Trifluoroethanol nucleophilicity

Substitution of chloropolymer is possible using a variety of nucleophiles. The most common are sodium salts of alcohols and phenols. Thermoplastics are obtained using a single substituent, whereas multiple substituents of sufficiently different size lead to elastomers (2). Liquid crystal behavior similar to polysHoxanes has been noted in most homopolymers. The homopolymer formed using trifluoroethanol as a substituent has received a fair amount of academic scmtiny (7). 

In fluorinated alcohols such as 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-isopropanol, only alkoxy-de-diazoniation and substitution by the anion of the diazonium salt are observed (Sec. 8.3), because these alcohols are extremely weak nucleophiles. 

The 15N content was indeed lower when the experiment was performed This result justified the publication of a preliminary communication (Bergstrom et al., 1974). Later work (Hashida et al., 1978 Szele and Zollinger, 1978a Maurer et al., 1979) involving sophisticated statistical treatments suggested that, in a weakly nucleophilic solvent such as trifluoroethanol, the phenyl cation is formed in two steps and not in one, as in mechanism B (see Scheme 8-4 in Sec. 8.3), the first intermediate being a tight ion-molecule pair. 

Activated esters of halogenated alcohols, such as 2-chloroethanol, 2,2,2-trifluoroethanol, and 2,2,2-trichloroethanol, have been often used as substrate for enzymatic synthesis of esters, owing to an increase in the electrophilicity (reactivity) of the acyl carbonyl and avoid significant alcoholysis of the products by decreasing the nucleophilicity of the leaving alcohols. ... 

The use of trifluoroethanol as solvent or absorption of the dienone on silica gel promotes the photoconversion of dienones into bicyclic ketenes.<47) For the photolysis<48 60) of (63) it has been shown by low-temperature infrared and ultraviolet spectroscopy that the initial photolysis gives a ketene which can be efficiently trapped by cyclohexylamine or, in the absence of a good nucleophile, thermally rearranges by a OA, + 20) allowed process to a bicyclic ketone (64) ... 

The determination of large values of the rate constant ratio ks/kpfrom the low yields of alkene product that forms by partitioning of carbocations in nucleophilic solvents. These rate constant ratios may then be combined with absolute rate constants for the overall decay of the carbocation to give absolute values of kp (s ).14 16 For example, the reaction of the l-(4-methylphenyl)ethyl carbocation in 50/50 (v/v) trifluoroethanol/water gives mainly the solvent adducts and a 0.07% yield of 4-methylstyrene from proton transfer to solvent, which corresponds to kjkp = 1400. This can be combined with ks = 6 x 109 s V4 to give kp = 4.2 x 106 s l (Table 1). 

Fig. 5 Logarithmic plots of rate-equilibrium data for the formation and reaction of ring-substituted 1-phenylethyl carbocations X-[6+] in 50/50 (v/v) trifluoroethanol/water at 25°C (data from Table 2). Correlation of first-order rate constants hoh for the addition of water to X-[6+] (Y) and second-order rate constants ( h)so1v for the microscopic reverse specific-acid-catalyzed cleavage of X-[6]-OH to form X-[6+] ( ) with the equilibrium constants KR for nucleophilic addition of water to X-[6+]. Correlation of first-order rate constants kp for deprotonation of X-[6+] ( ) and second-order rate constants ( hW for the microscopic reverse protonation of X-[7] by hydronium ion ( ) with the equilibrium constants Xaik for deprotonation of X-[6+]. The points at which equal rate constants are observed for reaction in the forward and reverse directions (log ATeq = 0) are indicated by arrows.

The addition of two ortho-methyl groups to Me-[8+] to give Me-[10+] results in a 70-fold decrease in the rate constant ks for nucleophilic addition of 50/50 (v/v) trifluoroethanol/water.27... 

Fig. 14 Typical log k/YBr plots for assisted and unassisted alkene brominations. Allylbenzene and 1-pentene, less crowded than cis-methyl-t-butylethylene and methylideneadamantane, exhibit the smallest m-values. The points corresponding to acetic acid (O) and trifluoroethanol (A), two weakly nucleophilic solvents, are below the regression line for water, methanol, ethanol and their aqueous mixtures ( ) of similar nucleophilicity. In contrast, they are on the line for the branched alkenes where steric crowding inhibits nucleophilic assistance by alcoholic solvents (Ruasse et al, 1991, Ruasse and Motallebi, 1991).

A mechanistic scheme, (Scheme 4) similar to that previously reported (72) for nucleophilic substitution, in which pre-association, free-ion and ion-pairs pathways compete, can therefore also be proposed for bromination. Based on this scheme, the stereochemical behaviour depends on both solvent and substituents. In trifluoroethanol, the reaction occurs independently of the substituents on the double bond, via free ions ... 

Rate constants and products have been reported for solvolysis of benzhydryl chloride and /7-methoxybenzyl chloride in 2,2,2-trifluoroethanol (TFE)-water and-ethanol, along with additional kinetic data for solvolysis of r-butyl and other alkyl halides in 97% TFE and 97% hexafluoropropan-2-ol. The results are discussed in terms of solvent ionizing power Y and nucleophilicity N, and contributions from other solvation effects are considered. Comparisons with other 3 nI reactions show that the solvolyses of benzhydryl chloride in TFE mixtures are unexpectedly fast an additional solvation effect influences solvolysis leading to delocalized cations. 

Figure 2.5. Nucleophile selectivities determined from product analysis for the reactions of ring-suhstituted 1-phenylethyl derivatives (X-l-Y) with azide ion, acetate ion and methanol in 50 50 (v/v) water/trifluoroethanol. The selectivities are plotted against the appropriate Hammett substituent constant or a. Leaving group Y ( ) ring-suhstituted benzoates ( ) chloride (T) dimethyl sulfide (A) tosylate.

Nucleophilic Substitution at Benzyl Derivatives. The sharp break from a stepwise to a concerted mechanism that is observed for nucleophilic substitution of azide ion at X-l-Y (Figs. 2.2 and 2.5) is blurred for nucleophilic substitution at the primary 4-methoxybenzyl derivatives (4-MeO,H)-3-Y. For example, the secondary substrate (4-MeO)-l-Cl reacts exclusively by a stepwise mechanism through the liberated carbocation intermediate (4-MeO)-T, which shows a moderately large selectivity toward azide ion ( az/ s = 100 in 50 50 (v/v) water/ trifluoroethanol). The removal of an a-Me group from (4-MeO)-l-Cl to give (4-MeO,H)-3-Cl increases the barrier to ionization of the substrate in the stepwise reaction relative to that for the concerted bimolecular substitution of azide ion. The result is that both of these mechanisms are observed concurrently for nucleophilic substitution of azide ion at (4-MeO,H)-3-Cl in water/acetone solvents. These concurrent stepwise and concerted nucleophilic substitution reactions of azide ion with (4-MeO,H)-3-Cl show that there is no sharp borderline between mechanisms for substitution at primary benzylic carbon, but instead a region of overlap where both mechanisms are observed. 

For example, the PET reaction of 1-phenylcyclohexene (110) in the presence of nucleophiles (KCN acetonitrile / 2,2,2-trifluoroethanol) proceeds by anti-... 

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