Non-nucleophilic medium

The formation of stable disulfonium dications from certain bis-sulfides provided an impetus for re-evaluating the mechanisms of some old reactions. The isomerization of sulfoxide 124, using trifluoroacetic acid, involved an acid-catalyzed migration of an oxygen atom from a sulfoxide to sulfide (see Equation 36). This was one of the first examples in which an intermediate formation of an S-S dication was proposed. Recently, such a dication 125 was detected in a non-nucleophilic medium such as sulfuric acid <1995HAC145>. 

Nitrone Oxidation in Non-Nucleophilic Medium Treatment of nitrones with strong oxidants such as Pb02, Mn02 (506) and CIO2 (507), in... 

If phenylcyclopropylcarbene (522) is generated in a non-nucleophilic medium such as benzene, a high yield of phenylcyclobutene is obtained in a reaction which bears a formal similarity to the cyclopropylmethyl-cyclobutyl... 

The decomposition of organic hydroperoxides by the action of SO2 depends on the reaction medium for example, cumyl hydroperoxide (CHP) is quantitatively decomposed into phenol and acetone if the reaction is carried out in an anhydrous weakly nucleophilic or non-nucleophilic medium (e.g., CCI4, CH3CN, CH3CH2CI, CH2=CHC1). This type of decomposition, which proceeds through an ionic mechanism without formation of radicals, can also be obtained [256,257] with perchloric acid, ferric chloride in benzene, and sulfuric acid. It is, therefore, inferred that SO2 behaves as a strong acid toward the decomposition of CHP in anhydrous, weakly nucleophilic or non-nucleophilic solvents. 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

Addition of non-nucleophilic electrolytes (e.g. nitrates, Table 2.5, entry 3) shows that the consequent increased rate is due to the increase in the ionic strength of the medium, further supporting the trapping mechanism. A comparison of the effects of added bromide and chloride (entries 2 and 5) illustrates the common ion effect, i.e. trapping Ar2CH+ by chloride to regenerate starting material retards solvolyses of A CHCl. 

The rearrangement of [13] bears a close resemblance to the transannular reactions observed in medium sized rings that have been reviewed by Prelog and Traynham (1963) and Cope et al. (1966). Recently Sorensen and coworkers have studied medium sized cycloalkyl cations under stable ion conditions in non-nucleophilic media and demonstrated that their structures are ji.-hydrido-bridged. The bonding situation in these ions contrasts sharply with that in the ions described above and rather corresponds to that of transition states (or intermediates) for intramolecular hydride transfer in these ions. 

Bromine Addition to Alkenes. Alumina can advantageously replace protic solvents thus avoiding secondary reactions due to their nucleophdicity. This situation is evidenced in the bromation of alkenes [14]. When performed in methanol, bromine addition leads to a mixture of a frans-dibromo adduct and a trans-bromo ether compound. The latter results from competitive attack by pro-tic solvent on the bromonium ion intermediate. This byproduct can be suppressed using Br2/alumina, as the support behaves as a non-nucleophilic polar medium (Scheme 3). 

The extent to which rearrangement occurs depends on the structure of the cation and the nature of the reaction medium. Capture of carbocations by nucleophiles is a process with a very low activation energy, so that only very rapid rearrangements can occur in the presence of nucleophiles. In contrast, in non-nucleophilic media, in which the carbocations have a longer lifetime, many rearrangement steps may occur. This accounts for the fact that the most stable possible ion is usually the one observed in superacid systems. 

A very non-nucleophilic anion, such as perchlorate, can replace the leaving group at the solvent-separated ion pair stage. Upon reversion to a contact ion pair but with perchlorate, the perchlorate cannot form a stable compound with the carbenium ion. Hence, this salt becomes involved in the mechanism at a stage that blocks internal return, converting the carbenium ion to a more reactive form. This increases the rate of product formation more than an increase in the dielectric constant of the medium due to the polarity of the salt. 

The repeating unit isomerization of poly(chloromethylthiirane) occurs in bulk and in non-nucleophilic solvents such as chloroform, dichloromethane and nitrobenzene. Regardless of the medium, the rearrangement appears to stop after isomerization of about 60% of... 

One of the most comprehensive studies has been carried out by Bruice et al. [19] who studied the rate of solvolysis of neutral, positively and negatively charged esters when incorporated into non-functional and functional micelles of neutral, positive and negative charges. The second-order rate constants for alkaline hydrolysis, /cqh [0H ] were found to decrease with increasing concentration of surfactant for all cases studied. The association of the esters with non-nucleophilic micelles must either decrease the availability of the esters to OH attack or provide a less favourable medium for the hydrolysis reaction to occur. This is another circumvention of the simple electrostatic rules as the kinetic effect seems to have nothing to do with the concentration or restriction of access of the hydroxyl ions in the Stern layer of the micelles. Presumably the labile ester bond is not positioned near the surface of these micelles, but the molecules are oriented as shown in Fig. 11.2. 

When non-nucleophilic salts, for example, L1C104, are included in the reaction medium, products indicative of a more reactive intermediate with carbocationic character are observed ... 

In a non-coordinating medium like THF, die intramolecular coordination between the sulfonyl oxygen atom of the imine 5 and the positively charged iodine (III) of the ylide 2 should be possible. This would lead to more tightened transition states during the nucleophilic addition step that could be represented as 15 and 16. Undoubtely 15 is considerably less crowded than 16 and hence should be preferentially formed, finally leading to ds-aziridines 6 as major reaction products (Scheme 31.8). 

It is easy to understand the lower reactivity of non-ionic nucleophiles in micelles as compared with water. Micelles have a lower polarity than water and reactions of non-ionic nucleophiles are typically inhibited by solvents of low polarity. Thus, micelles behave as a submicroscopic solvent which has less ability than water, or a polar organic solvent, to interact with a polar transition state. Micellar medium effects on reaction rate, like kinetic solvent effects, depend on differences in free energy between initial and transition states, and a favorable distribution of reactants from water into a micellar pseudophase means that reactants have a lower free energy in micelles than in water. This factor, of itself, will inhibit reaction, but it may be offset by favorable interactions with the transition state and, for bimolecular reactions, by the concentration of reactants into the small volume of the micellar pseudophase. 

An important feature of K-region arene oxides, which is not shared by the unsubstituted non-K-region oxides, is their susceptibility to nucleophilic attack and production of dihydrodiols. When there are electron-withdrawing substituents on the non-K-region arene oxides, their behavior is also similar to that of the K-region arene oxides. Later work has shown that in the study of 1 reported above, the chloride ions used in the medium were taking part, and... 

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