DE1670696A1 - Process for the preparation of basic alkylated naphthalene (1,4,5,8) tetracarboxylic diimides - Google Patents
Process for the preparation of basic alkylated naphthalene (1,4,5,8) tetracarboxylic diimidesInfo
- Publication number
- DE1670696A1 DE1670696A1 DE19641670696 DE1670696A DE1670696A1 DE 1670696 A1 DE1670696 A1 DE 1670696A1 DE 19641670696 DE19641670696 DE 19641670696 DE 1670696 A DE1670696 A DE 1670696A DE 1670696 A1 DE1670696 A1 DE 1670696A1
- Authority
- DE
- Germany
- Prior art keywords
- basic
- propyl
- preparation
- ethyl
- alkylated naphthalene
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung basisch alkylierter Naphthalin-(1, 4,5,8)-tetracarbonsäurediimide Es wurde gefunden, da3 basisch alkylierte Naphthalin- (1, 4, 5, 8)-tetracarbonsOurediimide der allgemeinen Formel in der A ein durch Halogen substituierter Arylrest und B ein"basischer Rest"ist, gute Wirkungen gegen Tuberkulose, Amöben, Lamblien und Oxyuren besitzen.Process for the preparation of basic alkylated naphthalene- (1, 4,5,8) -tetracarboxylic acid diimides It has been found that basic alkylated naphthalene- (1, 4, 5, 8) -tetracarboxylic acid diimides of the general formula in which A is a halogen-substituted aryl radical and B is a "basic radical", have good effects against tuberculosis, amoebas, lamellae and oxyurs.
Als"baa@ scher Rest"sollen hier stickstoffhaltige Gruppen bestichaet werden, die zur Salzbildung befahigt sind, z. Bo B-Dipropylamino-äthyl-, ß-Dioutylaminoäthyl-, ß-Pyrrolidinoäthyl-, ß-Piperidinoäthyl-, ß-Hexamethylen-imino-äthyl-, ß-Dimethylamino-äthyl-, γ-Diäthylamino-propyl-, γ-Dibutylamino-propyl-, γ-N-Propyl-N-outylamino-propyl-, γ-Piperidinopropyl-, γ-N-wethylpiperazino-propyl-, γ-Diäthylamino-butyl-, γ-Dimathylamino-ß-dimethyl-propyl, γ-Diäthylamino-ß-dimethylpropyl-, (N-Äthylpiperidyl-2)-methyl-, ß-3,3-Dimethyl-pyrrolidino -äthyl-, γ-Dimethylamino-propyl-, ß-(ß'-Phenyläthyl)-aminoäthyl-, γ-Diäthylamino-ß-hydroxy-propyl-, γ-Cyclohexylamino-propyl-, ß-(ß'-Phenyl-ß'-hydroxy-äthyl)-aminoäthyl-, ß-Isobutylaminoäthyl-, ß-Hydroxy-γ-(N-äthyl-N-p-chlorphenylamino)-propyl-, B- olyl-äthyl)-aminoUthyl-, γ-(4-Methylpiperidin@)-propyl, γ-(2-Methyl-piperidino)-propyl-, γ-(2-Äthylpiperidino)-propyl-, γ-(N-Methyl-N-cyclohexyl)-aminopropyl-, γ T-Hesamethylen-iminopropyl-, γ-(Di-cyclohexylmethylen-amino)-proply-, γ-(N-Meethyl-N-ß-äthoxyäthyl)-amino-propyl-, γ-(3,3-4,4-tetramethyl-pyrrolidino)-propyl-, ß-(N-Methyl-piperazino)-äthyl-, ß-Deca-hydrochinolino-äthyl-, ß-Decahydroisochinolinoäthyl-, ß-Dibenzylamino-äthyl-, γ-Piperidino-ß-dimethyl-propyl-, γ-Morpholino-ß-dimethyl-propyl-, ß-Diisobutylamino-äthyl-, ß-1,2,3,4-Tetrahydrochinolinäthyl-, ferner basische