Hofmann elimination degradation

Uleine methiodide underwent a facile Hofmann degradation to give an optically inactive compound (CCXLVIII), which retained the two nitrogen atoms and had carbazole UV-absorption. A further Hofmann degradation eliminated Nb and gave a product (CCXLIX) with somewhat extended carbazole absorption, which underwent ready catalytic reduction with saturation of one double bond to give a substituted... 

A second exhaustive methylation and Hofmann degradation eliminates the nitrogen of a-methyltropidine as trimethylamine. These last two reactions demonstrate that the tertiary nitrogen of tropidine (and hence of tropine)... 

Exhaustive methylation of a-methyltropidine followed by a Hofmann degradation eliminates the nitrogen as trimethylamine and the low boiling cycloheptatriene (tropilidene) was isolated in good yield (22,121). Tropane may be converted through the intermediate methyltropane to A -cyclo-heptadiene (hydrotropilidene) by a similar process. In the conversion of methyltropane methohydroxide to cycloheptadiene (139), 20% of the methyltropane is reformed by the loss of methanol, a side reaction which occurs in most Hofmann degradations to a greater or lesser extent. Cycloheptatriene and cycloheptadiene have been reduced to cycloheptane (194) which in turn has been oxidized (nitric acid) to pimelic acid. 

Hoechst slurry process Hoeppler viscometer Hoffman degradation Hoffman eliminations Hofmann degradation... 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

Base-catalysed quaternary ammonium salts give alkenes and 3° amines. This reaction is known as Hofmann elimination or Hofmann degradation. Amines can readily be converted to quaternary ammonium salt by the treatment of excess primary alkyl halides, and then Ag20 and H2O. Quaternary ammonium salts undergo E2 elimination, when heated with NaOH to give alkenes and tertiary amines. Thermal decomposition of a quaternary ammonium salt by NaOH to an alkene is known as Hofmann elimination. 

In 1882 Hofmann discovered that when amides are treated with bromine in basic solution, they are converted to amines with one carbon less than the starting amide.180 He also isolated the N-bromo amine (114) and the isocyanate (115) as intermediates on the reaction path. The mechanism in Equation 6.56 accounts for the products and the intermediates. This reaction (or the analogous rearrangement of the N-chloro amine) is now known as the Hofmann rearrangement or, because of its synthetic usefulness in eliminating a carbon atom, the Hofmann degradation. 

Sometimes referred to as the Hofmann Degradation. This elimination reaction of alkyl trimethyl amines proceeds with anti-stereochemistry, and is generally suitable for producing alkenes with one or two substituents. The reaction follows the Hofmann Rule. 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

This and other evidence (16) indicated that eseretholemethine (VI R = C2H5) was a pseudo base or carbinol amine. Thus, on oxidation with silver nitrate an oxindole was obtained (dehydroeseretholemethine, VII R = C2H5), which on subsequent Hofmann degradation and reduction of the Hofmann elimination product gave 5-ethoxy-l,3-dimethyl-3-ethyloxindole (13). The methyl homolog (VII R = CHa),... 

Roe and Gates attempted to apply the Hofmann degradation to Aa-methylnorgelsemine carbinol methohydroxide (XXI), but instead of the expected elimination of formaldehyde (dotted arrows in XXI), an intramolecular displacement occurred, and the only product isolated was the unstable trimethylene oxide derivative (XXII). The latter could not... 

At 140° in methanol, a much more extensive decomposition of akuammicine occurs, and the products isolated are 3-ethylpyridine and 2-hydroxycarbazole (XXXV). The formation of 3-ethylpyridine is presumably the result of a normal Hofmann degradation of the pyri-dinium ester corresponding to XXXIII the other product should consequently have been methyl 3-vinyl-2-indolylacetate (XXXIV), but this was not obtained. It was accordingly suggested that the 2-hydroxycarbazole obtained was formed from XXXIV by intramolecular nucleophilic attack of the vinylogous enamine methylene group on the carbomethoxy group (arrows in XXXIV), followed by elimination of methanol and aromatization (39). 

A number of methods involve the rearrangement of carboxylic acid derivatives via nitrenes. The best known of these is the Hofmann degradation of amides. This involves treating an amide with bromine and alkali. The A-bromo compound undergoes an a-elimination in the presence... 

Hinsberg reaction, 412 Hoffmann, 130 Hofmann degradation, 404 elimination, 413 Huckel s rule, 193, 196 Hund s rule, 14... 

Conversion of acid derivatives into amines with the loss of the carbonyl group can be done in i.-ious ways. In Chapter 40 we recommended either the Curtius rearrangement or the Hofmann tejradation (p. 1073). The Hofmann degradation is easier starting with an ester. We convert into . imide with ammonia and treat with bromine in basic solution. The N-bromo derivative forms a afcene by a-elimination that rearranges to an isocyanate. 

In this reaction two different procedures have been used. The first is the classical Hofmann degradation, which prepares the alkene by thermal decomposition of the quaternary ammonium hydroxide. Hofmann orientation is generally observed in acyclic and Zaitsev orientation in cyclohexyl substrates. The second is the treatment of quaternary ammonium halides with very strong bases, e.g. PhLi, KNH2 in liquid NH3. The formation of the alkene proceeds via an 1 mechanism, which means a syn elimination in contrast to the anti elimination which is observed in most of the classical Hofmann degradations. In some cases this type of elimination can also be accomplished by heating the salt with KOH in polyethylene glycol monomethyl ether. 

The work which conclusively established the structure of thalicberine ((9 -CIV) and 0-methylthalicberine (SS-CY) was reported in 1963 by Tomimatsu and Kano (85). Ozonolysis of the Hofmann elimination product CVII furnished, among other products, the diaminodialdehyde CVIII. Hofmann degradation of the dimethiodide of compound CVIII yielded the divinyl compound CIX, which was converted by catalytic hydrogenation to compound CX. Clemmensen reduction of the latter furnished compound CXI whose structure was established by synthesis. 

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