DE546144C - Process for the preparation of derivatives of 5, 5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine which are readily soluble in water - Google Patents
Process for the preparation of derivatives of 5, 5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine which are readily soluble in waterInfo
- Publication number
- DE546144C DE546144C DESCH90001D DESC090001D DE546144C DE 546144 C DE546144 C DE 546144C DE SCH90001 D DESCH90001 D DE SCH90001D DE SC090001 D DESC090001 D DE SC090001D DE 546144 C DE546144 C DE 546144C
- Authority
- DE
- Germany
- Prior art keywords
- water
- arsenopyridine
- dioxy
- diamino
- preparation
- 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
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 6
- -1 salts sodium formaldehyde sulfoxylate Chemical class 0.000 claims description 2
- 101100119767 Caenorhabditis elegans fat-4 gene Proteins 0.000 claims 1
- 101100468762 Caenorhabditis elegans ric-3 gene Proteins 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- HRKQOINLCJTGBK-UHFFFAOYSA-N dihydroxidosulfur Chemical class OSO HRKQOINLCJTGBK-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- HRKQOINLCJTGBK-UHFFFAOYSA-L dioxidosulfate(2-) Chemical compound [O-]S[O-] HRKQOINLCJTGBK-UHFFFAOYSA-L 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001495 arsenic compounds Chemical class 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 229940017705 formaldehyde sulfoxylate Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- SBGKURINHGJRFN-UHFFFAOYSA-N hydroxymethanesulfinic acid Chemical compound OCS(O)=O SBGKURINHGJRFN-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure 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
- C07F9/66—Arsenic compounds
- C07F9/70—Organo-arsenic compounds
- C07F9/80—Heterocyclic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Compounds Of Heavy Metals (AREA)
Description
Verfahren zur Darstellung von in Wasser leicht löslichen Derivaten des 5, 5'-Diamino-6, 6'-dioxy-3, 3'-arsenopyridins Das durch die nachstehende Formel versinnbildlichte 5, 5' - Diamino - 6, 6' - dioxy-3, 3'-arsenopyridin, das aus der z-OYy-3-aminopyridin-5-arsinsäure durch Reduktion mit unterphosphoriger Säure erhalten werden kann, besitzt den Nachteil, daß es nur in Form seines alkalisch reagierenden Natriumsalzes in injektionsfähige Form gebracht werden kann. Es wurde nun gefunden, daß sich dieseVerbindung in leichterZVeise mit Sulfoxylaten, wie z. B. Formaldehydsulfoxylat, umsetzt unter Bildung der entsprechenden Kondensationsprodukte,- die sich leicht mit neutraler Reaktion in Wasser lösen. Beim Arbeiten in sauren Medien bilden sich die entsprechenden Sulfoxylsäuren, die sich dann z. B. durch Behandeln mit Natriumcarbonat in die leicht löslichen Sulfoxylate verwandeln lassen.Process for the preparation of readily water-soluble derivatives of 5,5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine that by the following formula Symbolized 5, 5 '- diamino - 6, 6' - dioxy-3, 3'-arsenopyridine, which can be obtained from z-OYy-3-aminopyridine-5-arsinic acid by reduction with hypophosphorous acid, has the disadvantage that it can only be brought into injectable form in the form of its alkaline sodium salt. It has now been found that this compound reacts easily with sulfoxylates such as e.g. B. formaldehyde sulfoxylate, converts to form the corresponding condensation products - which easily dissolve in water with a neutral reaction. When working in acidic media, the corresponding sulfoxylic acids are formed. B. can be transformed into the easily soluble sulfoxylates by treating with sodium carbonate.
Der glatte Verlauf der Umsetzung war nicht vorauszusehen. Denn es hat sich z. B. gezeigt, daß die in a- bzw. 4-Stellung befindlichen Aminogruppen des Pyridins solchen Urnsetzungen überhaupt nicht zugänglich sind. In dem vorliegenden Falle war die oben beschriebene Reaktion aber auch für die in der 3- bzw. 5-Stellung befindliche Aminogruppe durchaus nicht als selbstverständlich vorauszusehen. Und zwar deshalb, weil die Ausgangsverbindung sich überraschenderweise trotz der in, der 3- bzw. 5-Stellung befindlichen Aminogruppe weder in wässeriger noch in alkoholischer Salzsäure löst, eine Eigenschaft, die aber sonst allen Aminen zu eigen ist, die mit Sulfoxylaten Kondensationen einzugehen imstande sind.The smooth course of implementation could not be foreseen. For it has z. B. shown that the amino groups in a- or 4-position of pyridine are not at all accessible to such reactions. In the present The reaction described above was also a trap for those in the 3- or 5-position Amino group located in this way cannot be foreseen as a matter of course. and because the starting compound surprisingly turns out to be in spite of the the 3- or 5-position located amino group neither in aqueous nor in alcoholic Hydrochloric acid dissolves, a property that is otherwise common to all amines are able to enter into condensation with sulfoxylates.
Ganz überraschend erfolgt nun die Kondensation nicht etwa erst unter besonders scharfen Bedingungen wie z. B. bei besonders hoher Temperatur, sondern im Gegenteil außerordentlich leicht.Quite surprisingly, the condensation does not take place just below particularly severe conditions such as B. at a particularly high temperature, but on the contrary, extremely easy.
