US631760A - Alkylized xanthin and process of making same. - Google Patents
Alkylized xanthin and process of making same. Download PDFInfo
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- US631760A US631760A US67254398A US1898672543A US631760A US 631760 A US631760 A US 631760A US 67254398 A US67254398 A US 67254398A US 1898672543 A US1898672543 A US 1898672543A US 631760 A US631760 A US 631760A
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- xanthin
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- 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
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
Definitions
- HN-GO is denominated 2-G-dioxypurin and chlorocaffein, having the formula:
- the invention forming the subject-matter of the present application consists in the preparation of 3'alkyl-xanthin, and, specifically,
- the xanthin is thereby gradually brought into solution, while the adhering coloring-matter remains undissolved. Upon cooling after such solution is efiected the methyl-chloro-xanthin crystallizes in anhydrous, fine, colorless, shining foliated crys tals or scales.
- This new base as a xanthin, gives a strong murexid reaction only with chlorin water, while if it is evaporated together with moderately-concentrated nitric acid it yields a slightly-colored residue, which is dissolved in strong potash-lye, and thus forms a clear It requires from three hundred to three hundred and thirty parts of boiling water for solution, but is readily soluble in dilute alkalies and ammonia and also in concentrated sulfuric or hydrochloric acid.
- An ammoniacal solution of the same when added to a solution of nitrate of silver, gives rise to a colorless silver salt consisting of fine needles. This silver salt dissolves in a large excess of ammonia on heating and remains unchanged on boiling.
- 3-methyl-xanthin has no melting-point. lVhen heated above 360 centigrade, it begins to become yellow, and on raising the temperature above 400 centigrade it is decomposed without melting.
- This new body differs from the compound heteroxanthin described in Patents Nos. 617,985 and 617,986, dated January 17, 1899, only in the location of the methyl group. ⁇ Vhile in the latter compound this group is in the position 7, in the present compound it occupies the position 3.
- this new compound-the S-methylxanthin- may be readily converted into higher alkylized Xanthins by alkylizin g methods. Thus, e. g.
- ,I may obtain either dimethyl-- and trimethyl-xanthins, or, in other words, theobromin and caffein by the same alkylizing agents, potash-lye combined with methyliodid under the influence of heat by simply varying the proportions of the ingredients.
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Description
UNITED STATES PATENT OFFICE.
FRITZ AOH, OF MANNHEIM, GERMANY, ASSIGNDR TO C. F. BOEHRINGER &
SOEHNE, OF WALDHOF, GERMANY.
ALKYLIZED XANTHIN AND PROCESS OF MAKING SAME.
SPECIFICATION formingpart of Letters Patent No. 631,760, dated August 22, 1899. Application filed March 4, 1898. Serial No. 672,543. (Specimens) T to whom it may concern.-
Be it known that I, FRITZ ACH, a citizen of the German Empire, residing at Mannheim,
, ration of 3-alkyl-Xanthins.
In carrying out my invention I proceed from 3-alkyl-uric acids-such, for example, as 3-methyl-uric acidfirst converting the same into 3-methyl-chloro-xanthins by the action of phosphorus-ox-y-chlorid,and thereupon converting the chloro-xanthin into a xanthin proper or 3-alkyl-2-6-dioxy-purin by the aid of reducing agents.
Before proceeding with the specification I will state that I have herein adopted the nomenclature and system of numbering the carbon and nitrogen atoms of the purin nucleus, which has been introduced by Prof. Emil Fischer and described in Berichte der Deuischen Ohemischen Gesellschctft, Vol. 30, page 549. According to this system the purin nucleus is arranged and its atoms are numbered thus:
(mowu) (3)N C-N(9) According to this nomenclature and system, xanthin, e. g., Whose formula is:
HN-GO is denominated 2-G-dioxypurin and chlorocaffein, having the formula:
cri is-co oo o-NoI-I, ooi
OH .N-CN is 1-3-7-trimethyl-S-chloro-Xanthin or 1-3-/'- trimethyl-8-chloro-2-6-dioxy-purin.
