Nature of the leaving group

TABLE 14. Decreasing facility order for cleavage of the leaving group 

0 R R means that the R groups is cleaved more easily than the R group, but in a competitive way. 

Activity refers to maximal TIC value at stated dose, where applicable. 

For the glutarate ligand, a crystal structure of [Pt(NH3)2(glutarate)] shows a bridging structure rather than an eight-membered chelate ring 

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We will discuss shortly the most important structure-reactivity features of the E2, El, and Elcb mechanisms. The variable transition state theoiy allows discussion of reactions proceeding through transition states of intermediate character in terms of the limiting mechanistic types. The most important structural features to be considered in such a discussion are (1) the nature of the leaving group, (2) the nature of the base, (3) electronic and steric effects of substituents in the reactant molecule, and (4) solvent effects. 

For E2 eliminations in 2-phenylethyl systems with several different leaving groups, both the primary isotope effect and Hammett p values for the reactions are known. Deduce from these data the relationship between the location on the E2 transition state spectrum and the nature of the leaving group i.e., deduce which system has the most El-like transition state and which has the most Elcb-like. Explain your reasoning. 

However, eclipsing effects are not the only factors that affect the cis/trans ratio in anti E2 eliminations. Other factors are the nature of the leaving group, the base, the solvent, and the substrate. Not all these effects are completely understood. ... 

The functionalized phenaceturates 16 (Fig. 11.10) are substrates of class A and C [3-lactamases, especially the class C enzymes, as observed with the parent unfunctionalized phenaceturates 15. They are also modest inhibitors of these enzymes and the serine DD-peptidase of Streptomyces R61. The inhibition of class C [3-lactamases is turnover dependent, as expected for a mechanism-based inhibitor. Inhibition is not very dependent on the nature of the leaving group, suggesting that the QM is generated in solution after the product phenol has been released from the active site. It therefore... 

In inert systems such as technetium and rhenium, ligand substitution reactions-including solvolysis-proceed under virtually irreversible conditions. Thus, the nature of the reaction center, the nature of the leaving group, and the nature and position of the other ligands in the complex affect the rates and activation parameters in a complicated manner. Most substitution reactions take place via interchange mechanisms. This is not too surprising when the solvent is water - or water-like - and where, in order to compete with the solvent,... 

Y = NMe3) stated that alkene will predominate which has least alkyl substituents on the double bond carbons , i.e. (37) above (b) Saytzev (1875 working on RBr compounds, i.e. Y = Br) stated that alkene will predominate which has most alkyl substituents on the double bond carbons , i.e. (38) above. Both generalisations are valid as the figures quoted above indicate. It is thus clear that the composition of the alkene mixture obtained on elimination is influenced by Y, the nature of the leaving group, and an explanation is required about how this influence may be exerted. 

E The Nature of the Leaving Group 1. Good Leaving Group ... 

Potassium acetate, for example, can be readily alkylated by the use of an equivalent amount of an alkylating reagent (for example, an alkyl halide) in the presence of the phase-transfer catalyst Aliquat 336 (10 mol%) (Scheme 4.7) [16]. Yields are always near quantitative within a few minutes of microwave irradiation, irrespective of the chain length and the nature of the leaving group. This procedure has been scaled-up from 50 mmol to 2 mol scale in a large batch reactor [17]. 

There is a considerable difference in rate of substitution depending on the nature of the leaving group. For the reaction... 

The bis(jS-diketonato) Ti(IV) complex [Ti(bzac)2(OEt)2] 35 (budoti-tane, shown as the predominant cis,cis,cis isomer) entered phase I clinical trials in Germany in 1986 for the treatment of colon cancer (186). The complex is very susceptible to aquation, and to minimize this, the coprecipitate (Cremophor EL, 1,2-propylene glycol in ethanol and 35) is dissolved in water prior to administration. As for titano-cene dichloride, liver damage is the dose-limiting side-effect (187). The activity of this class of complexes shows little dependence on the nature of the leaving group (e.g., OEt, Cl), but aromatic substituents... 

By saturating the co-ordination sites of the cation with a crown ether, the relative contribution of the syn-pathway decreases, as was shown by Zavada et ai (1972) for t-BuOK-promoted eliminations from 5-decyl tosylate. Furthermore, trans/cis ratios in both anti- and syn-eliminations were affected by the presence of dicyclohexyl- 18-crown-6 and the nature of the leaving group (Zavada et ai, 1976). Fiandanese et ai (1973) observed that elimination from fluorosulphonylethanes [177] promoted by potassium phenoxide in dioxan... 

When a bond is broken the nature of the leaving group is important in determining the energy of activation. The basicity of the group is related to its nucleophilicity and if the basic nature of the leaving group is diminished so also will be the tendency to re-form the broken bond ... 

Some cephalosporins can be both substrates and inhibitors of /3-lactamases. The acyl-enzyme intermediate can undergo either rapid deacylation (Fig. 5.4, Pathway a) or elimination of the leaving group at the 3 -position to yield a second acyl-enzyme derivative (Fig. 5.4, Pathway b), which hydrolyzes very slowly [35][53], Thus, cephalosporins inactivate /3-lactamases by a mechanism similar to that described above for class-II inhibitors. It has been hypothesized that differences in the rate of deacylation of the acyl-enzyme intermediates derive from their different abilities to form H-bonds. A H-bond to NH in Fig. 5.4, Pathway a, may be necessary to assure a catalytically essential conformation of the enzyme, whereas the presence of a H-bond acceptor in Fig. 5.4, Pathway b, may drive the enzyme to an unproductive conformation. The ratio between hydrolysis and elimination, and, consequently, the relative importance of substrate and inhibitor behaviors of cephalosporins, is determined by the nature of the leaving group at C(3 ). An appropriate substitution at C(3 ) of cephalosporins may, therefore, increase the /3-lactamase inhibitory properties and yield potentially better antibiotics [53]. 

Important remarks are that starting from mixtures of ElZ enol derivatives, only the (Z)-vinylic tellurides are obtained, and comparative experiments demonstrate that alkyl tellurolates ( -,. t- and f-BuLi) react faster than the aromatic (PhMgBr, 2-ThLi), and that the reaction time is not influenced by the nature of the leaving group (phosphate, acetate, tosylate and triflate). 

A similar approach using a nitro derivative as precursor of the amino alcohol was developed to synthesize [4- F]- and [6- F]fluorometaraminols.Here again, the radiochemical yields of the radiofluorination appear strongly dependent on the position and the nature of the leaving group (Scheme 31)[167j. 

Since this reaction, an overall substitution, depends upon the presence of a suitable leaving group in the substrate, it is not surprising to find that the level of reactivity depends very much upon the nature of the leaving group. We have already... 

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