DE2946066A1 - Antibacterial 2-formyl-quinoxaline 1,4-di:oxide imine derivs. - prepd. e.g. by reaction of benzo:furoxane cpds. with alpha, beta-unsatd aldehyde e.g. crotonaldehyde imine(s) - Google Patents
Antibacterial 2-formyl-quinoxaline 1,4-di:oxide imine derivs. - prepd. e.g. by reaction of benzo:furoxane cpds. with alpha, beta-unsatd aldehyde e.g. crotonaldehyde imine(s)Info
- Publication number
- DE2946066A1 DE2946066A1 DE19792946066 DE2946066A DE2946066A1 DE 2946066 A1 DE2946066 A1 DE 2946066A1 DE 19792946066 DE19792946066 DE 19792946066 DE 2946066 A DE2946066 A DE 2946066A DE 2946066 A1 DE2946066 A1 DE 2946066A1
- Authority
- DE
- Germany
- Prior art keywords
- formyl
- quinoxaline
- dioxide
- imine
- formula
- 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.)
- Withdrawn
Links
- -1 crotonaldehyde imine Chemical class 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 title claims description 11
- 150000002466 imines Chemical class 0.000 title claims description 9
- 150000001299 aldehydes Chemical class 0.000 title claims description 6
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 title description 5
- 230000000844 anti-bacterial effect Effects 0.000 title description 3
- UJEHWLFUEQHEEZ-UHFFFAOYSA-N quinoxaline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CN=C21 UJEHWLFUEQHEEZ-UHFFFAOYSA-N 0.000 title description 2
- 125000005605 benzo group Chemical group 0.000 title 1
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 15
- XTQMQWWCGMMOJF-UHFFFAOYSA-N (1-oxido-4-oxoquinoxalin-4-ium-2-yl)methanimine Chemical class C1=CC=C2N([O-])C(C=N)=C[N+](=O)C2=C1 XTQMQWWCGMMOJF-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- OVGGLBAWFMIPPY-UHFFFAOYSA-N methyl N-[(1,4-dioxidoquinoxaline-1,4-diium-2-yl)methylideneamino]carbamate Chemical compound C1=CC=CC2=[N+]([O-])C(C=NNC(=O)OC)=C[N+]([O-])=C21 OVGGLBAWFMIPPY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000000543 intermediate Substances 0.000 abstract description 7
- JZJFIUXMPBVEFS-UHFFFAOYSA-N 1-oxido-4-oxoquinoxalin-4-ium-2-carbaldehyde Chemical class C1=CC=C2N([O-])C(C=O)=C[N+](=O)C2=C1 JZJFIUXMPBVEFS-UHFFFAOYSA-N 0.000 abstract description 2
- 150000007857 hydrazones Chemical class 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- OKEAMBAZBICIFP-UHFFFAOYSA-N 3-oxido-2,1,3-benzoxadiazol-3-ium Chemical compound C1=CC=CC2=[N+]([O-])ON=C21 OKEAMBAZBICIFP-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 4
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229940117916 cinnamic aldehyde Drugs 0.000 description 4
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 4
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 4
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- JOODWJXLRIMVMC-UHFFFAOYSA-N C(=O)(OC)NN=CC1=[N+](C2=CC=CC=C2[N+](=C1C)[O-])[O-] Chemical compound C(=O)(OC)NN=CC1=[N+](C2=CC=CC=C2[N+](=C1C)[O-])[O-] JOODWJXLRIMVMC-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KSGAAWJLYHYMLT-UHFFFAOYSA-N 2,6-dimethylcyclohexan-1-amine Chemical compound CC1CCCC(C)C1N KSGAAWJLYHYMLT-UHFFFAOYSA-N 0.000 description 1
- IRDBMNHHHAOWBM-UHFFFAOYSA-N 3-chloro-4-oxidoquinoxalin-1-ium 1-oxide Chemical compound C1=CC=C2N([O-])C(Cl)=C[N+](=O)C2=C1 IRDBMNHHHAOWBM-UHFFFAOYSA-N 0.000 description 1
