Special ortho effects

The idea that hydrogen bonding, as a special ortho effect of the substrate, may be involved in the transition state of the reactions with amines was first proposed by Chapman et al. Attempting to test this hypothesis, Hawthorne investigated the hydrogen-isotope effect in the reaction of o- and p-chloronitrobenzene with... 

Group Branch Extension of Aromaticity Sigma/Rho Fragment Interaction Special ortho effects Crowding Intramolecular Hydrogen Bonding... 

Further aza substitution ortho or para in the same ring deshields the nitrogen the effect is moderate for a para-, and large for an ort/io-nitrogen. The latter is probably a special azo effect , since the nitrogens of a simple azo group absorb at still lower field (-130 p.p.m., in ether). 

Where ortho effects and special entropy factors control the relation of the reaction rates, it seems more appropriate to evaluate relative activation from the energies of activation. 

Much effort has been devoted to the attempt to set up scales of cr values of general applicability. Only very limited success has been achieved in this direction and it seems naive to suppose that any simple LFER analogous to the Hammett equation could be successful in connection with the ortho-effect, except in rather limited and special situations. On the whole the various essays at scales of cr values have not involved sulfinyl or sulfonyl... 

These two experiments make a number of important points. An <7-HMP will not react with an ortho position as long as a para reaction site is available. A p-HMP will react with unoccupied ortho position at about half the rate that it reacts with a substituted para position. This suggests that there is something special about the repulsion between the phenolic hydroxyls. Since the pH was only 8, it is clear that there was ample opportunity for a salted 2-HMP to find and react with an unsalted 2-HMP. Both species were present. On this basis, we cannot invoke repulsion of like-charged ions. According to Jones salted species probably react with unsalted species and this is one reason that reaction rate drops rapidly when PF pH gets much above 9.0 [147]. Yet the phenolic hydroxyl appears to be the cause of the reduced reactivity of the ortho position. Unfortunately, Jones did much of his work in a carbonate buffer. He did not realize the pH-dependent accelerating effects of carbonate on PF condensation. 

The relation of activation by para vs. ortho ring-nitrogen in bicy-clics is altered by these special cases. For example, 4-chloroquinazoline (4-Cl-l,3-diaza) is much more reactive than the 2-chloro isomer (2-Cl-l,3-diaza) for two reasons, one being the poor activation in 2-Le-3-aza compounds. 4-Chloro-l,8-naphthyridine will be decreased in reactivity relative to its 2-chloro isomer due to the very poor activation in 4-Le-8-aza compounds and it may be only slightly more reactive than the mono-aza analog 4-chloroquinoline. The greater reactivity at the 2-position of 2,4-dichloro-l,8-naphthyri-dine 3 can be ascribed to this 4-Le-8-aza effect. ... 

Thus, ketone enolates easily substitute chlorine in position 2 of the electrophilic nucleus of pyrazine (1,4-diazabenzene), and even in the dark, the reaction proceeds via the Sj l mechanism (Carver et al. 1981). It is expected that the introduction of the second chlorine in the ortho position to 4-nitrogen in the electrophilic nucleus of pyrazine promotes the ion-radical pathway even more effectively. However, 2,6-dichloropyrazine in the dark or subjected to light reacts with the same nucleophiles by Sr.,2 and not S nI mechanism (Carver et al. 1983). The authors are of the opinion that two halogens in the pyrazine cycle facilitate the formation of a-complex to the extent that deha-logenation of anion-radicals in solution and a subsequent nucleophilic attack of free pyrazine radical become virtually impossible. Thus, the reaction may either involve or exclude the intermediate a-complex, and only special identification experiments can tell which is the true one. 

Now we consider the solvent effects on the mutual relationship between the p/C, values of different adds. Figure 3.2 shows the relations between pfC, of non-ortho-substituted phenols and the Hammett er-values of the substituents [8]. Good linear relations are observed in four solvents.3 It is of special interest that the slopes in AN, DMF and DMSO are almost the same and are nearly 2.0 times the slope in water. Similar linear relations have also been obtained for non-ortho-sub-... 

The analysis is based on the implicit assumption that steric effects of ortho groups are nearly constant except for very bulky groups having special structures (e.g., f-butyl) for which an additional dummy parameter D is required. The complete equation is thus... 

The special effect of an ortho-vairo group, noted by Chapman et al in reactions with primary or secondary amines but not with tertiary... 

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