405

XLVI.-The Alkalo'ids of the Veratrums. Part 11. The Alkaloids of Veratrum Album.

By C. R. ALDER WRIGHT, D.Sc. (Lond.), and A. P. LUFF.

6 1. Isolation of Constituent Alkaloids.

ALTHOUGH numerous chemists and pharmacists have partially ex- amined the alkalo'ids contained in Veratruna album and other allied species (V. viride, V. Lobelianunz, &c.), yet very little exact knowledge has been gained as to the chemical characters of the bodies isolated, whilst in many cases the identity and homogeneity of the educts obtained are open to considerable doubt, no analyses having been made of them.

In 1819 Pelletier and Caventou (Ann. Chim. Phys. [el, 14, 69), obtained from V. album roots a sternutatory alkalo'idal body, which they appear to have regarded as identical with the so-called " veratria " from V. Subadilla seeds, and also with the active principle of Colchicum Auizcnmale. E. Simon showed in 1837 (Pogg. Ann., 41, 569), that besides so-called " veratria," V. album contains a base to which he applied the name jervine, readily crystallisable from alcohol, and cha- racterised by forming a very insoluble sulphate : this " jervine " was analysed by Will (Ann. Chem. Phurm., 35, 116), who obtained the following numbers (recalculated from the original data) :-

Water of crystallisation in crystallised base. 6.88 6.88 Carbon in base dried at 100". ............. 74.91 74.55 Hydrogen ,, ,, ................ 9.57 9.74 Nitrogen (estimated by volume) .......... Platinum in platinum salt. . .............. 14.33 14.55

5.38

from these numbers he deduced the formula C6,H4,NZO, (C = 6, 0 = S), for which latter chemists, following Gerhardt, have substituted C30H16N203.

This same non-sternutat,ory crys tallisable base has also been regarded by Peuguet, C. L. Mitchell and others, as existing in 7. uiride, whilst recently Tobien has stated (Inaugural Dissertation, Dorpat, 1877 ; Pharm. J. TYCI.?LS., April 13, 1878, p. 808) that i t is also contained in V, Lobelianum. Tobien's analyses, however, led him to a formula considerably different from that deduced from Will's numbers, viz., to Ca7H47N208, the hydrochloride being Cz7 H47N208, HCl.

The identity of the " jervine " from V. viaide with Simon's base, on the other hand, has been denied by Bullock and others, by some of

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406 WRIGHT AND LUFF ON THE

whom the term vil-idine has been applied to the cryst,allisable alkaloid from V. viride: as, however, few if any of the observers who have worked on tlie subject have opsrated in such a way as to inspire con- fidence in the purity and homogeneity of their products, and as more especially the substances examined have, as a rule, neither been analysed nor separated into fractions of constant character, o r other- wise treated so as to exclude the possibility of their being mixtures of several substances, it is evident that the relationship of tlie crystal- lisable alkalo'idal constituents of these different species is still an open question ; whilst the results obtained in Part I with V. SabadiZZa render it not improbable that the so-called " veratria '' of V. album (termed veratralbine'by some), and that of V. viricle (sometimes distinguished as veratro'idiae) may be mixtures of more than one difficultly crystal- lisable or non-crystalline base.

To throw some light on this quedion, 27 lbs. (about 1 2 kilos,) of crushed dried roots of V. aZbum obtained from Messrs. Bopkin and Williams were percolated with 4 gallons of alcohol containing 60 grams of tartaric acid (0.5 per cent. of the weight of the roots), and several gallons more unacidulated alcohol, the pepcolators being worked in series, so that the weak liquor from a partially exhausted batch was used to wash a newer one, and so on, the object being to obtain as concentrated a liquor as possible, and so to introduce less chance of alteration by continued exposure t o heat on evaporating off the alcohol. The percolate concentrated to a small bulk by distillation was then mixed with water, strained from the resin that separated, rendered slightly alkaline with caustic soda, and shaken many times with about its own bulk of ether, the ethereal solution being separated and shaken with aqueous tartaric acid, and the ether then used over again, so that an acid solution of tartrates of alkalo'ids was thus 'obtained, whilst resinous matters, &c., remained dissolved in the ether. After some seven or eight treatments with ether scarcely any appreciable amount of alkalo'idal matter was further taken up by the ether, nor was any clissolvd by fuse1 oil ; a notable quantity of a brown flocculent alka- lo'idal substance was, however, suspended in the aqueous liquid: this was collected on a calico filter, and purified by solution in acetic acid, filtration from undissolved resinous matter, and precipitation by soda ; the gelatinom brownish precipitate obtained, when drained, washed, and dried, dissolved in boiling alcohol with the exception of some llumus-like flakes insoluble in acids ; the filtered solution deposited nearly white crystals on cooling, the mother-liquors of which gave a little more on spontaneous evaporation, with a small quantity of amor- phous basic matter readily soluble in cold alcohol. These crystals are hereafter referred to as fraction 1.