- DHPQXIQZZCNOLI-UHFFFAOYSA-N 5-chloro-1-oxido-2,1,3-benzoxadiazol-1-ium Chemical compound C1=C(Cl)C=CC2=[N+]([O-])ON=C21 DHPQXIQZZCNOLI-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- KDSNLYIMUZNERS-UHFFFAOYSA-N isobutyl amine Natural products CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
- C07D241/52—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Verfahren zur Herstellung von neuen 2-Formyl-chinoxalin-Process for the production of new 2-formyl-quinoxaline
1,4-dioxid-iminen Die vorliegende Erfindung betrifft ein neues, chemisch eigenartiges Verfahren zur Herstellung von neuen 2-Formyl-chinoxalin-1,4-dioxid-iminen, die als Zwischenprodukte für die Synthese von pharmazeutischen Wirkstoffen verwendet werden können.1,4-dioxide-imines The present invention relates to a new chemical peculiar process for the production of new 2-formyl-quinoxaline-1,4-dioxide-imines, which are used as intermediates for the synthesis of active pharmaceutical ingredients can be.
Es ist schon bekannt geworden, daß Benzofuroxan (a) mit Iminen (b) in Form ihrer tautomeren Enamine (c) zu orthochinoiden Zwischenprodukten (d) reagieren, welche unter Abspaltung des Aminteils in Chinoxalin-di-N-oxide (e) übergehen. Falls sich im Imin (b) nur ein ß-ständiges Wasserstoffatom befindet, bleibt die Reaktion auf der Zwischenstufe (d) stehen. (vgl. K. Ley et al, Synthesis 1975, 415). Diese Reaktion wird durch das nachstehende Formelschema erläutert. It has already become known that benzofuroxan (a) react with imines (b) in the form of their tautomeric enamines (c) to form ortho-quinoid intermediates (d), which convert into quinoxaline di-N-oxides (e) with elimination of the amine moiety. If there is only one ß-hydrogen atom in the imine (b), the reaction on intermediate (d) stops. (see K. Ley et al, Synthesis 1975, 415). This reaction is illustrated by the equation below.
Es wurde gefunden, daß man die neuen 2-Formyl-chinoxalin-1,4-dioxid-imine der Formel in welchen R1 und R2 gleich oder verschieden sind und für Wasserstoff oder Halogen stehen, R3 für Alkyl oder Cycloalkyl steht und R4 für Wasserstoff, Alkyl oder Aryl steht, erhält, wenn man Benzofuroxane der Formel in welcher R1 und R2 die oben angegebene Bedeutung haben, in Gegenwart eines Verdünnungsmittels bei Temperaturen zwischen 0°C und 1000C mit Iminen der Formel R4-CH=CH-CH=N-R3 (III) in welcher R3 und R4 die oben angegebene Bedeutung haben, oder mit Aldehyden der Formel 4 R -CH=CH-CH=O (1V) in welcher R4 die oben angegebene Bedeutung hat und mit Aminen der Formel H2N-R3 (V) in welcher R3 die oben angegebene Bedeutung hat, umsetzt.It has been found that the new 2-formyl-quinoxaline-1,4-dioxide imines of the formula in which R1 and R2 are identical or different and represent hydrogen or halogen, R3 represents alkyl or cycloalkyl and R4 represents hydrogen, alkyl or aryl, are obtained when benzofuroxanes of the formula in which R1 and R2 have the meaning given above, in the presence of a diluent at temperatures between 0 ° C. and 1000 ° C. with imines of the formula R4-CH =CH-CH =N-R3 (III) in which R3 and R4 have the meaning given above or with aldehydes of the formula 4 R -CH = CH-CH = O (1V) in which R4 has the meaning given above and with amines of the formula H2N-R3 (V) in which R3 has the meaning given above.
