No. 1151.

SEPTEMBER 20, 1845.

LECTURESON

ORGANIC CHEMISTRY:DELIVERED DURING THE WINTER SESSION, 1844-45, IN THE

University of Giessen.

BY JUSTUS LIEBIG, M.D., PH. D., F.R.S., M.R.I.A.Professor of Chemistry in the University of Giessen.

- GENTLEMEN,—Notwithstanding the great length of time whichve have occupied with the consideration of uric acid, its meta-morphoses, and the properties and relations of those bodies de-rived from it, I cannot lay it aside and proceed to other subjectsuntil I have communicated to you the results of an investigationnpon alloxanic acid and the products of its decomposition, whichhas been instituted and just now brought to a conclusion in my

I’laboratory, by Mr. Adolphus Schlieper.In the first place, it being highly desirable to have a large i

.quantity of alloxan for the production of the alloxanic acid, on iwhich to operate, a better method than any hitherto pursued formaking alloxan was to be devised. M. Schlieper, therefore, afterhaving repeatedly gone through all the old methods, which I have Jfully explained to you, such as oxydizing uric acid by means of Initric acid, &c., with variable and uncertain results, directed his I’researches to accomplish this object, and he found, that by making.use of a mixture of hydrochloric acid, and chlorate of potass as Ithe oxydizing agent, he was able to obtain with the greatest cer- Itainty the largest quantity of alloxan. This method, therefore, Imust always in future be preferred.A NEW AND ADVANTAGEOUS 31ETUOD OF OBTAINING ALLOXAN. IAbout four ounces of uric acid are mixed and stirred together iwith eight ounces of hydrochloric acid into a magma, and one iounce of finely-powdered chlorate of potash added very gradually. iThe uric acid becomes decomposed with the greatest readiness, Iand is converted directly into alloxan and urea, without even abubble of carbonic acid being disengaged.The success, however, of this process depends wholly upon the

very slow addition of the chlorate of potass ; not the least traceof chlorine need be disengaged during the operation. If, how-ever, you attempt to hasten the process, by adding the chlo-rate too fast, and allow the temperature to rise too high, the de.sired result will not be obtained.When the greater part of the uric acid has become dissolved,

- cold water is to be added to the heated mass, to about double itsamount, and the part of the uric acid which remains undissolvedallowed to subside.The solution now will contain alloxan, urea, and chloride of

potassium, which are not easily separated directly, owing to theirgreat solubility. ·

In order to effect their separation, the alloxan must be trans-formed into alloxantine, and this is accomplished thus :-Aboutfive-sixths of the whole fluid is to be perfectly saturated with sul-phuretted hydrogen, by which alloxantine is formed, together witha small quantity of dialuric acid; the latter is reoxydized intoalloxantine on the addition of the remaining sixth part of theoriginal fluid; the manner of this change is well known to you.The alloxantine thus obtained is freed from sulphur by crystalli-zation. It may then be converted into alloxan, a change besteffected by means of nitric acid in the following manner:-

Half the amount of the alloxantine which is to undergo thisprocess of conversion into alloxan, is heated to simmering withdouble its amount of water, and nitric acid added drop by dropuntil the solution begins to effervesce. The vessel containing itis then to be placed in a water-bath of boiling water, and afterthe alloxantine is completely dissolved, the remaining half is to beadded gradually as long as any action is perceptible. If theaction ceases too soon, a few drops of nitric acid are sufficientto restore it. The process must be carried on so far that atthe end a small quantity of alloxantine is left. The boiling fluidis filtered, and after the alloxantine in solution is destroyed bythe addition of a few drops of nitric acid, it is allowed to cool.When the solution has cooled, a quantity of alloxan is-depositedin a crystalline form.As another product of this process, a considerable quantity of

urea may be obtained. The fluid from which the alloxantine hasbeen separated by filtration is freed from excess of hydrochloricacid by means of oxide of lead; it is then filtered, and by addingexcess of nitric acid, the urea is precipitated as a nitrate.

ALLOXANIC ACID.

During the investigation of uric acid, made by myself, in con-nexion with Professor Wohler, our analysis of the alloxanate ofsilver led us, as I told you in a former lecture, to the formula-

C, N H 0,for the anhydrous alloxanic acid. The results of a more accurateexamination of the alloxanates have, however, shown that allox-anic acid must be considered as a bibasic acid, and that its equiva-lent must be expressed by the formula-

C, N, H, OsThe hydrate of the acid is therefore-

Cs N2 H, 0, + 2 H 0.In the alloxanates, this amount of water is entirely, or partly,

replaced by the bases.ALLOXANATES.

