Chapter 6

6. _Lait Antiphélique_.--(Candès and Co., Paris.)--Each bottle contains 140 grammes of a milky fluid, smelling strongly of camphor, and having an acid reaction. It contains alcohol, camphor, ammonic chloride, half per cent. of corrosive sublimate, albumen, and a little free hydrochloric acid.

7. _Lait de Concombres_.--The bottle contains 160 grammes of a very inelegantly made emulsion, smelling of very common rose-water, with an unpleasant twang about it, and giving a strongly alkaline reaction. It consists of soap, glycerin, and cotton seed oil, made into a semi-emulsion.

8. _Crême de Fleurs des Lys; Blanc de Ville Onctueux_.--About 30 grammes of a kind of weak ointment contained in a small pomatum pot prettily ornamented. It is simply a salve made of wax oil, and possibly lard, mixed with a large proportion of zinc oxide, and smelling of inferior otto of roses.

9. _Páte de Velonas_.-This paste consists of almond, and possibly other meal mixed with soap powder, and has a strong alkaline reaction. It is scented with orris-root.

10. _Rouge Végétal_.--The box contains 8½ grammes of raspberry colored powder, consisting chiefly of China clay and talc, tinted to the proper depth with extract of cochineal.

11. _Rouge Extra Fin Foncé_.--A small square bottle containing 11 grammes of a deep red solution, smelling of otto of roses and ammonia. It consists of a solution of carmine in ammonia, with an addition of a certain amount of alcohol.

12. _Rouge de Dorin_.--_Extract des Fleurs des Indes_.--A round pot containing a porcelain disk, covered with about 6 grammes of a bright red paste, which is a mixture of carthamin or safflower with talc. This rouge, which differs from all the others, is harmless and effectual, but must bear a high profit seeing that the ingredients cost only a few half-pence, while it sells in St. Petersburg at about 4s. 9d. a pot.

13. _Etui Mystérieux ou Boite de Maintenon_.--A prettily got-up box containing red and white paint, and two sticks of black and blue cosmetic for the eyebrows and veins, with camel's hair pencils for applying the latter. Sells in St. Petersburg at 6s. 4d.

14. _Philidore_.--_Remède Specifique pour oter les Pellicules de la tête, etc_.--The bottle contains 100 grammes of a strong alkaline solution smelling strongly of ammonia, and containing potash, ammonia, alcohol, glycerin, and eau de cologne.

15. _Colorigène Rigaud_.--A blue bottle containing 160 grammes of a clear fluid with a slight black deposit, consisting of a mixture of equal parts of a 14 per cent. solution of sodic hyposulphate, and a 4 per cent. solution of lead acetate. Of course the longer this solution is kept the more lead sulphate it deposits. It sells in St. Petersburg at 8s. per bottle. It is also stated to be much more powerful if used in conjunction with the _Pommade Miranda Rigaud_. This beats Mrs. Allen completely out of the field.--_Pharmaceutische Zeitschrift für Russland_.

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ON THE MYDRIATIC ALKALOIDS.

By ALBERT LADENBURG.

We translate the following important article, says the _Chemists' Journal_, from the _Moniteur Scientifique_ of last month. It may be explained for the sake of our student readers that the word _mydriatic_ is derived from the Greek _mudriasis_, which means paralysis of the pupil.

The synthetical researches which I have undertaken with a view to explain the constitution of atropine have shown me the necessity of studying the connection of atropine with the other alkaloids, which have an analogous physiological action. According to the early researches we could not discover any of these relationships which only become evident when we come to study the new discoveries which have been made in connection with the tropines, to which class belong both duboisine and hyoscyamine, which, although differing from atropine, are equally mydriatic in their action.

I.--ATROPINE.