Es ist als ausgesprochen überraschend zu bezeichnen, daß nach der erfindungsgemäßen Umsetzung die neuen 2-Formylchinoxalin-1,4-dioxid-imine entstehen, da nach oben ausgeführtem Stand der Technik zu erwarten wäre, daß Benzofuroxane mit Iminen, bzw. mit Gemischen aus Aldehyden und Aminen, welche in Form ihrer tautomeren Enamine reagieren, unter Addition zu dem obengenannten orthochinsiden Zwischenprodukt (d) reagieren. Tatsächlich erfolgt jedoch bei der erfindungsgemäßen Reaktion eine Addition an die Doppelbindung des t ,ß-ungesättigten Aldehyds bzw. Imins mit nachfolgender Oxydation durch das überschüssige Benzofuroxan.It can be described as extremely surprising that after the According to the invention, the new 2-formylquinoxaline-1,4-dioxide-imines arise, since according to the state of the art set out above, it would be expected that benzofuroxanes with imines, or with mixtures of aldehydes and amines, which in the form of their tautomeric Enamines react with addition to the above-mentioned ortho-insidic intermediate (d) respond. In fact, however, one occurs in the reaction of the present invention Addition to the double bond of the t, ß-unsaturated aldehyde or imine with the following Oxidation by the excess benzofuroxane.
Nach dem erfindungsgemäßen Verfahren werden die neuen Verbindungen in glatter Reaktion, hervorragender Ausbeute und hoher Reinheit erhalten. Das erfindungsgemäße Verfahren stellt somit eine Bezeichnung der Technik dar.According to the process of the invention, the new compounds obtained in smooth reaction, excellent yield and high purity. The inventive Process is therefore a designation of the technology.
Verwendet man Benzofuroxan und das Imin aus Crotonaldehyd und tert.-Butylamin als Ausgangsstoffe, so kann der Reaktionsablauf durch folgendes Formelschema wiedergegeben werden. If benzofuroxan and the imine from crotonaldehyde and tert-butylamine are used as starting materials, the course of the reaction can be represented by the following equation.
Verwendet man Benzofuroxan Zimtaldehyd und Cyclohexylamin als Ausgangsstoffe, so kann der Reaktionsablauf durch folgendes Formelschema wiedergegeben werden. If benzofuroxan, cinnamaldehyde and cyclohexylamine are used as starting materials, the course of the reaction can be represented by the following equation.
In den Formeln steht R1 und R2 für Wasserstoff oder Halogen, insbesondere Fluor, Chlor und Brom, vorzugsweise Fluor und Chlor.In the formulas, R1 and R2 stand for hydrogen or halogen, in particular Fluorine, chlorine and bromine, preferably fluorine and chlorine.
R3 bedeutet gradkettiges oder verzweigtes Alkyl mit vorzugsweise 1-6, insbesondere 1-4 Kohlenstoffatomen.R3 denotes straight-chain or branched alkyl with preferably 1-6, especially 1-4 carbon atoms.
Beispielhaft seien Methyl, Ethyl, n- und i-Propyl und n-, i- und t-Butyl genannt.Examples include methyl, ethyl, n- and i-propyl and n-, i- and t-butyl called.
R3 bedeutet ferner Cycloalkyl mit vorzugsweise 3-8, insbesondere 5-6 Kohlenstoffatomen. Beispielhaft seien Cyclopentyl und Cyclohexyl genannt.R3 also denotes cycloalkyl with preferably 3-8, in particular 5-6 Carbon atoms. Cyclopentyl and cyclohexyl may be mentioned as examples.
R3 bedeutet außerdem geradkettiges oder verzweigtes Alkyl mit vorzugsweise 1-4 Kohlenstoffatomen. Beispielhaft seien Methyl, Ethyl, n- und i-Propyl und n-, i-und t-Butyl genannt.R3 also denotes straight-chain or branched alkyl with preferably 1-4 carbon atoms. Examples are methyl, ethyl, n- and i-propyl and n-, Called i- and t-butyl.
