Isocarbostyrils. I. Electrophilic Substitution Reactions

Abstract

The electrophilic substitution of N-alkylated isocarbostyrils was examined in considerable detail. Bromination, acylation, nitration, and acid-catalyzed condensation with formaldehyde occurred exclusively at C-4 under relatively mild conditions. The acylation of isocarbostyrils has heretofore not been reported.The bromination of 2-methyl-5-nitroisocarbostyril in aqueous acetic acid gave 2-methyl-3,4-dihydro-3-hydroxy-4-bromo-5-nitroisocarbostyril (7) of unknown stereochemistry, as the sole product. When heated above its melting point, 7 lost the elements of water to give the "normal" product of bromination 8.In aqueous acetic acid, excess bromine was shown to convert isocarbostyrils to the corresponding 3,4-dihydro-3-hydroxy-4,4-dibromo derivatives whose structures were supported by spectral and degradative evidence.

Isocarbostyrils. II. The Conversion of 2-Methyl-4-acyl-5-nitroisocarbostyrils to 2-Substituted Indole-4-carboxylic Acids

“…120") was prepared in 85-95% yield by the alkaline ferricyanide oxidation of 2-methyl-5-nitroisoquinolinium iodide (see ref. 9).…”

“…1-3, for example). In the preceding paper (9), it was reported that N-alkylisocarbostyrils were readily acylated at the 4-position. This was an important observation, since it was apparent to us that 2-methyl-5-nitroisocarbostyril (2) was a potential source of 4-carbonyl indoles if acylation could be effected at C-4.…”

“…9. observation is that Vilsmeier-Haack complexes may ZTo whom inquiries concerning this paper should be have greater steric requirements than solvated acylium addressed.…”

Novel Diels-Alder Reaction of 4-Nitro-1(2H)-isoquinolones

“…Substitution reactions 1,2) of 1(2H)-isoquinolone derivatives have been reported, however, little attention has been focused on addition reactions. Dyke et al reported a Diels-Alder (DA) reaction of 2-methyl-1(2H)-isoquinolone derivatives as the diene.…”

“…DA Reaction of 4-Nitro-1(2H)-isoquinolones First, DA reactions of 2-methyl-(1a) 9) and 2-unsubstituted-1(2H)-isoquinolones (1b) 9) bearing a nitro group at the 4-position with 1-methoxy-1,3-butadienes (2a-c) were examined under atmospheric pressure conditions, as shown in Table 1 (entries [1][2][3][4][5][6][7][8] and Chart 1. Reaction of 1a with 1-methoxy-1,3-butadiene (2a) gave the 6-methyl-5(6H)-phenanthridone (4a 10) : 59%; entry 1 and 26%; entry 2) at 180°C for 3 d in 1,2-dimethoxyethane (DME) and o-xylene (pathway A).…”