Solvent systems weakly nucleophilic

Table S.16 presents data on some representative nucleophilic substitution processes. The first entry illustrates the use of 1-butyl-l-r/p-bromobenzenesulfonate to dononstrate at primary systems react with inversion, even under solvolysis conditkms in formic acid. The observation of inversion indicates a concerted mechanism in fids weakly nucleophilic solvent.

We have recently reported ( ) several synthetic studies of weak nucleophile SnAr reactions. In the latter cases (26f-1), new synthetic methodology was reported for the direct introduction of fluoroalkoxy groups into a variety of aromatic systems. These reports represent synthetically useful procedures for obtaining some otherwise inaccessible fluoroalkoxy materials but, unfortunately, they require the use of a dipolar, aprotic solvent (usually hexamethylphosphoramide, HMPA) and, in some cases, elevated temperatures. However, because of their diverse and important applications ( ), the syntheses of these and other organofluoro compounds continue to be of interest. For example, two recent reports of useful fluoroalkoxy materials include the insecticide activity exhibited by fluoroalkoxy substituted 1,3,4-oxadiazoles... 

As a mechanistic tool in the investigation of acid- or base-catalysed reactions in aqueous solution, the measurements in isotopically mixed solvents are most useful for reactions where a certain amount is already known about the mechanism. In particular, the study of mixed solvents is also a good deal more informative whenever it is possible to measure product isotope effects in addition to rate isotope effects. In such cases (and A-Sb2 reactions spring to mind as a good example) solvent isotope effect studies can add considerably to the detailed picture of a transition state. The phenomena are as yet less suited to the ah initio assignment of reaction mechanism, such as the decision between weak nucleophilic participation of water in an acid-catalysed reaction and an A-l mechanism, when no information beyond the kn-n relation is available. For these reasons it is likely that mechanistic investigation by this method will increasingly be directed towards systems where both rate and product isotope effects are obtainable. 

The addition of N2F4 to unsaturated systems was first studied in detail by Petry and Freeman (235). They found that in most cases vicinal bis(difluoroamines) resulted in good yield. Only with weakly nucleophile olefins, such as tetracyanoethylene, was there no addition. The aliphatic olefins reacted smoothly at about 100°C, the electron-rich olefins reacting more readily than those which were electron-poor. Thus, perfluoropropylene required a temperature of 140°C, whereas dimethyl styrene absorbed N2F4 even at room temperature. Reactions were usually carried out under pressure and in a solvent such as chloroform or chlorobenzene. 

However, in the good ionizing but only weakly nucleophilic solvent 2,2,2-trifluoroethanol (TFE), Rhodes and coworkers found kinetic as well as product evidence (Scheme 17) that the j5-cyclopropyl group does indeed participate to a small extent. Also, Rhodes and Takino have demonstrated cyclopropyl participation in a sterically hindered neopentyl type system (125). 

In aprotic solvent, F becomes more nucleophilic and HF a weak acid. However, the reactivity of F is quite sensitive to the water content of the electrolysis system because a hydrated F is a weak nucleophile [7,8]. Drying of both the solvent and electrolyte is therefore necessary to optimize the formation of fluorinated products. 

If the nucleophile is different from the electrophile we can get a bit more information about the course of the reaction. When butadiene is treated with bromine in methanol as solvent, two adducts are formed in a 15 1 ratio along with some dibromide. Methanol is a weak nucleophile and adds to the bromonium ion mainly at the allylic position (black arrow below) only a small amount of product is formed by attack at the far end of the allylic system. Note that no attack occurs at the other end of the bromonium ion (green dotted arrow). 

Examination of Solvent Effect on Nucleophilic Fluorination with KF/ dicvclohexano-18 crown-6. Using 1-bromodocosane (12) as substrate and KF/DC-18-C-6 as reagent system, solvent effect was examined. Solvents were chosen from common dipolar aprotic solvent [acetonitrile, hexa-methylphosphoric triamide (HMPT), dimethylsulfoxide (DMSO), diglyme], from weakly basic dipolar aprot c solvents (sulfolane, ethylene carbonate, propylene carbonate) " and from acid amide solvents [N,N-dimethylformamide (DMF), N,N-diethylacetamide (DEA), N-methyl-pyrrolidone (NMP), tetramethylurea]. ... 

The use of chiral substrates has allowed the importance of solvent and nucleophile-associated cation to be probed. For example, as shown in Scheme 7.10, when chiral 1-chloro-l-phenylethane is heated in ethanoic acid (acetic acid,CH3C02H]) at 50°C in the presence of potassium ethanoate (potassium acetate, CH3C02 K+), the ethanoic acid (acetic acid, CH3CO2H) ester of 1-phenylethanol is obtained. In this weakly nucleophilic system, about 15% excess inverted product is found (i.e., 85% of the product is racemic and the substitution reaction occurred with about 57.5% inversion and 42.5% retention). Presumably, the carbocation formed first and then... 

There has been a review commentary of substitutions in non-polar media addressing the question, are weak interactions responsible for kinetic catalytic behaviour in 5 NAr reactions A kinetic study of the reactions of picryl fluoride with alcohols in carbon tetrachloride shows that the order in alcohol is greater than unity. This is interpreted as evidence for specific interaction between the substrate and alcohol prior to rate-limiting reaction with a further alcohol molecule. Self-association of amine molecules to form dimers which act as the effective nucleophile is an alternative explanation for the high kinetic orders observed in non-polar solvents. Results for the reaction of l-chloro-2,4-dinitrobenzene with aromatic amines in toluene - " and in benzene-hexane mixtures have been interpreted on this basis. Rate constants have been measured for reactions of l-halo-2,4-dinitrobenzenes with primary and secondary amines in a variety of aprotic binary solvent systems and correlations have been attempted with solvatochromic data, including t(30) values. ... 

Elimination of the multidentate interaction of a counterion with the siloxane chain is crucial. Otherwise, as mentioned before, the equilibration reactions would make the precision polymerization impossible. Specific initiator-solvent systems used for this purpose may be divided into three groups (1) basic solvent and a hard counterion, which interacts with solvent stronger than with siloxane, for example, lithium/THF (2) bulky and soft counterions, for example, Me4N BtuP, and phosphazenium cations, which weakly interact with nucleophiles (3) basic promoters strongly interacting with counterions, such as HMPT, DMSO, DMF, cryptands, and crown ethers. ... 

The retrogradation of the dissociation equilibrium is brought about by addition to the reaction medium of common ion salts whose cation is inert toward the polymerization system. As for the nature of the counterions, those that bring about a certain covalency of the active centers are preferred. Addition of a weak nucleophile is also an efficient means to curb the reactivity of carbocations. The following systems (monomer, initiating system, solvent) qualify, more or less perfectly, for the category of living polymerizations ... 

This type of ring interconversion is represented by the general expression shown in Scheme 15. Analogous rearrangements occur in benzo-fused systems. The known conversions are limited to D = O in the azole system, i.e. cleavage of the weak N—O bond occurs readily. Under the reaction conditions, Z needs to be a good nucleophile in its own right or by experimental enhancement (base catalysis, solvent, etc.) and Z is usually O, S, N or C. 

However, unlike most conventional solvents, many ionic liquids combine high solvating power for polar catalyst complexes (polarity) with weak coordination (nucleophilicity) [38], It is this combination that enables a biphasic reaction mode with these ionic liquids even for catalyst systems which are deactivated by water or polar organic solvents. 

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