Point of attack

M.o. theory has had limited success in dealing with electrophilic substitution in the azoles. The performances of 7r-electron densities as indices of reactivity depends very markedly on the assumptions made in calculating them. - Localisation energies have been calculated for pyrazole and pyrazolium, and also an attempt has been made to take into account the electrostatic energy involved in bringing the electrophile up to the point of attack the model predicts correctly the orientation of nitration in pyrazolium. ... 

From the preceding examples it can be seen that oxidants and electrophilic reagents attack pyrroles and furans at positions 2 and 5 in the case of indoles the common point of attack is position 3. Thus autoxidation of indoles e.g. 99) gives 3-hydroperoxy-3H-indoles (e.g. 100). Lead tetraacetate similarly reacts at the 3-position to give a 3-acetoxy-3H-indole. Ozone and other oxidants have been used to cleave the 2,3-bond in indoles (Scheme 30) (81BCJ2369). 

At the present time, the greatest importance of covalent hydration in biology seems to lie in the direction of understanding the action of enzymes. In this connection, the enzyme known as xanthine oxidase has been extensively investigated.This enzyme catalyzes the oxidation of aldehydes to acids, purines to hydroxypurines, and pteridines to hydroxypteridines. The only structural feature which these three substituents have in common is a secondary alcoholic group present in the covalently hydrated forms. Therefore it was logical to conceive of this group as the point of attack by the enzyme. 

A second theoretical index, and one for which there appears to be more justification in its application to free-radical reactions, is the atom localization energy. This index is a measure of the energy required to localize one electron of the 7r-electron system in the aromatic molecule at the point of attack of the radical. The formation of the intermediate adduct in a free-radical aromatic substitution may be regarded as the sum of two processes one, the localization of an electron at the point of attack and the other, the pairing of this... 

As indicated above, the bicarbonate ion inhibits the process, which does not occur, therefore, in many supply waters attack is most likely in waters which by nature or as a result of treatment have a low bicarbonate content and relatively high chloride, sulphate or nitrate content. The number of points of attack increases with the concentration of aggressive anions and ultimately slow general corrosion may occur. During exposure of 99-75% tin to sea-water for 4 years, a corrosion rate of 0-0023 mm/y was observed . Corrosion in soil usually produces slow general corrosion with the production of crusts of oxides and basic salts this has no industrial importance but is occasionally of interest in archaeological work. 

The points of attack are primarily the waterline (where oxygen pitting may also occur), in areas where steam-water velocities are highest, and at points where stresses are inherent. These include ... 

In benzene itself the charge at the point of attack will be not 1.00c, as has been assumed heretofore, but (1.00 + (43/108)5,)c. (Since 5,-is small, the results of the perturbation treatment can be applied directly.) In other molecules the ease of reaction at the ith carbon atom will then be greater than that of benzene if the charge at that point is greater than (1.00 + (43/108)5 )e, and conversely. 

Fig. 6. Points of attack of RGAE on acetyl esters in MHR (upper part) and possible points of attack of PAE on acetyl esters in beet pectin (see text for explanation).

The reaction of a chain radical with a unit of a previously formed polymer represents an additional possible chain transfer process not previously considered in Chapter IV. The point of attack might again be located in the substituent X, or it might involve removal of the tertiary hydrogen on the substituted chain carbon. The following sequence of reactions, in which the latter alternative has arbitrarily been assumed, would then lead to a branched polymer molecule as indicated. ... 

A more general reaction between kojic acid and aldehydes is a trimolecu-lar condensation discovered by Barham and Reed." By a process of elimination, they arrived at the conclusion that C6 of kojic acid was most probably the point of attack two molecules of kojic acid reacted with one molecule of the aldehyde, with the elimination of one molecule of water, giving a product of structure LXXV. Such compounds were prepared from kojic acid and the following aldehydes the normal alkanals from formaldehyde to heptanal, benzaldehyde, cinnamaldehyde, hydrocinnamaldehyde, 2-furaldehyde, and acrolein. The compound derived from kojic acid and benzaldehyde (LXXV, R = phenyl) was also obtained by treating LXXII (R = phenyl) with hot, aqueous sodium carbonate.92... 