In my application filed February 18, 1898, Serial No. 67 0,847, (Case J I have described and claimed generically the method of proceeding from alkyl-uric acids, having no alkyl in the position (9) first to alkylized chloroxanthins by the agency of phosphorus-oxychlorid and then from such alkylized chloro- Xanthins to higher alkylized products by alkylization and reduction, or vice versa. In that application I have also described and claimed the more specific method of applying the above treatment to 3-alkyl-uric acids and more particularly 3-methyl-uric acid. Among other things I claim in that application the method of preparing 3-alkyl-chloro-Xanthin and specially 3-methyl-chloro-xanthin from 3-methyl-uric acid and also the said new compound 3-methyl-chloro-xanthin.
The invention forming the subject-matter of the present application consists in the preparation of 3'alkyl-xanthin, and, specifically,
.3-methy1-Xanthin from .3-alkyl-chloro-xanthin, and, specifically, 3-methyl-chloro-Xanthin in the new compound thus produced, and also in the methods of proceeding therefrom to higher alkylized xanthius, such as theobromin and caffein.
In order to fully disclose my invention, I will first describe the method of preparing the starting material, 3-methyl chloro-xanthin from S-methyl-uric acid, it being understood that this method and the resulting compound are not herein claimed, since they form the subject-matter of the claims of my aforesaid application.
1. Preparation of -meihyl-chloro-asanthin from 3-meth yZ-uric acid-One part of anhydrous 3-methyl-uric acid is added to five parts, by volume, of phosphorus-oXy-chlorid and heated under pressuree. g. in a digester-to from to centigrade, and maintained at this temperature for from three to four hours, the mass being steadily agitated. lhe resulting clear reddish brown solution is then evaporated in vacuo for the purpose of completely removing the phosphorusoxychlorid. The brownish residue, which has a tough varnish-like consistency, is thereupon brought into solution by boilingthe same with about five times its quantity of alcohol or water. The alcoholic solution, which at first is clear, but soon becomes turbid on account of the precipitation of granular crys talline Inethyl-chloro-xanthin, is boiled for from two to three hours with reflux and then allowed to cool. Upon then filtering the methyl-chloro-xanthin remains on the filter as a yellow, granular, crystalline mass. The filtrate is then evaporated, wherebya second crystallization ensues, resulting in a further yield of the above product, methyl-chloroxanthin. The crude product so obtained is brought into solution with dilute alkali, such as two-per-cent. potash-lye, treated with animal charcoal or other decolorizing agent, and finally precipitated with dilute sulfuric acid. On cooling the new compound is obtained in the form of yellow-hued coarse crystals, from whose analysis are obtained figures which show the formula of this compound to be O H N O Ol+H O. Its structural formula is found to be:
IIN-CO oc c-nn c or o1i,.N-c-N such formula being established by the fact of the ready conversion of this compound into chloro-cafiein (see under 11.) I therefore designate this new compound as 3- inethyl-chloro-xanthin or 3-methyl-8- chloro-Xanthin. The tenaciously-adherin g yellow tint,which is very difficult of removal, has no influence on the percentage composition of the product. Absolute decoloration of the methyl-chloroxanthin may be attained by thoroughly boiling it with a large quantity (thirty parts to one part of the methyl-chloro-xanthin) of aceton. The xanthin is thereby gradually brought into solution, while the adhering coloring-matter remains undissolved. Upon cooling after such solution is efiected the methyl-chloro-xanthin crystallizes in anhydrous, fine, colorless, shining foliated crys tals or scales.
