Methiodides preparation

This procedure is based on the method of Lindsay and Hauser as modified slightly by Osgerby and Pauson. N,N-dimethyl-aminomethylferrocene methiodide has also been prepared by heating formylferrocene with dimethylamine and hydrogen in the presence of Raney nickel catalyst to give dimethylamino-methylferrocene, which was quaternized with methyl iodide. ... 

A solution of 10.0 g. (0.25 mole) of sodium hydroxide in 250 ml. of water is prepared in a 1-1. round-bottomed flask equipped with a reflux condenser and a mechanical stirrer. Twenty-five grams (0.065 mole) of N,N-dimethylaminomethylferrocene methiodide is added to the solution. The resulting suspension is heated to reflux temperature with stirring. At this point the solid is in solution. Within 5 minutes oil starts to separate from the solution and trimethylamine starts to come off. At the end of 3.5 hours, at which time the evolution of the amine has virtually ceased, the reaction mixture is allowed to cool to room temperature. The oil generally crystallizes during the cooling. The mixture is stirred with 150 ml. of ether until the oil or solid is all dissolved in the ether. The ether layer is separated in a separatory funnel and the aqueous layer is extracted with two additional 150-ml. portions of ether. The combined ether extracts are washed once with water and dried over sodium sulfate. 

Hydroxymethylferrocene has been made by condensing ferrocene with N-methylformanilide to give ferrocenecarboxalde-hyde, and reducing the latter with lithium aluminum hydride, sodium borohydride, or formaldehyde and alkali. The present procedure is based on the method of Lindsay and Hauser. A similar procedure has been used to convert gramine methiodide to 3-hydroxymethylindole, and the method could probably be used to prepare other hydroxymethyl aromatic compounds. 

Hantzsch prepared this betaine by treating nicotinic acid methiodide with silver hydroxide and. lahns subsequently identified trigonelline with Hantzsch s synthetic base. 

Syntheses of members of the lobeline group have been effected by Wieland and Drishaus and by Seheuing and Winterhalder. JiorLobelane was prepared by the former authors by condensing 2 6-dimethylpyridine with benzaldehyde to 2 6-distyrylpyridine (IX), which was then reduced by sodium in alcohol, giving a mixture of meso-and trans- forms of 2 6-di-(3-phenylethylpiperidine (worlobelane). From this by crystallisation of the mixed hydrochlorides, meso-norlobelane was separated, which on A-methylation yielded lobelane (X) as the methiodide. 

Constitution. The alkaloid yields a crystalline semicarbazone, m.p. 169°, a liquid hydrazone, b.p. 154-5°/29 mm., and a liquid oxime, b.p. 160°/12 mm., from which a crystalline picrate, m.p. 106°, can be prepared. The methiodide crystallises in cubes, m.p. 156°. On oxidation with chromic acid in sulphuric acid solution the base yields A -methylpiperdine-... 

Tropinone, CgHi30N. This substance, first prepared by Willstatter, crystallises in spear-shaped needles, m.p. 41°, b.p. 219-20°/714 mm., dissolves in ordinary solvents, is a strong base and has the properties of a ketone, giving an oxime, m.p. 111°, and a semicarbazone, m.p. 212°. It is a tertiary base and the methiodide is decomposed by alkalis producing dimethylamine and dihydrobenzaldehyde. When reduced by sodium... 

Poroidine, C42H2i02N. The synthetic product was isolated as the hydrobromide, colourless plates, m.p. 224-5°. A mixture (10 parts) of this with synthetic isoporoidine hydro bromide (1 part) had m.p. 220° which was not depressed by addition of the hydro bromide of either natural or racemised base Z. The other salts prepared included oxalate, m.p. 301-2°, picrate, m.p. 172° and methiodide, m.p. 289°. 

