CH556811A - N-aryl-1,3-dioxo-cyclohexane-carboxamides - and thio analogues, with antibacterial and antimycotic activity - Google Patents
N-aryl-1,3-dioxo-cyclohexane-carboxamides - and thio analogues, with antibacterial and antimycotic activityInfo
- Publication number
- CH556811A CH556811A CH1762371A CH1762371A CH556811A CH 556811 A CH556811 A CH 556811A CH 1762371 A CH1762371 A CH 1762371A CH 1762371 A CH1762371 A CH 1762371A CH 556811 A CH556811 A CH 556811A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- carbamoylcyclohexanedione
- isocyanate
- sodium
- antibacterial
- Prior art date
Links
- 230000001857 anti-mycotic effect Effects 0.000 title abstract description 3
- 230000000844 anti-bacterial effect Effects 0.000 title abstract 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 125000001624 naphthyl group Chemical group 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- -1 tetrahydrofuran Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- FYWJWWMKCARWQG-UHFFFAOYSA-N 1,2-dichloro-3-isocyanatobenzene Chemical compound ClC1=CC=CC(N=C=O)=C1Cl FYWJWWMKCARWQG-UHFFFAOYSA-N 0.000 description 1
- PEQMJVGRHNZPAM-UHFFFAOYSA-N 1,4-dichloro-2-isocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=O)=C1 PEQMJVGRHNZPAM-UHFFFAOYSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- MOZSVHZOUDIZMF-UHFFFAOYSA-N 1-(4-isocyanatophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N=C=O)C=C1 MOZSVHZOUDIZMF-UHFFFAOYSA-N 0.000 description 1
- CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
- HHIRBXHEYVDUAM-UHFFFAOYSA-N 1-chloro-3-isocyanatobenzene Chemical compound ClC1=CC=CC(N=C=O)=C1 HHIRBXHEYVDUAM-UHFFFAOYSA-N 0.000 description 1
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
- DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 description 1
- NFIUJHJMCQQYDL-UHFFFAOYSA-N 1-fluoro-4-isothiocyanatobenzene Chemical compound FC1=CC=C(N=C=S)C=C1 NFIUJHJMCQQYDL-UHFFFAOYSA-N 0.000 description 1
- JRVZITODZAQRQM-UHFFFAOYSA-N 1-isocyanato-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1N=C=O JRVZITODZAQRQM-UHFFFAOYSA-N 0.000 description 1
- CPPGZWWUPFWALU-UHFFFAOYSA-N 1-isocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=O)=C1 CPPGZWWUPFWALU-UHFFFAOYSA-N 0.000 description 1
- RTXDHIPQKZLDJD-UHFFFAOYSA-N 1-isocyanato-4-methyl-2-nitrobenzene Chemical compound CC1=CC=C(N=C=O)C([N+]([O-])=O)=C1 RTXDHIPQKZLDJD-UHFFFAOYSA-N 0.000 description 1
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 1
- OLBJNSPBWLCTOT-UHFFFAOYSA-N 2,4-dichloro-1-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C(Cl)=C1 OLBJNSPBWLCTOT-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- UKTKKMZDESVUEE-UHFFFAOYSA-N 2-chloro-4-isocyanato-1-methylbenzene Chemical compound CC1=CC=C(N=C=O)C=C1Cl UKTKKMZDESVUEE-UHFFFAOYSA-N 0.000 description 1
- MFUVCHZWGSJKEQ-UHFFFAOYSA-N 3,4-dichlorphenylisocyanate Chemical compound ClC1=CC=C(N=C=O)C=C1Cl MFUVCHZWGSJKEQ-UHFFFAOYSA-N 0.000 description 1
- MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical compound CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
1, 3-Diketones of formula (I) are new: where X is O or S; A is naphthyl, or phenyl opt. mono- or di-substd. by Cl, Br, I, F, lower alkyl, NO2, acetyl, N(R)2, COOR and/or OR; R is lower alkyl. (I) have antibacterial activity (MIC"1-50 mug/ml) and antimycotic activity (MIC=0.3-50 mug/ml).