3-methyl-chloro-xanthin is soluble in about two hundred and fifty parts boiling water, and on cooling the solution slowly the same crystallizes therefrom in coarse.needles,which under the microscope are found to be elongated flat prisms and which contain one molecule of water of crystallization. This water of crystallization escapes on protracted heating at 120 centigrade. It is difficult of solution in boiling alcohol, in aceton, aceticether, benzene, or chloroform, readily solucoarse colorless prismatic crystals.
ble in dilute alkalies, in ammonia, and soda or potash solutions. It is equally soluble in concentrated sulfuric acid and fuming hydrochloric acid. From a solution in the latter the original product is precipitated by water on standing for some time. Heated with chlorin Water or with dilute nitric acid it gives a strong murexid reaction. An ammoniacal solution of the same added to an ammoniacal silversolution yields a gelatinous silver salt,which remains unchanged on boiling.
3-methyl-chloroxanthin has no meltingpoint, but on being rapidly heated it begins to turn yellowat 320 centigrade and at about 345 centigrade it decomposes with efiervescence. The 3-methyl-chloro-xanthin is then converted into the chlorin-free-xanthin by reducing methodse. g., as follows:
2. Preparation of 3-meth'yl-2-6-d'iowypu-rm or S-methyZ-manthin from 3-methg Z chlorozccmtht'n.lf one part, by weight, of 3-methylchloro-xanthin, described under head 1, is heated with ten times its weight of fuming hydriodic acid, a gradual solution and reduction of the chloro compound takes place,
which is attended by a liberation of iodin.
The heating (at a temperature of 90 to centigrade) is continued and phosphoniumiodid added from time to time until a clear colorless solution is formed. The solution is then evaporated, whereby the iodohydrate of this new base is thrown out in the form of After the evaporation has been continued to complete dryness the residue is taken up with water, which causes the iodohydrate to be decomposed and the methyl-Xanthin to be isolated in the form of fine colorless needles. The practical yield corresponds to the theoretical. The base is recrystallized from boiling water and so obtained in the form of fine shining needles. Its formula is (J PI IQQO or,
structurally HN-CO 0O O-NH 1! on i OH .NO-N
The reaction, as a result of which it is ob tained, is expressed in the equation:
HN- O0 00 (ll-Nil +H,:
deep-yellow solution.
This new base, as a xanthin, gives a strong murexid reaction only with chlorin water, while if it is evaporated together with moderately-concentrated nitric acid it yields a slightly-colored residue, which is dissolved in strong potash-lye, and thus forms a clear It requires from three hundred to three hundred and thirty parts of boiling water for solution, but is readily soluble in dilute alkalies and ammonia and also in concentrated sulfuric or hydrochloric acid. An ammoniacal solution of the same, when added to a solution of nitrate of silver, gives rise to a colorless silver salt consisting of fine needles. This silver salt dissolves in a large excess of ammonia on heating and remains unchanged on boiling.
If a solution of the 3-methyl-xanthin in dilute nitric acid is added to nitrate of silver, a double salt, consisting of coarse acicular crystals intermeshed in the form of bunches, is thrown out. This double salt is readily soluble in hot water.
3-methyl-xanthin has no melting-point. lVhen heated above 360 centigrade, it begins to become yellow, and on raising the temperature above 400 centigrade it is decomposed without melting. This new body differs from the compound heteroxanthin described in Patents Nos. 617,985 and 617,986, dated January 17, 1899, only in the location of the methyl group. \Vhile in the latter compound this group is in the position 7, in the present compound it occupies the position 3. I have found that this new compound-the S-methylxanthin-may be readily converted into higher alkylized Xanthins by alkylizin g methods. Thus, e. g. ,I may obtain either dimethyl-- and trimethyl-xanthins, or, in other words, theobromin and caffein by the same alkylizing agents, potash-lye combined with methyliodid under the influence of heat by simply varying the proportions of the ingredients.