Neutral alloxanate of potass is obtained by mixing togetherequal volumes of concentrated alloxan and solution of potass,and adding alcohol until a lasting dimness of the liquid ensues.After two or three hours the salt is deposited in fine hard crys-tals, which, by repeated crystallization from solution in water,can be obtained perfectly colourless. This salt is insoluble inalcobopand ether, and has a neutral reaction. When dried atthe common temperature, it is composed according to the for-mula-

.

Cg NjJ HjJ Og + 2 K 0 + 6 aq.At a temperature of 200°, 5 eq. of water escape.Acid al!oxanate of potass is obtained in the same manner as

the neutral salt; an excess of alloxan (three or four parts ofalloxan to one part potass) is, however, used. It is a granular,crystallized, white powder, rather difficult of solution in water, butmore easily soluble in alcohol than the neutral salt. Its formulai-

It is immediately converted into the neutral salt on the additionof potass. The attempts to obtain pure soda combinations wereunsuccessful.

Neutral alloxanate of ammonia is exceedingly unstable. It isobtained by adding ammonia to a solution of the acid salt, andprecipitating it with alcohol. There subsides a concentratedsolution, which, after standing some time, deposits a crystallinemass, consisting mostly of neutral alloxanate of ammonia, butalso containing some of the acid salt.Acid alloxanate of ammonia is easily obtained by saturating

free alloxanic acid with ammonia. This compound cannot beobtained by acting upon alloxan with ammonia directly, as is thecase with the potass salts, for under such circumstances, as youmay remember, mykomelinate of ammonia is formed. Theformula of acid alloxanate of ammonia is-

C8 N2 H2 O8 + N H4 OC8 N2 H2 O8 + N H4 Or- N2 IT O8 + { N H40Cs N2 H2 Os + HOSubject to dry distillation, this salt yields carbonic acid,

prussic acid, cyanic acid, ammonia, urea, and oxamide. Stillmore characteristic of the bibasic nature of alloxanic acid thanthe salts just described, are the combinations of this acid withthe earths. It forms a neutral and an acid salt with barytes aswell as lime.

I have already described to you the mode of procuring neutralalloxanate of barytes, and its composition. A mixture of chlorideof barium with potass ley is used with advantage, if it is wishedto obtain larger quantities of this salt for making the acid itself.To a solution of chloride of barium, alloxan is added; it is thenmixed with potash ley as long as a lasting precipitate is formed ;after a few moments the whole liquid solidifies to a heavy granularcrystalline mass. If less sulphuric acid be added to the neutralsalt than is necessary for its entire decomposition, acid alloxanateof barytes is produced. This salt may also be obtained by doubledecomposition of the acid alloxanate of ammonia with chloride ofbarium. It crystallizes in small white tubercles, is much moresoluble in water than the neutral salt, and is likewise soluble inalcohol. Its comnosition is-

The neutral alloxanate of lime is obtained in the same manneras the alloxanate of barytes, to which salt it is likewise similarin its properties. It is, however, rather more soluble in water,and is insoluble in alcohol. Its composition is

, Cs Na Hs Os + 2 Ca 0 + 10 aq.i Acid alloxanate of lime.-The same that has been said of

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the corresponding barytic compound holds good for this salt.When dried at the common temperature its formula is

The 5 eq. of water escape at a temperature of 100°.The alloxanate of magnesia-

C, N2 H2 0, + 2 Mg 0 + 10 aq.is obtained by mixing together concentrated solutions of chlorideof magnesium and alloxanate of potass.

Neutral alloxanate of zinc is unknown. The acid zinc salt isprocured by treating carbonate of zinc with an excess of allox-anic acid. The clear solution dries up to a gummy mass, whichgradually becomes crystalline. The formula of this salt is

Schlieper has likewise examined a basic zinc salt, which he Ifound to consist of if

There have been no less than four combinations of alloxanic acidwith oxide of lead examined, among which is a very remarkableacid salt. The following are the formulae of the salts dried at100°:—

