9 Dr. Gregory on the Decomposition of Uric Acid. LX XXVI. Fzlrther Contributions to the Chemical History of the Products of the Decomposition of Uric Acid. By WIL- LIAM GREGORY M.D. F.R.S.E. I N 1840 I described at the Glasgow Meeting of the British Association an improved and very productive method of preparing alloxan murexide &c. ; and I showed from the occurrence of urea among the products of the action of hy- permanganate of potash on uric acid that Liebig and Wohler’s view according to which urea pre-exists in uric acid must be admitted in the present state of our knowledge as well- Dr. Gregory on the 10 founded ; thus giving additional probability to the supposition of the existence of the acid supposed by them to be present in uric acid combined with urea and called hypothetically urilic acid= C N 04.Since that period I have been frequently occupied with the subject of uric acid. In 1841 Professor Liebig having en- trusted to me the treatment of upwards of 2 lbs. of urate of ammonia I extracted the uric acid from this and converted nearly the whole of it into alloxan of which I obtained i$ Ib. in large and absolutely pure crystals. 'This not only enabled me to study the preparation of several of the other products but led me to economise as much as possible the very abun- dant mother-liquid of the alloxan which contained a large quantity of that substance but so much mixed with nitrate of ammonia and free nitric acid that the alloxan could not be purified by crystallization even if the liquid could have been concentrated by heat without decomposition.I shall now state the results of my experiments as far as these are to- lerably ascertained. There is still much to be done and se- veral investigations are in an imperfect state in my laboratory. As it may be some time however before I may be able to re- turn to them I think it right in the mean time to describe the results hitherto obtained. 1. Alloxanti7ae. This compound is best obtained from the mother-liquid of alloxan as prepared according to my process*. The acid solution is diluted with two or three parts of water and a cur- rent of snlphuretted hydrogen gas is passed through as long as it produces any effect. Sulphur is first deposited and sub- sequently a large quantity of alloxantine.'rhe mixed pre- cipitate is drained washed with a little cold water and then boiled with water acidulated with hydrochloric acid until all the alloxantine is dissolved which requires from a quarter to half an hour even when enough water is present for the final solution of the whole. The solution is filtered while hot which takes place very rapidly and deposits on coding an abundant crop of crystals of alloxantine. The quantity rexhes its maximum in twenty-four hours and the amount retained in the acidulous mother-liquor is but small. I t may however be obtained by concentration. By this method the mother- liquid of the alloxan above mentioned although some part of it was used for other experiments yielded upwards of 8 oz.of pure alloxantine. * See Turner's Chemistry 7th edition. 11 Products of the Decomposition of Uric Acid. 2. Diabrate of Ammonia. This salt may be also obtained in abundance from the mother-liquid of alloxan as well as from that of alloxantine. Animonia is to be cautiously added in the cold so as to leave a slight excess of acid and hydrosulphuret of ammonia is to be then added in excess so as to redissolve any sulphur that may be at first thrown down. The dialurate is formed in the cold so abundantly as to cause the whole to become thick. It may be dissolved in the liquid by the aid of heat and it is then deposited on cooling in crystals. We ought to see thet nothing is left undissolved by the hot liquid; should this oc- cur it is probably owing to sulphur and in that case a little hydrosulphuret of ammonia clears all up.The crystallized dialurate of ammonia is collected on a filter and washed at first with a weak solution of hydrosulphuret of ammonia then with alcohol to which enough hydrosulphuret has been added to give it a pale yellow colour aid finally with pure alcohol till the latter passes through quite colourless and pure. The salt is quickly submitted while still on the filter to pressure between folds of bibulous paper and is finally dried in vamo over sulphuric acid. Should it not appear pure the process of dissolving it in water with the addition of hydrosulphuret of ammonia of crystallizing,A and washing as above is to be repeated. By this method I have prepared this salt in large quantity and have obtained it dry and quite pure with only a faint tinge of flesh colour in fact almost