WRIGHT AXD LUFF OS THE ALKALOIDS, ETC. 151

XIX. The dlkalods of the Aconites. Part 11. On the Alkaloids con- tained in Aconitum Feroz.

By C. R. A L D E R WRIGHT, D.Sc., Lecturer on Chemistry, and A. P. LUFF, Demonstrator of Chemistry, in St. Mary's Hospital Medical School.

8 1. Composition of Pseudacoizitine. FOR some years it has been known that the mixtures of alkalo'ids ex- t,racted commercially from A. NapeZZus and A, ferox are not at all identical, and it has been shown by von Schro f f , T . B. Groves , and others, that the approximately pure alkalo'ids isolated from the two species, and purified by crystallisation from ether, alcohol, &c., differ in this respect, that whilst the N~peZZus base yields well cryatallised salts with facility, that from A. feroz does not form any kind of crys- tallisable salt at all (as shown below, we have found that there are exceptions to this rule), Accordingly, the terms aconitine and pseudaconitine have been employed t o designate the two alkalolds. These two substances have probably baen confused together by most of the older experimenters on the aconite alkaloids, who moreover did not obtain the crystallisable bases free from uncrystallisable alkalo'ids accompanying them (or formed from them by decomposition during extraction ?).

The results detailed in Part I of these researches (this JowfiaZ, 1877, i, 143) tend to show that the crystallisable physiologically active base

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152 WRIGHT AND LUFF ON THE

of A. N a y e l l u s is a uniform homogeneous alkalond indicated, when per- fectly pure (to obtain which condition is a matter of some difficulty), by the formula C33HA3N0,2 ; for the perfectly pure base isolated from several specimens of roots exhibited exactly the same properties, and gave identical numbers agreeing well with this formula. Further ex- periments, which will be given in detail in a future paper, show that under certain conditions this base readily loses the elements of water, forming a well crystallised anhydro-derivative, closely resembling the parent base ; the somewhat irregular numbers obtained with different specimens of aconitine nearly, but not perfectly purified, are probably in many cases due to varying admixture of this derivative (produced during the process of extraction) with the unaltered aconitine. When subjected to the action of saponifying agents, it breaks up in accord- ance with the equation-

forming belzzoic acid and a new alkaloid. The crystallisable physio- logically active base of A. fwox is in many respects very similar to aconitine. Like that base, it forms a derivative closely resembling the parent alkalo?d, by loss of the elements of water ; and the presence of this derivative, formed during the process of extract'ion, in the base obtained from the roots can, under certain conditions, be recognised : the action of sapoiiifying agents, however, sharply distinguishes the A . f erox base, pseudnconitine, from the aconitine of A. NapeZlzcs : for it splits up, by a reaction parallel t o the above, forming an acid identified

as d i ~ e t h y ~ r o t o c a t e c h u i c acid, C6H3 O.CH, , together with a new

alkalo'id altogether different from that produced in like manner from aconihe.

In Part I it was incidentally stated that pseudaconitine is repre- sent,ed by the formula C3sH,,NOll : since these earlier experiments were made, we have found that the base then examined was not wholly pure, as it contained an admixture of the anhydro-derivative, upopseud- aco?zitiue, above referred to : pseudaconitine, when perfectly pure, is represented by the formula, C36H49N012, apopseudaconitine being formed from it by the reaction,

COOH

{0CH3

The specimen of alkaloi'd from which these earlier results were obtained was prepared by Mr. T. B. Groves (Year-book o j Pharmacy, 1873, 500) by exhausting the powdered roots with methylated spirit acidulated with hydrochloric acid in the proportions of 2 drachms to the gallon (1 in 640 by volume, corresponding to about 0.06 per cent. by

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ALKALOIDS O F THE ACONITES. 153

weight of anhydrous HCl), evaporating to a small bnlk, aud extract- ing alkaloids by means of ammonia and ether, the ethereal solution being allowed to evaporate spontaneously, and the crystals thus formed separated from noncrystalline matter by filtration, pressure and crys- tallisation from alcohol. Owing to accidental circumstances, how- ever, some six or seven weeks elapsed between the concentration of the alcoholic extract to a small bulk and the further treatment of the con- centrated liquid ; probably this circumstance (or perhaps some over- heating during evaporation, &c.) was the cause of the partial dehy- dration of the pseudaconitine ; for other batches of roots worked up by Messrs. H o p k i n and Wil l iams (with the sole difference that 30 grains of strong sulphuric acid were used per gallon of alcohol instead of 120 of aqueous hydrochloric acid, which is not far from the same proportion of actual anhydrous acid) yielded, as described below, an alkalo'id which had not been noticeably dehydrated at all ; whilst the results detailed in Ej 4 show that contact with excess of dilute hydro- chloric acid at 100" for some hours suffices entirely to convert psenda- conitine into apopseudaconitine. The following numbers were obtained :-

(A). Crystallised base as received from Mr. Groves dissolved in a rnixtu1.e of alcohol and ether, and recovered by spontaneous evaporation :-

0.3165 gram dried at 100" gave 0.7410 CO, and 0.2180 H20. 0.8090 gram gold-salt gave 0.1575 Au.

(B). Second crop of crystals regained from mother-liquors of A by further spontaneous evaporation :-

0.2925 gram dried at 100" gave 0.6805 CO, and 0.1970 H,O. 1.3260 gram gold-salt gave 0.2565 Au. 0.5730 gram of base burnt with soda-lime gave 0.0845 Pt.

Calculated for Found. C36H49N012. C3RK7NOll. A. B.

Carbon in base.. . . 62.88 64.38 63.84 63-45 Hydrogen ?, .. .. 7-13 7-03 7.65 7.48 Nitrogen ,, . . . . 2.04 2.09 - 2.09 Gold in gold-salt . . 19-10 19.44 19.46 19.34

Manifestly these numbers agree well with mixtures of pseudaconi- tine and apopseudaconitine, the latter being contained in larger proportion in Specimen 4, as might be expected from its somewhat less solubility i i i alcohol and ether (vide § 4).

Another sample of pseudaconitine prepared by Mr. Groves from a different batch of roots, and purified not only by numerous crystal- lisations, but also by conversion into mercuriodide and regeneration

VOL. XXYIII. N

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154 WRIGHT AND LUFF ON THE

therefrom, gave numbers closely accordant with the formula C,,H,,NO 12-

0.3540 gram gave 0.8140 GO2, and 0.2410 H,O. 0.3195 gram gave 0.7365 CO,, and 0.2200 H,O.

Calculated for C,,H,J012. Found.

Carbon .......... 62-88 62.71 62.87 Hydrogen.. ...... 7.13 7.57 7-65

Unfortunately this specimen was too small in quantity for any extended examination.

