CH343402A - Process for the production of new quinones - Google Patents
Process for the production of new quinonesInfo
- Publication number
- CH343402A CH343402A CH343402DA CH343402A CH 343402 A CH343402 A CH 343402A CH 343402D A CH343402D A CH 343402DA CH 343402 A CH343402 A CH 343402A
- Authority
- CH
- Switzerland
- Prior art keywords
- bis
- acylamino
- benzoquinone
- benzoquinones
- dichloro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 150000004053 quinones Chemical class 0.000 title claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- -1 alkyl radical Chemical class 0.000 claims description 3
- 229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- KKSCCSVQHNQDBX-UHFFFAOYSA-N n-[2,5-dichloro-3,6-dioxo-4-(propanoylamino)cyclohexa-1,4-dien-1-yl]propanamide Chemical compound CCC(=O)NC1=C(Cl)C(=O)C(NC(=O)CC)=C(Cl)C1=O KKSCCSVQHNQDBX-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QLHPOTDBWHTTBM-UHFFFAOYSA-N 2,5-diamino-3,6-dichlorocyclohexa-2,5-diene-1,4-dione Chemical compound NC1=C(Cl)C(=O)C(N)=C(Cl)C1=O QLHPOTDBWHTTBM-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- RCDDYOVHUCQAMN-UHFFFAOYSA-N N-[4-(butanoylamino)-2,5-dichloro-3,6-dioxocyclohexa-1,4-dien-1-yl]butanamide Chemical compound ClC=1C(C(=C(C(C1NC(CCC)=O)=O)Cl)NC(CCC)=O)=O RCDDYOVHUCQAMN-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000224432 Entamoeba histolytica Species 0.000 description 1
- 241000224421 Heterolobosea Species 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 210000003001 amoeba Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 150000004054 benzoquinones Chemical class 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940007078 entamoeba histolytica Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
- C07D203/14—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom with carbocyclic rings directly attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Description
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Verfahren zur Herstellung neuer Chinone Gegenstand der vorliegenden Erfindung ist ein Verfahren zur Herstellung von 2,5-Bis-äthylenimino- 3,6-bis-acylamino-p-benzochinonen, worin die Acyl- aminogruppe diejenige einer mindestens drei Kohlenstoffatome enthaltenden aliphatischen Canbonsäure, wie zum Beispiel Propion- oder Buttersäure, ist.
Die neuen Benzochinone sind gegen Amöben, wie zum Beispiel gegen Entamoeba histolytica, sowie gegen Bakterien wirksam; zudem zeigen sie eine ausgeprägte tumorhemmende Wirkung.
Die neuen Verbindungen werden hergestellt, indem man 2,5-Dihalogen-3,6-bis-acylamino-p-benzo- chinone, worin die Acylaminogruppe diejenige einer mindestens drei Kohlenstoffatome enthaltenden ali- phatischen Carbonsäure ist, mit Äthyleniminen zu 2,5 - Bis - äthylenimino- 3 , 6 -bis - acylamino -p-benzo- chinonen umsetzt.
Besonders geeignet zu dieser Umsetzung sind die 2,5-Dichlor- und 2,5-Dibrom-3,6- bis-acylamino-p-benzochinone. Neben dem unsubsti- tuierten Äthylenimin können auch C-alkylierte Äthy- lenimine, wie zum Beispiel das C-Methyl-äthylen- imin, verwendet werden.
Vorzugsweise arbeitet man in Lösungsmitteln, wie zum Beispiel Dioxan, Äthyl-, Isopropyl- oder Butyl- alkohol, Isopropyläther und dergleichen und gegebenenfalls in Gegenwart von Kondensationsmitteln, wie zum Beispiel tert. Basen. Dabei kann die Reaktion bei Zimmertemperatur oder bei erhöhter Temperatur durchgeführt werden.
Die Ausgangsstoffe sind bekannt oder können in an sich bekannter Weise hergestellt werden.
Die verfahrensgemäss hergestellten Chinone können als Bakterizide sowie als Heilmittel besonders bei Krebserkrankungen oder durch Amöben verursachte Erkrankungen, zum Beispiel in Form pharmazeutischer Präparate, Verwendung finden. In den nachfolgenden Beispielen sind die Temperaturen in Celsiusgraden angegeben.