harnstoffe, Thioharnstof@@, basische Urethane und Thiourethane, basische heteroeyclishe Ringe wie Pyridin, Pyrrolidin und substituierte und unsubatituierte Guanidine.Nitrogen-containing groups are supposed to be the "baa @ scher remainder" that are capable of salt formation, e.g. Bo B-Dipropylamino-ethyl-, ß-Dioutylaminoäthyl-, ß-pyrrolidinoethyl, ß-piperidinoethyl, ß-hexamethylene-imino-ethyl-, ß-dimethylamino-ethyl-, γ-diethylamino-propyl-, γ-dibutylamino-propyl-, γ-N-propyl-N-outylamino-propyl-, γ-piperidinopropyl-, γ-N-wethylpiperazino-propyl-, γ-diethylamino-butyl-, γ-dimethylamino-ß-dimethyl-propyl, γ-diethylamino-ß-dimethylpropyl, (N-ethylpiperidyl-2) -methyl-, β-3,3-dimethyl-pyrrolidino -ethyl-, γ-dimethylamino-propyl-, ß- (ß'-phenylethyl) -aminoethyl-, γ-diethylamino-ß-hydroxy-propyl-, γ-Cyclohexylamino-propyl-, ß- (ß'-phenyl-ß'-hydroxy-ethyl) -aminoethyl-, ß-isobutylaminoethyl-, ß-Hydroxy-γ- (N-ethyl-N-p-chlorophenylamino) -propyl-, B-olyl-ethyl) -aminoUthyl-, γ- (4-methylpiperidino) -propyl, γ- (2-methyl-piperidino) -propyl-, γ- (2-ethylpiperidino) -propyl-, γ- (N-methyl-N-cyclohexyl) -aminopropyl-, γ T-hesamethylene-iminopropyl-, γ- (Di-cyclohexylmethylene-amino) -proply-, γ- (N-Meethyl-N-ß-ethoxyethyl) -amino-propyl-, γ- (3,3-4,4-tetramethyl-pyrrolidino) -propyl-, ß- (N-methyl-piperazino) -ethyl-, ß-Deca-hydroquinolino-ethyl-, ß-Decahydroisoquinolinoethyl-, ß-Dibenzylamino-ethyl-, γ-piperidino-ß-dimethyl-propyl-, γ-morpholino-ß-dimethyl-propyl-, ß-diisobutylamino-ethyl, ß-1,2,3,4-tetrahydroquinoline ethyl, also basic ureas, thiourea @@, basic urethanes and thiourethanes, basic heteroyclic rings such as pyridine, pyrrolidine and substituted and unsubstituted guanidines.
Die Verbindungen beeinflussen ale solche oder in Form ihrer Salse mit nicht-toxischen anorganischen oder organischen dauren die genannten Infektionen günstig. Im Vergleich dazu sind die bekannten nichtbasischen Imide der Naph6thalin-(1,4, 5, 8)-tetracarbonsäure [D.R.P. 552,760 ; H. Vollman, H. Becker, M. Corell, E. Streeck u. G. Langbein A. 531, 1 (1937); H.E.Fierz-David und C. Rassit helv. Chi. Acta 21, 1466 (1938) ; U. S Patent 2*914. 5317 unwirksam.The compounds affect all of these or in the form of their salts with non-toxic inorganic or organic acids, the infections mentioned cheap. In comparison, the known non-basic imides of the naph6thalene (1,4, 5, 8) tetracarboxylic acid [D.R.P. 552,760; H. Vollman, H. Becker, M. Corell, E. Streeck and G. Langbein A. 531, 1 (1937); H.E. Fierz-David and C. Rassit helv. Chi. Acta 21, 1466 (1938); U.S. Patent 2 * 914. 5317 ineffective.
Die neuen Verbindungen haben außerdem laxierende Wirkung.The new compounds also have a laxative effect.