Description
Die Erfindung betrifft ein Verfahren zur Herstellung neuer 1,3-Diketone der Formel I (siehe Formelblatt), worin X für Sauerstoff oder Schwefel und A für einen Naphthylrest oder für einen Rest der Formel II, wobei R, und R2 je für Wasserstoff, Chlor, Brom, Jod, Fluor, eine niedere Alkylgruppe, die Nitrogruppe, die Acetylgruppe,
EMI1.1
<tb> eineR <SEP> -, <SEP> eine
<tb> COOR- oder OR-Gruppe, worin R niederes Alkyl bedeutet, stehen und Rt -und R2 gleich oder verschieden sein können.
Erfindungsgemäss gelangt man zu den Verbindungen der Formel I, indem man eine Verbindung der Formel III, worin Me für ein Alkalimetall steht, mit einer Verbindung der Formel IV, worin X und A obige Bedeutung besitzen, umsetzt.
Das erfindungsgemässe Verfahren kann z. B. folgendermassen ausgeführt werden: Zu der Aufschlämmung einer Verbindung der Formel III in einem unter den Reaktionsbedingungen inerten Lösungsmittel, z. B. in einem cyclischen Äther wie Tetrahydrofuran, setzt man eine Verbindung der Formel IV zu und lässt bei erhöhter Temperatur, vorzugsweise bei der Siedetemperatur des Reaktionsgemisches reagieren. Nach Beendigung der Reaktion, z. B. nach 2 bis 10 Stunden, vorzugsweise nach 3 bis 6 Stunden, isoliert man das Reaktionsprodukt nach an sich bekannten Methoden, z. B.
durch Versetzen mit einer Säure, Abfiltrieren des Niederschlags und Trocknen im Vakuum. Anschliessend kann es noch gegebenenfalls gereinigt werden, z. B. durch Umkristallisation aus einem geeigneten Lösungsmittel.
Die durch R, Rt und R2 symbolisierten niederen Alkylgruppen besitzen vorzugsweise 1 bis 4 Kohlenstoffatome und bedeuten insbesondere die Methylgruppe.
Soweit die Herstellung der Ausgangsprodukte nicht beschrieben wird, sind diese bekannt oder nach an sich bekannten Verfahren bzw. analog zu den hier beschriebenen oder analog zu an sich bekannten Verfahren herstellbar.
Die Verbindungen der Formel I und gegebenenfalls ihre pharmakologisch verträglichen Salze besitzen bei geringer Toxizität interessante pharmakodynamische Eigenschaften und können daher als Heilmittel verwendet werden. Sie stellen wertvolle Chemotherapeutika dar und entfalten ihre Hemmwirkung gegen Bakterien bei minimalen Hemmkonzentrationen zwischen etwa 1 bis 50,ug/ml. Weiters zeigen die erfindungsgemässen Substanzen auch eine antimykotische Wirksamkeit, die sich bei minimalen Hemmkonzentrationen zwischen etwa 0,3 bis 50 50,ug/ml manifestiert.
In den nachfolgenden Beispielen, die die Erfindung näher erläutern, ihren Umfang aber in keiner Weise einschränken sollen, erfolgen alle Temperaturangaben in Celsiusgraden.
Beispiel 1
2-(2,3 -Dichlorphenyl)carbamoylcyclohexandion-1 ,3
Eine Aufschlämmung von 20 g des Natriumsalzes des Dihydroresorcins in 200 ml absolutem Tetrahydrofuran wird mit 35 g 2,3-Dichlorphenylisocyanat versetzt und das Gemisch 3 Stunden unter Feuchtigkeitsausschluss am Rückfluss erhitzt. Dann wird das Lösungsmittel unter vermindertem Druck abdestilliert, und das Reaktionsgemisch zerkleinert und in 500 ml Wasser aufgeschlämmt. Man säuert mit konzentrierter Salzsäure an, nutscht ab, wäscht mit Wasser und trocknet im Vakuum. Das Rohprodukt wird anschliessend mit 400 ml Chloroform bei Zimmertemperatur gerührt, filtriert und das Filtrat unter vermindertem Druck eingeengt.
Der feste Rückstand wird aus Propanol-1 umkristallisiert.
Smp.122-125".
