Rate acceleration, electrophilic

Electron-donor substituents are known to accelerate the rate of electrophilic substitution on benzene, while electron-withdrawing groups are known to retard the reaction. One explanation is that electron donors stabilize the positive charge in the benzenium ion intermediate while electron-withdrawing substituents destabilize the positive charge. 

These equations show the general theoretical basis for the empirical order of rate constants given earlier for electrophilic attack on an aromatic ligand L, its metal complex ML, and its protonated form HL, one finds kt > n > hl. Conflicting reports in the literature state that coordination can both accelerate electrophilic aromatic substitution (30) and slow it down enormously (2). In the first case the rates of nitration of the diprotonated form of 0-phenanthroline and its Co(III) and Fe(III) complexes were compared. Here coordination prevents protonation in the mixed acid medium used for nitration and kML > h2l. In the second case the phenolate form of 8-hydroxyquinoline-5-sulfonic acid and its metal chelates were compared. The complexes underwent iodination much more slowly, if at all, and kL > kML ... 

The foregoing results indicate that a powerful anchimeric rate-accelerating effect (38) must operate in the transition state of the electrophilic substitutions of II which exceeds the electron-with drawing effect of the immonium form D in the mono-positive cation II ... 

The Hammett cr+ constant for the 4(5)-position of imidazole is around -1 for C-2 it is of the order -0.8 (86CHE587). The electrophilic substitutions which do occur at the 2-position invariably involve preformation of an anion at that position. The 2-proton, which should be the least active in a conventional SEAr sense, turns out to be the most labile over a wide pH range, and there is a marked rate acceleration on going from imidazole to imidazolium cation. Any negative charge generated at C-2 is stabilized by the adjacent pyrrole-type nitrogen (see Section 3.4.1.8.2). 

Oxidation of alkyl phenyl sulfides by pyridinium bromochromate (PBC) is accelerated by electron-donating alkyl groups or aryl substituents, indicating an electron-deficient sulfur centre in the transition state this is accounted for in terms of rate-determining electrophilic oxygen attack from PBC to the sulfide in an. S -like process.7... 

Menger et al. synthesized a Ci4H29-attached copper(II) complex 3 that possessed a remarkable catalytic activity in the hydrolysis of diphenyl 4-nitrophenyl phosphate (DNP) and the nerve gas Soman (see Scheme 2) [21], When 3 was used in great excess (ca. 1.5 mM, which is more than the critical micelle concentration of 0.18 mM), the hydrolysis of DNP (0.04 mM) was more than 200 times faster than with an equivalent concentration of the nonmicellar homo-logue, the Cu2+-tetramethylethylenediamine complex 9, at 25°C and pH 6 (Scheme 4). The DNP half-life is calculated to be 17 sec with excess 1.5 mM 3 at 25°C and pH 6. The possible reasons for the rate acceleration with 3 were the enhanced electrophilicity of the micellized copper(II) ion or the acidity of the Cu2+-bound water and an intramolecular type of reaction due to the micellar formation. On the basis of the pH(6-8.3)-insensitive rates, Cu2+-OH species 3b (generated with pK3 < 6) was postulated to be an active catalytic species. In this study, the stability constants for 3 and 9 and the thermodynamic pvalue of the Cu2+-bound water for 3a —> 3b + H+ were not measured, probably because of complexity and/or instability of the metal compounds. Therefore, the question remains as to whether or not 3b is the only active species in the reaction solution. Despite the lack of a detailed reaction mechanism, 3 seems to be the best detoxifying reagent documented in the literature. 

Now, some addition reactions will be considered, the solvent dependences of which have been reviewed [77, 78]. Addition of uncharged electrophiles [e.g. Br2, ArS—Cl, NO—Cl, R—CO3H) to carbon-carbon multiple bonds leads to the development of a small, usually dispersed charge in the activated complex. In more polar solvents, this is accompanied by a slight rate acceleration. In reactions with substantial charge development in the activated complex, larger rate accelerations with increasing solvent polarity are observed. 