colourless.If dried in the air without the use of the alcohol and hydrosulphuret in washing and with the aid even of a gentle heat it becomes blood-red. The pure dialurate forms minute prismatic crystals which are united together when dried in light bulky masses of a faint silky lustre. I took advantage of the possession of a large stock of this salt to repeat the analysis of it determining the nitrogen by the process of Varrentrapp and Will. Se- veral analyses made by myself and one made by Mr. Keller yielded results which I shall not detain the Society by re- peating as they agreed entirely with those of Liebig and Wiihler.3. Dialuric Acid. Liebig and Wohler failed to obtain this acid in a separate form owing doubtless to their being compelled to make their experiments on very small quantities. I found that it is easily obtained when the preceding salt is dissolved with the aid of heat in an excess of diluted hydrochloric acid. The liquid deposits 011 cooling a quantity of sparingly soluble crystals Dr. Gregory on the not uiilike those of alloxantine yet quite distinguishable froin them; these crystals are dialuric acid. They have a strong acid reaction and readily neutralize the alkaline bases form- ing with ammonia the preceding salt; with potash a spa- ringly soluble salt in hard crystals; and with baryta an inso- luble or very slightly soluble powder.The latter salts are fornied when dialuric acid is added to solutions of the soluble salts of potash and baryta so that the affinities of the acid are powerful. 12 P Dialuric acid is not however very permanent in its uncom- bined form that is to say when dissolved in water. It gra- dually passes into alloxantine when exposed to the air oxy- aen no doubt being absorbed. The change may be traced i n the colour of the precipitate produced by barytic water. If it be white the acid has not yet undergone a change ; but if it be pale pink reddish-purple or violet this indicates the gradually increasing proportion of alloxantine. Even the crystals of dialuric acid when left in the liquid tiotn which they have been deposited for a day or two are found to be partially changed into alloxantine.I made several analyses both of the acid itself and of its compounds with potash and baryta. The details shall appear hereafter at present I may state that these analyses corre- namely C N H 0 = C N H 0 + HO in which HO spond to the hypothetical formula given by Liebig and Wijhler seems to be capable of replacement by MO in the salts. It is important to observe that urile or urilic acid C N 0 + H4 0, =4 atoms of water contains the elements of dialuric acid. I t is proper to state that Liebig and Wohler did obtain by the same process as I adopted the crystals of dialuric acid which however appear to have been partially converted into alloxantine before they were examined *. Indeed my experi- ments lead me to believe that the substance described by these chemists as dimorphous alloxantine is nothing but dialuric acid more or less completely converted into alloxantine and retaining probably its original form.Or they may have exa- mined a mixture of the crystals of both in which those of dialuric acid happened to be the largest and best formed. Such a mixture if analysed would of course yield results closely approximating to those derived from alloxantine as the latter body consists of the same elements as dialuric acid + 1 at. of hydrogen and 2 at. of oxygen only. Liebig and Wohler have already observed and my experiments confirm the statement that the liquid obtained by boiling dialurate of ammonia with an acid deposits when allowed to stand for.* Ann. deer Pharm. xxvi. 280. 13 Products of the Decomposition of Uric Acid. some time after cooling crystals of alloxantine which will of course be found mixed with the dialuric acid deposited during refrigeration unless the latter be first separated. The salts of dialuric acid in the dry state are quite perma- nent. I am still occupied with the study of this remarkable acid and its salts. 