Activating group explanation

Acifluorfen, synthesis of, 683 Acrolein, structure of, 697 Acrylic acid, pKa of, 756 structure of. 753 Activating group (aromatic substitution), 561 acidity and, 760 explanation of, 564-565 Activation energy, 158 magnitude of, 159 reaction rate and, 158-159 Active site (enzyme), 162-163 citrate synthase and, 1046 hexokinase and, 163... 

Not only are there substrates for which the treatment is poor, but it also fails with very powerful electrophiles this is why it is necessary to postulate the encounter complex mentioned on page 680. For example, relative rates of nitration of p-xylene, 1,2,4-trimethylbenzene, and 1,2,3,5-tetramethylbenzene were 1.0, 3.7, and 6.4, though the extra methyl groups should enhance the rates much more (p-xylene itself reacted 295 times faster than benzene). The explanation is that with powerful electrophiles the reaction rate is so rapid (reaction taking place at virtually every encounter between an electrophile and substrate molecule) that the presence of additional activating groups can no longer increase the rate. ... 

The oxidation of thiols in the form of L-cysteine, penicillamine, and thioglycollic acid by [Mo(CN)g] in aqueous acidic solution also formed disulfides as final products 111). The reactions show a second-order substrate dependence, and the rates are found to decrease with increasing hydrogen ion concentration. This is attributed to the deprotonation of the —SH and —COOH groups in these thiols prior to electron transfer. The reactions are interpreted in terms of outer-sphere activation. An explanation for the second-order dependence on thiol concentration involves ion association between the cyano complex and a protonated form of the thiol, followed by reaction of this complex with a second thiol molecule. 

While the equations look the same at a first glance, some striking differences can be seen on a closer inspection. First, the vertebrate, but not the bacterial DHFR equations contain an electronic parameter in addition to lipophilicity and molar refractivity terms. Second, in the case of L. casei (eq. 137) the 5-position of the benzyl group does not at all contribute to biological activities. An explanation could be derived by a comparison of the 3D structure of L. casei DHFR with the E. coli DHFR structure. The active sites of both enzymes are more or less identical in the geometries of the protein backbone and the amino acid side chains. However, there is one significant difference E. coli DHFR contains a methionine side chain in the area where the 5-substituents bind, while there is a relatively rigid leucine side chain in the L. casei DHFR which obviously interferes with the 5-substituents. Therefore, the active site of L. casei DHFR is sterically more constrained and the positive lipophilicity and polarizability contributions of the 5-substituents are counterbalanced by their steric hindrance [432, 682]. 

The factors that determine the steric course of these cycloaddition reactions are still not completely clear. It appears that a number of forces operate in the transition state and the precise composition of the product depends on the balance among these. The preference for the endo adduct, in which the dienophile substituents are oriented over the residual unsaturation of the diene in the transition state, has been rationalized by Woodward and Hoffmann in terms of secondary orbital interactions. In this explanation, the atomic orbital at C-2 (and/or C-3) in the HOMO of the diene interacts with the atomic orbital of the activating group in the LUMO of the dienophile. However, there is no evidence for this secondary orbital interaction and the stereoselectivities in the Diels-Alder reaction can be explained in terms of steric interactions, solvent effects, hydrogen-bonding, electrostatic and other forces (3.70). ... 

Use resonance theory to explain why the hydroxyl group of phenol is an activating group and an ortho-para director. Illustfate your explanation by showing the arenium ions formed when phenol reacts with a Br ion at the ortho, meta, and para positions. 

Generally only one of them, i.e., the endoAsorntr is realized. With the cyclopentadiene only 1.5% of the xo-isomers are obtained. The explanation for the endo preference given by Alder and Stein is interpreted as follows The diene and dienophile are preoriented in a sandwichlike structure. The transition state forms in such a way as to allow maximum concentration of double bonds. The suggested maximum concentration includes the tt system as well as the activating groups. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

The system aluminum/water belongs to group II where represents the pitting potential and lies between -0.8 and -1.0 V according to the material and the medium [22,23,36,39,42]. Since alkali ions are necessary as opposite ions to the OH ions in alkalization, the resistance increases with a decrease in alkali ion concentration (see Fig. 2-11). In principle, however, active aluminum cannot be protected cathodically [see the explanation of Eq. (2-56)]. 

This study suggests a radically new explanation for the nature of Lewis acid activation in the Simmons-Smith cyclopropanation. The five-centered migration of the halide ion from the chloromethylzinc group to zinc chloride as shown in TS2 and TS4 has never been considered in the discussion of a mechanism for this reaction. It remains to be seen if some experimental support can be found for this unconventional hypothesis. The small energy differences between all these competing transition states demand caution in declaring any concrete conclusions. 

On the other hand, the catalytic effect of water as a base is stronger at the 2-position. This result can be explained if one assumes that the proton is transferred by a water molecule which solvates the O- group in the reagent 3-sulfo-l-naphth-oxide dianion. As can be seen in 12.148, the base is already in the optimum position when the stage of the o-complex is reached. This explanation is supported by a comparison of the entropies of activation for reaction at the 2- and 4-positions. 

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