In order to subject pseudaconitine to a thorough examination several ounces were purchased of the rough alkaloid extracted from A. ferox roots by DiIessrs. H o p k i n and W i l l i a m s by percolation with alcohol acidulated with sulphuric acid in the proportion of 30 grains to the gallon (about 0.05 per cent. by weight) ; from this the crystallised base was prepared by dissolving in ether, filtering from a little undissolved matter, and allowing to evaporate spon- taneously after admixture with about half its bulk of “ light petroleum distillate ” (that portion of the ‘‘ benzoline ” of the oil-shops which dis- tilled off in a water-bath). A large crop of crystals mixed with a, little resinous matter was thus obtained, from which the crystals were sept-Lrated by stirring up with a little alcohol (which dissolved the resinous matter with some of the crystals) and filter-pumping. These crystals were again crystallised from e ther-petroleum, furnishing a crop of apparently homogeneous crystals (1). To see whether these consisted of the pure base they were purified by solution in hot alcohol, addition of hot water till a milkiness appeared, clearing up by addition of a few drops of alcohol, a n d slow cooling ; white cauli- flower-like crystals thus formed (2). Another portion of crystals (1) were crystallised four times more from ether-petroleum (3). From these three specimens the following numbers were obtaioed :-

Specimen (1).

Specimen (2).

0.3225 gram gave 0.7465 CO, and 0.2135 H,O. 0.3840 gram gold-salt gave 0.0750 Au. 0.9395 gram gave 0..5540 GO, and 0.1610 H,O. 0.5105 gram burnt with soda-lime gave 0.0765 Pt. 0.704-5 gold-salt gave 0.1385 Au. 0.2380 gram gave 0.5460 CO, and 0.1580 H20. 0-3025 gram gold-salt gave 0.0590 Au.

Calculatrd for Found.

Specimen (3).

C36H,,NOU. (1 .) (31.1 (3 .> Carbon ............ 62.88 63.11 63.09 62.57 Hydrogen ........ ’7.1 3 7.36 7.47 7.37 Nitrogen.. ........ 2.04 - 2.12 - Gold in An-salt .... 19.10 1 9 5 3 19.66 19.50

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ALKALOIDS OF THE ACOKITES. 155

It is evident from these numbers that the crystallised base thus obtained was essentially pseudaconitine, but the high percentage of gold found in the gold-salt seems to indicate that (just as with aconitine, Part I), mere crystallisation of the free base from ether, alcohol, &c., does not suffice to free it entirely from accompanying substances ; a circumstance clearly proved by the following numbers obtained with base purified by conversion into recrystallised nitrate, regeneration, and crystallisation from ether-petroleum.

Specimen A.-Nitrate prepared from the crude material supplied by Messrs. H o p k i n and W i l l i a m s ; crystals of the salt were prepared by rubbing in a mortar the rough nlkalo'id with enough dilute nitric acid t o dissolve it, adding a few drops of concentrated nitric acid, and vigorously rubbing for some time, whereby a thick magma of crystals was formed ; this was drained on the filter-pump, washed with weak nitric acid, dissolved in warm water, and made to crystallise again by addition of a few drops of concentrated nitric acid, and stirring. The crystals thus obtained were perfectly white after filter-pumping and washing with dilute nitric acid ; they were again crystallised in the same way, and then decomposed by dissolving in water, adding sodium carbonate and shaking with ether ; the base which crystallised fyom the ether on spontaneous evaporation was washed with a little alcohol on the pump-filter, and then constituted a snow-white crystdine mass :-

0.2775 gram dried at lob" gave 0.6400 CO, and 0.1845 H,O. 0.2920 gram dried in a current of air at 80" gave 0.6700 CO, and

0.5015 gram gold-salt gave 0.0970 Au. Specimen B.-Similarly prepared, the purified alkaloid recrystallised

from ether and petroleum several times (Specimen 3, supTa) being employed in the first instance instead of the impure base obtained from Messrs. H o p k i n and Wil l iams.

0.1980 H,O.

0.2880 gram dried a t 100" gave 0*6630 CO, and 0.1920 H20. 0.5655 gram gold-salt gave 0.1085 Au. 0.3090 gold-salt gave 0.0592 du . PO230 gram of base dried at 100" gave by vacuum-combustion

Specimen 0.-The preceding sample of base, B, again converted

0.2750 gram dried at 100" gave 0.1845 H,O and 0.6330 GOz. 0.4640 gram burnt with soda-lime gave by titration of the evolved

ammonia 0.00945 gram N ; by conversion into platinum salt, 0.0695 Pt.

process 0.000473 gram nitrogen.

into nitrate, recrystallised, and regenerated from the salt :-

0.5550 gram gold-salt gave 0.1070 An. N 2

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156 WRIGHT AND LUFF OK THE

Fouii d . A. B. C.

Calculatcd. ,----- 7 Mean. C,, ...... 432 62.88 62-90 62.57 62.59 62.77 62.71 Hi, ...... 49 7-13 7-39 7.53 7.41 7.45 7.44

N . . ...... 14 2.04 - - 2.06 2.03 2.12 2-07 01, - - ...... 192 27.95 -

-- - - -

Calculated for Found. C3,H,SN0,2,HCI,AuCl,. A. B. C. Mean.

Gold = 19-10 19.34 19-18 19.16 19.28 1924 -

The determination of the nitrogen in B was made by combustion with oxide of copper and metallic copper in a Sprengel vacuum. 0.0230 gram of base thus gave 27-95 C.C. of GO2, and 0.377 of N a t 0" and 760 mm. (corrected by subtracting the minute amounts of each gas obtained in a blank experiment made simultaneously), or 0.0150 gram carbon, and 0.000473,of nitrogen. These values give 65.2 per cent. of carbon, somewhat too high, but not more so than the experimental errors might account for ; the volume ratio of N to GO, is 0.377 - 1 1 'L7.y5 - - - - 74.2, giving the ''atom "- ratio -, the calculated ratio

37 1 1

being 36- Pseudaconitine is far more readily soluble in alcohol and ether than

aconitine ; when crystallised from ether, or, better, ether and petro- leum spirit, it f o r m transparent needles and sandy crystals ; but if the evaporation be not extremely slow, and especially from alcoholic solu- tions, it is apt t o separate as a varnish at the upper edge of the solution, soon becoming a confused mass of milk-white cauliflower-like crystal- line efflorescence : the crystals, when air-dry, are hydrated, the water of crystallisation being lost a t 80" in a current of dry air without any fcsion or fritting ; if heated to loo", the hydrated crystals lose their water with fritting more or less marked (the anhydrous base also frits a t looo, but less quickly).

Crystals from Specimen No. 3 of base purified by several cry stallisations from etber-petro- leum ; 0.6640 gram of air-dry crystals lost a t 100" 0.0175.. ........................ = 2-65 per cent.

Crystals from base purified by conversion into nitrate and regeneration (Specimen Aszqwa) ; 1.2770 gram lost a t 80" in a current of dry air 04360 ............................ = 2.82 ,,

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ALKALOIDS O F THE ACONITES. 157

Base from nitrate (Specimen C supra) ; 1,0020 gram lost at 100" 090270 ................ = 2.69 per cent.

