US667388A - Trimethyl-pseudo-uric acid and process of preparing same. - Google Patents
Trimethyl-pseudo-uric acid and process of preparing same. Download PDFInfo
- Publication number
- US667388A US667388A US66408397A US1897664083A US667388A US 667388 A US667388 A US 667388A US 66408397 A US66408397 A US 66408397A US 1897664083 A US1897664083 A US 1897664083A US 667388 A US667388 A US 667388A
- Authority
- US
- United States
- Prior art keywords
- uric acid
- acid
- pseudo
- trimethyl
- uric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
Definitions
- This invention relates to the preparation of uric acid and its derivatives, and in particular the manufacture of the same from the corresponding pseudo-uric acids.
- Hitherto pseudo-uric acid could only be converted into uric acid by fusing or melting it together with oxalic acid.
- dimet-hyl-pseudo-uric acid in which the two methyl groups are bound to the two nitrogen atoms of the alloxan nucleus the same result was also obtained by boiling with the anhydrid of acetic acid and zinc chlorid, as set forth in the article by E. Fischer and L. Ach in Berichte der Deatschen-Ohemr'schentechnik, Vol. 28, page 2473. Both processes are impracticable for industrial purposes and are only scientifically valuable.
- hydrochloric acid instead of a twenty-per-cent. hydrochloric acid a one-per-cent. acid may be employed; but in this case it is necessary to boil for from eight to ten hours.
- the reaction takes place according to the equation If instead of the twelve-per-cent. hydrochloric acid a one-per-cent. acid is employed, the reaction takes place in the same way, but requires a correspondingly longer heating.
- the crystallization of the gamma monomethyl-uric acid then begins after the lapse of about a half-hour, and after one and one-half hours the amount of the resultant uric acid will have already reached two-thirds of the pseudo-uric acid employed.
- the cooperation of the mineral acid is not even necessary, since the same reaction takes place when heating a mere aqueous solution of the methyl-pseudo-uric acid to 100 centigrade. Only under these conditions it is m uch slower.
- the same is constant in the cold and may be obtained in a crystalline form in the following manner: Five grams of commercial solution of methyl amin containing about thirty-three per cent. of the base are saturated with sulfur dioxid, and then about five grams more of methylamin are added until the odor of the base becomes perceptible. Thereuponthe same is neutralized with carbonic-acid gas, whereupon asolutiou of five grams dimethyl-alloxan in five grams water is added. It the liquid remains at the ordinary temperature, colorless needles are soon separated out in copious quantity, which are then recrystallized from a small quantity of warm water.
- the 1-3-7-triinethyl-uric acid is very readily prepared from the trimethyluramil by heating the latter with a solution of cyanate of potassium.
- the crude product may be directly employed for this purpose if the same has been freed from ammonium salts by careful washing with cold water. For example, three grams of the 1-3-7-trimethyluramil are heated on the water-bath with two grams pure potassium dissolved in five cubic centimeters of water. A clear solution soon forms and after heating for half an hour the conversion will have been completed. If after cooling the resulting colorless liquid is treated carefully with hydrochloric acid, the 1-3-7-trimethyl-uric acid will be precipitated in the form of a crystalline powder.
- the trimethylpseudo-uric acid so obtained is soluble in about four parts hot Water and on cooling crystallizes therefrom in the form of colorless obliqely-truncated prisms of considerable size which contain one molecule of water of crystallization.
- This acid has no constant melting-point. On heating the same rapidly it will melt with attendant decomposition in the neighborhood of 195 centigrade. When slowly heated, a partial melting takes place between 180 and 190 centigrade, a product of decomposition being then formed which does not melt at 300 centigrade. In alcohol it is only soluble with difficulty even when heated. In forming hydrochloric acid (specific gravity 1.19) it is readily soluble at ordinary temperature.
- This trimethylpseudo-uric acid is, as I have found, readily converted into the corresponding trimethyluric acid or hydroxycaffein.
- one part of the trimethyl-pseudo-uric acid is heated, together with ten parts of hydrochloric acid of one-per-cent. strength, on the water-bath.
