Quinoxaline ring

Scarcely a single issue of Chemical Abstracts is published without reference to medicinal compounds containing the pyrazine or quinoxaline ring in some form, and hence it is impractical to list all applications of pyrazines, quinoxalines and phenazines. Some of the more important applications and natural products, particularly the more recent developments, are mentioned in this Section. 

Echinomycin (131) has been shown to be an antitumor agent and to have antiviral and antibacterial properties. Its structure elucidation represents a triumph for and mass spectral studies (75JA2497). It has been demonstrated that echinomycin functions by inhibiting RNA synthesis in organisms such as Staphylococcus aureus. Echinomycin, levomycin and actinoleutin are members of the quinoxaline-peptide antibiotic family and all contain one or more quinoxaline rings (67MI21402). 

The numbering of the quinoxaline ring system is as shown, the 2 and 3 positions are designated alternatively a positions. 

Diphenol/thiophenol is one of the most important polymer precursors for synthesis of poly(aryl ethers) or poly-(aryl sulfides) in displacement polymerizations. Commonly used bisphenols are 4,4 -isopropylidene diphenol or bisphenol-A (BPA) due to their low price and easy availability. Other commercial bisphenols have also been reported [7,24,25]. Recently, synthesis of poly(aryl ethers) by the reaction of new bisphenol monomers with activated aromatic dihalides has been reported. The structures of the polymer precursors are described in Table 2. Poly(aryl ether phenylquinoxalines) have been synthesized by Connell et al. [26], by the reaction of bisphenols containing a preformed quinoxaline ring with... 

Note A surprising aminolytic displacement of a phenylethynyl group has been observed when it occupies a position adjacent to a chloro substituent on the quinoxaline ring. 

Scheme 3) <05TL2189>. However, in this case the reaction did not afford the expected DA adduct, the product being the porphyrin derivative 10 resulting from the tetradehydrogenation of the corresponding adduct. The porphyrin derivative 11 was also obtained although in minor amount this product must result from a cyclization reaction between the beta-fused quinoxaline ring and the adjacent maso-aryl group. Also, bisadducts 12 and 13 were isolated these are the result of site specific bisaddition to opposite pyrrolic rings followed by oxidative processes.

Reaction temperatures above 100°C are avoided to prevent branching. PPQs can also be synthesized from monomers that contain the quinoxaline ring [Maier, 2001],... 

A particular class of quinoxaline A-oxides can be synthesized by a reaction sequence starting from condensation of anilines with a-oximino ketones (Scheme 50) <1998S1769>. The key step is oxidation of the oxime to an a-acetoxy nitroso group, which behaves as an electrophile leading to the formation of the quinoxaline ring. 

Olaquindox is an antibacterial also used as a growth promoter for swine at an incorporation rate in feeds of 25-100 ppm. In swine, olaquindox is metabolized either by oxidation of the alcohol group on the side chain or removal of one or both of the A-oxide groups at the positions 1 and 4 on the quinoxaline ring. 

Bromocyclobutanone and o-phenylenediamine condense to give the strained ring system cyclobuta[6]quinoxaline,33 and the cyclopenta[6]-quinoxaline ring system is similarly synthesized from suitable cyclo-pentanedione derivatives.34... 

Steroidal quinoxalines of the type 248 have been synthesized,240 and the quinoxaline ring has also been incorporated into the C and D ring of steroids to give 11,14-diazaestrapentaenes (e.g., 249).241... 

The quinoxaline ring is produced by the reaction between ortho-phenylene diamine and glyoxal... 

In valence bond terms, the quinoxaline ring may be represented as a resonance hybrid of a number of canonical structures. Molecular dimensions obtained by X-ray structure analysis are presented in the table and, as e.xpected, all interbond angles are close to 120°. The low symmetry of quinoxaline results in increa.sed disorder in the crystal state. 

The numbering for the quinoxaline ring system 1 proceeds clockwise from nitrogen an alternative name is 1,4-diazanaphthalene. Compound 2 is named accordingly as 3-methylquinoxaT in-2(I//)-one, and compound 3 as 2-chloroquinoxaline 4-oxide. 

Quinoxaline 1,4-dioxides possess antibacterial activity, " as well as being fungicides, insecticides, and herbicides. Quinoxaline-2-carboxylic acid 1,4-dioxide has been isolated from cultures of Sireplomyces ambrofaciens and this compound has been shown to have antibiotic properties. Echinomycin, from the quinoxaline-peptide antibiotic family, contains one or more quinoxaline rings and is an antitumor agent. Quinoxaline derivatives are also antagonists at the jV-methyl-D-aspartate (NMDA) receptor of the glycine modulatory site. Poly(phenylquinoxalines) are used as high temperature polymers. 

Condensation reactions using different fragments are very important for the synthesis of quinoxaline derivatives. Some of these condensation reactions lead, in the first step, to a partially saturated derivative of the heteroaromatic system which can be further oxidized with appropriate reagents. The most widely used method for the synthesis of the quinoxaline ring is the condensation of benzene-1,2-diamine with a two-carbon synthon. 

Irradiation of quinoxaline-2(17T)-thiones 24 in the presence of alkenes gives 2-(2-sulfanyl-alkyl)quinoxalines 25 via ring cleavage of an intermediate aminothietane with aromatization of the quinoxaline ring. The latter is formed by [2 + 2] photocycloaddition of the C-S double bond of the quinoxaline-2(l/j)-thione and the C-C double bond of the alkene. ... 

The addition of cyanogen to 3 4-diaminophenylarsinic acid leads to the production of a di-imino-dikydroquinoxcdine (I), and the addition of w-bromoacetophenone leads to a phenyl-dihydroquinoxaline (II). No method has been found which will decide the position of the phenyl group in the quinoxaline ring. ... 

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