Structure pyridine azomethines

Table 30.1.2 Pyridine azomethines - structure-activity relationship.

Heterocycles which contain an azomethine unit (C=N) as part of their ring structure - pyridines, quinolines, isoquinolines, 1,2- and 1,3-azoles, etc. - do not utilise the nitrogen lone pair in their aromatic n-system (cf. section 1.2) and therefore it is available for donation to electrophiles, just as in any simpler amine. In other words, such heterocycles are basic and will react with protons, or other electrophilic species, at nitrogen, by addition. In many instances the product salts, from such additions, are isolable. 

Interesting structures can be formed by combinations of ring and side-chain substituents in special relative orientations. As indicated above, structures (28) contain the elements of azomethine or carbonyl ylides, which are 1,3-dipoles. Charge-separated species formed by attachment of an anionic group to an azonia-nitrogen also are 1,3-dipoles pyridine 1-oxide (32) is perhaps the simplest example of these the ylide (33) is another. More complex combinations lead to 1,4-dipoles , for instance the pyrimidine derivative (34), and the cross-conjugated ylide (35). Compounds of this type have been reviewed by Ramsden (80AHCl26)l). 

When the azomethine group is part of an electron-deficient ring, such as pyridine, pyrimidine or thiazole, the compounds exist as tetrazoles in the solid state, and at equilibrium with the azido form in solution . The equilibrium constants depend on the solvent, the nature of the substituents and the temperature . 2-Azido-4,6-dimethylpyrimidine (288a) thus exists in equilibrium with tetrazolo-pyrimidine (288b). Its chemical behaviour is, however, in accord with the azide structure 288a, including dipolar addition reactions and nitrene reactions . 

Since Huisgen et al. first demonstrated the 1,3-dipolar character of pyridine N-imine in 1962,182 the 1,3-dipolar cycloaddition reactions of the heteroaromatic JV-imines have been explored extensively. The reactivity stems from the azomethine structure of the JV-imines.183 The cycloaddition of a variety of activated alkynes and alkenes to the JV-imines yields fused dihydro-pyrazoles and tetrahydropyrazoles, respectively. However, the aromaticity of the heteroaromatic ring is destroyed at this stage, so that such primary cycloadducts usually undergo further reaction to achieve stabilization in various ways as shown in Scheme 4 (i) aromatization, (ii) hydrogen transfer, (iii) rearomatization by rearrangement, and (iv) rearomatization by N—N... 

Hydroperoxides (/-butyl hydroperoxide, cumyl hydroperoxide, and hydrogen peroxide) add to the azomethine bond of pyridine iV-aryl-imines.138 The primary addition product reacts as indicated in Eq. (13) and leads to 1,6-dihydropyridazine derivatives (97). Unsymmetrically substituted iV-arylimines furnish two products the structure of the hydroperoxide has no influence upon the nature of the final product. 

ICC1063) and di- 318 (02JCS(D)441) azine-coordinated nickel complexes can be prepared from pyridine-containing aldimines of 2,6-diformyl-4-methylphenol. A nickel cationic complex of a 2,6-bis-azomethine derivative contains two coordinated pyridine N-substituents 319 (M = Ni, R = H, R = Me, = MeOH) (96T3521). Zinc chelate 319 (M = Zn, R = R = Me, no L) has a similar structure (02IC6426). Tetranuclear manganese poly-chelate contains two coordinated pyridine... 

As suggested by their structures of cyclic azomethine, pyridines add organolithiums as nucleophiles at a nitrogen-neighboring site. This reaction was discovered by Karl Ziegler and K. Zeiser and was extended to other azines such as quinoline, isoquinoline, and acridine by the same authors and to phenanthridine by Henry Gilman and J. Eisch. ... 

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