The rate acceleration and the TT-face selectivity were explained in terms of the coordination of the Lewis acid to the acyl oxygen atom. The binding Lewis acid moiety interacts with the cis- 8-substituent, which forces the olefinic bond to adopt the conformation XXII, approximately orthogonal to the acyl group. The olefinic bond is thus rendered more nucleophilic, accounting for the rapid reaction, and the electrophile E preferentially approaches the face not shielded by the iron auxiliary (Sch. 25). 

Since both BF3 or SbFs form adducts with SO2, the rate acceleration [20,000 times for W(tj -CsH5)(Me)(CO)3] can be explained by an increase of the electrophilic character of sulfur in the presence of the Lewis acid. Insertion of the chalcogen dioxides EO2 has been reported with the tropylium derivative of molybdenum(O) Mo(>7 -C7H7)(R)(C0)2 ... 

The modulation of the coordination to the transition metal has not necessarily positive implications on the reactivity. For instance, we observed [50] that the copper(II) complex (8) of tetramethyl-l,2-diaminoethane catalyzes the hydrolysis of the phosphoric acid triester PNPDPP via an electrophilic mechanism which involves the pseudointramolecular attack of deprotonated water, as illustrated in (9). The electrophilic mechanism contribution to the hydrolytic process totally disappears in micellar aggregates made of the amphiphilic complex (10). Clearly, micellization does not allow the P O group of the substrate to interact with the metal ion. This could be a result of steric constraint of the substrate when bound to the micelle and/or the formation of binuclear dihydroxy complexes, like (11), in the aggregate. So, in spite of the quite large rate accelerations observed [51] in the cleavage of PNPDPP in metallomicelles made of the amphiphilic complex (10), the second-order rate constant [allowing for the difference in pXa of the H2O molecules bound to copper(II) in micelles and monomers] is higher for (8) than for (10) (k > 250). 

The same type of rate-acceleration effect by the a-fluorine substituent is known in electrophilic substitution on the aromatic ring. Fluorine accelerates bromination, while chlorine... 

The putative general base catalyst, Glu-43, and electrophilic catalysts, Arg-35 and Arg-87, have been specifically mutated to Asp (9/, 92) and Lys (93) residues, respectively, in the author s laboratory to assess the roles of these amino acid residues in catalysis. Other amino acids were also introduced at these positions, but the present discussion will briefly outline the results obtained with the conservative substitutions. As mentioned previously, the rate acceleration characteristic of the SNase-catalyzed hydrolysis of DNA is approximately 10. The Asp substitution for Glu-43 (E43D) decreased the catalytic efficiency approximately 10, and the Lys substitutions for Arg-35 (R35K) and Arg-87 (R87K) decreased the catalytic efficiency approximately 10 and 10, respectively. While such decreases in catalytic efficiency have been used to describe quantitatively the roles of various active site residues in catalysis, such interpretation is clearly unwarranted in the case of these active site mutants of SNase. The melting temperatures of all three of these mutant enzymes differ significantly... 

Later, during their studies on rate acceleration of MBH reactions in polar solvents, Aggarwal et al found that the use of 5 equiv of form amide gave faster rates than reactions conducted in water. An additional acceleration was achieved in the presence of Yb(OTf)3 (5mol.%) and formamide. The MBH reaction of various Michael acceptors with benzaldehyde and a range of electrophiles with ethyl acrylate were investigated under the new conditions (Scheme 2.222). 

It may be risky to raise mechanistic conclusions on quatitative observations regarding rate accelerations upon changes on any reaction variable in complex catalytic processes such as cross-coupHng reactions. Nevertheless, some interesting hints can be obtained from work aimed at developing new conditions for the coupHng of the less reactive organic substrates such as aryl chlorides [99,100] and alkyl electrophiles [101]. 

The first example of dihalocarbene insertion into a saturated C—H bond of an organometallic complex has been reported using a phase-transfer catalyst The first example of phase-transfer catalysts for electrophilic substitution involved an azo-coupling reaction in water-dichloromethane using sodium 4-dodecylbenzene-sulphonate giving a rate acceleration of ca. 200-fold. ... 

Alternatively, the rate acceleration found for allyl and benzyl groups in Sn2 reactions can be viewed as an inductive effect. The electron withdrawing nature of the sp hybridized carbons of a vinyl or phenyl group makes the carbon more electrophilic, and therefore more reactive toward nucleophilic attack. Both effects are likely involved. 

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