The acid salt-the existence of which furnishes perhaps astronger argument than anything for the bibasic nature of allox-

anic acid, as acid salts of lead are very rare-is obtained by ,,

treating newly precipitated carbonate of lead with alloxanic acid.The filtered liquid dries up to a gummy mass, which graduallychanges to thick tuberculated crystals, consisting of fine silkyneedles, and containing 2 eq. of water. This salt is soluble inwater. Alcohol decomposes it; the products are free alloxanicacid and it basic alloxanate qf lead, which is precipitated as a curdymass, retaining 8 eq. of water, when dried in vacuo. This saltis remarkable for the change it undergoes by the action of water.It is converted directly into the acid and neutral alloxanates.The neutral salt is left deposited as a loose white powder.The fourth salt of which I have spoken is formed on mixing asolution of alloxan with basic acetate of lead. The white preci-pitate contains, when dried in vacuo, 1 eq. of water, which itloses at 1000.The analysis of an alloxanate of ethyl would have been of

great interest for the determination of the constitution of thealloxanic acid : the trials which were instituted for that purposehave, however, led only to negative results.

PRODUCTS OF THE DECOMPOSITION OF ALLOXANIC ACID.

In order to perfect the sketch I have given to you, in thelast lectures, of the metamorphoses of uric acid, it is necessarythat I should make you acquainted with some changes peculiarto alloxanic acid. You will remember the change that boilingmakes on a solution of alloxan; carbonic acid being developed, andalloxantin and parabanic acid formed. A solution of alloxanicacid cannot be evaporated without also undergoing a change;disengagement of carbonic acid takes place, and the alloxanicacid is decomposed into an acid and an indifferent body, ofwhich the former has been termed leucoturic acid, and the latter,difluan.

LEUCOTURIC ACID.

For the production of this acid, a solution of alloxanic acid isheated in a water-bath as long as the clear gummy mass disen-gages carbonic acid. On the addition of water the new acid is

separated, in the form of a snow-white granular crystalline pow-der, insoluble in cold, but soluble in boiling water.The solution expels carbonic acid from carbonates. Acids-

even nitric acid-do not work any change on leucoturic acid ; thealkalies take it up unchanged, but it becomes, after some time,transformed into oxalic acid and ammonia.The ammonia salt of leucoturic acid crystallizes, on evaporation,

in fine large needles; a solution of this salt gives a whiteprecipitate with nitrate of silver, which soon becomes of a coffee-brown colour, from metallic silver separating. The solution

then contains oxalic acid. The analysis of leucoturic acidled to the following formula :-

C6 N2 H8 06, By determining the relative proportion of the volumes of

carbonic acid and nitrogen, which the ammonia salt yields onburning, the following formula was obtained for this salt:-

C6 Ns H2 06 + N H4 0;according to which, the hydrate of leucoturic acid is,

C6 N2 H, 0, + H 0.This formula easily explains the transformation of leucoturic

acid into oxalic acid and ammonia.

DIFLUAN.

This body is contained in the fluid from which leucoturic acidhas been separated by filtration. On adding absolute alcohol itbecomes precipitated in white flocks, which, being kept from thecontact of air, are washed with alcohol or ether, and dried oversulphuric acid. A loose powder is obtained, which becomes fluiddirectly when exposed to air, and thence its name. Difluan iseasily dissolved in water. The solution may be boiled, withoutany change taking place; it has a feeble acid reaction, and abitter taste. Difluan combines with the oxides of lead and silver;nevertheless, it does not possess the character of an acid. It canbe separated in its primitive state from these combinations bymeans of sulphuretted hydrogen ; alkalies decompose it readilywhen cold; ammonia and oxalic acid are formed. Difluan islikewise decomposed by nitric acid.

’

The elementary analysis of difluan gave the following formulafor the composition of this body:-

C6 N2 H2 0,which has, however, not, as yet, been confirmed by the analysisof its compounds. The formulae of leucoturic acid and difluanafford a general view of the manner in which- these bodies areformed from alloxanic acid.Two equivalents of alloxanic acid contain the elements of one"

equivalent of leucoturic acid, one equivalent of difluan, four equiva-lents of carbonic acid, and one equivalent of water ; thus

I must, however, tell you that this table is only hypothetical; fordifluan is formed, on the decomposition of alloxanic acid, in an un-equal and larger proportion to the leucoturic acid ; there is like-wise a third product formed, which has, however, at present, beenstudied very imperfectly.On evaporation of the alcoholic fluid which has been filtered

off from the difluan, crystalline crusts are deposited, which arenot difluan. This substance has only been obtained in very smallquantities, so that only a very imperfect analysis could be made ofit, but which led to the formula,

C, N, H5 0, (?)Should this formula be correct, the following very remarkablerelation exists between these three bodies :-

Leucoturic acid ......... C6 N2 Hg 06Difluan .................. C6 N2 H4 O5Third body............... 06 Ns Hs 04

A series, in which, in proportion as the number of hydrogenequivalents decreases, the number of oxygen equivalents in-creases.

