Tropin

Tropanol (Tropine) [120-29-6] M 141.2, m 63°, b 229°/760mm, pK 3.80. Distd in steam and crystd from diethyl ether. Hygroscopic. 

Blount and Robinson have extended this mode of synthesis to the preparation of iV-methyl/iomogranatonine (XXII) by the use of adipaldehyde, CHO. [CH2]4. CHO. The base, on reduetion with sodium in butyl aleohol, yields A -methyl/mmogranatoline (XXII CO — CHOH), the benzoyl derivative of which possesses marked local anaesthetic aetion. Similarly Blount, by eondensing /3-(o-formylphenyl)propaldehyde, CHO. CgH4. CHj. CHj. CHO, with methylamine and calcium acetonedicarboxylate, has prepared 8 9-benz-d - -feomogranatene-3-one (XXIII), which was reduced to the -alcohol (cf. reduction of tropinone to -tropine) and the latter converted to the benzoyl-derivative (m.p. 98°),... 

The names, formulae and structures of these alkaloids are given in the following table. The esters of tropine or -tropine are known as tropeines or -tropeines respectively. The first eleven items in the table are sometimes called the solanaceous alkaloids, but they are not the only alkaloids, or even the only type of alkaloid, found in the botanical family Solanaceas. They are also sometimes referred to as the mydriatic alkaloids though other alkaloids also exert this action. 

When heated with acids or alkalis, hyoscyamine undergoes hydrolysis into tropine and dZ-tropic acid probably via conversion into atropine, and it is this alkaloid which is hydrolysed. According to Gadamer, when hyoscyamine is hydrolysed with cold water the products are inactive tropine and Z-tropie acid. Amenomiya has shown that Ladenburg and Hundt s partially synthetic d- and Z-atropines were probably mixtures of atropine with d- and Z-hyoscyamines. He resolved dZ-tropic acid into the d- and Z- forms, esterified these with tropine in 5 per cent, hydrochloric acid, and so obtained d- and Z-hyoscyamines, the latter identical with the natural alkaloid, d- and Z-Hyoscyamines have also been obtained by Barroweliff and Tutin by the resolution of atropine by means of d-camphorsulphonic acid. 

The results so far recorded are those upon which Ladenburg chiefly based his formulae representing tropine and tropidine as A-methyl-J -tetrahydropyridines, substituted in position 2 by the residues. CHa. CH OH (or. CHOH. CH3) for tropine (XIV) and, CH CH for tropidine (XV) thus ... 

The inadequacy of these formulae became evident when the oxidation of tropine was studied. With potassium permanganate, in presence of acid, or with chromic acid, tropine and tropidine give rise to a series of oxidation products, the interrelationships of which are shown in the scheme on p. 75. 

Tropigenine (nortropine), C,Hi30N. This product of the action of potassium permanganate on tropine is a strong base, which crystallises from ether in colourless needles, m.p. 161° b.p. 233° (picrate, m.p. 170-1° ... 

The formation of these oxidation products, and, in particular, o tropinic acid, led Merling to represent tropine as a bieyclic systen composed of a piperidine and a hexahydrobenzene ring with four carbo ... 

Willstattcr s formula for tropine was confirmed by his syntheses of tropidine, tropine and 0-tropinc from the heptacyclic ketone, suberone as a starting-point. The latter was converted into the oxime, whieh was... 

The conversion of a-methyltropidine into tropidine methiodide was subsequently achieved in another way. By saturating a solution of the base in hydrochloric acid with hydrogen chloride, the elements of the latter were added on in the J -position and the product on treatment with sodium carbonate solution yielded methyl- -tropine. The latter was next brominated in positions 4 and 5, The dibromide, thus formed,... 

This synthetic tropidine was converted into bromodihydrotropidine by hydrogen bromide in aeetie aeid, and the solution heated with 10 per cent, sulphurie acid at 200-10°, when it passed into -tropine,and, sinee this may be partially converted into tropine by oxidation to tropinone and reduction of the latter by zinc dust and hydriodic acid, this series of reactions affords a complete synthesis of tropine and of the tropeines. Combining the formula given above for tropine with that of tropic acid, atropine and hyoscyamine are represented as follows ... 

Though the dialdehyde-tropinone synthesis does not succeed when the dialdehyde is replaced by a diketone, Blount and Robinson have shown that 1-methyltropinone (XXXV) can be obtained by the interaction of the keto-aldehyde, laevulinaldehyde. Me. CO. CH. CH. CHO, with methylamine and calcium acetonedicarboxylate, and from this by reduction to 1-methyl- -tropine and benzoylation, 1-methyl tropacocaine (b.p. 210°/15 mm. picrate, m.p. 163-4°) has been prepared. 

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