Solvolysis Studies

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

The occurrence and extent of rearrangement of the 2-butyl cation have also been investigated by solvolysis studies using isotopic labeling. When 2-butyl tosylate is solvolyzed in acetic acid, C-2/C-3 rearrangement occurs only to the extent of 9% in the 2-butyl acetate which is isolated.Thus, under these conditions, most of the reaction proceeds by direct participation of the solvent. 

The results of the methanolic solvolysis study shown in Fig. 7.15 reveals that nucleophilic attack on the cyclopropyl quinone methide by methanol affords the pyrido[1,2-a]indole (73 ppm) and azepino[l,2-a]indole (29ppm) trapping products. Initially, nucleophilic attack on the cyclopropane ring affords the hydroquinone derivatives (see Scheme 7.17) that oxidizes to the quinones upon aerobic workup. 

Extrapolation of the data to zero time suggests that the endo acetates (65) and (67) are produced in amounts as great as or greater than the exo isomer. Solvolysis studies of the bicyclo[3.1.0]hex-2-en-6-yl cation reveal that nucleophilic capture occurs preferentially from the exo side to give (66) rather than (67). Similarly, solvolysis of cation (63) leads to exo product (64) in at least a 90% yield. Photolysis of benzene in deuteriophosphoric acid results in (68), in which all the deuterium is incorporated into the 6-endo position ... 

Solvolysis studies - Aa11 reactivity 60 Nucleophilic substitution reactions - SN2 reactivity 70 Thermal decomposition reactions 90... 

IV-acyloxy-iV-alkoxyamides, biological activity, 97-115 anticancer activity of, 115 mutagenicity of, in Ames Salmonella/ microsome assay, 97-115 IV-acyloxy-iV-alkoxyamides, chemical reactivity, 59-96 factors contributing, 59-60 nucleophilic substitution reactions, see Nucleophilic substitution reactions solvolysis studies, see Solvolysis... 

The parent trishomocyclopropenyl cation [47], first proposed by Winstein et al. (1959), has been invoked as an intermediate in various solvolysis studies, observed under stable ion conditions by NMR spectroscopy, and studied theoretically (see Story and Clark, 1972 Paquette, 1978). Similarly, the related ions [48]—[51] have all been advanced as trishomoaromatics (see Story and Clark, 1972 Paquette, 1978). 

Interest in solvolysis studies of phosphate esters appears to have sagged during the year, but such studies as have appeared include those on the acid-catalysed hydro-... 

The dehydration of norbornanols was carried out at 280° and 310° over acidic alumina and over alumina modified by piperidine (73). The rate of dehydration of norbornanols is about three to six times slower than that of the corresponding bornanols. 2-ea o-Norbornanol dehydrates six times faster than 2-ewdo-norbornanol. These results agree with those obtained by Winstein and Trifan (74) from the solvolysis studies of the corresponding j-toluenesulfonates and chlorides. 

Solvolysis studies of meta- and para-substituted phenyl phosphates (240) in anhydrous Bu OH and in Am OH have revealed that generally reactions of dianions are much faster in alcohols than in water. For example, the dianion of p-nitrophenyl phosphate (240 X = 4-NO2) reacts 7500- and 8750-fold faster in Bu OH and Am OH, respectively, than in water." The results of a theoretical study of the reactivity of phosphate monoester anions in aqueous solution do not support the generally accepted view that Brpnsted coefficients fhg = —1.23 and jSnuc = 0.13 determined more than 30 years ago for the uncatalysed reaction of water and a monophosphate dianion (241) represent conclusive evidence for the dissociative mechanism. It is suggested that, instead, the observed LFERs could correspond to a late transition state in the associative mechanism." ... 

A wealth of chemistry has emerged from the solvolysis studies of cyclobutylmethyl sulfonates and related compounds, which are able to undergo ring enlargement to cyclopentyl systems via the cations. A schematic representation of this reaction is shown. Some ring-expansion reactions to be classified under this category are also shown and further examples are discussed.27 24... 

The relative rate data closely parallel the results obtained in the solvolysis studies. Such a result might be expected from reactions proceeding through similar transition states. The observed order of relative rates may result from better overlap as the size of the central metal atom and the polarizability of its electron shell increase. This would result in increased stabilization and therefore ease of formation of the carbonium ions, proceeding from lighter to heavier metal complexes. 

The /-effect of silicon has so far found little application in organic synthesis, apart from the solvolysis studies described previously. 

The 7-Norbornyl Cation. 7-Norbomyl derivatives were found to be extremely unreactive in solvolysis studies and product formation was shown to occur with predominant retention of configuration.917 920 These observations led to the suggestion by Winstein et al.917 that the cationic intermediate is a nonclassical ion. Attempts to isolate the 7-norbomyl cation under stable ion conditions in superacid... 

The procedure adopted to portray the scope and utility of a linear free-energy relationship for aromatic substitution involves first a determination of the p-values for the reactions. These parameters are evaluated by plotting the values of log (k/ka) for a series of substituted benzenes against the values based on the solvolysis studies (Section IV, B). The resultant slope of the line is p, the reaction constant. The procedure is then reversed to assess the reliability and validity of the Extended Selectivity Treatment. In this approach the log ( K/ H) observations for a single substituent are plotted against p for a variety of reactions. This method assays the linear or non-linear response of each substituent to variations in the selectivity of the reagents and conditions. Unfortunately, insufficient data are available to allow the assignment of p for many reactions. It is more practical in these cases to adopt the Selectivity Factor S as a substitute for p and revert to the more empirical Selectivity Treatment for an examination of the behavior of the substituents. 

The o -values evaluated from the solvolysis study are in the inverse order (Table 27). As noted in Section IV, solvent effects are apparently significant to the minor extent necessary to effect these small changes. 

The cr+-parameters determined by the application of the Selectivity Treatment of the few data for substitution of the deactivated mono-substituted benzenes offer a preliminary indication of the use of the o-+-constants from the solvolysis study. However, major uncertainties exist for the charged groups. 

Although most laser flash photolysis studies have been performed in acetonitrile, transient vinyl cations have also been observed in acetonitrile/methanol mixtures and even in pure methanol309. In acetic acid, the solvent of choice for most thermal solvolysis studies of vinylic halides, the presence of polar additives such as sodium acetate is necessary for transient vinyl cations to be observed335. 

Schleyer and coworkers investigated the nature of the 9-barbaralyl cation by solvolysis studies of the corresponding tosylate. The acetolysis of 9-deuterio-9-barbaralyl tosylate gave 9-barbaralyl acetate with complete deuterium scrambling, whereas solvolysis in more nucleophilic aqueous acetone gave the product alcohols with the label exchanged to only positions C3, C7 and C9 (equation 50). Solvolysis of 4-deuteriobicyclo[3.2.2]nona-2,6,8-trien-4-yl 3,5-dinitrobenzoate also resulted in the formation of the 9-barbaralols with deuterium scrambled to positions 1, 2, 8, 4, 5 and 6, with only trace amounts at C3 and (equation 51). 

Triflales have been used extensively in solvolysis studies. 

This problem was originally investigated by solvolysis studies, and the structure of the intermediate ion and the nature of the delocalization was inferred from rate and product studies, which made extensive use of isotopically labeled substrates. These earlier studies have been thoroughly reviewed ... 

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