WRIGHT ON TRE ALKALOIDS OF THE ACONITES. 143

IV.-The Alkaloids of the Aconites. Part I. On the Crystallisable Alkaloi’ds contained in Aconitum ATape71w.

By C. R. A L D E R WRIGHT, D.Sc., Lond., Lecturer on Chemistry in St. Mary’s Hospital Medical School.

IN a prelimirtary notice read before the Chemical Society in 1875 a i d printed amongst the abstracts in the Chern. SOC. J o u m a ~ [2], xiii, 1265, the author and Mr. G. H. B e c k e t t described the first results obtained from the examination of various products extracted by Mr. T. B, Groves (Weymouth), fimom Aco@tum ferox and A . NqueZZtcs, the mode of extraction adopted being percolation of the ground dry roots with alcohol slightly acidulated with hydrochloric acid, evapo- ration to a small bulk of the extract thus obtained, precipitation of bases by ammonia, and extraction by ether of the alkalo’ids thus pre- cipitated. In this way there was isolated from the A. f w o x an alka- loid crystallisable from ether, but yielding salts that wholly refused t o crystallise, drying up to varnishes readily soluble in water: appa- rently this substance is the main ingredient in the preparations which have been designated by various chemists “ English aconitine,” “ pseudoaconitine,” “ acraconitine,” &c. On analysis, this body gave numbers represented by the formula C3,HI9NOl1, the gold salt beiny C36134,NOl,.HGI.AuC13. Further experiments on the “ constitution .’

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144 WRIGHT ON THE ALKALOIDS O F THE ACONITES.

of this substance are in progress, and will be described in a subsequent memoir.

Very different results, however, were obtained with A. Napellus. Few substances of high physiological activity have formed the subject of examination by more chemists and pharmacists than this body ; and with few, if any, have more contradictory results been obtained : this want of uniformity in results appears to arise from many causes. In the first place, it seems excessively probable that due care in selecting the roots examined was not always exercised, so that the roots of different species were probably mixed together : there seems, from the results obtained by Mr. Groves and the author, some reason for supposing that entirely different bases are obtainable from different species. In the next place, the mode of extraction employed was, in most instances, such as must inevitably have caused a large amount of alteration and decomposition of the alkaloids present during the pro.. cess of extraction, the alcoholic extracts having generally been heated in contact either with a mineral acid or with an alkali, or both ; as the active principle of aconite roots is known to be of a highly unstable character, the chances of uniform results being obtained by such pro- cesses are very small. Lastly, with only one or two exceptions, the substances isolated have not been subjected to analysis, and absolutely no numerical results have been given by the majority of writers and experimenters.

Thus, the only numerical values that the author has been able to find recorded prior to 1870 are those of von P l a n t a (AnmaZen der Clzenzie, lxxiv, 25'7) : and that the substance examined by this chemist did not present satisfactory iudications of purity, and indeed of authen- ticity, is manifest from the circumstance that the material examined was purchased from Merck, who had not prepared it himself, and that it wits an amorphous powder. No history of its preparation from the root is given, but presumably it was extracted by the process of Geiger and Hesse, who first discovered the alkalo'idal character of the active principle of A. NapelZus roots ; this process involves heat- ing the alkalojid in ccmtact first with lime, and secondly wit?h sul- phuric acid, which could hardly fail to bring about considerable alteration in so unstable a body as the active principle is known to be. F o r these reasons, therefore, the formula arrived at by von P l a n ta, vie., C30H47N07, the hydrochloride being C,H4,N07.2HC1 (!) must be regarded as open to grave objection (vide imfra).

