Hofmann and Emde Degradations

The Hofmann and Emde degradation of tetrahydro-j8-carboline derivatives has been reported in a number of instances, but only in one... 

Several syntheses of secoquettamines have been performed. Seco compounds 234 and 235 were semisynthesized from quettamine (236) by Hofmann and Emde degradations, respectively (179). Chattopadhyay and Shamma (184) conducted a total synthesis of these bases with the intermediacy of quettamine (236) (Scheme 36). In this approach Reissert compound 237 served as substrate. On reaction with 4-benzyloxybenzaldehyde 237 supplied the addition product 238, which after N-methylation and sodium borohydride reduction afforded amino carbinol 239. Compound 239 was cyclized to... 

Tetramethoxydehydrolaudanosoline iodide (14), now named 0-methylcryp-taustoline iodide, was used in Hofmann and Emde degradations (Scheme 3). The... 

The Hofmann and Emde degradations led to many interesting transformations, none of which, however, helped to shed light on the structural problem. 

More recently Bertho (95) has given an exhaustive review of the researches on the structure of conessine and suggested formula XVI. Spath and Hromatka (96) had already degraded conessine by a combination of Hofmann and Emde degradations to a hydrocarbon, C21H30 (m.p. 74°), which had three double bonds and was reducible to C21H36 (m.p. 56-58°) but which they did not identify. The nature of this hydrocarbon was... 

EMDE DEGRADATION. Modification of the Hofmann degradation method for reductive cleavage of the carbon-nitrogen bond by treatment of an alcoholic or aqueous solution of a quaternary ammonium halide with sodium amalgam. Also used as a catalytic method with palladium and platinum catalysts. The method succeeds with ring compounds not degraded by the Hofmann procedure. 

The application of the Emde degradation conditions (0.1 N KOH/C2H5OH, H2/Pt) to the quaternary curare alkaloid, mavacurine iodide (VIII/94), led to the so-called e2-dihydromavacurine (VIII/95), a tertiary base, Scheme III/18. Protonation (e.g. HC1/H20) or methylation (CH3I) of VIII/95 led to the trans-annular reaction products, VIII/96 and VIII/97, respectively. The quaternary compound, VIII/96, returns to tertiary VIII/95 (reversible Hofmann elimination) in the presence of base or on tic (silica gel) [55]. 

The codeimethines can be esterified [5, 32-34, 14, 16-17, 20, 35-37] and methylated. Methylation can be accomplished by methyl sulphate or methyl iodide and cold 1 N. alkali, when quaternary salts of the methyl ethers are obtained [38-39]. The methyl ethers, however, are best prepared by degradation of the corresponding codeine methyl ethers. In this way a- [39-40], y- [41], and e- [41-42] codeimethine methyl ethers have been prepared, and the first two named can be converted to the /3- and 8-isomers respectively on heating with alcoholic alkali [39, 41]. Emde degradation of codeine methyl ether metho-chloride affords exclusively a-codeimethine methyl ether [43]. Hofmann degradation of the methiodides of /3- [38] and e- [42] codeimethine methyl ethers affords methylmorphenol [xvi, R = Me], ethylene, trimethylamine, and methanol. 

Corydalis ochotensis Turcz. contains, among other alkaloids, the pair ochotensine, C21H21O4N, and ochotensimine [noncrystalline methiodide, mp 225°], the 0-methyl ether of the former. Attempted Hofmann degradation led to insoluble polymeric products but Emde degradation... 

Corynoline and corynoloxine are converted by Emde or Hofmann degradation into the common compound 187, which provides evidence confirming the steric and structural relationship of these two substances (97). 

Von Bruchhausen and Bersch (21, 22) reinterpreted Gadamer s data in conjunction with the later findings of Kling (28) and of Schwarz (29), who subjected chelidonine to Emde and Hofmann degradations. When its methine is oxidized with permanganate there results a mixture of hydrastic acid (II) and a dimethylaminomethylmethylenedioxybenzoic acid. The latter was erroneously formulated by Schwarz, whose formula indicated... 

With strychnine the basic nitrogen although undergoing Hofmann, Emde and von Braun reactions did not furnish compounds suitable for further degradation but these studies generated... 

Neostrychnine. Neither the Hofmann, Emde, or cyanogen bromide reactions have been particularly useful as starting points for systematic degradations of strychnine because of the stereochemistry which is not suitable for eliminations and instead a multiplicity of Sn2 products were usually formed. It was a study of the Hofmann degradation that first led to neostrychnine (Chart 6.4), a double bond isomer (J20,2i Qf strychnine, a compound more readily made by heating strychnine with selenium or Raney... 

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