DE904286C - Process for the production of solid water-soluble salts of phosphoric acid amides - Google Patents
Process for the production of solid water-soluble salts of phosphoric acid amidesInfo
- Publication number
- DE904286C DE904286C DEF8340A DEF0008340A DE904286C DE 904286 C DE904286 C DE 904286C DE F8340 A DEF8340 A DE F8340A DE F0008340 A DEF0008340 A DE F0008340A DE 904286 C DE904286 C DE 904286C
- Authority
- DE
- Germany
- Prior art keywords
- phosphoric acid
- soluble salts
- acid amides
- acid
- production
- 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
Links
- 150000003839 salts Chemical class 0.000 title claims description 10
- 239000007787 solid Substances 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 3
- 150000003012 phosphoric acid amides Chemical class 0.000 title claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- 239000002253 acid Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- -1 butylammonium - N - p - chlorophenyldiamidophosphate Chemical compound 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/222—Amides of phosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von festen wasserlöslichen Salzen von Phosphorsäureainiden Das p-Chloranilin-N-phosphinsäureamid (N-p-Chlorphenyldiamidophosphorsäure) wird nach Gomori (Proc. Soc. Exp. Biol. Med. 1948, Bd.69, S. 407) als Reagens für den Nachweis von Phosphoramidasen zui Krebsdiagnose verwendet. Zu diesem Zweck ist es nötig, die Substanz in überschüssiger Ammoniaklösung zu lösen und mit Essigsäure zu neutralisieren. Diese Stammlösung kann dann im Eisschrank kurze Zeit aufbewahrt werden, nach Gomori einige Wochen, nach E b n e r und S t r e c k e r (D. M. W. 1951, Nr. 41, S. 12,68) nur einige Tage.Process for the preparation of solid water-soluble salts of phosphoric acid amides The p-chloroaniline-N-phosphinic acid amide (Np-chlorophenyldiamidophosphoric acid) is used according to Gomori (Proc. Soc. Exp. Biol. Med. 1948, Vol. 69, p. 407) as a reagent for the detection of phosphoramidases for cancer diagnosis. For this purpose, it is necessary to dissolve the substance in excess ammonia solution and neutralize it with acetic acid. This stock solution can then be stored in the refrigerator for a short time, according to Gomori a few weeks, according to Ebner and S trecker (DMW 1951, No. 41, p. 12, 68) only a few days.
Es wurde nun gefunden, daß sich feste Salze der obigen Verbindung mit Ammoniak, primären und sekundären Aminen, auch mit Alkalien herstellen lassen. Überraschenderweise stößt die Isolierung und Aufbewahrung der Salze der empfindlichen Amidosäuren, die in isoliertem Zustand bisher nicht bekannt waren, auf keine besonderen Schwierigkeiten. Sie können mit Vorteil an Stelle der freien Verbindung für die Ausführung der Krebsdiagnose verwendet werden, da die umständliche Herstellung der wenig haltbaren Lösung nach der oben angegebenen Vorschrift fortfällt. Außerdem können sie direkt oder als Zwischenprodukte therapeutisch verwendet werden. Die Herstellung der festen Salze erfolgt in der Weise, daß man eine Lösung oder Suspension von N-p-Chloranilin-N-phosphinsäureamid in einem wasserfreien oder wasserarmen Lösungsmittel mit Ammoniak, einem primären oder sekundären Amin oder Alkalien bzw. Alkalicarbonaten behandelt und das, gegebenenfalls nach Einengen, abgeschiedene oder durch eine organische Fällflüssigkeit ausgefällte Salz isoliert.It has now been found that solid salts of the above compound with ammonia, primary and secondary amines, also with alkalis. Surprisingly, the isolation and preservation of the salts encounters the sensitive Amido acids, which were previously not known in their isolated state, were not identified in any particular way Trouble. You can take advantage of the free connection for the Execution of cancer diagnosis can be used because of the cumbersome preparation of the no longer stable solution according to the instructions given above. aside from that they can be used therapeutically directly or as intermediates. the The solid salts are prepared in such a way that a solution or suspension is obtained of N-p-chloroaniline-N-phosphinamide in an anhydrous or low-water solvent with ammonia, a primary or secondary amine or alkalis or alkali carbonates treated and that, optionally after concentration, deposited or by an organic Precipitating liquid precipitated salt isolated.
