OF SIMPLE QUINOXALINES

Recently reported physical data for quinoxaline and its salts etc are collected under quinoxaline in the Appendix (Table of Simple Quinoxalines), at the end of this book. More notable studies on the properties of quinoxaline or reduced quinoxaline are briefly indicated here with references. 

This table is a reasonably comprehensive alphabetical list of simple quinoxalines described up to the end of 2002. For each compound are recorded (1) melting and/ or boiling points(s) (2) an indication of reported spectra or other physical properties (3) any reported salts of simple derivatives, especially when the parent compound was poorly characterized (4) an indication of any complexes reported and (5) direct references to the original literature from 1977 onward, preceded by any pages in parentheses, for instance, (// 242) or E 64), on which earlier published data have been recorded in Simpson s Hauptwerk or in Cheeseman and Cookson s Ergdnzungswerk, respectively. 

ALPHABETICAL LIST OF SIMPLE QUINOXALINES REPORTED TO THE END OF 2002 Quinoxaline Melting Point (°C) etc. Reference(s)... 

The topical mosquito-repellent activity of a range of simple quinoxaline derivatives, including 6-chloro- and 6-methoxyquinoxalines, has been tested, but none of the compounds tested was superior to diethyl-toluamide7 ... 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

No syntheses of simple pyridopyrazines by [5 +1] type cyclizations are known, but a few syntheses of pyrido[3,4-f ]quinoxalines are described. 

There is an extensive literature on the use of 2,1,3-benzoxadiazole 1-oxide [often called benzofuroxanie) (BFO) (462)] as a substrate for the primary synthesis of quinoxaline 1,4-dioxides and occasionally quinoxaline mono-A -oxides or even simple quinoxalines. Very few substituted derivatives of the parent substrate (462) have been employed in recent years. The general mechanism clearly involves a fission (usually amine-catalyzed) of the oxadiazole ring followed by reaction with an ancillary synthon. The following examples are divided according to the type of synthon employed. 

Some typical examples of recently reported reactions of unsubstituted quinoxaline, hydroquinoxalines, or simple A -alkylquinoxalinium salts are mentioned here. 

The condensation of 1,2-diaminonaphthalene with an a-dicarbonyl compound to give a benzo[/]quinoxaline represents a simple extension of the classical quinoxaline synthesis. As a result of the unsymmetrical structure of the diamine, isomeric mixtures of benzo[/]quinoxalines can in principle be formed when the dicarbonyl compound is also unsymmetrical (Scheme 1). In practice only one isomer may be formed in appreciable quantities and be thus readily isolated. The orientation of a number of the products obtained from the condensation reactions of 1,2-diaminonaphthalene is uncertain, though, as discussed in the following sections, unambiguous syntheses of benzo[/]quinoxalines may be achieved using o-aminonitroso- and o-aminophenylazonaphthalenes. 

The combination of soluble polymer-supported synthesis with MW technology provided a highly versatile platform for the generation of chiral quinoxalin-2-one libraries. A simple work-up and cleaner products were achieved compared with... 

As example of the application of AdSV in flow-through systems the determination of Cyadox, one of the quinoxaline-N-dioxide derivatives used as growth promoter in animal breading can be mentioned. A simple detector slipped on to the capillary of a static mercury... 

In 2008, Itami reported a transition-metal-free C-H arylation of simple azines such as pyrazines, pyrimidines, pyridazines, and quinoxalines with aryl iodides under the influence of KOt-Bu. Unfortunately, this reaction showed no regios-electivity due to its radical reaction pathway (e.g., the ratio for the arylation of... 

An interesting method for preparation of fluorinated quinoxaline AA -dioxides 1094 relies on reaction of benzofuroxanes 1093 with flnorinated p-dicarbonyl componnds - a fluoro version of the so-called Beirut reaction (named after the city where it was discovered) (Scheme 232). The reaction has attracted some attention due to the products 1094 revealed high antitumor and anti-trypanosomatid activity [665-667], The method gave satisfactory results when at least one of the starting components was symmetric otherwise, the reaction was not always regioselective. The approach was also used for simple fluorinated ketones in this case, the corresponding products 1095 were obtained in low to moderate yields (16-48 %) [668]. 

Thus, a new simple, convenient, and general method of the synthesis of various quinoxalin-2-one A-oxides was presented. The synthesis started from easily accessible substrates, that is, alkyl cyanoacetic esters and 2-nitroso-N-aiylaniIines which can be prepared from appropriate nitroarenes and anilines. Diversity of the compounds can be achieved by simply varying the substituents in each reagent. 

This subsection covers not only the conversion of one simple alkylquinoxaline into another but also the conversion of a (functionally substituted alkyl)quinoxaline into another such quinoxaline provided the alkyl portion, and not just the functionality, is changed. The following classihed examples illustrate typical processes involved. 

Note Only a few simple examples of the metal complexes formed by quinoxaline oxides and dioxides are given here. 

To avoid an unmanageably long table, the following categories of quinoxalines have been excluded on the grounds that they are not simple. 

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