From Hofmann degradation

The primary evidence for the structure of a-erythroidine had come from Hofmann degradation of the reduction product XV. With one... 

Dihydrodesoxycodeine-D [xm], the only non-phenolic dihydro-desoxycodeine, can be prepared by the catalytic hydrogenation of a-chlorocodide [rv] [29], /3-chlorocodide [v, It = Cl] [7, 29], bromocodide [v, R = Br] [29], and desoxycodeine-C [ix] hydrochloride [6], It has also been reported to be formed by catalytic reduction of codeinone oxime [xlii] hydrochloride [30]. Dihydrodesoxycodeine-D methine [xlhi] results from Hofmann degradation of the methiodide [7], and a substance that is presumably the dihydromethine [xliv] is obtained by catalytic reduction of a-chlorocodeimethine [xlv] [26]. 

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). 

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. 

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). 

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,... 

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). 

At first, acid-catalyzed cyclization of Hofmann degradation products was undertaken however, the cyclization proceeded via the 5-exo-trigonal mode instead of the 6-endo-trigonal mode, resulting in no benzo[c]phenanthridine skeleton. Dyke and Brown (114-117) reinvestigated Perkin s results (118,119) and established the structure of the cyclized products 196 and 197 derived from the methine base 194 (Scheme 36). Onda et al. (120,121) obtained the five-membered spiro compounds 198 and 199 by treatment of 195 with dilute hydrochloric acid. 

Lead tetraacetate oxidation was applied to construct a benzo[c]-phenanthridine skeleton. The Hofmann degradation product 224 derived from the phenolic protoberberine 59a was oxidized with lead tetraacetate to afford the p-quinol acetate 225, which was cyclized to the benzo[c]-... 

Shammaet al. (144-146) utilized Hofmann degradation of 8-benzyltetrahy-droprotoberberine for selective C-8—N bond cleavage (Section II,A,1). Benzylidene products 17 and 271, derived from berberine (15) and coptisine (65), were subjected to Lemieux-Johnson-Pappu oxidation to provide (+)-canadaline (272) and ( )-aobamine (273), respectively, the latter of which was... 

Kametani et al. (37-40) reported an abnormal Hofmann degradation of tetrahydroprotoberberine metho salts which resulted in secoberbines. From a synthetic point of view, however, this method appeared to be of little importance since other degradation products were formed as well. Furthermore, it was applicable only to derivatives with phenolic hydroxy groups at C-9 and/or C-l. 

In the synthesis of methyl corydalate (55) Nonaka et al. (65) used the methiodide of (-t-)-tetrahydrocorysamine (65) as substrate and the Hofmann degradation method for ring opening (Scheme 16). The methine base (66) on hydroboration afforded alcohol 67, identical with a product obtained from 55 by lithium aluminium hydride reduction. 

The enol lactones were synthesized by Hofmann degradation of metho salts of classic phthalideisoquinoline alkaloids. The biogenetically relevant transformations were highly stereospecific. In this way aobamidine (96) was obtained from the methiodide of (erythro) bicuculline (88) (2), and ad-lumidiceine enol lactone (97) was produced from both (threo) isomeric adlumidiceine (89) and capnoidine (90) methiodides (14,15,91-93). (Z)- (98) and ( )-N-methylhydrastine (99) were obtained from / - (91, erythro) and a-N-methylhydrastinium (92, threo) iodides (5,87,91,96-98), respectively, as were (Z)- (101) and (JE)-narceine enol lactones (102) synthesized from a- (94, erythro) and /J-narcotine (95, threo) quaternary N-metho salts (87,90), respectively. In a similar process /J-hydrastine (91) JV-oxide heated in chloroform yielded enol lactone 124 of Z configuration (99) however, a-narcotine (94) N-oxide was transformed to benzoxazocine 125 (99). ... 

Steric hindrances may also be the reason why quaternary salts of 8-alkylnarcotoline (130) were transformed during Hofmann degradation to analogous keto acids (131) (111,112) and not to the enol lactones (Scheme 24). In some cases (5,87) the keto acids and their esters have been synthesized from the corresponding enol lactones by hydration (Section III,A,2). Nornarceine (107) was prepared from JV-benzyl-(—)-a-narcotinium bromide (139, X = Br) by Hofmann degradation followed by N-debenzylation and ester hydrolysis (109). 

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