R4 bedeutet Wasserstoff, Alkyl mit 1-4 C-Atomen oder Aryl, insbesondere Phenyl.R4 denotes hydrogen, alkyl with 1-4 carbon atoms or aryl, in particular Phenyl.
Als Beispiele für erfindungsgemäße Verbindungen der Formel I seien genannt [6 - (7-) bedeutet, daß Gemische aus Verbindungen vorliegen, die in 6- oder in 7-Stellung substituiert sind.Examples of compounds of the formula I according to the invention are called [6 - (7-) means that there are mixtures of compounds in 6- or are substituted in the 7-position.
2-Formyl-chinoxalin-1,4-dioxid--N-methylimin, -N-ethylimin, -N-i-propylimin, -N-tert.-butylimin, -N-cyclohexylimin; 2-Formyl-6-(7-) chlor-chinoxalin-1,4-dioxid--N-tert.-butylimin, N-cyclohexylimin; 2-Formyl-3-methyl-1 ,4-dioxid--N-tert.-butylimin, N-cyclohexylimin; 2-Formyl-3-methyl-6(7-)chlor-chinoxalin-1,4-dioxid-N-tert.-butylimin; 2-Formyl-3-methyl-6(7-)fluor-chinoxalin-1,4-dioxid-N-cyclohexylimin; 2-Formyl-3-phenyl-chinoxalin-1,4-dioxid-N-tert.-butylimin, -N-cyclohexylimin.2-formyl-quinoxaline-1,4-dioxide - N-methylimine, -N-ethylimine, -N-i-propylimine, -N-tert-butylimine, -N-cyclohexylimine; 2-formyl-6- (7-) chloro-quinoxaline-1,4-dioxide - N-tert.-butylimine, N-cyclohexylimine; 2-formyl-3-methyl-1,4-dioxide - N-tert-butylimine, N-cyclohexylimine; 2-formyl-3-methyl-6 (7-) chloro-quinoxaline-1,4-dioxide-N-tert-butylimine; 2-formyl-3-methyl-6 (7-) fluoro-quinoxaline-1,4-dioxide-N-cyclohexylimine; 2-Formyl-3-phenyl-quinoxaline-1,4-dioxide-N-tert-butylimine, -N-cyclohexylimine.
Die Ausgangsverbindungen der Formel II sind bereits bekannt [vgl. H. Greene et. al., J. chem. Soc.: 101, 2452 (1912); 103, 897, 2023 (1913)J.The starting compounds of the formula II are already known [cf. H. Greene et. al., J. chem. Soc .: 101, 2452 (1912); 103, 897, 2023 (1913) J.
Die Ausgangsverbindungen der Formel III sind ebenfalls bekannt [vgl. K. Taguchi, I. org. Chem.: 36 1570 (1971)].The starting compounds of the formula III are also known [cf. K. Taguchi, I. org. Chem .: 36 1570 (1971)].
Als Beispiele für die Ausgangsverbindungen der Formel IV seien genannt: Acrolein, Crotonaldehyd und Zimtaldehyd.Examples of the starting compounds of the formula IV include: Acrolein, crotonaldehyde and cinnamaldehyde.
Als Beispiele für die Ausgangsverbindungen der Formel V seien genannt Methylamin, Ethylamin, n-Propylamin, i-Propylamin, n-Butylamin, i-Butylamin, tert. -Butylamin, Cyclopentylamin, Cyclohexylamin, 2 ,6-Dimethyl-cyclohexylamin.Examples that may be mentioned of the starting compounds of the formula V are Methylamine, ethylamine, n-propylamine, i-propylamine, n-butylamine, i-butylamine, tert. -Butylamine, cyclopentylamine, cyclohexylamine, 2,6-dimethyl-cyclohexylamine.
Als Verdünnungsmittel kommen beim erfindungsgemäßen Verfahren alle inerten organischen Lösungsmittel in Frage.All diluents can be used in the process according to the invention inert organic solvents in question.
