Solvent nucleophilicity determination

The nature of the solvent also determines the chemoselective outcome in the reaction products. Products arising from the incorporation of one solvent molecule are formed (besides dibromides) in alcohols, acetic acid and acetonitrile (Id-e), whereas dibromo derivatives are formed exclusively in chlorinated solvents, nitromethane and in ionic liquids. (9) Chemoselectivity depends on the relative nucleophilicity of the solvent and the counterion, although it is affected also by other phenomena (ion pairing, and ion dissociation) in methanol the addition process gives quasi-exclusively bromo-methoxy adducts, whereas in acetic acid dibromides are the main products, formed in addition to smaller amounts of the bromo-acetoxy derivatives. (70)... 

In SjvAr involving amines as the nucleophiles, abundant recent studies afford evidence of the importance of the nature of the solvent in determining whether the formation or the decomposition of the zwitterionic intermediate will be the rate-determining step1,36,20. 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

The value of kd was obtained from the determination of triplet lifetimes by measuring the decay of phosphorescence and found to be insensitive to changes in solvent polarity. The k2 values derived from Eqs. 10 and 11 were correlated with solvent parameters using the linear solvation energy relationship described by Abraham, Kamlet and Taft and co-workers [18] (Eq. 12), which relates rate constants (k) to four different solvation parameters (1) or the square of the Hildebrand solubility parameter (solvent cohesive energy density), (2) n or solvent dipolarity or polarizability, (3) a, or solvent hydrogen bond donor acidity (solvent electrophilic assistance), and (4) or solvent hydrogen bond acceptor basicity (solvent nucleophilic assistance). 

The purpose of this chapter is to give an introduction to the subject of nucleophilicity. The chapters of the present volume are collected into five groups (1) Marcus theory, methyl transfers, and gas-phase reactions (2) Br0nsted equation, hard-scft acid-base theory, and factors determining nucleophilicity (3) linear free-energy relationships for solvent nucleophilicity (4) complex nucleophilic reactions and (5) enhancement of nucleophilicity. The present chapter is divided in the same way, giving an introduction to each of the five topics followed by a description of key points in each chapter as they relate to current studies of nucleophilicity and the other chapters of the book. 

In Chapter 18, Bentley reviews development of scales of solvent nucleophilicity and applies the Bentley-Schleyer equation to determine N and Y values for sulfuric acid. Also, Bentley examines here the validity of the Taft... 

We first applied the solvatochromic equation (SCE) to solvolysis of tert-butyl chloride (t-BuCl) to determine if the method could give a reasonable result for this much-studied reaction (7). Abraham et al. (11) had previously attempted correlation of these rates with the SCE without the cavity term, but as Bentley and Carter (12) have noted, an unsatisfactory result was achieved (7). First, TFE and hexafluoroisopropyl alcohol (HFIP) did not fit the correlation. Second, no rate dependence on solvent nucleophilicity 0 was found, despite other works indicating a weak dependence on this parameter (12, 13). Also, different correlations were observed for hydroxylic and nonhydroxylic solvents Bentley considered this finding to indicate that the dehydrohalogenation transition state (in nonhydroxylic solvents) and the solvolysis transition state (in hydroxylic solvents) were significantly different and thus concluded that the two types of reactions should not be included in the same correlation. 

A comparison of the rates of solvolysis of the tert-butyldimethylsulfonium ion and the 1-adamantyldimethylsulfonium ion presents strong evidence that the solvent dependence of the tert-butyldimethylsulfonium ion solvolysis rates is governed primarily by solvent nucleophilicity effects. Leaving-group contributions based upon 1-adamantyldimethylsulfonium ion solvolyses are better incorporated into the establishment of the solvent nucleophilicity scale based upon triethyloxonium ion solvolysis. Alternative solvent nucleophilicity scales based upon the solvolysis of S-methylbenzo-thiophenium ions are discussed. Analyses of the extent of nucleophilic participation by the solvent in the solvolyses of methyldiphenyl-sulfonium and benzhydryldimethylsulfonium ion will be presented. The relative nucleophilicities of various anionic and neutral nucleophiles toward the triethyloxonium ion in ethanol have been determined. 

From the deviations, a scale of nucleophilicity was derived. Halogenated acetic acids were included, on the basis of reactivities with halonium ions. Other scales appeared from the Schleyer group (5, 6) at about the same time. The various nucleophilicity scales were used to correlate solvolysis rates by now familiar four-parameter equations AG = N + mY or AG = sN + mY. (G — free energy N = solvent nucleophilicity Y = solvent ionizing power s = sensitivity m = sensitivity.) Previously, parameters for such equations had not been determined. 

DFT studies of the hydrolysis of acetyl and chloroacetyl chloride and of variously substituted benzoyl chlorides supported an S 2 mechanism. An extended Grunwald-Winstein equation correlation for the specific rates of solvolysis of 3,4,5-trimethoxybenzoyl chloride gave sensitivities towards changes in solvent nucleophilic-ity (/-value) of 0.29 and solvent ionizing power (m-value) of 0.54. The low m-value allowed specific rates to be determined in highly ionizing fiuoroalcohol/H20 mixtures. A parallel correlation of the specific rates of solvolysis of 2,4,6-trichlorobenzoyl chloride revealed that solvolyses in 100% and 90% ethanol or methanol did not appreciably follow the ionization pathway indicated for solvolyses in the other solvents and it was proposed that, despite the two or//to-substituents, the addition-elimination pathway had become dominant. ... 

Kinetic studies of the aminolysis of bis(Y-phenyl) chlorophosphates ([YCgH40]2 (P=0)C1 Y = H, 4-Me, 4-MeO, 3-MeO) by anilines and deuterated anilines showed that the reaction proceeded via a stepwise mechanism, with rate-determining breakdown of the trigonal bipyramidal intermediate. The effects of solvents and solvent mixtures upon the rates of hydrolysis of diphenyl and bis-(2,4-dichlorophenyl) chlorophosphate showed that there were large sensitivities towards changes in solvent nucleophilicity, consistent with an 5 ivf2(P) process. ... 

Attack by a nucleophile or the solvent can occur at either of the ion pairs. Nucleophilic attack on the intimate ion pair would be expected to occur with inversion of configuration, since the leaving group would still shield the fiont side of the caibocation. At the solvent-separated ion pair stage, the nucleophile might approach fiom either fece, particularly in the case where solvent is the nucleophile. Reactions through dissociated carbocations should occur with complete lacemization. According to this interpretation, the identity and stereochemistry of the reaction products will be determined by the extent to which reaction occurs on the un-ionized reactant, the intimate ion pair, the solvent-separated ion pair, or the dissociated caibocation. 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

---