Beispiel 1 31,92 g 2,5-Dichlor-3,6-bis-propionylamino-p- benzochinon werden in 340 cm3 Dioxan suspendiert, und unter gutem Rühren wird bei Zimmertemperatur ein Gemisch von 16,9 cm3 Äthylenimin und 22,25 g Triäthylamin in 65 cm?, Dioxan innert 15 bis 20 Minuten zugetropft. Die Temperatur steigt allmählich auf 40 und wird nach dem Abklingen der leicht exothermen Reaktion weitere 7 Stunden auf 45 gehalten. Die gelben Kristalle des Bis-propionylamino- dichlorchinons sind nach dieser Zeit verschwunden, und an ihrer Stelle ist ein Brei von roten Kristallen entstanden.
Diese werden abgesaugt, mit Dioxan gewaschen und in 150 cm3 Wasser suspendiert, um das entstandene Triäthylamin-hydrochlorid abzutrennen. Die suspendierten Kristalle werden wieder durch Absaugen isoliert und mit Äthanol gewaschen. Das so erhaltene 2,5-Bis-äthylenimino-3,6-bis-propionyl- amino-p-benzochinon der Formel
EMI1.64
schmilzt bei 213 unter rascher Zersetzung.
Das als Ausgangsstoff verwendete 2,5-Dichlor- 3,6=bis-propionylamino-p-benzochinon kann wie folgt erhalten werden: 62,1 g 2,5-Dichlor-3,6-diamino-p-benzochinon werden in 260 crn3 Propionsäureanhydrid suspendiert
<Desc/Clms Page number 2>
und tropfenweise mit 1,75 cm3 konzentrierter Schwefelsäure versetzt. Die Temperatur steigt um etwa 5 bis 10 an. Anschliessend rührt man 5 Stunden im Wasserbad von 45 und lässt über Nacht stehen. Unter Eiskühlung werden langsam 200 cm3 Äthanol zugegeben und das entstandene, gelbe Kristallisat abgesaugt, gründlich mit Äthanol gewaschen und aus Eisessig umkristallisiert.
Man erhält gelbe Nadeln des 2,5-Dichlor-3,6-bis-propionylamino - p - benzochinons vom F. 253 (Zers.).
Beispiel 2 .
31,25 g 2,5-Dichlor-3,6-bis-butyrylamino-p- benzochinon werden in 300 cm33 Dioxan suspendiert, und bei Zimmertemperatur wird ein Gemisch von 15,3 cm?- Äthylenimin und 20,33 g Triäthylamin in 60 cm3 Dioxan unter Rühren in 20 Minuten zugetropft. Die Temperatur steigt von selbst auf 35 . Anschliessend wird unter Erwärmen auf 45 noch 7 Stunden weitergerührt. Aufgearbeitet wird wie in Beispiel 1. Man gewinnt so rote Kristalle des 2,5-Bis- äthylenimino - 3,6 -bis-butyrylamind-p-benzochinons der Formel
EMI2.18
vom F. 214 (Zers.).
Das als Ausgangsstoff verwendete, ockergelbe Kristalle vom F. 251 bis 252 bildende 2,5-Dichlor- 3,6-bis-butyrylamino-p-benzochinon kann erhalten werden durch Umsetzung von 2,5-,Dichlor-3,6-di- amino-p-benzochinon mit Buttersäureanhydrid, analog wie im Beispiel 1 beschrieben.
Beispiel 3 Zu einer Suspension von 15,96 g des nach der in Beispiel 1 erwähnten Weise erhältlichen 2,5-Dichlor- 3,6-bis-propionylamino-p-benzochinons in 200 cms Dioxan wird ein Gemisch von 11,65 cm3 C-Methyl- äthylenimin und 12,65 g Triäthylamin in 35 cm 3 Dioxan zugetropft. Die Temperatur steigt allmählich auf 35 und wird dann mit einem Wasserbad 9 Stunden bei 45 gehalten. Man arbeitet auf wie in den Beispielen 1 und 2 beschrieben und erhält so hellrote Kristalle des 2,5-Bis-(methyl-äthylenimino)-3,6-bis- propionylamino-p-benzochinons der Formel
EMI2.37
vom F. 209 .
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Process for the preparation of new quinones The present invention relates to a process for the preparation of 2,5-bis-ethyleneimino-3,6-bis-acylamino-p-benzoquinones, wherein the acylamino group is that of an aliphatic canboxylic acid containing at least three carbon atoms, such as for example propionic or butyric acid.
The new benzoquinones are effective against amoebas, for example against Entamoeba histolytica, as well as against bacteria; they also show a pronounced tumor-inhibiting effect.
