THE PUNGENT PRINCIPLE OF GINGER. PART I. 777 LXV.-The Pungent Principle of Ginger. Part I. The Chemical Characters and Decomposition Products of Thresh’s ( ( Gi.lzgero1.” By ARTHUR LAPWORTH (MRs.) LEONORE KLETZ PEARSON and FRANK ALBERT ROYLE. THE pungent principles of ginger the rhizome of Ziizgiber oficinale, were studied by Thresh ((( Year-Book of Pharmacy,” 1879 426 ; 1884 516; Pharm. J. 1882 [iii] 12 721). The pungency was attributed to an active principle ( ( gingerol,” an inodorous sub-stance having the general characters of the class of compounds now known as ('oleo- resin^," which he isolated by means of a somewhat complicated fractionation of the alcoholic extract of the drug. He attributed to it the approximate formula sC,H80 and found that on oxidation with chromic acid i t yielded ‘( apparently ” acetic and caproic acids (‘( Year-Book of Pharmacy,” 1884 520) together with a volatile oil.Thresh seems to have abandoned the work a t an early stage. Garnett and Grim (Pharm. J. 1907 [iv] 25 118; ( ( Year Bookof Pharmacy,” 1909 344 ; compare also ibid. 1907 443) re-examined the pungent oleo-resin gingerol and simplified and improved the method of isolation and purification used by Thresh. They frac-tionated the crude mixture of oleo-resins with the aid of petroleum, and ultimately obtained a (‘clear viscous oil of a pale straw colour distilling within a range of 235O C. t o 250° C.,” the pressure referred t o being 18 mm. They add “It could not be assumed without further proof that this body” (that is, the distillate) (‘was not either a product of destructive dis-tillation or that it was not contaminated with such products ” ; they showed however that the distillate had the pungency and many other characteristics of the original gingerol.I n the course of their experiments they noted that gingerol was possessed of phenolic characters gave a green colour in alcoholic solution with ferric chloride a precipitate with bromine and that the solution in alkalis especially when warm undergoes a change which results in a loss of the pungent character in the dissolved oil. The latter observation was made use of in devising a simple means of distin-guishing between extracts of ginger and of capsicum respectively, as the latter is not affected in pungency by alkalis and is often used t o adulterate or fraudulently to replace the former.Ths present authors were invited by Messrs. Garnett and Grier to continue the work on gingerol and carried out the experiments described in this paper with a large sample of an alcoholic extrac 78 LAPWORTH PEARSON AND ROYLE : of African ginger the most pungent variety on the market. This extract was kindly made fmor them by James Woolley and Sons, Manc he st er. Method Used in Isolatilbg Gingerol. The residue from the alcoholic extract was treated repeatedly with aqueous alcohol of 35 per cent. strength which is considerably weaker than was used by Thresh o r by Garnett and Grier; it was found that this dissolved the inactive resins much less freely and gave a more rapid separation. Alcohol was removed from the clear extract by evaporation in a vacuum a t the lowest possible tempera-ture the oil which separated being freed from as much water as possible and re-extracted with alcohol of about 50 per cent.strength. Milk of lime was then added as suggested by Thresh, until only a very slight deposition of calcium compounds took place, when the whole was allowed t o settle and the clear liquid made neutral to litmus by addition of dilute hydrochloric acid and again freeld from alcohol by distillation under diminished pressure. The resulting oil was separated from the bulk of water by decantation, dissolved in a solvent such as chloroform which was subsequently dried and removed by evaporation. The dry crude gingerol was then extracted fractionally with hot petroleum and those portions retained which dissolved freely in the hot petroleum but were redeposited on cooling.After removing all traces of petroleum, the “refined gingerol” was obtained as a viscous faintly yellow oil entirely soluble in dilute aqueous alkali and generally having all the properties assigned to the material by Garnett and Grier, Many various methods were tried for the further purification of the refined gingerol but even the best samples obtained were almost certainly not homogeneous materials and could be frac-tionate’d by means of light petroleum into portions having some-what different solubilities. As many of the less soluble fractions of the oils