Calculated for C36H19N012,Hz0. ..... = 2.55 .. The salts of psendaconitine, for the most part, are so extremely diffi- cult to crystallise that hitherto they have only been obtained as varnishes by spontaneous evaporation ; the kind of treatment above described, which yielded a crystallised nitrate, did not answer with the snlphate, hydrochloride, acetate, oxalate, &c. If the alkaloyd be dissolved in just sufficient dilute warm nitric acid t o form a nearly neutral salt, the liquid generally dries up t o a varnish without crystal- lising ; if, however, a crystal of nitrate be placed in the liquid and the whole well stirred, the dissolved salt gradually separates in crystals : crystallisation takes place, however, with far greater facility on adding a few drops of concentrated nitric acid and stirring vigorously. The following numbers were obtained with a specimen of the salt r e c r p tallised from a nearly neutral aqueous liqclid :-

0.7920 gram of air-dry salt Iost at 100" 0.0570 = 7.19 per cent.

0.2680 gram of dry substance gave 0.5740 GO, and 0.1805 H20. Calculated for C36H4,N0,2,HN03,3H20 = 6.72 ,,

Calculated. Found. Carbon .......... 57.60 58.39 Hydrogen ........ 6.67 7-48

The condensed water was strongly acid, as might have been expected in the combustion of a nitrate; whence also the high value for the carbon found.

The gold-salt of pseudaconitine is distinctly crystalline when pre- cipitated from a dilute solution : after drying over sulphuric acid it can be readily crystallised from boiling alcohol in minute needles only sparingly soluble in cold alcohol : when air-dry the crystals are an- hydrous. The following combustions of different specimens of gold- salt were made, the high percentage of carbon found being apparently due to the escape of a minute quantit>y of chlorine liberated on heat- ing the gold-salt ; for the condensed water contained chlorine, and strongly acted on iodide and starch-paper.

(A) Gold-salt prepared from base only purified by repeated crystal- lisation from ether-petroleum-

(B) Another sample similarly prepared-

0,3215 gram gave 0.5025 CO, and 0.154,5 H,O.

0.2'330 gram gave 0.4600 COs and 0.1410 H,O.

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158 WRIGHT AND LUFF ON THE

(C) Prepared from base regenerated from nitrate-

(D) Another specimen similarly prepared- 0.4660 gram gave 0.7280 GO, and 0.2205 H,O.

0.3250 gram gave 0.5125 CO, and 0.1560 H,O.

C~~H,SNOI.?,HCI,-~UCI~. A. B. C. D. Carbon . . . . 42.11 412.61 42-82 42.60 42-99 Hydrogen .. 4.87 5.34 5.35 5.25 5.33

Calculated for Found.

Although crystallisalde, the auro-chloride does not seem t o be as well suited for the final purification of the nearly pure base as is the nitrate ; a sample of salt prepared from the nearly pure base crystal- lised several times from ether-petroleum (Specimen (3) supm), and containing originally 19.50 per cent. of gold was recrystallised from boiling alcohol: the crystals dried over sulphuric acid and finally a t 100" were not perceptibly altered; 0.8095 gram gave 0.1575 Au = 19.47 per cent. On the other hand, as above stated, when the same sample of base was converted into nitrate, recrystallised, and the base regenerated, the gold-salt finally obtained contained 19.18 and 19.16 per cent. Au (Specimen 13, szq~ra), the theoretical value being 19.10. It is noteworthy that just the same thing is observable with aconitine, no diminution in porcentage of gold being noticeable on crystallising from alcohol the gold-salt (prepared from the alkaloid cryatallisecl from ether, &c., only), whilst as shown in Part I, a diminution of 0-2 to 0-3 per cent. is brought about by conversion into hydrobromide and i*ecrystallising and regenerating the base, the pure alkalo'i d thus ob- tained furnishing a gold-salt containing the theoretical percentage of gold, whilst the original approximately pure base contained too high an amount by 0.2 to 0.3 per cent.

The mercuriodide of pseudaconitine prepared by precipitating R

solution of tbe base in acetic acid by potassium mercuriodide, is an amorphous, flocculent, white precipitate, very sparingly soluble in water : after washing and drying at 100'-

0.5510 gram gave 0.2970 AgI Calculated for C36H49N012,HI,Hg'12 ,, = 30.02 ,,

Iodine = 29.12 per cent.

Pseudaconitine is sparingly soluble in water and in fixed caustic alkalis, somewhat more readily in ammonia and sodium carbonate ; from the latter solution, if saturated, it can be regained in an impure state (owing to incipient saponification) by quickly evaporating, when the alkaloyd separates as a resinous film which yields crystals on solu- tion in ether, addition of petroleum spirit, and spontaneous evapora- tion, if it have not been too long exposed to the action of the hot : lkaline fluid. I n its qualitative reactions it closely resembIes aconi-

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ALKALOIDS OF THE ACONITES. 159

tine, being precipitated by mercuric chloride (precipitate redissolved on moderately large dilution) ; potassium mercurobromide (precipitale only sparingly soluble on adding water) ; potassium mercuriodide (precipitate 1-ery sparingly soluble) ; tannin ; iodine dissolved in potas- sium iodide ; gold chloride ; caustic potash, soda, and ammonia ; sodium carbonate, &c.; the precipitates being more or less readily dissolved on largely diluting with water. Platinic chloride only forms a precipitate in concentrated solutions, the salt being pretty readily soluble in water and also in alcohol. From aconitine pseudaconitine differs sharply in molecular weight, and in solubility in alcohol and ether ; also in crystallising with H,O (aconitine crystallises anhydrous, Part I) ; and more especially in melting point : as stated above pseu- daconitine slightly frits a t 100"; in a capillary tube it melts to an extremely viscid, transparent fluid a t about 104-105", the exact point of fusion not being very distinctly marked ; whilst pure aconitine first melts completely at 189" (corrected), a slight fritting and browning being noticeable a few degrees below the melting point. As shown below, the action of saponifying agents on pseudaconitine gives rise to dimethyl protocatechuic acid ; whilst under the same conditions, as will be shown in a future paper, aconitinc gives rise to bcnzoic acid.

Pseudaconitine can be heated to 105" for some hoiirs without mate- rially da,rkenirig in colour or losing in weight (if deprived of its water of' crystallisation previously) : at somewhat higher temperatures, how- ever, it turns yellowish, and then brownish, and finally dark chestnut, losing in weight several per cents. The loss of weight, however, ap- pears to be due, a t least in part, to the removal of substances other than water, as the increase in carbon percentage does not correspond t o that due to the loss of weight, assuming water only to be removed: thus, after four hours' heating to 135", 8-38 per cent. in weight was lost, but the chestnut-coloured varnish produced contained carbon 64.30, hydrogen 7-22; had the 8-38 per cent. lost been due to the removal of water only, the percentages should have been-carbon, 68.63 ; hydrogen, 6.77. The varnish, when dissolved in tartaric acid and precipitated by sodium carbonate, yielded a base soluble in ether with brown flakes not dissolved by that menstruum ; the ethereal solu- tion furnished, by spontaneous evaporation, only a nearly colourless varnish from which no crystals or crystallised salts could be obtained : this amorphous alkaloid contained carbon, 65-51 ; hydrogen, 7-50, whilst the composition, 2CXHi9NOL2-3Hz0, would require-carbon, 65.45 ; hydrogen, 6.97. A precisely similar substance was obtained in an experiment made with a view to see if pseudxconitine resembles quinine and cinchonine in the formation of an isomeride by heating the acetate: acetate of pseudaconitine was heated to 130-140" for an hour, and the somewhat ccloured mass dissolved in aqueous t.a.rtaric

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160 VRIGIHT AND LUFF ON THE

acid and treated with sodium carbonate and ether : the residue left on spontaneous evaporakion of the ethereal solution would not yield crys- tals nor crystalline salts ; it contained carbon, 66.27 ; hydrogen, 8.2$, the composition, C36H49N012-2H20, requiring-carbon, 66.36 ; hydro- gen, 6.91.

