September 17, 1903] 



NATURE 



477 



•whether phloroglucinol from various sources had the same 

 constitution, and, further, whether there might not be two 

 isomeric forms of the compound present in equal proportions 

 in a solution of the substance. Specimens of phloroglucinol 

 prepared in five different ways from different materials gave 

 curves of molecular vibrations which were identical : this 

 decided the question absolutely ; they are one and the same 

 substance. If the constitution of the substance is that of 

 a trihydro.Kybenzene or phenol, then the trimethyl ether 

 should exhibit an absorption curve differing but slightly 

 in detail from that of the parent substance ; and, further- 

 more, the latter should exhibit a general resemblance to 

 the curves of pyrogallol and phenol. This was found 

 actually to be the case in both particulars. 



Finally, with regard to tautomerism, it may be considered 

 as decided that no evidence has been obtained based upon 

 either physical measurements or chemical reactions of, first, 

 the presence of a " wandering " atom of hydrogen as a 

 characteristic of compounds which exhibit tautomerism ; 

 secondly, that solutions of tautomeric compounds do not 

 contain equal quantities of the two substances, or enolic 

 and ketonic forms in equilibrium, and that if both are pre- 

 sent one so greatly preponderates over the other that no 

 trace of any but the one compound can be detected ; thirdly, 

 it has been observed that some substances do change spon- 

 taneously from one form to another, and that this change 

 sets in very quickly after the substance has been dissolved ; 

 fourthly, that substances change from one form to another 

 under the influence of different reagents, as, for instance, 

 cotarnine, as Dobbie and Lauder (1903) have shown, in 

 presence of methyl alcohol or of caustic soda, and again in 

 presence of potassium cyanide. In fact it appears that 

 under the influence of different reagents one €«• other of the 

 two compounds is the more stable, and the more stable 

 substance is then formed. 



A reaction is recorded in the researches of Emil Fischer 

 where it appears that two tautomeric forms are produced 

 simultaneously from oxycaf6ine. When the silver salt of 

 this substance is heated with methyl iodide it yields a 

 mixture of tetramethyl uric acid and methoxycaf^ine, the 

 characteristic groupings in which are — NH — CO— and 

 — N = COH — , the hydrogens being methylated. This is a 

 singular reaction which has not yet been studied spectro- 

 graphically. 



O 

 C 



'CH,— n/^C— N 



OCl 



>co 



.C— N< 



N 

 I 

 CH, 



Tetramethyluric Acid. 



XH, 



O 



c 



CH3— N'^'^C-N< 



OC. .C— N^ 

 N 

 I 

 CH, 



Methoxycaf^ine. 



.CH3 



^C— OCH3 



Ihe Absorption Spectra of Alkaloids. 



The interest attached to an examination of the absorption 

 spectra of the alkaloids is not alone the fact that a means 

 of recognising, detecting, and estimating such substances 

 was devised, but still more that we may learn something 

 of their chemical constitution. Many of the poisonous 

 alkaloids give no distinctive chemical reactions, and in 

 certain cases the means of recognising them are restricted 

 to observations on their crystalline form and their physio- 

 logical action. The physiological action of certain alkaloids 

 of an extremely deadly character is remarkable enough to 

 prove a means of their identification when the effect on 

 the human subject is under observation. The first experi- 

 mental work on the absorption spectra of the alkaloids 

 arose out of a celebrated trial for murder, which engaged 

 much attention in the year 1882. It was proved that the 

 lethal drug administered was aconitine. 



To identify this substance, of which there are several 

 varieties, it was necessary at that time to resort to physio- 

 logical tests made upon small animals. 



Such a course always affords an opportunity for forensic 

 arguments based upon the evidence adduced. To substitute 

 absolute physical measurements for physiological tests 

 seemed to present facilities for securing justice by removing 



NO. 1768, VOL. 6H] 



any doubt of the identity of an unknown substance with the 

 nature of one which is known. Alkaloids yield spectra of 

 two kinds, those which do not and those which do exhibit 

 absorption bands, the difference between the two classes of 

 substances being one dependent on the constitution of the 

 nucleus or ultimate radical of the compound. It is possible 

 not only to identify substances, but also to determine the 

 quantity present in a mixture or solution, and this has 

 actually been done. 