Discovered by Mein in 1831 in the roots of belladonna. More thoroughly studied some time after by Geiger and Hesse, who confirmed Mein's results. Liebig next published an analysis of the alkaloid, which was afterward shown to be incorrect. He consequently modified his formula, and gave the following as the composition of atropine; C_{17}H_{23}NO_{3}. Liebig's amended analysis was afterward confirmed by Planta, who further showed that the alkaloid itself melted at 194° F., and its double gold salt at 275° F. It is worthy of remark that the first figure was considered correct until my researches proved the contrary. The physiological action of atropine, especially in relation to the eye, has been most carefully studied by several celebrated ophthalmologists, such as Graef, Donders, Bezold, and Bloebaum. Its chemical properties have also been the object of very extensive researches by Pfeiffer, Kraut, and Lassen. Pfeiffer first discovered that benzoic acid was one of the products of decomposition of atropine, and Kraut split atropine by means of baryta water into atropic acid, C_{9}H_{6}O_{2}, and tropine, C_{8}O_{15}NO. Lassen, who used hydrochloric acid, discovered the true products of the splitting up of atropine, viz., tropic acid, C_{9}H_{8}O_{3}, and tropine, C_{8}H_{15}N, and proved at the same time that atropic acid is easily formed by the action of boiling baryta water on tropic acid, while hydrochloric acid at all temperatures forms isatropic acid, an isomer of atropic acid. Kraut confirmed these results, and showed that atropic acid as well as cinnamic acid gives benzoic acid by oxidation, and hydratropic acid (the isomer of phenylpropionic acid) by reduction with sodium amalgam. These results are sufficient to show that tropic acid may have one of the following two formulae.

I II

CH_{2}OH CH_{3} / / C_{4}H_{5}CH or C_{8}H_{5}--C--OH \ \ OOHO COOH

Fittig and Wurster, who discovered atrolactic acid, C_{2}H_{10}O_{3}, an isomer of tropic acid, gives tropic acid the second formula, while Burgheimar and myself have shown that it is the true formula of atrolactic acid. Lately we have succeeded in performing the complete synthesis of atropic acid, and the artificial preparation of atropine has been greatly facilitated since I have shown that we can easily reconstruct atropine by starting from its products of decomposition, tropic acid, and tropine.

Before my researches nothing was known of the constitution of tropine. New unpublished researches into this problem have shown that it closely resembles neurine,[1] a body which I hope will speedily lead us to the complete synthesis of atropine.

[Footnote 1: As we shall probably hear a great deal about this alkaloid, it may be as well to state that, although found in the brain and liver, it may be prepared synthetically by the action of ethylene oxide, (CH_{2})_{2}O, water, H_{2}O, and trimethyiamine, N(CH_{3})_{3}. Its constitution is that of trimethyl-ethylene-hydrate-ammonic-hydrate, and has the following constitutional formula:

{ (CH_{2})_{2}OH { CH_{3} N { CH_{3} { CH_{3} { OH

or in other words, it is the hydrate of trimethyl-hydrethylene-ammonium.]

The fusing point of atropine is not 194° F., as stated by Planta, but 237° F. Crystallized from not too dilute alcohol it forms crystals which are aggregations of prisms. Toluene, alcohol, and chloroform all dissolve atropine readily. Its double gold salt is very characteristic. It is generally precipitated in the form of an oil which solidifies rapidly and may be crystallized from hot water after the addition of a little hydrochloric acid. This clouds in cooling, and after a certain time it separates in small crystals of indeterminate form which unite in warty concretions. After drying the salt forms a dull powder, melting between 275° F. and 280° F. It also melts in boiling water, and its aqueous solution exposed to the light is partially reduced, 100 grammes of water acidulated with 10 cubic centimeters of 1.190° solution of hydrochloric acid dissolves 0.137 gramme of the gold salt at 136° F. to 140° F.

I should fancy that the above particulars are sufficent to completely differentiate atropine from all the other mydriatic alkaloids.

II.--THE ATROPINE OF DATURA STRAMONIUM.