4. Acid Thionurate of Ammonia. This salt from which according to Liebig and Wohler the uramilic acid is best obtained may be prepared in any quantity by dissolving the neutral thionurate of ammonia in hot water and adding exactly as much hydrochloric acid calculated from the specific gravity by means of the published tables of liquid hydrochloric acid as corresponds to 1 eq.of hydrochloric acid for 1 eq. of the salt which contains 2 eq. of ammonia. One of these is removed by the hydrochloric acid and when the liquid is gently evaporated to a small bulk it deposits the acid (monobasic) thionurate of ammonia in soft crusts which frequently fall to the bottom and are composed of very minute prisms. I have not yet succeeded in obtaining uramilic acid either from this salt or in any other way; and Prof. Liebig informs me that neither he nor Prof. Wohler has been so fortunate as to succeed in procuring it again. I t can hardly be doubted however that with an easy and sure method of preparing the acid thionurate we shall soon ascer- tain all the conditions essential to the formation of uramilic acid.The acid thionurate itself as well as all the compounds now- mentioned I have prepared by ounces at a time without once failing. 5. Altoxnno- sulphurous Acid. Liebig and Wohler mention that a solution of alloxan in sulphurous acid when slowly evaporated deposited large ta- bular acid crystals which not only were not thionuric acid (which requires the elements of ammonia besides those of al- loxan and sulphurous acid) but when mixed with ammonia did not produce the thionurate of that base but a totally dif- ferent salt of a gelatinous aspect which has not been further examined. I have not examined those tabular crystals nor indeed have I as yet seen them; but I have by other means obtained a salt the acid of which appears to be composed of alloxan and sulphurous acid.To obtain this salt dissolve alloxan in the smallest possible quantity of cold water and add to the solution a slight excess of a saturated solution of sulphurous acid in water. Then add with care caustic potash in solution till there is the Dr. Gregory on the Decomposition of Uric Acid. 14 slightest possible alkaline reaction. There will be deposited very soon partly even at once in the cold solution a salt in hard brilliant crystals which may easily be obtained by re- crystallization of considerable size and are very beautiful from their perfect whiteness their transparency and brilliant lustre. This new salt may be procured in any quantity and with the utmost facility. I have not yet succeeded in isolating the acid but the analysis of the salt indicates that the acid consists of two atoms of sulphurous acid and one of alloxan.I t thus differs from thionuric acid by the absence of 1 eq. am- monia and probably also in being nionobasic while thioriuric acid is bibasic. The analytical details concerning this new acid which I propose to call the alloxano-sulphurous will appear when I have completed my investigation of its pro- perties. I t is probable that the large tabular crystals above mentioned as obtained by Liebig and Wohler are nothing more than the alloxano-sulphurous acid in a free state. 6. Alloxanic Acid. When pure alloxantine is dissolved in distilled water and the cold solution allowed to stand it slowly loses the property of giving a violet precipitate with barytic water and finally yields a white precipitate.The liquid is now acid and if gently evaporated to dryness yields crystals which are very soluble both in water and al- cohol and which possess all the chemical characters of allox- anic acid. Professor Liebig did me the favour to examine these crystals as obtained by me and considered them to be alloxanic acid as I had previously done. I did not consider them pure enough for analysis and besides their analysis could throw little light on the subject as the crystallized al- loxaiiic acid has the same composition in 100 parts as anhy- drous alloxan ; and differs therefore from alloxantine only by containing 1 eq. of hydrogen less. Should this observation be confirmed it seems difficult to account for the production of alloxanic acid in this experiment.No other compound appears to be formed and the change seems to takeplace as well in tightly corked and filled vessels as in the air. Besides when alloxantine is oxidized it yields not alloxanic acid but alloxan arid there is no base present that might be supposed to give rise to the production of the acid. I t is possible that this acid may not be really alloxanic acid although agreeing with it in its reactions. In that case it appears rnost probable that it may be isomeric with allox- antine as alloxanic acid is with alloxan. At all events it is Mr. W. H. Balmain mi Bthogm. 