E. V. Kabanova

Synthesis and isomerization recyclization of pyrazino[1,2-α]indoles

A method for synthesis of pyrazinol[1,2-a]indoles with alkyl substituents in position 1 was developed based on indole and isomerization recyclization of their quaternary salts into 9-aminopyrido[1,2-a]indole derivatives was conducted.

Recyclization of pyrrolo[1,2-a]pyrazinium salts into 6- and 8-aminoindolizines

Recyclization of 3-alkylpyrrolo[1,2-a]pyrazinium salts in the presence of base afforded derivatives of 6-aminoindolizine. Rearrangement of 1,3-dialkylpyrrolo[1,2-a]pyrazinium salts proceeded in two directions, giving rise to both 6- and 8-aminoindolizines, though the latter predominated in terms of yield. In the absence of alkyl substituents at positions 1 and 3 the pyrazine ring was cleaved on treatment with base, yielding derivatives of 2-acylpyrrole.

Acylation of 3,4-Dihydropyrrolo[1,2-a]pyrazines

The direction of trifluoroacetylation with trifluoroacetic anhydride of 3,4-dihydropyrrolo[1,2-a]pyrazines containing an alkyl or aralkyl substituent in position 1 depends on both the structure of the 3,4-dihydropyrrolo[1,2-a]pyrazine starting materials and on the ratio of reagent:substrate. It may lead to both mono- and disubstituted products. Trifluoroacetylation of 1-methyl-3,4-dihydropyrrolo[1,2-a]pyrazines occurs at the methyl group. Acetylation of 3,4-dihydropyrrolo[1,2-a]pyrazines leads only to N-acetyl-substituted reaction products.

Reamination in the recyclization of pyrrolo-[1,2-a]pyrazine salts into 6- and 8-aminoindolizines. General process scheme

Rearrangement of the methyl iodides of 1- and 3-alkyl-substituted pyrrolo[1,2-a]pyrazines in the presence of various alkylamines afforded a mixture of 8- and 6-aminoindolizines, respectively, with and without exchange of the methylamine fragment. The ratio of the products of direct and exchange recyclization was dictated by the size of the N-alkyl substituents in the reagent and starting salt. Rearrangement of the 1-alkylpyrrolo[1,2-a]pyrazinium salts proceeded via the breaking of the C(3) -N(2) bond, and rearrangement of the 3-alkylpyrrolo-[1,2-a]pyrazinium salts via the breaking of the C(1) -N(2) bond.

Synthesis and properties of pyrrolo[1,2-a]pyrazines (review)

The synthesis and properties of pyrrolo[1,2-a]pyrazines are reviewed.

Conversion of pyrrolo[1,2-α]pyrazinium salts to 8-aminoindolizines

The recyclization of pyrrolo[1,2-a]pyrazinium salts under the influence of a base leads to 8-aminoindolizine derivatives and is a new method for the synthesis of indolizines, as well as the first example of the Kost—Sagitullin rearrangement in the pyrazine series.