Facile 5-endo ring closures to the azo group. A free radical synthesis of indazoles

Abstract

Five 1-alkyl-3-methylindazoles were prepared by treatment of l-(2-bromophenyl)-l-methoxy-l-(2-alkylazo)ethanes with tri-n-butyl stannane and AIBN at 80°C in benzene. Yields in the radical cyclization step ranged from 39 to 92%. 1-Phenyl-3-methylindazole was prepared by an analogous route but in very poor yield (<5%). Rate constants for the 5-endo radical closures ( k: O: : ) , estimated by the radical clock method, were 5.2 X 10's-' and 9.2 X 10's-' for two of the alkyl systems. Rate constants for analogous 5-endo cyclizations of aryl radicals onto C-C double bonds are much smaller than those for cyclizations to the azo functional group.

Hydrazone initiators for vinyl polymerizations

“…Hydrazone 1 14, 15 was prepared by general method A. The reaction solution was heated to reflux for 8 h. After workup and concentration, a yellow oil was obtained, which was distilled under reduced pressure.…”

“…The material was allowed to stir at ambient temperature overnight. The isolated acetophenone, phenyl hydrazone ( 11 )14 solids were isolated by suction filtration, and the filtercake was washed with both water and hexanes. The yield was 52% of off‐white solids.…”

5-Endo-Trig Radical Cyclizations

“…Treatment of aryl bromide 277 with Bu 3 SnH/AIBN produced aryl radical 278, which underwent 5-endo-trig cy- clization onto an N=N bond followed by an elimination of methanol from 280 to give indazole 281 in 70% yield (Scheme 88). 79 The possibility of the formation of 279 by a consecutive 4-exo cyclization of 278 and neophyl-type rearrangement of the resulting radical 282 cannot be ruled out, however no compound derived from 282 was detected by 1 H NMR spectroscopy of the reaction mixture.…”

Nitrogen-Centered Radical Scavengers

“…49 With a shorter (i.e., one-carbon) spacer between the aryl group and the azo moiety such as in 121, the radical cyclization of 122 must occur by way of either the 4-exo or the 5-endo mode (Scheme 30). 50 For dialkyl azo compounds 121 (R = alkyl), the 5-endo cyclization to 123 appears to be clearly favored since good to high yields of 1-alkylindazoles 124 were obtained from the reaction involving an elimination of methanol from 125 as final step. For alkylaryl azo compounds 121 (R = aryl), only trace amounts of product 124 could be isolated.…”