- a clear solution first forms, and after the lapse of about a half-hour the trimethyl-uric acid begins to separate out. At the end of one and one-half hours the mass is allowed to cool, and the crystalline precipitate which has formed is separated by filtration. The reaction proceeds almost quantitatively.
- the trimethyl-uric acid is identical with hydroxycaffein, which, according to my recent researches, does not possess the molecular structure formerly attributed to it, but must have the formula:
- the reaction will take place also in the absence of mineral acids; but in that case a much longer time is required for its completion. If, for example, a ten-per-cent. aqueous solution of the trimethyl-pseudo-uric acid is heated to 100 centigrade, the crystallization of hydroxycafiein does not begin until after the lapse of several hours, and even after five hours the conversion will be scarcely half completed.
- hydrochloric acid may be replaced by su1 furic acid and other mineral acids, and it is to be observed, therefore, that my invention, generically considered, is not confined to the particular mineral acid employed.
- pseudo-uric acid as employed in the claims is to be understood as covering both the pseudo-uric acid proper as well as its alkyl derivationsthe alkyl-pseudo-uric acids.
- trimethylpseudo-uric acid having the formula above given and which dissolves in about four parts of hot water, and crystallizes therefrom in colorless, obliquely-truncated prisms which contain one molecule of water of crystallization.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
UNITED STATES PATENT ()EFIQE.
EMIL FISCHER, OF BERLIN, GERMANY, ASSIGNOR TO 0. F. BOEHRINGER & SOEHNE, OF WALDHOF, GERMANY.
TRlMETHYL-PSEUDO-URIC ACID AND PROCESS 0F PREPARING SAME.
SPECIFICATION formingpart of Letters Patent No. 667,388, dated February 5, i901. Application filed December 28, 1897. serial No. 664,083- (No specimens.)-
To all whom, it Wtay concern.-
Be it known that I, EMIL FISCHER, a citizen of the Empire of Germany, residing at Berlin, in the Empire of Germany,- have invented certain new and useful Improvements in Preparing Uric Acids and Their Derivatives; and I do hereby declare the following to be a full, clear, and exact description of the invention, such as Will enable others skilled in the art to which it ap pertains to make and use the same.
This invention relates to the preparation of uric acid and its derivatives, and in particular the manufacture of the same from the corresponding pseudo-uric acids.
Hitherto pseudo-uric acid could only be converted into uric acid by fusing or melting it together with oxalic acid. In operating with dimet-hyl-pseudo-uric acid in which the two methyl groups are bound to the two nitrogen atoms of the alloxan nucleus the same result was also obtained by boiling with the anhydrid of acetic acid and zinc chlorid, as set forth in the article by E. Fischer and L. Ach in Berichte der Deatschen-Ohemr'schen Gesellschaft, Vol. 28, page 2473. Both processes are impracticable for industrial purposes and are only scientifically valuable. I have found that these conversions may be efiected in a practically available manner if the pseudouric acids are acted on in the wet way, preferably in the presence of mineral acids, although in some cases the mere heating of an aqueous solution is suflicient.
In order to make my invention, which consists in the methods, steps, and features pointed out in the claims hereunto annexed, fully and clearly understood by those skilled in the art, I will now describe a number of examples embodying the same. The proportions are all given by Weight.
1. Conversion of pseudo-aria acid into aria acid.To one part of finely-powdered pseudouric acid I add five hundred parts of hydrochloric acid of tWenty-per-cent. strength and boil the mixture until complete solution takes place, which occurs after some time. The liquid is then evaporated over an open fire until it is reduced to about the one-fifteenth part of its original volume. As a result of this treatment the largest portion of the uric acid which has been formed is separated out or precipitated in crystalline form. This separation takes place already while the liquid is still warm. The liquid is then allowed to cool and diluted with Water (about ten parts) and then filtered. If pure starting material is employed in this process, the uric acid obtained is completely colorless and the yield represents over eighty per cent. of the pseudouric acid employed.