shared the characters of the most soluble portion it was suspected that gingerol either tends to polymerise or to decompose into simpler products such as those mentioned later, with subsequent recombination of these t o products more complex than gingerol proper.The most highly purified samples obtained were distilled in a cathode-ray vacuum ; they passed over almost completely when the temperature of the bath was 135-140° and the distillate was in such cases a clear faintly yellow oil. Even under these) conditions there was evidence of slight decomposition (odour of fatty alde-hydes) and only traces of camphoraceous solid separated from the oil after many months THE PUNGENT PRINCIPLE OE‘ GINGER. PART I. 779 Messrs. Gariiett and Grier directed the authors’ attention a t the commeiiceinent of the work t o the fact that some samples of gingerol give a crystalline product when they are shaken with a solution of sodium hydrogen sulphite; the present authors found that the1 most highly purified samples do not give any such product, but do so after they have been distilled or otherwise somewhat strongly heated or treated with dilute alkalis under certain con-ditions.Analysis of the1 best samples of gingerol obtained gave: C=71*4; H=9.2; C=71*6; H=9*4. C17H2e04 requires C = 69.4 ; H = 8.8 per ce’nt. C18H2804 , C=70.1; H=9.1 , ,, Thresh found C=71*27 71.39 71.43 and H=9*61 9.82 9-52. Determination of methoxyl in gingerol : Found Me = 7.3 7.7. lMeO in C17H2oO4 requires Me0 = 10.5 ; in C,8H,804 MeO=10*05 per cent. (This for reasons which appear later would indicate a purity of only about 75 per cent.) Other P w p e r t i e s of ( ( G’iiigerol.” The presence of one hydroxyl group a t least is indicatesd by the phenolic character of gingerol.The alkaline solution when treated with benzoyl chloridel benzenesulphonyl chloride and similar com-pounds or wi€h chloroformic esters deposited neutral non-pungent oils wliich did not show any s i p s of assuming crystalline form. The oil yielded 110 crystalline oxime or seniicarbazone although theire was some evidence that a nitrogelnous compound was formed on treating it with hydroxylamine. Slight heat was evolved on mixing phenylhydrazine with gingerol ; but neither with that sub-stance nor with substituted phenylhydrazinee benzyl- o r naphthyl-hydrazines did ginger01 give any crystalline derivatives. The sole derivative of gingerol which was obtained in definitely crystalline form was its monomethyl derivative.As this was easily purified whilst the purity of gingerol could not be guaranteed all conclusions as to the true composition and constitution of ‘’ gin-gerol ” have been based on an examination of ‘‘ methylgingerol.” Preparation and Properties of ( ( illethylgitzgerol.” Refined gingerol is dissolved in methyl alcohol and treated with methyl sulphate and potassium hydroxide successively. From the product ether extracts a neutral oil which deposits crystals and these can b drained and recrystallised from light peltroleum. About 15 grams of methylgingerol melting a t 6 4 O can be obtained from 24 grama of the best gingerol which the authors have pre 780 LAPWORTH PEARSON AJXD ROYLE : pared; this is again 'indicative of the mixed charactefrs of gingerol.Analyses of different samples of methylgingerol gave the follow-ing results: C = 70.21 70.44 70.17 70.15 70.05 70.2. H=8.64 9.08 8.92 9.46 9.19 9.0. Me0 = 22.6 19.8 19.8. Qualitative tests and analysis by the Dumas method showed that no nitrogen was present : C,,H,,04 requires C = 70.1 ; H = 9.2 ; 2Me0 = 20.1 per cent. ClgH,,O , C=71.2; H=8-75; 2Me0=20.0 , ,, C,gH,,O4 , C=70.75; H=9.4; 2Me0=19.9 , ,, The molecular weight of I' methylgingerol " was determined by the cryoscopic method in benzene. The numbers obtained were 271 309 308 316 323 323 the numbers required for C,,H,,O and clgHa04 being 308 and 322 respectively. I' Methylgingerol " crystallises in slender needles melting a t 64O.It is insoluble in cold alkalis or acids but is altered by these if hot (compare later). It is also slmowly decompose'd when it is heated above 150° and rapidly near its boiling poinb-the odour of fatty aldehydes becoming perceptible. It is optically active in 2 per cent. solution in chloroform 'having [a]$ + 27.3'. Ketonic Properties of '' Met Jtylgingerol." Methylgingerol appears to be attacked slowly by phenylhydr-azine etc. but the products were not obtained in a crystalline form. When it is warmed in alcoholic solution with hydroxylamine hydro-chloride and sodium acetate however