Planta has already tried to show that atropine is identical with the daturine obtained by Geiger and Hesse, founding his opinion on facts which we nowadays look upon as doubtful. This identity was generally admitted by all chemists. The pharmacologists, headed by Soubeiran, Erhardt, Schroff, and Poehl, were much more reserved in their judgment. I thought it as well, therefore, to recommence the study of daturine, the more so as I had already determined the incorrectness of the long accepted point of fusion of atropine, and that my researches on hyoscyamine convinced me that this base is an isomer of atropine, although very analogous to it. I have also shown that Merck's daturine differs from atropine, and is merely pure hyoscyamine. A short time afterward there appeared a paper by Schmidt which again asserted the identity of daturine and atropine. I therefore requested Mr. Merck, of Darmstadt, to send me all the bases which he obtained from datura. This eminent manufacturer was good enough to comply with my request, and sent me two products, one of which was marked "light daturine," the other "heavy daturine," the separation of which was effected in the following manner: The solution of crude daturine in concentrated alcohol was mixed with a little hot water; this treatment caused the deposition of the "heavy daturine," while the "light daturine" remained in the mother liquor. The "heavy daturine," of which only a small quantity is obtainable, is far from being a body of definite composition, that is to say, it is a mixture of atropine and hyoscyamine. If we convert the base into a double gold salt we obtain by a single crystallization a dull looking salt, melting at from 275° F. to 280° F., the appearance of which is very different to that of atropine. I have succeeded in splitting up "heavy daturine" by two different methods. By recrystallizing the gold salt six times from boiling water, the salt of hyoscyamine, which melts at from 316° F. to 323° F., crystallizes our first, and by the successive evaporation of the mother liquor at last obtain the pure gold salt of atropine, which melts at 275° F. to 280° F. If we only want to isolate the atropine, it is better to crystallize the free base two or three times from alcohol at 50 per cent., always taking the earliest formed crystals.

These facts prove the presence of atropine in datura; but while Planta and Schmidt assert that only this alkaloid is found in the plant, I have proved that the proportion of atropine in it is but small, while its richness in hyoscyamine is great. I think, therefore, that both Planta and Schmidt must have worked with a mixture of atropine and hyoscyamine. It is true that Schmidt had received pure atropine under the name of daturine, for I have proved most conclusively that the so-called daturine supplied by Trommsdorff, of Erfurt, is pure atropine and nothing else. It has no action whatever on polarized light.

III.--HYOSCYAMINE FROM HYOSCYAMUS.

Discovered by Geiger and Hesse in 1833. It was first obtained in the form of needles, which were much more soluble than atropine. In the pure state it forms a viscous mass with a repulsive odor. These researches were repeated by Thibout, Kletinski, Ludwig, Lading, Bucheim, Wagymar, and Renard.

Hoehn and Reichardt have recently studied hyoscyamine in a very complete manner. They have obtained the body in the form of warty concretions as soft as wax, and melting at 194° F., having a formula according to them of C_{15}H_{23}NO_{3}. They have also studied the splitting up of the alkaloid by means of baryta water, and have obtained an acid which they have named hyoscinic acid, and which melts at about 219° F., and a basic body, hyoscine, C_{6}H_{13}N. They represent the reaction as follows:

C_{15}H_{23}NO_{3} = C_{9}H_{10}O_{3} + C_{6}H_{13}N.

According to this view hyoscyamine ought to be the hyoscinate of hyoscine, or at any rate an isomer of this body. It is to be remarked that they compare hyoscinic acid not with tropic acid, of which it possesses the composition, but with atropic acid, C_{9}H_{8}O_{2}. I have worked with the hyoscyamine of both Merck and Trommsdorff, as well as with a product which I obtained from hyoscyamus seeds myself. The best way of purifying the alkaloid is by recrystallizing its gold salt several times, so as to obtain it in brilliant yellow plates, melting at 320° F. By passing a stream of hydrosulphuric acid gas through the liquor the gold is precipitated in the form of sulphide. The liquid is filtered and evaporated, precipitated by an excess of a strong solution of potassium carbonate, and the alkaloid extracted by chloroform. The solution is dried over carbonate of potassium, and part of the chloroform is distilled off. By leaving the solution to evaporate spontaneously the alkaloid is obtained in silky crystals. The crystals are then dissolved in alcohol, which, on being poured into water, parts with them in the same form.

Hyoscyamine crystallizes in the acicular form, with greater difficulty even than atropine, it also forms less compact crystals. Its fusing point is 149.6° F. I have not yet succeeded in crystallizing any of its more simple salts. The double platinum salt melts at 392° F., with decomposition. The double gold salt, which has been described above, does not melt in boiling water, and its aqueous solution is reduced neither by boiling nor by long exposure to light. By leaving the hot saturated solution to cool it does not cloud, but the double salt separates pretty rapidly in the form of plates.

