Base-Assisted Removal

The hydroxide ion can modify the reactivity of a system in acid medium. This has been known for a long time and an example is used in Section 1.1. The ability of hydroxide to modify a reactant is probably most important in the base-assisted hydrolysis of metal ammine and amine complexes. The overwhelming bulk of these studies have been with Co(III), for example, 

Co(NH3)5X2+ -I- oh- Co(NH3)50H2+ + X-and these will be considered first. The kinetics are usually second-order, V = AtohICo ] [OH-] 

Unimolecular solvolysis of this conjugate base in steps (4.45) and (4.46) produces an aqua amide complex that rapidly converts to the final product (4.47)  

This mechanism termed (formerly S ICB) was developed by Basolo and Pearson and their groups in the 1950 s in the face of a good deal of healthy opposition from Ingold, Nyholm, Tobe and their co-workers who favored a straightforward A (82 2) attack by OH ion on the complex. For a mechanism, in general, 

In the unlikely event that k2 k, Atqh = mAt, and the act of deprotonation becomes rate limiting, affording powerful evidence for the necessity of (4.44) in the base reaction. Changes of rds with conditions show up in changing values of Ai/ (but surprisingly not AV ) with temperature (Sec. 2.6). 

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Waldmann et al. developed a second exo-linker following a new approach [43-44] which makes use of a safety-catch linker. It is based on the enzymatic cleavage of a functional group embodied in the linker. In this way an intermediate is generated, which subsequently cyclizes intramolecularly according to the principle of assisted removal [54—58] and thereby releases the desired target compounds (Scheme 10.11). 

This level of ionization is particularly relevant in some enzymic reactions where histidine residues play an important role (see Section 13.4.1). This means that the imidazole ring of a histidine residue can act as a base, assisting in the removal of protons, or, alternatively, that the imidazolium cation can act as an acid, donating protons as required. The terminology used for such donors and acceptors of protons is general acid catalyst and general base catalyst respectively. 

In some of the mechanisms shown in the answers, a series of protonations and deprotonations occur. These steps convert the initial tetrahedral intermediate into an intermediate that more easily loses a leaving group. These deprotonations may be brought about by the solvent, by the conjugate base of the catalyst, by other molecules of the carbonyl compound or may occur intramolecularly. When a "proton transfer" is shown as part of a mechanism, the base that removes the proton has often not been shown. However, it is implied that the proton transfer is assisted by a base the proton doesn t fly off the intermediate unassisted. 

The model studies imply mechanistic paths in the enzyme that would accommodate much of the rate enhancement and are consistent with the observations above. These are displayed in Scheme 14. The phosphate ester binds to both Zn ions, which activates the P center to attack by the coordinated deprotonated serine nucleophile. Binding the serine hydroxyl to the metal ion enhances its deprotonation and gives an efficient intramolecular nucleophile, as we have seen from model studies. Such a process would also be assisted by an enzyme base to remove the proton intramolecularly and protonation of the alkoxide leaving group by an enzyme acid would be helpful. In addition, inversion of configuration would ensue at the P center. A coordinated water at the second Zn + ion could then be deprotonated to function as the intramolecular nucleophile which eliminates the serine alkoxide ion. Both aspects would be assisted by an enzyme base and acid, respectively. The stereochemistry of the processes would lead to inversion and therefore to net retention overall consistent with the expectation from the experiments by Jones et al. (89). 

Electrophilic aromatic substitution is an important reaction that allows the introduction of many different functional groups onto an aromatic ring. A general form of the reaction is given by Equation 15.1, where Ar-H is an aromatic compound, an arene, and represents an electrophile that replaces an H on the ring. This equation is oversimplified because the electrophile is usually generated during the reaction, and a Lewis base assists in the removal of... 

Nickel catalysts promoted the addition of nitrogen nucleophiles to internal alkynes [138] TMS-protected alkynes are excellent snbstrates for the base-assisted anti-Markovnikov selective hydroamination reaction [143]. No need to remove the protecting group prior to the hydroelementation reaction Tetrahydropyridines have been generated through the treatment of dihydropyrans with aniline precursors [149]... 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

Porosity constitutes a important criterion in a description based on straining. Porosity is determined by the formula V /Vc, in which V c is the total or apparent volume limitated by the filter wall and is the free volume between the particles. The porosity of a filter layer changes as a function of the operation time of the filters. The grains become thicker because of the adherence of material removed from the water, whether by straining or by some other fixative mechanism of particles on the filtering sand. Simultaneously the interstices between the grains diminish in size. This effect assists the filtration process, in particular for slow sand filters, where a deposit is formed as a skin or layer of slime that has settled on the... 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

It is clear from the results that there is no kinetic isotope effect when deuterium is substituted for hydrogen in various positions in hydrazobenzene and 1,1 -hydrazonaphthalene. This means that the final removal of hydrogen ions from the aromatic rings (which is assisted either by the solvent or anionic base) in a positively charged intermediate or in a concerted process, is not rate-determining (cf. most electrophilic aromatic substitution reactions47). The product distribution... 

Specific base catalysis is predicted if the extent of substrate ionization is reduced from almost complete. Depends on whether an ion pair assists in removal of leaving group. 

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