The crude acid tartrate solution obtained from the first ethereal

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ALKALOIDS O F THE VERATRUMS. 407

extract was then precipitated by caustic soda and shaken again with fresh ether in much smaller quantity than a t first ; a portion thus dis- solved, whilst a considerable amount remained insoluble even after two or three such treatments with ether : to remove all the more soluble con- stituents mechanically retained., the undissolved portion was dissolved in tartaric acid and treated again with soda and ether ; the substance then left undissolved is referred to as fraction 2. The ethereal soln- tions thus obtained deposited on spontaneous evaporation a quantity of crystals, fraction 8, the mother-liquors of which dried up to a honey- like viscid mass, fkxctz'on 4.

I n this way a first rough separation of alkalo'idal constituents was effected, based on their differing solubilities in ether, or in ether con- taining resinous matters, more soluble alkalo'ids, &c., in solution. Fractions 1, 2, md 3 were cqstalline to 2t greater or lesser extent, whilst fraction 4 was wholly amorphous ; this last fraction contained Che whole of the sternutatory alkalo'idal constituents, none of the first three producing 'the peculiar provocation to sneeee characteristic of " veratrin."

On further working up these different fractions, it was foiind that although no one of them was pure and homogeneous, in each a different alkalo'id predominated. Fraction 1 consisted almost entirely of a well crystallised alkalo'id, C29H43N0,, which we propose to term, provisionally a t least, pseudojeruine, inasmuch as whilst it resembles jervine in several respects, it differs therefrom notably in many points, Fraction 2 contained some pseudojervine and some jervine (which when pure we find to be indicated by C26H3~N0,), but chiefly consisted of an amorphous base, probably indicated by the formula C,sH1,N05. Fraction 3 consisted of jervine, with a small quantity of a third crys- tallisable base, C,,H,,NOr, giving a colour reaction with snlphuric acid quite different from that of jervine; whilst fi-action 4 contained a minute quantity of jervine, and a t least two uncrystallisable alkaloPds, one of which, present only in small quantity, is the chief sternutatory ingredient, and is very probably identical wihh the veratrine (of Conerbe) from V. Xabaclilln, as it yields veratric acid on saponification, whilst the other is the amorphous base just referred to as probably indicated by C,8H4,N@5. The total quantity of dkaloidal matters ob- tained from the 12 kilos. of roots employed was about 50 parns or 0.42 per cent. Of this, rather more than.one-half consisted of non-crys- tslline bases, the sternutatory prodnct constituting fraction 4 weighing some 6-7 grams, and the amorphous base of fraction 2 nearly 20 grams. The total jervine present was about 16-17 grams, that of pseudo-jervine being 4-5 grams, whilst about 3 grams of the third crystallisable base (which we propose to term ruBIj'erviue) were present. As, how- ever, r;hese bases were more or less intermixed in the different frac-

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408 WRIGHT AND LUFF ON THE

tions, the quantities of pure substances ultimately separated from one another were by no means equal to the total quantity present.

9 2. Ezamination of Fractiort 3.

The results obtained by the further examination of this fraction are first described, as they throw light on those obtained with the other fractions. The crystals that separated from ether as just described, when well washed with ether were but very sparingly soluble in that menstmum, although they dissolved far more readily in ether already containing in solution the amorphous bases constituting fraction 4. As a first preliminary trial these crystJals were analysed along with those obtained by recrystallising fraction 1, when the following num- bers and properties were observed, clearly showing non-identity :-

Water of crystallisation in air-dry crystals ....

Carbon in base dried at 100" ................

Eydrogen ............ Melting point (corrected) Effect on stirring with

dilute sulphuric acid.

Fraction 1.

0.92

67-86 8.75

Dissolved to a clear solution depositing crystals on stand- ing, which after se- paration from the excess of acid by the filter-pnmp, were very sparingly soluble in cold water, but readily soluble iu boiling water.

280"

Practioii 3.

5.81 5.27

75.99 10.09

Did not dissolve, but became an indis- tinctly crystalline s e m i - g e l a t i n o u s magma, which after separation from the excess of acid by the filter-pump, were as p o d as insoluble in water, whether cold or boiling. The acid filtrate contained a litt'le of a different base (rubijervine).

231"

Fraction 3 accordingly agrees in general characters and analj tical numbers sufficiently well with Simon's jervine to indicate that the same alkalo'id in a more or less pure state constituted the majority both of Simon's product and of fra.ction 3,-whilst fraction 1 chiefly consisted of a wholly different alkaloid.

