Diazines aromaticity

The cyclization of hydrazides of aromatic and heteroaromatic acids is likely to give four most probable products diazepines, diazines, 5-iV-aminolactams, and y -iV-aminolactams. 

With this in mind, the coordination chemistry of 52 with different diazine structural isomers was investigated. There were no detectable changes in the H NMR spectrum of 52 in a THF-Jg solution when either pyrazine or pyrimidine were added in 1 1 or 1 2 molar ratios, which suggested that only weak interactions might occur between 52 and these bases. In contrast, incremental addition of pyridazine or phthalazine to a THF-Jg solution of 52 at 25 °C resulted in an upheld shift of the aromatic NMR resonances of the diindacycle 52 thus reflecting the formation of complexes between 52 and the 1,2-diazines. Analysis of the tritration data clearly indicated the formation of 1 1 Lewis acid-diazine complexes 52-pyridazine-(THF)2 and 52-phthalazine-(THF)2 whose stability constants are equal to 80 ( 10) and 1000 ( 150) M respectively (Scheme 29). These data, as a whole, indicate that 52 is a selective receptor for 1,2-diazines. 

Unsaturated 5(4//)-oxazolones derived from aromatic and heterocyclic aldehydes including phthalic anhydride/ antipyrine/ " chromone/ indoles/ pyridines/" ° quinolines/" diazines/" benzoxazoles/" and benzimidazoles " " have been prepared. Reaction with nitrogen nucleophiles and subsequent cycliza-tion leads to the expected 5(477)-imidazolones. 

Deprotonation from the azonium group leaves a lone pair of electrons on the nitrogen atom, and a neutral aza substituent. The known parent monocyclic azines (see Scheme la) include all the possible diazines and triazines, but only one tetrazine, the 1,2,4,5-isomer. Some 1,2,3,5-tetrazines have been reported, but only when heavily substituted or fused. Some aromatic bicyclic 1,2,3,4-tetrazines have been prepared (see Section 4.4.8.2.3) as well as reduced 1,2,3,4-tetrazines (see CHEC 2.21). No pentazines are known. All attempts to prepare hexazine also failed though several claims about fixation of the latter in a matrix have appeared. 

There have been comprehensive reviews on the coordination chemistry of aromatic JV-oxides by Garvey et al. (up to 1968)67 and Karayannis et al. (up to 1971),68 the latter including a short section on aliphatic amine (V-oxides and secondary amine nitroxide free radicals. A further review by Karayannis et al. (up to 1975)69 covers mono- and di-oxides of bipyridyl, o-phenanthroline and some diazines. 

The most interesting compounds described in this paragraph are meso-ionic naphtho[reactions with olefinic compounds. For instance, the reaction with acetylenedicarboxylates gives rise to adducts 458, which are dehydrogenated spontaneously to the new heteroaromatic systems 459 with the aromatic 147r-electron contour [75JCS(PI)556]. 

The diazines (pyridazine, pyrimidine, and pyrazine) are six-membered aromatic heterocycles that have two nitrogens in the ring. Cytosine, thymine, and uracil are derivatives of pyrimidine that are important bases in nucleic acids (DNA and RNA). Heterocyclic analogs of the aromatic hydrocarbon naphthalene include pteridines, which have four nitrogens in the rings. Naturally occurring pteridine derivatives include xanthopterin (a pigment) and folic acid (a vitamin). Methotrexate is a pteridine used in cancer chemotherapy. 

Know the meaning of heteroatom, aromatic heterocycle, nonaromatic heterocycle, diazine, azole. 

Mechanistically, the Beirut reaction is a heterocycle expansion-process where the nucleophile attack conducts, after atomic rearrangements, to a new diazine system. In general, a further elimination—i.e., of H2O, amines, acetate—aromatizes the new heterocycle. 

Formal replacement of a CH unit in pyridine 5.1 by a nitrogen atom leads to the series of three possible diazines, pyridazine 10.1, pyrimidine 10.2, and pyrazine 10.3. Like pyridine they are fully aromatic heterocycles. The effect of an additional nitrogen atom as compared to pyridine accentuates the essential features of pyridine chemistry. Electrophilic substitution is difficult in simple unactivated diazines because of both extensive protonation under strongly acidic conditions and the inherent lack of reactivity of the free base. Nucleophilic displacements are comparatively easier. 

Tomer, K.B., Harrit, N., Rosenthal, I., Buchardt, O., Kumler, P.L. and Creed, D. (1973) Photochemical behaviour of aromatic 1,2-diazine N-oxides. Journal of the American Chemical Society, 95 (22), 7402-7406. 

Pyrazines have considerable aromatic character and therefore in the majority of their reactions tend to revert to type. The main features of their reactivity may be predicted by regarding them as pyridines into which a nitrogen has been inserted in the para position. Pyrazines also show close similarity in their reactions to the other diazines, pyrimidines, and pyridazines. 

Quinoxaline-3-ketoximes in the presence of pyridine can be cyclized the reaction proceeds by addition of the oxime hydroxy group to the electron-deficient diazine to form a cyclic dihydro derivative which expels the ring function substituent to regain aromaticity, e.g. (45) (66HCA2426). 

Meta-cyclizations are often called meta-bridging reactions, since they yield polycyclic meta-bridged structures (74ACR181). In the series of aza-aromatic compounds, these reactions are mostly found with 3-nitro-substituted azines or with 1,3-diazines, as illustrated by Scheme 54 (77JOC2589). 

Successive introduction of nitrogen atoms into benzene causes a gradual reduction in aromatic stabilization. The diazines still show typical aromatic behavior in that in most of their reactions they revert to type. However, with the triazines and tetrazines, decreasing aromaticity increases the ease of both thermal and photochemical fragmentations and rearrangements, and of cyclic transition state reactions with other reagents. 

---