48: 



jVA TURE 



[September i 2, 189; 



phuric acid which united to form the siilphovinic acid are re- 

 covered. In the same (xjper he shows that he had verj' clear 

 views as to the process of etherification. Hennell's work 

 appears to have been somewhat dimmed by (he brilliancy of his 

 contemporaries who were labouring in the same field : but it is 

 not tix) much to claim for him. after the lapse of nearly seventy 

 years, the position of one of the pioneers of chemical synthesis. 

 Of course in his time the synthesis was not complete, because he 

 did not start from inonpjnic materials. The olefiant gas used by 

 Farailay had been obtaine<l from coal-gas or oil-gas. Moreover, 

 in 1S26-1S2S alcohol was not generally regarded as a product of 

 vital activity, and this is, no doubt, the reason why the discovery 

 failed to produce the same excitement as the formation of urea. 

 But the synthesis of alcohol from ethylene had, nevertheless, 

 been accomplished, and this hydrocarbon occupied at that time 

 precisely the same position as ammonium cyanate. The latter 

 salt had not then been synthesised from inorganic materials, and 

 the form-iiion of urea, as Schorlemmer points out ("The Rise 

 and Development of Organic Chemistry," p. 195), w.^s also not 

 a complete synthesis. The reputation of Wiihler, the illustrious 

 friend and colleague of the more illustrious Liebig, will lose not 

 a fraction of its brilliancy by the raising of this historical question. 

 Science recognises no distinction of nationality, and the future 

 historian of s)-nthetical chemistry will not begrudge the small 

 niche in the temple of fame to which Hennell is entitled. 



Like many other great discoveries in science, the artificial for- 

 mation of natural products began, as in the case of alcohol and 

 urea, with observations arising from experiments not primarily 

 directed to this end. It was not till the theory of chemical 

 structure had risen to the rank of a scientific guide that the more 

 complicated syntheses were rendered possible by more exact 

 methods. We justly credit structural chemistry with these 

 triumphant achievements. In arriving at such results any defects 

 in the theory of structure are put out of consideration because — 

 and this point must never be lost sight of — all doubt as to the 

 possibility of this or that atomic grouping Iwing stable is set 

 aside at the outset by the actual occurrence of the compound in 

 nature. The investigator starts with the best of all assurances. 

 From the time of Wohler and Hennell the course of <liscovery in 

 this field has gone steadily on. The announcement of a new 

 synthesis h.-is ceased to produce that excitement which it did in 

 the early days when the so-called " organic " compounds were 

 regarded as products of a special vital force. The interest among 

 the uninitiated now rises in proportion to the technical value of 

 the compound. The present list of 180 odd synthetical products 

 comprises, among the latest discoveries, gentisin, the colouring- 

 matter of the gentian root (Gentiaita liiica), which has been 

 prepared by Kostanecki and Tambor, and caffeine, synthesised 

 by Emil Fischer and Ltirenz .\ch, starting from diniethylurea 

 and malonic acid. 



I have allowed myself no lime for those prophetic flights of 

 the inuigination which writers on this subject generally indulge 

 in. When we know more about the structure of highly cimiplex 

 molecules, such as starch and albumin, we shall |)robal)ly be able 

 to synthesise these compounds. It seems to me more important 

 just at present to come to an understanding as to whiit is meant 

 by an organic s)'nthesis. There appears to \x an impression 

 among many chemists that a synthesis is only effected when a 

 com|>iund is built up from simpler molecules. If the sin)])ler 

 molecules can l)C forme<l directly from their elements, then the 

 synthesis is considered to lie complete. Thus urea is a complete 

 synthetical product, because we can make hydrogen cyanide 

 from its elements ; from this we can prepare a cyanate, and 

 finally urea. In dictionaries and text-books we find synthetical 

 processes generally separatefl from mwles of formation, and the 

 latter in their turn kept distinct from methods of preparation. 

 The distinction t)etween formation and preparation is obviously 

 a goo<l one, Ijccause the latter has a pr.iclical significance for the 

 investigator. But the cx[>cricnce giiined in drawing up the tables 

 of synthesised com|xiun<l5, to which I have referred, has resulted 

 in the conclusion that the terms "synthesis" and "mode of 

 formation " h.ave Iwen either unnecessarily confused or kept dis- 

 tinct without sufficient reason, and that it is impossible now to 

 draw a hardan'l-fast line between them. Some recent writers, 

 .^uch, for example, as l)r. Karl KIbs, in his .idmirable work on 

 this subject (" Uic synthetischen Darslcllungsmethoden der 

 Kohlcnstoffverbindungen," Leipzig, 18S9), have expanded the 

 meaning of the word synthesis so as to comprise generally the 

 building up of organic molecules by the combination of carlM»n 

 with carUjn, without reference to the circumstance whether the 



NO. 1350, VOL. 52] 



