Azoles and azines

Dr. Wojciech Szczepankiewicz was born in Wolbrom, Poland, in 1959. He received his M.Sc. in polymer chemistry from the Silesian University of Technology in Gliwice, Poland, in 1985 and his Ph.D. in 1994 under the supervision of Prof. Jerzy Suwiriski at the same university. In 2002-03, he spent a period at Hasselt University (Belgium) with Prof. Dirk Vanderzande s lighting polymer research group. His research area is focused on the synthesis and reactivity of heterocyclic compounds in the azole and azine series. 

The one-bond coupling constants JCH of pyridine ring carbons behave similarly to those of benzenes substituted by electron acceptors such as cyano and nitro groups (Table 3.7). In azole and azines, JCH increases with the number of nitrogen atoms in the ring (Table 3.7). 

The phenyl derivatives of azoles and azines are widely used as C,N-ligand systems on their basis the following complexes were obtained 378 (A = NR [13,693,694] S [679]) and 379 (A = CH [695,696] N [697]). The examples of C,N-coordination of alkyltrimethylsilyl derivatives of pyridine and quinoline have been reviewed [8]. 

Use of coordinated azole and azine system containing donor-active nitrogen atoms as metal ligands open wide possibilities for obtaining homo- and heteronuclear complexes. Thus, such reactions are known where the complexes of coordinatively unsaturated pyrazole (3.221) [490] and triazole (3.222) [491] take part ... 

The tautomers of azole and azine derivatives, stabilized as a result of complex formation, are widely found [11,15,16,18,261-269]. Thus, the metal-cyclic structures with anionic ligands are formed in chelates of 2-hydroxy- 436, 438) and 2-mercapto-substituted (484, 485) derivatives of these nitrogen-containing heterocycles described above. At the same time, the ketone (thion) isomers are stabilized in molecular adducts. In this respect, the syntheses (4.64) [266], (4.65) [267], and (4.66) [269] are quite representative for this group ... 

In contrast to purines, the combination of azole and azine rings in indolizine gives rise to an electron-rich species as a consequence, only cation-radicals have been reported. The transient existence of a simple cation-radical is implied by the observation of oxidative dimerization of 1,2-dimethylindolizine on treatment with Fe(CN) " to give 179 (R1 = R2 = Me).593 The cation-radical of 179 (R1 = Ph R2 = Me) was synthesized by Colonna et al,461 This group also obtained the azaviolene cation-radical 180 (X = N) and related species.594,595... 

In the reaction of imidoyl halides with azide ions, imidoyl azides (31) are obtained, which caused some interest on account of their ring-chain tautomerism (31)/(32) (Scheme 43)." - ° It is not possible, however, to discuss this point in detail here. ° The final elucidation of a series of dubious structural assignments had to wait until the advent of modem spectroscopic methods. As expected, the position of this equilibrium is influenced by the nature of substituents R/R as well as by temperature and solvents. Electron-withdrawing ligands seem to favor the formation of the tetrazole isomer (32). The equilibrium (31)/(32) does not always operate — there are a number of cases known which show a comparatively high activation barrier.The same problems are encountered with the reaction products from 2-halo-azoles and -azines with azide ions. " °... 

Sulfur is a useful link for heterocycles because its use as a leaving group (or better, after conversion to sulfoxide or sulfone) can bring about cleavage from the support combined with addition of a nucleophile. This method has been nsed for both azoles and azines, as shown below. 

O-Mesitylenesulfonyl)hydroxylamine (X) is used as a reagent for electrophilic NH2 transfer to the pyridine-like N of azoles and azines (cf p 273). The resulting N-aminated systems can be subjected to acylation, deprotonation (to give dipolar N-imides) and other transformations [76]. The following sequence of reactions may serve as an example ... 

Aryl and 1 -dioxoindanyl derivatives of azoles and azines 07KGS1603. 

J With enamines. l-Oxa-2-azulenones (as tethered heptafulvenes) with enamines undergo [8+2] cycloaddition as well (85HOU(5/2c)127, p. 218 98SL950). This way, in the case of heterocyclic enamines (such as 40), azuleno[l,2]-fused azoles and azines are formed (Schemes 13 and 14) The reactions of oxaazulenone 37 with the isomer mixtures of enamines 40a or 40b yield mixtures of isomeric dihydrothiophenes 41 and 42 that are dehydrogenated by 2,3-dichloro-5,6-dicyano-p-benzoqui-none (DDQ) to yield thiophenes 43 and 44, respectively (83CL1721). Whereas the latter [l,2-c]-fused compound is unstable because of its o-quinonoid structure, thiophenes 43a and b are demethoxycarbonylated to yield substances 45a and b. 

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. 

N-Substituents in hetarylazomethine ligands are represented by three-and five-membered rings with one heteroatom as well as azole and azine heterocycles. They may not always participate in the formation of metallacycles and thus play the role of coordination-active or inactive constituents of the hetarylazomethine ligands. A great majority of coordination compounds includes mononuclear complexes, although di- and oligonuclear structures are also known. 

Various reviews have been published about this topic. Jeschke and Leroux [2] pubhshed about the medical apphcation of a-fluorinated ethers. Leroux and Pazenok [1] wrote about the synthesis and the properties of trifluoromethyl ethers. Leroux, Jeschke and Schlosser [3b] reviewed the properties of a-fluorinated ethers, thioethers and amines. The work of Boiko [4a] is dedicated to aromatic and heterocyclic perfluoralkyl sulfides. Vovk and Gakh [4b] gave a detailed review about trifluoro-methoxy containing azoles and azines. This review summarized the literature data on synthesis and biological activity of trifluoromethoxy, difluoromethoxy and a-fluorinated sulfides derivatives of five and six membered heterocycles. 

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