Beispiel 2 2-(4-Methylphenyl)carbamoylcyclohexandion-1 ,3
Eine Aufschlämmung von 13,4 g Dihydroresorcin Natriumsalz wird mit 15 ml 4-Methylphenylisocyanat versetzt. Anschliessend verfährt man wie in Beispiel 1 beschrieben. Smp. 113-114 (aus Propanol-1 umkristallisiert).
Beispiel 3 2-(2-Nitrophenyl)carbamoylcyclohexandion
13,4 g Dihydroresorcin-Natriumsalz werden in 100 ml absolutem Tetrahydrofuran suspendiert und mit 16,4 g 2 Nitrophenylisocyanat versetzt. Das Gemisch wird 3 Stunden unter Feuchtigkeitsausschluss am Rückfluss gekocht, das Lösungsmittel unter vermindertem Druck abdestilliert, der Rückstand in 800 ml siedendes Wasser eingetragen und nach 10 Minuten Kochen heiss filtriert. Das Filtrat wird mit Aktivkohle behandelt, noch einmal zum Sieden gebracht, heiss filtriert, und das noch warme Filtrat mit konzentrierter Salzsäure angesäuert. Nach dem Abkühlen wird der Niederschlag abgenutscht, mit Wasser gewaschen und im Vakuum getrocknet. Aus Propanol-t umkristallisiert, schmilzt die im Titel genannte Verbindung bei 132135O.
Beispiel 4 2-(4-Fluorphenyl)thiocarbamoylcyclohexan
Ein Gemisch aus 6,7 g Dihydroresorcin-Natriumsalz, 7,7 g 4-Fluorphenylisothiocyanat und 50 ml Tetrahydrofuran wird 6 Stunden unter Rückfluss gekocht. Das Lösungsmittel wird unter vermindertem Druck abdestilliert, der Rückstand in 200 ml Wasser gelöst und mit konzentrierter Salzsäure angesäuert, wobei die im Titel genannte Verbindung kristallin ausfällt. Nach dem Abnutschen, Waschen und Trocknen wird die Verbindung aus Äthanol umkristallisiert. Schmp. 95-98 .
Analog wie im Beispiel 1 beschrieben können auch folgende Verbindungen der Formel I erhalten werden:
Beispiel 5
2 -(2,5 -Dichlorphenyl)carbamoylcyclohexandion-l
Man setzt Dihydroresorcinnatrium mit 2,5-Dichlorphenylisocyanat um und erhält die Titelverbindung vom Schmp.
127-128".
Beispiel 6
2 -(4-Acetylphenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 4-Acetylphenylisocyanat um und erhält die Titelverbindung vom Schmp.
169-173".
Beispiel 7
2-(3 -Methylphenyl)carbamoylcyclohexandion-l
Man setzt Dihydroresorcinnatrium mit 3-Methylphenylisocyanat um und erhält die Titelverbindung vom Schmp.
98-99".
Beispiel 8 2-(2,4-D ichlorphenyl) carbamoylcyclohexandion-l ,3
Man setzt Dihydroresorcinnatrium mit 2,4-Dichlorphenylisocyanat um und erhält die Titelverbindung vom Schmp.
175-1779.
Beispiel 9 2 -(4-Methyl-2-nitrophenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 4-Methyl-2-nitrophenylisocyanat um und erhält die Titelverbindung vom Schmp. 175-178 .
Beispiel 10
2-(3 -Chlor-4-methylphenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 3-Chlor-4-methylphenylisocyanat um und erhält die Titelverbindung vom Schmp. 105-107 .
Beispiel 11 2-(3-Chlorphenyl)carbamoylcyclohexandion
Man setzt Dihydroresorcinnatrium mit 3-Chlorphenylisocyanat um und erhält die Titelverbindung vom Schmp.
92-94".
Beispiel 12 2-(3,4-Dichlorphenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 3,4-Dichlorphenylisocyanat um und erhält die Titelverbindung vom Schmp.
132-133 .
Beispiel 13 2-(1 -Naphthyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 1-Naphthylisocyanat um und erhält die Titelverbindung mit Schmp. 144 bis 146O.
Beispiel 14
2-(4-Fluorphenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 4-Fluorphenylisocyanat um und erhält die Titelverbindung vom Schmp. 105 bis 107".