In 1860, Mr. Groves succeeded in isolating from A. NapeZZw a crystalline alkaloid possessing high physiological activity and forming well crystallised salts (€'harm. J. Trans. [2], viii, 121) ; this was exhi- bited in the Exhibition of 1862 (as was also a specimen of a crystal- lised alkaloid obtained by Morson, but which was apparently not

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WRIGHT ON THE ALKALOIDS OF THE ACONITES. 145

derived from A. NapeZZus). Unfortunately, Mr. Groves’ product was not analysed at the time, but a portion of the nitrate of the sample thus obtained has subsequently been examined by the author and Mr. Becket t : the crystals of base regenerated from the nitrate by ammonia and ether, gave the following values :-

0.2270 gram gave 0.5235 CO, and 0.1480 H,O. 0.29 75 ,, ,, 0.6845 ,, ,, 0.1 9 5 5 ,, 0.5795 ,, of gold salt gave 0.1200 An.

Calculated for Calculated for C3&b3NO10. C33I-IGNO I,. Found.

Carbon in free base . . 63.89 62.34 62.90 62.75 Hydrogen .......... 7.1 5 6.9 7 7.24 7.30 Gold in gold salt .... 20.85 20.50 20.71

From the results detailed below, the conclusion is unavoidable that this product either was imperfectly purified, or else had been some- what altered and diminished in molecular weight during its extrac- tion; the latter is not a t all improbable, as the specimen had been purified by conversion in to the insoluble mercuric iodide compound, and regeneration from this substance. The author has found, in the case of the base derived from A. ferox, above alluded to, that the mer- curic iodide process actually does cause a considerable amount of change of this character.

Some years subsequently (1871 and 1872) M. Duquesne l succeeded in isolating from Aconitzwn napellus a well-crystallised base t o which he gave the name “ aconitine crystallis6e,” to distinguish it from the amorphous preparations met with in commerce under the name of aconitine. Tlie process employed was extraction with alcohol acidu- lated with tal-taric acid, evaporation of the extract at temperatures not exceeding 60°, precipitation by sodium bicarbonate, and crystal- lisation of the precipitate from a mixture of ether and light petroleum spirit (Coinpt. rend., lxxiii, 207 ; also Ann. Chint. Plzys. [4], 25, 151). &I. Duquesnel gave the following numbers as obtained from this preparation :-

Carbon.. .............. 59.96 60.18 Hydrogen. ............. 7.35 7.54 Nitrogen .............. 2.58 2.69

from which he deduced the formula C,,H4,,N0,,. The experiments described below clearly show that this product could not have been pure, inasmuch as frequently repeated crystallisation does not suffice to separate completely t h e crystallisable alkaloid contained in A . N ( t - pellus from another amorphous substance of lower molecular weight obtained along with it by M. Duquesnel’s process.

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146 WRIGHT ON THE ALKALOIDS OF THE ACONITES.

In 1874, wishing to obtain a larger supply of the crystalline base from A. Napellus isolated by him in 1860, Mr. Groves operated on two batches of 1 cwt. each of roots purchased as Aconitunz Napellus, and presenting the appearance of that species ; whether, however, there was not a large admixture of some other species, or whether the roots examined were of abnormal character from some peculiarity of soil or climate, is open to question, from the totally unexpected nature of results obtained with these roots. Qn working up the extract obtained by means of alcohol acidulated with hydrochloric acid, a well-crystal- lised mass was obtained consisting of the mixed nitrates of two entirely dissimilar bases (Year-book of Pharmacy, 1874, 507). Of these one, when in the free state, crystallised readily from ether, and has been found by the writer to be identical with the alkaloid obtained in an imperfect,ly pure condition by M. Duquesne l ; the other wholly refused to crystallise from ether or any other solvent when in the free state, although the varnish-like products obtained on evapora- tion of the solutions of the base readily formed well-ci.ystallised salts on moistening with dilute mineral acids. Curiously enough, whilst the former base was highly active physiologically, the latter was almost inert, half-grain doses being taken internally by Mr. Groves without the production of any marked symptoms. It seems not a t all im- probable that the very varying activity exhibited by different com- mercial preparations sold as ' 6 aconitine " may be at least partly due to the circumstance that the usual modes of preparation of the drug are not calculated to effect any separation of the active alkaloi'd from the inert base, should the latter be contained in the roots employed.