Anhalonine and Lophophorine. Spath and Gangl showed that each of these alkaloids contains a methylenedioxy group and that the quarternary iodide prepared from dZ-anhalonine is identical with lophophorine methiodide so that lophophorine must be N-methylanhalonine. Anhalonine was synthesised from 3 4-methylenedioxy-5-methoxybenzaldehyde by condensation with nitromethane, reduction of the product to the corresponding -ethylamine, the acetyl derivative (VII) of which, on treatment with phosphoric anhydride, condensed to 6-methoxy-7 8-methylenedioxy-l-methyl-3 4-dihydrofsoquinoline, m.p. 60-2°. This, on reduction, furnished the corresponding tetrahydrofsoquinoline, which proved to be anhalonine (VIII), and on conversion to the quaternary methiodide the latter was found to be lophophorine (IX) methiodide. The possible alternative, 8-methoxy-6 7-methylenedioxy-l 2-dimethyl-l 2 3 4-tetrahydrofsoquinoline, was prepared by Freund s method and the methiodide shown not to be identical with lophophorine methiodide. 

Papaveraldine (Xanthaline), C2oHij05N. This substance forms colourless scales, m.p. 210°, yields well-crystallised yellow salts, which are dissociated in water, and reacts as a tertiary base, forming a methiodide, m.p. 133-5°. It gives an oxime existing in two stereoisomeric forms, and contains foru methoxyl groups. The demethylated product, papaveraldoline, Ci0H,ON(OH)4, has been prepared by Oberlin. Miss Dobson and W. H. Perkin have shown that the alkaloid, Xanthaline, isolated from opium by T. and H. Smith, is identical with papaveraldine. On reduetion with... 

Bicuculline, C2oHi,06N. (Items 1, 9, 10, 13, 14, 18, 20, 23-26, 34, 35, 38 list, p. 169). This alkaloid exists in two forms, m.p. 177° and m.p. 196°, and has [a], ° + 130- 5° (CHCI3). The hydrochloride has m.p. 259° (dec.) and from the methiodide, W-methylbicuculline, plates, m.p. 246°, has been prepared. Bicuculline contains no methoxyl groups it behaves as a lactone and is convertible by alkalis into bicucine, which is possibly the corresponding hydroxy-aeid (see below). It simulates hydrastine in its reactions and differs from that base by CH, indicating that a methylene-dioxy group replaces two methoxyl groups, and this view is supported by comparison of the products of oxidative hydrolysis of the two alkaloids. Both yield hydrastinine (p. 163) as the basic product, but while hydrastine provides as the second product, opianic acid,... 

CjHj) picrate, m.p. 235° methiodide, m.p. 257°. To be distinguished from phenolic dihydrothebaine, m.p. 154° prepared by reduction of thebaine with sodium in alcohol. 

EtOH) methiodide, m.p. 273°. To be distinguished from the better-known dihydrothebainol, m.p. 138-142°, [a] ° — 46-2°, prepared by reducing dihydrothebainone with sodium amalgam (Speyer and Siebert ). 

Codeinone, CjaHijOgN. This ketone (XLVII) corresponds to the secondary alcohol codeine and its stereoisomeride wocodeine. It may be prepared by oxidising codeine with potassium permanganate in acetone or with potassium dichromate in dilute sulphuric acid and in various other ways. Codeinone can be reduced to codeine electrolytically or by chemical methods. It crystallises from alcohol in prisms, m.p. 185-6, [a]J, ° — 205° (EtOH). The hydrochloride, B. HCl. HjO, has m.p. 179-80°, picrate, m.p. 205°, methiodide, B. CHjI. 2H2O, m.p. 180°. 

Floripavidine, CjjHjgOjN. This occurs in the crude mixture of non-phenolic bases, and is separated from fioribundine by repeated crystallisation of the mixed hydrochlorides from water. The base crystallises from alcohol in prisms, has m.p. 241-2°, and [a]n — 156-25° (MeOH) the hydrochloride, m.p. 209-10°, hydriodide, and methiodide, m.p. 228-30°, were prepared. The alkaloid contains no hydroxyl group (Zerewitinoff), but a methoxyl, a dioxymethylene, and a methylimino group are present. 

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