2. Preparation of gamma-dimethyZ-aric acid.I take one part of the dimethyl-pseudouric acid, which has been described by Techow in Berichte der Deatschen- C'herm'schen Gesellschaft, V01. 27, page 3088, and add to it seven parts of hydrochloric acid of twenty-percent. strength and heat on the water-bath. A clear solution forms in the beginning of the action, and after about fifteen minutes the resultant gamma-dimethyl-uric acid crystallizes out of the solution. After thus heating for an hour the mass is allowed to cool and the crystals are separated by filtration. In this process the yield also represents about eighty per cent. of the pseudo-compound employed.
Instead of a twenty-per-cent. hydrochloric acid a one-per-cent. acid may be employed; but in this case it is necessary to boil for from eight to ten hours.
3. Preparation ofgammamonomethyZ-aric acid-By a reaction the same as that employed for the production of pseudo-uric acid (see Liebig and Wohler in Annalen, Vol. 26, page 266, and Baeyer, Ibt'd, Vol. 127, page 3) I may obtain monomethyl-pseudo-uric acid having the formula HN-OO I oo O.HN.OO.NH2
HNOO
if in the place of the sulfite of ammonium there employed a solution of sulfite of methylamin is taken. The resultant gamma methylpseudo-uric acid dissolves in about twentythree parts of boiling water, and on cooling the solution it is thrown out in the form of very small colorless crystals containing one molecule of water of crystallization. The conversion into the corresponding uric acid takes place more rapidly than in the two abovedescribed examples. If this monomethylpseudo-uric acid is heated to boiling with twenty times its quantity of hydrochloric acid of twelve-per-cent. strength a clear solution is first formed, and the crystallization of the resultant gamma-monomethyl-uric acid begins already after the lapse of a few minutes and while the liquid is warm. After having heated the mass for about half an hour the reaction is closed. The same is then allowed to cool, when the balance of the methyl-uric acid is thrown out to the largest extent in the form of crystals. In this case also the reaction proceeds almost quantitatively, and the resultant product is in every respect identical with the gamma-monomethyl-uric acid which has first been obtained by me from theobromin. (See Bem'chtc, Vol. 28, page 2492.)
The reaction takes place according to the equation If instead of the twelve-per-cent. hydrochloric acid a one-per-cent. acid is employed, the reaction takes place in the same way, but requires a correspondingly longer heating. The crystallization of the gamma monomethyl-uric acid then begins after the lapse of about a half-hour, and after one and one-half hours the amount of the resultant uric acid will have already reached two-thirds of the pseudo-uric acid employed. In this example the cooperation of the mineral acid is not even necessary, since the same reaction takes place when heating a mere aqueous solution of the methyl-pseudo-uric acid to 100 centigrade. Only under these conditions it is m uch slower.
If, e. g., an approximately-saturated aqueous solution of monomethyl-pseudo-uric acid is heated on the water-bath, the separation of the gamma-monomethyluric acid commences after the lapse of three-quarters of an hour;
. but even at the end of three hours the con l o orLucoNH OI-I .N O0
and which is a new compound, first discovered es /Less by me, may be obtained from di methyl-alloxan according to known reactions by employing sulfite of methylamin instead of the sulfite of ammonium. (See E. Fischer, Berichte der Deutschen- O hemischc'n Gesellsc hrtfi, Vol. 30, page 564.) This method of preparation in detail is as follows: When acting on dimethyl-alloxan with neutral sulfite of methylamin, there is formed first a product of addition corresponding to the compounds of the ketones with bisulfites. The same is constant in the cold and may be obtained in a crystalline form in the following manner: Five grams of commercial solution of methyl amin containing about thirty-three per cent. of the base are saturated with sulfur dioxid, and then about five grams more of methylamin are added until the odor of the base becomes perceptible. Thereuponthe same is neutralized with carbonic-acid gas, whereupon asolutiou of five grams dimethyl-alloxan in five grams water is added. It the liquid remains at the ordinary temperature, colorless needles are soon separated out in copious quantity, which are then recrystallized from a small quantity of warm water. If, however, the above mixture of dimethyl-alloxan and methylamin sulfite, together with the separated crystals, is allowed to stand at ordinary temperatu re, the crystals will go into solution after the lapse of about twenty-four hours, and the solution now evidently contains the salt of a thio acid, since on heating with dilute hydrochloric acid abundant quantities of sulfuric acid are formed. On heating the solution to from to centigrade and maintaining this temperature for one hour this thio salt is rapidly formed, this reaction being attended by a further reaction which leads to the formation of 1-3-7-trin1ethyluramil, which on cooling the solution is separated from the same in crystalline form. This trimethyluramil,which has the structural formula:
GH .N-CO
co cnntuon cn,..N co
and which forms the intermediate product in my method of preparing the above trimethylpseudo-uric acid, is a very stable body when dry and remains unchanged even in contact with air for a considerable time at ordinary temperatures. When in a moist condition or in aqueous solution, the access of air soon colorsitpurple-red. Whenheatedtoover100 centigrade in the capillary tube, it also turns red, and when rapidly heated to 200 centigrade it is entirely decomposed without any sharply-defined melting action. In hot water it is soluble with comparative facility, crystallizing out of the same in the form of colorless needles. It is still more soluble in dilute hydrochloric acid. It is also soluble in alkalies, but may be separated therefrom by im mediately neutralizing with acetic acid. It is destroyed on boiling with alkalies.
The 1-3-7-triinethyl-uric acid is very readily prepared from the trimethyluramil by heating the latter with a solution of cyanate of potassium. The crude product may be directly employed for this purpose if the same has been freed from ammonium salts by careful washing with cold water. For example, three grams of the 1-3-7-trimethyluramil are heated on the water-bath with two grams pure potassium dissolved in five cubic centimeters of water. A clear solution soon forms and after heating for half an hour the conversion will have been completed. If after cooling the resulting colorless liquid is treated carefully with hydrochloric acid, the 1-3-7-trimethyl-uric acid will be precipitated in the form of a crystalline powder. The trimethylpseudo-uric acid so obtained is soluble in about four parts hot Water and on cooling crystallizes therefrom in the form of colorless obliqely-truncated prisms of considerable size which contain one molecule of water of crystallization. This acid has no constant melting-point. On heating the same rapidly it will melt with attendant decomposition in the neighborhood of 195 centigrade. When slowly heated, a partial melting takes place between 180 and 190 centigrade, a product of decomposition being then formed which does not melt at 300 centigrade. In alcohol it is only soluble with difficulty even when heated. In forming hydrochloric acid (specific gravity 1.19) it is readily soluble at ordinary temperature. This trimethylpseudo-uric acid is, as I have found, readily converted into the corresponding trimethyluric acid or hydroxycaffein. For this purpose one part of the trimethyl-pseudo-uric acid is heated, together with ten parts of hydrochloric acid of one-per-cent. strength, on the water-bath. A clear solution first forms, and after the lapse of about a half-hour the trimethyl-uric acid begins to separate out. At the end of one and one-half hours the mass is allowed to cool, and the crystalline precipitate which has formed is separated by filtration. The reaction proceeds almost quantitatively. The trimethyl-uric acid is identical with hydroxycaffein, which, according to my recent researches, does not possess the molecular structure formerly attributed to it, but must have the formula:
0H,.N-OO
I I Cl-I oo O-N oo I ll oH,.N-o-NH since by methylating in the wet way it is readily converted into tetramethyl-uric acid.
cH,.N-co
I o on.N.oo.NH,-
Just as in the previous example, the reaction will take place also in the absence of mineral acids; but in that case a much longer time is required for its completion. If, for example, a ten-per-cent. aqueous solution of the trimethyl-pseudo-uric acid is heated to 100 centigrade, the crystallization of hydroxycafiein does not begin until after the lapse of several hours, and even after five hours the conversion will be scarcely half completed.
In the hereinbefore-described processes the hydrochloric acid may be replaced by su1 furic acid and other mineral acids, and it is to be observed, therefore, that my invention, generically considered, is not confined to the particular mineral acid employed.
The term pseudo-uric acid as employed in the claims is to be understood as covering both the pseudo-uric acid proper as well as its alkyl derivationsthe alkyl-pseudo-uric acids.