compound occurs as a natural product or not. But although 

 this definition is sufficiently wide to cover the whole field of the 

 production of carbon compounds from less complex molecules, 

 It is in some respects too restricted, because it excludes such 

 well-known cases as the formation of hydrogen cyaniile from its 

 elements, or of urea from ammonium cyanate. I should not 

 consider the discussion of a mere question of terminology of 

 sufficient importance to occupy the attention of this Section were 

 it not for a matter of principle, and that a principle of the very 

 greatest importance, which I believe to be associated with a clear 

 conception of chemical synthesis. The great interest of all work 

 in this field arises from our being able, by laboratory processes, 

 to obtain compounds which are also manufactured in nature '^ 

 laboratory — the living organism. It is in (his direction that our 

 science encroaches upon biology through ])hysiology. Now, if wt- 

 confine the notion of synthesis to the building up of molecules 

 from simpler molecules or from atoms, we exclude one of nature ^ 

 methods of producing many of these very compounds which de- 

 claim to have synthesised. There can be no manner of doubt thu! 

 a large proportion, if not a majority, of the natural products 

 which have been prepared artificially are not synthesised by the 

 animal or plant in the sense of building up at all. They are 

 the results of the breaking down — of the degradation — of com- 

 plex molecules into simjjler ones. I urge, therefore, that if in 

 the laboratory we can arrive at one of these products by decom- 

 posing a more comjilex molecule by means of suitable reagents, 

 we have a perfect right to call this a synthesis, provided always 

 that the more comjilex molecide, which gives us our com]Hmnd, 

 can be in its turn synthesised, by no matter how many steps, 

 from its constituent atoms. Thus oxalic acid has been directly 

 synthesised from carbon dioxide by Kolbe ami Drechsel by 

 passing this gas over potas,sium or sodium amalgam healed to 

 360°. Whether the plant makes oxalic acid directly out of 

 carbon dioxide we cannot at present state ; if it does it certainly 

 does not employ Kolbe and Drechsel's jirocess. On the other 

 hand this acid may, for all that is known, exist in the plant as 

 a product of degradation. Many more complex acids, such as 

 citric and tartaric, break down into oxalic acid when fuse<l 

 with potash. Both citric and tartaric acids can now be com- 

 pletely synthesised ; therefore the formation of oxalic acid from 

 these by potash fusion is a true synthesis. 



The illustration given will make clear the point which I am 

 urging. The distinction between a synthesis and a m<Kle of 

 formation vanishes when we can obtain a comimund by the 

 breaking down of a more coniplex molecule in all those cases 

 where the latter can be completely built up. If we do not ex- 

 pand the meaning of synthesis so as to comprise such cases we 

 are simply shutting the door in nature's face. It must be liorne 

 in mind that the actual yield of the compound furnislied by the 

 laboratory process does not come into consideration, because it 

 may be generally asserted that in most cases the artifical |iro- 

 cesses are not the same as those which go on in the animal or 

 plant. The information of real value to the physiologist which 

 these syntheses give is the suggestion that such or such a com- 

 pound may possibly result from the degradation of lliis or that 

 antecedent compound, and not from a process of buikling up 

 from simpler molecules. 



The Bkarim: oi' Chkmicai, Svmiiksis on Vitai. 



ClIKMIStRV. 



With these views — the outcome of structural clieniistiy — 

 the chemist and physiologist may join hands and nu)ve fearlessly 

 onwards towards the great n>yslery of vital chemistry. In con- 

 sidering the results of organic synthesis two <|ueslions always 

 arise as it were spontaneously : I low does nature produce these 

 complicated molecules withtail the use of strtmg reagents and at 

 ordinary temperatures? What bearing have our laboratory 

 achievements on the mechanism of vitality? The light shed 

 upon these questions by experimental investigation has as yet 

 flickered only in fitful gleams. We are but dwellers in the outer 

 gates, wailing for the guide who is to show us the bearing of 

 modern research on the great ]irt)blem which confronts alike the 

 physicist, the chemist, and the biologist. The chemical pro- 

 cesses that go on in the living organism are complex to an extent 

 that is diflicull to realise, (if (he various compounds of animal 

 or vegetable origin that have been produced synthetically some 

 are of (he nature of waste products, resulting from metabolic 

 degriid.ition ; others are the result of zymolytic action within the 

 organism ; aiul others, again, areseconilary products arising from 

 the action of associated bacteria, the relationship between the bac- 



