994 DCJNST-4N AND JOWETT :

LXX.-Contributions t o our Knowledge of the Aconite Al.knloi&. Par t VII. On some Moda$cations of Aconitine Azwichloride.

By WYNDHAM R. DUNSTAK, M.A., F.R.S., and H. A. D. JOWETT, Redwood Scholar in the Research Laboratory of the Pharmaceuti- cal Sociely.

IN Part I of this inquiry an account was given of the properties of aconitine nurichloride, C33H15N012,HA~C: I,, and its melting point w a s recorded as 135.5" (cow.). Since then we have frequently had occasion to prepare this compound as a means of identifying aconitine, and have observed that when crystalliaed under slightly diEerent condi- tions its melting point is subject to considerable irregularity. It was satisfactorily proved that this irregularity was not the result of impurity, and, since its occurrence interfered with the use of this compound, as evidence of the identity of an alkalojid with aconitine, we have made experiments with the view of ascertaining the cause. When a solution of aconitine hydrochloride is mixed with aqueous auric chloride, an amorphous, pale-yellow precipitate is abundantly produced. Tbe precipitate, when dried on a porous tile in a vacuous desiccator, melts somewhat inde6nitelg near 137". It dissolves readily in alc01101, chloroform, and acetone, but is scarcely soluble in ether or in water. The solutions deposit the componnd in ci-ystals on slow evaporation, but crystallisation is best effected by the addition of

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SOME MODIFICATIONS OF ACONITINE AURICHLORIDE. 995

water to a strong solution in alcohol or acetone until a faint, perma- nent turbidity appears ; 011 standing, crystals separate, and a further quantity is obtained by adding more water to the mother liquor. Similarly, the solution in chloroform furnishes crystals when it is mixed with ether and allowed to stand in a closed bottle. A very large number of experiments have been made with these solvents under different conditions, but it will not be necessary to describe them in detail. It is suficient to state that by using different solvents three distinct crystalline compounds have been obtained, diff eriiig in melting point. Analyses have proved that these three substances possess the mme composition, and are not different hydrates of aconitine aurichloride or compounds containing a different proportion of hydrogen chloride. Noreover, it has been shown by regenerating the alkalo'id in each case, that they are true aconitine derivatives, and are not compounds of an isomeric alkaloid or of decomposition pro- ducts of acouitiue itself.

The results of these experiments may be summarised as follows. Start'ing with pure crystalline aconitine (m. p. 188-189", corr.),

and converting it into the hydrochloride by dissolution i n weak aqueous hydrochloric acid, the solution was precipitated with an excess of aqueous auric chloride and the amorphous precipitate col- lected, washed, and dried in a desiccator. The three modifications, distinguished as a , @-, and y, are obtained by the following methods.

Aconitine a- aurichloride, C,,H4,N012,HAuC14, is obtained when the aporphous substance is dissolved in acetone and the solution mixed with a little water. This liquid deposits rosettes of needle-shaped crystals which, after drying in a desiccator, or at loo", melt, with effervescence, at 135" (corr.). That this salt is not a hydrate was proved by heating it for three hours a t loo", when it lost no weight, and its melting point remained nnchnmged.

The gold and the chlorine were determined in the substance by the following method, which rendered it possible to make the two deter- minations with one and the same quantity of material.

A b u t 0.3 gram is dissolved in alcohol arid mixed with aqueous hydrogen sulphide, drop by drop, until, after vigorous shaking, a slight excess can be detected. The go16 sulphide is filtered off, washed, dried, ignited, and the residue of metal weighed ; sometimes the gold was estimated by igniting the original salt. Through the mixed filtrate and washings a current of air is passed until the slight excess of hydrogen sulphide has disappeared. Tbe liquid is then exactly neutralised with ammonia and the chlorine determined volumetri- cally by means of a solution of silver nitrate. The precipitate of silver chloride is afterwards filtered off, the filtrate made alkaline with ammonia, and the wonitine extracted by shaking with cllloro-

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996 DUNSTAN AND JOWETT :

form. By weighing the residue left on evaporation of the chloroform the amount of aconitine may be determined ; this, however, has only been done where confirmatory evidence of the composition was needed; but in all cases the melting point of the regenerated and crys tallised alkaloid has been ascertained. The a-aurichloride furnished the following data.

0.0644 of salt gave 0.0127 Au. 092509 ,, = 19.75 C.C. AgN03 (2107 C.C. = 3.55 Cl). C1 = 14.43.

C,H4,NOlZ,HAuCl4 requires Au = 19.87 ; C1 = 14-40 per cent.

