Degradation s. a. Hofmann

Degradation (s. a. Aromatiza-tion, degradative, Hofmann degradation)... 

Hofmann degradation of isocodeine follows the same course as the degradation of codeine, giving in the first step y-codeimethine the C-6 epimer of [xxi], which can be isomerized to S-codeimethine, the C-6 epimer of [xxn], and in the second step methylmorphenol [xxrv] [252, 410] (see Chap. VI). Dihydroisocodeine can be degraded to a methine base and a nitrogen-free substance [295]. 

This compound undergoes rearrangement to 6-O-demethylsalutaridine (139) in the presence of Claisen s alkali.147 The product has been correlated with salutari-dine and a mechanism involving SN2 attack by base on the allylic bromide function to form the intermediate (140 X = OH) has been proposed. Compound (139) has also been obtained independently by treatment of 7-bromoneopinone (140 X = Br) perchlorate with sodium acetate-acetic acid and several pertinent mechanistic observations on this reaction have been presented.149 Attempts to prepare the proposed intermediate (140 X = OH) from (140 X = Br) perchlorate by treatment with aqueous silver nitrate at room temperature gave no reaction, while under reflux a quantitative yield of (139) perchlorate was obtained. Compound (140 X = Br) perchlorate was stable to base in the cold while at reflux temperature a Hofmann degradation product was obtained.150 It is interesting to... 

B. M. Willie, R. D. Bloebaum, S. Ashrafi, C. Dearden, T. Steffensen, and A. A. Hofmann. Oxidative degradation in highly cross-linked and conventional polyethylene after 2 years of real-time shelf aging. Biomaterials 27 (10), 2275-2284 (2006). 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

Pyridine (and quinoline) which in so many respects are aromatic and comparable to benzene, lose this character completely on hydrogenation to piperidine (and hydroquinoline), which are entirely of the same nature as secondary aliphatic amines. The completely hydrogenated heterocyclic bases undergo degradation reactions which have become important particularly in the investigation of the constitution of alkaloids. A. W. Hofmann s method of opening rings by means of exhaustive methylation may be illustrated with piperidine. By thermal decomposition of the quaternary ammonium base a C—N-link-age is broken and at the same time water is eliminated. 

The preparation of a chiral bicyclic hydrazine, (15,35,5S)-2-amino-3-methoxymethyl-2-azabi-cyclo[3.3.0]octane (SAMBO, 3), was reported32 in 1990. (12 S, 31 S,51 5 )-2-Azabicyclo[3.3.0]-octane-3-carboxylic acid was resolved into its enantiomers. The (lS ,35,55)-enantiomer was converted to the chiral hydrazine 3 in six steps, utilizing Hofmann degradation, which is also employed in the preparation of SAMP. 

The Hofmann degradation of echitinolide methiodide is one aspect of the chemistry of echitamine which has not been explained entirely satisfactorily. The production of two methine bases, the amorphous Hofmann base A and the isomeric base B, mp 182°-187°, was earlier used as an argument against Conroy s structure for echitamine. The structures of base A and base B, and the precise nature of the conversion... 

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