15 impossible to see how the 1 eq. of hydrogen bas been removed if the acid be really the atloxanic.I am still engaged in re- searches on this part of the subject the results of which I shall forward to the Society at a future period along with those of the other investigations briefly described above. The study of the products of the decomposition of uric acid is still very far from being completed and I hope at no very distant period to follow up this paper with another on the same subject. Dr. Gregory on the Decomposition of Uric Acid. 9 LX XXVI. Fzlrther Contributions to the Chemical History of By WIL-I N 1840 I described at the Glasgow Meeting of the British Association an improved and very productive method of preparing alloxan murexide &c. ; and I showed from the occurrence of urea among the products of the action of hy-permanganate of potash on uric acid that Liebig and Wohler’s view according to which urea pre-exists in uric acid must be admitted in the present state of our knowledge as well-the Products of the Decomposition of Uric Acid.LIAM GREGORY M.D. F.R.S.E 10 Dr. Gregory on the founded ; thus giving additional probability to the supposition of the existence of the acid supposed by them to be present in uric acid combined with urea and called hypothetically, urilic acid= C N 04. Since that period I have been frequently occupied with the subject of uric acid. In 1841 Professor Liebig having en-trusted to me the treatment of upwards of 2 lbs. of urate of ammonia I extracted the uric acid from this and converted nearly the whole of it into alloxan of which I obtained i$ Ib.in large and absolutely pure crystals. 'This not only enabled me to study the preparation of several of the other products, but led me to economise as much as possible the very abun-dant mother-liquid of the alloxan which contained a large quantity of that substance but so much mixed with nitrate of ammonia and free nitric acid that the alloxan could not be purified by crystallization even if the liquid could have been concentrated by heat without decomposition. I shall now state the results of my experiments as far as these are to-lerably ascertained. There is still much to be done and se-veral investigations are in an imperfect state in my laboratory. As it may be some time however before I may be able to re-turn to them I think it right in the mean time to describe the results hitherto obtained.1. Alloxanti7ae. This compound is best obtained from the mother-liquid of alloxan as prepared according to my process*. The acid solution is diluted with two or three parts of water and a cur-rent of snlphuretted hydrogen gas is passed through as long as it produces any effect. Sulphur is first deposited and sub-sequently a large quantity of alloxantine. 'rhe mixed pre-cipitate is drained washed with a little cold water and then boiled with water acidulated with hydrochloric acid until all the alloxantine is dissolved which requires from a quarter to half an hour even when enough water is present for the final solution of the whole. The solution is filtered while hot, which takes place very rapidly and deposits on coding an abundant crop of crystals of alloxantine.The quantity rexhes its maximum in twenty-four hours and the amount retained in the acidulous mother-liquor is but small. I t may however be obtained by concentration. By this method the mother-liquid of the alloxan above mentioned although some part of it was used for other experiments yielded upwards of 8 oz. of pure alloxantine. * See Turner's Chemistry 7th edition Products of the Decomposition of Uric Acid. 11 2. Diabrate of Ammonia. This salt may be also obtained in abundance from the mother-liquid of alloxan as well as from that of alloxantine. Animonia is to be cautiously added in the cold so as to leave a slight excess of acid and hydrosulphuret of ammonia is to be then added in excess so as to redissolve any sulphur that may be at first thrown down.The dialurate is formed in the cold so abundantly as to cause the whole to become thick. It may be dissolved in the liquid by the aid of heat and it is then deposited on cooling in crystals. We ought to see thet nothing is left undissolved by the hot liquid; should this oc-cur it is probably owing to sulphur and in that case a little hydrosulphuret of ammonia clears all up. The crystallized dialurate of ammonia is collected on a filter and washed at first with a weak solution of hydrosulphuret of ammonia then with alcohol to which enough hydrosulphuret has been added to give it a pale yellow colour aid finally with pure alcohol till the latter passes through quite colourless and pure. The salt is quickly submitted while still on the filter to pressure between folds of bibulous paper and is finally dried in vamo over sulphuric acid.Should it not appear pure the process of dissolving it in water with the addition of hydrosulphuret of ammonia of crystallizing,A and washing as above is to be repeated. By this method I have prepared this salt in large quantity and have obtained it dry and quite pure with only a faint tinge of flesh colour in fact almost colourless. If dried in the air without the use of the alcohol and hydrosulphuret in washing and with the aid even of a gentle heat it becomes blood-red. The pure dialurate forms minute prismatic crystals which are united together when dried in light bulky masses of a faint silky lustre. I took advantage of the possession of a large stock of this salt to repeat the analysis of it determining the nitrogen by the process of Varrentrapp and Will.Se-veral analyses made by myself and one made by Mr. Keller, yielded results which I shall not detain the Society by re-peating as they agreed entirely with those of Liebig and Wiihler. 