In gleicher Weise können auch die Amide anderer Substitutionsprodukte der Anilin-N-phosphinsäure, wie der p-Toluidin-N-phosphinsäure, p- Jodanüin-N-phosphinsäure und der Anilin-N-phosphinsäure selbst, in lösliche Salze verwandelt werden.The amides of other substitution products can also be used in the same way of aniline-N-phosphinic acid, such as p-toluidine-N-phosphinic acid, p-iodine-N-phosphinic acid and the aniline-N-phosphinic acid itself, can be converted into soluble salts.
Beispiel 1 165 g N-p-Chlorphenyldiamidophosphorsäure (J.Am. Chem. SOC. 1949, 71. 3561) werden in 5oo ccm g5°/oigem Alkohol suspendiert. Unter Rühren leitet man bis zur Sättigung unter Kühlung einen kräftigen, dann noch 3 Stunden einen schwachen Ammoniakstrom ein. Man läßt über Nacht stehen, trennt das abgeschiedene Salz durch Absaugen von der Mutterlauge, wäscht mit 95o/oigem Alkohol nach und trocknet im Vakuum. Man erhält das gebildete Ammonium-N-p-chlorphenyldiamidophosphat in einer Ausbeute von 162 g als farbloses, kristallinisches Pulver vom F. 164 bis 165° (unter Zersetzung). Es hat nach der Analyse die Zusammensetzung Es löst sich leicht in Wasser zu neutraler Lösung auf. Versetzt man die Lösung unter Kühlung mit verdünnter Salzsäure, so fällt das Ausgangsmaterial vom F. 156° aus.Example 1 165 g of Np-chlorophenyldiamidophosphoric acid (J.Am. Chem. SOC. 1949, 71, 3561) are suspended in 500 ccm of 5% alcohol. While stirring, a vigorous stream of ammonia is passed in until it is saturated, followed by a gentle stream of ammonia for 3 hours. The mixture is left to stand overnight, the precipitated salt is separated from the mother liquor by suction, washed with 95% alcohol and dried in vacuo. The ammonium Np-chlorophenyldiamidophosphate formed is obtained in a yield of 162 g as a colorless, crystalline powder with a melting point of 164 ° to 165 ° (with decomposition). According to the analysis, it has the composition It easily dissolves in water to form a neutral solution. If the solution is mixed with dilute hydrochloric acid while cooling, the starting material precipitates with a melting point of 156 °.
Beispiel 2 41,2 g N-p-Chlorphenyldiamidophosphorsäure werden in 15o ccm gg°/oigem Alkohol gerührt. Unter Kühlen werden bei io° 2o ccm Butylamin langsam eingegeben. Dann rührt man io Stunden bei 2o°, saugt ab und erhält nach Trocknen im Vakuum das Butylammonium - N - p - chlorphenyldiamidophosphat als wasserlösliches farbloses kristallinisches Pulver vom F. 145 bis 146° (unter Zersetzung). Die Zusammensetzung ist Beispiel 3 Unter Kühlen im Eisbad und Rühren versetzt man die Suspension von 41,2 g N-p-Chlorphenyldiamidophosphorsäure in ioo ccm ggo/oigem Alkohol langsam mit 2o,5 ccm Diäthylanvn. Dann rührt man noch i Stunde bei Zimmertemperatur, filtriert die nun klare Lösung und fällt mit Zoo ccm Aceton. Nach Trocknen im Vakuum erhält man das Diäthylammonium-N-p-chlorphenyldian-lidophosphat als farbloses kristallinisches Pulver, das sich, in Wasser löst, vom F. z22 bis z23°. Die Zusammensetzung ist Beispiel 4 Man bereitet eine äthanolische Kalilauge, von der 5 ccm 15,6 ccm 1-n - HCl verbrauchen. Davon rührt man unter Kühlen 64 ccm in die Suspension von 41,2 g N-p-Chlorphenyldiamidophosphorsäure in 5o ccm ggo/oigem Alkohol ein, filtriert die fast klare Lösung und kühlt sie über Nacht auf - 6°. Man erhält das Kalium-N-p-chlorphenyldiamidophosphat als eine in farblosen Blättchen kristallisierte Substanz, die bei 25o° noch nicht schmilzt. Die Zusammensetzung ist Beispiel 5 48gN-Phenyldiamidophosphorsäure (J. Chem. Soc.Example 2 41.2 g of Np-chlorophenyldiamidophosphoric acid are stirred in 150 cc.% Alcohol. While cooling, 20 cc of butylamine are slowly added at 10 °. The mixture is then stirred for 10 hours at 20 °, filtered off with suction and, after drying in vacuo, the butylammonium - N - p - chlorophenyldiamidophosphate is obtained as a water-soluble, colorless crystalline powder with a melting point of 145 ° to 146 ° (with decomposition). The composition is EXAMPLE 3 While cooling in an ice bath and stirring, the suspension of 41.2 g of Np-chlorophenyldiamidophosphoric acid in 100 cc of g / o alcohol is slowly mixed with 20.5 cc of diethylanvn. The mixture is then stirred for another hour at room temperature, the now clear solution is filtered and precipitated with zoo cc of acetone. After drying in vacuo, the diethylammonium Np-chlorophenyldianlidophosphate is obtained as a colorless crystalline powder which dissolves in water, from a temperature of 22 to 23 °. The composition is Example 4 An ethanolic potassium hydroxide solution is prepared, 5 cc of which consume 15.6 cc of 1-n-HCl. 64 cc of this is stirred with cooling into the suspension of 41.2 g of Np-chlorophenyldiamidophosphoric acid in 50 cc of g / o alcohol, the almost clear solution is filtered and cooled to -6 ° overnight. The potassium Np-chlorophenyldiamidophosphate is obtained as a substance which has crystallized in colorless flakes and does not yet melt at 250 °. The composition is Example 5 48gN-phenyldiamidophosphoric acid (J. Chem. Soc.
