The synthesis and reactivity of 7-azaindolizines.

Kong Thoo Lin, Paul Vee Siew

Abstract

Synthetic routes leading to 7-azaindolizines and the reactivity of this system together with other azaindolizines have been briefly reviewed. A number of simple alkyl, aryl, carboethoxy, methoxy, chloro and amino substituted 7-azaindolizines have been synthesised via the Chichibabin reaction between suitably substituted methylpyrazines and a-bromoketones. The structures of the products obtained have been confirmed spectroscopically (mainly by pmr spectroscopy) and elemental analysis. Examination of the pmr spectra of 7-azaindolizines in trifluoroacetic acid showed solely protonation at the non-bridgehead nitrogen. Similarly quaternisation was found to occur at the non-bridgehead nitrogen. Lithiation of 8-methyl-7-azaindolizine showed the 8-methyl group of 2,8-dimethy1-7-azaindoilzine to be acidic. Reaction between 2,3,8-trimethyl-7-azaindolizine and ethoxalyl chloride gave a diketodipyrrolo[1 ,2-a:2,1-c]pyrazine system. A number of electrophilic substitution reactions occurred at C-3 position. Nucleophilic replacement of chlorine by methoxide and amino from 8-chloro-2-methyl-7-azaindolizine occurred readily. A number of simple alkyl, aryl, and carboethoxy substituted dipyrrolo[1 ,2-a;2,1-c]pyrazines have been obtained by the Chichibabin reaction between appropriate substituted 8-methyl-7-azaindolizines and a-bromoketones. The structures of these products have been established spectroscopically. An examination of the pmr spectra of dipyrrolo-[1,2-a:2,1-c]pyrazines in trifluoroacetic acid showed this system preferentially protonates at C-3 and C-8 postions. When positions 3 and 8 are substituted the C-3 conjugate acid cation predominates together with minor amounts of the C-1 cation. Dipyrrolo[1,2-a:2,1-c]pyrazines undergo electrophilic substitution preferentially at C-3(C-8) and when 3,8-disubstituted, substitution then occurs at C-1(C-10). A brief survey of reaction between relevant nitrogen heteroaromatics and DMAD has been reviewed. The reaction between 7-azaindolizines and DMAD gave products involving bonding at the non-bridgehead nitrogen and the adjacent C-8 position or 8-substituent.

Citation

KONG THOO LIN, P.V.S. 1986. The synthesis and reactivity of 7-azaindolizines. Robert Gordon's Institute of Technology, PhD thesis. Hosted on OpenAIR [online]. Available from: https://doi.org/10.48526/rgu-wt-1993226

• Thesis Type: Thesis
• Deposit Date: Aug 22, 2024
• Publicly Available Date: Aug 27, 2024
• DOI: https://doi.org/10.48526/rgu-wt-1993226
• Public URL: https://rgu-repository.worktribe.com/output/1993226
• Award Date: Nov 30, 1986