3. Dialuric Acid. Liebig and Wohler failed to obtain this acid in a separate form owing doubtless to their being compelled to make their experiments on very small quantities. I found that it is easily obtained when the preceding salt is dissolved with the aid of heat in an excess of diluted hydrochloric acid. The liquid deposits 011 cooling a quantity of sparingly soluble crystals 12 Dr. Gregory on the not uiilike those of alloxantine yet quite distinguishable froin them; these crystals are dialuric acid.They have a strong acid reaction and readily neutralize the alkaline bases form-ing with ammonia the preceding salt; with potash a spa-ringly soluble salt in hard crystals; and with baryta an inso-luble or very slightly soluble powder. The latter salts are fornied when dialuric acid is added to solutions of the soluble salts of potash and baryta so that the affinities of the acid are powerful. Dialuric acid is not however very permanent in its uncom-bined form that is to say when dissolved in water. It gra-dually passes into alloxantine when exposed to the air oxy-aen no doubt being absorbed. The change may be traced i n the colour of the precipitate produced by barytic water.If it be white the acid has not yet undergone a change ; but if it be pale pink reddish-purple or violet this indicates the gradually increasing proportion of alloxantine. Even the crystals of dialuric acid when left in the liquid tiotn which they have been deposited for a day or two are found to be partially changed into alloxantine. I made several analyses both of the acid itself and of its compounds with potash and baryta. The details shall appear hereafter at present I may state that these analyses corre-spond to the hypothetical formula given by Liebig and Wijhler, namely C N H 0 = C N H 0 + HO in which HO seems to be capable of replacement by MO in the salts. It is important to observe that urile or urilic acid C N 0 + H4 0, =4 atoms of water contains the elements of dialuric acid.I t is proper to state that Liebig and Wohler did obtain by the same process as I adopted the crystals of dialuric acid, which however appear to have been partially converted into alloxantine before they were examined *. Indeed my experi-ments lead me to believe that the substance described by these chemists as dimorphous alloxantine is nothing but dialuric acid more or less completely converted into alloxantine and retaining probably its original form. Or they may have exa-mined a mixture of the crystals of both in which those of dialuric acid happened to be the largest and best formed. Such a mixture if analysed would of course yield results closely approximating to those derived from alloxantine as the latter body consists of the same elements as dialuric acid + 1 at.of hydrogen and 2 at. of oxygen only. Liebig and Wohler have already observed and my experiments confirm the statement that the liquid obtained by boiling dialurate of ammonia with an acid deposits when allowed to stand for. * Ann. deer Pharm. xxvi. 280. Products of the Decomposition of Uric Acid. 13 some time after cooling crystals of alloxantine which will of course be found mixed with the dialuric acid deposited during refrigeration unless the latter be first separated. The salts of dialuric acid in the dry state are quite perma-nent. I am still occupied with the study of this remarkable acid and its salts. 