Hierzu gehören vorzugsweise Ether, Diethylether, Tetrahydrofuran urd Dioxan, sowie Alkohole, wie Methanol, Ethanol und Propanole und hitrile, insbesondere Acetonitril, und Dimethylformamid.These preferably include ethers, diethyl ether, tetrahydrofuran and Dioxane, as well as alcohols such as methanol, ethanol and propanols and hitriles, in particular Acetonitrile, and dimethylformamide.
Die Umsetzung wird bei Temperaturen zwischen 0° und 1000C, vorzugsweise zwischen 200 und 80"C durchgeführt.The reaction is carried out at temperatures between 0 ° and 1000 ° C., preferably performed between 200 and 80 "C.
Bei der Durchführung des erfindungsgemäßen Verfahrens setzt man auf 2 Mol Benzofuroxan 1 Mol Imin, bzw. 1 Mol Aldehyd und mindestens 1 Mol Amin ein. Das Molverhältnis kann jedoch über einen weiten Bereich verändert werden, ohne daß das erfindungsgemäße Verfahren hierdurch besonders nachteilig beeinflußt wird.When carrying out the process according to the invention, one sets up 2 moles of benzofuroxane, 1 mole of imine, or 1 mole of aldehyde and at least 1 mole of amine. The molar ratio however, it can be changed over a wide range are without the process according to the invention thereby particularly adversely affected will.
Die neuen Verbindungen werden nach allgemeinüblichen Methoden gereinigt, z.B. durch Umkristallisieren.The new connections are cleaned according to common methods, e.g. by recrystallization.
Die erfindungsgemäßen Chinoxalin-di-N-oxide sind neu.The quinoxaline di-N-oxides according to the invention are new.
Sie können als Zwischenprodukte zur Herstellung von antibakteriell und nutritiv wirksamen Hydrazonen von 2-Formylchinoxalin-1,4-dioxiden dienen £DE-AS 1 620 114J.They can be used as intermediates in the manufacture of antibacterial and nutritionally active hydrazones of 2-formylquinoxaline-1,4-dioxides serve £ DE-AS 1 620 114J.
Das erfindungsgemäße Verfahren sei anhand der folgenden Beispiele erläutert.The process according to the invention is illustrated by the following examples explained.
Beispiel 1 2-Formyl-3-methyl-chinoxalin-1 ,4-dioxid-N-tert.-butyl-imin 27,2 g (0,2 Mol) Benzofuroxan werden in 60 ml Methanol suspendiert und tropfenweise mit 12,5 g (0,1 Mol) Crotonaldehyd-N-tert.-butylimin versetzt. In stark exothermer Reaktion bildet sich eine dunkelrote Lösung aus der nach ca. 2 Stunden 18 g (69,5 %) gelbe Kristalle von 2-Formyl-3-methyl-chinoxalin-1 ,4-dioxid-N-tert.-butyl-imin ausfallen, die nach dem Umlösen aus Methanol bei 1419 schmelzen.Example 1 2-Formyl-3-methyl-quinoxaline-1,4-dioxide-N-tert-butyl-imine 27.2 g (0.2 mol) of benzofuroxan are suspended in 60 ml of methanol and added dropwise 12.5 g (0.1 mol) of crotonaldehyde-N-tert.-butylimine were added. In strongly exothermic The reaction forms a dark red solution from which 18 g (69.5 %) yellow crystals of 2-formyl-3-methyl-quinoxaline-1,4-dioxide-N-tert-butyl-imine precipitate, which melt at 1419 after being redissolved from methanol.