These products obtained by Mr. Groves have been subjected to careful examination by the author with the following results :-

A. ComparativeZy inert Base. Picraconiti?ae.-The s d ts of the com- paratively inert base when tasted do not produce the peculiar prickling of the tongue characteristic of aconite roots, but simply have a bitter taste ; for which reason it is suggested that the term " picraconitine " may be conveniently employed to designate this base. It was at first thought by Mr. Groves that this substance might be identical with the body isolated by B r o ug h ton from zlconitunz 1LeterophgZZu.m (called atees in India) and termed by him atisine, but the numerical values obtained and other circumstances are quite inconsistent with the identity of the two bodies. Thus Broughton found (Medical Press ami! Circular, May 27, 1874) that atisine melted at 85", formed crys- talline salts only with difficulty, and gave a platinum salt pretty readily; from this last the formula C4,H,IN2Q5 was deduced; picm- conitine, on the other hand, does not fuse at loo", forms crystalline salts with great ease, forms a platinum salt so soluble in water that it is only precipitated in very concentrated solutions, and cannot be

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WRIGHT ON THE ALKALOIDS O F THE ACONITES. 147

washed without almost wholly dissohing ; and, lastly, yields numbers leading to the formula C3,HP5NO10.

(1) Crystals of picraconitine hydrochloride prepared by Mr. G r o v e s (Zoc. ci t . ) and purified by several recrystallisations, 0-61.90 gram (air- dry) lost at 100" 0.0295 gram.

(2) Ditto, recrystallised from water, 0.4725 gram (air-dry) lost a t 100" 0.0230 gram.

(3) Ditto, again recrystallised from water, 0.5260 gram (air-dry) lost at 100" 0.0190 gram. (4) Ditto, yet again recrystallised from water, 0-91.90 gram (air-

dry) lost a t 100" 0.0380 gram. Found.

Calculated for C31H45NO~~,HC1,1~Hz0. (1.) (2 . ) (3.) (4.) 4-13 4-77 4.87 3.61 4.13

Specimen (1) 0.2680 gram, dried at loo", gave 0.5755 GO, and

Specimen (1) 0,4490 gram, dried at loo", gave 0.1000 AgC1. Specimen (4) 0.3520 gram, dried at loo", gave 0.7555 CO, and

Specimen (4) 0.3320 gram, dried a t loo", gave 0.0750 AgCl.

0.1850 H,O.

0.2400 HZO.

7, ,, 0.5050 ,, 9 , 7 7 ,, 0.1100 9 7

9 9 ,, 0.4790, burnt with soda lime, gave 0.0735 Pt.

Calculated. (1.) (4.) Found.

C,l ............ 372 59.29 58-56 58-53 H46 ............ 46 7.33 7-67 7.58 N.............. 14 2.23 - 2.18 O,, ............ 160 c1 ............ 35.5 5-66 5.51 5-59 5.44

25.49 - -

Picraconitine, precipitated from hydrochloride No. 4 dissolved in ether and obtained as a varnish by spontaneous evaporation, not fusible at 100". 02460 gram gave 0.5675 COz and 0.1745 H,O.

Calculahed. Found. c31 .......... 3 72 62.95 62.91 H, .......... 45 7.61 7.88 N ............ 14 2.37 01, .......... 160 27.07

C31H45NO1,. ... 591 100??0

Picmconitine aurochloride is precipitated in canary-yellow flakes not

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148 WRIGHT ON THE ALKALOIDS OF THE ACONITES.

perceptibly crystalline and exceedingly sparingly soluble in water on addition of gold chloride t o picraconitine hydrochloride solution. After drying over sulyhuric acid it does not alter at 100”.