§ 3. Act ion of Alkalis o n Psezcdaconitine. When pseudaconitine is heated to 100" in sealed tubes wit,h alcoholic

soda for 12 hours or more, it becomes completely broken up, with as- similation of the elements of water, into dimethyl protocatechuic acid and a new base, to which it is proposed to apply the term Pseudnco- nine ; thus-

A small quantity of a yellowish resinous bye-product of feebly acid character is also formed by the further action of the alkali on the pseudaconine, but the amount of colouring-matter produced is but small. If, instead of allowing the reaction to take place in a sealed tube, a boiling alcoholic solution of soda be employed, an inverted condenser being attached, complete saponification is also brought about in less than 24 hours, but the amount of resinona bye-product is increased; on the other hand it is diminished if , in the sealed tube, the air be displaced by coal-gas before closing the tube. Thus the follow- ing values were obtained, the dimethyl protocatechuic acid formed being extracted by evaporating off the alcohol from the product of the reaction, and trea,ting the residue with hydrochloric acid and ether ; three agitations of the acidified aqueous fluid with about its on-n bulk of ether were found to remove completely the dimethyl protocatechuic acid, which was obtained in a weighable form by simply allowing the ethereal extract to evaporate spontaneously and drying the residue at 100'. As the residue thus obtained contained small quantities of feebly acid resinous amber-coloured bye-product, its alkali-saturating power was carefully determined with decinormal soda solution : the percent- ages of acid calculated from the weight of the residue and from the soda neutralised in three experiments were as follows :-

(A) 1.0720 gram of pure anhydrous psendaconitine heated to 100" for 24 hours with alcoliolic soda in a tubc from which the air had been displaced by coal-gas before sealing up. Residue dried at 100", weighed 0.3060 gram: soda solution neutralised cor- responded to 0.2917 gram of the monobasic acid, C9H,,Oa.

(B) 1.3105 gram similarly treated, save that the air was not dis- placed by coal-gas. Residue weighed 0.3860 ; soda solution neutrnlised was eqiiivalent to 0.3733 gram C,HI0O4.

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ALEALOIDS OF THE ACONITES. 161

(C) 1.3730 gram boiled with alcoholic soda 24 hours. Residue weighed 0.4440 gram : soda neutralised was equivalent to 0,4372 gram CgH1004.

Calculated for above equation.

26.49 Percentage of C,H,,O4 obtained from C36H49N012. ... Found.

A. B. C. From weight of residue .......... 28.54 29.45 32.34 From result of titration .......... 27.21 28.48 31.84

The coloured resinous feebly acid bye-product was present in sensibly larger quantity in €3 than in A, and to a considerably larger amount still in C : whence it is evident that the amounts of pure dimethyl protocatechuic acid actually formed in these experiments were very close to the theoretical quantity, t.he higher numbers obtained above being manifestly due to the increasing amount of this bye-product. The complementary product, C27H4,NOg, pseudaconine, formed in these three experiments, did not contain any undecomposed pseudaconitine, as on subjecting it to a second saponification no dimethyl protocate- chuic acid at all was formed, although the resinous bye-product was produced in small quantity.

The dimethyl protocatechuic acid thus obtained dissolved in boiling water, leaving behind a minute amount of resinous matter ; on cooling i t crystallised out in anhydrous needles. After recrystallisation from boiling water two different specimens (one derived from Mr. Grove's batch of alkalo'id (9 l), and the other from Messrs. H o p k i n and Williams' batch) melted respectively at 176-177" and 177-178" (corrected). On fusion with caustic potash at 250", acidifying the " melt," and shaking with ether, protocatechuic acid was abundantly formed, easily identified by its peculiar colour-reactions with ferric chloride, &o.

0.2325 gram gave 0.5030 CO, and 0.1175 HzO.

C g . . . . . . . . . . . . . . 108 59.34 59.01 H,, ............ 10 5-49 5.62 0 4 .............. 64 35.1 7

On analysis the following numbers were obtained :-

Calculated. Found.

- ~~ ~

CgH1oOa ........ 182 100.00

The melting point, physical properties, and qualitative reactions (especially the formation of a gelatinous silver-salt on the addition of silver nitrate t o the neutral ammonia-salt) of this substance exactly agreed with synthetically prepared dimethyl protocatechnic acid ; Becket t and Alder-Wright , however, found (this JozmzaZ, 1876, i,

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162 WRIGHT AND LUFF ON THE

304) that the latter crystallised with H,O : on the other hand, Koelle describes synthetically prepared dimethyl-protocatechuic acid as an- hydrous (Liebig's AmaZen , clix, 240), as is also that prepared by the oxidation of methyl-eugenol (Graebe and B o r g m a n n , ibld., clviii, 282) ; the acid from pseudaconitine crystallised anhydrous both from boiling water and from ether containing water.*

Attempts yet further to identify this acid as dimethyl protocatechuic acid by distilling it with soda-lime led to but little result on account of the minute yield: Koe l l e obtained (Zoc. cit.) dimethyl-pyrocnte- chin (in an impure state) by the reaction-

C O . 0 H C6H3 O.CH, { O.CH,

the yield being not more than 5 per cent. : we obtained a small quantity of an oil resembling in appearance and odour the dimethyl pyrocate- chin obtained from hemipinic acid by similar treatment ( B e c k e t t and A l d e r - W r i g h t , this JournnZ, 1876, i, 281) ; the quantity was too small to determine the boiling point, or to purify fo r combustion, but, on heating with amorphous phosphorus n"nd hydriodic acid to 100" for some time and shaking with ether, a substance was dissolved out readily soluble in water, and giving with ferric chloride the colour reaction of yyrocatechin : the original oily matter did not do this, SO

that there can be no doubt that the oily body really was dimethyl pyrocatechin converted into pyrocatechin by the hydriodic acid as shown by B e c k e t t and Alde r -Wr igh t (Zoc. cit.), thus:-

It is noteworthy that the mixture of pseudaconitine and apopseuda- conitine, crystallised from alcohol, and nearly but not quite pure, pre- pared by Mr. G r o v e s ( 5 11, and also the crude alkalo'idal mixture, manufactiired by Messrs. H o p k i n and Williams, furnished on saponification an acid, from which minute amounts of benzoic acid were separalsle by distillation with a large bulk of water, dimethyl- protocatechuic acid not being thus carried over. By neutralising the distillate with soda, evaporating to a small bulk, acidifying, and shak- ing with ether, small quantities of benzoic acid were obtained, melting at 120- 121" in each instance. The pseudaconitine regenerated from