One liter of water containing 10 cubic centimeters of hydrochloric acid at 1.19° dissolves 65 centigrammes of the salt at 146° F.

These characteristics allow us to differentiate atropine and hyoscyamine, the reactions of which are almost identical, as will be seen from the following table, which shows the action of weak solutions of the acids named on the hydrochlorates of the bases:

_Reagents_. _Hyoscyamine_. _Atropine_.

Picric acid. An oil solidifying Crystalline precipitate. immediately into tabular crystals.

Mercuropotassic White cheesy Same. iodide. precipitate.

Iodized potassic An immediate A brown oil crystallizing iodide. precipitate of after a time. periodate.

Mercuric chloride. Same as picric acid. Same.

Tannic acid. Slight cloud. Cloud hardly visible.

Platinum chloride. O. O.

_(To be continued.)_

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DETECTION OF SMALL QUANTITIES OF MORPHIA.

By A. JORISSEN.

The solution of morphia, free from foreign bodies, is evaporated to dryness, and the residue is heated on the water bath with a few drops of sulphuric acid. A minute crystal of ferrous sulphate is then added, bruised with a glass rod, stirred up in the liquid, heated for a minute longer, and poured into a white porcelain capsule, containing 2 to 3 c.c. strong ammonia. The morphia solution sinks to the bottom, and where the liquids touch there is formed a red color, passing into violet at the margin, while the ammoniacal stratum takes a pure blue. The reaction is very distinct to 0.0006 grm. Codeine does not give this reaction. If sulphuric acid at 190° to 200° is allowed to act upon morphia, there is ultimately formed an opaque black green mass. If this is poured dropwise into much water, the mixture turns bluish, and if it is then shaken up with ether or chloroform, the form takes a purple and the latter a very permanent blue. Codeine gives the same reaction, but no other of the alkaloids. This reaction can be obtained very distinctly with 0.0004 grm. of morphia.

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ON THE ESTIMATION OF MANGANESE BY TITRATION.

[Footnote: _From Jernkontorets Annaler_, vol. xxxvi.--_Iron_.]

By C. G. SARNSTROM.

If we dissolve black oxide of manganese, permanganate of potash, or any other compound of manganese of a higher degree of oxidation than the protoxide in hydrochloric acid, we obtain, as is well known, a dark colored solution of perchloride of manganese, which, when heated to boiling loses color pretty rapidly, chlorine being given off, until finally only protochloride remains. This decomposition also proceeds at the common temperature, though much more slowly, and we may therefore say that manganese when dissolved in hydrochloric acid always tends to descend to its lowest, and, considered as a base, strongest degree of oxidation, which is not raised to a higher degree even by chameleon solution. In slightly acid, neutral, or alkaline solutions on the other hand, protoxide of manganese absorbs oxygen with great avidity and forms with it different compounds, according to the means of oxidation employed. Thus, for example, manganese is slowly deposited from an ammoniacal solution, when it is permitted to take up oxygen from the air, as hydrated sesquioxide, and from neutral or alkaline solutions, as hydrated peroxide on the addition of chlorine, bromine, or chameleon solution. For if to an acid solution of protochloride of manganese we add a solution of bicarbonate of soda, as long as carbonic acid escapes or till the free acid is saturated and the protochloride of manganese converted into carbonate of protoxide of manganese, which forms with bicarbonate of soda a soluble double salt, resembling the carbonate of lime and magnesia, we obtain a solution which is, indeed, acid from free carbonic acid, but has a slight alkaline reaction with litmus paper, and with the greatest ease deprives chameleon solution of its color, the permanganic acid being reduced and the protoxide of manganese being oxidized to peroxide, which is precipitated as hydrate. This reaction proceeds according to the formula,