The new compounds are prepared by 2,5-dihalo-3,6-bis-acylamino-p-benzoquinones, in which the acylamino group is that of an aliphatic carboxylic acid containing at least three carbon atoms, with ethyleneimines to give 2.5 - Bis - ethylenimino 3, 6 -bis - acylamino-p-benzoquinones.
The 2,5-dichloro- and 2,5-dibromo-3,6-bis-acylamino-p-benzoquinones are particularly suitable for this reaction. In addition to the unsubstituted ethyleneimine, C-alkylated ethyleneimines, such as C-methylethyleneimine, can also be used.
It is preferable to work in solvents, such as, for example, dioxane, ethyl, isopropyl or butyl alcohol, isopropyl ether and the like, and optionally in the presence of condensing agents, such as tert. Bases. The reaction can be carried out at room temperature or at an elevated temperature.
The starting materials are known or can be prepared in a manner known per se.
The quinones produced according to the process can be used as bactericides and as remedies, particularly in the case of cancer or diseases caused by amoebae, for example in the form of pharmaceutical preparations. In the following examples, the temperatures are given in degrees Celsius.
Example 1 31.92 g of 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone are suspended in 340 cm3 of dioxane, and a mixture of 16.9 cm3 of ethyleneimine and 22.25 g is obtained at room temperature with thorough stirring Triethylamine in 65 cm ?, dioxane was added dropwise within 15 to 20 minutes. The temperature gradually rises to 40 and is held at 45 for a further 7 hours after the slightly exothermic reaction has subsided. The yellow crystals of bis-propionylamino-dichloroquinone have disappeared after this time, and a paste of red crystals has formed in their place.
These are filtered off with suction, washed with dioxane and suspended in 150 cm3 of water in order to separate off the triethylamine hydrochloride formed. The suspended crystals are isolated again by suction and washed with ethanol. The 2,5-bis-ethylenimino-3,6-bis-propionyl-amino-p-benzoquinone of the formula obtained in this way
EMI1.64
melts at 213 with rapid decomposition.
The 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone used as starting material can be obtained as follows: 62.1 g of 2,5-dichloro-3,6-diamino-p-benzoquinone are in 260 cm3 Propionic anhydride suspended
<Desc / Clms Page number 2>
and 1.75 cm3 of concentrated sulfuric acid are added dropwise. The temperature rises by about 5 to 10. The mixture is then stirred for 5 hours in a 45 water bath and left to stand overnight. While cooling with ice, 200 cm3 of ethanol are slowly added and the yellow crystals formed are filtered off with suction, washed thoroughly with ethanol and recrystallized from glacial acetic acid.
Yellow needles of 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone of F. 253 (decomp.) Are obtained.
Example 2.
31.25 g of 2,5-dichloro-3,6-bis-butyrylamino-p-benzoquinone are suspended in 300 cm33 of dioxane, and at room temperature a mixture of 15.3 cm? - ethylene imine and 20.33 g of triethylamine in 60 cm3 of dioxane was added dropwise with stirring in 20 minutes. The temperature rises to 35 by itself. The mixture is then stirred for a further 7 hours with heating to 45. Work-up is carried out as in Example 1. Red crystals of 2,5-bis-ethyleneimino-3,6-bis-butyrylamine-p-benzoquinone of the formula are obtained in this way
EMI2.18
from F. 214 (decomp.).
The ocher yellow crystals used as the starting material with a temperature of 251 to 252 forming 2,5-dichloro-3,6-bis-butyrylamino-p-benzoquinone can be obtained by reacting 2,5-, dichloro-3,6-di- amino-p-benzoquinone with butyric anhydride as described in Example 1.
Example 3 To a suspension of 15.96 g of the 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone obtainable in the manner mentioned in Example 1 in 200 cms of dioxane, a mixture of 11.65 cm3 of C- Methyl ethylene imine and 12.65 g of triethylamine in 35 cm 3 of dioxane were added dropwise. The temperature gradually rises to 35 and is then held at 45 for 9 hours with a water bath. The procedure is as described in Examples 1 and 2, and light red crystals of 2,5-bis (methyl-ethyleneimino) -3,6-bis-propionylamino-p-benzoquinone of the formula are obtained
EMI2.37
from F. 209.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH343402T | 1956-08-27 | ||
| CH338193T | 1959-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH343402A true CH343402A (en) | 1959-12-31 |
Family
ID=25736819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH343402D CH343402A (en) | 1956-08-27 | 1956-08-27 | Process for the production of new quinones |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH343402A (en) |
-
1956
- 1956-08-27 CH CH343402D patent/CH343402A/en unknown
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