Hammett analysis

Hammett analysis and finding of corresponding LFERs (see Chapter 9, Section 9.2.3) suggests that the mechanism of an enzyme reaction in organic solvents is the same as in aqueous solution (Kanerva, 1989). 

A variety of spectroscopic evidence, notably UV-Vis spectroscopy, has been used to determine the tautomeric equilibria in substituted 2-hydroxypyridines <2002ARK198>. Electron-donating substituents favor the hydroxy-pyridine form, while electron-withdrawing substituents favor the pyridone form Hammett analysis of the substituent effects gives a p value of -4. The effect of solvent in this case is not as marked, with polarity being of greater significance than proticity. 

A recent DFT study has shown that retention of configuration observed for the above reactions is in agreement with the insertion of singlet nitrene and a concerted product formation [150 is the transition state for the reaction shown in Equation (6.135)]. Du Bois and coworkers have performed detailed mechanistic investigations of the intramolecular sulfamate ester C-H amination reaction catalyzed by a dirhodium complex. Reactivity patterns, Hammett analysis, and kinetic isotope effect studies have provided support for the concerted, asynchronous transition structure 151. A similar conclusion was arrived at for an analogous intermolecular process. ... 

Because of the extraordinary strength of the carbon-fluorine bond, transition metal-mediated activation of fluoroalkanes and arenes is not easy to achieve. Nevertheless, activation of the C-F bond in highly electron-deficient compounds such as 2,4,6-trifluoropyrimidine, pentafluoropyridine, or hexafluorobenzene is possible with stoichiometric amounts of bis(triethylphosphano) nickel(O) [101] (Scheme 2.45). More recently Herrmann and coworkers [102] have described a variant of the Kumada-Corriu cross-coupling reaction [103] between fluorobenzene and aryl Grignard compounds which uses catalytic amounts of nickel carbene complexes. Hammett analysis of the relative kinetic rate constants indicated that the reaction proceeds via initial oxidative addition of the fluoroaromatic reactant to the nickel(O) species. 

Linear k,, vs dye concentration plots, equivalent to Figure 2, and hence k2 values were also obtained for the seven derivatives of Acid Orange 12 with substituents on the meta or para position of the phenyl ring (Table 1). A Hammett analysis of the rate data reveals a good correlation of the log kj values against with a p value of -1.66 (R = 0.981) (Figure 4), whereas... 

Dirhodium tetracarboxylate complexes are among the most successful and well-studied catalysts for C-H amination. Early work by Miiller provided support for a concerted asynchronous reaction mechanism for intermolecular amination reactions using Rh2(OAc)4 and NsN=IPh [22-24]. Du Bois and coworkers have shown that carbamate and sulfamate esters can engage in oxidative cyclization reactions promoted by these same types of Rh complexes using PhI(OAc)2 as the terminal oxidant [93-96]. Mechanistic studies, which include Hammett analysis (p = 0.55... 

In the case of the C sp )-0 elimination reaction shown in Fig. 7, it was established that a dissociation of the carboxylate ligand trans- to the aryl from the starting Pd complexes 13 does occur at temperatures much lower than those required for the C-O reductive elimination reaction. This observation suggests that the reaction might proceed via a cationic intermediate 6 and follow a reaction path shown in Fig. 11 with a solid line. If so, the transition state TSd which corresponds to the carboxylate dissociation is of a noticeably lower energy compared to the TSc corresponding to the R-Z elimination step. A Hammett analysis of the kinetics of the reaction in Fig. 7 showed that increased nucleophilicity of the benzoate /5-XC6H4COO in complexes 13 leads to a faster kinetics (p-OMe > p-Me > H > p-OPh > p-F > p-Cl > p-Ac > P-CF3 > p-CN > P-NO2), a trend opposite to that observed for trimethyl Pt complexes 8 involved in an S iv2-type reaction shown in Fig. 5. As the electronic requirements to the nucleophilicity of Z for the... 

Kallenberg A, van Rantwijk F, Sheldon R (2005) Immobilization of penicillin G acylase the key to optimum performance. Adv Synth Catal 347 905-926 Kamat S, Beckman E, Russell, A (1995) Enzyme activity in fluids. Critic Rev Biotechnol 15 41-71 Kanerva LT, Klibanov AM (1989) Hammett analysis of enzyme action in organic solvents. J Amer Chem Soc 111 6864-6865... 

