Heterocyclics benzo cinnolines

The diazines pyridazine, pyrimidine, pyrazine, and their benzo derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine once again played a central role in many investigations. Progress was made on the syntheses and reactions of these heterocycles, and their use as intermediates toward broader goals. Some studies relied on solid-phase, microwave irradiation, or metal-assisted synthetic approaches, while others focused attention more on the X-ray, computational, spectroscopic, and natural product and other biological aspects of these heterocycles. Reports with a common flavor have been grouped together whenever possible. 

Cinnolines, one of the two benzo derivatives of pyridazines, attracted considerable attention due to the variety of pharmacological activities exhibited by these heterocycles. 

Thus, while the 3-hydroxyisoquinoline-3-isoquinolinone equilibrium (80 81) and that of the cinnoline derivatives (82 83) favour the keto forms (81, 83), the proportion of hydroxy tautomers is considerably greater than in the corresponding unfused systems. The benzo-fusion in 2- and 4-quinolinone and in 1-isoquinolinone has the effect of reducing the aromaticity of the heterocyclic ring, and consequently of lowering the proportion of the hydroxy tautomers. 

Isolated and benzo-fused diazine rings are key structural elements in many natural and synthetic compounds of current, active interest. This contribution relates highlights from many of the studies on the diazines pyridazine, pyrimidine, pyrazine, and their benzo-fused derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine published in English in the journal literature during 1995, as covered by Chem. Abstr. through volume 124, issue 9. Review articles published in 1994 and not cited in Prog. Heterocycl. Chem. have been included. 

The reduction of compounds suitably substituted with reducible functional groups can be advantageously used for the preparation of heterocyclic ring systems 15 5 The guiding principle here is to form a nucleophilic center in the molecule by cathodic reduction of a functional group and then have this to react with an electrophilic center (which may also be formed in an electrochemical process or be present in the starting material) suitably positioned for ring closure. Thus, 2,2-dinitrobiphenyl can be reduced to benzo[c] cinnoline in acid solution ... 

This update covers material that appeared in Chemical Abstracts in the 10-year period to the end of 1993, with limited reference to subsequent papers. Over 7600 references to pyridazines or to phthalazines, cinnolines, and their benzo derivatives were identified for this period. While many are not concerned primarily with pyridazine and its benzo derivatives, it is interesting to consider their composition. The majority, about two thirds, refer to pyridazine derivatives, while the remainder are concerned mainly with phthalazines, cinnolines, and their benzo derivatives, with a few containing material common to both pyridazine and its benzo derivatives. Approximately a quarter of all of the references are to patent applications, and while these include some in which a pyridazine function is a nonessential part of the invention, a significant number include pyridazine and benzo derivatives as an important part of the invention. The patent activity is an indication of the expansion of industrial interest in these heterocyclic derivatives. Analysis of a representative sample of patent applications in the early 1990s revealed that in approximately 30% the diazine was an important part of the invention, while the distribution of end uses was pharmaceuticals (43%), agrochemicals (31%), other materials such as photographic reagents and liquid crystals (18%), and analytical applications (8%). 

Condensed heterocyclic systems can also be obtained in this way when 2,2 -azonaphthalene is heated with aluminum chloride in methylene dichloride under reflux for 1 h, a 90% yield of benzo[/]naphtho[2,l-c]cinnoline is pro-... 

Cumulative Index of Heterocyclic Systems Benzo[c]pyrazolo[l,2-a]cinnoline (280)... 

Section 15.6 contains tables of magnetic data obtained from anion radicals of azo compounds. This includes cyclic azo compounds which might also have been entered under the section on heterocycles as it was felt that this was the more natural classification. The data have been divided into subsections consising of aliphatic azoaUcenes benzo[c]cinnolines and azobenzene derivatives arylazophosphonates bidiazines andtet-razines. Where appropropriate, these subsections have been further subdivided, for instance, aliphatic azoaUcenes has been further divided into open chain azoaUcenes, cychc azoalkenes and azopolycycloalk-enes. 

Quinoxaline is a bicyclic heterocycle consisting of a benzene ring fused to a pyrazine, hence a quinoxaline is also called Benzo[a]pyrazine, Benzopyrazine, Benzoparadiazine, 1,4-Benzodiazine, Phenopiazine, Phenpiazine, Quinazine, and Chinoxalin. It is isomeric with quinazoline, phthalazine, and cinnoline. 

Abbott PJ, Acheson RM, Foxton MW, Raulins NR, Robinson GE (1972) Addition reactions of heterocyclic compounds. Part L. Reactions of 1-alkylbenzotriazoles and benzo[c]cinnolines with dimethyl acetylenedicaiboxylate. J Chem Soc, Perkin Trans 1 2182-2190. doi 10.1039/ P19720002182... 

To study the effect of the cinnoline heterocycle on the reactivity of 10-membered enediynes, the rates of Bergman cyclization of compound 3.824 and 3,4-benzocyclodeca-l,5-diyne-7-ol 3.827 were compared at 75°C in 2-propanol. The products were analyzed by high-performance liquid chromatography (HPLC). The reaction obeys first-order kinetics and enediyne 3.824 is four orders of magnitude more active than benzo-fused analog 3.827 [381a]. 

---