Azines ring metallation

In the last year, a lot of attention has been paid to the efficient directing effects of 2-pyridyl groups to facilitate a number of useful synthetic transformations. Mongin and co-workers have examined 2-pyridyl groups to direct metalation of 2-phenylpyridines 37 <04JOC6766>. Under the kinetic conditions studied no nucleophilic addition to the azine ring was observed. Lithiation occurred cleanly at the 2 -position of the benzene ring, as shown in Scheme 16, to yield compounds 38. 

Finally, those organometallic derivatives of azines in which the metal is separated from the ring by one carbon atom are considered under the corresponding alkyl compound (Section 3.2.3.3). 

Reedijk and co-workers have prepared and studied a variety of Ru(ll) complexes of pyridyl- and pyrazinyl-substituted 1,2,4-triazoles of which 26 is an example. In ail cases the heterocyclic ligands were chelated to the metal center via one azole and one azine nitrogen atom and, in addition to various electrochemical and spectroscopic studies, pKa values for the pyrrole proton of the triazole ring were obtained. The Ru(bpy)2 + com-... 

Hydrogen attached to ring carbon atoms of neutral azines, and especially azinium cations, is acidic and can be replaced by a metal formally being removed as a proton. Alkyllithiums can be used as bases for this purpose however, the reaction can be accompanied by addition of the alkyl anion to the ring C=N bond. To avoid this, sterically hindered bases with strong basicity but low nucleophilicity can be utilized. Among these are lithium tetramethylpiperidide (LiTMP) and lithium diisopropylamide (LDA). If the anion contains an ortho halogen atom, then this can be eliminated to form a pyridyne (see Section 3.2.3.10.1). 

A pyrrole ring may be formed from azines and either anhydrous nickel chloride or paUadium(II) chloride. Palladium-assisted C—C bond formation connecting one benzene ring to another is also a useful method. A review of transition metal-mediated heterocyclizations was published in 1980 [B-S6]. Bis(methyl-thio)methylenemalonic acid derivatives annulate two methylene groups [2881]. 

Since the positions of the Is,min are the locations, on the average, of the most easily removed electrons, these should also be the sites that are most reactive toward electrophilic attack. This has been fully confirmed for a group of monosubstituted benzene derivatives [10,21]. The Is,min correctly predict the ortho/para- or meta- directing tendencies of the substituents, even the rather unusual NH3+, which is a metal para director [22]. Furthermore, the magnitudes of the Is,min relative to that of unsubstituted benzene correctly indicate whether each substituent activates or deactivates the aromatic ring toward electrophiles. These analyses have been extended to other aromatic systems, including azines and azine N-oxides [18,23,24]. 

Metal chelates are preser t in the complexes of Schiff bases of amino-(X = NR2), hydroxy- (X = O), and mercapto- (X = S) derivatives of monoheteroaromatic five-membered systems, azoles, and azines. A few publications on the complexes of azomethines of the monoheteroaromatic five-membered systems have appeared only recently. The X-ray structural study of copper(II) bis(2-N-n-octyliminomethyl)benzo[ 7]thio-phene-3-olate) 199 (04ZNK1696) is interesting in the sense that its square-planar structure is complemented by an extended octahedral one due to the intermolecular contacts of the thiophene sulfur with the copper site. Among the azole complexes, azomethine derivatives of p3Tazole (Equation (32)) prevail (05RCR193). There are several types of coordination units (N,N-, N,0-, N,S-, N,Se-) created by variation of the donor sites X in position 5 of the pyrazole ring. When X = O, S, Se, tautomer b is realized, whereas when X = NR, tautomer a predominates (Equation (32)). However, irrespective of the type of tautomer, in the chelates the coordination units have practically equalized bonds. 

A plethora of electron-deficient arenes can enter the VNS reaction carbocyclic and heterocyclic aromatic compounds activated by the nitro group and arenes that are active electrophiles due to their electronic configuration, such as azulene [35, 36], electron-deficient annulenes [37], tropylium cation [38], and particularly azines and azinium cations. Interestingly, q -transition metal complexes of arenes, such as benzene tricarbonylchromium, do not enter the VNS reactions. Although the addition of carbanions to these electron-deficient rings proceeds efficiently, and these adducts can be oxidized to form the products of ONSH, the p-elimination of HCl from the o adducts of a-halocarbanions does not occur [39, 40]. 

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