Beispiel 15 2-(4-Bromphenyl)carbamoylcyclohexandion-
Man setzt Dihydroresorcinnatrium mit 4-Bromphenylisocyanat um und erhält die Titelverbindung vom Schmp.
98-102".
Beispiel 16 2-(4 -Chlorphenyl)carbamoylcyclohexandion-1,3
Man setzt Dihydroresorcinnatrium mit 4-Chlorphenylisocyanat um und erhält die Titelverbindung vom Schmp.
114-115
EMI2.1
EMI2.2
A-N=C=X IV
The invention relates to a process for the preparation of new 1,3-diketones of the formula I (see formula sheet), in which X is oxygen or sulfur and A is a naphthyl radical or a radical of the formula II, where R and R2 are each hydrogen or chlorine , Bromine, iodine, fluorine, a lower alkyl group, the nitro group, the acetyl group,
EMI1.1
<tb> aR <SEP> -, <SEP> a
<tb> COOR or OR group, in which R is lower alkyl, and Rt and R2 can be identical or different.
According to the invention, the compounds of the formula I are obtained by reacting a compound of the formula III, in which Me is an alkali metal, with a compound of the formula IV, in which X and A are as defined above.
The inventive method can, for. B. carried out as follows: To the slurry of a compound of formula III in a solvent inert under the reaction conditions, e.g. B. in a cyclic ether such as tetrahydrofuran, a compound of formula IV is added and allowed to react at an elevated temperature, preferably at the boiling point of the reaction mixture. After completion of the reaction, e.g. B. after 2 to 10 hours, preferably after 3 to 6 hours, the reaction product is isolated by methods known per se, for. B.
by adding an acid, filtering off the precipitate and drying in vacuo. It can then be cleaned if necessary, e.g. B. by recrystallization from a suitable solvent.
The lower alkyl groups symbolized by R, Rt and R2 preferably have 1 to 4 carbon atoms and are in particular the methyl group.
If the production of the starting products is not described, these are known or can be produced by processes known per se or analogously to those described here or analogously to processes known per se.
The compounds of the formula I and, if appropriate, their pharmacologically acceptable salts have interesting pharmacodynamic properties with low toxicity and can therefore be used as medicaments. They are valuable chemotherapeutic agents and develop their inhibitory effect against bacteria at minimal inhibitory concentrations between about 1 to 50 μg / ml. Furthermore, the substances according to the invention also show an antimycotic activity which manifests itself at minimal inhibitory concentrations between approximately 0.3 to 50 μg / ml.
In the following examples, which explain the invention in greater detail but are not intended to limit its scope in any way, all temperatures are given in degrees Celsius.
example 1
2- (2,3-dichlorophenyl) carbamoylcyclohexanedione-1,3
35 g of 2,3-dichlorophenyl isocyanate are added to a suspension of 20 g of the sodium salt of dihydroresorcinol in 200 ml of absolute tetrahydrofuran, and the mixture is refluxed for 3 hours with exclusion of moisture. The solvent is then distilled off under reduced pressure and the reaction mixture is crushed and slurried in 500 ml of water. It is acidified with concentrated hydrochloric acid, filtered off with suction, washed with water and dried in vacuo. The crude product is then stirred with 400 ml of chloroform at room temperature, filtered and the filtrate is concentrated under reduced pressure.
The solid residue is recrystallized from 1-propanol.
122-125 ".
Example 2 2- (4-methylphenyl) carbamoylcyclohexanedione-1,3
15 ml of 4-methylphenyl isocyanate are added to a slurry of 13.4 g of dihydroresorcinol sodium salt. Then proceed as described in Example 1. 113-114 (recrystallized from 1-propanol).
Example 3 2- (2-Nitrophenyl) carbamoylcyclohexanedione
13.4 g of dihydroresorcinol sodium salt are suspended in 100 ml of absolute tetrahydrofuran, and 16.4 g of 2-nitrophenyl isocyanate are added. The mixture is refluxed for 3 hours with exclusion of moisture, the solvent is distilled off under reduced pressure, the residue is introduced into 800 ml of boiling water and, after boiling for 10 minutes, filtered while hot. The filtrate is treated with activated charcoal, brought to the boil again, filtered while hot, and the still warm filtrate is acidified with concentrated hydrochloric acid. After cooling, the precipitate is filtered off with suction, washed with water and dried in vacuo. Recrystallized from propanol-t, the compound mentioned in the title melts at 132135O.
