S 44. The synthesis of thyroxine and related substances. Part III. The synthesis of thyroxine from 2 : 6-dinitrodiphenyl ethers

Aromatic Nucleophilic Substitution Reactions.

“…The N-(2,4-dinitrophenyl)pyridinium ion, which may be formed by the action of pyridine on l-chloro-2,4-dinitrobenzene, 2,4-dinitrophenyl p-toluenesulfonate, or 2,4,2',4'-tetranitrodiphenyl ether, reacts with phenoxides to form 2,4dinitrophenyl aryl ethers (73). A reaction of this sort constitutes an essential step in a recent synthesis of thyroxine in relatively high yield (72). Chloride ion may also effect replacement of ammonio groups; the action of hydrochloric acid on (6-methyl-2,4-dinitrophenyl)pyridinium p-toluenesulfonate gives 1-chloro-6-methyl-2,4-dinitrobenzene (78).…”

REACTIONS OF THE IODOMETAMECONINES1

“…(1). (6). Two further instances of the catalytic dehalogenation of the aryl halide by the copper catalyst were noted, (a) 7-iodometameconine and the copper salt of methyl p-hydroxybenzoate, heated together with copper bronze under nitrogen at 200-210°for 4 hours, gave metameconine, identified by m.p.…”

Amination by Reduction

“…The reduction of 3-nitroso-2-phenyl-l-ethylindole in ethanol with platinum oxide to give the 3-amino compound has been described (89). Borrows et al (5) have found that catalytic hydrogenation of 5-[3,5-dinitro-4-(p-hydroxyphenoxy )benzyl Jhydantoin in acetic acid using palladium on charcoal gives the corresponding diamine in 70% yield. Weisblat and Lyttle (SB) have reported that the reduction of ethyl <*-nitro-/3- (3-indole) propionate over Raney nickel at 100°C.…”

“…A contact time of 0.5 second is used with a temperature of 820°F. Two moles of ammonia are used with each mole of alcohol (5).…”