In order to obtain the constituents of fraction 3 as pure as possible in a separate condition, the crystals from ether were digested witth warm dilute sulphuric acid, and the semi-gelatinous magma thoroughly drained and washed, and then suspended in boiling water and again filtered. This last filtrate contained scarcely any appreciable amount

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ALKALOIDS OF THE VERhTRUAlS. 409

in solution, clearly showing that the alkaloydal sulphate is very sparingly soluble, even in boiling water. From this insoluble sulphate the base was regenerated by boiling with alcohol and sodium carbo- nate. The filtered liquid deposited, on cooling, light white flaky crystals, which yielded the following numbers :-

Specimen I.-Base prepared as just described and crystallised from alcohol.

0.5165 gram of air-dry base lost a t 100" 0.0325 gram. 0.256 gram of dried base gave 0.709 CO, and 0.220 H,O.

Specimen 11.-Specimen I again converted into sulphate by rubbing in a mortar with dilute sulphuric acid, and after filtration and wash- ing regenerated by means of sodium carbonate and alcohol (no more than traces of base soliible in sulphuric acid were thus separated).

0.4850 gram of air-dry crystals lost a t 100" 0.0360 gram. 0.2515 ,, 0.399 ,,

of base dried a t 100" gave 0.7150 CO, and 0.219 HzO. burnt with soda lime gave by titration 0,0133 nitrogen,

by conversion into platinum salt, 0.093 Pt.

Specimen 111.-Obtained by spontaneous evaporation from the

0.3749 gram lost at 100" 0.0255.

These numbers agree with the formula CZ6H3,NO3,l~H2O, bnt i t is highly probable that the crystals really contained 2H20, and that the deficiency in water of crystallisation is due to separation of a little anhydrous base from hot or strong alcohol (v ide i@ra 9 4).

mother-liquors of Specimen 11.

Calculated for Found. C,,HqNO,, l+H,O. 2H20. I. 11. 111.

Water. . .... 6-16 8.05 6.29 7.42 6.82

Found. Calculated. I. 11.

CZ6 ...... 312 75-91 75.53 75.73 H37 ...... 37 9.00 9.54 9.45 N ........ 14 3.41 - 3.33 3.29 0 3 I I ........ 48 11.68

411 100*00

The gold salt gave the following numbers. It was precipitated from a solution of the base in highly diluted hydrochloric acid by addition of gold chloride, and was distinctly crystalline, only becoming anhydrous at 100" slowly.

BOL. xxxv. 2 F

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410 WRIGHT AND LUEF ON THE

0.428 gram of air-dry salt lost at loo", 0.0125 . . . . . . . . = 2.92 Calculated for C&f&NO,, HCI, AuCI,, H,O . . . . . . . . = 2.34

0.415.5 gram of dried salt gave 0.1065Au . . . . . . , . . . . = 25.63 Calculated for CZsH,,NO3, HCI, AuCI3.. .. . . . . . . . . . = 26-13

On rubbing the base with dilute hydrochloric acid, a magma of crystals resulted, only very sparingly soluble in water even when boil- ing, the solubility being diminished by the presence of free hydro- chloric acid. In acetic acid i t dissolved, the solution yielding with potassium nitrate solution a very insoluble precipitate of nitrate.

The corrected melting points of the different specimens of base were found to be-

Specimen I.. . . . . 11. . . . . ,

111. . , . . . 231", with slight previous browning, 237' ; no previous browning, 231" ; slight previous browning,

,, ,,

the fused mass being in each case much darker than the original substance, being distinctly browned.

The base C26H,7N0, thus obtained agreed well in all its characters wit,h the " jervine" of Simon and Will ; moreover, it yielded with cold strong sulphuric acid the peculiar colour reaction usually ascribed to jervine, viz., dissolving to a yellow fluid, which speedily becomes sue- cessively dark yellow, brownish- yellow^, and the peculiar greenish- brown tint obtained when a somewhat stale solution of potassium ferricyanide is mixed with ferric chloride. After standing some little time, dependent on the humidity of the atmosphere, &c., a green tint is developed ; when only a speck of crystallised base is used, and a drop or two of acid inn white porcelain basin, the green appears first a t the edges, and extends until the whole is a dark green. Large quantities in a test-tube do not become green until after some hours' standing, but the green shade is irnniediately developed on very slightly diluting with water the greenish-brown fluid formed after standing for half-an- hour or so, the t int becoming successively olive-green, dark chrome- green, and finally dark emerald, as the addition of water progresses. With more water the tint becomes lighter, until finally a nearly colourless fluid results, with a few brownish-yellow flakes suspended therein. This peculiar colour reaction, however, is not confined to jervine, the pseudojervine described below also yielding just the same tints, whilst the other alkaloidal constituents give with cold sulphuric acid yellow solutions, becoming quickly brown-yellow, brown, reddish- brown, and finally more or less red in tint, in this respect being more analogous to veratrine and ceradine (Part I), which form with eulphuric acid yellow solutions, gradually clianging to dark yellow, brownisli-yellow, chestnut, dull scarlet, and deep blood-red. These

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ALKALOIDS OF THE VERATRUMS. 411

two last alkaloids are indistinguishable from one another by trans- mitted colour only, but are differentiated in that cevadine gives a dark green-fluorescent red solution, whilst veratrine (of Couerbe) gives no fluorescence. On standing some hours so as to absorb mois- ture, or on adding to the blood-red solution a minute quantity of water, the colour changes in each case to a lovely crimson or magenta shade, permanent for many weeks.

