Benzene rings conjugation with

Substituents cannot directly conjugate with /3-pyridine-like nitrogen atoms. Azole substituents which are not a or y to a pyridine-like nitrogen react as they would on a benzene ring. Conjugation with an a-pyridine-like nitrogen is much more effective across a formal double bond thus the 5-methyl group in 3,5-dimethyl-l,2,4-oxadiazole (323) is by far the more reactive. 

Dehydration sometimes occurs under the conditions in which the aldol addition is carried out, without additional heating. In such cases, the S-hydroxycarbonyl compound is an intermediate and the enone is the final product of the reaction. For example, the 8-hydroxyketone formed from the aldol addition of acetophenone loses water as soon as it is formed, because the double bond formed by loss of water is conjugated not only with the carbonyl group, but also with the benzene ring. Conjugation stabilizes the dehydrated product and therefore makes it relatively easy to form. 

Benzylic and aUylic halides readily undergo E2 reactions, because the new double bond in the product is relatively stable, and therefore easily formed, since it is conjugated with a benzene ring or with a double bond. 

The ready pyrrolization of 2-acetylcoumarone 0-vinyl oxime in comparison with the furan analog is evidently caused [231-233] by specific effect of the benzene ring annulated with the furan cycle, that is, by the formation of more extended conjugation system (and hence thermodynamically more stable) due to the incorporation of the pyrrole ring into it. 

A point in case is provided by the bromination of various monosubstituted benzene derivatives it was realized that substituents with atoms carrying free electron pairs bonded directly to the benzene ring (OH, NH2, etc) gave 0- and p-substituted benzene derivatives. Furthermore, in all cases except of the halogen atoms the reaction rates were higher than with unsubstituted benzene. On the other hand, substituents with double bonds in conjugation with the benzene ring (NO2, CHO, etc.) decreased reaction rates and provided m-substituted benzene derivatives. 

Synthesis The ketone will enolise on the side we want because of conjugation with the benzene ring. It turns out that both alkylations happen at once ... 

Substituents containing boron are of interest because of the possibility which the boron atom offers of conjugation of a vacant orbital with the 77-electrons of the benzene ring (—717). The case of phenylboronic acid has been discussed ( 5.3.4). 

Another group of conjugated thiophene molecules for future appHcations are those being developed as nonlinear optical (NLO) devices (75). Replacement of benzene rings with thiophene has an enormous effect on the molecular nonlinearity of such molecules. These NLO molecules are able to switch, route, and modulate light. Technology using such materials should become available by the turn of the twenty-first century. 

In the section dealing with electrophilic attack at carbon some results on indazole homocyclic reactivity were presented nitration at position 5 (Section 4.04.2.1.4(ii)), sulfon-ation at position 7 (Section 4.04.2.1.4(iii)) and bromination at positions 5 and 7 (Section 4.04.2.1.4(v)). The orientation depends on the nature (cationic, neutral or anionic) of the indazole. Protonation, for instance, deactivates the heterocycle and directs the attack towards the fused benzene ring. A careful study of the nitration of indazoles at positions 2, 3, 5 or 7 has been published by Habraken (7UOC3084) who described the synthesis of several dinitroindazoles (5,7 5,6 3,5 3,6 3,4 3,7). The kinetics of the nitration of indazole to form the 5-nitro derivative have been determined (72JCS(P2)632). The rate profile at acidities below 90% sulfuric acid shows that the reaction involves the conjugate acid of indazole. 

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