Lead tetraacetate, Hofmann rearrangement

Generally yields are good. R can be alkyl or aryl. Modern variants of the Hofmann rearrangement use lead tetraacetate" or iodosobenzene instead of hypo-bromite. 

Treatment of amides with bromine in alkaline medium promotes the Hofmann rearrangement, which may or may not involve a free nitrene intermediate." The oxidation of primary amides with lead tetraacetate and the resulting Lossen rearrangement also produces isocyanates, with the possible intervention of an acylni-... 

Hofmann rearrangements Primary amides are converted into amines in high yield by reaction with this owdant at room temperature in aqueous acetonitrile (equation I). The reaction is rslated to a recent method using lead tetraacetate (6, 316) however, the intermet iate isocyanate in this case is not trapped as the carbamate, but is hydrolyzed alirectly to the amine. 

The oxidative Hofmann rearrangement of primary carboxamides occurs by use of lead tetraacetate (LTA) and several hypervalent organoiodine compounds IF5 (28), PhI(OCOCP3)2 (29), PhI(OH)OTs (30) and PhIO (31) under mildly acidic conditions. 

The enantioselective total synthesis of (-)-epibatidine was accomplished in the laboratory of D.A. Evans." The key steps in the synthetic sequence included a hetero Diels-Alder reaction and a modified Hofmann rearrangement. The primary carboxamide was subjected to lead tetraacetate in fert-butyl alcohol that brought about the rearrangement and gave the corresponding A/-Boc protected primary amine in good yield. A few more steps from this intermediate led to the completion of the total synthesis. 

Simons, S. S., Jr. Lead tetraacetate and pyridine. New, miid conditions for a Hofmann-iike rearrangement. New synthesis of 2-oxazoiidinones. J. Org. Chem. 1973, 38, 414-416. 

Oxidative rearrangement. A reaction related to the Hofmann rearrangement of N-hromoamides occurs on oxidation of an aromatic amide with lead tetraacetate lo give the isocyanate or a derived product in moderate to excellent yield. Simple aliphatic amides react rapidly in dimethylformamide containing triethylamine. 

Rearrangement of amides. Primary amides undergo oxidative rearrangement to isocyanates when treated with lead tetraacetate. The reaction is generally carried out in an alcohol (t-butanol generally), in which case the product is isolated as the carbamate. Triethylamine or stannic chloride catalyzes this reaction. This oxidation provides a useful alternative to the classical Hofmann, Schmidt, and Curtius rearrangements. 

Carbamates are also formed by one-stage, two-step processes involving isocyanates as intermediates and precursors. Thus, carbamates are prepared under modified Hofmann rearrangement conditions, using NBS/NaOMe as the reagent [443], by Curtius rearrangement of the acyl azide if the reaction is carried out in alcohol, by the reaction of amides with lead tetraacetate [444], or by the Lossen rearrangement, if the carbamates are not sensitive to the presence of base. 

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