Reaction Zinc Dust Distillation

REACTION ZINC DUST DISTILLATION Example Anthracene from Alizarin or Quinizarin 

The sublimed anthracene is dissolved by heating in a test-tube with a little glacial acetic cid it is treated with about double its weight of chromic anhydride, and heated a short time to boiling. The solution is then diluted with several times its volume of water, the anthraquinone separating out is filtered off, washed with some dilute sulphuric acid, then with water, and is finally crystallised in a test-tube from a little glacial acetic acid. Long colourless needles of anthraquinone, which melt at 2770, are thus obtained. 

1 As described under Carbon Monoxide, the test may also be made by filling a test-tube with the gas over water, and applying a match to the mouth of the tube. 

Zinc dust is, especially at high temperatures, an excellent reducing agent (Baeyer, A. 140, 295), which can be used for the reduction of almost all aromatic oxygen compounds derived from hydrocarbons, e.g.  

Also ketone-oxygen, as the above example shows, can be replaced by hydrogen. The reaction given under Alizarin possesses an historical interest, since, by means of it, Grabe and Liebermann, in 1S68, discovered that alizarin, which had been previously obtained from madder root, was a derivative of anthracene, and could be prepared synthetically from it. (B. 1, 43.) 

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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... 

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. 

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)]. 

Structure CXXXVTI is compatible with several miscellaneous reactions and properties of tazettine. It accounts for the production of phenanthridine derivatives by zinc dust distillation (128a) and Oppen-auer oxidation (55) more satisfactorily than CXXXII. The double bond of tazettine is sufficiently removed from the nitrogen atom to have no effect on the basicity of the alkaloid. The allylic methyl ether may be cleaved with hydrochloric acid to a mixture of two epimeric allylic alcohols, tazettinol (CLI) and isotazettinol (CLII). Methylation of tazettinol afforded 0-methyltazettine methiodide, identical with that obtained by the methylation of tazettine. Under similar conditions, isotazettinol afforded the epimeric 0-methylisotazettine methiodide. Both methiodides gave 2-(4-methoxyphenyl)-4,5-methylenedioxyben-... 

The last two in a later publication were shown to yield mellophanic acid on appropriate oxidation reactions and were therefore regarded as being aporphines. Zinc dust distillation of some of their derivatives yielded phenanthrene. 

Kirby showed that quinamine and the substances derived from it gave indole color reactions, and isolated 2,3-dimethylindole from zinc dust distillation of the alkaloid (252). Henry, Kirby, and Shaw oxidized quinamine with chromic acid, and obtained the quinuclidine acid (CCVII) (253). It was thus clear that quinamine contained the vinylquinuclidine system of the major cinchona alkaloids, attached to an easily oxidizable residue, CioHioO (c/. Section V, 1). Decisive clarification of the character of the residue was achieved, and quinamine was shown to have the structure CCXIII, when Goutarel, Janot, Prelog, and Taylor found (248) that quinamine is reduced to cinchonamine (OCX) by lithium... 

ZINC-DUST DISTILLATION. The products of this reaction, during which the mixture was heated to 360 , and then subsequently reduced catalytically in acetic acid with platinum were the following ... 

Ajmaline. The presence of the indoline was established by colour reactions, substitution reactions, e.g. bromoajmaline, and by ultraviolet absorption spectroscopy. Its N-methyl was fixed onto the indoline nitrogen since potassium permanganate oxidation in acetone gave N-methylisatinacetone and soda lime or zinc dust distillation furnished N-methylharman. 

In the flask were succesively placed 0.10 mol of the sulfinate (note 2), 25 ml of dry, pure HMPT (note 3), 4 g of powdered sodium iodide, 40 g of zinc dust and some boiling stones. After swirling for a few seconds the flask was connected with the other parts of the distillation apparatus, the system was evacuated immediately by means of the water pump (note 4) and the flask was then heated cautiously (free flame). A vigorous reaction started suddenly and the cumulene and part of the HMPT passed over. When the distillation had stopped completely... 

Hydroxyisoquinolines. Hydroxy groups in the 5-, 6-, 7-, and 8-position show phenoHc reactions for example, the Bucherer reaction leads to the corresponding anainoisoquinolines. Other typical reactions include the Mannich condensation, azo-coupling reactions, and nitrosation. Both 0-methyl and /V-methyl derivatives are obtained from the methylation of 1-hydroxyisoquinoline, indicating that both tautomeric forms are present. Distillation of various hydroxy compounds, eg, 1- and 4-hydroxyisoquinoline, with zinc dust removes the oxygen. Treatment of 1-isoquinolinol with phosphoms tribromide yields 1-bromoisoquinoline [1532-71 -4] (178). 