Erfindungsgemä# werden die basisch alkylierten Naphthalin-(1,4,5,8)-tertracarbonsäurediimide dadurch hergestellt, daß man ein Anhydrid der allgemeinen Formel oder die entsprechende Tetracarbonsäure mit Aminen der allgemeinen Formel in Gegenwart eines Lösungsmittels oder in der Schmelze umsetzt. Als besonders günstig hat sich die Verwendung von Toluol und Xylol als Lösungsmittel erwiesen. Bei der bei Siedetemperatur rasch verlaufenden Reaktion läßt sich das entstehende Wasser durch azeotrope Destillation am Wasserabscheider in einfacher Weise entfernen. z Die Brzeugnisse des-erfindungsgemäBen Verfahrens zeichnen sich durch eine gute Wirkung gegenüber solchen Tuberkelbazillen aus, die gegen eine Behandlung durch Isonicotinsäurehydrasid (INH) und Thiosemicarbazon resistent geworden sind.According to the invention, the basic alkylated naphthalene- (1,4,5,8) -tertracarboxylic acid diimides are prepared by using an anhydride of the general formula or the corresponding tetracarboxylic acid with amines of the general formula in the presence of a solvent or in the melt. The use of toluene and xylene as solvents has proven to be particularly favorable. In the reaction, which proceeds rapidly at the boiling point, the water formed can be removed in a simple manner by azeotropic distillation on a water separator. The products of the method according to the invention are distinguished by a good action against those tubercle bacilli which have become resistant to treatment with isonicotinic acid hydraside (INH) and thiosemicarbazone.
Sie zeigen auch gegendber anderen klinisch bedeutsamen Tuberkulootatika wie Streptomycin und p-Aminosalicylsäure keine Kreuzreeistenz.They also show against other clinically important tuberculotatics like streptomycin and p-aminosalicylic acid no cross-resistance.
Die minimale Hemmkonzentration des erfindungsgemäß hergestellten N, N'-Bis-[N"-(ß-Diäthylaminoäthyl)-N"-(4-chlorphenyl)-amino7-naphthalin- (1, 4, 5, 8)-tetracarbonsäurediimids in 7-/mol Eimedium, die für eine Unterdrückung des Wachstums von gegen INH resistenten Mykobakterien erforderlich war, wurde mit der Hemmkonzentration des Isonicotinsäurehydrazids verglichen.The minimum inhibitory concentration of the N produced according to the invention, N'-bis- [N "- (ß-diethylaminoethyl) -N" - (4-chlorophenyl) -amino7-naphthalene- (1, 4, 5, 8) -tetracarbonsäurediimids in 7- / mol egg medium, which for a suppression of the growth of INH-resistant mycobacteria was required, was increased with the inhibitory concentration of isonicotinic hydrazide compared.
Die Versuche wurden an einem Laborstamm (125) durchgeführt, der ursprünglich aus Patientenmaterial isoliert worden ist.The experiments were carried out on a laboratory strain (125) that originally has been isolated from patient material.
Verbindung Minimale Hemmkonzentration γ/ml Eimedium, INH resistenter Stamm 125 INH > 100 Verfahrensprodukt 10 Beispiel 15 g Naphthalin-1, 4, 5, 8-tetracarbonsäuredianhydrid werden in Toluol unter Rühren zum Sieden erhitzt. Man tropft 36 g N, N- (γ-Dimethylaminopropyl)-3-chlorphenylhydrazin langsam zu und kocht am Wasserabscheider bis die Reaktion beendet ist.Compound Minimum inhibitory concentration γ / ml egg medium, INH more resistant Strain 125 INH> 100 process product 10 Example 15 g of naphthalene-1, 4, 5, 8-tetracarboxylic dianhydride are heated to the boil in toluene with stirring. 36 g of N, N- (γ-dimethylaminopropyl) -3-chlorophenylhydrazine are slowly added dropwise and boils on the water separator until the reaction has ended.
Nach dem Erkalten wird mit verdann-ter Essigsäure ausgeschüttelt, der essigsaure Auszug abgetrennt und alkalisch gestellt. Der ausfallende Niederschlag läßt sich aus Trockensprit unter Zusatz von etwas Chloroform umkristallibieren.After cooling, it is extracted with diluted acetic acid, the acetic acid extract separated and made alkaline. The falling precipitation can be recrystallized from dry spirit with the addition of a little chloroform.
21 g N,N'-Bis-[N"-(γ-dimethylaminopropyl)-N"-3-chlorphenylamino7-naphthalin- (1, 4, 5, 8)-tetracarbonsäurediimid, F. 189°C.21 g of N, N'-Bis- [N "- (γ-dimethylaminopropyl) -N" -3-chlorophenylamino7-naphthalene- (1, 4, 5, 8) -tetracarboxylic acid diimide, mp 189 ° C.