4. Acid Thionurate of Ammonia. This salt from which according to Liebig and Wohler, the uramilic acid is best obtained may be prepared in any quantity by dissolving the neutral thionurate of ammonia in hot water and adding exactly as much hydrochloric acid, calculated from the specific gravity by means of the published tables of liquid hydrochloric acid as corresponds to 1 eq.of hydrochloric acid for 1 eq. of the salt which contains 2 eq. of ammonia. One of these is removed by the hydrochloric acid, and when the liquid is gently evaporated to a small bulk it deposits the acid (monobasic) thionurate of ammonia in soft crusts which frequently fall to the bottom and are composed of very minute prisms. I have not yet succeeded in obtaining uramilic acid either from this salt or in any other way; and Prof. Liebig informs me that neither he nor Prof. Wohler has been so fortunate as to succeed in procuring it again.I t can hardly be doubted however that with an easy and sure method of preparing the acid thionurate we shall soon ascer-tain all the conditions essential to the formation of uramilic acid. The acid thionurate itself as well as all the compounds now- mentioned I have prepared by ounces at a time without once failing. 5. Altoxnno- sulphurous Acid. Liebig and Wohler mention that a solution of alloxan in sulphurous acid when slowly evaporated deposited large ta-bular acid crystals which not only were not thionuric acid (which requires the elements of ammonia besides those of al-loxan and sulphurous acid) but when mixed with ammonia, did not produce the thionurate of that base but a totally dif-ferent salt of a gelatinous aspect which has not been further examined.I have not examined those tabular crystals nor, indeed have I as yet seen them; but I have by other means obtained a salt the acid of which appears to be composed of alloxan and sulphurous acid. To obtain this salt dissolve alloxan in the smallest possible quantity of cold water and add to the solution a slight excess of a saturated solution of sulphurous acid in water. Then add with care caustic potash in solution till there is th 14 Dr. Gregory on the Decomposition of Uric Acid. slightest possible alkaline reaction. There will be deposited very soon partly even at once in the cold solution a salt in hard brilliant crystals which may easily be obtained by re-crystallization of considerable size and are very beautiful, from their perfect whiteness their transparency and brilliant lustre.This new salt may be procured in any quantity and with the utmost facility. I have not yet succeeded in isolating the acid but the analysis of the salt indicates that the acid consists of two atoms of sulphurous acid and one of alloxan. I t thus differs from thionuric acid by the absence of 1 eq. am-monia and probably also in being nionobasic while thioriuric acid is bibasic. The analytical details concerning this new acid which I propose to call the alloxano-sulphurous will appear when I have completed my investigation of its pro-perties. I t is probable that the large tabular crystals above mentioned as obtained by Liebig and Wohler are nothing more than the alloxano-sulphurous acid in a free state.6. Alloxanic Acid. When pure alloxantine is dissolved in distilled water and the cold solution allowed to stand it slowly loses the property of giving a violet precipitate with barytic water and finally yields a white precipitate. The liquid is now acid and if gently evaporated to dryness yields crystals which are very soluble both in water and al-cohol and which possess all the chemical characters of allox-anic acid. Professor Liebig did me the favour to examine these crystals as obtained by me and considered them to be alloxanic acid as I had previously done. I did not consider them pure enough for analysis and besides their analysis could throw little light on the subject as the crystallized al-loxaiiic acid has the same composition in 100 parts as anhy-drous alloxan ; and differs therefore from alloxantine only by containing 1 eq.of hydrogen less. Should this observation be confirmed it seems difficult to account for the production of alloxanic acid in this experiment. No other compound appears to be formed and the change seems to takeplace as well in tightly corked and filled vessels as in the air. Besides when alloxantine is oxidized it yields, not alloxanic acid but alloxan arid there is no base present that might be supposed to give rise to the production of the acid. I t is possible that this acid may not be really alloxanic acid although agreeing with it in its reactions. In that case it appears rnost probable that it may be isomeric with allox-antine as alloxanic acid is with alloxan. At all events it i Mr. W. H. Balmain mi Bthogm. 15 impossible to see how the 1 eq. of hydrogen bas been removed, if the acid be really the atloxanic. I am still engaged in re-searches on this part of the subject the results of which I shall forward to the Society at a future period along with those of the other investigations briefly described above. The study of the products of the decomposition of uric acid is still very far from being completed and I hope at no very distant period to follow up this paper with another on the same subject