Beispiel 2 2-Formyl- 3-methy l-chinoxal in- 1 , 4-d ioxid-N- tert . -butyl- imin 27,2 g (0,2 Mol) Benzofuroxan und 7 g Crotonaldehyd werden in 40 ml Acetonitril gelöst und tropfenweise mit 14,6 g (0,2 Mol) tert.-Butylamin versetzt. Die Temperatur des Reaktionsgemisches steigt dabei auf 810C an. Aus der entstandenen dunkelroten Lösung fallen beim Abkühlen auf Raumtemperatur 20 g (77 %) gelbe Kristalle aus, die mit der in Beispiel 1 erhaltenen Verbindung identisch sind.Example 2 2-Formyl-3-methyl-quinoxaline-1,4-dioxide-N-tert . -butyl- imine 27.2 g (0.2 mol) benzofuroxan and 7 g crotonaldehyde are in 40 ml of acetonitrile dissolved, and 14.6 g (0.2 mol) of tert-butylamine were added dropwise. The temperature of the reaction mixture rises to 810C. From the resulting dark red solution, 20 g (77%) of yellow crystals fall on cooling to room temperature which are identical to the compound obtained in Example 1.
Beispiel 3 Nach der selben Verfahrensweise wie in Beispiel 2 erhält man bei Verwendung von 5-Chlorbenzofuroxan anstelle von Benzofuroxan 2-Formyl-3-methyl-6(7-)chlor-chinoxalin-1,4-dioxid-N-tert.-butyl-imin vom Schmelzpunkt 1850 (Ethanol).Example 3 Obtained by the same procedure as in Example 2 instead of using 5-chlorobenzofuroxane of benzofuroxan 2-Formyl-3-methyl-6 (7-) chloro-quinoxaline-1,4-dioxide-N-tert-butyl-imine of melting point 1850 (ethanol).
Beispiel 4 2-Formyl-3-methyl-chinoxalin-1 , 4-dioxid-N-cyclohexyl-imin 27,2 g (0,2 Mol) Benzofuroxan werden zusammen mit 7 g (0,1 Mol) Crotonaldehyd in 40 ml Methanol vorgelegt und tropfenweise mit 20 g (0,2 Mol) Cyclohexylamin versetzt.Example 4 2-Formyl-3-methyl-quinoxaline-1,4-dioxide-N-cyclohexyl-imine 27.2 g (0.2 mol) of benzofuroxan together with 7 g (0.1 mol) of crotonaldehyde in Submitted 40 ml of methanol and treated dropwise with 20 g (0.2 mol) of cyclohexylamine.
Nach kurzer Zeit steigt die Temperatur auf 550 an und das Benzofuroxan geht mit roter Farbe in Lösung.After a short time the temperature rises to 550 and the benzofuroxan goes into solution with red paint.
Nach 3 Stunden fallen 21 g (74 %) gelbe Kristalle von 2-Formyl-3-methyl-chonxalin-1 ,4-dioxid-N-cyclohexylimin aus, die nach dem Umlösen aus Ethanol bei 1170C schmelzen.After 3 hours, 21 g (74%) of yellow crystals of 2-formyl-3-methyl-chonxalin-1 fall , 4-dioxide-N-cyclohexylimine, which melt after dissolving from ethanol at 1170C.
Beispiel 5 Analog Beispiel 4 erhält man be Verwendung von 5-Chlorbenzofuroxan anstelle von Benzofuroxan 2-Formyl-3-methyl-6 (7-)chlor-chinoxalin-1 ,4-dioxid-N-cyclohexylimin vom Schmelzpunkt 1640C (Ethanol).Example 5 Analogously to Example 4, 5-chlorobenzofuroxan is obtained using 5-chlorobenzofuroxane instead of benzofuroxan, 2-formyl-3-methyl-6 (7-) chloroquinoxaline-1,4-dioxide-N-cyclohexylimine with a melting point of 1640C (ethanol).