The acid filtrate from the jervine sulphate obtained on first treating fraction 3 with dilute sulphuric acid was found to contain an alkaloid wholly different from jervine, though probably closely allied thereto. The liquid was treated with a slight excess of caustic soda, and the precipitate drained and washed. I n this state it dissolved wholly in it few drops of dilute sulphuric acid, lea,ving no trace of jervine sulphate undissolved. The solution deposited crystals on standing, readily soluble in hot water, or in cold water acidulated with sulphuric acid, but less easily dissolved by cold water free from acid. The free base after crystallisation from alcohol was anhydrous. In dilute hydrochloric acid it readily dissolved, a magma of crystals readily soluble in water being formed when a drop or two of somewhat stronger acid wasused instead of dilute acid. With concentrated sulphuric acid it dissolved to a clear yellow fluid, becoming successively dark yellow, brownish- yellow, and brownish blood-red, changing after several hours to a brownish-purple. On diluting slightly with water the brownish blood- red liquid, it became successively crimson, purple, dark lavender, dark violet, and ultimately light indigo.

The following numbers were obtained :-

0.2330 gram of base dried at 100" gave 0.6620 C02and 0.2285 H,O. 0.3520 ,, ,, burnt with soda-lime gave by titration 0.01165

gram N, and by platinum salt 0.0835 Pt. Calculated. Bound.

C26 .......... 312 i7.81 7 7.48 Hi, ........ 43 10.72 10.89 N .......... 14 3.49 3.31 3.38 0, ......... 32 7-98 -

~ ~~~

Cz6H4,N02.. .. 401 100.00

The gold salt formed a light yellow, indistinctly crystalline, in- soluble precipitate, of which-

0.2215 gram dried at 100' gave 0.0595Au.. = 26.86 per cent. Calculated for C26HuN02, HC1, AuCl, . . = 26.49 ,,

The crystallised base melted at almost exactly the same temperature as jervine, 236' being the corrected melting point obtained with the purest crystals, and 228" that with a small quantity of less pure

2 F 2

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412 WRIGHT AND LUFF ON THE

crystals obtained by spontaneous evaporation from their alcoholic mother-liquors.

From the probable connection between this base and jervine sng- gested by their occurrence together and notl widely different formulae, together with the difference in colour-reaction with sulphuric acid, we propose to distinguish the base C2,Hd3N02 provisionally as rubijervine, i.e., the jervine-like alkalo'id which gives it red colour with sulphuric acid.

When perfectly free from other alkalo'idal matter more readily soluble in ether, neither jervine nor rubijervine are easily dissolved by that menstruum, although a little of each is taken up on shaking therewith a solution of any salt and a little caustic soda ; i f , however, they be mixed with the more soluble alkaloids constituting fraction 4, ether dissolves them much more freely. This is also the case with pseudojervine ; but under any circumstances the solubility of this latter in ether is much less than that of either jervine or rubijervine.

tj 3, Exnnzination of Fraction 1. The crude crystals, obtained as above described, when recrystallised

from hot alcohol formed a snow-white mass much resembling jervine in appearance, but melting a t a much higher temperature (280" cor- rected), and giving with cold concentrated sulphuric acid a succession of colours nearly the same as those yielded by a specimen of pure jervine tested side by side, but exhibiting in certain stages a redder or browner shade, suggesting that with a body giving the colour reaction of jervine, a small quantity of something else giving a red colour was intermixed (presumably rubijervine) ; this was subsequently found to be actually the case.

On treatment with warm considerably dilute sulphuric acid, these crystals almost wholly dissolved, leaving behind only a minute quan- tity of jervine sulphate ; the solution on standing deposited crystals which, when drained from the acid mother-liquor, were only sparingly fjoluble in cold water, but readily soluble in hot water. The solution of sulphate thus practically freed from jervine was precipitated by soda, and the washed and drained precipitate stirred up with dilute hydrochloric acid in very slight excess : a crystalline magma was thus formed, which, after draining from the acid liquor, was only sparingly soluble in water, even when hot, but was much more readily dissolved in water slightly acidulated with hydrochloric acid. The hydrochlo- ride left undissolved by washing with hot water, was boiled with alcohol and sodium carbonate, and the base which crj-stalliscd from the alcoholic liquors again converted into hydrochloride and filter- puinped to free from any possibly adherent traces of any other base yielding a more soluble hydrochloride, but mechanically retained. By

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ALKALOIDS OF THE VERATRUMS. 413

means of alcohol and sodium carbonate, the base was finally regene- rated from the hydrochloride, and obtained in crystals much re- sembling jervine in appearance, and now yielding precisely the same colour-reaction with sulphuric acid.

