Nucleophile mechanism

Not all the reactions in this chapter are actually nucleophilic substitutions. In some cases the mechanisms are not known with enough certainty even to decide whether a nucleophile, an electrophile, or a free radical is attacking. In other cases (such as 10-79), conversion of one compound to another can occur by two or even all three of these possibilities, depending on the reagent and the reaction conditions. However, one or more of the nucleophilic mechanisms previously discussed do hold for the overwhelming majority of the reactions in this chapter. For the alkylations, the Sn2 is by far the most common mechanism, as long as R is primary or secondary alkyl. For the acylations, the tetrahedral mechanism is the most common. 

The oxidation of aldehydes to carboxylic acids can proceed by a nucleophilic mechanism, but more often it does not. The reaction is considered in Chapter 14 (14-6). Basic cleavage of (3-keto esters and the haloform reaction could be considered at this point, but they are also electrophilic substitutions and are treated in Chapter 12 (12-41 and 12-42). 

However, if we consider the alternative nucleophilic displacement, it is known that nucleophilic processes are accelerated by ionic liquids, but more pertinent is the fact that the Sn2 displacement of iodide from alkyl iodide (Mel) by Rh(CO)2l2 is slightly accelerated by ionic liquids (7). Unfortunately, ionic liquids would also be expected to accelerate the nucleophilic displacement of iodide from ethyl iodide by propionic acid to form ethyl propionate (Reaction 8). In fact, as an Sn2 Type II displacement (the interaction of two neutral species), the ester formation from propionic acid and ethyl iodide would be expected to be significantly increased compared to the reaction of Rh(CO)2l2 with EtI. Therefore, by operating in iodide containing ionic liquids, we had set up a situation in which we suppressed the normally predominant hydride mechanism, slightly accelerated the alternative nucleophilic mechanism, but dramatically increased the ethyl propionate by-product forming pathway. 

Noting that the reaction of cycloheptaamylose with diphenyl pyrophosphate produces equal amounts of phenol, monophenyl phosphate, and phosphorylated cycloheptaamylose, Hennrich and Cramer (1965) proposed a nucleophilic mechanism (Scheme IV). According to this mechanism, a rapid, reversible association of the pyrophosphate with cycloheptaamylose... 

Although kinetic evidence for prior equilibrium inclusion was not obtained, competitive inhibition by cyclohexanol and apparent substrate specificity once again provide strong support for this mechanism. Since the rate of the catalytic reaction is strictly proportional to the concentration of the ionized hydroxamate function (kinetic and spectrophotometric p/Cas are identical within experimental error and are equal to 8.5), the reaction probably proceeds by a nucleophilic mechanism to produce an acyl intermediate. Although acyl derivatives of N-alkylhydroxamic acids are exceptionally labile in aqueous solution, deacylation is nevertheless the ratedetermining step of the overall hydrolysis (Gruhn and Bender, 1969). 

A polar nucleophilic mechanism has also been advanced (86) (Fig. 4.34C). The mechanism is characterized by a nucleophilic attack of the amine on the 4a position of FAD to form the amine adduct followed by base-catalyzed elimination to the imine and FADH2. 

By way of example, compare the transition state [16] for a typical general base catalysed reaction (E.1.6) with that for the corresponding reaction involving a nucleophilic mechanism [17] (A.2.35). We have already seen that the EM s for these mechanisms are 13 M and 2.6 x 107 M, respectively. In the... 

Evidence for the ST+-nucleophile mechanism under thermal conditions 105... 

Evidence for the ST -nucleophile mechanism under thermal conditions... 

In other systems, similar kinetic laws were observed when studying the effect of added pyridine, although differentiation with the dimer nucleophile mechanism is made in the interpretation of the experimental results (see below). Rationalizations of the involved phenomena are based on the strong hydrogen-bond interactions between the nucleophile and the pyridine, and on the catalytic effect of a third amine molecule in the decomposition of the zwitterionic intermediate in non-polar solvents. 

The reaction is acid-catalyzed and yields isocyclosporin A (iso-CsA, 6.58, Fig. 6.23) as the major product. At 50°, the kinetics of the first-order reaction were k=l x 10 6 s 1 (tV2 ca. 1.1 d) at pH 1, and k= 1. 7 x 10 8 s 1 (tv2 ca. 1.2 y) at pH 4. Iso-CsA (i.e., the O-peptide) had a much greater chemical stability than CsA (i.e., the A-peptide) under acidic conditions, in contrast to other findings where the opposite was true. Interestingly, O-acclyl-CsA did not yield iso-CsA and exhibited a much greater stability than CsA, consistent with the nucleophilic mechanism mentioned above. 

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