it gives a crystalline deriv-ative which was obtained in slender needles from light petroleum. Found c=64-9 64 0 64.1 64.5; H=9*1 9.4 9.0 9.2; N=4*3.C,,H,gO,N,H,O requires C= 63.3 ; H= 9.1 ; N = 4.1 per cent. ClgH3,04N,H20 , C=64.2; EL'=9*3; N=3*9 , ,, The analyses indicate that the substance is methylgingerol oxime hydrate. When heated a t 110-115° for four hours it lost 4.09 per cent. in weight whilst the theoretical loss for 1H,O is about 5.1. The treatment was not pressed as there were signs of more profound decomposition. The oxime dissolves in cold hydrochloric acid and is reprecipi-t a t 4 by alkali. When it is hydrolysed by acids it is reconverted into methylgingerol and hydroxylamine the former after recrystal-lisation being unchanged in melting point. When this oxime is subjected to Piloty's test f o r ketoximes it gives a definite positiv THE PUNGENT PRINCIPLE OF GINGER. PART I.781 reaction a yellowish-green coloration being obtained in the ethereal layer. The whole of the phenomena observed during the various stages i f the test are not to be distinguished from those observed when the related methylzingeroneoxinw (p. 786) is treated in the ~ a m e way. Methylgingerol is a t once attacked by chromic acid giving a black compound (chromate?) much as many alcohols (for example men-thol) do. It is instantly attacked by phosphorus pentachloride o r thionyl chloride and hydrogen chloride is evolve'd. A cold solution of methylgingerol in chloroform does not a t once discharge the colour of bromine in the same solvent but an action takes place only on heating when hydrogen bromide is evolved. Pure methyl-gingerol is also stable towards cold permanganate in acetone solu-tion; even after long heating with excess of this reagent the bulk of the compound is recovered unchanged and this fact may be utilised t o purify the crude substance from more easily oxidisable materials.Prolonged action of hot aqueous perinanganate destroys methyl-gingerol fatty acids veratric acid and carbon dioxide being formed. It is not reduced in the cold by sodium amalgam or by hydrogen in the presence of oolloidal platinum or palladium. Tests far the Hydroxyl Group in Methylgingerol. I n order to ascertain whether methylgingerol contained free hydroxyl the compound in amyl ether was treated with mag-nesium methyl iodide in the same solvent in an apparatus similar to that used by Sudborough for the determination of hydroxyl by this method.On mixing the two solutions a white precipitate of an additive compound was instantly formed but no trace of methanel or other permanent gas was detected even when excess of magnesium methyl iodide was used and the temperature was raised nearly t o looo. The1 experiment was repeated seveaal times and always gave the same result. On the other hand methylgingerol is quickly attacked by cold acetyl chloride thionyl chloride or phos-phorus chlorides and hydrogen chloride is evolved ; this change takes place rapidly on heating. Again when methylgingerol is sealed up in a tube with rather less than one molecular proportion of phenylcarblamide it does not a t first dissolve in it but after some weeks in the cold the solid disappears and a clear viscid liquid is formed in which the odour of phenylcarbamide cannot be detelcted.No crystalline delrivatives were isolate'd in either in-stance but the observations more especially the last one are very difficult to explain escept on the assumption that methylgingerol contains a free hydroxyl group and the same remark applies to it 782 LAPWORTH PEARSON AND ROYLE : behaviour with chromic acid. The failure of the substance to give methane with magnesium niethyl iodide is possibly due to the insolubility of the additive product which the reagent seems to form by uniting with the compound at the ketonic carbonyl group. Oxidation of Ginger01 with Chromic Acid. Pormntiou of n-Heptoac and (probably) n-Hexoic Acid. Thresh oxidised gingem1 with chromic acid and obtained what he considered to be probably acetic and caproic (hexoic) acids together with a volatile oil (Zoc.cit. 1884 520). The present authors dis-solved about 50 grams of refined gingerol in warm acetic acid of about 90 per cent. Btrength and added solid chromic acid in small quantities a t a time until further addition caused no immediate effervescence. The liquid was then subjected to distilla-tion in a current of steam the latter portions of the dist'illats being collected extracted with ether and the1 latter evaporated. The re'sidue was