Quinoxaline macrocycles

Quinoxaline macrocycles Quinoxallnes Quinoxalinoporphyrazines Resorcin[4]arenes. 

The formulas of macrocycles— predecessors of quinoxaline macrocycles are presented below. 

In the formation of the first representatives of quinoxaline macrocycles, namely, N, AT"-deca(dodeca) methylenequinoxalin-2,3(lH,4fl)-diones 10 quinoxaline system supplies a four-atomic N-C-C-N fragment. They were obtained in 1975, (1975JCS(P2)212) by the interaction of oxalyl chloride with the N,AT-polymethylene-l,2-diaminobenzene derivatives 1. 

Cyclic diketones can be the predecessors of quinoxaline macrocycles, obtained in one stage with the oxidation of cyclic alkenes with potassium permanganate (1971JA3303) or in two stages by the cyclotrimerization of cyclic alkynes and subsequent ozonolysis of compounds 18 (1986JOC3257). Along with the formation of diketone 4 the latter reaaion leads, to the unstable hexaketone 19. The reaction of the mixture of compounds 4 and 19 with the DAB leads to macrocycles 20 and 21 with one or three quinoxaline fr pients, respectively, with 10% and 3% yields, calculated in two st es.The synthesis of the macrocycle 20a from the analytically pure diketone 4a was in quantitative yield. 

Quinoxalin-2,3(lH,47i)-dione 58, 2,3-dichloroquinoxalines 59, quinoxalin-2,3(lH,4/i)-dithione 60, 2,3-dibromomettylquinoxalines 61, 4-[3-(4-hydroxyphenyl)-2-quinoxalinyl]phenol(62a),4-[3-(4-mercaptophenyl)-2-quinoxalinyl]thiophenol (62b), 2,3-dipyrrolylquinoxaUnes 63 and 64b, 2,3 dicyanoquinoxaline 65a and its benzo[/]- 65b and the dibenzo[ /i]-65c annulated derivatives as well as 6,7-dicyanoquinoxalines 66 were used among the numerous derivatives of quinoxaline as key compounds for designing of the quinoxaline macrocycles (Chart 2). 

Chart 2 Quinoxaline derivatives—precursors of the quinoxaline macrocycles. 

Commercially available 2,3-dibromomethylquinoxaline 61a was widely used for the synthesis of quinoxaline macrocycles. Its interaction with l,l-bis(imidazolyl)methane 91a, 2,6-bis(imidazolylmethyl)pyridine 91b, 2,3-bis(imidazolylmethyl)quinoxaline 91c, and l,l -bis(imidazolylmethyl) ferrocene 91d leads to the quinoxaline macrocycles 92a—d, respectively, which are fluorescent receptors on anions (2008JCS(D)3694,20070L485, 2010CSR1457). 

In addition to the above three groups of methods of constructing quinoxaline macrocycles there are other methods that are based neither on any quinoxaline derivatives nor on podand quinoxaline terminal fragments or macrocycles. 

There are three types of the quinoxaline macrocyclic compounds known with important pharmacological properties.They differ in whether the quinoxaline fragment enters the structure of the macrocyclic system and if it does, then what follows. 

There are a number of methods for the synthesis of quinoxaline macrocycles that have been successfitlly implemented for constructing quinoxalinoporphyrins, quinoxalinoporphyrazines, quinoxalinocrown ethers, quinoxalinocavitands, quinoxalinohemispherands, and hybrid ... 

There have been obtained macrocycles the framework of which also includes other heterocyclic systems, e.g., pyrrole, pyridine, imidazole, ferrocene, indolizine, triazolothiadiazole, and benzopyrazole except the quinoxaline moiety. As a rule, a constandy growing interest is attached to the mutual influence of the heterocyclic fragments closely located toward each other. This is due to interest in the ample opportunities they hold for their practical application. Thus, the quinoxaline macrocycles with imidazole, pyrrole, or ferrocene moieties are sensors for some anions and cations for the heavy metals. The combination in one molecule of macrocycles of quinoxaline, pyrrolidine, and benzopyrazolne fragments leads to the selective inhibition of the kinase, and the presence of pyrrolidine and amide fragments leads to an antihepatitis effect. Mono-, bis-, and tris- quinoxalinoporphyrins the macrocyclic skeleton of which included pyrrolequinoxaline and pyrrole moieties are attractive for the development of optical devices and materials. 

Professor Mamedov (A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Federation) describes many new methods for the construction of quinoxaline macrocycles, which are gaining importance because of their apphcation to optical devices and materials. 

Cyclic diketones can be the predecessors of quinoxaline macrocycles, obtained in one stage with the oxidation of cyclic alkenes with potassium permanganate... 

---