In analoger Weise erhält man man N, N'-Bia-/N"-(ß-diäthylaminoäthyl)-N"-4-chlorphenyl-amino7-naphthalin- (-1, 4, 5, 8)-tetracarbonsäurediimid, F. 220°C.In an analogous manner, one obtains N, N'-Bia- / N "- (ß-diethylaminoethyl) -N" -4-chlorophenyl-amino7-naphthalene- (-1, 4, 5, 8) -tetracarboxylic acid diimide, mp 220 ° C.
Die bei den Umsetzungen verwendeten basisch substituierten Hydrazinverbindungen werden durch Alkylierung des Hydrazons aus Chlorphenylhydrazin und Aceton mit T-Dimethylami. nopropylchlorid bzw. B-Diäthylamino-äthylchlorid und anschließende Spaltung des Hydrazons dargestellt.The basic substituted hydrazine compounds used in the reactions are obtained by alkylating the hydrazone from chlorophenylhydrazine and acetone with T-dimethylami. nopropyl chloride or B-diethylamino-ethyl chloride and subsequent cleavage of the Hydrazone shown.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF0049139 | 1964-06-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
DE1670696A1 true DE1670696A1 (en) | 1970-11-12 |
Family
ID=7102764
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19641670696 Pending DE1670696A1 (en) | 1964-06-05 | 1964-06-05 | Process for the preparation of basic alkylated naphthalene (1,4,5,8) tetracarboxylic diimides |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE1670696A1 (en) |
-
1964
- 1964-06-05 DE DE19641670696 patent/DE1670696A1/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE2847621A1 (en) | PHTHALAZINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING SUCH DERIVATIVES | |
DE2304609A1 (en) | 3-HALOGEN-5-ALKYL-DELTA HIGH 2-THIADIAZOLIN-4-ONE AND THEIR USE AS PESTICIDES | |
DE1230031B (en) | Process for the preparation of derivatives of naphthalene-1, 4, 5, 8-tetracarboxylic acid diimide | |
DE1670696A1 (en) | Process for the preparation of basic alkylated naphthalene (1,4,5,8) tetracarboxylic diimides | |
DE2305517C3 (en) | 2-Imino-13-dithiacyclobutanes, process for their preparation and warm-blooded protective agents against tick-insects containing them | |
DE1239292B (en) | Process for the preparation of guanylhydrazones of araliphatic carbonyl compounds | |
DE1225191B (en) | Process for the preparation of derivatives of naphthalene-1, 4, 5, 8-tetracarboxylic acid diimide | |
DE1593212C3 (en) | Process for the preparation of maleamic acid derivatives | |
DE1695804C3 (en) | N Acyl 2 methyl 3 indolylcarbonic acids, process for their preparation and pharmaceuticals | |
DE1228267B (en) | Process for the preparation of derivatives of naphthalene-1, 4, 5, 8-tetracarboxylic acid diimide | |
DE2133450C3 (en) | Crotonic acid amide derivatives and their use | |
DE2128905B2 (en) | HALF-SIDED ETHYLENE DIAMINE DERIVATIVES AND THE PROCESS FOR THEIR PRODUCTION | |
DE706198C (en) | Process for the preparation of o- and peri-dinitriles from o- and peri-dicarboxylic acids | |
DE610235C (en) | Process for the preparation of substituted nitrobenzenes | |
DE935667C (en) | Process for the preparation of phenanthridinium salts | |
AT214448B (en) | Process for the preparation of the new 10- (N-β-hydroxyethyl-piperazinyl-N'-propyl) -2-chloro-phenothiazine-5-oxide | |
AT223324B (en) | Process for the preparation of nitriles of the tetracyclines | |
AT214440B (en) | Process for the preparation of 3-iminoisoindolin-1-ones | |
DE1569604C3 (en) | Process for the preparation of basic oxazine dyes | |
AT272337B (en) | Process for the preparation of new 5-nitroimidazole derivatives | |
DE630967C (en) | Process for the preparation of N-nitramines from primary aromatic amines | |
DE1042591B (en) | Process for the preparation of 2-amino-1,3,4-thiadiazoles substituted in the 5-position | |
CH405560A (en) | Process for the preparation of pure crystal forms of substituted quinacridine-7,14-diones | |
DE2264903A1 (en) | PIPERIDINE DERIVATIVES | |
DE1941860A1 (en) | Trisubstituted hydrazines |