Zinc-dust distillation

Hi) Dehydrogenation. j3-Carboline derivatives may be obtained from tetrahydro-)3-carbohnes by zinc dust distillation or high temperatmre dehydrogenation with selenium or palladium black. Many of the complex indole alkaloids may be degraded, with bond cleavage, to yield simple )3-carbolines under these conditions and this approach has become a standard method in structural elucidations. Examples are numerous but outside the scope of this review. 

Other procedures include zinc-dust distillation, not generally useful except for exhaustive degradation of phenols to hydrocarbons, and various sodium and liquid ammonia cleavages of phenol ethers.3-7 These latter reactions lack generality and are often unpredictable. They require conditions too harsh for... 

Zinc dust distillation of I yielded the 1- and 2- methylindoles. The milder degradation of eseroline (II) or the ethyl ether (IV) to the Physostigmol verified the presence of the indole nucleus in the original structures. 

Attempts to prepare this hydrocarbon from benzanthrone by the Wolff-Kishner method (formation and hydrolysis of the hydrazone) or its modifications, by Raney nickel reduction, or by zinc-dust distillation were either unsuccessful or gave the desired hydrocarbon in poor yield. The successful reduction using synthesis gas demonstrates further the potentialities of this new hydrogenation procedure in problems of synthetic organic chemistry. 

The UV-spectrum of mitragynine differs notably from the spectra of the other Mitragyna alkaloids. Whereas the absorption of the latter indicate the presence of oxindole nuclei, the spectrum of mitragynine shows a greater resemblance to that of the ajmalicine group of alkaloids (5). The presence of an indole nucleus is also suspected from its color reactions (2) and confirmed by the isolation of indole derivatives (so far unidentified) and 5-methoxy-9-methylharman (I) from the products of zinc dust distillation (6). The identification by synthesis (51) of this degradation product is of some interest, since the alkaloid itself does not apparently contain an iV-methyl group. Moreover, this was the first demonstration of the occurrence of a 4-hydroxyindole derivative in nature. 

The presence of an oxindole nucleus in mitraphylline is established by the results of zinc dust distillation. The basic products include isoquinoline and 3,4-diethylpyridine, while the neutral fraction affords 3-spirocyclopropano-oxindole (IV), mp 179°-181° (55, 56). This degradation product is of the greatest importance in this series of alkaloids it was first obtained from the calcium oxide distillation of rhynchophyllic acid (19), and has since been obtained by zinc dust distillation of uncarine-A (58), by hydrogenation and pyrolysis of uncarine-A methiodide (59), and by zinc dust distillation of formosanine (uncarine-B) (60). The structure of this neutral degradation product was first proposed by Wenkert and Reid (61), who pointed out that its properties were very similar to those... 

Potash fusion of gelsemine gives a mixture of bases, together with an indole derivative (57), later identified as 3-ethylindole (62) since the nitrogen atom in this degradation product is unsubstituted, it is probable that in gelsemine N, carries the methyl group. Zinc dust distillation yields skatole and two bases, which are suspected to be isoquinoline derivatives (62). 

Zinc dust distillation of the indole base A (X) gives comparatively high yields of 3-ethyl-2-methylindole and 3-ethylpyridine. Thus, it is possible to account for all the carbon atoms of X, and the structure of the latter is confirmed, with the exception of the point of attachment of the asterisked carbon atom (C-16) to the piperidine ring (32). 

Zinc dust distillation of the amorphous material obtained when akuammine decomposed in methanol solution gave an indolaceous substance (probably skatole), a volatile base identified as 3-ethyl-pyridine (23), and carbazole (31). Hydrogenation studies were inconclusive, and although evidence for the formation of a dihydro derivative was obtained, this was not fully characterized (23). 

EtOH), were first isolated in 1872 and 1877, respectively (14). Quin-amine was observed to give indole color reactions (7, 15), and 2,3-dimethylindole was a result of zinc dust distillation of the alkaloid (15). With chromic acid (9), the quinuclidine carboxylic acid (III) was obtained, and with nitric acid 3,6,8-trinitro-4-hydroxyquinoline was isolated (15, 16). This quinoline is a consequence of fission of the indole and recyclization, with nitration preceding and following these steps [cf. ozonolysis of yohimbine to furnish a 2,3-disubstituted 4-hydroxy-quinoline (17)]. 

The determination of the structure of quebrachamine (I) followed on that of aspidospermine (II), and was indeed suggested at the time that this latter structure was published (11, 12, 13, 14). In work prior to this, Witkop and his co.-workers were able to show that the two alkaloids were related, since both gave on zinc dust distillation a mixture from which... 

The closure of a bond between positions 12 and 19, presumably involved in the natural synthesis of aspidospermine-type alkaloids from quebrachamine, has been shown (18) to occur during the zinc dust distillation of the latter when a compound IX was isolated whose mass spectrum was exactly comparable with that of the indolenine VII, except for the 30-unit shift in the indole-containing fragments (Table V). Substance IX has subsequently been found in nature (Section II, E). 

The indolenine corresponding to aspidospermidine was also isolated (28,51a). It was denominated Alkaloid 280A [later named 1,2-dehydro-aspidospermidine (51)] and has structure IX. This compound had previously been obtained by the zinc dust distillation of quebrachamine (18, Section II, B) and was subsequently found in R. stricta (51). It is... 

The evidence already presented encompasses all the aliphatic carbon atoms of the alkaloids, the dihydroindole structure of rings A and B resting on UV-, NMR-, and mass spectral data as well as on the production of indole derivatives during the zinc dust distillation and alkali... 

The isolation of 3-ethylpiperidine by the zinc dust distillation of aspidospermatidine and deacetylaspidospermatine made it probable that the m/e 136 peak derived from a piperidine ring incorporated in the aliphatic part of the molecule. An ideal model compound, dihydro-decarbomethoxyakuammicine (CCII, mol. wt. 266) was known (19). Its... 

C-curarine came from zinc dust distillation of norcurarine, which yields 3-methylindole, 3 ethylindole, 3-ethylpyridine, carbazole, and methyl-carbazole (128). 

The A-methyl was fixed on the indoline nitrogen since potassium permanganate oxidation of ajmaline in acetone gave A-methylisat inacetone (34), and soda lime or zinc dust distillation afforded A-methylharman (I). 

It has been reported (111) that permanganate oxidation of deoxytubulo-sine (17) yielded m-hemipinic acid (124), whereas selenium dehydrogenation and zinc dust distillation of 17 and alangimarckine (18) produced harman (125). 

The NMR-spectrum of macrorine shows, besides an iV -methyl group, only aromatically linked protons and the IR-spectrum contains only aromatic bands. Macrorine is stable to zinc dust distillation and to alkali fusion. With hydrogen and platinic oxide it gives a tetrahydro derivative which contains an NH group and has a UV-spectrum resembling that of l,2,3,4-tetrahydroquinoline-2-carboxyamide NMR-spectroscopy also suggests a 1,2,3,4-tetrahydroquinoline structure. 

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