Beispiel 6 2-Formyl-chinoxalin-1,4-dioxid-N-tert.-butyl-imin 27,2 g (0,2 Mol) Benzofuroxan werden zusammen mit 5,9 g (0,1 Mol) Acrolein in 40 ml Methanol vorgelegt. Dazu tropft man bei Raumtemperatur 14,6 g (10,2 Mol) tert.-Butylamin. Aus der roten Lösung scheiden sich 15 g (67 %) 2-Formyl-chinoxalin-1 ,4-dioxid-N-tert.-butyl-imin als gelbe Kristalle ab, die nach dem Umlösen aus Methanol bei 1810C schmelzen.Example 6 2-Formyl-quinoxaline-1,4-dioxide-N-tert-butyl-imine 27.2 g (0.2 mol) of benzofuroxan along with 5.9 g (0.1 mole) acrolein presented in 40 ml of methanol. 14.6 g (10.2 mol) are added dropwise at room temperature tert-butylamine. 15 g (67%) of 2-formylquinoxaline-1 separate from the red solution , 4-dioxide-N-tert-butyl-imine as yellow crystals, which after dissolving from methanol melt at 1810C.
Beispiel 7 2-Formyl-3-phenyl-chinoxalin-1 ,4-dioxid-N-tert -butyl-imin 27,2 g (0,2 Mol) Benzofuroxan werden zusammen mit 13,2 g (0,1 Mol) Zimtaldehyd in 40 ml Acetonitril vorgelegt und mit 14,6 g (0,2 Mol) tert.-Butylamin versetzt. Beim Erwärmen auf 400C setzt man nach 30 Minuten eine exotherme Reaktion ein, wobei die Temperatur auf 650C ansteigt.Example 7 2-Formyl-3-phenyl-quinoxaline-1,4-dioxide-N-tert -butyl-imine 27.2 g (0.2 mol) of benzofuroxan together with 13.2 g (0.1 mol) of cinnamaldehyde in 40 ml of acetonitrile and mixed with 14.6 g (0.2 mol) of tert-butylamine. At the Heating to 40 ° C., an exothermic reaction occurs after 30 minutes, with the Temperature rises to 650C.
Anschließend versetzt man den Ansatz mit 150 ml Wasser und saugt den ausgefallenen Niederschlag ab. Man erhält 26 g (81 %) gelbe Kristalle von 2-Formyl-3-phenylchinoxalin-1,4-dioxid-N-tert.-butyl-imin, die nach dem Umlösen aus Ether bei 1540C schmelzen.Then the batch is mixed with 150 ml of water and sucked the precipitated from. 26 g (81%) of yellow crystals of 2-formyl-3-phenylquinoxaline-1,4-dioxide-N-tert-butyl-imine are obtained, which melt after dissolving from ether at 1540C.
Beispiel 8 2-Formyl-3-phenyl-chinoxalin-1t4-dioxid-N-cycloheXyl-imin 27,2 g (0,2 Mol) Benzofuroxan werden zusammen mit 13,2 g (0,1 Mol) Zimtaldehyd und 20 g (0,2 Mol) Cyclohexylamin in 50 ml Acetonitril vorgelegt und 2 Stunden bei 400C gerührt. Anschließend wird abgekühlt und abgesaugt. Man erhält 24 g (69 %) 2-Formyl-3-phenyl-chinoxalin-1,4-dioxid-N-cyclohexyl-imin als gelbe Kristalle, die nach dem Umlösen aus Ethanol/DMF bei 1460C schmelzen.Example 8 2-Formyl-3-phenyl-quinoxaline-1t4-dioxide-N-cyclohexyl-imine 27.2 g (0.2 mol) of benzofuroxan together with 13.2 g (0.1 mol) of cinnamaldehyde and 20 g (0.2 mol) of cyclohexylamine in 50 ml of acetonitrile and 2 hours at 40 ° C touched. It is then cooled and suctioned off. 24 g (69%) of 2-formyl-3-phenyl-quinoxaline-1,4-dioxide-N-cyclohexyl-imine are obtained as yellow crystals which melt at 1460C after dissolving from ethanol / DMF.