* Since this paragraph was written it has been shown by K a e t a U k i m o r i &;I a t s mo t o (Deut. Chem. Ges. Ber., xi, 122) that dimethylprotocatechuic acid crptallises anhydrms from hot solutioils when the crystals form at a temperature above 50") and v-ith H,O from dilute solutions below 50"

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ALKALOIDS O F THE ACONITES. 163

the nitrate, after recrystallisation of that salt, however, did not furnish sensible quantities of benzoic acid by this mode of treatment. It has been stated abore, and will be demonstrated in a future paper! that benzoic acid is a product of the saponification of aconitine, whence it appears extremely probable that these two preparations contained small quantities of aconitine, removed by conversion iuto nitrate, and recrystallising. The amount of aconitine (if aconitine i t were) thus present represented only about 0.5 per cent. of the total alkaloids in the case of the first substance, and 1 per cent. in the case of the second. Whether the base furnishing benzoic acid is a natural constituent of A.ferox, or whether it arose in the presen-i; instances from admixture of ft few roots of A . NapeZZus, or some other species containing aconitine, with the A . ferox roots, cannot be determined ; this latter is extremely probable, although the former is also very likely, the more so as we have found that the rough alkalo'idal matters obtained from the roots sold as A. NapeZlus furnish a little dimethylprotocatechuic acid on saponification along with much benzoic acid.

Pseudaconine is obtainable in a state of considerable purity by ren- dering alkaline with sodium carbonate, and evaporating to dryness on the water-bath, the acid liquid obt'ained by saponifying pure pseudaco- nitine with alcoholic soda, and removing the dimethylprotocatechnic acid and resinous bye-product formed by shaking with ether. From the residue alcohol dissolves out pscudaconine, which can be purified by evaporating off the alcohol from the clear filtrate, and dissolving the residue in ether, in which it is readily soluble. On spontaneous eva3po- ration a clear, slightly yellow varnish, fusible in the water-bath, is obtained, pretty readily soluble in water, forming a solution of strongly alkaline reaction and bitter taste, n o t prodwing the slighfest lip tingZing. The following numbers were obtained with the varnish dried a t lOO", till constant in weight :-

0.2970 gram gave 0.2105 H,O and 0.6680 CO,. 0.2510 gram gave 0.1795 H20 and 0.5630 CO,. 0.9645 gram burnt with soda-lime gave by titration of the evolved

ammonia 0.02533 gram N.

Calculated. Found. C 2 7 .......... 324 61.95 61.34 61.17 HdI .......... 41 7.84 7.87 7-94 N ............ 14 2-67 2.62 O9 - .......... 144 27-54

C17H*,NO, .... 523 100.00

As yet it has not been found practicable to obtain pseudaconine

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164 WRIGHT AND LUFF OK THE

in a ci*ystallised state in any quantity ; but if a thin film of the base be left on a watch-glass by evaporation of its ethereal solution, and set aside for some weeks, it gradually becomes converted into a mass of well defined acicular crystals a quarter of an inch in length. None of its salts have yet been obtained crystallised.

Unlike pseudaconit'ine, pseudaconine can be heated to '120-130" for two hours, without losing in weight more than traces ; it darkens in colour somewhat by the treatment, however. A t higher temperatures it probably loses water, forming an anhydro-derivative (vide § 3). The aqueous solution throws down a brown precipitate of silver hydrate from the nitrate, becoming black, a,nd evidently reduced on beating ; it reduces ammoniacal silver nitrate on boiling, and gold chloride in the cold on standing, but produces no appreciable reduction of cuprous oxide from F e h l i n g ' s solution, el-eri when boiled therewith for some time. It readily neu tralises acids, requiring quantities of titrated soh - tions, corresponding to the equivalent 523 ; the salts have as yet not been obtained otherwise than as varnishes, or scale-preparations. The hydrochloride throws down from gold chloride a yellow precipitate, which either decomposes whilst washing and drying, G r else contains reduced gold, as it exhibits no constant composition. Three different specimens contained 23.65, 25.41, and 25.85 per cent. of gold respec- tively, the formula, C2,H41N09,HC1,AuC13, requiring 22.74 per cent. ; an aqueous solution of the gold-salt deposited reduced gold on standing over sulphuric acid i n the dark.

As a check on the molecular weight, the mercuriodide was prepared by dissolving the base in acetic acid, and adding potassium mer- curiodide ; it formed a white, amorphous precipitate, of which, after washing and drying over sulphuric acid, and finally at loo", 0.7240 gram gave 0.4650 AgI, and 0.1540 HgS.

Calculated for C27H,,,N09,HI,HgI,. Found.

Iodine ........ 34.48 39-71 Mercury.. ....... 18.10 18.31

In most of its qualitative reactions pseudaconine resembles pseuda- conitine, the precipitates being usually somewhat more soluble in water. Caustic potash in excess precipitates it from moderately con- centrated solutions, but not from dilute ones. Sodium carbonate does not precipitate saving from the most concentrated solutions, e.g., when a solution in excess of sodium carbonate is evaporated down until the salt begins to crystallise out ; the baae then partially separates as a fluid mass.

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AIJKALOIDS OF THE ACONITES. 165

9 3. A c t i o n of XaponiJying Agents on PsezcdcLconiti?ie at Temperatures above 100".

If the saponification of pseudaconitine with alcoholic soda be carried out a t a temperature of about 140", the ultimate products formed differ from those produced a t 100", in this respect, that the base comple- mentary to dimethylprotocatechuic acid contains the elements of H,O less than pseudaconine, and may therefore be termed apopseudacoruhe. In all probability this is formed by the removal of water from pseuda- conitine, forming apopseudaconitine (8 4), and the subsequent saponi- fication of the base thus produced.

and not by the direct dehydration of pseudaconine ; for, as above stated ($ 2), pseudaconine is not perceptibly altered by heating to a tem- perature of about 130°, whilst pseudaconitine loses the elements of water a t a temperature considerably below this.

I n general and physical properties apopseudaconine closely resenzbles pseudaconine, the only noticeable difference between them being the numbers given on combustion ; no marked increase in the amount of colouring matter and resinous bye-product appears to accompany the employment of the higher temperature for saponification ; on the other hand, if water alone be employed instead of alcoholic soda, sa,poni&a- tion is brought about a t 140", though not so rapidly as with the alkali, only about 85 per cent. of the pseudaconitine being decomposed in 24 hours ; the dimethylprotocatechuic acid thus produced is, how- ever, almost perfectly free from the colouring matter and resinous bye- product formed to a greater or lesser extent when alcoholic soda is used. Thus in two experiments, 22.15 and 22.8 per cent. of dimethylproto- catechnic acid were found (calculated, 26.49) after 24 hours' digestion at about 140" ; the alkalojid extracted from the product of the reaction, when obtained as a varnish by the evaporation of its ethereal solution, and digested with water, did not wholly dissolve, but left behind solid particles of altered pseudaconitine, which furnished dimethylproto- catechuic acid on further saponification ; on first moistening the resinous mass with water, it became white and opaque on the surface, and pre- sented the appearance (to the naked eye, not under the microscope) of a crystalline film ; this appearance is not presented by pure apopseuda- conine, freed from all traces of substances capable of saponification (pseudaconitine and the products of the action of heat thereon) by the action of alcoholic alkali. In a preliminai-y report t o the Pharma-

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166 WRIGHT AXD LUFF ON THE

ceutical Conference ( Y e w - b o o k of Pharmacy, 1877,444), this appearance was erroneously supposed to be characteristic of pseudaconine, which was then confounded with apopseudaconine, the exact formula of pseudaconitine not having at that time been arrived at , the method of purifying the base by conversion into crystallised nitrate not having then been found out.

