Regioselectivity substituted quinoxalines

Ford and co-workers reported regioselective substitutions of 2,3-dichloro-6-amino-quinoxaline 270 with various dialkylamines to study the biological properties of substituted quinoxalines <00TL3197>. For example, 2,3-dichloro-6-aminoquinoxaline 270 reacted with nucleophiles to give the opposite regioisomer to that seen with 2,3-dichloro-6-nitroquinoxalines 267. 

The proper choice of the A-heterocyclic carbene (NHC) ligand in Ru-NHC complexes allowed the regioselective ligand-controlled hydrogenation of either the heterocyclic or the carbocyclic ring of a substituted quinoxaline in quantitative yields. 

The regioselectivity observed in Eq. (6) with diprotonated quinoxaline (reaction performed in 96% H2S04) is of particular interest. Whereas in monoprotonated quinoxaline (Eq. 1) the C-2 carbon atom has the lowest electron density and substitution occurs at C-2 position only, in diprotonated quinoxaline (Eq. 6) the electron density of the equivalent C-2 and C-3 is as low as that of the equivalent C-6 and C-7 carbon atoms (NMR and IN DO calculations) [9] and substitution occurs at both C-2 and C-6 positions. To minimize polysubstitution, the conversions in Eq. (6) were limited to about 50 % (selectivity, based on the reacted bases, is >90 % in any case). Another feature of Eq. (6) is the exceptional selectivity of hydrogen abstraction from the C-5 position of w-hexyl derivatives by the aminium radical i-Bu2NH+, generated from i-Bu2NHCl+ and Fe(II) [2]. 

With substituted unsymmetrical benzene-1,2-diamines and unsymmetrical reagents this type of reaction leads to isomeric products. Regioselective synthesis of quinoxaline derivatives and the effect of substituents at C3 in the aromatic ring on annulation has been studied for unsymmetrically substituted starting benzene-1,2-diamine derivatives. ... 

In the reaction of benzofuroxan with unsymmetrical 1,3-diketoncs, or of unsymmetrically substituted benzofuroxan,however, two different isomeric products can be formed. Stehc and electronic effects influence the regioselectivity of this reaction and determine which group forms the acyl and which the quinoxaline substituent in the product. ... 

Larionov and coworkers developed a direct, catalytic, and regioselective synthesis of 2-aryl-substituted pyrazines and quinoxalines from their respective N-oxides (Scheme 58) (140L864). Reaction of (4-methoxyphenyl) magnesium iodide in the presence of magnesium chloride and copper(l) chloride with quinoxaline-N-oxide or in diethyl ether afforded... 

This approach for the synthesis of macrocycles with quinoxaline moieties involves the development of methods for the introduction of amino groups to the adjacent carbon atoms of the planned unit of the macrocycle system. Two methods (Crossley et al. 1996a) have been developed for the synthesis of diaminoporphyrin 6. The first involves the reduction of the nitro group to the amino group of the compound 53 with sodium borohydride in the presence of the Pd/C and subsequent regioselective nitration (Scheme 5.13). The second one is the nucleophilic substitution of hydrogen by NaNHCHO and subsequent hydrolysis. Both methods lead to... 

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