Schlieper obtained several times, when oxydizing uric acidwith nitric acid, for the purpose of procuring alloxan, beside thelatter substance, and alloxantin, parabanic and oxalic acids,another body, crystalline, and of a yellow colour, which proved to-be the acid-ammonia-salt of anew acid. As this body has, however,not as yet been prepared intentionally, I shall give a short descrip-tion of the new acid, which has been denominated hydurilic acid.On treating the hydurilate of ammonia with animal charcoal, it iseasily obtained white; it is not decomposed by acids. To

separate the acid, the ammonia salt must be heated to simmer-ing with potash ley, until all ammonia is expelled; hydrochloric-acid is then added to the hot solution of the potass salt. The

hydurilic acid is thus precipitated as a white crystalline powder,consisting of fine needles, nearly insoluble in cold, but moresoluble in hot water, and insoluble in alcohol. It is easily takenup by alkalies. On the application of heat, it expels the carbonicacid from carbonates.

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The analysis of hydurilic acid led to the following formula-CI2 Ns Hs Om = ()IS Ns Hs 09 + 2 H 0

The analysis of different salts have led to the same result.Hydurilate of silver, which is obtained as a white precipitate on

adding nitrate of silver to a solution of neutral hydurilate ofammonia, is composed according to the formula-

C,2-Ns Hs 09 + 2 ag. 0Hydurilate of soda is deposited in form of a crystalline powder,

if carbonate of soda is added to a solution of hydurilate acid,.as long as evolution of carbonic acid takes place. It is insolublein alcohol, and has the following formula-

C12 Ns Hs 09 z- 2 Na 0 + 5 aq.Neutral hydurilate of ammonia is obtained by dissolving the

acid salt in ammonia. It crystallizes in long, flatly compressedneedles, of silvery lustre, which are easily soluble in water. Onaddition of acids, the acid salt is re-precipitated. This salt is-composed according to the formula-

CIs Ns H, 0, + 2 N H, 0 + H 0Hydurilic acid can be regarded as a combination of the already

mentioned hypothetical urilic acid with water. One equivalent’of hydurilic acid contains the elements of three equivalents ofurilic acid and eighteen of water. To obtain, however, a clearinsight into the constitution and mode of formation of this body,new investigations must be made with it, and particularly as toits metamorphoses. At present, only one has been studied, andthat imperfectly. By the action of nitric acid, a compoundwas obtained, beside other products, which was composed ac-cording to the empirical formula-

Cs Ns Has 014and was termed nitrohydurilic acid.Of two other acids which Schlieper obtained as products of

the decomposition of alloxantin, I will only mention the names andcomposition, as the mode of producing them is not yet sufficientlydeveloped. The one acid is the allitunc acid, which is formedby the action of hydrochloric acid on lloxantin, and is composedaccording to the empiric formula-

C6 N Hs 04The other acid is the dilituric acid, which was obtained on the

mother liquid of the other acid, being first treated with sul-

phuretted hydrogen, and then with nitric acid. The effortsmade to obtain this remarkable acid, the salts of which have acharacteristic yellow colour, in a state of purity, have as yet notsucceeded. The analysis of some few of the salts gave thefollowing formulea-

The last-mentioned metamorphoses certainly merit furtherexamination, but these investigations are attended with no smalldifficulties.

Gentlemen, I now at last bring to a close the subject of uricacid and its products. In my next lecture, I shall explain toyou the Benzoyl class, the development of which has been, as youwill see, of great importance for the progress of organic chemistry.

BOTH KIDNEYS ON THE SAME SIDE OF THE SPINAL COLUMN.

Dr. J. REID narrates the following rare anatomical ano-maly :-

" When in charge of the dissecting-rooms in Old Surgeon’sHall, Edinburgh, I found that in one of the bodies which wasbeing dissected by the students, the kidney was wanting on theleft, and that there were two kidneys on the other side. Theone was placed below the other, and the lower end of the upperone, and the upper end of the under one, were fused together.The renal artery supplying the upper kidney was given off bythe aorta, near its usual origin; the one supplying the lowerkidney arose from the aorta, near its division into the two primi-tive iliaes. The ureter from the lower kidney passed across themesial line, after entering the pelvis, so that these two tubesentered the bladder in the usual manner. The preparation isnow in my collection. A case where the kidneys presented ex-actly the same appearance is described and figured by Dr. JohnHunter, in the third volume of the Medical Transactions ofthe College of Physicians in London,’ vol. iii. p. 250,1785."-Cormack’s Monthly Journal.