The following numbers were obtained :-

A. Apopseudaconine obtained by the action of water at 140" for 24 hours-

02410 gram gave 0.5630 CO,, and 0.1815 H,O.

0.2410 gram gave 0.5600 C02, and 0.1815 H,O.

0.2460 gram gave 0.5690 CO,, and 0.1860 H,O.

B. Another specimen similarly obtained-

C. Prepared by alcoholic soda at 140" for 24 hours-

Fouii d . Calculated. A. B. C.

C27 .......... 324 64.16 63.71 63.36 63.10 HS9 .......... 39 7-75? 8.37 8.37 8.40 N .......... 14 2.77 0 s .......... 128 25.35

- I - - L -

C27H,,NOa .... 505 100.00

8 4. Action of Acids on Pseudaconiti.ne.

When pseudaconitine is heated in contact with dilute or concentrated mineral acids, it quickly becomes saponified and altered, dimethylpro- tocatechuic acid being extractable by ether froni the prodnct of the action in larger or smaller quantity, according to circumstances ; the saponification, however, does not seem to be as rapid as a rule as with alkalies ; thus, solutions of pseudaconitine in cxcess of dilute hydro- chloric, nitric, or sulphuric acid may be allowed to stand for weeks in the cold, and even gently warmed for some time without the formation of more than traces of (and often of not any) dimethylprotocatechuic acid; whilst if a pseudaconitine salt be diluted with water, and an alkali added in excess, on standing for some time (a few hours to a few days) dimethylprotocatechuic acid is always formed to a con- siderable extent, even in the cold. On heatiiig to 100" a solution of pseudaconitine in excess of a mineral acid, saponification is brought about rapidly, especially with a concentrated acid ; thus about 40 per cent. of the alkali is saponified on heating to 100" for 3 hours, with about 10 parts of concentrated hydriodic acid. No methyliodide is thus formed, and no protocatechuic acid is obtained, showing that

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ALKALOIDS O F THE ACONITES. 167

the dimethylprotocatechuic acid generated is not demethylised at 100' by hydriodic acid. Hydrochloric, hydrobromic, and sulphuric acids produce analogous results ; the product of the continued boiling for some hours with dilute sulphuric acid does not reduce F e hling's solu- tion. Organic acids, however, such as tartaric and acetic, act very differently ; scarcely a perceptible trace of dimethylprotocatechuic acid is formed when pseudaconitine is heated to 100", with a large excess of glacial acetic acid, or of almost saturated solution of tartaric acid for several hours ; or even if boiled with moderately concentrated tar- taric acid solution for several hours. Other changes, however, are produced by these organic acids ; thus after 8 hours' heating t o loo", with nearly saturated solution of tartaric acid, the pseudaconitine becomes converted into q o p e z L d u c o m X h e by the reaction-

C J L N O i , = 8 2 0 + C J L N O i i . The product of the action was diluted with water and treated with

cmstic soda and ether : from the ethereal solution there separated on spontaneous evaporation crystals of apopsendaconitine so closely re- sembling the original base that it is somewhat difficult to distinguish them ; apopseudaconitine, however, appears to be decidedly less ex- tremely soluble in alcohol and ether, although its solubility in these menstrua is still considerable. When anhydrous it slightly frits at 100" (like peeudaconitine) and melts t o a thick viscid mass at 103- 103", or slightly lower than pseudaconitine which fuses similarly at about 105" ; when the two are compared side by side, it is distinctly seen that apopseudaconitine melts some 2" below pseudaconitine.

When crystallised from ether by spoiltaneons evaporation apopseuda- conitine is represented by the formula C3,H,,N0,,,H20 ; i e . , it is iso- meric with pseudaconitine deprived of its water of crystallisation : like the crystallised parent base it readily becomes anhydrous a t 100".

0.5645 gram of air-dry base lost a t 100" 0.0160 = 2.83 per cent.

0.2310 gram of base dried at 100" gave 0.5480C02 and 0.1685 H,O.

The base furnishes a well-crystallised nitrate on rubbing with excess of dilute nitric acid, or on dissolving in sufficient dilute acid, adding a few drops of concentrated acid, and stirring vigorously. From the crystals of nitrate thus prepared the base was regenerated by means of soda and ether ; of the resulting substance, 0.2745 gram dried a t lij0" gave 0.6445 COz and 0.1925 H20.

Calculated for C36HliNOll,H20 = 2.62 ,,

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168 WRIGHT AND LUFF ON THE

Calculated. Found. c36 ........ 432 64-57 64.69 64.03 HJ, ........ 47 7-03 8.10 7-79 N .......... 14 2.09 O,, ........ 1'76 26.31

- - - -

The gold-salt, when precipitated from weak solutions of the hydro- chloride, is crystalline ; when dried over sulphuric acid it can readily be crystallised from hot alcohol in minute anhydrous needles.

0.3005 gram gave 0.0585 Au = 19.46 per cent. Calculated for C3GHB,N011,HC1,AuC13 = 19.44 ,,

I n order to see if inorganic acids also cause the dehydration of pseudaconitine as well as its saponification, pure pseudaconitine was heated with about 15 parts of an aqueous solution containing 5 per cent. of HCl to 100" for 8 hours. On shaking the acid liquid with ether, dimethyl protocatechuic acid was dissolved out to an extent indi- cating that about a twentieth part of the pseudaconitine used had been saponified. On adding soda and ether, and allowing to evaporate spontaneously, crystals formed, less readily soliible in alcohol and ether than pseudttconitine, giving rise to a crystalline gold-salt and a well-crystallised nitrate : these crystals, however, were slightly mixed with a non-crystalline base (presumably pseitdaconine formed by the saponifhation) ; they mere converted into nitrate, filter-pumped and washed with weak nitric acid ; from the salt thus obtained the base was regenerated corresponding in all respects with the apopseudaconi- tine prepared by means of tartaric acid.

0.2475 gram dried at 100" gave 0.5815 CO, and 0.1825 H,O.

Calculated. Found. Carbon .......... 64.57 64.08 Hydrogen ........ 7.03 8-19

From these results there can be little doubt that the specimen of pseudaconitine prepared by Mr. G r o v e s by means of alcoholic hydro- chloric acid (§ I.) actually contained apopseudaconitine, formed by the action of the hydrochloric acid during the extraction.

