Hydrogen Bonding and Catalysis of Solvolysis of 4-Methoxybenzyl Fluoride

Abstract

Values of k(o) = 8.0 x 10(-3) s(-1) and k(H) = 2.5 x 10(-2) M(-1) s(-1), respectively, were determined for the spontaneous and the acid-catalyzed cleavage of 4-methoxybenzyl fluoride (1-F) to form the 4-methoxybenzyl carbocation (1+). Values of k(F) = 1.8 x 10(7) M(-1) s(-1) and k(HF) = 7.2 x 10(4) M(-1) s(-1) were determined for addition of F- and HF to 1+ for reaction in the microscopic reverse direction. Evidence is presented that the reversible addition of HF to 1+ to give 1-F + H+ proceeds by a concerted reaction mechanism. The relatively small 250-fold difference between the reactivities of fluoride ion and neutral HF toward 1+ is attributed to the tendency of the strong aqueous solvation of F- to decrease its nucleophilic reactivity and to the advantage for the concerted compared with the usual stepwise pathway for addition of HF. There is no significant stabilization of the transition state for cleavage of 1-F from general acid catalysis by 0.80 M cyanoacetate buffer at pH 1.7. The estimated 3 kcal/mol larger Marcus intrinsic barrier for heterolytic cleavage of 1-F than for cleavage of 1-Cl is attributed to a lag in the development at the transition state of the ca. 30 kcal/mol greater stabilizing solvation of the product ion F- compared with Cl-. The decrease in the electronegativity of X along the series X = F, OH, Cl is accompanied by a ca. 10(10)-fold increase in the carbon basicity compared with the proton basicity of X-.

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates SNAr Reactions of Heterocycles with Arylamines

“…The results in Table 3 imply that although the p K a determines the concentration of free aniline, it is the p K a of the nitrogenous heteroaryl substrate that is the key parameter dictating the optimal quantity of TFA. On account of the similarity of TFE and water with respect to polarity (E N T for TFE: 0.90; for water: 1.00),33 p K a values of anilines in TFE are likely to be similar to those measured in water (compare p K a values of anilines in methanol and ethanol, which correlate closely with the polarities of these solvents relative to water) 34. It should be noted that at 25 °C, with or without TFA, no reaction was observed for 4,7‐dichloroquinoline and benzylamine (p K a 9.34) during 8.5 h in TFE.…”

“…A study of TFA‐catalysed reactions of 6‐halopurines (halo=F, Cl, Br and I) with aniline in acetonitrile concluded that loss of halide from the Meisenheimer–Jackson intermediate was indeed rate limiting 14. The importance of fluoride solvation in solvolysis of alkyl fluorides (e.g., 4‐methoxybenzyl fluoride in water) is well‐known 33. A marked effect of TFE relative to ethanol in solvolysis of glycosyl fluorides was ascribed to better solvation of fluoride by TFE 40.…”

“…[14] The importance of fluoride solvation in solvolysis of alkyl fluorides (e.g., 4-methoxybenzyl fluoride in water) is wellknown. [33] A marked effect of TFE relative to ethanol in solvolysis of glycosyl fluorides was ascribed to better solvation of fluoride by TFE. [40] In another recent study, it was shown that for reaction of 2,5,6-trifluoronicotinenitrile with the amino group of 3-isopropoxy-1H-pyrazol-5-amine in tetrahydrofuran, monoprotonated 1,4-diaza [2,2,2]-bicyclooctane assisted the loss of the 6-fluoro group from the intermediate.…”

Substituent effects on the formation and nucleophile selectivity of ring‐substituted phenonium ions in aqueous solution

“…[6][7][8][9] A value k s % 3 Â 10 12 s À1 (Scheme 1) has been estimated for addition of a largely aqueous solvent to a simple tertiary carbocation, and it was proposed that solvent reorganization with a rate constant k r % 10 11 s À1 is the rate-limiting step for the overall carbocation-nucleophile combination reaction. [10,11] Electron-donating a-substituents, such as methoxy [12] and 4-methoxyphenyl, [13][14][15] (Scheme 1), are sufficient to give a carbocation with a lifetime long enough to permit diffusion-controlled bimolecular trapping by added nucleophiles. Surprisingly, the lifetimes of a-substituted 4-methoxybenzyl carbocations are not strongly affected by a strongly electronwithdrawing substituent at the a-carbon, such as a-CF 3 and a-COOEt.…”

General Acid–Base Catalysis in Model Systems

“…Catalysis is seen only with the more stable substituted 1-phenylethyl carbocations, is most important for the reactions with weakly basic alcohols and disappears when diffusion processes begin to compete. HF has a pK a in the region of 3, depending on the solvent, so proton transfer to fluoride is not favorable from a general acid with pK a > 3, and none is observed by cyanoacetic acid (pK a ¼ 2:2) [18]. This behavior marks the borderline with specific acid catalysis of the hydrolysis reaction of the trifluorethyl ether: and probably also that of the corresponding fluoride [18].…”