CONTRIBUTIONS TO CLINICAL MEDICINE.BY JOHN TAYLOR, M.D.,

PROFESSOR OF CLINICAL MEDICINE IN UNIVERSITY COLLEGE, ANDPHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL, LONDON.

PERICARDITIS.

CASE 12.-A young man, two years ago, had acute rheumatism. withcardiac disease; after exposure to wet, was again seized withrheumatic ferer; on the fifth day, pericarditisfollowed, but dis-appeared within three days; on the fifteenth day, pneumonia ap-peared, followed in two days by -a return of pericarditis and ofrheumatism, all qf which were finally cured.-Remarks: Cureof the first attack of pericarditis without adhesion ; pneunzonianot at first distinguishable from pleurodynia; constitutional cha-racter qf rheumatism comparison of the first period of thedisease to that of the exanthemata ; pericarditis and pneumoniaindependent of metastasis.-Treatment: Occurrence of pneu-monia, and relapse of pericarditis and of 1’heumatism during theprogress ofptyalism.

WILLIAM H——, aged eighteen, admitted on Thursday, Sept.19th, 1844, of slight conformation, a bricklayer; has always badsufficient food and clothing; parents not subject to rheumatism;was in the hospital two years ago, under Dr. Williams, for anattack of rheumatism. The following signs were then observed:" A murmur with the first sound of the heart, heard distinctly atthe apex, but not in the carotids ; the impulse is greater thannatural, and there is dulness over an area of four inches."On Tuesday, Sept. 10th, he was exposed to wet whilst at work;

during the remainder of the week he had fits of shivering five eor six times a day, followed by increased heat of the body. OnMonday, the 16th, he felt pain in beth ankles and knees, whichwere also tender, but not red nor swollen.On admission, enlargement, with evident fluctuation of the

right knee, but no redness ; left knee less affected ; both anklesare very painful, but not red nor much swollen. When lyingperfectly still, without the least movement, he still complains ofpain in the extremities ; no pain or tenderness in the cardiacregion ; a systolic bellows-murmur at the apex of the heart.The respiration is audible all over the chest, and the lungsyield a clear sound on percussion; pulse 107. Ordered four

grains of calomel, with eight grains of Dover’s powder at bed-time, and the house physic next morning.

Sept. 20th, morning.-Pain and tenderness in the region of theheart; respiration oppressed; countenance anxious ; a morbidsound, apparently a friction-sound, is heard on a level with thenipple. Sixteen leeches were applied over the heart.-Noon.Pain and tenderness over the heart much less. A feeble morbidsound is heard between the nipple and the sternum, but it isdoubtful whether it is a friction-sound or a bellows-murmur. Totake four grains of calomel three times a day, and eight grainsof Dover’s powder night and morning.23rd.--The rheumatism is less ; no sign of effusion into the

right knee-joint; there is swelling and fluctuation, but no rednessof the left knee ; no morbid sound in the cardiac region, exceptthe bellows-murmur at the apex; the impulse is stronger, andmore heaving in character than natural. Dulness on percussionis complete up to the fourth costal cartilage, and incomplete upto the third; the gums are tender. To take the calomel twicea day only.25th.-No pain in the limbs; there is effusion still in the left

knee joint. Pulse 60, and tardy.27th.-No return of pain; no effusion into the knee-joint;

sleeps well. Omit the calomel and Dover’s powder. To havethree grains of iodide of potassium, in peppermint-water, threetimes a day, and to have the middle diet.30th.-Has been much purged for several days ; complains of

pain just below the right axilta ; the respiratory murmur, and theresonance, on percussion, are natural. To apply a sinapism tothe painful part, and to take ten grains of Dover’s powder atbed-time.

’ Oct. 2nd.—The pain in the joints returned in the course oflast night, and also the pain below the right axilla, which hadbeen relieved by the sinapism; below and to the inner side ofthe right nipple there is a double friction-sound ; it is audible,but less so at the left border of the sternum; it continues when therespiration is suspended, and is not more distinct when the patientis erect than when he is recumbent ; expectoration scanty,mucous, and tinged with blood; both sides of the chest are toodull on percussion, but the right side is the duller ; the respira-tion behind is bronchial, and accompanied with slight crepitation;the vocal vibrations are more strongly felt on the right than onthe left side ; has been purged seven or eight times in the night.