Hofmann rearrangement | EPFL Graph Search

The Hofmann rearrangement (Hofmann degradation) is the organic reaction of a primary amide to a primary amine with one less carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to give an isocyanate intermediate. The reaction can form a wide range of products, including alkyl and aryl amines. The reaction is named after its discoverer, August Wilhelm von Hofmann, and should not be confused with the Hofmann elimination, another name reaction for which he is eponymous. The reaction of bromine with sodium hydroxide forms sodium hypobromite in situ, which transforms the primary amide into an intermediate isocyanate. The formation of an intermediate nitrene is not possible because it implies also the formation of a hydroxamic acid as a byproduct, which has never been observed. The intermediate isocyanate is hydrolyzed to a primary amine, giving off carbon dioxide. Base abstracts an acidic N-H proton, yielding an anion. The anion reacts with bromine in an α-substitution reaction to give an N-bromoamide. Base abstraction of the remaining amide proton gives a bromoamide anion. The bromoamide anion rearranges as the R group attached to the carbonyl carbon migrates to nitrogen at the same time the bromide ion leaves, giving an isocyanate. The isocyanate adds water in a nucleophilic addition step to yield a carbamic acid (aka urethane). The carbamic acid spontaneously loses CO2, yielding the amine product. Several reagents can be substituted for bromine. Sodium hypochlorite, lead tetraacetate, N-bromosuccinimide, and (bis(trifluoroacetoxy)iodo)benzene can affect a Hofmann rearrangement. The intermediate isocyanate can be trapped with various nucleophiles to form stable carbamates or other products rather than undergoing decarboxylation. In the following example, the intermediate isocyanate is trapped by methanol. In a similar fashion, the intermediate isocyanate can be trapped by tert-butyl alcohol, yielding the tert-butoxycarbonyl (Boc)-protected amine.

Sustainable, recyclable and biodegradable castor oil-derived elastomers enabled by dynamic acetoacetyl formed amides

Youwei Ma, Zhiyong Liu

Developing sustainable, recyclable, and biodegradable elastomers with the mechanical properties comparable to commercial polymers presents a formidable challenge. To this end, we synthesize a kind of mechanically robust elastomers cross -linked by acetoace ...

Elsevier Science Sa2024

Enantioselective Total Synthesis of (+)-Stephadiamine

Qian Wang, Jieping Zhu, Baochao Yang, Guang Li

An asymmetric synthesis of (+)-stephadiamine has been accomplished featuring (a) an enantioselective dearomatizative Michael addition to generate a quaternary stereocenter; (b) a domino sequence involving reductive generation of nitrone from γ-nitro ketone ...

2023

Degradation study of a reversible solid oxide cell (rSOC) short stack using distribution of relaxation times (DRT) analysis

Jan Van Herle, Stefan Diethelm, Philippe Aubin, Suhas Nuggehalli Sampathkumar, Maria del Mar Perez Fortes

Reversible solid oxide cells (rSOC) can convert excess electricity to valuable fuels in electrolysis cell mode (SOEC) and reverse the reaction in fuel cell mode (SOFC). In this work, a five - cell rSOC short stack, integrating fuel electrode (Ni-YSZ) suppo ...

PERGAMON-ELSEVIER SCIENCE LTD2022