Chemistry 169 



(XXII) . The ester-like properties of these ethers are revealed in their 

 rapid hydrolysis to colchiceine and in their reactions with ammonia 

 and amines wherebv colchicamides are formed,-^'^ the rea(ii\e methoxyl 

 group being replaced by an amine residue. Hydrogenation of colchi- 

 ceine, or of colchicine, is complex, i^- ^■'- ^^- ^f- ^'^ but there is evidence 

 that hexahydrocolchiceine is a 1 :2-diol,i'' ^- and less fully hydrogen- 

 ated material shows ketonic properties.-'* Polarographic measure- 

 ments made by Santavy and by Brdicka,^"'' and infrared absorption 

 studies by Scott and TarbelH^ confirm the similarity between colchi- 

 ceine and tropolones. Moreover, r/Z/ocolchicine (XX) is at once seen 

 to be the benzenoid isomerization product of a methyl ether derived 

 from either (XXI) or (XXII) . Its production corresponds to that 

 of methyl benzoate from trojjolone methyl ether (Doering and 

 Knox-*'') and explains the origin of the trimellitic acid (benzene-l:2:4- 

 tricarboxylic acid) which ^\'indaus obtained from colchicine by suc- 

 cessive alkali fusion and oxidation. ^'^ 



6.5: Structure of Colchicine 



The tautomeric nature of colchiceine allows two possible formula- 

 tions of colchicine, its methyl ether. It is not easy by chemical means 

 to distinguish between these alternatives but the distinction can be 

 made by X-ray crystallographic analysis. King, De Vries, and Pepin- 

 sky-**' in this way examined an addition complex of colchicine and 

 methylene di-ioclide and not only confirmed the tricyclic structure 

 with its two fused 7-membered rings but also showed that colchicine 

 is the particular methyl ether (XXIII) . It follows that /.vocolchicine 

 has the methyl ether structure corresponding to (XXII) . 



6.6: Miscellany 



So far in this chapter discussion has been directed primarily to 

 the evidence on which the structural formula of colchicine rests. 

 There remain to be noted several reactions and items of chemical 

 interest, which are either at {^resent incompletely evaluated or only 

 indirectly related to the alkaloid's structure. For instance it is known 

 that nitration of colchicine yields a mononitro-colchicine, reducible 

 to an aminocolchicine, but the seat of substitution in these derivatives 

 is not yet definitely ascertained (Nicholls and larbelH') . Bromina- 

 tion of colchicine yields mono-, di-, and triljromo deri\aii\es (Zeisel 

 and Stockert^') . Bromination of colchiceine yields a tribromo acid 

 which Lettre, Fernholz, and Hartwig^^ formulate as (XXIV) by 

 analogy with the bromination of tropolones^" and because the com- 

 pound is readily decarboxylated to a tribromo derivative of A'-acetyl- 

 colchinol. Oxidation of colchicine ^vith chromic acid in aqueous solu- 

 tioti yields a ketone, namely oxycolchicine, C:,2H280-N, in \vhich a 



