Quinoxaline quaternization

A number of quinoxalines carrying substituents in the benzene ring base have been quaternized, including 5-ethoxy,6-methyl, 6-chloro, and some 2-phenyl derivatives, but in none of these cases has the position of quatemization been ascertained. 5-Hydroxy-quinoxaline gives a methiodide which can still form metal complexes, indicating that salt formation occurred on N-1. ... 

Four chapters in the present volume bring older reviews up to date. Those on the quinoxalines (Cheeseman and Werstiuk) and on hetero-aromatic quaternization (Zoltewicz and Deady) carry forward contributions on the same subjects in Volumes 2 (1963) and 3 (1964), respectively, of this Series, while those on the phenanthrolines (L. A. Summers) and the isatogens and indolones (Hiremath and Hooper) deal with topics previously covered elsewhere. The cyclazines, a relatively new field of chemistry, are reviewed by Flitsch and Kramer, and the azapentalenes— the wide variety of nitrogen-containing heterocycles formed by the fusion of two aromatic five-membered rings—are collected into one chapter by Elguero, Claramunt, and A. J. H. Summers. 

The reduction of quinoxalines was discussed in Part I1 newer investigations have confirmed the general scheme.312,313 The quaternized compound,... 

If the heterocyclic base contains several pyridine-type nitrogens select can also be observed. Indeno[l,2-b]quinoxalines, for example, are quaternized at the N-10 atom.110 The alkylation of heterocycles conta one pyrrole-type nitrogen and several pyridine-type nitrogens is appar selective (e.g., indolo[2,3-b]quinoxaline).201 The yields of quaternary however, are extremely low,201 even if phenacyl halides or a-halo ester used.207 Perhaps the resultant quaternary salts are dealkylated.200,207... 

Substituted quinoxalin-2(177)-ones have been shown to quaternize under drastic conditions... 

The reduction of quinoxaline derivatives or quaternized quinoxalines by titanium(lll) chloride leads to di- or tetrahydro compounds. Several reductions of quinoxalines to 1,2,3,4-tetrahy-droquinoxalines with hydrogen and a metal catalyst at room temperatures and pressure not exceeding 3 atmospheres have been described, the yields of which are sometimes strongly solvent dependent. At higher temperatures and pressures decahydroquinoxalines may be reaction products. ... 

Several different approaches have been adopted for the synthesis of pyrrolo[l,2-a]quinoxalines. Particularly useful are approaches involving cyclization reactions of o-aminophenylpyrroles. Alternative syntheses have involved the use of o-phenylenediamine, the cyclization of /3-quinoxalinylpropionic acids, quaternization of quinoxaline derivatives, as well as several other routes less amenable to classification. 

In general the quinoxaline ring system is quaternized only with difficulty, so that approaches to pyrrolo[l,2-a]quinoxalines that involve a quatemization step are unlikely to be very convenient. Nevertheless several different types of synthesis have been performed using quinoxaline quaternary salts. 

Quaternization of quinoxaline is neatly avoided by the synthesis of the azirino[l,2-a]quinoxalines 71 from o-phenylenediamine and the dibromo ketones 70. The azirino compound apparently acts as a 1,3 dipole and undergoes addition with a variety of dipolarophiles to give fused quinox-alines containing a bridgehead nitrogen atom. " Thus the acetylene derivatives 72 give the pyrrolo derivatives 73. The yields are much improved by the use of chloranil in situ to oxidize the presumed dihydro intermediates 74. 

Dehydration of the aminobenzimidazoles 96 with polyphosphoric acid gave the cyclized products 97. ° Compound 98 has also been prepared by the same approach. Chloroethylbenzimidazoles such as 99 have been cyclized to imidazo[l,5,4-de]quinoxalines, ° and the bis(chloroethyl)-amine 101 was similarly cyclized to the quaternized heterocycle 102. ... 

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