Beispiel zur Verwendung der erfindungsgemäßen Verbindungen als Zwischenprodukte zur Herstellung von antibakteriellen Stoffen (vgl. DAS 1 620 114).Example of the use of the compounds according to the invention as intermediates for the production of antibacterial substances (cf. DAS 1 620 114).
Beispiel 9 2-Formyl-3-methyl-chinoxalin-1 ,4-dioxid-carbomethoxyhydrazon 25,9 g (0,1 Mol) 2-Formyl-3-methyl-chinoxalin-1,4-dioxid-N-tert.-butyl-imin werden in 100 ml Methanol suspendiert und mit 10 g (0,11 Mol) Hydrazinokohlensäuremonomethylester versetzt. Man rührt 6 Stunden nach und saugt anschließend das gebildete 2-Formyl-3-methyl-chinoxalin-1,4-dioxid-carbomethoxyhydrazon ab.Example 9 2-Formyl-3-methyl-quinoxaline-1,4-dioxide-carbomethoxyhydrazone 25.9 g (0.1 mol) of 2-formyl-3-methyl-quinoxaline-1,4-dioxide-N-tert-butyl-imine suspended in 100 ml of methanol and with 10 g (0.11 mol) of hydrazinocarbonic acid monomethyl ester offset. The mixture is stirred for a further 6 hours and the 2-formyl-3-methyl-quinoxaline-1,4-dioxide-carbomethoxyhydrazone formed is then suctioned off away.
Ausbeute 23 g (83 %).Yield 23g (83%).
Schmelzpunkt 2450C (zers.).Melting point 2450C (decomp.).
Beispiel 10 2-FormYl-chinoxalin-1,4-dioxid-carbomethoxy-hydrazon Analog Beispiel 9 erhält man bei Verwendung von 2-Formylchinoxalin-1,4-dioxid-N-tert.-butylimin anstelle von 2-Formyl-3-methyl-chinoxalin-1,4-dioxid-N-tert.-butylimín.Example 10 2-FormYl-quinoxaline-1,4-dioxide-carbomethoxy-hydrazone analog Example 9 is obtained when using 2-formylquinoxaline-1,4-dioxide-N-tert-butylimine instead of 2-formyl-3-methyl-quinoxaline-1,4-dioxide-N-tert.-butylimín.
2-Formyl-chinoxalin-1 ,4-dioxid-carbomethoxy-hydrazon vom Schmelzpunkt 2400C.2-formyl-quinoxaline-1,4-dioxide-carbomethoxy-hydrazone of melting point 2400C.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792946066 DE2946066A1 (en) | 1979-11-15 | 1979-11-15 | Antibacterial 2-formyl-quinoxaline 1,4-di:oxide imine derivs. - prepd. e.g. by reaction of benzo:furoxane cpds. with alpha, beta-unsatd aldehyde e.g. crotonaldehyde imine(s) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792946066 DE2946066A1 (en) | 1979-11-15 | 1979-11-15 | Antibacterial 2-formyl-quinoxaline 1,4-di:oxide imine derivs. - prepd. e.g. by reaction of benzo:furoxane cpds. with alpha, beta-unsatd aldehyde e.g. crotonaldehyde imine(s) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2946066A1 true DE2946066A1 (en) | 1981-05-21 |
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ID=6086015
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792946066 Withdrawn DE2946066A1 (en) | 1979-11-15 | 1979-11-15 | Antibacterial 2-formyl-quinoxaline 1,4-di:oxide imine derivs. - prepd. e.g. by reaction of benzo:furoxane cpds. with alpha, beta-unsatd aldehyde e.g. crotonaldehyde imine(s) |
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| Country | Link |
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| DE (1) | DE2946066A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720548A (en) * | 1980-08-07 | 1988-01-19 | Angus Chemical Company | Quinoxaline adducts useful as anthelmintics |
-
1979
- 1979-11-15 DE DE19792946066 patent/DE2946066A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720548A (en) * | 1980-08-07 | 1988-01-19 | Angus Chemical Company | Quinoxaline adducts useful as anthelmintics |
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