Diprotonated intermediates

Prakash, Olah, and co-workers256 have prepared Mosher s acid analogs by the hydroxyalkylation of substituted benzenes with ethyl trifluoropyruvate [Eq. (5.95)]. Deactivated aromatics (fluorobenzene, chlorobenzene) required the use of excess triflic acid indicative of superelectrophilic activation.3 5 In contrast to these observations, Shudo and co-workers257 reported the formation gem-diphenyl-substituted ketones in the alkylation of benzene with 1,2-dicarbonyl compounds [Eq. (5.96)]. In weak acidic medium (6% trifluoroacetic acid-94% triflic acid), practically no reaction takes place. With increasing acidity the reaction accelerates and complete conversion is achieved in pure triflic acid, indicating the involvement of diprotonated intermediates. 

By studying stable ion chemistry of polycyclic aromatic systems, Laali et al.862 observed the ring closure of dicyanometacyclophanediene 254 with the involvement of diprotonated intermediate 255 [Eq. (5.318)]. When product 256 was treated again in superacids under different conditions, rearrangement took place to yield 1-cyanopyr-ene through mono- and diprotonated intermediates [Eq. (5.319)]. 

In addition to the above kinetics studies, the fluorene cyclization was studied using ab initio computational methods.323 It was found that the theoretically predicted barriers to the cyclizations for the dicationic intermediates agree well with the values obtained from the kinetic experiments. For example, geometry optimization and energy calculations at the B3LYP/6-31 level estimated that the activation energy (Ea) is 14.0 kcal/mol for the 4jt-electron conrotatory electrocyclization reaction involving compound 57 and the diprotonated intermediate (46, eq 13). 

This is indicative of the formation of the diprotonated intermediate 8 and its involvement in the rate-limiting step of the cyclization. 

In superacidic reactions, diprotonated imines form gitonic superelectrophiles.48 As described in Chapter 2, kinetic experiments have shown that diprotonated intermediates are involved in these conversions. Other experiments showed that the reaction provides higher yields in stronger acid systems (eq 32),... 

The different chemistry of the dications 99 and 101 seems to reflect the superelectrophilic nature of the gitonic dication. It has also been shown that simple peptides may be multiply protonated in acids like FSOsH-SbFs, generally being protonated at the terminal amino group, the carboxyl group, and at the peptide bonds. In a study of the chemistiy of /V-tosylated phenylalanine derivatives, the diprotonated intermediate (103) was proposed in a reaction with superacid CF3SO3H (eq 33).42... 

In the mechanism proposed to explain the formation of /l,y difluoro amines and a-fluoro ketones, two main, competing pathways are possible, after protonation of the 2//-azirine 1. One pathway leads to the / ,/ -difluoro amine 7 via the intermediates 2 and 6. A second possibility, via 2, 3 and 4, gives the observed a-fluoro ketone 5. Pyrazines are formed by the intermoleciilar reaction of the intermediates corresponding to 3, lo give diprotonated intermediates, e.g. 8. 

When aromatic pinacols are reacted with an acid, products often arise from dehydration and rearrangement.5 This general conversion is known as the pinacol rearrangement. The pinacol rearrangement may be promoted by both Brdnsted and Lewis acids.6 In the procedure described here, superacidic triflic acid is reacted with an aryl pinacol and a dehydrative cyclization occurs to give the substituted phenanthrene product. Related to this conversion, the chemistry of benzopinacol in sulfuric acid and triflic acid is contrasted in Scheme 1. We have proposed that the superacidic triflic acid causes the formation of diprotonated intermediates which promote the dehydrative cyclization.4... 

The acidity dependence of this reaction suggests that it passes through the diprotonated intermediate shown. B3LYP/6-31G and MP2/6-31G calculations find the to be considerably smaller for the dication than for the corresponding monocation. 

Nikitenko et al. (1984a, b, 1985) also observe the same mechanistic pathways for lanthanide EDTA and DTPA complexes. Nikitenko et al. (1984a) observe that the Nd(DTPA) -Yb exchange mechanism changes as a function of pH. At pH 4-4.5 the reaction proceeds via a dissociative mechanism with a diprotonated intermediate (RHjL ) at pH 4.5-5, via a monoprotonated intermediate (RHL) and at pH 5-6, via an associative mechanism and a dinuclear intermediate. At pH > 5, the dissociation rate is independent of pH. In Nikitenko et al. (1984b) the authors conclude that both of the exchanging metal ions (Nd(EDTA) -H Er " ", Gd ", Eu ", Pr + ) are coordinated in the intermediate. 

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