These crystals were anhydrous when air-dry, and melted at 299" (corrected), browning during fusion, but not perceptibly previously. The following numbers were obtained :-

I. Purest base obtained as just described-

0°2045 gram gave 0.161 H,O and 0.505 CO,. 0.3325 gram, burnt with soda-lime, gave 0.065 Pt.

11. Specimen of base still retaining a minute quantity of rubijer- vine (after treatment with sulphuric acid to separate jervine, but before conversion into hydrochloride to separate rubijervine)-

0.258 gram gave 0.642 CO, and 0.208 HzO.

Calculated Found. I. 11.

C, ........ 348 67-31 67.35 67-86 Hd3 ........ 43 8-32 8.75 8.95 N .......... 14 2.71 2.77 - O7 . . . . . . . . . . 112 21.66

0.1925 gram of gold salt from Specimen I, dried at loo", gave

Calculated for CZ9Hc3N07, HC1, AuCl, = 22-90 per cent. 0.0445 Au = 23-11 per cent.

The crystalline hydrochloride, when air-dry, contained C,,H ,,NO,, HCI, 2H20; 0.4115 gram dried at 100" lost 0.0325 gram = 7-90 per cent.

Calculated = 6.10 per cent.

From the partial similarity of this bas5 to jervine, we propose to term it pseuclojmiize. The mother-liqnors from which the crystalline hydrochloride of pseudojervine was separated, as just described, were precipitated with caustic soda, drained, and washed, and fhen rubbed with a slight excess of hydrachloric acid: some little quantity of pseudojervine hydrochloride was thus obtained in orystals ; the slightly acid liquid drained from this contained too little alkalo'id in solution to permit of a perfeot separation of pure rubijervine from it ; but that this base was actually present in small quantity is clearly indicated by the following numbers obtained on analysis of the mix- ture of pseudojervine and rnbijervine precipitated therefrom by soda and crystallised from a small bulk of alcohol :-

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414 ITRIGHT AXD LUFF ON THE

Carbon in free base.. ................ Hydrogen in free base . . . . . . . . . . . . . . . Gold in gold salt.. . . . . . . . . . . . . . . . . . . Melting point (corrected) . . . . . . . . . . . .

Pseudojer- Rnbi jerrine. Mixed bases 1 vine. 1 1 examined.

67 '31 77 %1 69 *85 8 '32 10 -72 9 -60

22 -90 26 -49 24 -48 %Yo 236" 268"

and also by the circumstance that the series of colours given with sulphuric acid by this mixture was indistinguishable from tha,t yielded by a mixture of pure psendojervine and rubijervine in which the former somewhat preponderated.

From these resnlts it is evident that fraction 1 consisted essentially of pseudojervine, a minute quantity of jervine and of rubijervine being also present ; the much less solubility in ether (containing more soluble alkalo'ids, resinous matters, &c.) of pseudojervine than of the other two bases is thus rendered evident, fraction 1 being the portion lefto undissolved by ether after many treatments therewith, whilst fraction 3 consisted of that portion of the crystallisable alkaloids present which were most readily dissolved by ether, having been taken up by that solvent in two successivc treatments therewith.

9 4. Examination of Fraction 2.

From the foregoing results it is evident that this fraction might, 2 priori, be expected to contain quantities of jervine, pseudojervine, and rubijervine intermediate between those found in fractions 1 and 3, i.e., that there would be present some considerable amount of jervine, a little pseudojervine, and some little rubijerviile. These bodies were actually found to be present, but, in addition, a considerable amount of an amorphous base was also present, the solubility of which in ether, though sufficiently great t o prevent any large quantity being found in fraction 1, was yet sufficiently small to prevent more than a portion of i t being taken up on the second treatment with ether per- formed to separate fraction 2 from fractions 3 and 4.

The whole mass of substance undissolved by ether on the second treatment therewith constituting fraction 2, mas warmed with dilute sulphuric acid, allowed to stand 24 hours, and filter-pumped. The filtrate contained a large amount of a readily soluble sulphate (or mixture of sulphates), whilst the residue on the filter consisted of jervine sulphate intermixed with pseudojervine sulphate, and a small quantity of rubijervine sulphate.

