The synthesis of annulated pyridazines by cycloaddition of azodicarboxylates to vinyl heterocycles

Abstract

Reaction between 2-vinyl pyridine and azodicarboxylates 2 or 5 gives N,N'-disubstituted tetrahydropyrido[3,2-c]pyridazines 3 and 6, and dihydro-3 H-pyrido[1,2-c]triazines 4 and 7; 2-(prop-1-en-1-yl)-pyridine 8 gives hydropyridopyridazines 10 and 11 but 2-(prop-1-en-2-yl)pyridine 9 gives mainly the ‘ene’ addition product 12. From 4-vinyl-pyridine and esters 2 or 5 diesters of tetrahydropyrido[3,4-c]pyridazine-1,2-dicarboxylic acid, 25 and 26 are obtained, and from 2-methyl-5-vinylpyridine both possible cyclisation products, the tetrahydro-pyrido[2,3-c]pyridazines 33 and 36, and -pyrido[4,3-c]pyridazines 34 and 37. The di- t-butyl esters 6, 11, 26, and 37 are quantitatively decarbalkoxylated in TFA, giving tetrahydropyridopyridazines 16, 18, 27, and 41; of these, the first three were oxidized to give pyrido[2,3-c]-pyridazine 15, its 3-methyl derivative 19, and pyrido[3,4-c]pyridazine 28 respectively. A dihydropyrido[4,3-c]-pyridazine 42 was obtained from compound 41. Thieno[2,3-c]-pyridazine 48 has been similarly prepared from 2-vinylthiophen, but 2-(prop-1-en-2-yl)thiophen gave an ene addition compound 51 and a dihydrothienopyridazine 50. Reactions with other vinylpyridines, and with vinylfurans, were unsuccessful.