the differences in solvation between aromatic rings and alkyl groups; this difference is largest for binary aqueous mixtures with methanol > ethanol > aprotic solvents.The complex rate-rate profile for similar solvolytic reactions of benzoyl chloride is dissected quantitatively into contributions from two competing reaction channels, one of which shows only a small "dispersion" in a correlation with solvolyses of 2; these results are consistent with a mainly dissociative reaction channel for solvolyses of benzoyl chloride in highly aqueous media.

Nucleofugality of the Sulfinate Group in Carbocation-Forming Processes

The solvolytic reactivity of a variety of sulfones and sulfinate esters has been determined which allows one to place the sulfinate leaving group in a relative nucleofugality scale.Cumyl trifluoromethyl sulfone (1) reacts in a variety of solvents to give substitution products.The mOTs value of 0.82 is indicative of the involvement of the cumyl cation (9) formed in kc process.In terms of rate, 1 is 170 times less reactive than cumyl chloride but 286 times more reactive than cumyl p-nitrobenzoate.The analogous cumyl methyl sulfone (2) and cumyl phenyl sulfone (3) solvolyze approximately 107 times more slowly than 1.The sulfinate esters cumyl methanesulfinate (6) and cumyl p-toluenesulfinate (7) are considerably more reactive than the analogous sulfones.Methanolysis of 6 was also subject to acid catalysis, where a mechanism analogous to the AAL1 mechanism of hydrolysis of esters of carboxylic acids was suggested.The less hindered α-phenethyl trifluoromethyl sulfone (4) and p-methoxybenzyl trifluoromethyl sulfone (5) solvolyzed at rates that approached those of the analogous p-nitrobenzoates.This was indicative of the importance of relief of steric congestion in solvolyses of the more hindered tertiary sulfone 1.