rendered alkaline with sodium hydroxide and once more treated with a current of steam when a small quantity of a neutral oil probably identical with that rr,entioned by Thresh passed over. This oil was not examined more closely but the alkaline residues in the flask were acidified extracted with ether and the latter dried and fractionated.After some water and acetic acid had distilled, the main bulk of the residue amounting t o about 7 grams passed over a t 210-225O and was clearly a mixture of saturated fatty acids ; on refractionation the range was not appreciably altered (a-hexoic acid boils a t 205O; 11-heptoic acid a t 223O). The fractions, except the highest and lowest were mixed an& a sample wr?s titrated with standard alkali in the presence of phenolphthalein as indicator. The equivalent found was 125 which corresponds with about one part of hexoic acid and two parts of heptoic acid The portion of the oxidation product which was not volatile in steam was small and nothing definite could ble isolated from it.Oxidatiom of Methylgingerol. As the presence of phenolic hydroxyl in gingerol evidently led to destruction of the aromatic portion of the molecule by the oxidising agent the oxidation of 8 grams of methylgingerol by means of chromic acid in acetic acid solution was carried out and the products were worked up as in the immediately preceding descrip-tion. A mixture of fatty acids was obtained as before but from that part of the product which was not volatile in steam about 0.9 gram of acid was obtained on extraction with ether. This when Forrnatioq% of Fatty Acids and Veratric Acid THE PUNGENT PRJNCIPLE OF GINGER. PART I. 783 purified by crystallisation from hot water formed flat needles melt-ing a t 180-181° and its equivalent fo’und by titration with standard alkali using phenolphthalein as indicator was 184.It was readily identified as veratric acid (equivalent = 182). Fusion of Gingerol with Potnssiztnz Hydroxide. Formation of Stenhouse and Groves (T.> 1877 31 i 533) found protocatechuic acid in the product obtained by fusing cruds ginger resins with potassium hydroxide. The present authors tried the same experi-ment with refined gingerol and although the great bulk of the material carbonised a small quantity of protocatechuic acid was isolated from the product and identified. Prototechzcic ,4 cid. L4ction of Heat a12d of Hydrolytic Agents o n Gingerol. Formntioii of Aliphatic Aldehydes (maidy n-Heptaldehydr) and a Ketone ‘( Zingerone.” It has been nientioned that Messrs.Garnett and Grier had noticed that some specimens; of gingerol gave a quantity of mixed crystalline solids when shaken with aqueous sodium hydrogen sul-phitel. The present authors find that this is only the case with old specimens or material which have been heated alone or with acids or alkalis and such specimens have a peculiar’odour whilst pure ones are practically odourless. If a sample of gingerol which has been distilled under diminished pressure is subjected to a current of steam a certain quantity of a volatile oil with an odour resembling cenantliol (heptaldehyde), passes over. This if extracted from the distillate by ether is obtained as a colourless oil. If the ethereal solution is shaken with freshly prepared sodium hydrogen sulphite the bulk of the con-tained oil is converted into a mixture of crystalline additive com-pounds with the reagentl and theset after washing and draining, can be decomposed with aqueous potassium carbonate.The result-ing oil consists almost wholly of addehydes of the fatty series, mainly heptaldehyde ; when shaken with aqueous hydroxylamine acetate it loses its characteristic odour and yields more than one-half its weight of crystals which after being drained and recrystallised once from methyl alcohol form plates melting a t about 5 3 O . (Found C = 65.4 ; H= 12.0. C,H,,:NOH requires C = 65.1 ; H = 11.7 per cent.) The compound was compared with heptaldoxime (m. p. 53-55O) prepared from commercial enanthol ; the substances were identical in all respects 784 LAPWORTH PEARSON AND ROYLE : For the further proof that the compound forming the bulk of the above oil is n-heptaldehyde its cyanohydrin was prepared from the crystalline hydrogen sulphite compound and hydrolysed.The resulting hydroxy-acid (m. p. 66-67O) on titration gave the equiva-lent 162 (C,H,,O requires 160) and direct comparison of the corre-sponding substance from commercial cenanthol afforded proof of its identity with a-hydroxy-n-octoic acid. The oily residue left after