From hydrochloride (1) 0.6790 gram gave 0.1430 Au = 21.06 per cent. 7, ,, (2) 0.6995 ,, ,) 0.1475 ,, 21.09 ,,

1.1170 ,, ,) 0.2380 ), 21-35 ,,

Average. ............. 21.15 --

Calculated for C31H4,NOlo,HCl,AuCI,. ..... 21.07

It is noteworthy that no indications of the presence of this base were observed by Mr. Groves in his former experiments (1860), nor was any such body obtained in the author’s experiments described below ; the circumstance, however, that roots purchased as Aconitum NapeZZus were found on this one occasion to yield a crystallised pro- duct (nitrate), of which by far the larger proportion was a substance inert as compared with the active principle of the roots, is of great pharmaceutical importance, as tending to throw light on the great discrepancies sometimes noticed in the physiological potency of dif- ferent specimens of the drug met with in commerce under the name of “ aconitine.”

B. Physio2ogically active Base. Aconitine-The base, crystallisable from ether and possessing high physiological activity, was separated by the author from the mixture of nitrates of this alkaloid and of picraconitine obtained by Mr. Groves (Zoc. c i t ) by simply dissolving in ether the mixture of bases precipitated from the mixed nitrates by ammonia and leaving the solution to evaporate spontaneously ; in this way a small quantity of crystals was obtained which, after two recrys- tallisations from ether, gave the following numbers :-

Carbon in free base.. ............ 62.90 Hydrogen. ..................... 7.45

20.32 Gold in gold salt. ............... These numbers agree fairly with those required for the formula

C33H45NO11, and are almost identical with those obtained from the crystallised base isolated by Mr. Groves in 1860 (supra). The two products agreed closely in all their characters, and, moreover, they exactly agreed with M. Du quesnel’s description of his “ aconitine crystallis&e.” The experiments which follow clearly demonstrate that each one of these three bodies must have consisted essentially of the Same alkalojd, but not in a state of purity; when pure, this base (to which it is proposed to restrict the term aconitiize for scientific pur- poses) is indicated by the formula C33H43N0I2.

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WRIGHT ON THE ALKALOIDS OF THE ACONITES. 149

The imperfectly purified crystalline base obtained from the mixed nitrates as above described did not materially alter in molecular weight by recrystallisation and appeared to be uniform in character ; but on dissolving it in slightly warm dilute hydrochloric (or better hydrobromic acid) and allowing the solution to crystallise, a salt was produced from which a base was regenerated by sodium carbonate and ether, apparently identical with the original substance, but giving somewhat different numbers. On repetition of the process no fur- ther change in the base was produced, whence i t is evident that aconitine (like eertain other alkaloids, e.g., papaverine) has so strong a tendency to adhere t o other substances found along with it, that simple crystallisation of the free base several times successively is insufficient to purify it completely, although conversion into a crystal- lisable salt and recrystallisation of the latter effects a complete sepa- ration, The following numbers were obtained with the pure base thus regenerated from the hydrobromide :-

0.2845 gram gave 0.5080 CO, and 0.1370 H20.

Calculated. Found. c33 .......... 396 61.39 61.71 Ha3 .......... 43 6.67 6-78 N.. . . . . . . . . . . 14 2-17 01, ........... 192 29.77

CaH&"la .... 645 100.00

After solution in warm dilute hydrochloric acid, crystals of the hy-

0.5140 gram lost at 100" 0.0390 gram ........ = 7-59 per cent. The formula C33H43N012,HC1,3H30 requires 7.34

0.4'750 gram of dry salt gave 0,0995 AgCl , . C1 = 5.18 Calculated for C3,H4,N01,,HC1. ..... C1 = 5.21

drochloride were formed ; of these, when air-dry,

,, ,, ,,

The hydrobromide, recrystallised from water, gave the following values :-

0.4087 gram (air-dry) lost at 100" 0.0250.. .. =

0.3837 gram of dry salt gave 0.1000 AgBr.. Br = 11.09 = 11.02

On addition of auric chloride to the aqueous solution of phis hydro- chloride, pale-yellow amorphous flakes of a gold salt, very sparingly soluble in water, were thrown down ; after complete drying over sul- phuric acid in the dark, these lost no weight at 100" ; in a thin film,

6.11 per cent. Calculated for C3,H4,NOl2,HBr,2+H2O. . = 5.83 ,,

,, Calculated for C33H43N012,HBr ......... ,,

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150 WRIGHT ON THE ALKALOIDS O F THE ACONITES.

however, the salt slightly darkened in the light in the course of a day or two at the ordinary temperature.