Constitution. When coniine is distilled with zinc dust or heated with silver acetate/ a new base, coiiyrine, CgH N, differing from coniine by six atoms of hydrogen, is formed. This on oxidation yields pyridine-2-carboxylic acid and, since it is not identical with 2-isopropylpyridine, must be 2-propylpyridine (I). When coniine is heated with hydriodic acid at 300° it yields w-octane (II). These and other observations due mainly to A. W. Hofmann, made it clear by 1885 that coniine was probably a-propylpiperidine (III), and this has been amply confirmed by other reactions of the alkaloid and by syntheses. Thus, Wolffenstein showed that on oxidation with hydrogen peroxide, coniine is converted into amino-w-propylvaleraldehyde (IV) ... 

In 1931 Ing pointed out that formula (II) and (III) do not contain methyl or potential methyl groups in j ositions 6 and 8 which they occupy in cytisoline. Further, a partially reduced quinoline ought to oxidise easily to a benzenecarboxylic acid and so far the only simple oxidation, products recorded from cytisine were ammonia, oxalic acid and isovaleric acid. Distillation of cytisine with zinc dust or soda-lime yields pyrrole and pyridine, but no quinoline. On these grounds Ing suggested that cytisine should be formulated without a quinoline nucleus, and that the reactions which indicate the presence of an aromatic nucleus in the alkaloid can be accounted for by an a-pyridone ring. This a-pyridone nucleus can... 

Rauwolscine gives colour reactions like those of yohimbine and the absorption curves of the hydrochlorides of the two alkaloids are very similar. Heated to 300°/5 mm. rauwolscinic acid forms barman (p. 490) and 3-ethylindole and on fusion with potassium hydroxide decomposes into indole-2-carboxylic acid, isophthalic acid, barman and an unidentified indole derivative. Rauwolscine itself on distillation with zinc dust produces barman, 2-methylindole (scatole) and tsoquinoline. It is suggested that the alkaloid has the skeletal strueture suggested by Seholz (formula XIV, p. 508) for yohimbine, the positions of the hydroxyl and earbomethoxy grouf s being still imdetermined. 

Toluene from Toluidine.—It is often desirable to obtain tbe hydiocarbon from the base. The process of diazotisntion offers the only convenient method. The diazonium salt may be reduced by alcohol (Reaction 1, p. 162) or, as in the piesent instance, by sodium stannite. Less direct methods are the con-veision of the diazonium compound into (i) the hydrazine (see p. 174), (2) the acid and distillation with lime (p. 200), (3) the halogen derivative and reduction with sodium amalgam, 01, finally (4) the phenol and distillation with zinc dust. 

It h-ds been prepared artificially by Wallach as a bye-product in the reduction of nitrosopinene, C Hj NOH. It is best prepared as follows Five grams of nitrosopinene are dissolved in 40 c.c. of warm glacial acetic acid, and sufiScient water added to produce a slight cloudiness. A large amount of zinc-dust is then added. After the reaction has become gradual, the mixture is heated on a water-bath under a reflux condenser for four hours, i he liquid is then filtered, and the filtrate steam distilled. Ihe distillate is exhausted with ether, the ether evaporated... 

Synthetic Method 1 6-(dimethylamino)-3-(N-acetyl-N-methylamino)-10-acetylphenothiazine 8a (procedure from US. Patent 4,652,643).5 A mixture of 9.0g of 6-(dimethylamino)-3-(methylamino)phenothiazin-5-ium chloride (Azure B), 150.0ml of acetic anhydride, and lO.Og of zinc dust was maintained at reflux temperature for approximately 4 hs. After the reaction mixture was cooled to ambient temperature, it was poured into ice water with stirring and 300ml of toluene was added. After stirring for approximately 30 min the toluene layer was separated and washed twice, once with tap water and once with saturated aqueous sodium chloride solution. The toluene was then distilled off at reduced pressure. The residue which remained was dissolved in ethyl acetate and separated into various components by subjecting the solution to column chromatography using silica gel as substrate. Elution with ethyl acetate yielded a white-colored solid. 

Distillation of phenols with zinc dust [617] or with dry lithium aluminum hydride [618] also results in hydrogenolysis of phenolic hydroxyls but because the reaction requires very high temperatures hardly any other function in the molecule can survive, and the method has only limited use. 

To a flask equipped with stirrer, condenser, and dropping funnel is added 40.0 gm (0.61 gm-atom) of zinc dust in 40 ml of absolute ethanol. After the condenser outlet is connected to a series of Dry Ice-acetone traps cooled to —80° to —70°C, the mixture is heated to gentle reflux while 20.3 gm (0.0852 mole) of l,2-dibromo-l,l-difluoropropene in 30 ml of 95% ethanol is added dropwise over a 2 hr period. The reaction mixture is heated for an additional hour, and then the gaseous products which are condensed in the Dry Ice traps are purified by several vaporization distillations to afford 3.6 gm (56 %) b.p. 

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