The small chromogenic substrates used in this study are only cleaved at the heterosidic bond with release of the aryl aglycon. In a double-displacement mechanism, deglycosylation will be the same for all lactoside substrates, while glycosylation will be influenced by the substituents on the phenol group. The effect of these substituents on the rate constants can be evaluated by means of a Hammett analysis (See e.g. (20, 21, 34, 35) for application in glycosidase research). The reaction constant (the slope in a log kcat or a log versus... 

Eckert and coworkers have used a Hammett analysis to identify that the hydrolysis of benzoate esters in HTW occurs via acid and not base eatalysis (Scheme 3.3). The Hammett equation (eqn (3.12)) quantifies how substituents on a substrate bearing an X-substituted benzene ring alter tbe rate constant of a reaction k lk in comparison to the referenee aeid dissoei-ation of benzoic acid defined by ctx-... 

This system, however, is much more complex than the simple description in Figure 5.45 suggests. The proper analysis of such systems has to involve the Curtin-Hammett analysis of interconversion of reactive and unreactive conformers and the evolution of stereoelectronic effects along the interconnected reaction pathways. The critical examination of APL theory by Perrin also suggested that the role of conformational equilibria of reactive species, the involvement of syn-periplanar lone pairs, and the different stability of products should be included in the analysis. We will continue our discussion of cooperativity and anti-cooperativity between stereoelectronic effects in Chapter 11. 

Recall that p, the parameter that characterizes a particular reaction in a Hammett analysis, is the slope obtained from the plot of x/ h vs. a. The plot must give a straight line to get a p value. What does it mean if a Hammett plot is not linear ... 

Hammett analysis of the latter reaction shows that —M substituents at G(4> in pyridine influence the nitrogen atom only by their inductive effects. 

In their seminal paper on the rhodium(ll)-catalyzed C—H insertion with PhI=NNs, the group of Muller reached the conclusion that the reaction proceeds through the concerted asynchronous insertion of a rhodium-bound nitrene species.This hypothesis was supported by a Hammett analysis (/9= —0.90 vs. tr+), the absence of ring-opened products in reactions involving cyclopropyl radical clocks, and the stereospecific C(sp )—H ami-nation of (Ji)-2-phenylbutane that occurs with complete retention of configuration. However, the very low yields obtained for these test reactions as well as the kinetic isotope effect measured for the reaction from (1,3-D2)-adamantane (KIE = 3.5 0.2) put this conclusion into question as these did not rule out the possible involvement of radicals that could undergo fast recombination. Nevertheless, this initial study already highlighted the discrepancies that could be observed between the carbene and nitrene chemistries in terms of mechanism. The electronic structure of nitrenes, contrary... 

The results uncovered by Muller have been corroborated by the subsequent studies from the Du Bois group, particularly with respect to the intramolecular reaction. The stereospecific C(sp )—H insertion of the carbamate-derived nitrene depicted in Scheme 6A was the first relevant reaction in favor of the asynchronous concerted addition.More significantly, the extensive analysis of the rhodium-catalyzed intramolecular C(sp )-H amination of sulfamates has led to the same conclusion. The Hammett analysis (/0= —0.55 vs. and the kinetic isotope effect observed from the monodeuterated phenylpropyl sulfamate 9 (KIE = 2.6 0.2) clearly argue in favor of this mechanistic scenario (Scheme 17). Additionally, the reaction from the cyclopropyl radical clock 12 supports this hypothesis by furnishing a single product isolated with an excellent yield of 91%. 

Parallel investigations of the rhodium-catalyzed intermolecular reaction have shown that, at first glance, its mechanism is identical in aU respects to the intramolecular process. " The Hammett analysis ip = — 0.73 vs. the... 

Figure 5.12 Curtin-Hammett analysis for (kcalmoh 298K) are with respect to sep-the relative energies of the four mechanisms arated substrate and catalyst (PMejAu+) for the [3,3]-rearrangement of vinyloxy- computed at the B3LYP/LANL2DZ-CH2CI2-...

A Hammett Analysis In a Multlstep Reaction Rhodium(ll)-Catalyzed Decomposition of a-Diazo Esters... 

Hammett analysis in multistep reactions is not always a simple task. The rate-determining step is not necessarily the first step of the reaction and in a reaction sequence, substituents that favor a step could favor or disfavor the next one. This situation sometimes complicates evaluation of the influence of electron-withdrawing or electron-donating groups on the overall reaction mechanism. 

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