The filtrate was precipitated by caustic soda, and the precipitate drained, washed, and dissolved in hot alcohol : after long standing and spontaneous evaporation a f e a crysbals separated, which, after collec-

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tion, washing, and recrystallisation, were anhydrous, and gave num- bers agreeing with pseudojervine, the melting point being 287", and the colour-reaction with sulphuric acid almost precisely identical with that of pure pseudojervine tested side by side. The mother-liquors of these few crystals dried u p to a varnish which would not yield crystalline salts, and was devoid of sternutatory properties : on analysis this yielded the following percentages :-

Carbon, in base, dried a t 100". ........... 69.36 9-21

Nitrogen (by soda lime) ,, .......... 2.86 Gold in gold salt dried at 100" .......... 23.18

Hydrogen, in base, dried at 100". . . . . . . . . .

These numbers fall somewhat below those calculated for the formula C28H43N05, which requires carbon, 71.04 ; hydrogen, 9.09 ; nitrogen, 2-96 ; and gold in Au salt, 24-14 ; but are just those which would be obtained with a mixture of a substance of this composition with a little pseudojervine (containing carbon, 67.31 ; hydrogen, 8.32 ; nitro- gen, 2-71 ; gold in Au salt, 22.90) : since the varnish-like base from these mother-liquors must necessarily have contained some pseudo- jervine, whilst the substance described in § 5 (which was doubtless cssentially the same body as this amorphous base, but also containing a minute quantity of veratrine) gave numbers approximating t o the formula C2BH47W05, it is evident that this formula is at any rate an approximation to the true formula of the amorphous base, which we propose to term (at any rate provisionally) zeratralbim, this name having been applied by lllitchell and others to the amorphous bases solilble in ether obtained from V. album, the which bases as shown in fj 5 consist almost entirely of C,,H,NO,, the sternutatory proper- ties being due to the presence of a small percentage of veratrine (or at least of a base yielding veratric acid on saponification).

Veratralbine is unchanged by boiling with alcoholic potash for 24 liours: tlie amorphous mixture of vcratralbine and a little pseudo- jervine, jiist described, when treated in this way yielded no trace of any kind of acid saponification-product ; the residual base formed a gold salt containing 22.91 per cent. of gold ; inasmuch as the original substance formed a gold salt containing 23.18 per cent. of Au, it is evident that no diminution in molecular weight, took place during the treatment with alcoholic potash.

With sulphuric acid veratralbine gives a series of colours closely akin to those developed by cevadine, and far more resembling those produced by rubijervine than those yielded by jervine or pseiidojervine ; the solution of a speck of the base in strong sulphuric acid becomes successively yellow, dark-yellow, brownish-orange, and brownish blood- red, with a strong green fluorescence.

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416 WRIGHT AND LUFF ON THE

The mixt,ure of sulphates left on the filter contained so much pseudojervine Chat a complete separation of that base by washing with cold water or by regenerating the alkaloids (by alcohol and sodiuni carbonate), reconversion into sulphates by dilute sulphuric acid and filtering, appeared to be impracticable ; pure jervine sulphate, how- ever, was readily obtained by boiling the mixed sulphates (washed from the majority of the excess of sulphuric acid) with water and filter-pumping hot : by regenerating the base, by means of alcohol and sodium carbonate, jervine was obtained identical with that described above, melting a t 339" (corrected) and yielding the following numbers (after drying at 100') agreeing with C26H37N03.

0.2195 gram gave 0.6075 CO, and 0.182 H20. 0.235 9 ) 0.6465 ,, 0.205 ,,

Calculated. Found. Carbon . . * . . . . . . . 75.91 75.48 75.03 Hydrogen. ... . . . . . 9.00 9.23 9-69

The colour reaction with sulphuric acid was identical with that yielded by jervine from fraction 3.

Two different specimens of impure jervine isolated from the sulphate pnrtiaIly freed from paeudojervine sulphate by washing with cold water, &c., gave carbon 74.08, hydrogen 9-20, and carbon 74.41, hydro- gen 9-43, respectively ; the numbers obtained by Will (quoted in § 1 ) lie between these and those obtained as above stated with pure jervine, from which it may be inferred that Simon's product examined by Will was essentially jervine but containing a small admixture of pseudojervine, which would account also for the low percentage of platinum found in the platinum salt (found 14.55 and 14.33 ; calcu- lated for ( C2,H3,NO3,HCI),PtCl4 = 16.03).

The water of crystallisation found in these specimens of pnre and nearly pure jervine was found to vary considerably ; when the crystals were formed from very strong alcohol (90 per cent. spirit) or began to separate whilst the solution was skill warm, smslicr amounts were found than when the alcohol contained a little more water (70-80 per cent. alcohol) c r when the crystals formed in the cold. Thus with five different samples the following numbers were obtained :-

Calculated for Calculated for Found. C2,H 0, , 2 4 H,O . C&E&,NO,, HZO. 8-20

8.12 4.1 9 8.05 6.84 5.49 5-19

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ALKALOIDS OF THE VERATRUMS. 417

69.33 8 .93 -

245' I

Hence, as above stated (§ 2) it is probable that the normal crystals are CzsH3?N03, 2H20, b u t that a little anhydrous base also separakd from hot a,nd very strong alcoholic solutions.