3. Preparation of 3-7 -dt'mcthyZ-xanth'in (theobromin) from d-methyZ-ocanthin.Seven parts, by weight, of 3-methyl-xanthin are dissolved in twenty-six parts, by volume, of potash-lye (potassium-hydrate solution) of double normal strength, and fifty parts, by volume, of water, and after adding thereto eight parts, by weight, of methyl-iodid, heated to centigrade, and maintained at this temperature for three hours while constantly agitating the same. After cooling the liquid will be found to be filled with a pulpy mass of colorless crystals. The mother-liquor is removed from these crystals by suction or otherwise, and they are then redissolved in and recrystallized from boiling water. The colorless crystals so obtained possess all of the characteristic properties of natural theobromin.
4. Preparation of 1-3-7-tr-imethyZ-manth in (caflei n) from 3-meihyZ-manthin.Qne part, by weight, of 3-methyl-xanthin is dissolved in 6.8 parts, by volume, of double normal potash-lye, (potassi u m-hydrato solution,) and fifteen parts, by volume, of water and heated to 80 centigrade, together with two parts, by weight, of methyl-iodid, this temperature be ing maintained for three hours and the mass constantly agitated. The clear liquid so obtained is highly evaporated and then extracted with chloroform. The fine acicular crystals resulting from this treatment have the melting-point 232 centigrade and all of the other properties of caffein. The reaction takes place according to the equation:
HN-CO on,.N o-N orI,.N oo
The yield in caffein obtained corresponds to the theoretical yield.
It will be seen, thus, that this new body-3- 1n ethyl-Xanthin-is readily susceptible of conversion into higher alkylized products, such as the important compounds, theobromin and caffein.
WVhat I claim, and desire to secure by Letters Patent of the United States, is
1. The process which consists in submitting 3-alkyl' chloroxanthin to the action of a reducing agent, whereby a 3-alkylxanthin is produced.
2. The process which consists in submitting 3-methyl-chloroxanthin to the action of a reducing agent for the purpose of preparing 3- methyl-xanthin.
3. In the process of obtaining Xanthins the step which consists in heating S-methyl-chloroXanthin with hydroiodic acid and phosphonium-iodid.
4. The process which consists in adding hy droiodic acid and phosphonium-iodid to 3- ITO methyl-chloro-Xanthin and heating the mixture all in the proportions and under the conditions, substantially as specified, then evapfrom boiling water in the form of fine shining.
needles, which has no melting-point, but becomes yellow on being heated above 360, centigrade, and decomposes at a temperature above 400, centigrade, which gives dissolved in dilute nitric acid with silver nitrate a double salt consisting of coarse acicular crysand then reducing the resulting 3-methylchloro-Xanthin.
10. The process which consists in treating 3- methyl-nric acid with phosphorus-oXy-chlorid in the manner substantially as set forth, then reducing the resultant 3-methyl-chloro- Xanthin, and finally alkylizing the resultant 3-methyl-xanthin.
In testimony whereof I affix my signature in presence of two witnesses.
FRITZ ACH.
\Vitnesses:
LORENZ AoH, JACOB ADRIAN.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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US67254398A US631760A (en) | 1898-03-04 | 1898-03-04 | Alkylized xanthin and process of making same. |
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US67254398A US631760A (en) | 1898-03-04 | 1898-03-04 | Alkylized xanthin and process of making same. |
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US67254398A Expired - Lifetime US631760A (en) | 1898-03-04 | 1898-03-04 | Alkylized xanthin and process of making same. |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4450163A (en) * | 1979-05-22 | 1984-05-22 | Societe D'assistance Technique Pour Produits Nestle S.A. | Process for the preparation of 1,3,7-trialkyl xanthines and di(3,7-dimethylxanthin-1-yl)methane as a medicament |
-
1898
- 1898-03-04 US US67254398A patent/US631760A/en not_active Expired - Lifetime
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4450163A (en) * | 1979-05-22 | 1984-05-22 | Societe D'assistance Technique Pour Produits Nestle S.A. | Process for the preparation of 1,3,7-trialkyl xanthines and di(3,7-dimethylxanthin-1-yl)methane as a medicament |
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