passing steam through distilled gingerol if dissolved in ether and then shaken with aqueous sodium hydrogen sulphite frequently furnishes a small quantity of a solid hydrogen sulphite compound of a ketone; the bulk of this may remain dissolved in the aqueous layer from which as well as from the solid the ketone can be recovered by adding a slight excess of hydrochloric acid boiling off sulphur dioxide and extracting with ether.I n this way there is usually obtained a sweet-smelling oil with a very pungent taste. zingerone ” is proposed, was not obtained in solid form until a highly purified synthetic specimen solidified ; various specimens of the compound obtained from gingerol subsequently set t o solid masses by infection. I n order to obtain supplies of the ketone from extract of ginger, the authors Save since utilised the fact that gingerol is readily in part decomposed by hot baryta water into aldehydes mainly volatile in steam and the new ketone. By boiling crudel extracts of the drug with baryta water so long as t.he d o u r of cenanthol is perceptible in the distillate acidifying the residue extracting with ether and subsequently dealing with the ethereal extract in the manner above indicated the new ketone is conveniently and quickly obtained.The yield of zingerone from gingerol is very much below that theoretically possible ; this is doubtless due to the occurrence of polymerisation or secondary re-condsenlsation of the sensitive products of hydrolysis. The new ketone f o r which the name Decomposition of it! ethglgingerol. Formation of Fatty Aldehydes and Methylzingerone. Purified methylgingerol behaves towards hydrolytic agents and when heated alone in much the same way as does gingerol itself. The yields of the simpler products were in this case however more satisfactory especially when boiling baryta water was used and the fatty aldehydes were removed with the steam as soon as formed.Even from recrystallised methylgingerol the fatty aldehydes were of mixed character and this is in agreement with the mixed nature of the fatty acids obtained on oxidation (p. 782). The ket.onic product is in this instance not soluble in alkalis ha,s no perceptibl THE PUNGENT PRINCIPLE OF GINGER. PART I. 785 odour and as i t is but very slightly volatile in steam most of it remains in the flask after removal of fatty aldehydes. It is recovered by extraction with ether and is readily obtained in crystalline form. The properties of this compound which is the monomethyl ether of zingerone are described later. Properties of t h e New Ketone CllHI4O3.The compound when pure is a colourless solid which dissolves somewhat freely in most of the' usual organic media with the sxcep tion of petroleum and crystallises from ether in needles rhombo-hedra or large lustrous platels melting at 31-34". It has a difr tinct sweet odour reminiscent of salicylaldehyde and t o a less extent of vanillin. It has an e'xtremely pungent taste like that of ginger itself but quantitative comparisons have not yet been carried out. When warmed with concentrated mineral acids best with hydro-bromic acid it gives a striking colour reaction. The liquid a t first faintly yellow passes through brownish-yellow reddish-brown to brown tints then becomes opaque purple and blue in thin layers, and ultimately deelp purple; on careful addition of alkali the colour becomes blue then faintly green or nearly colourless.Zingerone is but slightly volatile in steam. As it was not obtained in crystalline form until the research was otherwise com-pleted no attempt was ever made t o determine the composition of the product from gingerol by direct analysis. The formula was deduced from those of its solid and more easily purified derivatives. The substance dissolves only very sparingly in water but freely in dilute aqueous sodium or potassium hydroxides being reprecipi-tated by carbon dioxide. I n alcoholic solutions i t gives a green coloration with ferric chloride. I t s alkaline solutions give neutral, non-pungent insoluble products when treated with benzoyl or sulphonyl chlorides and with chlorocarbonic esters.These observa-tions show that zingerone has a phenolic character. It is optically inactive in alcohol or benzene. Zingerone also1 has the character of a ketone and readily yields a crystalline phelnylhydrazone (plates m. p. about 1 4 3 O ) and semi-carbazone (needles m. p. about 1 3 3 O ) ; but these as well as other hydrazones and oximes were found very difficult t o purify as they quickly