Degradation Hofmann

We have meet NO2 and CN before, but a primary amine can also be made from an amide by the Hofmann degradation (see Norman p.446-7 or Tedder, vol.2, p.281-2). 

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

Subsequent chlorination of the amide takes place ia a two-phase reaction mixture (a dispersion of diamide ia hydrochloric acid) through which a chlorine stream is passed. The temperature of this step must be maintained below 10°C to retard the formation of the product resulting from the Hofmann degradation of amides. Reaction of the A/,A/-dichloroamide with diethylamine [109-89-7] ia the presence of base yields /n j -l,4-cyclohexane-bis-l,3-diethylurea (35), which is transformed to the urea hydrochloride and pyroly2ed to yield the diisocyanate (36). 

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

Pyrimidine-5-carboxamide, 4-amino-purine synthesis from, 5, 582 Pyrimidine-5-carboxamide, 4-amino- N- pheny synthesis, 3, 122 Pyrimidinecarboxamides Curtius degradation, 3, 82 dehydration, 3, 82 Hofmann degradation, 3, 82 hydrolysis, 3, 81 reactions, 3, 81 synthesis, 3, 127 Pyrimidinecarboxamides, thio-synthesis, 3, 128... 

Synthesis of lower homolog aldehydes from o,0-unsaturated carboxamides (via Hofmann degradation)... 

Putrescine dihydrochloride has been prepared by the Hofmann degradation of adipamide 3.. s by the Curtius degradation of adipyl hydrazide through the urethane by the Curtius degradation of adipyl azide obtained from adipyl chloride and sodium azide by the Schmidt degradation of adipic acid with hydrogen azide by the reduction of succinonitrile, succinaldoxime, or 7-phthalimidobutyronitrile with sodium and from N-ben-zoyl-7-iodobutylamine ... 

Later Goto and Shishido prepared di-3-ethoxy-5 6-dimethoxy-A -ethylnoraporphine ethiodide, m.p. 186-7°, and this, by the Hofmann degradation process, gave the ethiodide of the de-At-ethyl base, m.p. 194°, from which the dimethoxyethoxyvinylphenanthrene, m.p. 108°, was obtained, identical with that from natural Z-tuduranine. The latter is therefore 3-hydroxy-5 6-dimethoxy-A -H0)aporphine. A later paper (1941) also relating to tuduranine is not yet accessible. 

Unlike most alkaloids of the group, glaueine was assigned a formula without the use of the Hofmann degradation process, but since then this process has been applied to glaueine or its derivatives by a number of workers, especially in connection with the investigation of boldine (p. 325) and of laurotetanine (p. 320). 

A-methylanonaine, prepared from the natural alkaloid by the action of formaldehyde and formic acid, was isolated as the hydriodide, m.p. 246-7° (dec.). dZ-A-methylanonaine was also synthesised and characterised as the hydriodide, m.p. 244° (dec.), and methiodide, m.p. 210-1°. It is regarded as identical with dZ-rcemerine (p. 314), and it may be noted that the melting-point of the Hofmann degradation product of rcemerine is very similar to that of anonaine (IV NMe NH) (Barger and Weitnauer). "... 

IV-Methyllaurotetaninc, C20H23O4N. This alkaloid was obtained by Spath and Suominen from Litsea citrata. It distils at 205-15° (air-bath temperature) urder a pressure of 0-01 mm. and is dextro-rotatory. Diazomethane converts it into glaucine and Hofmann degradation of the ethyl ether yields 3 5 6-trimethoxy-2-ethoxy-8-vinylphenanthrene, m.p. 140-1°, identical with that obtained from laurotetanine (see above). The alkaloid is therefore represented by formula II (NMe replacing NH). 

Phaeanthine, C3JH42O0N2. (Item 8 list, p. 350.) This alkaloid was isolated by Santos.It has m.p. 210°, [a]u°° — 278° (CHCI3), yields a hydriodide, m.p. 268°, picrate, m.p. 263°, aurichloride, m.p. 170-1°, and a platinichloride, m.p. 280° (dec.), and contains four methoxyl and two methylimino groups. By the Hofmann degradation process it yields an optically inactive methine base A, m.p. 173°, which is oxidised by potassium permanganate in acetone to 2-methoxy-5 4 -dicarboxydiphenyl ether (p. 348). A comparison of the properties of phseanthine and tetrandrine by Kondo and Keimatsu indicates that these two alkaloids are optical antipodes, so that phseanthine will be represented by either (XXXIX) or (XL) as given on p. 348, 1 and of these two formula (R = Me) one must represent oxyacanthine methyl ether and the other berbamine methyl ether (centres of asymmetry d- and 1-) tetrandrine (centres of asymmetry both d-) and phseanthine (centres of asymmetry both 1-). 

Ahl and Reichstein have pointed out that though it is certain that the structure of emetine includes one, and possibly two, 6 7-dimethoxy-tetrahydroisoquinoline nuclei, the suggestions so far made as to the nature of the rest of the molecule are speculative. They investigated the Hofmann degradation of A-acetylemetine, m.p. 97-9°. This forms a monomethiodide, m.p. 2ia-6°, from which, by the action of silver oxide and potassium hydroxide, followed by eautious tbermal deeomposition and reacetylation,... 

A similar Hofmann degradation of dihydrobrucidine, ending in desaza-brucidine, C23H27O3N, m.p. 133-4°, has been described. 

Hofmann degradation of l,l-dimethyl-2-methylenepyrrolidinium hydroxide furnishes dimethylamine and dimethyl-3-pentynylamine 198). 1,1,4,4-Tetramethyltetrahydropyridinium hydroxide was obtained from l-dimethylamino-4,5-dibromopentane by means of silver oxide. Hofmann degradation of the product gives I,4,4-trimethyl-/j -tetrahydropyridine 199). 

An attempt at Hofmann degradation of 4-carboxamidobenzo-furoxan failed to give any 4-amino compound. - Nitro groups appear to stabilize aminobenzofuroxans. however 4-amino-5-nitro, 5-anilino-6-nitro- and several substituted 4-ammo-7-nitro- and 5-amino-4-mtrobenzofuroxans have been isolated. 

---