The liquors filtered from the jervine sulphate undissolved by water (cold or hot), were precipitated by soda, collected and washed, and again treated with warm dilnte sulphuric acid to separate any trace of jervine still present ; scarcely appreciable amounts of jervine sulphate were left undissolved ; the filtrate contained too little alkaloidal matter in solution to permit of complete separation of the pseudojervine and rubi jervine which it undoubtedly contained, although a partial separa- tion was effected by means of ether; the following numbers were obtained :-

A. Bases precipitated by soda from the filtrate just mentioned and

B. Fraction of this mixture left undissolved by agitation with a

C. Fraction dissolved by the ether.

recrystallised from alcohol.

large bulk of ether.

69.25 8-95

23'02 268"

-- Carbon, in base, dried a t 100" Hydrogen ,, Y )

Gold in gold salt ,) Melting point (corrected). . . ,

Pseudo- jervine.

67 -31 8.32

22 *go 299"

Rubi- jervine.

7'1 -81 10 a 7 2 26 -49 236"

i A. 1 B.

-1- ' I ~

0.

'72 -96. 10 *10

e a 0 -

All three of these substances gave with sulphuric acid a colour reaction like that yielded by a mixture of pseudojervine and rubijer- vine, the alteration of the green tints being more marked with C than with the other two.

From these results it appears that fraction 2 consisted of jervine with a little pseudojervine and somewhat less rubijervine, together with a majority of a different alkalojid, apparently amorphous and approximating to C2,H,,NO5, to which we propose to limit the term uerntralbine.

8 5. Exanaination of Bb-action 4. The varnish left on evaporation of the ethereal mother-liquor consti-

tuting this fraction was powerfully sternntatory in its action when in powder ; all attempts to mystallise i t from ether, petroleum, benzo- line-ether, alcohol, &c., entirely failed, nor could any erystnllised salts be obtained ; on solution in ether, addition of light petroleum distillate, and spontaneous evaporation, a few centigrams of jervine were ob- tained, the mother-liquors of which were hopelessly non-crystalline.

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418 WRIGHT AND LUFF ON THE

With sulphuric acid, the resinous alkalo'id left on evaporat,ion of these final mother-liquors gave exactly the same coloration as the amorphous substance (impure verntralbine) described in 5 4; evidently from the mode of separation of the different fractions, the same amorphous base must have been present to a large extent in both fractions, fraction 2 containing that part of it not dissolved by ether on the second treat- ment of the alkalojidal matters therewith, and fraction 4 containing that portion of it which was so taken up by the ether.

On analysis the following numbers were obtained approximating to the composition C2,HEI,,N0, :-

Calculated. Found. Carbon in base.. .......... 71.04 70.96 Hydrogen ................ 9-09 9-27 Nitrogen ................. 2.96 2-80 Gold in gold salt .......... 24.14 23.66

Apparently, therefore, this varnish consisted of the non-sternutatory amorphous base, sparingly soluble in ether, above referred to, and provisionally designated veratralbine, with a minute quantity of a s ternutatory alkalo'id, probably the veratrine (of Couerbe) described i n Part I intermixed therewith : for on cohobation for 20 hours with alcoholic potash a small quantity of veratric acid was formed, whilst the sternutatory action was wholly or almost wliolly destroyed. The veratric acid amounted to 2.5 to 3.0 per cent. of the alkaloidal matter thus treated, indicating an admixture of not more t'han 10 per cent. of veratrine with 90 per cent. or more of non-saponifiable alkaloidal matter ; it' was recognised by its melting point, and the formation of protocatechuic acid on fusion with caustic potash. No trace of cevadic acid was formed during the saponification indicating the absence of cevadine. The admixture of 10 per cent. of veratrine (containing carbon = 64.63, hydrogen 7.71, gold in gold salt 19.10) with an alka- lojid of composition CZeH,,NO,, would only diminish the percentages of carbon and hydrogen found, and of gold in the gold salt by trifling amounts.

Assuming, as it is highly probable from these results, that the alka- lojid thus present yielding veratric acid on saponification was actually veratrine, and that the sternutatory action of fraction 4 (and conse- quently of the whole roots examined) was solely due t o its presence, it results that the quantity of active alkaloid present in the roots examined must have been very small : since fraction 4 constituted only about an eighth of the total alkaloids, the quantity of veratrine could not. have exceeded 1.25 per cent. of the total alkalo'ids, equal to 0.004 per cent. of the roots examined.

