Studies on Nitrogen-containing Heterocyclic Compounds. XXXIII. Syntheses of 3-Alkoxyisoquinolines and 7-, 8-Substituted-1, 6-naphthyridines from Isoquinoline and 1, 6-Naphthyridine

Abstract

1, 3-Dialkoxy-4-bromo-2-cyano-1, 2, 3, 4-tetrahydroisoquinolines (2ab, 8ab to 11ab) are obtained quantitatively by the addition of cyanogen bromide to isoquinoline (1) dissolved in the corresponding alcohol, followed by application of bromine and saturated sodium carbonate solution. These products are a mixture of stereoisomers with the hydrogen atoms in 3- and 4-positions in cis (main) and trans configuration. Dehydrobromination of the cis-type compounds with potassium cyanide easily gives 3-alkoxyisoquinolines (7, 12-15). Hydrolysis of with conc. hydrochloric acid affords 4-bromoisoquinoline (5a) from cis-type compounds and 4-chloroisoquinoline (5b) from trans-type compounds. It had been difficult to obtain compounds 7 and 12 to 15. 4-Bromo-5-nitroisoquinoline (21) was obtained from 5-nitroisoquinoline (18) by the application of the above reaction but 3-methoxy-5-nitroisoquinoline (22) could not be obtained. Application of this reaction to 1, 6-naphthyridine easily gave 8-bromo-1, 6-naphthyridine (27) and 7-methoxy-1, 6-naphthyridine (28), compounds in which a substituent had been introduced into the 7- and 8-positions that had never been attempted so far.