decomposed in solution. The e t hy lcarb ona t o-deriva tive C,,H ,,O,*O*CO,Et was prepared by cautiously adding ethyl chloroformate t o an ice-cold solution of the ketone in aqueous sodium hydroxide. The resulting solid was collected dried and crystallised from ether 786 LAPWORTH PEARSON AND ROYLE : Found C=63.1 63.2; H-6-7 6.7. It formed large flat calcite-like prisms melting a t 45-47O.The methyl derivative (rnet<hylzingerone) C,,H,,O,*OMe was pre-pared by shaking an ice-cold solution of zingerone in aqueous sodium hydroxide with methyl sulphate. It is also obt’ained as has already been mentioned by heating o r hydrolysing ‘‘ methylgin-gerol.” It dissolves readily in most of the usual organic media with the exception of petroleum; it is insoluble in water or alkalis, and crystallises from alcohol in colourlees neledles melting a t 5 5 -5-5 6*Z0. CI4Hl8O requires C = 63.2 ; H = 6.7 per cent. Found C = 68.9 ; H = 7.7. C,,H,,O requires C = 69.2 ; H = 7.7 per cent. The methyl derivative has no phenolic properties but it gives the same colour reactions with hydrochloric acid as does zingerone itself.It displays ketonic characters gives crystalline derivatives with semicarbazide phenylhydrazines and hydroxylamine. It is fully saturated and does not reduce cold permanganate in acetone solution or decolorise bromine in chloroform. When oxidised with permanganate in dilute aqueous sulphuric acid i t gives veratric acid (m. p. 1 7 9 O ; proof by mixed melting point method). Jf et7~yZziii~ero~aeox~me C‘,,H,,O,*NOH was prepared by warming the foregoing compound in alcoholic solution with hydroxylamino hydrochloride and excess of sodium acetate. It was isolated by diluting with water and extracting with ether. It crystallises from light petroleum or ether in slender needles melting a t 91-92O. Found C=65*0; H=7.8; N=6*7. C,,H,,O,N requires C = 64.6 ; H = 7.6 ; N = 6.3 per cant.When dissolved in a little pyridine and ether treated with bromine water in excess and then with hydrogen peroxide (Piloty’s test f o r ketoximes) it gives a definite although not very intense yellowish-green colour (bromonitroso-compound) which passee into thel ethereal layer. Cons ti t u t i o n of Met h ylzingero n e and Zingerone. As the sensitive phenolic hydroxyl group of zingerone is absent in the methyl derivative the latter was considered to be the most suitable compound with which to begin experiments with t’he view of throwing light on the structure of these substances. Attempts t o bring about the Beckmann change in the oximel were not fruitful but the oxidation of methylzingerone itself gave the necessary clue. When the methyl ether was warmed with aqueous sodium hypo THE PUNGENT PRINCIPLE OF GINGER.PART I. 787 bromite the odour of broinoform won became perceptible and the solid passed into solution. A t the end of some hours’ interaction, sodium sulphite in excess was added to’ destroy unchanged hypo-bromite steam was passed through the solution t o remove carbon tetrachloride and other impurities then the acid products were liberated by addition of mineral aqid and extracted with ether. The latter extracted a mixture which on repeated recrystallisatioii from ether was resolved into two main portions one containing halogen and the other free from it. The latter formed plates and when recrystallised from water was found t o be hydrated but after exposure in a vacuum became anhydrous and melted a t 95-97O: 0.6573 Gram required 31.5 C.C.N / 10-NaOH for neutralisation with phenolphthalein as indicator whence the equivalent = 208 ; that required for a monobasic acid C,,H,,O,*CO,H being 210. The acid agreed in general characters with B-3 4-dimethoxy-OM6 OMe phenylpropionic acid (I) and this inference appeared to be more probable as gingerol had yielded protocatechuic acid and methyl-gingerol veratric acid (11). It was clear that methyl zingerone must be the methyl ketone of the acid or C,,H,,O,*CO~CH,, and therefore probably OMe Me0 /-\C ET;CH,-CO*C K3. Synthetic experiments described in Part II. have established the truth of this inference. Moreover a synthesis of zingerone itself, which is described in the same communication has shown that of the two alternative formula deducible from that of the methyl ether the formula \-/ OMo HO/ ‘ClI,*CH2*CO*CH,.must be assigned t o zingerone; the latter is therefore 4-liydroxy-3-met hox yphenylethy 1 me thy1 ketone. \-/ The Coiistitution of Ginyerol. There is no reason t o doubt that except for the numbers of carbon atoms contained in the