Es erfolgt so z. B. die Kondensation des Sulfoxylates mit der freien Base bereits durch einfaches Aufeinanderwirken der beiden Komponenten bei gewöhnlicher Temperatur in quantitativer Ausbeute.It takes place so z. B. the condensation of the sulfoxylate with the free Base by simply interacting the two components with ordinary Temperature in quantitative yield.
Die Kondensation erfolgt je nach der Menge des angewandten Sulfoxylates unter Eintritt von einem oder mehreren Sulfoxylsäureestern.The condensation takes place depending on the amount of sulfoxylate used with entry of one or more sulfoxylic acid esters.
Die so erhaltene Sulfoxylverbindung zeigt neben einer ausgezeichneten therapeutischen Wirkung eine sehr hohe Verträglichkeit.The sulfoxyl compound thus obtained shows an excellent one besides therapeutic effect a very high tolerance.
So werden von mitTrypanosomen (Naganastamm Prowaczek) infizierten Mäusen o,8 mg/g Maus vertragen, wobei o,o5 mg Heilung bewirken. Der therapeutische Index beträgt somit i : 16, während die entsprechende Verbindung der Benzolreihe nach K o 11 e - Z i e 1 e r, Handbuch der Salvarsäntherapie 1924, Bd. i, S. 192, Tabelle IV, einen Index i : 9 besitzt. Beispiel i 3=7 g 5, 5'-Diamino-6, 6'-dioxy-3, 3'-arsenopyridin werden mit einer Lösung von 3,8 g Natriumformaldehydsulfoxylat in 2o ccm Wasser mehrere Stunden lang verrührt, wobei eine klare gelbe Gallerte entsteht, die durch ihre saure Reaktion in Wasser gekennzeichnet ist. Die Umsetzung kann auch durch Erwärmen auf etwa 8o° beschleunigt werden. Nachdem der gesamte Ausgangsstoff sich in eine klare Gallerte verwandelt hat, wird mit 4o ccm Wasser und 4 ccm fünffach normaler Natronlauge oder mit der entsprechenden Menge Natriumcarbonat aufgenommen. Man fällt die klare dunkelgelbe Lösung durch Eingießen in 5oo ccm Methanol. Die Verbindung ist hellgelb und löst sich leicht mit neutraler Reaktion in Wasser. Die Lösung hält sich längere Zeit an der Luft ohne. sichtbare Veränderung. Mit verdünnter Salzsäure entsteht kein Niederschlag.They are infected with trypanosomes (Nagana strain Prowaczek) Mice 0.8 mg / g mouse tolerated, with 0.05 mg causing healing. The therapeutic index is thus i: 16, while the corresponding compound the benzene series according to K o 11 e - Z i e 1 e r, manual of salvarsant therapy 1924, Vol. I, p. 192, Table IV, has an index i: 9. Example i 3 = 7 g of 5,5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine are mixed with a solution of 3.8 g of sodium formaldehyde sulfoxylate Stirred in 20 cc of water for several hours, with a clear yellow jelly which is characterized by its acidic reaction in water. The implementation can also be accelerated to about 80 ° by heating. After all of the raw material has turned into a clear jelly, becomes fivefold with 4o cc of water and 4 cc normal sodium hydroxide solution or with the corresponding amount of sodium carbonate. The clear, dark yellow solution is precipitated by pouring into 500 cc of methanol. the Compound is light yellow and easily dissolves in water with a neutral reaction. the Solution stays in the air for a long time without. visible change. With diluted Hydrochloric acid does not form a precipitate.
Beispiel e Die unter i genannte Arsenoverbindung wird mit etwa der fünffachen Menge von 40 %iger methylalkoholischer Salzsäure 2 Stunden geschüttelt. Das entstandene Hydrochlorid wird wie bei i mit Natriumformaldehydsulfoxylat umgesetzt und entsprechend der dort gegebenen Vorschrift weiter aufgearbeitet.Example e The arsenic compound mentioned under i is used with approximately the Shaken five times the amount of 40% methyl alcoholic hydrochloric acid for 2 hours. The hydrochloride formed is reacted with sodium formaldehyde sulfoxylate as in i and further processed according to the regulation given there.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DESCH90001D DE546144C (en) | 1929-04-13 | 1929-04-13 | Process for the preparation of derivatives of 5, 5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine which are readily soluble in water |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DESCH90001D DE546144C (en) | 1929-04-13 | 1929-04-13 | Process for the preparation of derivatives of 5, 5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine which are readily soluble in water |
Publications (1)
Publication Number | Publication Date |
---|---|
DE546144C true DE546144C (en) | 1932-03-10 |
Family
ID=7444289
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DESCH90001D Expired DE546144C (en) | 1929-04-13 | 1929-04-13 | Process for the preparation of derivatives of 5, 5'-diamino-6, 6'-dioxy-3, 3'-arsenopyridine which are readily soluble in water |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE546144C (en) |
-
1929
- 1929-04-13 DE DESCH90001D patent/DE546144C/en not_active Expired
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