Alkaloids which are derived from benzenoid hydrocarbons, 

 pyridine, quinoline, or phenanthrene give evidence of their 

 origin by their spectra. It is therefore advantageous to 

 make a careful study of the absorption spectra of the sub- 

 stances themselves and of the various products derived from 

 them when studying their constitution. It was remarked 

 while the work was in progress that the quinine spectrunri 

 curve was probably due to the conjugation of four pyridine 

 or two quinoline nuclei. It is known now to be a 

 substance of a complicated structure containing one 

 quinoline nucleus. It differs from cinchonine only 

 by one methoxyl group in the /)ara-position. Observations 

 made on simple bases differ from those made on substitution 

 products, such as alkyl derivatives, in this respect, that 

 the bases are the more diactinic, while addition products, 

 such as hydrogenised compounds, and also salts of the 

 alkaloids such as hydrochlorides, are more diactinic than 

 the simple bases. It was shown by the researches of Alder 

 Wright that different preparations of aconitine can yield 

 substances slightly differing in constitution. On examin- 

 ing them it was shown that these preparations yielded 

 different absorption curves the variations in which were 

 due to differences in the constitution of the different pre- 

 parations. To state a particular case of a well-defined 

 character, the aconitine from aconitum napellus and jap- 

 aconitine from a Japanese aconite prepared by Alder Wright 

 had practically the same absorption spectrum and yielded 

 similar curves ; but that of japaconitine was just what 

 might be expected from a substance with a nucleus of a 

 similar constitution, but about twice the molecular weight 

 of aconitine ; in other words, a condensation of two mole- 

 cules of aconitine into one — namely, what was observed in 

 the spectra of morphine and apomorphine,. a much greater 

 absorptive intensity with a similar absorption curve. 



It was shown that japaconitine has a constitution modified 

 in such a manner; it being, in fact, what was termed by 

 Alder Wright a sesquiapoaconitine ; and the formulae given 

 for these substances are respectively : Aconitine, 

 Cj^H^jNO,! ; japaconitine, CgeHgjNjOji, which is in agree- 

 ment with the spectrum observations. It has, however, 

 been supposed by Freund and Beck that the two substances 

 are identical. 



Strychnine and brucine are two alkaloids evidently closely 

 related, but little is known about their constitution ; both 

 seem to contain a pyridine nucleus united to what is prob- 

 ably a pyrrolic nucleus, the two constituting a conjugated 

 nucleus resembling that of quinoline. The difference 

 between brucine and strychnine is said to be simply that 

 the former contains two methoxyls. The absorption curves 

 show a wider difference than this, and it was predicted 

 that strychnine appears to be a derivative of pyridine, but 

 brucine is more probably a derivative of tetrahydroquinoline, 

 or an addition product of quinoline of the same character, 

 since there is a remarkable similarity between the curves 

 of the two substances. I would suggest that for the future 

 evidence from their spectra be taken into account in study- 

 ing their constitution. 



Stereo-isotnerism in the Alkaloids. 

 Many alkaloids having the same formula are stereo- 

 isomerides, and those related in this manner exhibit mole- 

 cular absoi-ption curves which are identical. The following 

 examples are quoted by Dobbie and Lauder (1903) as the 

 result of their investigations : dextro-corydaline and inactive 

 corydaline ; narcotine and gnoscopine ; tetrahydroberberine 

 and canadine. Where two compounds are known to have 

 the same formula, and one of these is optically active, the 

 other inactive, it may be inferred, as Dobbie and Lauder 

 have pointed out, that they are not optical isomerides if 

 their absorption curves are different,; thus canadine and 

 papaverine have the same formula, but their absorption 

 curves show that they are structurally different. 