What I claim, and desire to secure by Letters Patent, is-
1. The process of preparing trimethylpseudo-uric acid which consists in treating dimethyl-alloxan with sulfite of methylamin.
2. As a new chemical compound, trimethylpseudo-uric acid having the formula above given and which dissolves in about four parts of hot water, and crystallizes therefrom in colorless, obliquely-truncated prisms which contain one molecule of water of crystallization.
3. The process of preparing a uric acid which consists in heating a pseudo-uric-acid solution.
4. The process of preparing a uric acid which consists in heating a pseudo-uric acid in the presence of a mineral acid.
5. The process of preparing a uric acid which consists in adding hydrochloric-acid solution to a pseudo-uric acid and heating the mixture.
6. The process of preparing trimethyl-uric acid or hydroxycafi'ein which consists in heating trimethyl-pseudo-uric acid in solution.
7. The process of preparing trimethyl-uric acid which consists in heating trimethylpseudo-uric acid in the presence of a mineral acid.
8. The process of preparing trimethyl-uric acid which consists in adding hydrochloric acid to trimethyl-pseudo-uric acid and heating the mixture.
9. The process of preparing trimethyl-uric acid which consists in adding one part of tri-
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66408397A US667388A (en) | 1897-12-28 | 1897-12-28 | Trimethyl-pseudo-uric acid and process of preparing same. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66408397A US667388A (en) | 1897-12-28 | 1897-12-28 | Trimethyl-pseudo-uric acid and process of preparing same. |
Publications (1)
Publication Number | Publication Date |
---|---|
US667388A true US667388A (en) | 1901-02-05 |
Family
ID=2735944
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US66408397A Expired - Lifetime US667388A (en) | 1897-12-28 | 1897-12-28 | Trimethyl-pseudo-uric acid and process of preparing same. |
Country Status (1)
Country | Link |
---|---|
US (1) | US667388A (en) |
-
1897
- 1897-12-28 US US66408397A patent/US667388A/en not_active Expired - Lifetime
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US2450386A (en) | Manufacture of compounds containing amidine groups | |
US667388A (en) | Trimethyl-pseudo-uric acid and process of preparing same. | |
Coffey et al. | 197. Ethyl esters of β-arylaminocrotonic acids | |
US3128286A (en) | Process for preparing analogues | |
US2829157A (en) | Novel hydantoic acids and their alkyl esters | |
US2462009A (en) | Amino trimethyl hexenoic acids and their lactams | |
JPS61229852A (en) | Production of 1-methyl-5-hydroxypyrazole | |
US2688023A (en) | 5-(3-cyanopropyl) hydantoin and its preparation and use to prepare 5-(4-aminobutyl) hydantoin | |
US707812A (en) | Alkoxy-caffein and process of making same. | |
US814496A (en) | Process of making barbituric acids. | |
US3461143A (en) | Production of sulfaguanidine | |
US3245998A (en) | Processes for the production of picolinic acid dericatives | |
Bailey et al. | THE ACTION OF MONOCHLOROACETIC ACID ON SEMICARBAZIDE AND HYDRAZINE. | |
Sato et al. | Studies on Organic Sulfur Comqounds. I. Thioformyl Phenylhydrazine | |
US631708A (en) | Oxypurin and process of making same. | |
US3145229A (en) | Process for the production of nu-substituted-1-phenylcyclohexylamines | |
US631705A (en) | Process of making theobromin. | |
US2516830A (en) | Fluorinated nicotinic compounds | |
US625441A (en) | Emil fischer | |
US607028A (en) | Emil fischer | |
Litzinger et al. | Researches on Pyrimidines. CLIV. Pyrimidine Side Chain Reactions Useful for the Synthesis of 1, 3-Diazines Related Structurally to Vitamin B11 | |
US632828A (en) | Process of making uric-acid derivatives. | |
US631707A (en) | Xanthin derivatives and process of making same. | |
US631757A (en) | Xanthin derivative and process of making same. | |
US631706A (en) | Oxypurin and process of making same. |