Mercury can influence ion, water, and nonelectrolyte transport in different cells [ 14, 77]. The cell membrane is believed to be the first point of attack by heavy metals however, intracellular enzymes and metabolic processes may also be inhibited [70, 78, 79]. The attachment of heavy metals to ligands in or on the plasma membrane may result in changes in passive permeability or selective blockage of specific transport processes. Many membrane transport systems are known to be sensitive to sulphydryl-group modification [ 14, 80, 81]. 

Cyclobutane has not been polymerised cationically (or by any other mechanism). Thermochemistry tells us that the reason is not thermodynamic it is attributable to the fact that the compound does not possess a point of attack for the initiating species, the ring being too big for the formation of a non-classical carbonium ion analogous to the cyclopropyl ion, so that there is no reaction path for initiation. The oxetans in which the oxygen atom provides a basic site for protonation, are readily polymerizable. Methylenecyclobutane polymerises without opening of the cyclobutane ring [72, 73]. 

The l.d. of a typical fluoroacetate varies considerably from species to species moreover, the pharmacodynamic action of the material is very varied. The main point of attack may be the central nervous system or the heart or sometimes both. Death can result from (i) respiratory arrest after convulsions, (ii) cardiac failure or ventricular fibrillation, or (iii) gradual depression... 

Applied to benzene this conception provides for a structure which is much more saturated than that possible in olefines with several double bonds. In benzene the points of attack, which are always present in the open chain, are lacking ... 

The first product of the oxidation of alcohol is acetaldehyde and an important end-product is fulminic add, which latter can, however, only be isolated if silver or mercury ions are present. With these ions it forms salts—fulminates—which are stable towards nitric add in them, it must be presumed, the linkage with the metal is homopolar and non-ionogenic, as in mercuric cyanide. The formation of fulminic acid takes place because the carbonyl group of the aldehyde confers reactivity on the adjacent methyl group which then forms a point of attack for the nitrous acid. The various stages in the process are indicated by the following formulae ... 

Anthracene can be oxidised directly to its wi so-quinone, anthra-quinone, by means of chromic acid. For almost all its reactions the middle ring of anthracene provides the point of attack. 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

At a slightly deeper level, the difficulty of this approach lies in its acceptance of a transition complex in which the original classification into a and tt electrons has been broken consequently pure tt electron theory is inadequate for the prediction of energy changes, and a complete analysis must await the inclusion of the a bond modifications at the point of attack. Preliminary attempts to include such effects have invoked hyper conjugation (Muller et al., 1954 Fukui et al., 1954a) and other factors (Dewar et al., 1956), but little progress has yet been made towards a more detailed theoretical interpretation based on more complete calculations. 

Restriction enzymes hydrolyse DNA at points marked by arrows. Sample A has one more point of attack than sample B. 

Drugs Since virases use much of the machinery of the host cell for proliferation, only enzymes catalysing reactions that are specific to the virus offer points of attack. Antiretroviral drugs inhibit one of two such enzymes ... 

Once the virus makes a polyprotein, it must cut that molecule apart to release all of the individual proteins it needs to continue its replication. The compound it uses to accomplish this task is HIV protease. Proteases are enzymes, a class of compounds that break down other proteins. Researchers realized that the protease step represented a possible point of attack in dealing with HIV. If they could find a way to inactivate the HIV protease, the virus s polyprotein would not be broken down into its component parts, and the components from which new viruses are made would not be available. 

Specific damage to bacteria is particularly practicable when a substance interferes with a metabolic process that occurs in bacterial but not in host cells. Clearly this applies to inhibitors of cell wall synthesis, because human and animal cells lack a cell wall. The points of attack of antibacterial agents are schematically illustrated in a grossly simplified bacterial cell, as depicted in (2). 

Reactions at ring atoms consist mainly of electrophilic attack at nitrogen and cycloadditions. Examples of the reaction of 2-substituted 1,3,4-oxadiazoles with bifunctional compounds at both ring nitrogen and at the substituent, leading to cyclic systems, are included in Section 4.06.5.2 irrespective of where the initial point of attack took place. A few examples of nucleophilic attack at unsubstituted carbon are described, the more common nucleophilic attack at substituted carbon being included under reactions of the appropriate substituent (Sections 4.06.7.1-7.5). 

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