residues which furnish the fatty aldehydes on hydrolysis the structure of the two or more pungent constituents of gingerol are essentially similar and therefore 788 LAPWORTH PEARSON AND ROmE : mutatis mzczandis the following remarks are applicable t o all such constituents. The molecule of that component of gingerol which furnishes heptaldehyde clearly has the composition of a compound of that aldehyde with zingerone that is C,H,,O + C,,H,,(OMe) *OH, methylgingerol being C,H,O + C,,,H,,(OMe),.The ketonic charac-ter of these two compounds is not a matter reasonably admitting of doubt but the function of the fourth oxygen atom is ce'rtainly not quite clear. It is eatre8mely difficult if not impossible t o depict a condensa-tion product of one molecule of heptaldehyde with one of methyl-zingerone which accords with the above conclusions without assum-ing that thO fourth oxygen atom has hydroxylic functions. The only reasonable alternative would appear t o involve one of the following assumptions (1) that the carbonyl groups in the ketone and the aldehyde are jointply engaged in the grouping but this is not in accordance with the ready hydrolysis of gingerol and methylgingerol with baryta water as such complexes are normally stable t o alkalis; or (2) that the molecule contains a peroxide-like grouping such as : 0-0 O- 0 .I t or I I , but the two substances have none of the characters of peroxides. Again neither of these assumptions is in harmony with th0 fact that methylgingerol reacts with hydroxylamine giving a ketoxime which yields unchanged methylgingerol once more by mild hydro-lysis. The authors have been forced to infer therefore that the fourth oxygen atom has hydroxylic functions and that the failure of methylgingerol to give methane with magnesium methyl iodide is due to the primary reaction of the reagent with the carbonyl group and the insolubility of the additive product; the reaction of methyl-gingerol with acetyl chloride and more especially with phenyl-carbamide are fully in agree'ment with this view.I f the presence of the hydroxyl group in methylgingerol is assumed then this compound and gingerol itself appear as " aldols," and tho whole of their properties including the optical activity with one signal difficulty are readily understood and the pungent constituents of gingerol can be represented by one of the two general formulze : -C c! H,* C- -(j-c- 9 I I I THE PUNGENT PRINCIPLE OF GINGER. PART r. 789 CH,*CH,*CO*CH,*CH(OH)*(CK~]~*CH~ /\ ()OMe OH or where the residue CzHm+l is a saturated alkyl radicle probably normal in all cases and n=5 and either 4 or 3 (or both). Having regard to the very general occurrence in natural products of open, straight-chain aliphatic residues the firsti of the two general formulze appears the more probable.The optical activity of the compounds is explicable on the basis of either of the formulz suggested. Summary. The oleo-resin gingerol the pungent principle of Zingib er oficinaie which was first investigated by Thresh and more recently by Garnett and Grier is essentially a mixture of optically active saturated phenolic compounds derived from a residue of zingerone, or 4-hydroxy-3-methoxyphenylethyl methyl ketone in association with a molecular proportion of the residue of a saturated aliphatic aldehyde which in the main constituent is n-heptaldehyde. The constituents are probiably '' aldols " (P-hydroxy-ketones) of the general type : C,H,(OH)(OMe)*CH,*CH,-CO*CH,-CH(OH)*[CH2],*CH,, where n in the principal constituent is 5 and 4 or possibly 3 in the main secondary constituent. Only traces of solid matter of camphoraceous appearance have been observed in gingerol but methylgingerol a mixture of the monomethyl ethers of the gingerol constituents and methylgingerol oxime has been obtained in crystalline form. The work described in this paper and in Part 11. was begun early in 1914 and carried to its present stage in July 1915. We desire to express our very cordial thanks t o Messrs. Garnett and Grier for entrusting us with the continuance of their investiga-tions and for the considerable trouble they took t o facilitate its progress. Grateful acknowledgments are also due t o James Woolley and Sons Mancbester for carrying out the large-scal 790 LAPWORTH AND WYKES: extraction of th0 drug and to tlie British Pharmaceutical Confer-ence for the! use of a grant from which part of the expenses of the research was defrayed. ORGANIC CHENZICAL LABORATORIES, THE UNIVERSITY MANCHESIER. [Recsived April 27th 1917.