Example 4 2- (4-Fluorophenyl) thiocarbamoylcyclohexane
A mixture of 6.7 g of dihydroresorcinol sodium salt, 7.7 g of 4-fluorophenyl isothiocyanate and 50 ml of tetrahydrofuran is refluxed for 6 hours. The solvent is distilled off under reduced pressure, the residue is dissolved in 200 ml of water and acidified with concentrated hydrochloric acid, the compound named in the title precipitating in crystalline form. After suction filtration, washing and drying, the compound is recrystallized from ethanol. M.p. 95-98.
The following compounds of the formula I can also be obtained analogously to that described in Example 1:
Example 5
2 - (2,5-dichlorophenyl) carbamoylcyclohexanedione-l
Dihydroresorcin sodium is reacted with 2,5-dichlorophenyl isocyanate and the title compound is obtained with a melting point.
127-128 ".
Example 6
2 - (4-acetylphenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 4-acetylphenyl isocyanate and the title compound is obtained with melting point.
169-173 ".
Example 7
2- (3 -Methylphenyl) carbamoylcyclohexanedione-l
Dihydroresorcin sodium is reacted with 3-methylphenyl isocyanate and the title compound is obtained with a melting point.
98-99 ".
Example 8 2- (2,4-dichlorophenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 2,4-dichlorophenyl isocyanate and the title compound is obtained with a melting point.
175-1779.
Example 9 2 - (4-Methyl-2-nitrophenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 4-methyl-2-nitrophenyl isocyanate and the title compound is obtained with a melting point of 175-178.
Example 10
2- (3-chloro-4-methylphenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 3-chloro-4-methylphenyl isocyanate and the title compound is obtained with a melting point of 105-107.
Example 11 2- (3-Chlorophenyl) carbamoylcyclohexanedione
Dihydroresorcin sodium is reacted with 3-chlorophenyl isocyanate and the title compound is obtained with a melting point.
92-94 ".
Example 12 2- (3,4-Dichlorophenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 3,4-dichlorophenyl isocyanate and the title compound is obtained with melting point.
132-133.
Example 13 2- (1-Naphthyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 1-naphthyl isocyanate and the title compound with melting point 144 to 146O is obtained.
Example 14
2- (4-fluorophenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 4-fluorophenyl isocyanate and the title compound is obtained with a melting point of 105 to 107 ".
Example 15 2- (4-bromophenyl) carbamoylcyclohexanedione
Dihydroresorcin sodium is reacted with 4-bromophenyl isocyanate and the title compound is obtained with a melting point.
98-102 ".
Example 16 2- (4-Chlorophenyl) carbamoylcyclohexanedione-1,3
Dihydroresorcin sodium is reacted with 4-chlorophenyl isocyanate and the title compound is obtained with a melting point.
114-115
EMI2.1
EMI2.2
A-N = C = X IV
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1762371A CH556811A (en) | 1971-12-03 | 1971-12-03 | N-aryl-1,3-dioxo-cyclohexane-carboxamides - and thio analogues, with antibacterial and antimycotic activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1762371A CH556811A (en) | 1971-12-03 | 1971-12-03 | N-aryl-1,3-dioxo-cyclohexane-carboxamides - and thio analogues, with antibacterial and antimycotic activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH556811A true CH556811A (en) | 1974-12-13 |
Family
ID=4426810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1762371A CH556811A (en) | 1971-12-03 | 1971-12-03 | N-aryl-1,3-dioxo-cyclohexane-carboxamides - and thio analogues, with antibacterial and antimycotic activity |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH556811A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4159386A (en) * | 1972-10-25 | 1979-06-26 | Hoffmann-La Roche Inc. | Synthesis of cyclopentanol |
-
1971
- 1971-12-03 CH CH1762371A patent/CH556811A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4159386A (en) * | 1972-10-25 | 1979-06-26 | Hoffmann-La Roche Inc. | Synthesis of cyclopentanol |
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