M. p. of regenerated aconitine 189.3" (corr.) ; m. p. of pure aeon- itine 188-189" (corr.).

The compound is, therefore, an aurichloride of aconitine. It may also be produced by crys tallising the amorphous aurochloride from a mixture of chloroform and ether, o r from dilute alcohol. When crystallised from dilute alcohol, the a-compound generally sepa- rates in rectangular plates, and not in the rosettes of needles which are invariably obtaiued from aqueous acetone. This method of produution is, however, not to be recommended, as it some- times leads to the formatioti of the /3-aurichloride, or of a mixture of the two modifications. If aconitine a-aurichloride is dissolved in strong alcohol and the solution slowly evaporated, the p-aurichloride melting at 152" crystallises out.

Acomtine 13-aurichloride crystallises in rosett'es from the solution of the amorphous aurichloride or of the a-compound in strong alcohol. A t 152" it melts to a clear liquid without effervescence, and closely resembles the a-aurichloride in appearance, but may not be identical in form. The crystals lose no water when heated for three hours to 100-130", and do not afterwards exhibit any alteration in melting point. On analysis by the method above described, they afford results corresponding with aconitine nurichloride, and the regenerated alkaloid is found to be aconitine.

AU = 19.72.

0.2768 of salt gave 0.05522 Au, and required 23.6 C.C. AgNOs (2107 C.C. = 3-55 Cl). Au = 19.95 ; Cl = 14.34.

C,H,,NO,,HAuCl, requires Au = 19.87 ; C1 = 14.40 per cent.

M. p. of regenerated alkaloid 188.8" (corr.) ; m. p. of aconitine 188-189" (corr.).

When the compound is diesolved in acetone and crystallised by the addition of it little water, it undergoes conversion into the a-auri- chloride, the solution furnishing crystals of this modification which melt a t 135-5" (corr.). When dissolved in chloroform and crystallised by the addition of etber, the P-compound is converted into the y-corn- pound melting a t 176".

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SOME MODIFICATIONS OF ACOKITINE AURICHLORIDE. 997

Aconitina ry-aurichloride is ohtnined, as mentioned above, by add'ng ether to a solution of the /3-aurichloride i n chloroform. I t crystallises in prisms which become pasty at about 154' and melt to a clear liquid at 176" (corr.)* without effervescence, The melting point is not changed, and no loss in weight, is produced by heating the crystals for some hours at 100". That they consist of aconitine aurichloride is proved by the following analytical results.

02915 of salt pave 0.0576 Au, and required 24.75 C.C. AgNO, (2017 C.C. = 3.55 C) ; An = 19.76; C1 = 14.31.

C93H45N012,HAuC14 requires Au = 19-87 ; C1 = 14.40 per cent.

M. p. of regenerated alkaloxd 188" (corr.); m. p. of aconitine

When this substance is recrystdlised from a mixtare of acetone and water, it passes into the a-aurichloride (m. p. 135*5"), and into the P-nurichloride (m. p. 152") when recrystallised from strong alcohol.

It is remarkable that this y-anrichloride cannot apparently be pro- duced direct from the amorphous aurichloride or frcm the a-auri- chloride ; all experiments having failed which were made wit,h the view of obtaining the ry-aurichloride from these two compounds, which are probably eswntially the same, as they melt at about the same temperature. When crystallised from a mixtore of acetone and water, or from a mixture of chloroform and ether, the amorphous aurichloride yields the a-compound ; when alcohol alone is iised as the solvent, the p-componnd is obtained. R,ecrystallisation of the a-compound from a mixture of chloroform and et.her produces no change, whilst recryst allisation from alcohol converts it into the p-compound.

188-189" (COIT.).

Transformation of Isomeric Aurichlorides. (The arrow-heads indicate the direction of the change.)

* In determining the melting point of all these snbstances, tjhe compound was introduced into the bath already heated to about 100". If introduced at a higher temperature than this, the observed melting point may be lower than the number above recorded.

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998 PICRERING: A STUDY OF THE

The */-compound can, therefore, only be obtained from the z-corn- pound indirectly.

The changes of the three isomeric aurichlorides into each other are clearly shown in the t w o following diagrams.

Both the y and /3-modifications pass at their melting points into the a-modification ; the fused compound when cold melts again, in each case, near 136".

It is possible that the crystalline form of each compound may be different, but, owing t,o the small amount of material which has been at our disposal, a s well as to the great difficulty of obtaining large, well-defined crystals, i t has not been possible to make measurements.

Since very little is at present known as to the constitution of aconitine, it is not possible to offer any explanation of the existence of these three isomeric forms of the aurichloride. The demonstra- tion of their existence is, however, of practical importance in connec- tion with the identification of this alkalo'id, for i t is now possible to produce one or all three forms of the compound of constant melting point ; although slight variations in the conditions may lead to the production of some other than the expected modification. For pur- poses of identXcatinn, it generally suEces t o produce the j3-com- pound by crystallisation of the amorphous aurichloride from strong alcohol.

Research Laboratory, Pharmaceutical Society,

London.

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