81, 1367 (igo2) werden unter Eiskühlung in ioo ccm ggo/oigem Alkohol gerührt, wobei man einen kräftigen Ammoniakstrom einleitet. Nach 8 Stunden saugt man das nun wasserlösliche Produkt ab und erhält nach Trocknen im Vakuum das Ammonium-N-phenyldiamidophosphat als ein farbloses kristallinisches Pulver vom F. 149° (unter Zersetzung). Die Zusammensetzung ist Beispiel 6 5o g N-p-Jodphenyldiamidophosphorsäure in Zoo ccm 99o/oigem Alkohol werden wie in Beispiel 4 mit Ammoniak behandelt, wobei man eine klare Lösung erhält. Nach Filtrieren läßt man über Nacht bei - 6° stehen, saugt von den ausgeschiedenen Kristallen ab und fällt mit Zoo ccm Aceton. Man erhält nach Trocknen im Vakuum eine farblose feinkristallinische Substanz vom F. 154 bis z55°, die sich in Wasser klar löst. Die Zusammensetzung ist Die Darstellung der in diesem Beispiel verwendeten N-p- Jodphenyldiamidophosphorsäure gelingt auf demselben Wege wie die der N-p-Chlorphenyldiamidophosphorsäure (J. Am. Chem. Soc. 71, 3561, (z949) aus p- Jodanilinchlorhydrat über das N-p- Jodphenylamidophosphorsäuredichlorid.81, 1367 (igo2) are stirred in 100 cc of g / o strength alcohol with ice cooling, a vigorous stream of ammonia being introduced. After 8 hours, the now water-soluble product is filtered off with suction and, after drying in vacuo, the ammonium N-phenyldiamidophosphate is obtained as a colorless crystalline powder with a melting point of 149 ° (with decomposition). The composition is Example 6 50 g of Np-iodophenyldiamidophosphoric acid in zoo cc of 99% alcohol are treated with ammonia as in Example 4, a clear solution being obtained. After filtering, the mixture is left to stand at -6 ° overnight, the crystals which have separated out are suctioned off and precipitated with zoo cc of acetone. After drying in vacuo, a colorless, finely crystalline substance with a melting point of 154 to z55 ° is obtained, which dissolves to give a clear solution in water. The composition is The preparation of the Np-iodophenyldiamidophosphoric acid used in this example succeeds in the same way as that of the Np-chlorophenyldiamidophosphoric acid (J. Am. Chem. Soc. 71, 3561, (z949) from p-iodoaniline chlorohydrate via the Np-iodophenylamidophosphoric acid dichloride.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF8340A DE904286C (en) | 1952-02-14 | 1952-02-14 | Process for the production of solid water-soluble salts of phosphoric acid amides |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF8340A DE904286C (en) | 1952-02-14 | 1952-02-14 | Process for the production of solid water-soluble salts of phosphoric acid amides |
Publications (1)
Publication Number | Publication Date |
---|---|
DE904286C true DE904286C (en) | 1954-02-18 |
Family
ID=7085803
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DEF8340A Expired DE904286C (en) | 1952-02-14 | 1952-02-14 | Process for the production of solid water-soluble salts of phosphoric acid amides |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE904286C (en) |
-
1952
- 1952-02-14 DE DEF8340A patent/DE904286C/en not_active Expired
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