0.4630 gram of gold salt dried at 100" gave 0.0925 Au gold = 19.98 per cent.

Calculated for C33H43NO12,HCI,AuC13 = 19.98 ,, These numbers clearly show that pure aconitine, when regenerated

from a crystallised pure salt, is expressed by the formula C33H43N012 :

the difficulty in obtaining tlie base pure by simply recrystallising it from ether is exactly that which is noticed in the case of papavel-ine, which, as was first pointed out by Hesse and subsequently by the author and Mr. Becket t (this Journal, May, 1876), cannot be ob- tained pure by simple recrystallisation, but is readily purified by con- verting the approximately pure substance into a crystallisable salt (acid oxalate), recrystallising this, and regenerating the alkalo'id from the product.

With the object of submitting aconiiiine to a thorough chemical investigation, 2 cwts. of Acoizitum Napellws roots were worked up by Messrs. Hopkinssand Wil l iams to a condensed extract in ac- cordance with the directions of M. Duquesnel, this " tartaric acid pro- cess '' being employed rather than one involving the use of a mineral acid, in order to avoid possible decomposition : it seems by no means improbable that the amorphous and ill-defined substances described by Hubsc hmann and others under the name of napelline, ecolyctine, lycoctonine, &c., may be really only aconitine or some allied body more or less altered and decomposed during the extraction process. The ground root was percolated by alcohol acidulated with tartaric acid (about 60 gallons of alcohol and 1 lb. of tartaric acid being em- ployed altogether), and the extract was evaporated to a small bulk at as low a temperature as possible. About 5 gallons of condensed extract were then obtained, which was worked up by the author as follows :-The liquid, consisting of a clear brown-red aqueous portion and a dark soft resin, was exposed to the air in shallow vessels for a few days to dissipate some of the remaining alcohol, and was then diluted with water and filtered from resin ; the aqueous filtrate was agitated with benzoline (light petroleum distillate) whereby some remaining resin was removed, and the aqueous liquid was then pre- cipitated by a slight excess of potassium carbonate : the filtrate con- tained a base soluble in carbonate of ptassinm, which gave a copious precipitate with mercuric iodide dissolved in potassium iodide : this precipitate when decomposed by sulphuretted hydrogen, finally yielded a small quantity of crystals of aconitine, but chiefly consisted of a base which appeared to be wholly non-crystalline and to form non- crystailline salts, and much resembling (if, indeed, not identical with)

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WRIGHT ON THE ALKALOIDS OF THE ACONITES. 151

the non-crystalline base or mixture of bases obtained, as described below, from the mother-liquors left on recrystallising the potassium carbonate precipitate.

The precipitate thrown down by the potassium carbonate was agi- tated with ether, and the ethereal solution thus obtained with tartaric acid solution ; the ether thus freed from base was used over again several times : finally the whole of the precipitate was thus dissolved with the exception of some humus-like flakes: the ether left after agitation with tartaric acid contained in solution a small qnantity of a clear soft yellow resin. The acid tartrate solution thus obtained was systematically worked up, in order to discover if more than one crys- talline alkaloid was present; it was first precipitated with sodium carbonate, and the precipitate agitated with successive small quanti- ties of ether, whereby finally a considerable portion was left undis- solved in the form of snow-white crystalline flakes: the ethereal solution thus obtained gave by spontaneous evaporation a copious crop of slightly coloured crystals, which were filter-pumped, dissolved in benzene, and precipitated by addition of benzoline (light petroleum spirit) : finally, the mother-liquors and drainings of these crystals were evaporated and the residue dissolved in dilute acetic acid, whereby a little resin was left undissolved : the solution was treated with a little sodium carbonate t o throw down colouring matter and remaining resin, and the filtrate with excess of sodium carbonate and ether ; this ethereal solution gave successive crops of crystals on spontaneous evaporation with a final syrupy rnother-Jiquor, which dried up to a varnish and refused to yield any crystalline salts on solution in acids and spontaneous evaporation : it could not therefore have contained any considerable amount of picraconitine : this final product gave the following numbers:-