Glacial acetic acid acts in a somewhat different fashion from aqueous tartaric acid : the elements of water are indeed removed from pseud- aconitine, but the resulting apopseudaconitine is further acted on form- ing acetyl! apopseudaconitine in accordance with the reaction

CJLNOii 1- C,H:,Q, = EL0 + CxHA,(C,H,O)NOII,

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ALKALOIDS OF TEIE ACONITES. 169

just as morphine and codeine give rise to acetylated derivatives by similar treatment (Alder-Wright, this Journal, 1874, 1031). Pseudaconitine was heated to 100' for 8 hours with about 12 parts of glacial acetic acid : on diluting the resulting fluid with water, adding soda and agitating with ether, and allowing the ethereal solution to evaporate spontaneously, a well-crystallised base was obtained sensibly less soluble in alcohol and especially in ether than pseudaconitine, though still readily soluble in either menstruum. When air-dry it contains one proportion of water of crystallisation (like pseudaconi- tine and apopseudaconitine) .

0.4955 gram of air-dry crystals lost a t 100" 0.0130 gram ............................ = 2.62 per cent.

Calculated for C,,H46(C,H,0)No,,,H,0. . = 2.47 ,, 0.2575 p m . of base dried at 100" gave 0.6080 GO2 and 0,1850 H20.

Calculated. Found. C, .................... 456 64-13 64.38 H4g .................. 49 6.90 7.9 8 N .................... 14 1.97 OI2 .................. 192 27-00

-

CS~H~~(C~H,O)NO~I .... 711 1OO.00

In order to determine the degree of acetylation, 0.5970 gram of anhy- drous base were dissolved in alcohol, exactly neutralised, and saponified in a soda-water bottle (at 100" for about 14 hours) with a measured excess of standard caustic soda solution. From the amount of soda neutralised the quantity of mixed acetic and dimethylprotocatechuic acids formed was calculated, being 0.2057 gram of a mixture of equi- valent quantities of CgH1,04 and C2H402. The whole was then acidi- fied and the acetic acid distilled off with water as long as any acid came over: by titration the distillate was found to contain 0.0510 gram of C2H4O2. Finally the dimethyl protocatechuic acid (and a trace of resinous decomposition-product) was extracted from the residue in the distillation-flask by means of ether, and the ethereal solution evaporated to dryness and weighed after drying at 100" : the residue weighed 0.1590 gram, and when titrated by standard soda neutralised alkali equivalent to 0.1550 gram of CyHL004.

Found. Calculated. By titretion. By weighing.

Acetic acid. ................. 8.44 8-53 - - Dimethyl-protocatechuic acid . . 25-59 25.96 - 26.63

Total acid .................. 34.03 34.51 34.46

Acetyl apopsendaconitine forms a well-crystallised nitrate on stir- ring with excess of dilute nitric acid: the gold-salt is thrown down

VOL. XXXIII. 0

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170 WRIGHT AND LUFF ON THE

in microscopic crystals from a dilute solution of the hydrochIoricle on adding auric chloride; it is readily crystallisable from hot alcohol, and is but sparingly soluble in cold alcohol. The anhydrous base melts at a somewhat higher temperature than pseudaconitine in a capil- lary tube, becoming a highly viscid transparent mass a t about 115", the melting point, like that of pseudaconitine, not being very distinctly marked: it slightly frits a t lOO", however, on heating for some time.

6 5. Actiort of Organic A n h y d r i d e s o n P s e d a c o n i t i n e a?Ld Pseudnconiwe. It has been shown by one of us (this Journal, 1874, 1031), that

whilst morphine furnishes, when treated with glacial acetic acid, an acetyl derivative containing only one acetyl group per 1 nitrogen symbol in the formula, it gives rise, by the action of acetic anhydride in excess, to a derivative containing twice as many acetyl-groups. In order to see if pseudaconitine behaves in a similar way, the anhydrous base was heated to 100" for an hour with twice its weight of acetic anhydride : to the colourless product a dilute solution of tartaric acid was added and the whole agitated with ether to remove any trace of resinoid bye-product. Soda was then added to the aqueous liquid and the whole agitated with ether. By spontaneous evaporation, crys- tals were obtained which on examination proved to be i d e l h h l wiih t h e ncetyl apopseudaconitiize formed by the action of glacial acetic acid (§ 4), and not a more highly acetylated product : it melted at 113" ; after drying at 100" 0.2615 gram gave 0.6180 CO, and 0.1875 H20.

Calculated. Found. C38 .................. 456 64-13 64.45 Hdg .................. 49 6-90 7-96 N.. .................. 14 1.9 7 012 .................. 192 27.00 -

-

On saponification, 0.7800 gram neatralised soda equivalent to 0.2710 gram of CgH,,O, + C,H40,. On distilling off the acetic acid formed and titration, 0.0'740 gram C2H402 were obtained: from the residue by means of ether there was extracted 0.19'70 gram of crude dimethyl protocatechuic acid, which on titration neutralised soda equivalent to 0.1965 gram C9HloOl.

Acetic acid.. ................ 8.44 9.48 - - Dimethyl protocatechuic acid.. 25.59 25.19 - 25.26

Found. Calculated. By titration. By weighing.

Total acid .................. 34.03 34.67 34.74

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ALKALOIDS OF THE ACONITES. 171

Hence the action of acetic anhydride on pseudaconitine is represented by the equation-

C36H19N012 + 2( C2H30)20 = 3C2&Oz + C36H46(CZH3O)NO11.

Benzoic anhydi-ide yields precisely similar results, benzoyl-apopseud- nconitine, C3sH4,( C7H50)NO11, being formed when benzoic anhydride is made to act on pseudaconitine, the reaction being-

C3JLNO12 + 2 (C,H,O)zO = 3C7H.502 + C ~ ~ H ~ ~ ( C ~ H ~ ~ ) N O I I -

Anhydrous pseudaconitine was mixed with twice its weight of benzoic anhydride and heated for two or three minutes to about 120" to render the whole fluid, the liquid being then kept at 1OOOfor from one to two hours. On cooling and standing, the whole solidified to a crystalline mass (containing much benzoic acid) : this was dissolved in a mini- mum of alcohol and largely diluted with ether, enough dilute solution of caustic potash added to set free any base present, and the whole well agitated and allowed to stand. The supernatant ethereal solu- tion of new base, together with undecomposed benzoic anhydride and resinous bye-products (formed only in very small quantity), was then separated and agitated with dilute tartaric acid solution ; and from the purified tartrate thus obtained, the base was regenerated by means of alkali and ether. On spontaneous evaporation, the ether left an indis- t,inctly crystalline residue, which did not crystalliss well on adding a few drops of alcohol and allowing to stand, but which was the hydrate of the benzoylated base, benzoyl-apopseudaconitine,

CB6H46( CiH5O)NOll, H2O.

0.2730 gram of air-dry substance lost a t 100" 0.0065 gram.. ............................ = 2.38 per cent.

Calculated for above formula ................ = 2.27 ,, 0.2665 gram of anhydrous base gave 0.6495 C 0 2 and 0.1890 H20.

