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Synthesis of sulfur and selenium heterocycles, including derivatives of imidazopyridine and benzimidazole

thesis
posted on 2024-09-02, 22:41 authored by Malin Björk

The chemistry developed in this thesis can be divided into two parts. The first part, which is the major part of the thesis, contains syntheses towards analogues to mutagenic heterocyclic amines found in e.g. meat fried at high temperatures. The second part concentrates on the palladium-(0)catalyzed cross-coupling reactions of 4- and 5-substituted 2,1,3-benzoselenadiazoles.

The heterocyclic amines described can be divided into the linear and the angular compounds. Five linear imidazo[4,5-b]pyridines were synthesised via the Friedländer reaction: 2-amino-1 - methylbenzothieno[2,3-e]imidazo[4,5-b]pyridine, 2-amino-1-methy-benzothieno [3,2-e] imidazo[4,5-b] pyridine, 2-amino-1-methylthieno[2,3-elimidazo[4,5-b]-pyridine, 2-amino-1methylthieno[3,2-e]imidazo[4,5-b]pyridine and the sulfur analogue to the cooked-food mutagen IFP, 2-amino- 1,6-dimethylthieno[2,3-e]imidazo[4,5-b]pyridine.

Attempts were made to form three thienoimidazo[4,5-b]pyridines via stepwise condensation. The first condensation between creatinine and 2-nitro-3-thiophene-carbaldehyde, 3-amino-2thiophenecarbaldehyde and 4-azido3-thiophenecarbaldehyde yielded thenylidenomethyleneimidazolinones, but only one of these gave the ring closed compound 2-amino-1-methylthieno[2,3-e]imidazo[4,5-b]pyridine by a second condensation. In addition, 2-amino- 1 methyl benzoth ieno[3,2-e] imidazo[4,5 -b] pyridine was transformed into the 2-nitro- and 2-hydroxy derivative. The last linear isomer 2-amino-1methylimidazo[4,5-b]benzothiophene, was synthesized by a different route.

The series of angular compounds are considered analogues to the food-mutagen IQx. A series of six homologues of 7-amino-imidazo[4,5-e]-2,1,3-benzoselenadiazoles. Four ring systems were obtained by treating 4-methylamino-3-nitro-phenylenedianmine with a range of biselectrophiles, namely: 2-amino-1-methylbenzo-thiadiazole, -triazole, -diazepinone and 2amino1-methylimidazobenzimidazole.

Among the palladium-(0)-catalyzed cros s- couplings, the Suzuki, Stille, Fleck and Sonogashira reactions were used. These were applied to 4-, or 5-bromo-2,1,3-benzoselenadiazoles. In addition, the 4- and 5-trimethyltin-2,1,3-benzoselenadiazole were synthesized.

List of scientific papers

I. Bjork M, Grivas S (2005). Synthesis of novel 2-aminoimidazo[4,5-b]pyridines, including the thieno analogue of the cooked-food mutagen IFP. J Heterocycl Chem. [Accepted]

II. Bjork M, Grivas S (2005). Synthesis of thienoimidazo[4,5-b]pyridenes and thienylidinoimidazolinones. Heterocycles. 65: 2369.

III. Bjork M, Grivas S (2005). Synthesis of imidazo[4,5-e]-2,1,3-benzoselenadiazoles and derivatives thereof. [Manuscript]

IV. Bjork M, Grivas S (2005). Classical conditions of Suzuki, Stille, Heck and Sonogashira couplings applied on 4- and 5-substituted 2,1,3-benzoselenadiazoles. [Manuscript]

History

Defence date

2005-12-15

Department

  • Department of Medicine, Huddinge

Publication year

2005

Thesis type

  • Doctoral thesis

ISBN-10

91-7140-597-6

Number of supporting papers

4

Language

  • eng

Original publication date

2005-11-24

Author name in thesis

Björk, Malin

Original department name

Biosciences and Nutrition

Place of publication

Stockholm

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