Carbon in base .......... 66.39 Hydrogen .............. 7.94 Gold in gold salt ........ 23.91

which are not far removed from the numbers found by v o n P l a n t s (Zoc. cit. supra), and from which he deduced the formula C30B47N0,, viz. :-

Another sample. Carbon in free base . . 67.81 68.34 67-95 64.83 66.95 Hydrogen .......... 8.82 8.90 8-64 8.14 8-59 Nitrogen ............ - 3.59 3.31 L - Gold in gold salt .... - 22.06 - - -

It can, therefore, hardly be doubted that the product examined by von P l a n t a consisted mainly of the non-crystalline base (or mixture

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152 WRIGHT ON THE ALEALOIDS OF THE ACONITES.

of decomposition-products formed during extraction 2) just described. It may be noticed that von Planta’s numbers represent the gold salt as being C3,H,7NOi.HC1.AuC13 + H20 (?), whilst what he regarded as a hydrochloride, C3,,H4,NO7.2HC1, must evidently have been formed by an action of the hydrochloric acid different from mere combination.

In this way three batches were obtained:- (A.) Left undissolved by ether at first (ether not employed in large

(B.) Crystals deposited from first ethereal solution and purified by

(C.) Crystals from mother-liquors. Each one of these batches,. when fractionally crystallised from ether,

yielded the same numbers, in all cases closely approximating to those required for the formula C33H43N0,2, but giving a gold salt containing a little too much gold; when, however, these approximately pure specimens were converted into hydrobromides, and the drained and washed crystals of that salt were treated with sodium carbonate and ether, crystals of base were obtained perfectly corresponding with the substance similarly purified from Mr. Groves’ products described above and designated aconitine, and giving exactly the numbers required for the above formula. Thus the following numbers were obtained with the substance purified only by crystallimtion from ether :-

Specimen No, 1. Crystals left undissolved by ether (A) converted into gold salt-

quautity).

benzene and petroleum.

0,8045 gram gave 0.1640 Au. 0.9210 ,, ,, 0.1875 ,,

No. 2. (A) treated with ether sufficient to dissolve one-third ; solu- tion crystallised by spontaneous evaporation-

0.2615 gram gave 0.5840 CO, and 0.1600 H,O. 0.4825 gram gold salt gave 0.0980 Au.

No. 3. Portion of (2) insoluble in ether similarly treated : crystds from this second ethereal fractional solution-

0.3545 gram gave 0.7880 COa and 0,2200 H,O. 0.2720 ,, ,, 0.6060 ,, 0.1670 ,, 0.5730 ,, gold salt gave 0.1165 Au.

No. 4. Crystals left undissolved from (3)-

0.2830 gram gave 0.6380 CO, and 0.1730 H,O. 0.2880 ,, ,, 0.6475 COz and 0.1800 H,O. 0.6760 ,, gold salt gave 0.1375 Au.

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WRIGHT ON THE ALKALOIDS O F THE ACONITES. 153

No. 5 . (B) recrystallised from ether--

0.2700 gram gave 0.5980 CO, and 0.1620 H,O. 0.5630 ,, gold salt gave 0.1140 Au.

No. 6. (C) recrystallised from ether- 0.2525 gram gave 0.5705 CO, and 0.1520 H,O. 0.5615 ,, gold salt gave 0.1135 Au. 0.5190 ,, , I ,, 0.1050 ,,

Carbon Hydrogen in base. in base.