Calculated. Found. Ca,. ................. 516 66.75 66.46 H51 ................ 51 6.60 7.8 7 N .................. 14 1.81 0 1 2 . . - ................ 192 24.84

-

On stirring up this base with just enough dilute nitric acid to dis- solve it, adding a little concentrated acid, and rubbing well, a finely crystallised nitrate was formed : the gold-salt also crystallised from hot alcohol in well-defined anhydrous rosettes.

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172 WRIGHT AND LUFF ON THE

0.4700 gram gave 0.0840 Au ................ = 17-87' per cent. Calculated for C,6R4,(C,H,0)N0,,,HCl,AuC13 . . = 17.63

0,7190 gram of the base dried at 100" was saponified by alcoholic potash at 100" in 8 soda-water bottle; on evaporation, treatment of residue with hydrochloric acid and ether, and spontaneous evapora- tion, 0.2940 gram of mixed acids were obtained with a minute quantity of resinous bye-product ; on titration, this nentralised alkali eq_nivalent to 0-2890 gram of C9H,,0,+ C,H,O,

,,

Found. Calcubted. By titration. By weighing.

CJ3,OOh + C7H6OZ .. 39.33 40.19 40.89

Analogous experiments with pseudaconine show that it is capable of yielding benzoylated and acetylated products ; experiments on this subject are in progress, as al<so attempts to synthesise pseudaconitine from its saponification-products b r inversion of the action taking place during saponihation.

$ 6. Constitutio.rt of Pseudacoizit Ine and its Derluccti7;e.s.

From the circumstance that pseudaconitine splits up by a reaction of sajponification into peudaconine, C27H41N0E, and dimethylproto-

catechuic acid, known to be indicated by C6H31 0.CH3 , it results

that pseudaconitine may be written-

CO.OH

1 0.CH3

The ready formation of apopseudaconitine by dehydration, and of acetyl and benzoyl apopseudaconitine by the action of glacial acetic acid and acetic and benzoic anhydrides, indicates moreover that pseud- aconitine is a trihydroxylated base ; so that the following formula? may be ascribed :-

Psendaconitine ............ ( C,7H37N05)~OH '0": L O . C0.CsH3( 0.CH3)2

A popseudaconitine ( Cz7H,,NO6)-0H do

Acetyl apopseudaconitine. ... ( C,,H,N05) do -O.C,H,O

........ 'O.CO.C,H,( O.CH,),

\O .GO GH, ( 0. CH,),

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ALEALOIDS OF THE ACOXITES. 173

Benzoyl apopseudaconitine . . ( C2,H,NO,)-O. //O C,H,O

’“0:

Apopseudaconine . . . . . , . . . . (CnH3,NO5)-0H Yo

‘0. C 0. C6H3( 0. C H,)

Pseudaconine . . . . . . . . . . . . . ( C2,H37N05)10H \OH

‘OH The relationship between pseudaconitine and pseudaconine would

therefore be expressible by applying to the former the unwieldy term “ dimethylprotocatechuyl - pseudaconine ” : whence acetyl-apo- pseudaconitine would become “ acetyl-dimethylprotocatechuyl-apo- pseudaconine,” and so on !

Experiments now in progress indicate that aconitine from A. nopel- Zu.s has an analogous constitution ; applying the term aconirm to the base, C2613:.9NOll, into which, together with benzoic acid, aconitine splits by saponification, the relationship of aconitine to this base is indicated by applying to the former the term “ benzoyl-aconine,” and the formula, ( C,H3,NOlo)-O-C7H50 ; which apparently may be

further dissected, thus, (C2sH,N07)-OH -OH , aconitine being a-

trihydroxylated base. Evidently the quadrivalent radicles, C27H3,N05, and C26H35N07, of

pseudaconitine and aconitine respectively are closely allied : experi- ments with a view to elucidating the “ structure ” of these radicles are in progress, though as yet no results of importance have been arrived at.

It is specially noteworthy that pseudaconitine is thus closely con- nected with the opium alkalo’ids narceine, narcotine, and oxynarcotine, all of which split up, giving rise to substances which are derivatives of dimethyl-protocatechuic acid (I3 ecket t and Alder-Wright , this Journal, 1875, 573 ; 1876, i, 281 and 461). Moreover i t is remarkable that all the natural alkalo’ids which have hitherto been split up by saponification-reactions yield acids of the aromatic series : thus with narcotine, nnrceine, oxynarcotine, pseudaconitine, aconitine, atropine (Kraut , Jahresbericht, 1865, 448), cocaine (Lossen, ibid., 4-51)> and piperine (von B abo and Keller) . Experiments now in progress with the alkalo‘ids of Sabadilla seeds, however, show that the so-called “ veratria” of commerce is a mixture of afkaloYds, t w o of which belong t o the saponifiable class, one giving rise to the same dimethyl- protocatechuic acid as peudaconitine, the other forming an acid of a

/ O H

‘0 .C,fl50

0 2

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174 WRIGHT AKD LUFF ON THE, ETC.

different kind, apparently identical, or isomeric, with CL ,zgcZic cccirb, C,H*O,.

§ 7. Otlzer Bases contained in Conwnercial (' Aeonithie " f i . 0 ~ ~ A. ferox.

In the preparation of pure pseudaconitine nitrate as above described (§ 1) from the crude drug supplied by Messrs. H o p k i n and Wil- l iams, there was obtained a nitric acid mother-liquor from which no crystals could be obtained, but which contained a considerable amount of alkaloidal matter. On dilution with water, this deposited some resinoid matter; from the filtrate from this alkalies threw down a copious white amorphous precipitate. The precipitate thus obtained with sodium carbonate dissolved readily in ether, but furnished no crystalline base or salt by any kind of treatment tried. The base recovered from the ethereal solution as a varnish, and dried at 100", contained-

Carbon ............... 63.37 Hydrogen ............ 8.01 Nitrogen.. ............ 3.21

and on saponification it formed dimethylprotocatechuic acid to the extent of 19.7 per cent. (calculated from weight of acid obtained from ether; 18.5 per cent. by titration), from which i t would appear it consisted largely of some substance closely allied to pseudaconitine, not improbably an alteration-product formed during extraction, and possibly identical with the amorphous base obtained by heating pseudaconitine acetate (9 1). The sodium carbonate filtrate from this precipitate was evaporated to dryness, and the residue treated with alcohol ; a quantity of brown amorphous alkalojidal matter was thus dissolved out : on evaporating to dryness and treating with water, a considerable portion dissolved, consisting apparently of impure pseu- dnconine, as i t formed only minute amounts of dinicthjl protocatechuic acid on saponification.

From these results it is evident that the commercial alkaloid is liable t o be admixed with considerable quantities of amorphous bases : i t was estimated that about a fifth of the material obtained from Messrs. H o p k i n and Wi l l i ams consisted of such substances ; al- though the amorphous bases were not destitute of physiological potency, yet they appeared to produce far less lip-tingling, &c., than pure pseudaconitine. The nitrate of pseudaconitine being almost in- soluble in nitric acid containing 8 to 10 per cent. of HNO,, it would appear desirable that only the crystallised salt, or the alkaloid thence regenerated, should be prepared for medicinal use, which could readily be accomplished in practice.

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