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ALKALOIDS O F THE VERATRURIS. 4 19

§ 6. Attempts to obtain Derivatives of Jei-vine amd i t s Congeners.

On cohobating jervine for several hours with alcoholic potash, no change whatever is produced in the alkaloid: no new products of any kind are formed. The base, after cohobation for 24 hours in one experiment, was recovered from the alcoholic liquor by evaporation, washed with alcohol, and converted into gold salt, of which

0.637 gram, dried a t loo", gave 0.1635 Au = 25.66 per cent. Calculated for CZ6H3,NO3, HC1, AuCl, = 26.13 ,, ,,

It melted a t 233" (corrected) ; the melting point previously being 236".

Similar negative results were obtained with pseudojervine as far as the limited amount of the material a t our disposal enabled us to judge ; as also with the amorphous alkalo'id obtained from fraction 3 (veratral- bine) : after cohobation wiilh alcoholic potash, the recovered base gave a gold salt containing 22-91 per cent. of gold, the original substance containing 23.18 per cent., whence no alteration in molecular weight had taken place.

An attempt to obtain a benzoylated jervine by fusion with benzoic anhydride led to no definite result; the product when dissolved in alcohol and trcated with ether and alkali yielded nothing to the ether capable of being withdrawn bg shaking with tartaric acid ; nor did it yield anything when boiled direct with tartaric acid, nor could any salt be separated from the excess of benzoic anhydride. Possibly this points to the formation of a benzoylated base, the tartrate of which is insoluble in water, and the free base in ether: we have not made any further attempts in this direction, however, as yet.

§ 7. Xuinrnnry of Results.

(1.) The Yeratrum album roots examined contained a t least five different alkalo'ids ; of these three are well-defined crystallisable non- sternutatory bases ; a fourth is amorphous and non-sternutatory ; whilst the fifth is highly sternutatory.

(2.) By the method adopted a rough separatinn of these alkalojidal constituents is readily effected, one of the cry stallisable alkalo'ids (pseudojervine) being left behind with but little admixture after the first prolonged treatment with ether ; this is, when pure, CZ9H4,NO7 ; i t crystallises anhydrous and is non-sternutatory ; it melts a t 299", and forms a crystallisable sulphate and hydrochloride, not of great solu- bility (especially the latter) in pure water, more soluble in presence of excess of acid and on heating. This base gives a peculiar series of colours with sulphuric acid.

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420 WRIGHT AND LUFF ON THE ALKALOIDS, ETC.

(3.) Of the bases dissolved by ether on the first prolonged treat- ment, some are much more readily soluble in ether than others, so that on conversion into tartrates, precipitation with soda, and treat- ment again with much smaller quantities of ether, some are almost completely dissolved out, whilst others are mostly left undissolved. The undissolved bases contain, besides a little pseudojervine, some quantity ofjervine (of Simon and Will) : this is, when pure, C,,H:,,NOJ, and is not a dinitrogenous base, as stated by previous observers ; i t crystallises with 2H20 (somewhat less if the solution be hot or very strongly alcoholic) ; its sulphate is all but insoluble in water even when hot, and its hydrochloride and nitrate are very insoluble salts. When auhydrous it melts a t 237" to 239" (purest specimens) or somewhat lower (not absolutely pure specimens) ; with sulphuric acid it gives the same tints a s pseudojervine. (4.) In addition, the insoluble portion contains a large quantity

of an amorphous non-sternutatery base, apparently indicated by CzeH4,N05: to this base we propose to limit the term "veratralbine ;" i t gives with sulphuric acid a colour reaction quite different from that of jervine and pseudojervine : a trace of the base mentioned in the next paragraph is also present.

(5.) The substances dissollved by ether on the second treatment appear to be free from any appreciable quantity of pseudojervine, but contain jervine, and a third crystallisable non-sternntatory base, m b i - jervine, C2,Hi3NO2 ; this crystallises anhydrous, melts a t close upon the same temperature as jervine (236" purest specimen), forms a hydro- chloride and sulphate distinctly more soluble than the jervine or pseudojervine salts, and gives with sulphuric acid an entirely different, colour reaction from that yielded by either of these two.

(6.) Jn addition, the most soluble portion contains a minute amount of a sternutatory alkalo'id Fielding veratric acid on saponi6cation (not improbably veratrine) ; the great majority, however, approximates to CP8H4DO5, and is non-saponifiable, and apparently non-sternutatory ; this substance gives with sulphuric acid a colour reaction identical with that of the amorphous base referred to in paragraph 4 as veratmZ- bine, with which indeed it is obviously essentially identical.

(7,) With the exception of the veratric acid-yielding constituent just referred to, none of the above alkaloids belong to the saponifiable class.

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