No. (1). - - ................... - . , ....................

(2) . ................... 60-91 (3) .................... 60.62 ,, .................... 60.76

,, .................... 61.32 (4) .................... 61.48

(5) .................... 60-40 (6) ...... ., ............. 61-62

- 6-79 6.89 6.82 6.79 6.94 6.6'7 6 69

- - Average .................. 61.02 6-79

Calculated for C,3H4,N0,2 .... 61.39 6-67 -

Gold in gold salt. 20.38 20.36 20.31 20.33

20.34

20.25 20.23 20.21

20.30

19.92

-

-

- -

Specimens Nos. 2, 3 and 4 (A) were mixed and converted into hy- The recrystallised

Purified hydrobromide I (from A) 0.3850 gram of air-dry salt lost

Purified hydrobromide I1 (from B) 1.3800 gram of air-dry salt lost

Calculated for C,,H4,N012,HBr,2~H,0 = 5.83 per cent.

I. 0.3620 gram dried at 100" gave 0,0945 AgBr

drobromides, as was No. 5 (B) and also No. 6 (C). salts gave the following numbers :-

at 100" 0,0230 = 5.97 per cent.

at 100" 0.0820 = 5.94 per cent.

Br = 11.11 p. c. 11. 0.5720 ,, ,, ,, ,, 0.1485 ,, 9 , 11.05 7 )

Calculated for C33H,3N0,,,HBr = 11-02 ,, The base regenerated from these three specimens gave these values-

Base from hydrobromide 1.--0*2660 gram gave 0.5955 GO, and 0.1600 H,O.

0.1520 H,O.

0.1850 H20.

7 , II.-0.24440 )) 0.5500 CO, and

,> III.-0*3005 ,, 0.6800 CO, and

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154 WRIGHT ON TEE ALKALOIDS OF THE ACONITES.

Found. Caleulst ed . I. 11. 111. Mean.

CS3. . ........ 396 61.39 61.06 61.47 61.71 61-41

N .......... 14 2.17 HQ. ......... 43 6-67 6-68 6.92 6.84 6.81

O I 2 . . - ....... 192 29.77 - - - -

- - - - C ~ & & ~ N O I ~ .. 645 100*00

The gold salts gave these values :- From I, 0.8445 gram gave 0.1690 Au = 20.01 per cent.

y y 11. 0.5725 ,, ,, 0.1145 ,) = 20.00 ,, ,, 111. 0.6210 ,, ,, 0.1240 ,, = 19.97 ,,

Average 19.99 ,,

,,

--

Calculated for C33H~NO12,HCl,AuC1~ = 19-92

From these numbers it is clear that the AconiiumNapellus roots examined contained only one base crystallisable from ether ; and that this base, when perfectly pure, was identical with the crcoyzitine, C,H,,N012, previoualy isolated in an approximately pure crystallised state by Groves, and subsequently by Duquesne l , the different formula arrived at by the latter being due to the imperfect purity of the alkaloid extracted by him.

The quantity of crystallised base, C33H43N0127 isolabed from the 2 cwts. of roots amounted to a little upwards of an ounce, the total amount of alkaloids (amorphous products included) being some 2iozs. ; this represents a yield of about 0.03 per cent. of crystallised base, and 0.07 per cent. of total bases. M. Duquesne l states that the amount of “aconitine cr~s~allisbe” obtainable from A. hTupeZZw varies from 0.6 gram, and even none a t all, to 4 grams per kilo., i.e., from 0.06 to 0.40 per cent,. It may be noticed in this connection that the values given by P r o c t o r , Z i n o f f s k i and others, as t o the amount of alka- loid present in aconite roots simply represent the total alkalo‘icls, crystalline and non-crystalline, and give no clue as to how much of either kind was present ; inasmuch, however, as these values differ with the country in which the roots were grown, &c., &c., it is extremely probable that the amount of crystalline base, C ~ ~ H * ~ O I ? , will be found to vary according to circumstances.

