290 DUNSTAN AND CARR: CONVF,RSION OF ACONITINE

XXX.-Contributio to our Knowledge of the Aconite Alkaloids. Par t X. Furthe/* O ~ S P I-vatims on. the Conversion if Aconitine into Isaconi t ine aad on the Byclrolysis of Aconitine.

By WYNDHAM R. DUKSTBN, M.A., F.R.S., and FRATCIS H. CARR, Assistant Demonstrator in the Research Laboratory of the Phar- maceutical Society.

IN a previous communication (Part VI, Trans., 1893, 991) we have shown that when certain aconitine salts are heated on the water-bath in aqueous solution, they are very gradually changed into the corre- sponding salts of isaconitine. Further experiments have proved that this conversion may be very rapidly and completely effected by heat- ino an aqueons solution of an aconitine salt in a closed tube at 120-130" for about three hours. The conversion of the aconitine is often so complete that the resulting solution produces no tingling sensation on the tongue, but now has the extremely bitter taste of isaconitine salts. The aconitine salts which answer best for this pur- pose are the sulphate and the hydrochloride in the form of from 3 to 5 per cent. solutions. Little or no benzoic acid is formed, and the solution is very little coloured. By this means me have been able to prodnce larger quantities of isaconi tine than has hitherto been possible, and to further examine the properties and constitution of this alkaloid. The observat.ions recorded in o u r preceding contribution (p. 176), which point to the conclusion that aconitine contains an acetyl group,

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INTO ISACONITINE AND ON HYDROLYSIS OF ACONITINE. 291

led us to ascertain whether acetic acid is separated in the conversion of aconitine into “ isaconitine.” We find that is the case, and, by dis- tilling the solution of the converted sulphate left in the tube, we have obtained an amount of acetic acid which corresponds with the loss of one molecular proportion of acetic acid by one molecule of aconitine. The determination of the amount of acetic acid liberated can also be ascertained by titrating the acidity of the solution of the snlphate, which was neutral before it was heated. In this way, the amount of acetic acid formed is found to be almost exactly 9.27 per cent. which is that corresponding with the equation

C S H d O , , + H2O = CzH*O, + C31H43NO11. This proves that aconitine is acety Zbenzoylaconine, isaconitine being

benzoylaconine, as we have previously shown by a study O€ its hydro- lysis (Part IV). When isaconitine was first obtained from the roots of A. Napellus, the analytical data furnished by its combustion agreed well with those afforded by aconitine (see Part IV, Trans., 1893, 63,

The numbers were, for carbon 61-11 and 61.03 per cent., and for hydrogen 6.96 and ‘7.15 per cent., whilst the percentages calculated from the formula of acouitine, C,HJYO12, are for carbon 61.25 per cent., for hydrogen 6-95 per cent. I n corcluding that aconitine and isaconitine are isomeric, we relied, in addition to the agreement of their analytical data, on the fact that, when hydrolysed, isasonitine furnished aconine and benzoic acid in the same proportions in which, according to the observations of Wright and Luff,they are formed in the hydrolysis of aconitine ; and these observers found no other acid thaa benzoic acid among the hydrolytic products of this alkalo’id. By synthetical experiments, too, Wright had apparently justified his con- clusion that aconitine is benzoylaconine, since he obtained what he believed to be benzoylaconitine by acting on aconine with bemoic anhydride, and in the course of our own enquiry we obtained in a preliminary experiment, where ethylic benzoate was heated with aconine, a small quantity of what seemed to be anhydro-aconitine.

We were now led to repeat Wright’s experiments on the hydrolysis of aconitine, and we find that, besides benzoic acid, a molecular pro- portion of acetic acid is invariably produced, whether the hydro lysis be effected by alkaii or acid, or by heating with water alone.

The hydrolysis of aconitine may thus be brought about in two stages. I n the first, which may‘ be effected by heating an aconitine salt with water, acetic acid and what must in future be known as benzoylaconine (isaconitine) are formed,

443).

C J L N O n + &O = CzH*Oz + C,,HaNO,, Acetylbenzoylaconine Acetic Benzoylaconine.

(aconitine). acid. VOL. LXV. X

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292 CONVERSION OF ACONITINE INTO ISACONITINE.

In the second stage, which may be brought about by heating with aqueous alkalis or acids, the benzoylaconine is resolved into aconine and benzoic acid,

C , , J L ~ O l I + H,O = C7H602 + C24H39NOlo Benzoy laconine. Aconine.

The demonstration of the correctness of the formula C,,H43NOl, for benzoylaconine, instead of C,H4,NOI2, which represents it as an isomeride of aconitine, rests on the observation that acetic acid is simultaneously formed when aconitine undergoes conversion. The results of the combustion of the alkaloid agree almost as well with the one formula as with the other, the differences between the results calculated from the two formulm being extremely small. Calculated for C,,H43011, C = 61.48, H = 7-10; for C,HJ3Ol2, C = 61.25, H = 6.96.

The careful determination of the gold in the remarkable aurichloro- derivative of benzoylaconine has, however, enabled us to obtain con- firmation of the new formula. The percentage of gold found (by ignition) is 22.18; whilst the percentage required by the new formula is 22.50, and by the old only 21.46.

Aconine must in future be represented by the formula CZ1H39N010, and not by the formula originally assigned to i t by Wright, C26H39NOll or c26&NOll*

The relationships of these three a1 kaloids from Aconitzcm Napellus

CzsHalNO Aco nine. C,,Hl0 (C6H5*C 0) NO C,,JI, (CH,*CO) ( C6Ha*CO) NOll, Acetylbenzoylaconine (aconitine) . During the past month we have been engaged in an attempt to

obtain these two last-named alkalo'ids from aconine by introducing successively a benzoyl and an acetyl group. The results of these preliminary experiments lead us to hope that ultimately we shall be successful in effecting these syntheses.

We have also made a series of experiments, which show that the estimation of the acetic acid liberated from a solution of aconitine snlphate of known strength, constitutes an accurate method for the quantitative determination of this alkaloid, and we find that it may be applied to the estimation of aconitine in the total alkaloids of Aconitum Napellus, since aconitine is the only alkaloid contained i n this plant which furnishes acetic: acid under these conditions. A detailed account of this method will be given in a future communica- tion.

are therefore represented by the formulze

Benzoy laconine.

Research Laboratory, Pharmaceutical Society, London.

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