Willstatter

The first breakthrough came m 1911 when Richard Willstatter prepared cyclooc tatetraene by a lengthy degradation of pseudopelletienne a natural product obtained from the bark of the pomegranate tree Today cyclooctatetraene is prepared from acetylene m a reaction catalyzed by nickel cyanide... 

Willstatter s most important work for which he won the 1915 Nobel Prize in chem istry was directed toward determining the structure of chlorophyll... 

Natural chelidonic acid is obtained from the herb celandine Chelidonium majus). The synthesis from ethyl oxalate and acetone was first described by Claisen the process was simplified by Willstatter and Pummerer and further improved by Ruzicka and Fornasir.- The present procedure is modelled after that of the last-mentioned investigators. 

Piccinini, therefore, adopted formula (XIV) for 0-pelletierine, which is based on Willstatter s tropinone formula (p. 77) by cliange from a heptamethylene to an octamethylene ring. ... 

Simple Bases. In addition to the alkaloids proper, 1 4-TETRAMETHYLDiAMiNoBUTANE, MCjN. (CHj) . NMCj, has been found in Hyoscyamus muticus by Merck and in H. reticulatus by Konovalova and Magidson. It was described by Willstatter and Heubner as a colourless liquid, 0-7941, b.p. 169°, with a pungent, acrid taste. The... 

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... 

A better yield was obtained when, in place of acetone, calcium acetonedicarboxylate was used, the initial product in this case being calcium tropinonedicarboxylate, from which the free dibasic acid is readily isolated and can be decarboxylated by heating in acid solution, yielding tropinone. This idea was taken up in Germany, and a number of processes for the production of tropinone derivatives have been described, mostly in patent literature. According to Willstatter and Pfannenstiel, a yield of... 

The close relationship of eegonine to tropine is brought out by its Oxidation products, which when chromic anhydride in acetic acid is the agent used are tropinone, CgHijON (p. 74), tropinic acid, CgHi304N (P- 75) and ecgoninic acid, C HnOgN. The latter crystallises from benzene in colourless needles, m.p. 93°, and has been shown by Willstatter and Bode to W-methylpyrrolidone-2-acetic acid, and this was confirmed by Willstatter and Hollander s synthesis of the acid. 

There are two probable formulae (II) and (HI) for ecgonine derivable from Willstatter s representation of tropine (p. 76). 

Willstatter and Bode converted tropinone into (/(-ecgonine by treating sodium tropinone with carbon dioxide and sodium, when it yielded sodium tropinonecarboxylate. This on reduction with sodium in alcohol gave some dZ-i/i-ecgonine (p. 97), which on esterification with methyl alcohol and benzoylation yielded a dhcocainc. A simpler synthesis of ( -eegonine was achieved by Willstatter and Bommer, and reference is made on p, 80 to this and other processes, some of which have been protected by patents. These improvements having enabled the prepara-... 

Tropine and -tropine are mutually convertible as already described. Mixtures of tropine and -tropine can be separated by means of the picrates, that of i/i-tropine being the more soluble in water (1-48 per cent, in water at 16°). By the action of sodium amyloxide on tropine, Willstatter has sliown that 4-tropinc is produced and this has been confirmed by Barrowcliff and Tutin, who also support Willstabter s view that both bases are internally compensated, the relation being that of cw-frans-isomerism. The synthesis of 4-tropine has been described already (p. 77). 

Hygric acid was synthesised by Willstatter by the following method. Ethyl bromopropylmalonate, CHaBr. GHj. GHj. GH(G02Et)2, obtained by condensation of trimethylene bromide with ethyl sodio-nmlonate, on bromination yielded ethyl 8-dibromopropylmalonate,... 

Schdpf and Thoma found that lupininic acid yielded a methyl ester (b.p. 120-2°/10 mm.) which had [aj — 19-4° to 5-8° in different batches. The f-ester furnished a gummy picrate, [a]J, ° — 41-8°, and on hydrolysis by hydrochloric acid gave a crystalline lupininic acid hydrochloride, m.p. 275°, — 13T°, identical with that described by Willstatter and Fourneau, whilst the d-ester, or ester of f-rotation below — 19-4°, furnished a crystalline picrate, m.p. 185°, [a]j, -f- 61-8°, from which pure d-epi-ester,-b.p. 126°/11 mm., [aJi, 54-8°, was prepared, this in turn yielding amorphous d-lupininie acid hydrochloride. The f-ester is convertible into ... 

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