It is proposed to study the chemical relationships and the “ constitu- tion” of this alkaloid, and the allied bases from A. ferox (pseudoco- nitine, C36H43N0,1). The physiological action of aconitine is excessively energetic, so much SO as to render working with it a matter of coil- siderable pain and difficulty, unless great care be taken in manipula- tion, and more especially in avoiding the inhaling of the dust of the

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WRIGHT ON THE ALKALOIDS OF THE ACONITES. 155

crystals of the base or its salts. A minute fragment, too small to be seen, if accidentally blown into the eye, sets up the most painful irri- tation and lachrymation, lasting for hours ; whilst similar particles, if inhaled, produce great bronchial irritation or profuse sneezing, and considerable catarrh or " sore throat," according to the part where they lodge.

The following sentences summarise the results obtained as above described from the work of Mr. Groves and the author.

1. Aconitum Napel lus roots, as met with in commerce, yield by appro- priate means a highly active, well-crystallised alkalo'id (nconitifze), which is represented by the formula, C33H4,N0,2 ; the crystallised bodies obtained formerly by Groves (1860), and by Duquesnel (1871), consisted mainly of this base, but were not perfectly pure.

2. It has happened in one instance that roots purchased as A. N q e Z Z w yielded only a small quantity of aconitine, and that a large amount of a nearly inert bitter base, yielding well crystallised salts (picracowitine) mas also present. The preparations usually met with in pharmacy under the name of " aconitine," or " nitrate of aconitine," must necessarily contain this inert base whenever it was present in the roots employed ; and consequently such pharmaceutical preparations cannot be relied on as of uniform physiological potency.

3. Besides aconitiize and picmconitine, A. Napel lus roots contain another alkalojid (alteration product of aconitine produced during extraction ?) of lower molecular weight, and incapable of yielding crystalline salts or of crystallising itself. Commercial " aconitine," when not crystallised, is liable to contain this substance as an impur- ity ; thus the body examined by von P l a n t a appears to have almost wholly consisted of this amorphous, uncrystallisable substance, which is perhaps identical with or may contain the body " napelline," and other analogous substances described by other chemists. 4. The physiologically active crystallisable alkalojid of A. NrpeZZus

(acon i t ine) appears to be wholly dissimilar from the crystallisable alkaloi'd of A. ferox (pseudaconitine), although the two are doubtless allied, and are similar in many of their properties. The inactive bitter base of A. Napellus (picraconitiilze) is not identical with Broughton 's atisine from A. heterophyllum.

5. The use of strong mineral acids and other reagents in the extrac- tion of aconite alkalo'ids from the roots (as in the older processes of Geiger and Hesse, of H o t t o t and Lihgeois, &c.) , is extremely likely to cause loss of crystallisable aconitine by alteration and decom- position ; and to this cause is to be attributed the statement of chemists who have used such processes, that the alknlold of A. Napellus is non- crystalline. Not improbably the " lycoctinine " and " acolyctine " of Hiilschmann, from A. Zycoctonum, are alteration-products thus

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156 HIGHT ON A PROPOSED METHOD OF

formed. The tartaric acid process of M. D u q u e s n e l is preferable, but in view of the first rough crystals of base thus produced being impure, and of the difficulty of separating a mixture of the crystallised salts of aconitine and picraconitine, it is desirable that in future the sub- stance employed medicinally should have been prepared and separatled from picraconitine (if present) by extracting the mixed alkaloids from the roots by Duquesne l ’ s process ; recrystallising the crude aconitine crystals thus obtained from ether or analogous solvents, so as to sepa- late picraconitine and the other non-crystalline bodies ; converting into a crystallised salt (for which purpose the hydrobromide is well fitted) ; and finally regenerating the alkaloid (if required in the free state) by sodium carbonate, and crystallising from ether ; in this way a perfectly defhite homogeneous substance is obtained, possessing in a high degree ‘the physiological powers of aconite root.

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