3MnCO_{3} + 2KMnO_{4} + H_{2}O = 2KHCO_{3} + 5MnO_{2} + CO_{2}

and it may be employed for estimating the content of manganese by titration. As follows from the formula two equivalents of permanganate of potash are required for the titration of three equivalents of protoxide of manganese, which has also been established by direct experiments, as well as that the escape of carbonic acid indicated by the formula actually takes place. The precipitate of manganese is dissolved either in water to which 0.5 per cent. of hydrochloric acid has been added, or in boiling nitric acid. When manganese occurs along with iron, which in general is the case, we must take care that the iron in the solution is in the state of peroxide, which is precipitated on the addition of the bicarbonate of soda, and is allowed to remain as a precipitate, because it does not affect the titration injuriously. The removal of this precipitate by filtering would be more loss than gain, partly because there would be a risk of losing manganese in this way, partly because the precipitate of manganese, which occurs immediately on the addition of the chameleon solution, proceeds both more rapidly and with greater completeness in the presence of the iron precipitate than otherwise. This appears to be caused by the iron precipitate as it were inclosing, and mechanically drawing down the light manganese precipitate, provided a weak chemical union between the two precipitates does not even take place, depending on the tendency of peroxide of manganese to behave toward bases, as, for instance, hydrate of lime as an acid. Hence it thus follows that it ought to be arranged that a sufficient quantity of iron[1] (at least the same quantity as of manganese) be present in the liquid at titration, also that time be given for the precipitate to fall, so that the color of the solution may be observed between every addition of chameleon solution.

[Footnote 1: For this in case of need a solution of perchloride of iron free of manganese may be employed.]

When the content of manganese is large, it is sometimes rather long before the solution is ready for titration. The reason of this appears to be that a part of the manganese is first precipitated as hydrated sesquioxide, which is afterward oxidized to hydrated peroxide, for the upper portion of the liquid may sometimes be colored by chameleon, while the lower portion, which is in closer contact with the precipitate, is less colored or absolutely colorless. From this we also see how advisable it is to stir the liquid frequently during titration. Toward the close of it, it is also advantageous, when the contents of manganese are large, to warm the solution to about 50° C., because the removal of color is thereby hastened. When the fluid, which is well stirred after each addition of chameleon, has obtained from it a perceptible color, which does not disappear after several stirrings, the whole of the manganese is precipitated and the color of the solution remains almost unchanged after the lapse of at least twelve hours.

When the content of manganese is large the solution may be divided into two equal portions, one of which is first to be roughly titrated to ascertain its content approximately, after which the whole is to be mixed together and the titration completed, which can thus be performed with greater speed and certainty. If too much chameleon has been added, one may titrate back with an accurately estimated solution of manganese, which is prepared most easily by evaporating fifteen cubic centimeters chameleon solution down to two or three cubic centimeters, boiling with two to three cubic centimeters hydrochloric acid so long as the smell of chlorine is observed, and then diluting the solution to ten cubic centimeters, when one cubic centimeter of it corresponds to the same measure of chameleon.

With respect to the delay which must take place during the titration in order to give the precipitate time to fall, it is advantageous, in order to save time, to work with several samples; but it is, in such a case, desirable to have a separate burette for each sample, in order to avoid noting every addition of the chameleon solution and afterward adding them up. If burettes are wanting, and one must be used for several samples, a Mohr's burette with glass cock is the most convenient to use. For the titration of iron with chameleon solution, the latter is commonly used of such a strength that 0.01 gramme of iron corresponds to about one cubic centimeter of chameleon solution, which is obtained by dissolving 5.75 grammes permanganate of potash in 1,000 cubic centimeters water. The titration is determined by means of iron, a salt of iron or oxalic acid. A drop of such a solution, corresponding to about one-twentieth cubic centimeter, or 0.0001 gramme Mn, is sufficient to give a perceptible reddish color to 200 cubic centimeters of water.

As what takes place in the titration of iron with chameleon is indicated by the following formula,

10FeO + 2KMnO_{4} = 5Fe_{2}O_{3} + K_{2}O + 2MnO_{2},

it appears, on making a comparison with the formula given above, that ten equivalents of iron correspond to three equivalents of manganese, and that there is thus required for three equivalents manganese as much chameleon solution as for ten equivalents iron. When we know the titration of the chameleon solution for iron, that for manganese is obtained by multiplying the former by (3 x 55)/(10 x 56) =0.295. If, for instance, one cubic centimeter chameleon solution corresponds to 0.01 gramme iron, the figure for manganese is 0.01 x 0.295 = 0.00295 gramme per cubic centimeter.